Melusin gene (ITGB1BP2) nucleotide variations study in hypertensive and cardiopathic patients.
Melusin is a muscle specific signaling protein, required for compensatory hypertrophy response in pressure-overloaded heart. The role of Melusin in heart function has been established both by loss and gain of function experiments in murine models. With the aim of verifying the hypothesis of a potential role of the Melusin encoding gene, ITGB1BP2, in the modification of the clinical phenotype of human cardiomyopathies, we screened the ITGB1BP2 gene looking for genetic variations possibly associated to the pathological phenotype in three selected groups of patients affected by hypertension and dilated or hypertrophic cardiomyopathy We analyzed ITGB1BP2 by direct sequencing of the 11 coding exons and intron flanking sequences in 928 subjects, including 656 hypertensive or cardiopathic patients and 272 healthy individuals. Only three nucleotide variations were found in patients of three distinct families: a C>T missense substitution at position 37 of exon 1 causing an amino acid change from His-13 to Tyr in the protein primary sequence, a duplication (IVS6+12_18dupTTTTGAG) near the 5'donor splice site of intron 6, and a silent 843C>T substitution in exon 11. The three variations of the ITGB1BP2 gene have been detected in families of patients affected either by hypertension or primary hypertrophic cardiomyopathy; however, a clear genotype/phenotype correlation was not evident. Preliminary functional results and bioinformatic analysis seem to exclude a role for IVS6+12_18dupTTTTGAG and 843C>T in affecting splicing mechanism.Our analysis revealed an extremely low number of variations in the ITGB1BP2 gene in nearly 1000 hypertensive/cardiopathic and healthy individuals, thus suggesting a high degree of conservation of the melusin gene within the populations analyzed.


Immunological adenovirus variant strains of subgenus D: comparison of the hexon and fiber sequences.
The fiber and hexon genes of the immunological adenovirus (Ad) variant strains Ad9/Hx and Ad15/Hx, belonging to subgenus D, were sequenced and compared to the corresponding sequences of the prototypes Ad9 and Ad15. It was found that the variants possessed a novel and identical hemagglutinin as they could not be distinguished by hemagglutination-inhibition tests. These serological data were now confirmed on DNA and protein level. The analyzed hexon regions of Ad15 and Ad15/Hx, and Ad9 and Ad9/Hx, respectively, were 100% identical on the amino acid level. The comparison between the variant fibers revealed that they possessed an identical fiber, which was distinct from the Ad9 and Ad15 fiber polypeptides. It seems likely that the donor of the novel fiber protein was a so far unidentified subgroup D adenovirus. The fiber polypeptides of Ad9 and the variants revealed the highest homology (73.7%), whereas the variants and the Ad15 fiber had only 64.2% of the amino acids in common. Most of the differences between the adenovirus serotypes were detected in the fiber knob. Seven conserved sequences found for subgenus D fibers could be confirmed for the fibers of the variants. Furthermore, the data presented complement the knowledge on the organization of subgenus D fiber genes.


Scanning Tunneling Microscopy of the Ultrastructure of Cotton Fiber.
The ultrastructure of the cotton fiber in Lumian No.11 was investigated with scanning tunneling microscope (STM), and the results were compared with that by scanning electron mincrocope(SEM). With SEM, fibrils could be seen, it was difficult, however, to further observe the fine structures in fibrils. Otherwise, with STM, fibrils could be seen clearly, and by making scan areas smaller, it could be observed that the fibrils were composed of microfibrils, and the microfibrils were composed of elementary fibrils, which were the smallest structural units of the fibril, which were arranged in parallel.


Different thresholds of bond percolation in scale-free networks with identical degree sequence.
Generally, the threshold of percolation in complex networks depends on the underlying structural characterization. However, what topological property plays a predominant role is still unknown, despite the speculation of some authors that degree distribution is a key ingredient. The purpose of this paper is to show that power-law degree distribution itself is not sufficient to characterize the threshold of bond percolation in scale-free networks. To achieve this goal, we first propose a family of scale-free networks with the same degree sequence and obtain by analytical or numerical means several topological features of the networks. Then, by making use of the renormalization-group technique we determine the threshold of bond percolation in our networks. We find an existence of nonzero thresholds and demonstrate that these thresholds can be quite different, which implies that power-law degree distribution does not suffice to characterize the percolation threshold in scale-free networks.


Towards smart environments using smart objects.
Barcodes, RFID, WLAN, Bluetooth and many more technologies are used in hospitals. They are the technological bases for different applications such as patient monitoring, asset management and facility management. However, most of these applications exist side by side with hardly any integration and even interoperability is not guaranteed. Introducing the concept of smart objects inspired by the Internet of Things can improve the situation by separating the capabilities and functions of an object from the implementing technology such as RFID or WLAN. By aligning technological and business developments smart objects have the power to transform a hospital from an agglomeration of technologies into a smart environment.


NPT1220-312, a TLR2/TLR9 Small Molecule Antagonist, Inhibits Pro-Inflammatory Signaling, Cytokine Release, and NLRP3 Inflammasome Activation.
Toll-like receptors (TLRs) play a critical role in innate immune system responses to damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). A growing body of evidence suggests that excessive TLR-mediated innate immune system activation can lead to neuronal damage and precipitate or perpetuate neurodegenerative diseases. Among TLR subtypes, both TLR2 and TLR9 have been implicated in neurodegenerative disorders with increased expression of these receptors in the central nervous system being associated with pro-inflammatory signaling and increased burdens of pathologic aggregated proteins. In the current study, we characterized the actions of a combined TLR2/TLR9 antagonist, NPT1220-312, on pro-inflammatory signaling and cytokine release in monocyte/macrophage-derived heterologous cells, human microglia, and murine and human whole blood. NPT1220-312 potently blocked TLR2- and TLR9-mediated release of inflammatory cytokines in monocyte/macrophage cells and in human microglia. NPT1220-312 also blocked TLR2-mediated activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome including IL-1β, IL-18, and apoptosis-associated speck-like protein containing a CARD (ASC) release to the culture medium of human differentiated macrophages. The ability of NPT1220-312 to inhibit TLR2 mediated pro-inflammatory release of chemokines and cytokines in situ was demonstrated using murine and human whole blood. Together, these findings suggest that blockade of TLR2 and TLR9 may reduce inappropriate production of pro-inflammatory cytokines and chemokines from peripheral and central immune cells and thus potentially provide therapeutic benefit in neuroinflammatory/neurodegenerative disorders.


Clinical significance of BIM deletion polymorphism in chemoradiotherapy for non-small cell lung cancer.
The standard treatment for locally advanced non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by anti-programmed cell death-ligand 1 (anti-PD-L1) treatment. BIM deletion polymorphism induces the suppression of apoptosis resulting from epidermal growth factor (EGFR)-tyrosine kinase inhibitors in EGFR-mutated NSCLC patients. We aimed to examine the effects of BIM polymorphism on CRT and anti-PD-L1/PD-1 treatment in NSCLC patients. In this retrospective study of 1312 patients with unresectable NSCLC treated at Higashi-Hiroshima Medical Center and Hiroshima University Hospital between April 1994 and October 2019, we enrolled those who underwent CRT or chemotherapy using carboplatin + paclitaxel or cisplatin + vinorelbine, or anti-PD-L1/PD-1 treatment. Of 1312 patients, 88, 80, and 74 underwent CRT, chemotherapy, and anti-PD-L1/PD-1 treatment, respectively, and 17.0%, 15.2% and 17.6% of these patients showed BIM polymorphism. Among patients receiving CRT, the progression-free survival was significantly shorter in those with BIM deletion than in those without. In the multivariate analyses, BIM polymorphism was an independent factor of poor anti-tumor effects. These results were not observed in the chemotherapy and anti-PD-L1/PD-1 treatment groups. In in vitro experiments, BIM expression suppression using small interfering RNA in NSCLC cell lines showed a significantly suppressed anti-tumor effect and apoptosis after irradiation but not chemotherapy. In conclusion, we showed that BIM polymorphism was a poor-predictive factor for anti-tumor effects in NSCLC patients who underwent CRT, specifically radiotherapy. In the implementation of CRT in patients with BIM polymorphism, we should consider subsequent treatment, keeping in mind that CRT may be insufficient.


The evolutionary origins and ecological context of tool use in New Caledonian crows.
New Caledonian (NC) crows Corvus moneduloides are the most prolific avian tool users. In the wild, they use at least three distinct tool types to extract invertebrate prey from deadwood and vegetation, with some of their tools requiring complex manufacture, modification and/or deployment. Experiments with captive-bred, hand-raised NC crows have demonstrated that the species has a strong genetic predisposition for basic tool use and manufacture, suggesting that this behaviour is an evolved adaptation. This view is supported by recent stable-isotope analyses of the diets of wild crows, which revealed that tool use provides access to highly profitable hidden prey, with preliminary data indicating that parents preferentially feed their offspring with tool-derived food. Building on this work, our review examines the possible evolutionary origins of these birds' remarkable tool-use behaviour. Whilst robust comparative analyses are impossible, given the phylogenetic rarity of animal tool use, our examination of a wide range of circumstantial evidence enables a first attempt at reconstructing a plausible evolutionary scenario. We suggest that a common ancestor of NC crows, originating from a (probably) non-tool-using South-East Asian or Australasian crow population, colonised New Caledonia after its last emersion several million years ago. The presence of profitable but out-of-reach food, in combination with a lack of direct competition for these resources, resulted in a vacant woodpecker-like niche. Crows may have possessed certain behavioural and/or morphological features upon their arrival that predisposed them to express tool-use rather than specialised prey-excavation behaviour, although it is possible that woodpecker-like foraging preceded tool use. Low levels of predation risk may have further facilitated tool-use behaviour, by allowing greater expenditure of time and energy on object interaction and exploration, as well as the evolution of a 'slow' life-history, in which prolonged juvenile development enables acquisition of complex behaviours. Intriguingly, humans may well have influenced the evolution of at least some of the species' tool-oriented behaviours, via their possible introduction of candlenut trees together with the beetle larvae that infest them. Research on NC crows' tool-use behaviour in its full ecological context is still in its infancy, and we expect that, as more evidence accumulates, some of our assumptions and predictions will be proved wrong. However, it is clear from our analysis of existing work, and the development of some original ideas, that the unusual evolutionary trajectory of NC crows is probably the consequence of an intricate constellation of interplaying factors.


