Regulation of IgE Responses by γδ T Cells.
Immunoglobulin E (IgE) antibodies play a crucial role in host defense against parasite infections. However, inappropriate IgE responses are also involved in the pathogenesis of allergic diseases. The generation of IgE antibodies is a tightly controlled process regulated by multiple transcription factors, cytokines, and immune cells including γδ T cells. Accumulating evidence demonstrates that γδ T cells play a critical role in regulating IgE responses; however, both IgE-enhancing and IgE-suppressive effects are suggested for these cells in different experimental systems. In this review, we examine the available evidence and discuss the role of γδ T cells in IgE regulation both in the context of antigen-induced immune responses and in the state of partial immunodeficiency.


Simultaneous determination of preservatives in soft drinks, yogurts and sauces by a novel solid-phase extraction element and thermal desorption-gas chromatography.
A novel solid-phase extraction element combined with thermal desorption-gas chromatography (TD-GC) using a pyrolysis-GC system was applied for the determination of the five preservatives - benzoic acid, sorbic acid, and methyl, ethyl and propyl esters of p-hydroxybenzoic acid - in soft drinks, yogurts and sauces. The extraction element is made of a titanium (Ti) tubing (30 mm x 1.2 mm i.d.x1.6 mm o.d.) coated with a chemically bonded layer of polydimethylsiloxane (PDMS) to a thickness of 500 microm. A sample pH of 2.0, sample volume of 5 ml, extraction time of 45 min with addition of salt (15% m/v NaCl) and TD temperature from 40 to 280 degrees C at a heating rate of 40 degrees Cmin(-1) and maintained at 280 degrees C for 9 min, were selected as optimum extraction and desorption conditions. The linearity of the method was satisfactory over a concentration range of 2-1000 mg L(-1) for benzoic acid and sorbic acid, 0.2-300 mg L(-1) for methyl ester of p-hydroxybenzoic acid, and 0.02-300 mg L(-1) for ethyl and propyl esters of p-hydroxybenzoic acid, and the correlation coefficients were higher than 0.997. The limit of detection ranged from 0.002 to 0.2 mg L(-1). The potential of the proposed method was assessed by applying it to the determination of preservatives in real samples. The recoveries (92-106%) and precisions (R.S.D.s of 0.9-4.6% (n=5)) of the method were examined by analyzing soft drink, yogurt and sauce samples spiked at levels of between 20 and 100 mg L(-1). This simple, accurate and highly sensitive method may be used in the determination of the preservatives in various water-based food samples.


Iron(III) Chloride Catalyzed Formation of 3,4-Dihydro-2H-pyrans from α-Alkylated 1,3-Dicarbonyls. Selective Synthesis of α- and β-Lapachone.
A mild, catalytic method for the synthesis of 3,4-dihydro-2H-pyrans is described. The FeCl3-catalyzed transformation of aryl- and alkyl β-diketones enables synthetic access to functionalized pyran core structures incorporated in many natural products and biologically active target structures. The method represents a mild alternative to currently available reaction protocols relying on stoichiometric reagents and harsh reaction conditions. This FeCl3-catalyzed transformation has enabled the selective synthesis of α-lapachone in two synthetic transformations and subsequently β-lapachone in three synthetic transformations, which is currently undergoing clinical trials as a potent anticancer agent.


Presaccadic spike potential: a computer model based upon motor unit recruitment patterns in the extraocular muscles.
Details are presented of a computer model of the presaccadic 'spike' potential based upon the discharge properties of motor units in the extraocular muscles. The model provides support for the hypothesis that the spike potential represents the summated electrical activity from the near-synchronous recruitment of motor units in the extraocular muscles by the presaccadic burst of motoneurone activity.


Feasibility and lessons learned on remote trial implementation from TestBoston, a fully remote, longitudinal, large-scale COVID-19 surveillance study.
Longitudinal clinical studies traditionally require in-person study visits which are well documented to pose barriers to participation and contribute challenges to enrolling representative samples. Remote trial models may reduce barriers to research engagement, improve retention, and reach a more representative cohort. As remote trials become more common following the COVID-19 pandemic, a critical evaluation of this approach is imperative to optimize this paradigm shift in research. The TestBoston study was launched to understand prevalence and risk factors for COVID-19 infection in the greater Boston area through a fully remote home-testing model. Participants (adults, within 45 miles of Boston, MA) were recruited remotely from patient registries at Brigham and Women's Hospital and the general public. Participants were provided with monthly and "on-demand" at-home SARS-CoV-2 RT-PCR and antibody testing using nasal swab and dried blood spot self-collection kits and electronic surveys to assess symptoms and risk factors for COVID-19 via an online dashboard. Between October 2020 and January 2021, we enrolled 10,289 participants reflective of Massachusetts census data. Mean age was 47 years (range 18-93), 5855 (56.9%) were assigned female sex at birth, 7181(69.8%) reported being White non-Hispanic, 952 (9.3%) Hispanic/Latinx, 925 (9.0%) Black, 889 (8.6%) Asian, and 342 (3.3%) other and/or more than one race. Lower initial enrollment among Black and Hispanic/Latinx individuals required an adaptive approach to recruitment, leveraging connections to the medical system, coupled with community partnerships to ensure a representative cohort. Longitudinal retention was higher among participants who were White non-Hispanic, older, working remotely, and with lower socioeconomic vulnerability. Implementation highlighted key differences in remote trial models as participants independently navigate study milestones, requiring a dedicated participant support team and robust technology platforms, to reduce barriers to enrollment, promote retention, and ensure scientific rigor and data quality. Remote clinical trial models offer tremendous potential to engage representative cohorts, scale biomedical research, and promote accessibility by reducing barriers common in traditional trial design. Barriers and burdens within remote trials may be experienced disproportionately across demographic groups. To maximize engagement and retention, researchers should prioritize intensive participant support, investment in technologic infrastructure and an adaptive approach to maximize engagement and retention.