[Demonstration of the knee joint with air. Technique and problems (author's transl)].
Despite the preference expressed by surgeons for arthroscopy, arthrography remains the method of choice for investigating lesions of the knee joint. In order to produce optimal contrast regularly, a standardised method for the examination must be used. Fifteen thousand pneumoarthrograms have been performed using the standard technique introduced by Möhlmann. The diagnosis of various lesions is discussed, with special reference to the problem of the medial posterior cornu. The results are analysed and the reliability of the method is evaluated.


Intra-cerebellar microinjection of histamine enhances memory consolidation of inhibitory avoidance learning in mice via H2 receptors.
Studies have demonstrated the relationship between the histaminergic system and the cerebellum, and we intend to investigate the role of the cerebellar histaminergic system on memory consolidation. This study investigated the effect of intra-cerebellar microinjection of histamine on memory retention of inhibitory avoidance in mice, and the role of H1 and H2 receptors in it. The cerebellar vermis of male mice were implanted with guide cannulae, and after three days of recovery, the inhibitory avoidance test was performed. Immediately after a training session, animals received a microinjection of histaminergic drugs: in the experiment 1, saline (SAL) or histamine (HA 0.54, 1.36, 2.72 or 4.07 nmol); experiment 2, SAL or 1.36 nmol HA 5 min after a pretreatment with 0.16 nmol chlorpheniramine (CPA) or SAL; and experiment 3, SAL or 1.36 nmol HA 5 min after a pretreatment with 2.85 nmol ranitidine (RA) or SAL. Twenty-four hours later, a retention test was performed. The data were analyzed using one-way analysis of variance (ANOVA) and Duncan's tests. In experiment 1, animals microinjected with 1.36 nmol HA showed a higher latency to cross to the dark compartment compared to controls and to 2.72 and 4.07 nmol HA groups. In experiment 2, the combined infusions revealed difference between control (SAL+SAL) and SAL+HA and CPA+HA; while in the experiment 3 the analysis indicated differences in retention latency between mice injected with SAL+SAL and SAL+HA. The groups that received the H2 antagonist RA did not show difference compared to control. These results indicate that 1.36 nmol HA enhances memory consolidation of inhibitory avoidance learning in mice and that the pretreatment with H2 antagonist RA was able to prevent this effect.


Does social support really help to eat a low-fat diet? Main effects and gender differences of received social support within the Health Action Process Approach.
Most theories of health-behavior change focus exclusively on individual self-regulation without taking social factors, such as social support, into account. This study's first aim was to systematically test the added value of received instrumental and emotional social support within the Health Action Process Approach (HAPA) in the context of dietary change. In the social support literature, gender effects emerge with regard to the effectiveness of social support. Thus, a second aim was the examination of gender differences in the association of social support with dietary behavior. Participants were 252 overweight and obese individuals. At baseline and 12 months later, participants completed questionnaires on HAPA variables; diet-specific received social support and low-fat diet. For the prediction of intentions 12 months later, instrumental support was more beneficial for men than for women over and above individual self-regulation. In terms of dietary behavior at T2, a moderate main effect of instrumental support emerged. Moreover, received emotional social support was beneficial for men, but not for women in terms of a low-fat diet 12 months later. Effects of received instrumental social support found in this study provide new evidence for the added value of integrating social support into the HAPA.


Spoken word classification in children and adults.
Preschool children often have difficulties in word classification, despite good speech perception and production. Some researchers suggest that they represent words using phonetic features rather than phonemes. In this study, the authors examined whether there is a progression from feature-based to phoneme-based processing across age groups and whether responses are consistent across tasks and stimuli. In Study 1, 120 three- to five-year-old children completed 3 tasks assessing use of phonetic features in classification, with an additional 58 older children completing 1 of the 3 tasks. In Study 2, all of the children, together with an additional adult sample, completed a nonword learning task. In all 4 tasks, children classified words sharing phonemes as similar. In addition, children regarded words as similar if they shared manner of articulation, particularly word finally. Adults also showed this sensitivity to manner, but across the tasks, there was a pattern of increasing use of phonemic information with age. Children tend to classify words as similar if they share phonemes or if they share manner of articulation word finally. Use of phonemic information becomes more common with age.


Distal embolic protection for infrainguinal interventions: how to and when?
Distal embolization is a well-recognized complication during lower extremity revascularization procedures. Preliminary work has shown safety and feasibility of the use of embolic protection devices in this vascular territory. While many interventionalists believe that this technology offers a clear benefit for infrainguinal use based on the clinical safety data seen in other vascular beds, others believe that the exact role is poorly defined. All clinical experience to date has been with devices designed for other vascular territories and this has created a unique set of technical obstacles and potential risks. At present, clinical use is increasing despite a lack of data regarding which patients are at greatest risk for distal embolization, which anatomy is appropriate for the use of this technology, and which device, if any, is ideally suited for the infrainguinal arterial circulation. In addition, the clinical relevance and effect of distal embolization in the lower extremity remains poorly understood. Ultimately, more trial data may be necessary to substantiate the increased use of distal protection devices in infrainguinal interventions to justify the increase in cost, complexity, and potential risks associated with the use of this technology.


Suppressive effect of fluticasone propionate on MMP expression in the nasal mucosa of allergic rhinitis patients in vivo.
The effects of intranasal corticosteroids on matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases (TIMPs)) in the nasal mucosa of patients with allergic rhinitis (AR) are not known. Nasal mucosa biopsy specimens were obtained from AR patients, with or without the administration of fluticasone propionate (FP) nose drops, and from healthy volunteers as controls. The specimens were analyzed by immuno-histochemistry and ELISA for MMP-2, MMP-9, TIMP-1 and TIMP-2. The MMP-9 levels in nasal mucosa extracts in the AR patients were significantly higher than in the controls. A significant suppressive effect of FP on the MMP-9 levels was shown. The control subjects showed no MMP- or TIMP-positive cells, whereas such positive cells were clearly present in the AR patients. No MMP- or TIMP-positive cells were detected after topical application of FP. These results suggest that the suppressive effect of FP on MMP expression is, in part, responsible for its clinical efficacy in AR.


Effects of prehypertension on admissions and deaths: a simulation.
The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recently released new clinical practice guidelines that target systolic blood pressure and identify persons with "prehypertension" (systolic blood pressure, 120-139 mm Hg), previously considered normal, as being at elevated risk and in need of intervention. We used a simulation model, fitted to longitudinal data from the first NHANES (National Health and Nutrition Examination Survey) Epidemiologic Followup Study, to estimate the effects of prehypertension and residual hypertension (systolic blood pressure, > or =140 mm Hg). The term residual hypertension recognizes that many people with hypertension have lowered their pressures through treatment, but not to less than 140 mm Hg. We applied the model to a representative sample of US adults aged 25 to 74 years from NHANES III. Except for women aged 25 to 44 years, more than a third of each age group in NHANES III had prehypertension. Approximately two thirds of persons aged 45 to 64 years and 80% of persons aged 65 to 74 years had prehypertension or residual hypertension. Together, prehypertension and residual hypertension accounted for 4.7% of hospital admissions per 10 000 adults aged 25 to 74 years, 9.7% of nursing home admissions, and 13.7% of deaths. Prehypertension alone accounted for 3.4% of hospitalizations, 6.5% of nursing home stays, and 9.1% of deaths. Numbers of events attributable to prehypertension are greatest for men aged 45 to 64 years and persons aged 65 to 74 years. Our results confirm the substantial public health consequences of prehypertension. If prehypertension were eliminated, hospitalizations, nursing home admissions, and premature deaths could decline substantially.


Double Trouble: A Unique Case of Hypercalcemia Caused by Two Underlying Etiologies.
Hypercalcemia has a variety of causes, with primary hyperparathyroidism and malignancies being the most frequently reported. We present the case of a patient presenting with chronic abdominal pain, constipation, and weight loss who was found to have hypercalcemia. The patient was initially diagnosed with colonic actinomycosis, but further investigations revealed an intra-abdominal diffuse large B-cell lymphoma (DLBCL). We suspect that the leading cause of hypercalcemia was the DLBCL, likely exacerbated by actinomycosis. Actinomycosis and DLBCL can have a similar presentation, so misdiagnosis or coexistence of both conditions should be suspected when a lack of response to one specific therapy is observed.


Theoretical analysis of H-Horn annular phased array system for heating deep-seated tumors.
This paper discusses a type of annular phased array system--H-Horn APA. The phase and amplitude control of power deposition patterns for this system are theoretically analyzed at a frequency of 200 MHz. The formulas for calculating E-field and SAR for this APA system are derived, and can be applied to other type APA systems. Models of computerized tomography (CT) scans from liver and lung regions have been used, respectively, for predicting optimization of E-field and SAR patterns in the case of the relative phase and amplitude changes. It is shown that the techniques of the phase and amplitude control of SAR patterns result in more selectively and effectively heating of tumors situated eccentrically and deeply within bodies of patients. The APA hyperthermia described in this paper shows great promise, and it looks very useful for developing clinical applications.


A comparative analysis of video-based surgical assessment: is evaluation of the entire critical portion of the operation necessary?
Previous studies of video-based operative assessments using crowd sourcing have established the efficacy of non-expert evaluations. Our group sought to establish the equivalence of abbreviating video content for operative assessment. A single institution video repository of six core general surgery operations was submitted for evaluation. Each core surgery included three unique surgical performances, totaling 18 unique operative videos. Each video was edited using four different protocols based on the critical portion of the operation: (1) custom edited critical portion (2) condensed critical portion (3) first 20 s of every minute of the critical portion, and (4) first 10 s of every minute of the critical portion. In total, 72 individually edited operative videos were submitted to the C-SATS (Crowd-Sourced Assessment of Technical Skills) platform (C-SATS) for evaluation. Aggregate score for study protocol was compared using the Kruskal-Wallis test. A multivariable, multilevel mixed-effects model was constructed to predict total skill assessment scores. Median video lengths for each protocol were: custom, 6:20 (IQR 5:27-7:28); condensed, 10:35 (8:50-12:06); 10 s, 4:35 (2:11-6:09); and 20 s, 9:09 (4:20-12:14). There was no difference in aggregate median score among the four study protocols: custom, 15.7 (14.4-16.2); condensed, 15.8 (15.2-16.4); 10 s, 15.8 (15.3-16.1); 20 s, 16.0 (15.1-16.3); χ2 = 1.661, p = 0.65. Regression modeling demonstrated a significant, but minimal effect of the 10 s and 20 s editing protocols compared to the custom method on individual video score: condensed, + 0.33 (- 0.05-0.70), p = 0.09; 10 s, + 0.29 (0.04-0.55), p = 0.03; 20 s, + 0.40 (0.15-0.66), p = 0.002. A standardized protocol for video editing abbreviated surgical performances yields reproducible assessment of surgical aptitude when assessed by non-experts.


Pain outcomes of inpatient pain and palliative care consultations: differences by race and diagnosis.
Pain management disparities exist among patients not receiving palliative care. We examined pain outcomes for disparities among patients receiving palliative care. At a 542-bed teaching hospital in Honolulu, The Queens' Medical Center Pain and Palliative Care Department collected patient characteristics and pain severity (initial, final) for each consultation from 2005 through 2009. Analyses compared pain levels by race (white, Asian, Hawaiian/Pacific Islander [PI], other) and consultation diagnosis (cancer, noncancer medical, surgical [59% orthopedic], other). Multiple regression models analyzed factors associated with lower final pain levels and pain reduction. Study population included 4658 patients. No final pain was reported by more non-white patients (33%-39%) than white (27%, p<0.0001) and more cancer and noncancer medical patients (45%-54%) than surgical/other patients (20%-31%, p<0.0001). Asian (adjusted odds ratio [aOR] 1.24; 95% confidence interval [CI] 1.06-1.46; p=0.007) and PI (aOR 1.46, 95% CI 1.20-1.77, p=0.0001) races had increased likelihoods of lower final pain severity versus whites, controlling for age, gender, Karnofsky score, preconsult length of stay, and initial pain severity. Surgical diagnoses had decreased likelihood of lower final pain levels versus cancer (aOR 0.38, 95% CI 0.32-0.46, p<0.0001). Among 2304 patients reporting moderate/severe initial pain, 1738 (75.4%) reported pain reduction to mild/no final pain. PI race was associated with pain reduction versus whites (aOR 1.57, 95% CI 1.17-2.10, p=0.003). Surgical diagnoses had decreased likelihood of pain reduction vs. cancer (aOR 0.52, 95% CI 0.39-0.71, p<0.0001). Pain outcomes were similar or better among non-white races than whites. Surgical patients reported more final pain than cancer patients.


Heterogeneity of keratin expression and actin distribution in benign and malignant mammary diseases.
Immunoreactivity of monoclonal anti-cytokeratin KL1, PKK1, K8.12 and anti-actin antibodies in 101 cases of diseased human breast lesions showed irregular keratin distribution in luminal cells of terminal ductal-lobular unit and basal layer cells of the interlobular and main duct. Actin staining was confined to myoepithelial cells. Benign lesions showed great heterogeneity in luminal cells of the terminal ductal-lobular units. Breast carcinoma showed a reduced staining for keratins, heterogeneity of keratin expression was found in solid tubular carcinoma, and actin was usually absent: however, papillo-ductal or comedo type had actin positive myoepithelial cells around carcinoma foci.


Evaluation of SARS-CoV-2 IgG antibody response in PCR positive patients: Comparison of nine tests in relation to clinical data.
SARS-CoV-2 antibody tests are available in various formats, detecting different viral target proteins and antibody subclasses. The specificity and sensitivity of SARS-CoV-2 antibody tests are known to vary and very few studies have addressed the performance of these tests in COVID-19 patient groups at different time points. We here compared the sensitivity and specificity of seven commercial (SNIBE, Epitope, Euroimmun, Roche, Abbott, DiaSorin, Biosensor) and two in-house LIPS assays (LIPS N and LIPS S-RBD) IgG/total Ab tests in serum samples from 97 COVID-19 patients and 100 controls, and correlated the results with the patients' clinical data and the time-point the test was performed. We found a remarkable variation in the sensitivity of antibody tests with the following performance: LIPS N (91.8%), Epitope (85.6%), Abbott and in-house LIPS S-RBD (both 84.5%), Roche (83.5%), Euroimmun (82.5%), DiaSorin (81.4%), SNIBE (70.1%), and Biosensor (64.9%). The overall agreement between the tests was between 71-95%, whereas the specificity of all tests was within 98-100%. The correlation with patients' clinical symptoms score ranged from strongest in LIPS N (ρ = 0.41; p<0.001) to nonsignificant in LIPS S-RBD. Furthermore, the time of testing since symptom onset had an impact on the sensitivity of some tests. Our study highlights the importance to consider clinical symptoms, time of testing, and using more than one viral antigen in SARS-CoV-2 antibody testing. Our results suggest that some antibody tests are more sensitive for the detection of antibodies in early stage and asymptomatic patients, which may explain the contradictory results of previous studies and should be taken into consideration in clinical practice and epidemiological studies.


Constructing Quantum Spin Liquids Using Combinatorial Gauge Symmetry.
We introduce the notion of combinatorial gauge symmetry-a local transformation that includes single spin rotations plus permutations of spins (or swaps of their quantum states)-that preserve the commutation and anticommutation relations among the spins. We show that Hamiltonians with simple two-body interactions contain this symmetry if the coupling matrix is a Hadamard matrix, with the combinatorial gauge symmetry being associated with the automorphism of these matrices with respect to monomial transformations. Armed with this symmetry, we address the physical problem of how to build quantum spin liquids with physically accessible interactions. In addition to its intrinsic physical significance, the problem is also tied to that of how to build topological qubits.


Plantar contact stress and gait analysis after resection of tarsal coalition.
The purpose of this study was to assess the foot loading characteristics and foot function of patients after operative correction of a tarsal coalition. Ten patients who had undergone operative treatment of a tarsal coalition were included in this study. One foot was affected in five patients and both feet in the other five. A calcaneonavicular coalition was present in 12 feet and a talocalcaneal coalition in three feet. Mean follow-up was 11.3 years. Clinical evaluation was based on a standardized questionnaire, a visual analogue scale for pain (VAS), the American Orthopaedic Foot and Ankle Society (AOFAS) Score and radiographic evaluation of the last radiographs. An objective analysis of foot loading characteristics was carried out with instrumented gait analysis and pedobarography. The clinical results were overall fair for pain, range of motion and walking distance. The AOFAS also showed fair results (mean: 78.1) at follow-up. Gait analysis revealed alterations in kinematic and kinetic parameters for the operated foot. Pedobarographic analysis showed altered loadings for heel and forefoot. In this study, operative treatment of tarsal coalition achieved fair clinical and radiographic results and did not restore physiologic gait and foot loading.


Identification by random amplification of polymorphic DNA of a common molecular type of Cryptococcus neoformans var. neoformans in patients with AIDS or other immunosuppressive conditions.
Sixty clinical isolates of Cryptococcus neoformans var. neoformans were analyzed by random amplification of polymorphic DNA (RAPD) using 12- to 22-mer primers in pairs. Five major profiles, which clearly distinguished between serotypes A (profiles I-III), AD (profile IV), and D (profile V), were identified. Forty-two of 58 serotype A isolates were assigned to profile I, 13 to profile II, and 3 to profile III. Profile I compromised 5 subtypes (profiles Ia-Ie), with 37 to 42 isolates in profile Ia. Twenty-seven of 28 isolates from patients with AIDS belonged to profile Ia (P<.001), as did 7 of 10 isolates from otherwise immunocompromised patients. Isolates from immunocompetent hosts were broadly distributed (profile I, 8 isolates; profile II, 10 isolates; profile III, 2 isolates). RAPD profiles were independent of body site and geographic origin of isolates. Isolates pairs from 3 patients produced identical profiles. A predominant genetic profile among serotype A strains from AIDS patients has not been reported previously.


[Research progress of silica-associated autoimmune diseases].
Silicosis is caused by long-term exposure to dust containing crystalline silica. However, silica exposure, which may lead to autoimmune dysfunction, is associated with autoimmune diseases such as rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, idiopathic inflammatory myopathy and anti-central granulocyte cytoplasmic antibody associated vasculitis. With silica exposure autoimmune diseases may exist with or without silicosis. This article reviews recent research on silica-associated autoimmune diseases such as the concept, epidemiology, clinical characteristics and potential mechanisms to improve the understanding of the disease and promote the formulation of diagnostic criteria and treatment plans.


Zinc Nutrition and Starch Metabolism in Phaseolus vulgaris L.
The effect of Zn nutrition on leaf starch metabolism was studied in two navy bean (Phaseolus vulgaris L.) varieties, Sanilac and Saginaw. Sanilac is much more susceptible to Zn deficiency than is Saginaw. The variables examined in these two strains were starch content, the activity of soluble starch synthetase (ADP-glucose: starch alpha-4-glucosyltransferase, EC 2.4.1.b), and the size and number of starch grains. All of these variables decreased during Zn deficiency. The reductions were much greater in Sanilac than in Saginaw. Thus, positive correlations exist between the relative changes in these variables in Sanilac and Saginaw under low Zn and their genotypic difference in growth response to low Zn. These results are taken to purport that the above observations most likely represent characteristic responses to Zn deficiency. We therefore suggest that, as a possible role in plant metabolism, Zn is involved in starch formation.


Controlled expression of the migratory phenotype affects oxidative status in birds.
High caloric intake can increase production of reactive oxygen and nitrogen species. We examined whether the emergence of the migratory phenotype, primarily signalled by increased food intake and fuelling, is accompanied by changes in oxidative status. We induced autumn migration followed by a non-migratory wintering phase in common quails (Coturnix coturnix). We compared three markers of oxidative status - oxidative damage to lipids expressed as thiobarbituric acid reactive substances (TBARS); superoxide dismutase (SOD); and glutathione peroxidase (GPx) - between birds sampled during the migratory and non-migratory phase. We found that the emergence of the migratory phenotype was associated with: (i) higher levels of TBARS in the liver; (ii) lower levels of SOD in red blood cells and, marginally, in the liver; (iii) higher levels of GPx in the pectoral muscle; and (iv) sex-specific changes in red blood cells and liver. We found no link between food intake and variation in markers of oxidative status in any of the tissues examined, despite food intake being higher in the migratory birds. However, the increase in body mass was positively correlated with muscle GPx activity as birds entered the pre-migratory fattening phase, while the amount of decrease in body mass was negatively correlated with muscle GPx as birds transitioned to the non-migratory phase. Such correlations were absent in red blood cells and liver. Our work suggests that during the emergence of the migratory phenotype, birds might strategically displace oxidative costs on the liver in order to safeguard the pectoral muscles, which have a fundamental role in successfully completing the migratory flight.