Linkage of functional and structural heterogeneity in proteins: dynamic hole burning in carboxymyoglobin.
Inhomogeneous broadening of the 760-nanometer photoproduct band of carboxymyoglobin at cryogenic temperatures has been demonstrated with a dynamic hole burning technique. Line-shape changes and frequency shifts in this spectral band are generated by ligand recombination and are shown not to be the result of structural relaxation below 60 K. The observation of dynamic hole burning exposes the relation between the structural disorder responsible for the inhomogeneous broadening and the well-known distributed ligand rebinding kinetics. The findings provide direct evidence for the functional relevance of conformational substrates in myoglobin rebinding. In addition, a general protocol for evaluating the relative contributions of structural relaxation and hole burning to the spectral changes accompanying rebinding in hemeproteins is presented.


Inpatient and outpatient opioid requirements after total joint replacement are strongly influenced by patient and surgical factors.
Currently, there is no single, comprehensive national guideline for analgesic strategies for total joint replacement. We compared inpatient and outpatient opioid requirements following total hip arthroplasty (THA) versus total knee arthroplasty (TKA) in order to determine risk factors for increased inpatient and outpatient opioid requirements following total hip or knee arthroplasty. Outcomes after 92 primary total knee (n = 49) and hip (n = 43) arthroplasties were analyzed. Patients with repeat surgery within 90 days were excluded. Opioid use was recorded while inpatient and 90 days postoperatively. Outcomes included total opioid use, refills, use beyond 90 days, and unplanned clinical encounters for uncontrolled pain. Multivariate modelling determined the effect of surgery, regional nerve block (RNB) or neuraxial anesthesia (NA), and non-opioid medications after adjusting for demographics, ength of stay, and baseline opioid use. TKAs had higher daily inpatient opioid use than THAs (in 5 mg oxycodone pill equivalents: median 12.0 vs 7.0; p < 0.001), and greater 90 day use (median 224.0 vs 100.5; p < 0.001). Opioid refills were more likely in TKA (84% vs 33%; p < 0.001). Patient who underwent TKA had higher independent risk of opioid use beyond 90 days than THA (adjusted OR 7.64; 95% SE 1.23 to 47.5; p = 0.01). Inpatient opioid use 24 hours before discharge was the strongest independent predictor of 90-day opioid use (p < 0.001). Surgical procedure, demographics, and baseline opioid use have greater influence on in/outpatient opioid demand than RNB, NA, or non-opioid analgesics. Opioid use following TKA and THA is most strongly predicted by surgical and patient factors. TKA was associated with higher postoperative opioid requirements than THA. RNB and NA did not diminish total inpatient or 90-day postoperative opioid consumption. The use of acetaminophen, gabapentin, or NSAIDs did not significantly alter inpatient opioid requirements.Cite this article: Bone Joint Open 2020;1-7:398-404.


Polymeric structure of a cyclic adenosine 3', 5',-monophosphate dependent protein kinase from the dimorphic fungus Mucor rouXII.
Adenosine 3', 5'-monophosphate (cAMP) dependent protein kinase from yeast cells of Mucor rouxii was partially purified and examined by sedimentation in sucrose density gradients. In the presence of histone and cAMP this procedure allowed the separation of the catalytic moiety from the cAMP binding activity, indicating that the enzyme had dissociated into subunits. The dissociation was accompanied by conversion of the enzyme activity from a cAMP dependent to a cAMP independent form.


What Matters in Radiological Image Segmentation? Effect of Segmentation Errors on the Diagnostic Related Features.
Segmentation is a crucial step in extracting the medical image features for clinical diagnosis. Though multiple metrics have been proposed to evaluate the segmentation performance, there is no clear study on how or to what extent the segmentation errors will affect the diagnostic related features used in clinical practice. Therefore, we proposed a segmentation robustness plot (SRP) to build the link between segmentation errors and clinical acceptance, where relative area under the curve (R-AUC) was designed to help clinicians to identify the robust diagnostic related image features. In experiments, we first selected representative radiological series from time series (cardiac first-pass perfusion) and spatial series (T2 weighted images on brain tumors) of magnetic resonance images, respectively. Then, dice similarity coefficient (DSC) and Hausdorff distance (HD), as the widely used evaluation metrics, were used to systematically control the degree of the segmentation errors. Finally, the differences between diagnostic related image features extracted from the ground truth and the derived segmentation were analyzed, using the statistical method large sample size T-test to calculate the corresponding p values. The results are denoted in the SRP, where the x-axis indicates the segmentation performance using the aforementioned evaluation metric, and the y-axis shows the severity of the corresponding feature changes, which are expressed in either the p values for a single case or the proportion of patients without significant change. The experimental results in SRP show that when DSC is above 0.95 and HD is below 3 mm, the segmentation errors will not change the features significantly in most cases. However, when segmentation gets worse, additional metrics are required for further analysis. In this way, the proposed SRP indicates the impact of the segmentation errors on the severity of the corresponding feature changes. By using SRP, one could easily define the acceptable segmentation errors in a challenge. Additionally, the R-AUC calculated from SRP provides an objective reference to help the selection of reliable features in image analysis.


Zinc sulphate: A reasonable choice for depression management in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled clinical trial.
Major Depressive Disorder (MDD) is known as one of the most common psychiatric disorders in patients with multiple sclerosis (MS). In recent years, zinc has been found to have beneficial effects on psychopathology and the therapy of depression. The aim of the present study was to examine the effect of zinc supplement on depression and neurological signs in patients with MS. The present randomized, double-blind, placebo-controlled clinical trial was performed on 43 patients with MS and who also demonstrated MDD based on the Beck questionnaire. These patients were randomly selected and were divided into two groups: the placebo group (n=22) and the intervention group (n=21). The patients received either zinc sulphate (220 mg containing 50mg zinc element) or a placebo for 12 weeks. Clinical examinations were obtained in terms of abnormal ocular movement, muscle power, and gait disorder. The results indicated that in the patients who received the zinc supplement, the mean score of depression was reduced compared to those in the placebo group, whereas the neurological examinations revealed that there were no differences between the treatment and control groups. Therefore, the zinc supplementation is an appropriate choice for the depression management in patients with MS.


Autologous apoptotic cell engulfment stimulates chemokine secretion by vascular smooth muscle cells.
Apoptosis of vascular smooth muscle cells (VSMCs) occurs in vivo under both physiological and pathological settings. The clearance of apoptotic cells may be accomplished in part by the surrounding normal VSMCs. However, the fate of internalized apoptotic cells, the rate of intracellular degradation, and the consequences of these processes to VSMC biology are unknown. Electron microscopy and confocal fluorescence imaging showed that rat VSMCs effectively bound and internalized autologous apoptotic VSMCs in vitro. Within 2 hours, the internalized apoptotic cells were delivered to lysosomes, and the majority of these internalized cells and their proteins were efficiently degraded by 24 hours. After degradation was completed, the phagocytic VSMCs remained viable with normal rates of proliferation. Clearance of apoptotic cells by VSMCs did not induce the release of vascular wall matrix proteases but was associated with a 1.6-fold increase in transforming growth factor-beta1 release. Interestingly, clearance of apoptotic cells stimulated VSMCs to secrete monocyte-chemoattractant protein-1 and cytokine-induced neutrophil chemoattractant. The coordinated release of transforming growth factor-beta1 and chemokines suggests that autologous apoptotic cell clearance stimulates VSMCs to release molecules that specifically recruit professional phagocytes while simultaneously dampening the inflammatory response and preventing vascular injury.


Relationship of urethral retro-resistance pressure to urodynamic measurements and incontinence severity.
The urethral retro-resistance pressure (URP) is a retrograde urethral pressure profile measured by a new urodynamic measurement system.1GYNECARE MoniTorr Urodynamic Measurement System (ETHICON, Inc., Somerville, NJ). URP is the pressure required to achieve and maintain an open sphincter. This clinical investigation focused on a comparison of URP to standard urodynamic measurements and an examination of their relationship to incontinence severity. Twenty-two centers enrolled 258 stress incontinent women in a randomized, crossover study of two groups: (1) test procedure followed by multichannel urodynamics, (2) multichannel urodynamics followed by test procedure. We defined incontinence severity categories using 24 hr urine loss and assessed these categories using incontinence quality of life (I-QOL), urinary incontinence severity score (UISS), incontinence visual analogue score (VAS), URP, maximum urethral closure pressure (MUCP), and leak point pressure (LPP). The mean age was 56.2 (+/-12) years. No order effect was present. The correlation coefficient between URP and MUCP was 0.31 (95% CI 0.19-1, P < 0.0001); between URP and LPP was 0.28 (95% CI 0.12-1, P = 0.003); and between MUCP and LPP was 0.14 (95% CI-0.04-1, P = 0.101). The mean values for URP across symptom severity categories were significantly different (P = 0.028) and decreased with increasing severity. The mean values for MUCP and LPP did not decrease with increasing severity. The study demonstrated that URP had a consistent relationship with incontinence severity. The data suggested that URP is a physiological measure of urethral function and may have clinical utility as a diagnostic tool. Future outcomes-based research is necessary to establish the predictive value of URP, MUCP, and LPP measurements in terms of incontinence cure rates and diagnosis of sphincter dysfunction.


Distortions in the Balance Between Teaching and Efficiency in the Operating Room.
The balance between teaching and operative efficiency (i.e., continuing operative case progression) is difficult for even the most experienced master surgeon educators. The purpose of this study was to explore influencing factors behind attending surgeons' decisions to break the balance between operative efficiency and teaching in the operating room. Semistructured interviews were conducted with surgeons across the United States via Web-based video conferencing. The interviews were audio-recorded and transcribed. Qualitative analysis using the framework method was utilized, and emergent themes were identified. Twenty-three attending surgeons from 8 academic institutions and 11 surgical specialties completed interviews (14 men and 9 women). Attending surgeons consider a variety of factors associated with their dual roles (surgeon versus teacher) when balancing operative efficiency and providing appropriate independence for residents with oversight to promote autonomy. These were divided into surgeon-role-related factors (patient safety, financial factors, scheduling factors, preservation of faculty reputation for efficiency, and mode of operation) as well as teacher-role-related factors (preparation, level, and technical skill of the resident). These factors then informed attending surgeons' determinations about how the case was progressing, which prompted them to intervene and reduce resident autonomy or allow the resident to continue. Surgeons consider numerous factors when deciding how to balance resident teaching and autonomy while preserving operative efficiency. These findings provide helpful insights for surgical departments to consider inclusion in faculty-development programs, resident education, and systematic improvements.


Collective Effects of Band Offset and Wave Function Dimensionality on Impeding Electron Transfer from 2D to Organic Crystals.
Excited-state electron transfer (ET) across molecules/transition metal dichalcogenide crystal (TMDC) interfaces is a critical process for the functioning of various organic/TMDC hybrid optoelectronic devices. Therefore, it is important to understand the fundamental factors that can facilitate or limit the ET rate. Here it is found that an undesirable combination of the interfacial band offset and the spatial dimensionality of the delocalized electron wave function can significantly slow down the ET process. Specifically, it is found that whereas the ET rate from TMDCs (MoS2 and WSe2) to fullerenes is relative insensitive to the band offset, the ET rate from TMDCs to perylene molecules can be reduced by an order of magnitude when the band offset is large. For the perylene crystal, the sensitivity of the ET rate on the band offset is explained by the 1D nature of the electronic wave function, which limits the availability of states with the appropriate energy to accept the electron.


Formation of bicyclic pyrroles from the catalytic coupling reaction of 2,5-disubstituted pyrroles with terminal alkynes, involving the activation of multiple C-H bonds.
Substituted bicyclic pyrroles are produced directly from the coupling reaction of 2,5-disubstituted pyrroles with terminal alkynes, involving the activation of multiple C-H bonds and regioselective cyclisation.