Self-determination theory: a framework for clubhouse psychosocial rehabilitation research.
The Clubhouse model is a widely used approach to psychosocial rehabilitation that has been a pioneer in supporting recovery-oriented programmes. Little consideration has been given however, to the theories that guide research of the recovery practices used by Clubhouses. In this paper, we provide a description of self-determination theory, including its philosophical background followed by explanation of its relevance to health care and Clubhouse contexts. We argue that self-determination theory provides a robust social constructionist theoretical framework that is well-suited to informing research related to psychosocial rehabilitation, recovery-oriented practices and the Clubhouse model.


Implantable bladder volume sensor based on resistor ladder network composed of conductive hydrogel composite.
An accurate bladder volume monitoring system is a critical component in diagnosis and treatment of urological disorders. Here, we report an implantable bladder volume sensor with a multi-level resistor ladder which estimates the bladder volume through discrete resistance values. Discretization allows the sensor output to be resilient to the long-term drift, hysteresis, and degradation of the sensor materials. Our sensor is composed of biocompatible polypyrrole/agarose hydrogel composite. Because Young's modulus of this composite is comparable to that of the bladder wall, the effect of mechanical loading of the sensor on the bladder movement is minimized which allows more accurate volume monitoring. We also demonstrate the patterning and molding capability of this material by fabrication various structures. Lastly, we successfully demonstrate the functionality of the multi-level resistor ladder sensor as a bladder volume sensor by attaching the sensor on the pig's bladder and observing the impedance change of the sensor.


Roles of GlcNAc-6-O-sulfotransferases in lymphoid and nonlymphoid tissues.
Recent studies using sulfotransferase-deficient mice have revealed various physiological functions of sulfated glycans. Studies using gene-targeted mice deficient in both N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST)-1 and GlcNAc6ST-2 showed that these sulfotransferases play critical roles in lymphocyte homing. Recent studies indicated that GlcNAc6ST-2 is expressed not only in lymph node high endothelial venules but also in the colonic epithelial cells in mice, and that this sulfotransferase plays a critical role in GlcNAc-6-O-sulfation of the colonic-mucins, as revealed by liquid chromatography coupled to electrospray ionization tandem mass spectrometry of the colonic-mucin O-glycans from wild-type (WT) and GlcNAc6ST-2-deficient mice. After induction of colitis by dextran sulfate sodium, significantly more leukocyte infiltration was observed in the colon of GlcNAc6ST-2-deficient mice than in that of WT mice. These studies demonstrate that GlcNAc-6-O-sulfotransferases play important roles not only in lymphoid tissues but also in nonlymphoid tissues. This chapter describes experimental procedures for assessing the functions of GlcNAc-6-O-sulfotransferases using gene-targeted mice.


[Complaints regarding lumbar disk herniation treatment reported to the Norwegian Compensation System].
Over the 1993-99 period the Norwegian Patient Compensation System made decisions in 4,041 orthopaedic treatment injury cases. 700 cases were randomly selected and analysed in order to elucidate the reasons for complaints. 58 cases were related to lumbar disc herniation treatment. Of these 58 cases, 52 complaints were lodged against hospitals; six against primary health care providers. Seven patients had been primarily observed or non-operatively treated; 55 were eventually operated on, eight with recurrent disease. Nearly all complaints were related to the outcome of surgery (72%) and delay of diagnosis/surgery (21%). Several serious complications occurred; one patient died. Five patients had cauda equina syndrome; a further seven had neurological deficits from distal spinal nerve roots. In 17 cases (29%) the complaints were accepted, while 41 complaints (71%) were rejected. In lumbar disc herniations both surgery, observation and non-operative treatment may lead to severe complications. It is important to select the right patients for surgery and to provide good information.


[Frame of internal functioning and innovative practices in a Day Center for psychotics].
The Day Center (DC) of EPAPSI (Scientific Association for Regional Development and Mental Health) offers complete psycho-social interventions for the psyhotic patients of the 5th Psychiatric Sector, in order to prevent them from relapsing, helps reduce hospitalisation and also works towards psychological and vocational rehabilitation; always aiming at improving the quality of patients' life. Working towards the continuum of care of its patients, the DC applies innovative practises such as: the creation of a community-based supportive network, the running of social clubs, participation in European Programmes concerning the social and vocational rehabilitation of patients, creation of KoiSPE (Limited Liability Social Co-operatives) in co-operation with the Local Authorities, application of new methods of caring and curing, involving the patients in co-running the "therapeutic contract". The successful application of "community psychiatry" and the continuation of psychiatric reform will be accommodated with the contribution and co-operation of "communal" services and the wider public sector as well as the application of new and pioneering programmes.


Sp1 and Sp3 transcription factors synergistically regulate HGF receptor gene expression in kidney.
We investigated the expression pattern and underlying mechanism that controls hepatocyte growth factor (HGF) receptor (c-met) expression in normal kidney and a variety of kidney cells. Immunohistochemical staining showed widespread expression of c-met in mouse kidney, a pattern closely correlated with renal expression of Sp1 and Sp3 transcription factors. In vitro, all types of kidney cells tested expressed different levels of c-met, which was tightly proportional to the cellular abundances of Sp1 and Sp3. Both Sp1 and Sp3 bound to the multiple GC boxes in the promoter region of the c-met gene. Coimmunoprecipitation suggested a physical interaction between Sp1 and Sp3. Functionally, Sp1 markedly stimulated c-met promoter activity. Although Sp3 only weakly activated the c-met promoter, its combination with Sp1 synergistically stimulated c-met transcription. Conversely, deprivation of Sp proteins by transfection of decoy Sp1 oligonucleotide or blockade of Sp1 binding with mithramycin A inhibited c-met expression. The c-met receptor in all types of kidney cells was functional and induced protein kinase B/Akt phosphorylation in a distinctly dynamic pattern after HGF stimulation. These results indicate that members of the Sp family of transcription factors play an important role in regulating constitutive expression of the c-met gene in all types of renal cells. Our findings suggest that HGF may have a broader spectrum of target cells and possess wider implications in kidney structure and function than originally thought.


Medical-care expenditures attributable to cigarette smoking during pregnancy -- United States, 1995.
An estimated 26% of women of reproductive age (i.e., 18-44 years) smoked in 1993, and approximately 19%-27% of women smoke during pregnancy. Smoking during pregnancy is causally associated with an annual estimated 32,000-61,000 low-birthweight infants and 14,000-26,000 admissions to neonatal intensive-care units. The estimated smoking-attributable direct medical-care costs for chronic conditions in 1993 were $50.0 billion; however, this estimate omitted the direct medical costs of tobacco exposure for infants and children and most of these costs for pregnant women. To derive 1995 estimates of the smoking-attributable costs for direct medical expenditures (i.e., inpatient, physician, hospital outpatient, and emergency department costs) related to pregnancy outcomes, the University of California at Berkeley and CDC analyzed data from the 1987 National Medical Expenditures Survey (NMES-2). This report summarizes the findings, which indicate substantial smoking-attributable direct medical expenditures for pregnant women and newborns.


Design Elements and Feasibility of an Organized Multiplayer Mobile Active Videogame for Primary School-Aged Children.
This article describes the design, development, and implementation feasibility of a purpose-built mobile active videogame (M-AVG) named "Pirate Adventure," which was designed for primary school-aged children to engage in physical activity (PA) and fundamental movement skills (FMS), such as hopping, sidestepping, jumping, or running, in an afterschool setting. The design of "Pirate Adventure" was the result of a collaboration between games designers and health researchers. "Pirate Adventure" was designed and developed using Android(®) (Google, Mountain View, CA) phone sensors to respond to player actions within a playground environment. Using an interactive game framework, players solve clues and complete PA and FMS challenges via sensing the physical world through marked-out key game locations. Fourteen primary school-aged children participated in the feasibility evaluation, which took place in four afternoon sessions. The game was evaluated using Android phone telemetry data and a post-gameplay survey for children on their opinions and enjoyment of the game. The "Pirate Adventure" game design facilitated an enjoyable treasure hunt game (average of 11 minutes of activity per game) with narrative elements supporting children's engagement with movement activities. The majority of children (n=9/13) reported that they would like to play the game again. Combining real world and virtual world content through "Pirate Adventure" was moderately successful, with multiple gameplay sessions occurring. Further implementation feasibility testing, under more controlled conditions, needs to be conducted to assert the benefits of using a M-AVG for children's PA and FMS.


Probing the Metabolic Landscape of Plant Vascular Bundles by Infrared Fingerprint Analysis, Imaging and Mass Spectrometry.
Fingerprint analysis is a common technique in forensic and criminal investigations. Similar techniques exist in the field of infrared spectroscopy to identify biomolecules according to their characteristic spectral fingerprint features. These unique markers are located in a wavenumber range from 1800 to 600 cm-1 in the mid infrared region. Here, a novel bioanalytical concept of correlating these spectral features with corresponding mass spectrometry datasets to unravel metabolic clusters within complex plant tissues was applied. As proof of concept, vascular bundles of oilseed rape (Brassica napus) were investigated, one of the most important and widely cultivated temperate zone oilseed crops. The link between mass spectrometry data and spectral data identified features that co-aligned within both datasets. Regions of origin were then detected by searching for these features in hyperspectral images of plant tissues. This approach, based on co-alignment and co-localization, finally enabled the detection of eight distinct metabolic clusters, reflecting functional and structural arrangements within the vascular bundle. The proposed analytical concept may assist future synergistic research approaches and may lead to biotechnological innovations with regard to crop yield and sustainability.