Contaminant residues in seabird eggs from the Canadian Arctic. II. Spatial trends and evidence from stable isotopes for intercolony differences.
Eggs of glaucous gulls (Larus hyperboreus), black-legged kittiwakes (Rissa tridactyla), thick-billed murres (Uria lomvia) and black guillemots (Cepphus grylle) were collected from several sites throughout the Canadian Arctic. Samples were analyzed for organochlorines as well as mercury and selenium. Glaucous gulls breeding at sites in the High Arctic showed higher levels of organochlorine contamination than those in the western Low Arctic. This was likely due to dietary differences among colonies as suggested by stable isotope data, although different overwintering areas may also play a role. Levels of sigmaPCB, sigmaDDT, sigmaCHLOR, sigmaCBz and dieldrin were significantly lower in thick-billed murres from Prince Leopold Island in the High Arctic compared with colonies in the eastcrn Low Arctic. This difference was likely due to the combined effects of different atmospheric deposition patterns in the High and Low Arctic and different overwintering areas since murres from Prince Leopold Island may winter farther north than murres from the other colonies sampled. Eggs from colonies at higher latitudes generally contained higher concentrations of mercury. The trophic and dietary differences/similarities suggested by stable-nitrogen and carbon isotope data in this study were useful in explaining the spatial patterns of contaminant concentrations observed among colonies of seabirds such as the glaucous gull and the black-legged kittiwake where variation in latitudinal atmospheric deposition patterns and different overwintering grounds did not appear to be confounding factors.


Testosterone metabolites in dog bile.
Testosterone-1,2-3H was injected intravenously into a male dog with a bile fistula and bile and urine collected. The radioactivity was excreted preponderantly in bile (52% of the injected dose) in 6 hours; only 12% appeared in the urine. Methods to study the biliary metabolites of testosterone in this and other animals were developed. Satisfactory conjugate patterns were obtained by fractionation on DEAE-Sephadex A-25 columns using two different elution systems. In addition to an unchanged fraction, six different monoglucuronide fractions were separated. No other conjugates were isolated. Lipidex 5000 column chromatography, TLC and paper chromatography were used for the isolation and purification of aglycone metabolites, which were further identified by co-crystallization methods. The biliary metabolites of testosterone were epiandrosterone (3beta-hydroxy-5alpha-androstan-17-one), etiocholanlone (3alpha-hydroxy-5beta-androstan-17-one), 5alpha-androstan-3beta, 17beta-diol, 5beta-androstan-3alpha, 17beta-diol and 5beta-androstan-3beta,17beta-diol.


Origins of Wohlfahrtia magnifica in Italy based on the identification of mitochondrial cytochrome b gene haplotypes.
To identify the geographical origins of larvae of Wohlfahrtia magnifica (Diptera: Sarcophagidae) causing myiasis of sheep in Italy, comparative DNA sequence analysis of the mitochondrial cytochrome b gene was performed, based on gene fragments amplified by PCR from genomic DNA isolated from individual specimens. DNA extractions of 19 larvae from Lazio, Molise, Puglia, and Sicilia generated 17 readable sequences homologous to 2 haplotypes, either CB_magn01 or CB_magn02; DNA extracts from 4 adult flies from Calabria (reared from larvae) produced 4 readable sequences belonging to the haplotype CB_magn01. The two haplotypes found represent both the East and West phylogenetic lineages of W. magnifica, which is consistent with the species' arrival from central/southeast Europe (East lineage) and/or from southwest Europe/northwest Africa (West lineage). This is the first report of the sympatric occurrence of the two lineages, which could have resulted from natural or human-assisted dispersal. Polymorphic nuclear loci will have to be characterized in order to explain the origins and lack of mitochondrial haplotype diversity of this pest in Italy, where it poses increasing veterinary problems.


Achalasia: Diagnosis, Management and Surveillance.
Achalasia is a rare chronic esophageal motility disorder characterized by incomplete relaxation of the lower esophageal sphincter and abnormal peristalsis. This abnormal motor function leads to impaired bolus emptying and symptoms of dysphagia, regurgitation, chest pain, or heartburn. After an upper endoscopy to exclude structural causes of symptoms, the gold standard for diagnosis is high-resolution esophageal manometry. However, complementary diagnostic tools include barium esophagram and functional luminal impedance planimetry. Definitive treatments include pneumatic dilation, Heller myotomy with fundoplication, and peroral endoscopic myotomy.


Respiratory chain deficiencies.
Mitochondrial functions are intimately associated with neurological symptoms. Various clinical and biological features are suggestive of energy depletion diseases, such as Leigh syndrome, Alpers syndrome, epilepsy (including myoclonic seizures and status epilepticus), stroke-like episodes, and acute cerebellar ataxia with high lactate peaks on magnetic resonance spectroscopy. Magnetic resonance imaging (MRI) discloses abnormalities in over 90% of the cases presenting with neurological symptoms. Basal ganglionic involvement, the most frequent imaging sign, can be isolated or combined with subtentorial atrophy of both the cerebellum and brainstem. MRS monovoxel proton spectroscopy is useful to reveal high lactate spikes if placed in the putamen and the cerebellar dentate nucleus. Lactate and pyruvate levels are required to exclude pyruvate dehydrogenase deficiency. However, lactate may be normal in the CSF. Clinical and biochemical investigations guide molecular studies, with two major heredities: mtDNA point mutations and autosomal recessive defects that program the majority of respiratory chain subunits. Muscle biopsy is the first test demonstrating the histochemical and ultrastructural alterations in mitochondria, even in diseases in which myopathy is not clinically prominent, and is also a good tissue for biochemical analysis, as the biopsy is not dangerous for the patient. Negative results in skeletal muscle do not exclude respiratory chain deficiency, and a liver biopsy may be necessary whatever the blood AST and ALT levels, to perform biochemical and molecular investigations. Only the identification of nuclear or mitochondrial mutation confirms the diagnosis.


Ventricular tachycardia risk prediction with an abbreviated duration mobile cardiac telemetry.
Ventricular tachycardia (VT) occurs intermittently, unpredictably, and has potentially lethal consequences. Our aim was to derive a risk prediction model for VT episodes ≥10 beats detected on 30-day mobile cardiac telemetry based on the first 24 hours of the recording. We included patients who were monitored for 2 to 30 days in the United States using full-disclosure mobile cardiac telemetry, without any VT episode ≥10 beats on the first full recording day. An elastic net prediction model was derived for the outcome of VT ≥10 beats on monitoring days 2 to 30. Potential predictors included age, sex, and electrocardiographic data from the first 24 hours: heart rate; premature atrial and ventricular complexes occurring as singlets, couplets, triplets, and runs; and the fastest rate for each event. The population was randomly split into training (70%) and testing (30%) samples. In a population of 19,781 patients (mean age 65.3 ± 17.1 years, 43.5% men), with a median recording time of 18.6 ± 9.6 days, 1510 patients had at least 1 VT ≥10 beats. The prediction model had good discrimination in the testing sample (area under the receiver-operating characteristic curve 0.7584, 95% confidence interval 0.7340-0.7829). A model excluding age and sex had an equally good discrimination (area under the receiver-operating characteristic curve 0.7579, 95% confidence interval 0.7332-0.7825). In the top quintile of the score, more than 1 in 5 patients had a VT ≥10 beats, while the bottom quintile had a 98.2% negative predictive value. Our model can predict risk of VT ≥10 beats in the near term using variables derived from 24-hour electrocardiography, and could be used to triage patients to extended monitoring.


Morbidity of hepatic resection for intermediate and advanced hepatocellular carcinoma.
According to current treatment guidelines, surgical resection of hepatocellular carcinoma (HCC) is mostly restricted to a limited subgroup of patients. Due to improved surgical techniques and perioperative management, liver resections may also be performed more extendedly and also in cirrhotic livers with clinical signs of portal hypertension in selected patients. In this study, the clinical and long-term outcomes of liver resection in HCC patients with or without liver cirrhosis were evaluated. One hundred fifty-eight patients undergoing liver resection for primary HCC at our institution were identified. Logistic and Cox regression analyses were used to identify prognostic parameters for postoperative complications and survival. In our cohort of patients, there was no association between clinical parameters or extent of surgical resection and postoperative morbidity. Only Barcelona Clinic Liver Cancer (BCLC) stage C patients were at significantly higher risk for major complications (OR 5.27, P = 0.009). Risk factors influencing long-term survival were patient age (HR 1.026, P = 0.027) and BCLC stage C (HR 3.47, P = 0.002). Compared to patients without liver cirrhosis, BCLC stage A and B patients undergoing resection were at similar risk for the development of severe complications and long-term mortality. Liver resection as potentially curative therapy can be performed in selected patients in BCLC stage B, as well as in patients with clinical signs of portal hypertension. The resection of HCC-classified BCLC stage C is feasible but associated with significant morbidity and mortality.


Porcupine disturbances and vegetation pattern along a resource gradient in a desert.
In the Negev Desert, Israel, the Indian crested porcupine, Hystrix indica, digs similar sized, discrete, elongated pits (257±21.3 cm3; n=144) while foraging for below-ground plant storage organs. In these digs, soil moisture content is higher than in the surrounding soil matrix. The digs disturb population and community structure due to porcupine consumption or damage of 18 species of plants, and repopulation by 55 plant species. Over the past 14 years we have studied dig dynamics on a rocky hillslope with three distinct habitats as regards soil moisture content. Midslope soil moisture is the highest, decreasing towards upper and lower slope. We have counted a total of 6,609 digs in the area: 2141 on the upper, 3211 in the middle and 1257 on the lower part of the slope. The number of digs at midslope is significantly higher than on the other parts of the slope (ANOVA; P<0.0001). There is a significant (P<0.05) correlation between the mean number of porcupine digs and the cumulative rainfall amount for the 2 years prior to dig formation. To study plant repopulation in digs, all plants in 144 digs along the slope and from equal sized plots in the undistarbed soil matrix were collected. In all, 288 samples with 20 584 plants were collected, 2042 from the matrix and 18,542 from digs. Of the 55 species, we focused on the abundance patterns of Filago desertorum, Picris cyanocarpa and Bromus rubens, which made up 69.5% of all the individuals in the digs and 68.3% in the matrix. Our results showed that all three species increased in abundance in the digs as compared to the matrix. F. desertorum density increased by a factor of 2.9, P. cyanocarpa by 9.5 and B. rubens by 12.0. There were species-specific responses in abundance to the location of the digs along the moisture gradient. The only species whose abundance responded to the moisture gradient was F. desertorum. P. cyanocarpa demonstrated peak abundance in the location with the poorest moisture regime, while B. rubens showed peak abundance at the intermediate part of the moisture gradient. We suggest a scheme for integrating the increase in density and the species-specific responses to the digs along a water gradient based on R.H. Whittaker's view of individual species abundances along an environmental gradient.


Corrigendum to "Three-Dimensional Cobalt Hydroxide Hollow Cube/Vertical Nanosheets with High Desalination Capacity and Long-Term Performance Stability in Capacitive Deionization".
[This corrects the article DOI: 10.34133/2021/9754145.].


Basal Forebrain Cholinergic Innervation Induces Depression-Like Behaviors Through Ventral Subiculum Hyperactivation.
Malfunction of the ventral subiculum (vSub), the main subregion controlling the output connections from the hippocampus, is associated with major depressive disorder (MDD). Although the vSub receives cholinergic innervation from the medial septum and diagonal band of Broca (MSDB), whether and how the MSDB-to-vSub cholinergic circuit is involved in MDD is elusive. Here, we found that chronic unpredictable mild stress (CUMS) induced depression-like behaviors with hyperactivation of vSub neurons, measured by c-fos staining and whole-cell patch-clamp recording. By retrograde and anterograde tracing, we confirmed the dense MSDB cholinergic innervation of the vSub. In addition, transient restraint stress in CUMS increased the level of ACh in the vSub. Furthermore, chemogenetic stimulation of this MSDB-vSub innervation in ChAT-Cre mice induced hyperactivation of vSub pyramidal neurons along with depression-like behaviors; and local infusion of atropine, a muscarinic receptor antagonist, into the vSub attenuated the depression-like behaviors induced by chemogenetic stimulation of this pathway and CUMS. Together, these findings suggest that activating the MSDB-vSub cholinergic pathway induces hyperactivation of vSub pyramidal neurons and depression-like behaviors, revealing a novel circuit underlying vSub pyramidal neuronal hyperactivation and its associated depression.