The role of fiber in the treatment of hypercholesterolemia in children and adolescents.
The effect of adding water-soluble fiber to a diet low in total fat, saturated fat, and cholesterol to treat hypercholesterolemic children and adolescents with elevated plasma low-density lipoprotein (LDL) cholesterol levels was assessed. In more than a half-dozen studies, the effect of water-soluble fiber on the LDL cholesterol level ranged from no change to as high as a 23% decrease using oat bran, psyllium, or locust bean gum. The wide range of effects in these studies may be related to the quality of the dietary intervention or to different methods of randomization, blinding, dietary assessment, and laboratory measurement. For example, the addition of supplemented soluble fiber (psyllium) to a step 1 diet may provide additional lowering of LDL cholesterol of 10% to 15%. However, in children consuming the more stringent step 2 diet, the addition of water-soluble fiber may have less additional effects on LDL cholesterol. As recommended by the National Cholesterol Education Program Expert Panel on Blood Cholesterol Levels in Children and Adolescents, dietary therapy, that is, a diet low in total fat, saturated fat, and cholesterol, remains the cornerstone of treatment for children and adolescents with elevated LDL cholesterol levels. The use of foods high in water-soluble fiber that contain no cholesterol and are low in saturated fat remains a good choice in children following a step 1 or step 2 diet. Additional clinical trials in larger numbers of well-defined subjects will be needed to assess further the utility of adding water-soluble fiber supplements to the National Cholesterol Education Program step 1 or step 2 diets.(ABSTRACT TRUNCATED AT 250 WORDS)


Sex differences in renal mitochondrial function: a hormone-gous opportunity for research.
Sex differences (biological distinctions between males and females) present a complex interplay of genetic, developmental, biological, and environmental factors. More and more studies are shedding light on the importance of sex differences in normal physiology and susceptibility to cancer, cardiovascular and renal conditions, and neurodegenerative diseases. This mini-review is devoted to the role of sex dimorphisms in renal function, with a focus on the distinctions between male and female mitochondria. Here, we cover the aspects of renal mitochondrial bioenergetics where sex differences have been reported to date, for instance, biogenesis, reactive oxygen species production, and oxidative stress. Special attention is devoted to the effects of sex hormones, such as estrogen and testosterone, on mitochondrial bioenergetics in the kidney in physiology and pathophysiology.


A weighted Kaplan-Meier estimator for matched data with application to the comparison of chemotherapy and bone-marrow transplant in leukaemia.
Studies on the comparison of transplantation with respect to standard therapy present a number of statistical challenges: they are usually not randomized, often retrospective (based on registry data) and the treatment assignment is time dependent (waiting time to transplant). Matching on known prognostic factors and waiting time to transplant can be used to select appropriate samples for the analysis. When a variable number of patients treated with conventional therapy matches each transplanted patient, the standard estimating and testing procedures need to be modified in order to account for the fact that matched data are highly stratified, with strata containing a few, possibly censored, observations. A weighted version of the Kaplan-Meier estimator, which accounts for a variable proportion of matching, is proposed and its statistical properties are studied. The problem of the comparison of the survival experience in the two treatment groups is also considered. Two tests, based on the distance between the survival estimates calculated at a prefixed time point, are examined and their behaviour is evaluated through simulations. The procedures proposed here are applied to data collected from an Italian study whose aim was the evaluation of bone marrow transplant, as compared to intensive chemotherapy, in the cure of paediatric acute lymphoblastic leukaemia.


Evaluating the Surface Topography of Pyrolytic Carbon Finger Prostheses through Measurement of Various Roughness Parameters.
The articulating surfaces of four different sizes of unused pyrolytic carbon proximal interphalangeal prostheses (PIP) were evaluated though measuring several topographical parameters using a white light interferometer: average roughness (Sa); root mean-square roughness (Sq); skewness (Ssk); and kurtosis (Sku). The radii of the articulating surfaces were measured using a coordinate measuring machine, and were found to be: 2.5, 3.3, 4.2 and 4.7 mm for proximal, and 4.0, 5.1, 5.6 and 6.3 mm for medial components. ANOVA was used to assess the relationship between the component radii and each roughness parameter. Sa, Sq and Ssk correlated negatively with radius (p = 0.001, 0.001, 0.023), whilst Sku correlated positively with radius (p = 0.03). Ergo, the surfaces with the largest radii possessed the better topographical characteristics: low roughness, negative skewness, high kurtosis. Conversely, the surfaces with the smallest radii had poorer topographical characteristics.


Genome-wide gene expression profile analysis of esophageal squamous cell carcinomas.
To identify the molecules involved in esophageal carcinogenesis and those applicable as novel tumor markers and for the development of new molecular therapies, we performed gene expression profile analysis of 19 esophageal squamous cell carcinoma (ESCC) cells purified by laser microbeam microdissection (LMM). Using a cDNA microarray representing 32,256 genes, we identified 147 genes that were commonly up-regulated and 376 transcripts that were down-regulated in ESCC cells compared with non-cancerous esophageal epithelial cells. A comparison of clinicopathological data with the expression profiles of the 19 ESCCs identified 20 genes whose expression levels could most significantly separate cases with lymph node metastasis from those without. In addition, immunohistochemical analysis of candidate tumor markers on tissue microarrays demonstrated transactivation of a secretory protein, transforming growth factor alpha (TGFA) in the great majority of 228 ESCC cases and an association of their expression with the poor prognosis of patients. Our data provide valuable information for establishing novel diagnostic markers for early diagnosis and choice of therapy, and identifying therapeutic target molecules for the development of novel anti-cancer drugs and immunotherapy in esophageal cancer treatment.


Enhanced immunogenicity in the murine airway mucosa with an attenuated Salmonella live vaccine expressing OprF-OprI from Pseudomonas aeruginosa.
We constructed an oral live vaccine based on the attenuated aroA mutant Salmonella enterica serovar Typhimurium strain SL3261 expressing outer membrane proteins F and I (OprF-OprI) from Pseudomonas aeruginosa and investigated it in a mouse model. Strains with in vivo inducible protein expression with the PpacC promoter showed good infection rates and immunogenicity but failed to engender detectable antibodies in the lung. However, a systemic booster vaccination following an oral primary immunization yielded high immunoglobulin A (IgA) and IgG antibody levels in both upper and lower airways superior to conventional systemic or mucosal booster vaccination alone. In addition, the proportion of IgG1 and IgG2a antibodies suggested that the systemic booster does not alter the more TH1-like type of response induced by the oral Salmonella primary vaccination. We conclude that an oral primary systemic booster vaccination strategy with an appropriate mucosal vector may be advantageous in diseases with the risk of P. aeruginosa airway infection, such as cystic fibrosis.


Comprehensive analysis of prognostic value, immune implication and biological function of CPNE1 in clear cell renal cell carcinoma.
Background: Elevated expression of Copine-1 (CPNE1) has been proved in various cancers; however, the underlying mechanisms by which it affects clear cell renal cell carcinoma (ccRCC) are unclear. Methods: In this study, we applied multiple bioinformatic databases to analyze the expression and clinical significance of CPNE1 in ccRCC. Co-expression analysis and functional enrichment analysis were investigated by LinkedOmics, cBioPortal and Metascape. The relationships between CPNE1 and tumor immunology were explored using ESTIMATE and CIBERSORT method. In vitro experiments, CCK-8, wound healing, transwell assays and western blotting were conducted to investigate the effects of gain- or loss-of-function of CPNE1 in ccRCC cells. Results: The expression of CPNE1 was notably elevated in ccRCC tissues and cells, and significantly correlated with grade, invasion range, stage and distant metastasis. Kaplan-Meier and Cox regression analysis displayed that CPNE1 expression was an independent prognostic factor for ccRCC patients. Functional enrichment analysis revealed that CPNE1 and its co-expressed genes mainly regulated cancer-related and immune-related pathways. Immune correlation analysis showed that CPNE1 expression was significantly related to immune and estimate scores. CPNE1 expression was positively related to higher infiltrations of immune cells, such as CD8+ T cells, plasma cells and regulatory T cells, exhibited lower infiltrations of neutrophils. Meanwhile, elevated expression of CPNE1 was characterized by high immune infiltration levels, increased expression levels of CD8+ T cell exhaustion markers (CTLA4, PDCD1 and LAG3) and worse response to immunotherapy. In vitro functional studies demonstrated that CPNE1 promoted proliferation, migration and invasion of ccRCC cells through EGFR/STAT3 pathway. Conclusion: CPNE1 is a reliable clinical predictor for the prognosis of ccRCC and promotes proliferation and migration by activating EGFR/STAT3 signaling. Moreover, CPNE1 significantly correlates with immune infiltration in ccRCC.


Anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis exhibit three clinical phenotypes with different prognoses.
We aimed to identify different subtypes of dermatomyositis (DM) patients positive with anti-melanoma differentiation-associated gene 5 antibody (DM-MDA5+) for customised treatments to improve the outcomes. Among 96 DM-MDA5+ patients, subgroups with similar phenotypes were delineated using hierarchical clustering analysis of the clinico-biological characteristics. Classification and regression trees were used to build a classification model and survival analysis was used to evaluate the prognoses of subgroups. Three subgroups were identified among 96 DM-MDA5+ patients, and patients in different subgroups had highly heterogenic manifestations and outcomes. Cluster 1 patients were referred to as mild group of rheumatologic patterns with good prognosis. Cluster 2 patients were referred to as young typical DM group with good prognosis. Cluster 3 patients were referred to as elderly rapidly progressive interstitial lung disease (RPILD) group with poor prognosis. A predictive model to classify patients was established, and three critical factors were found, including age, serum ferritin and myalgia. DM-MDA5+ patients have a poor short-term prognosis. Three clinical phenotypes with different prognoses were identified in DM-MDA5+ patients.


Fabrication and Hemocompatibility Evaluation of a Robust Honeycomb Nanostructure on Medical Pure Titanium Surface.
Thrombosis induced by blood-contacting medical devices is still a major clinical problem, resulting in some serious complications such as infarction, irreversible tissue damage, and even death. Therefore, seeking an effective and safe surface modification approach to improve the hemocompatibility of the material is still urgent. In this research, a novel and facile approach was proposed to fabricate a robust honeycomb nanostructure on medical pure titanium surface by two-step anodic oxidation, which effectively enhanced the physicochemical performance and hemocompatibility of the material. Especially, the honeycomb nanostructure that underwent annealing treatment at 500 °C (HN-Ti-500 °C) presented significant performance to suppress the coagulation cascade in the in vitro tests, the reason mainly ascribed to an overall repulsive interaction between the protein molecule related to thrombosis and material surface based on an extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory analysis. Furthermore, a vessel stent fabricated by HN-Ti-500 °C was implanted into the left carotid artery of rabbits for 1 month. The antithrombotic mechanism and biocompatibility of the modified surface were further verified. The results presented that no thrombus generated and adhered onto the inner surface of the modified stent, and no obvious disorder hyperplasia and inflammation were observed in the intima tissue of the vessel at the implantation site, which indicated that the modified surface could effectively decrease the risk of in-stent restenosis and thrombosis. This work offers a promising strategy for surface modification of blood-contacting medical titanium material to address the clinical complications associated with restenosis and thrombosis.