[Action of aminazine and tisercin in a changed functional state of the body].
Experiments with rats evidenced that the pain-allaying and hypothermal action of chlorpromazine and tisercin (5 and 1 mg/kg) remains intact with an upset homeostasis against the background of a phlogogenic mixture and inflammation effect, though it becomes less potent. These drugs increase the higher permeability of the blood-histological barrier of the suprarenals caused by the stress (introduction of an irritating mixture) and inflammation.


Potentiating the activity of rituximab against mantle cell lymphoma in mice by targeting interleukin-2 to the neovasculature.
There is increasing interest in the site-directed pharmacodelivery of therapeutic payloads to the tumor site using antibodies as transport vehicles. Here, we investigated the efficacy of L19-IL2, an antibody-cytokine fusion protein that specifically delivers IL-2 to the tumor site by homing to the extra-domain B of fibronectin (EDB-Fn) expressed on tumor-associated blood vessels, against mantle cell lymphoma (MCL) in mice. L19-IL2 was shown to selectively localize at lymphoma lesions in vivo and to mediate significant lymphoma growth retardation, which was potentiated by co-administration of the anti-CD20 antibody rituximab. When co-injected with rituximab, L19-IL2 induced complete remissions of localized MCL xenografts in 6/8 mice (75%), whereas the combination of rituximab and equivalent doses of non-targeted IL-2 only slightly delayed tumor growth. In disseminated MCL, combination therapy with L19-IL2 and rituximab exhibited a significant survival benefit over treatment with IL-2 and rituximab and completely eradicated the disease in 2/7 cases (28.6%). Mechanistically, histological analyses of post-therapeutic lymphoma tissues revealed a strong intratumoral accumulation of macrophages and natural killer cells after a single dose of the immunocytokine, whereas L19-IL2 had no significant impact on microvessel density or on tissue penetration of co-injected rituximab. Collectively, these results provide the scientific rationale for the clinical evaluation of L19-IL2 in combination with anti-CD20 immunotherapy in patients with MCL.


Tigliane diterpene esters with IFN γ-inducing activity from the leaves of Aleurites fordii.
Bioactivity-guided fractionation on the leaves of Aleurites fordii led to the isolation of a new tigliane diterpene ester, 12-O-hexadecanoyl-7-oxo-5-ene-16-hydroxyphorbol-13-acetate (1) along with four known compounds, 12-O-hexadecanoyl-7-oxo-5-ene-phorbol-13-acetate (2), 12-O-hexadecanoyl-phorbol-13-acetate (3), 12-O-hexadecanoyl-16-hydroxyphorbol-13-acetate (4), and 12-O-hexadecanoyl-4-deoxy-4α-16-hydroxyphorbol-13-acetate (5). The structures of these compounds were determined by interpretation of NMR (1D and 2D) spectroscopic data and MS data. All the isolates were evaluated for their effects on the induction of IFN-γ in NK92 cells. Compounds 3 and 4 exhibited the most potent responses in IFN-γ induction, comparable to the positive control, phorbol 12-myristate 13-acetate (PMA).


Enabling Chemistry Technologies and Parallel Synthesis-Accelerators of Drug Discovery Programmes.
There is a pressing need to improve overall productivity in the pharmaceutical industry. Judicious investments in chemistry technologies can have a significant impact on cycle times, cost of goods and probability of technical success. This perspective describes some of these technologies developed and implemented at AbbVie, and their applications to the synthesis of novel scaffolds and to parallel synthesis.


Targeting NPM1 in irradiated cells inhibits NPM1 binding to RAD51, RAD51 foci formation and radiosensitizes NSCLC.
The ability of chemo-radiation therapy to control locally advanced stage III non-small cell lung cancer (NSCLC) is poor. While addition of consolidation immunotherapy has improved outcomes in subsets of patients there is still an urgent need for new therapeutic targets. Emerging research indicates that nucleophosmin1 (NPM1) is over-expressed in NSCLC, promotes tumor growth and that over-expression correlates with a lower survival probability. NPM1 is critical for APE1 base excision activity and for RAD51-mediated repair of DNA double strand breaks (DSBs). YTR107 is a small molecule radiation sensitizer that has been shown to bind to NPM1, suppressing pentamer formation. Here we show that in irradiated cells YTR107 inhibits SUMOylated NPM1 from associating with RAD51, RAD51 foci formation and repair of DSBs. YTR107 acts synergistically with the PARP1/2 inhibitor ABT 888 to increase replication stress and radiation-induced cell lethality. YTR107 was found to radiosensitize tumor initiating cells. Congruent with this knowledge, adding YTR107 to a fractionated irradiation regimen diminished NSCLC xenograft growth and increased overall survival. These data support the hypothesis that YTR107 represents a therapeutic target for control of NSCLC.


A visual stimulator for orbiting light spots and equal energy annuli with continuously variable parameters.
When a light spot moves at high angular velocity along a circular path on a screen, an annulus is preceived. This principle is used in a simple annulus generator consisting of a plane mirror that rotates about an axis making an angle alpha with the normal in the center point of the mirror. Angle alpha can be varied with a micrometer screw to change the diameter of the annular path (orbit) followed by the light spot that is projected on a screen via the rotating mirror. This results in variable diameter equal energy annuli. The diameter of the light spot can be changed to manipulate the width of the annulus. Finally, at low angular velocities an orbiting light spot is obtained. It is shown in the companion paper (Molenaar and van de Grind, 1979) that this slow orbiting of the light spot allows a precise study of the fine structure of receptive fields.


Development of bioelectrical impedance-based equations for the prediction of body composition of Malawian adolescents aged 10-18 years: a cross-sectional study.
The accuracy of bioelectrical impedance analysis (BIA) depends on population-specific prediction equations and there is no population-specific equation for predicting fat-free mass (FFM) in Malawian adolescents. This study aimed at determining the agreement between FFM measured by deuterium oxide dilution technique (the reference) and FFM by BIA; and propose BIA-based prediction equations to estimate FFM for Malawian adolescents. This was a cross-sectional study. The study was conducted in Blantyre, Malawi PARTICIPANTS: 186 Malawian adolescents aged between 10 and 18 years were included in this study. Body composition was estimated by both the BodyStat BIA analyser and the deuterium oxide dilution method. BIA inbuilt equation underestimated FFM compared with deuterium oxide dilution (p=0.039). The new prediction equation for FFM (kg)=-4.316+ 0.425* height2(cm)/resistance (Ω)+1.287* sex (male=1, female=0)+0.307*age(years)+0.344* weight(kg)+0.019*reactance(Ω) yielded an R2 of 0.926. The equation for total body water (TBW) (kg)=-2.152 + 0.328*height2(cm)/resistance (Ω) 0.910*sex (male=1, female=0)+0.307 *age (years)+0.249*weight(kg)+0.015*reactance(Ω) yielded an R2 of 0.922. The Bland-Altman plot illustrated a good level of concordance between the FFM and TBW predicted by the new equations and the values derived using deuterium dilution method. The new BIA prediction equations for estimating FFM and TBW could be used to assess with very good accuracy and precision the body composition of Malawian and adolescents with similar characteristics.


Interaction of adrenalectomy and fenfluramine treatment on body weight, food intake and brown adipose tissue.
Three experiments have examined the interaction of adrenalectomy and fenfluramine on food intake, body weight and the binding of guanosine-5'-diphosphate (GDP) to interscapular brown adipose tissue (IBAT). In the first experiment, GDP-binding by IBAT mitochondria from adrenalectomized or sham-operated animals was measured for 3 hr after one of 3 doses of fenfluramine. Fenfluramine stimulated GDP-binding at lower doses in the adrenalectomized animals than in the controls. In the first chronic experiment, adrenalectomy prevented the restoration of normal food intake observed 8-10 days after the beginning of fenfluramine treatment. Adrenalectomy also increased weight loss and enhanced GDP binding to mitochondria from IBAT in rats treated with fenfluramine. In the second chronic experiment, the combination of fenfluramine and adrenalectomy led to a progressive weight loss, continuing hypophagia and stimulation of GDP-binding by IBAT, whereas rats treated with fenfluramine alone showed a recovery of food intake at a stabilized but lower body weight. These data are consistent with the hypothesis that adrenalectomy and fenfluramine disable two separate components of the food intake system and that when combined, produce a profound and persisting disturbance in energy or nutrient balance.


Myxoid lipoma of oral soft tissue. A clinical and ultrastructural study.
Myxoid lipoma is an unusual histologic type of lipoma. This article reports four cases of myxoid lipoma that arose in the mouth. In frozen sections stained with oil red O, the cytoplasm of tumor cells stained strongly positive. Intercellular mucoid material was PAS-positive and diastase-resistant. It also stained positively with alcian blue. Electron microscopic observations revealed that adipocytes were in different stages of differentiation, with lipid globules of variable size observed in the cytoplasm. Many pinocytotic vesicles appeared at the plasma membrane. Mature adipocytes were surrounded by a basal lamina. Fibroblasts, collagen fibers, and mucoid material were scattered among adipocytes. It appears possible that, in the histogenesis of myxoid lipoma, multipotent mesenchymal cells undergo multidirectional differentiation. Some cells differentiate to produce mucosubstance, while others differentiate to become adipocytes.


A Nationwide Survey of Gastroenterology Program Leadership Regarding Implementation of the GI Hospitalist Model.
Academic gastroenterology (GI) hospitalists are increasing, however the impacts on fellowship training and clinical care are unclear. Motivations for implementation of the GI hospitalist model are uninvestigated. We aimed to determine the prevalence of GI hospitalists, explore motivations for and against adoption of a GIH model, and investigate the model's effects on fellowship training. Leadership at current general GI fellowships were surveyed about current staffing models, as well as effects and perceptions of the hospitalist model. There was a total of 52 (26%) respondents and 12 (23%) reported having a GI hospitalist at their institution. A majority of respondents stated burnout and reduced time on service for other faculty was a primary reason for hiring a GI hospitalist. The largest perceived benefit of a hospitalist is reduced burnout and time on service for outpatient GI faculty. Many respondents also believed a GIH would improve fellowship education and quality of inpatient care.


Self-renewal versus transformation: Fbxw7 deletion leads to stem cell activation and leukemogenesis.
Recent reports have demonstrated that specific tumor suppressors are important for both maintaining hematopoietic stem cell (HSC) quiescence and preventing leukemia development, suggesting a connection between these two activities. Matsuoka and colleagues (pp. 986-991) have further illustrated this theme by demonstrating that inactivation of the tumor suppressor Fbxw7 leads to HSC depletion by active cell cycling and the initiation of leukemia.


Antagonistic action of lactic cultures toward spoilage and pathogenic microorganisms in food.
The antibacterial properties of cell-free filtrate from lactic cultures were assessed against 10 bacterial cultures. All the five species of lactic culture examined showed antimicrobial activity against tested bacteria. S. aureus was least sensitive of the tested bacteria, followed by E. coli and S. typhosa. E. aerogenes was the most sensitive one. L. casei had the greatest antimicrobial activity. Leu. mesenteroides weakly inhibited the growth of the tested bacteria. In general, inoculum density had little effect on inhibition.