[Down-regulation of SOCS3 expression by methylation correlates with lymph node metastases of NSCLCs.].
It has been proven that suppressor of cytokine signaling 3 (SOCS3) contributes to inhibition of cell overgrowth, induction of apoptosis and stabilization. In the present study, we addressed the SOCS3 expression in non-small cell lung cancer (NSCLC) and explored the relationship between SOCS3 expression and lymph node metastases as well as clinicopathological characteristics in lung cancer patients. Western blotting analysis was used to examine the expression of SOCS3 in 30 NSCLCs and non-tumor tissues. The methylated status of SOCS3 gene was determined by methylation-specific PCR (MSP) assay in the same 30 samples. Immunohistochemical staining was applied to determine SOCS3 expression in 90 NSCLC sections and the correlation of SOCS3 expression with lymph node metastases and clinicopathological characteristics was also analyzed. SOCS3 expression was much lower in 30 NSCLCs than tnat in non-tumorous counterparts of the same case (optical density were 26.3+/-12.3 and 78.4+/-14.5 respectively, P =0.000) by western blotting analysis. MSP showed that the methylated rate of SOCS3 gene was (20/30) 66.7% in NSCLCs, and (4/30) 13.3% in non-tumors, and SOCS3 expression was negatively correlated with methylation (r =-0.454,P =0.012). Furthermore, SOCS3 expression was observed in non-tumorous epithelial cells by immunohistochemiscal analysis, and the positive rate of SOCS3 expression in 90 NSCLC samples was (41/90) 45.6%. SOCS3 expression rate was lower in NSCLCs with lymph node metastases (35.4%) compared with non-metastatic NSCLCs (57.1%, P =0.039), and in NSCLCs of stage III (36.4%) than in stage I+II (60.0%, P =0.028). SOCS3 expression was not correlated with histological type or differentiation (P >0.05). The results of this study suggest that Downregulation of SOCS3 expression in NSCLC associated with methylation might be correlated with lymph node metastases as well as clinicopathological stage of NSCLCs.


Molecular Alterations and Everolimus Efficacy in Human Epidermal Growth Factor Receptor 2-Overexpressing Metastatic Breast Cancers: Combined Exploratory Biomarker Analysis From BOLERO-1 and BOLERO-3.
Two recent phase III trials, BOLERO-1 and BOLERO-3 (Breast Cancer Trials of Oral Everolimus), evaluated the addition of everolimus to trastuzumab and chemotherapy in human epidermal growth factor receptor 2-overexpressing advanced breast cancer. The current analysis aimed to identify biomarkers to predict the clinical efficacy of everolimus treatment. Archival tumor samples from patients in BOLERO-1 and BOLERO-3 were analyzed using next-generation sequencing, immunohistochemistry, and Sanger sequencing. Biomarker data were available for 549 patients. PIK3CA activating mutations and PTEN loss were reported in 30% and 16% of BOLERO-1 samples and in 32% and 12% of BOLERO-3 samples, respectively. PI3K pathway was hyperactive (PIK3CA mutations and/or PTEN loss and/or AKT1 mutation) in 47% of BOLERO-1 and 41% of BOLERO-3 samples. In both studies, differential progression-free survival (PFS) benefits of everolimus were consistently observed in patient subgroups defined by their PI3K pathway status. When analyzing combined data sets of both studies, everolimus was associated with a decreased hazard of progression in patients with PIK3CA mutations (hazard ratio [HR], 0.67; 95% CI, 0.45 to 1.00), PTEN loss (HR, 0.54; 95% CI, 0.31 to 0.96), or hyperactive PI3K pathway (HR, 0.67; 95% CI, 0.48 to 0.93). Patients with wild-type PIK3CA (HR, 1.10; 95% CI, 0.83 to 1.46), normal PTEN (HR, 1.00; 95% CI, 0.80 to 1.26), or normal PI3K pathway activity (HR, 1.19; 95% CI, 0.87 to 1.62) did not derive PFS benefit from everolimus. This analysis, although exploratory, suggests that patients with human epidermal growth factor receptor 2-positive advanced breast cancer having tumors with PIK3CA mutations, PTEN loss, or hyperactive PI3K pathway could derive PFS benefit from everolimus.


Plasma amino acid levels with a note on membrane transport: characteristics, regulation, and metabolic significance.
The plasma concentration of an amino acid (AA) is the result of its rates of appearance (Ra) in and disappearance (Rd) from plasma. As for most nutrients, AA Ra and Rd are tightly regulated and at the postabsorptive state Ra equals Rd. Factors controlling Ra are protein intake and tissue release; those controlling Rd are tissue uptake and body losses (urine, sweat, etc.). Regulation of plasma AA concentrations involves hormones, in particular insulin and glucagon, both of which induce hypoaminoacidemia (but for quite different reasons), and cortisol, which induces hyperaminoacidemia. In addition, in pathologic states, catecholamines, thyroid hormones, and cytokines modulate plasma AA levels. Peripheral availability of AAs after protein ingestion is controlled by the liver, with an activation of ureagenesis in hyperprotein feeding and repression during a hypoprotein diet. The arginine-to-citrulline pathway in the intestine plays a key role in this adaptative process. In some circumstances tissue uptake of AAs and further metabolism depend on plasma AA concentrations. Plasma glutamine level may be the driving force controlling the flux of this AA at the muscle level. Also, channeling of the arginine cellular pathways means that plasma arginine is a major controlling component of nitric oxide synthesis in endothelial and immune cells. All these features explain the excessive increase in glutamine and arginine demands, in particular for energy expenditure, leading to morbidity (e.g., gut atrophy, muscle wasting, and immune dysfunction) in stressed patients. Normoaminoacidemia is not synonymous with health because this state is observed in level 2 starvation (Ra and Rd decrease) or after minor injury (Ra and Rd increase). Hyperaminoacidemia may be the consequence of organ failure (Rd decreases) or excessive AA intake during parenteral nutrition (Ra increases). Hypoaminoacidemia is observed after organ removal (Ra decreases, e.g., decrease in citrulline concentration in short bowel syndrome) or in stress situations (Rd increases). Mere determinations of plasma AA concentrations at the basal state (i.e., postabsorptive) provide rather limited information. Their usefulness can be improved by measuring arteriovenous differences or performing time course measurements, but techniques based on stable isotopes are necessary to obtain more precise information on the behavior of a particular AA or group of AAs.


Proline-rich tyrosine kinase-2 activation by beta 1 integrin fibronectin receptor cross-linking and association with paxillin in human natural killer cells.
Recent evidence indicates that integrin ligation results in activation of focal adhesion kinase (pp125FAK), the prototype of a new subfamily of nonreceptor protein tyrosine kinase (PTK), including FAKB and the proline-rich tyrosine kinase 2 (PYK-2), also termed cell adhesion kinase-beta or related adhesion focal tyrosine kinase. We have previously shown that cross-linking of alpha 4 beta 1 and alpha 5 beta 1 fibronectin receptors on human NK cells stimulates tyrosine phosphorylation of two proteins migrating at 105 and 115 kDa. Here we report that cross-linking of beta 1 integrins on human NK cells stimulates tyrosine phosphorylation and PTK activity of PYK-2. PYK-2 tyrosine phosphorylation was maximal at 1 min and started to decline 20 min after stimulation. Engagement of alpha 4 beta 1 and alpha 5 beta 1 either with specific mAbs or after cell adhesion to fibronectin or its 120- and 40-kDa fragments also triggered PYK-2 tyrosine phosphorylation. Stimulation of PYK-2 tyrosine phosphorylation was inhibited by the tyrosine kinase inhibitor herbimycin A, but not by EGTA, indicating that PYK-2 tyrosine phosphorylation is PTK, but not calcium, dependent. We also demonstrate that PYK-2 is constitutively associated with paxillin, which undergoes tyrosine phosphorylation with the same kinetics of PYK-2 upon beta 1 integrin ligation.


Antimalarial, antiplasmodial and analgesic activities of root extract of Alchornea laxiflora.
Alchornea laxiflora (Benth.) Pax. & Hoffman (Euphorbiaceae) root decoctions are traditionally used in the treatment of malaria and pain in Nigeria. To assess the antimalarial, antiplasmodial and analgesic potentials of root extract and fractions against malarial infections and chemically-induced pains. The root extract and fractions of Alchornea laxiflora were investigated for antimalarial activity against Plasmodium berghei infection in mice, antiplasmodial activity against chloroquine sensitive (Pf 3D7) and resistant (Pf INDO) strains of Plasmodium falciparum using SYBR green assay method and analgesic activity against experimentally-induced pain models. Acute toxicity study of the extract, cytotoxic activity against HeLa cells and GCMS analysis of the active fraction were carried out. The root extract (75-225 mg/kg, p.o.) with LD50 of 748.33 mg/kg exerted significant (p < 0.05-0.001) antimalarial activity against P. berghei infection in suppressive, prophylactive and curative tests. The root extract and fractions also exerted moderate activity against chloroquine sensitive (Pf 3D7) and resistant (Pf INDO) strains of P. falciparum with the ethyl acetate fraction exerting the highest activity with IC50 value of 38.44 ± 0.89 μg/mL (Pf 3D7) and 40.17 ± 0.78 μg/mL (Pf INDO). The crude extract was not cytotoxic to HeLa cells with LC50 value >100 μg/mL. The crude extract and ethyl acetate fraction exerted significant (p < 0.05-0.001) analgesic activity in all pain models used. These results suggest that the root extract/fractions of A. laxiflora possess antimalarial, antiplasmodial and analgesic potentials and these justify its use in ethnomedicine to treat malaria and pain.


[Determination of U, Th and Tl in fourteen Chinese traditional medicines by microwave digestion-ICP-MS].
Fourteen Chinese traditional medicines were digested by microwave digestion, which are generally applied to treat tumor in clinic, and the contents of U, Th and Tl in the fourteen Chinese traditional medicines were determined by inductively coupled plasma mass spectrometry (ICP-MS), and the results show that the change ranges of the elements contents were: 0.005 153-0.1534 microg x g(-1) for U; 0.03501-0.4628 microg x g(-1) for Th; 0.00143-1.600 microg x g(-1) for Tl. The contents of U, Th and Tl in the fourteen Chinese traditional medicines were low, and not with one accord. The determination results of the fourteen Chinese traditional medicines were analyzed by SPSS 11.5, and the results show that there were not significant deviations(p>0.05) of the contents of U, Th and Tl between the medicine of treating the toxifying disease with poisonous agents and the medicines of heat-clearing. The study indicates that inductively coupled plasma mass spectrometry (ICP-MS) is a quick, accurate, sensitive method to determine the contents of U, Th and Tl in Chinese traditional medicine, and the results of this study provide reference data for using Chinese traditional medicine safely in clinic and developing Chinese traditional medicine.


[Psychopathological symptoms and personality traits in young adult cannabis-dependent treatment seekers: A comparative study].
The aim of this paper was to describe the psychopathological and personality profile associated with cannabis dependence in young adults and to compare it with those of non-addictive disorders and the normal population. The sample consisted of 141 cannabis-dependent subjects attending a psychiatric outpatient clinic, 140 psychiatric patients with non-addictive disorders and 140 subjects from the general population chosen to match the patient samples for age, gender and socioeconomic level. All participants were assessed with different instruments related to personality (Impulsiveness Scale, Sensation-Seeking Scale and STAI) and psychopathology (SCL-90-R, BDI, STAI and Inadaptation Scale). Patients from the clinical groups presented more anxiety and depression symptoms than healthy participants, and had more problems adjusting to everyday life, but there were no differences between the two clinical groups. Cannabis-dependent patients were specifically characterized by low educational level and by the presence of paranoid ideation; they were also more impulsive and sensation-seeking than those from the other two groups. We discuss the implications of this study for clinical practice and for further research.


DnaX complex of Escherichia coli DNA polymerase III holoenzyme. The chi psi complex functions by increasing the affinity of tau and gamma for delta.delta' to a physiologically relevant range.
An artificial operon that contains tandem holC-holD genes was used to overproduce a complex of the chi and psi subunits of the DNA polymerase III holoenzyme. Normally insoluble by itself, psi forms a tight soluble complex with chi. A purification procedure that yields pure, active chi psi complex in 100-mg quantities suitable for biophysical studies is reported. Sedimentation equilibrium studies demonstrate that chi psi is a 1:1 heterodimer. The presence of chi psi dramatically lowers the level of delta.delta' required to reconstitute holoenzyme to levels expected in vivo. That chi psi accomplishes this by binding to gamma or tau and increasing their affinity for delta.delta' was demonstrated by surface plasmon resonance using a Pharmacia BIA-core instrument. In the absence of delta.delta', chi psi binds to either the gamma or tau DnaX protein with Kd = 2 nM.


Meta-Analysis on the Association of ALDH2 Polymorphisms and Type 2 Diabetic Mellitus, Diabetic Retinopathy.
Type 2 diabetic mellitus (T2DM) is a disease with high prevalence and a major cause for death worldwide. Diabetic retinopathy (DR) is one of the major manifestation of diabetes. Aldehyde dehydrogenease 2 (ALDH2) detoxifies aldehyde produced during ethanol metabolism and oxidative stress. It has been found that the polymorphism in ALDH2 rs671 is probably associated with the risk of T2DM and DR. However, a lot of inconsistency and controversy still exists. In order to get a more precise and comprehensive estimation for the association between ALDH2 polymorphism with the risk of T2DM and DR, we conducted the present meta-analysis. A comprehensive literature search was conducted using databases, such as Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Database, for all related studies. The included studies met the inclusion criteria, such as being case-control studies about the association of ALDH2 polymorphism and T2DM or DR susceptibility, with sufficient data for the present analysis. Eight studies with 2374 cases and 6694 controls were involved in the present meta-analysis. The results indicated a significant lower risk of T2DM for *1/*1 genotype in homozygous models (*1/*1 vs. *2/*2, OR = 0.31, 95% CI = 0.11-0.89, p = 0.03) and in the dominant model (*1/*1 vs. *2/*2 + *1/*2, OR = 0.61, 95% CI = 0.37-1.00, p = 0.05). Subgroup analysis by ethnicity found a significant lower risk of T2DM in Chinese in all genotype models. No significant relation was found between ALDH2 rs671 and DR. In conclusion, the current meta-analysis indicated that ALDH2 rs671 was significantly related with T2DM. The ALDH2 rs671 might be able to be used as a predictor for the risk of T2DM. However, due to the existence of heterogeneity and publication bias in the involved studies, our results should be interpreted with caution.


Ultrasonic evaluation of superficial temporal artery-middle cerebral artery anastomosis.
Ultrasonic Doppler studies were made pre- and postoperatively in 22 patients undergoing STA-MCA anastomosis. A quantitative evaluation of the bypass was attempted by determining the STA blood flow velocity and pattern. The STA velocity on the Doppler sonogram was compared with the degree of intracranial vascular filling via anastomotic channels and the STA diameter on angiogram. The STA velocity was increased and the blood flow pattern of STA altered from an external carotid pattern to an internal carotid pattern in a patent bypass. The results were in good agreement with angiographic findings. The are of intracranial vascular filling via a vewly formed bypass on angiogram was proportional to the increase in STA velocity. As the STA diameter enlarged, the STA velocity increased progressively. It is suggested the Doppler flowmetry is reliable as a semi-quantitative means of evaluationg the STA-MCA anastomosis.


[Endoplasmic reticulum stress and angiogenesis].
The endoplasmic reticulum is a dynamic intracellular organelle with exquisite sensitivity to alterations in homeostasis, and provides stringent quality control systems to ensure that the only correctly folded proteins transit to the Golgi and unfolded or misfolded proteins are retained and ultimately degraded. The endoplasmic reticulum stress represents the unfolded protein response to cope with the accumulation of unfolded or misfolded proteins and is required to maintain the functional integrity of the endoplasmic reticulum. The endoplasmic reticulum stress is a fundamental phenomenon which provides a secure protection of the cells from different factors. This stress provides a wide spectrum of physiological roles in diverse developmental and metabolic processes, especially for professional secretory cells with high-level secretory protein synthesis, such as pancreatic beta cells, hepatocytes and osteoblasts and is required throughout the entire life. The endoplasmic reticulum stress and hypoxia are the obligate components of malignant tumor growth, are interconnected and activate angiogenesis via growth and metabolism control. The endoplasmic reticulum stress is mediated by three by three sensor and signaling pathways (PERK, ATF6 and ERN1), besides that blockade one (ERN1) leads to a decrease of tumor growth through suppression of angiogenesis and proliferation. The data concerning the interaction of signaling enzyme ERN1 and pro- and anti-angiogenic gene expressions is analyzed.


Physical Activity Drops During Summer Holidays for 6- to 9-Year-Old Children.
Regular physical activity (PA) reduces the health risk of childhood obesity and associated chronic diseases as well as mental health problems. Since PA declines as children age as well with future generations it is of highest importance to intervene in school and out-of-school settings. Out-of-school periods affect children's PA as it is mainly left to the interest and motivation of their parents. We compared accelerometer-based PA patterns in 93 6- to 9-year old children assessed four times: before (May/June), during (August), and after (September) summer holidays and at a 1-year follow up (May/June). Before summer holidays children were assessed also for anthropometry and motor tests. During summer holidays overall PA decreased by 18% (p < 0.001), physical inactivity increased by 5.5% (p < 0.001), moderate PA decreased by 53% (p < 0.001) and moderate to vigorous PA decreased by 45% (p < 0.001) when compared to before summer holidays. Furthermore, overall PA remained diminished also after summer holidays by 8.8% (p = 0.001) but recovered to baseline values at 1-year follow up. About 30% of overall PA and moderate to vigorous PA decrease during summer holidays could be explained by children's fitness level as a greater decrease was found in children with better results in standing long jump and 300-meter running time. Our finding detects an alarming summer holiday decrease in children PA that should not be neglected in future studies and intervention designs.


Effects of environmental tobacco smoke on the respiratory health of adults.
In this paper, current knowledge on the respiratory effects of environmental tobacco smoke among adults is synthesized, and the biological basis and methodological issues are discussed. The Medline database was searched from 1966 through October 2000. All of the related respiratory effects have been linked to both home and workplace exposures. Some evidence of a dose-response relation has also been detected for all respiratory conditions. The strongest evidence of a causal relation exists for chronic respiratory symptoms. Harmful effects on lung function have also been detected, mainly in countries and occupations with high exposure levels. There is limited evidence indicating an increased risk of its causing asthma and chronic obstructive pulmonary disease, and also for poor control of established asthma. More longitudinal studies with careful assessment of exposure are needed for better risk estimates. Despite these challenges for the future, the combination of toxicologic evidence, abundant evidence on respiratory effects among children, and the studies reviewed in this paper point to an urgent need for measures to prevent exposure to environmental tobacco smoke among adults.


Arthroscopic repair of massive rotator cuff tears: outcome and analysis of factors associated with healing failure or poor postoperative function.
Many patients with an unhealed cuff after repair show functional improvement. To evaluate outcomes of arthroscopically repaired massive rotator cuff tears and to identify prognostic factors affecting rotator cuff healing and functional outcome, especially in patients with failed rotator cuff healing. Case series; Level of evidence, 4. Among 173 patients who underwent arthroscopic repair of a massive rotator cuff tear, 108 patients with a mean age of 63.7 years were included. Outcome evaluation was completed both anatomically (CT arthrography or ultrasonography) and functionally at a minimum of 1 year postoperatively; mean follow-up period was 31.68 ± 15.81 months. Various factors affecting cuff healing were analyzed, and factors affecting functional outcome were evaluated in patients with failed repairs using both univariate and multivariate analyses. The anatomic failure rate was 39.8% in arthroscopically repaired massive rotator cuff tears; however, functional status significantly improved regardless of cuff healing (P < .05). Several factors were associated with failure of cuff healing in the univariate analysis, but only fatty infiltration (FI) of the infraspinatus was significantly related to healing failure in the multivariate analysis (P = .04). Among patients with failed rotator cuff healing, only reduced postoperative acromiohumeral distance (AHD) was related to poor functional outcome in the multivariate analysis (P = .01), with a cutoff value of 4.1 mm. Despite a high rate of healing failures, arthroscopic repair can be recommended in patients with massive rotator cuff tears because of the functional gain at midterm follow-up. Higher FI of the infraspinatus was the single most important factor negatively affecting cuff healing. In cases of failed massive rotator cuff repair, no preoperative factor was able to predict poor functional outcome; reduced postoperative AHD was the only relevant functional determinant in the patients' eventual functional outcome and should be considered when ascertaining a prognosis and planning further treatment strategies.


Heteromeric double helix formation by cross-hybridization of chloro-and fluoro-substituted quinoline oligoamides.
Oligoamides of 8-chloroquinoline have been synthesized and shown to assemble into double helical dimers both in solution and in the solid state, and to undergo cross-hybridization with 8-fluoroquinoline oligoamide analogues; the handedness of these double helices can be controlled via chiral residues.


A novel dose constraint to reduce xerostomia in head-and-neck cancer patients treated with intensity-modulated radiotherapy.
To investigate the predictors of incidence and duration of xerostomia (XT) based on parotid glands (PG), submandibular glands (SMG), and both glands taken as a whole organ (TG) in head-and-neck cancer patients treated with intensity-modulated radiotherapy. A prospective study was initiated in May 2003. Sixty-three head-and-neck patients (44 with nasopharynx cancer) were included in the analysis. Using the dose-volume histogram the PG, SMG, and TG mean doses were calculated. Unstimulated and stimulated salivary flow were measured and XT-related questionnaires were compiled before and at 3, 6, 12, 18, and 24 months after radiotherapy. Salivary gland toxicity was evaluated using the Radiation Therapy Oncology Group scale, and Grade >or=3 toxicity was used as the endpoint. The XT incidence was investigated according to descriptive statistics and univariate and multivariate analysis. The Bonferroni method was used for multiple comparison adjustment. After a reduced flow at 3 months after radiotherapy, recovery of salivary flow was observed over time. Primary site and salivary gland mean doses and volumes were identified in univariate analysis as prognostic factors. Multivariate analysis confirmed that TG mean dose (p = 0.00066) and pretreatment stimulated salivary flow (p = 0.00420) are independent factors for predicting XT. The TG mean dose correlates with XT as assessed by Radiation Therapy Oncology Group criteria, salivary output, and XT-related questionnaires. Our results suggest that TG mean dose is a candidate dose constraint for reducing XT, requiring considerably more validation in non-nasopharyngeal cancer patients.


Meta-USR: A Unified Super-Resolution Network for Multiple Degradation Parameters.
Recent research on single image super-resolution (SISR) has achieved great success due to the development of deep convolutional neural networks. However, most existing SISR methods merely focus on super-resolution of a single fixed integer scale factor. This simplified assumption does not meet the complex conditions for real-world images which often suffer from various blur kernels or various levels of noise. More importantly, previous methods lack the ability to cope with arbitrary degradation parameters (scale factors, blur kernels, and noise levels) with a single model. A few methods can handle multiple degradation factors, e.g., noninteger scale factors, blurring, and noise, simultaneously within a single SISR model. In this work, we propose a simple yet powerful method termed meta-USR which is the first unified super-resolution network for arbitrary degradation parameters with meta-learning. In Meta-USR, a meta-restoration module (MRM) is proposed to enhance the traditional upscale module with the capability to adaptively predict the weights of the convolution filters for various combinations of degradation parameters. Thus, the MRM can not only upscale the feature maps with arbitrary scale factors but also restore the SR image with different blur kernels and noise levels. Moreover, the lightweight MRM can be placed at the end of the network, which makes it very efficient for iteratively/repeatedly searching the various degradation factors. We evaluate the proposed method through extensive experiments on several widely used benchmark data sets on SISR. The qualitative and quantitative experimental results show the superiority of our Meta-USR.


Functional diversity buffers the effects of a pulse perturbation on the dynamics of tritrophic food webs.
Biodiversity decline causes a loss of functional diversity, which threatens ecosystems through a dangerous feedback loop: This loss may hamper ecosystems' ability to buffer environmental changes, leading to further biodiversity losses. In this context, the increasing frequency of human-induced excessive loading of nutrients causes major problems in aquatic systems. Previous studies investigating how functional diversity influences the response of food webs to disturbances have mainly considered systems with at most two functionally diverse trophic levels. We investigated the effects of functional diversity on the robustness, that is, resistance, resilience, and elasticity, using a tritrophic-and thus more realistic-plankton food web model. We compared a non-adaptive food chain with no diversity within the individual trophic levels to a more diverse food web with three adaptive trophic levels. The species fitness differences were balanced through trade-offs between defense/growth rate for prey and selectivity/half-saturation constant for predators. We showed that the resistance, resilience, and elasticity of tritrophic food webs decreased with larger perturbation sizes and depended on the state of the system when the perturbation occurred. Importantly, we found that a more diverse food web was generally more resistant and resilient but its elasticity was context-dependent. Particularly, functional diversity reduced the probability of a regime shift toward a non-desirable alternative state. The basal-intermediate interaction consistently determined the robustness against a nutrient pulse despite the complex influence of the shape and type of the dynamical attractors. This relationship was strongly influenced by the diversity present and the third trophic level. Overall, using a food web model of realistic complexity, this study confirms the destructive potential of the positive feedback loop between biodiversity loss and robustness, by uncovering mechanisms leading to a decrease in resistance, resilience, and potentially elasticity as functional diversity declines.


Nocturnal respiratory rate as a predictor of mortality in patients with acute coronary syndrome.
Patients with acute coronary syndrome (ACS) are at risk especially in the period shortly after the event. Alterations in respiratory control have been associated with adverse prognosis. The aim of our study was to assess if the nocturnal respiratory rate (NRR) is a predictor of mortality in patients with ACS presenting in the emergency department. Clinically stable consecutive patients with ACS aged ≥ 18 years were prospectively enrolled. The Global Registry of Acute Coronary Events (GRACE) score and left ventricular ejection fraction (LVEF) were assessed for all patients. The average NRR over a period of 6 hours was determined by the records of the surveillance monitors in the first night after admission. Primary and secondary endpoints were intrahospital and 2 years all-cause mortality, respectively. Of the 860 patients with ACS, 21 (2.4%) died within the intrahospital phase and 108 patients (12.6%) died within the subsequent 2 years. The NRR was a significant predictor of both endpoints and was independent from the GRACE score and LVEF. Implementing the NRR into the GRACE risk model leads to a significant increase of the C-statistics especially for prediction of intrahospital mortality. The NRR is an independent predictor of mortality in patients with ACS.


Early identification and intervention services for children with autism in Vietnam.
In high income countries in Europe and North America, early identification and intervention for autism spectrum disorders (ASD) have been linked to improved long-term outcomes. However, in most low and middle income countries (LMIC) little is known about use or availability of such services, which limits the ability of policy and development planning. The purpose of the present study was assess the use of ASD services in Vietnam, an Asian LMIC, in order to identify areas within the field that should be specifically targeted to improve ASD services in Vietnam. Surveys were conducted in six different cities across Vietnam with 90 parents/caregivers of children with ASD, 115 professionals working with children with ASD, and 10 directors of agencies providing ASD services. Parents/caregivers' survey assessed demographics and information regarding their child's symptoms and services the child received. Professionals' survey assessed their demographic and professional background, the ASD services they provide, and their perspective on the quality of ASD services at their agency. Directors' survey included these same questions as well as additional questions regarding the operation of the agency. Early identification and intervention ASD services are available in Vietnam, at least in major cities. However, there is a lack of well-trained professionals, the tools used for evaluation and diagnosis are limited, outdated and unstandardized, and the quality of services is questionable. Most importantly, a scientific evidence base for services is absent, and the country lacks an official governmental policy for supporting children with ASD. Research directly assessing the quality of ASD services in Vietnam is needed. Most centrally, efforts at facilitating governmental policy and support advocacy are needed to increase the likelihood that families and children with ASD will receive appropriate and effective services.


Design strategies for protein kinase inhibitors.
Deregulation of protein kinases due to mutation or overexpression is a hallmark of several diseases, for example, cancer, diabetes, inflammation and cardiovascular disorders. Consequently, there has been a growing interest in the discovery of protein kinase inhibitors as novel drugs. Here, we focus on key milestones and advances in protein kinase inhibitor drug discovery over the last year, with an emphasis on novel strategies such as targeting of single and multiple binding sites, inactive conformations of kinases, allosteric sites, regulatory domains and heat shock proteins. We will highlight recent developments for specific inhibitors in clinical studies for growth factor receptors, non-receptor tyrosine kinases and serine/threonine kinases.


The Postural Effect on the Memory of Manipulable Objects.
The grounded cognition approach posits the involvement of sensory-motor processes in the representation of knowledge. However, the functional impact of these processes on cognition has been questioned, and some authors have explored the effect of motor interference on memory to test causally this hypothesis. In a seminal study, Dutriaux and Gyselinck (2016) showed that keeping the hands behind the back during learning decreases the memory of manipulable objects, but not the memory of nonmanipulable objects. The aim of this paper is to shed light on the mechanism behind the effect of posture in memory observed by Dutriaux and Gyselinck. The present experiment replicated the posture manipulation during learning but asked participants to keep their hands behind the back during recall. Results showed a similar detrimental effect of the hands behind the back specific to manipulable objects. This shows that the mechanism behind this effect arises from postural interference rather than from a compatibility between the posture during learning and the posture during recall and adds new evidence in favor of the sensory-motor grounding of knowledge.


Block copolymer micelles with a dual-stimuli-responsive core for fast or slow degradation.
We report the design and demonstration of a dual-stimuli-responsive block copolymer (BCP) micelle with increased complexity and control. We have synthesized and studied a new amphiphilic ABA-type triblock copolymer whose hydrophobic middle block contains two types of stimuli-sensitive functionalities regularly and repeatedly positioned in the main chain. Using a two-step click chemistry approach, disulfide and o-nitrobenzyle methyl ester groups are inserted into the main chain, which react to reducing agents and light, respectively. With the end blocks being poly(ethylene oxide), micelles formed by this BCP possess a core that can be disintegrated either rapidly via photocleavage of o-nitrobenzyl methyl esters or slowly through cleavage of disulfide groups by a reducing agent in the micellar solution. This feature makes possible either burst release of an encapsulated hydrophobic species from disintegrated micelles by UV light, or slow release by the action of a reducing agent, or release with combined fast-slow rate profiles using the two stimuli.


Lifestyle and IVF Outcomes.
Whereas much has been written about the prognostic factors associated with outcomes of in vitro fertilization (IVF) such as female age, diagnosis, and ovarian reserve, relatively little attention has been devoted to patient-oriented lifestyles that may influence IVF outcomes. Patients are particularly interested in this topic because many patients wish to partner with their physicians and want to know specific behaviors to improve their chances of IVF success. This brief review is not intended as an exhaustive literature search of all possible lifestyles that may influence assisted reproductive outcome nor is it intended to be a comprehensive review of individual topics. It does give, however, a brief overview of a number of areas in which patient-specific behaviors may influence outcomes in assisted reproduction. Specifically, this review will look at the effects of smoking, alcohol consumption, caffeine, diet, exercise, and exposure to the reproductive toxin bisphenol A on IVF outcomes.