Lumen-apposing metal stent deployment failure.
Endoscopic ultrasound-guided transmural drainage has become a first-line therapy for pancreatic fluid collections (1). The appearance of lumen-apposing metal stents has resulted in an authentic revolution, due to their efficacy (clinical success rate of 93%) and easy deployment (technical success rate of 98%) (2). They are associated with a shorter procedure time, lower risk of migration and a wider lumen, which could provide a more effective drainage (3). We report the case of a 78-year-old male who developed an infected pancreatic pseudocyst as a late complication of an acalculous severe acute pancreatitis. An endoscopic ultrasound-guided transmural drainage was performed after a failed computed tomography-guided percutaneous drainage with placement of a pig-tail catheter. A gastrocystic fistula was created and an AxiosTM lumen-apposing metal stent (Boston Scientific; Massachusetts, United States) was inserted. Nevertheless, it remained lodged in the pancreatic pseudocyst at the time of deployment. A computed tomography scan confirmed stent placement inside the collection (Figure 1). After endoscopic balloon dilatation of gastrocystic fistulous tract, removal was unsuccessful with proximal traction of the lumen stent flange using biopsy forceps. Surgical treatment was decided and a gastrotomy was performed, the fistula was identified in the posterior gastric wall and the stent was removed. Endoscopic ultrasound-guided transmural drainage of pancreatic fluid collections using lumen-apposing metal stents is a safe procedure. However, it is not exempt of complications such as stent migration, bleeding, gastrointestinal perforation and air embolism (4). Technical failure of lumen-apposing metal stents deployment is a rare complication that may require surgical treatment if endoscopic removal is not possible.


Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure.
The purpose of this study was to determine the effects of systemic exercise training on endothelium-mediated arteriolar vasodilation of the lower limb and its relation to exercise capacity in chronic heart failure (CHF). Endothelial dysfunction is a key feature of CHF, contributing to increased peripheral vasoconstriction and impaired exercise capacity. Local handgrip exercise has previously been shown to enhance endothelium-dependent vasodilation in conduit and resistance vessels in CHF. Twenty patients were prospectively randomized to a training group (n=10, left ventricular ejection fraction [LVEF] 24+/-4%) or a control group (n=10, LVEF 23+/-3%). At baseline and after 6 months, peak flow velocity was measured in the left femoral artery using a Doppler wire; vessel diameter was determined by quantitative angiography. Peripheral blood flow was calculated from average peak velocity (APV) and arterial cross-sectional area. After exercise training, nitroglycerin-induced endothelium-independent vasodilation remained unaltered (271% versus 281%, P=NS). Peripheral blood flow improved significantly in response to 90 microg/min acetylcholine by 203% (from 152+/-79 to 461+/-104 mL/min, P<0.05 versus control group) and the inhibiting effect of L-NMMA increased by 174% (from -46+/-25 to -126+/-19 mL/min, P<0.05 versus control group). Peak oxygen uptake increased by 26% (P<0.01 versus control group). The increase in peak oxygen uptake was correlated with the endothelium-dependent change in peripheral blood flow (r=0.64, P<0. 005). Regular physical exercise improves both basal endothelial nitric oxide (NO) formation and agonist-mediated endothelium-dependent vasodilation of the skeletal muscle vasculature in patients with CHF. The correction of endothelium dysfunction is associated with a significant increase in exercise capacity.


An "olivomycin A" derivative from a sponge-associated Streptomyces sp. strain SP 85.
We isolated an actinobacterium, Streptomyces sp. strain SP 85 from the marine sponge Dysidea avara. Polyphasic identification of the microorganism showed that the strain SP 85 had high 16S rRNA gene similarity (99%) with Streptomyces olivaceus strain NBRC 12805, while some physiological and biochemical differences were observed. A cytotoxic compound, SP 85 was isolated from the active culture extract of the strain SP 85 by bioassay-guided purification over silica gel column chromatography, preparative TLC, and HPLC. The structure elucidation based on the spectroscopic analysis, including UV, ESI-MS, and 13C NMR data revealed that SP 85 compound is an analog of anti-tumor drug, "olivomycin A". The SP 85 compound showed high cytotoxic activity against three human cancer cell lines, including SW480, HepG2, and MCF7 with IC50 values of 16, 93, and 78 nM, respectively. SP 85 exhibited significantly (2-10 times) higher cytotoxicity against the tumor cell lines in comparison with HUVECs as the normal cell line, which also induced apoptosis in the tested cancerous cell line. This is the first report on the production of an "olivomycin A" derivative by a sponge-associated Streptomyces, showing the great potential of sponge-associated actinobacteria in producing cytotoxic natural products.


Influence of posttraumatic stress reaction and posttraumatic cognition on dissociative experiences according to the nature of traumatic experiences: A survey on Japanese young adults.
Although the relationship between dissociation and traumatic experiences has been debated, many studies focus on the context of traumatic experiences. Alternatively, basic research that examines the relationship of symptoms of posttraumatic experiences and cognitive characteristics of dissociation as an individual difference among experiencers has been lacking. To address this research gap, this study examines the influence of posttraumatic symptoms and cognition on dissociative experiences given the nature of traumatic experiences. This study administered the Events Checklist, the Dissociative Experiences Scale (DES), the Impact of Event Scale-Revised (IES-R), and the Japanese version of the Posttraumatic Cognitions Inventory to 1,036 Japanese adolescents. It investigated differences in dissociative experiences according to the presence of and cumulative traumatic experiences. Hierarchical multiple regression analysis was conducted to determine the influence of sex and the nature of traumatic experiences, posttraumatic symptoms (IES-R), and cognition on dissociative experiences. The results demonstrated no differences in DES based on the number of traumatic experiences. Moreover, this study observed the impact of cognition in posttraumatic experience on dissociation. This study provides essential data on the distribution of dissociative experiences among Japanese adolescents with traumatic experiences and exposure to adversity. Finally, it highlights the importance of focusing on posttraumatic cognitive characteristics, particularly negative self-perception, and discusses the implications to enhance understanding of dissociative experiences. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Spectral-Domain Optical Coherence Tomography for Determination of Retinal Thickness in Pediatric Patients with Mild-To-Moderate Chronic Kidney Disease: A Cross-Sectional Study.
Children with chronic kidney diseases (CKD) are at risk for neurological diseases at early adulthood. Spectral-domain optical coherence tomography (SD-OCT) of the retina is especially suitable for determination of intraretinal layer thickness. We wonder whether retinal thinning is already present in pediatric patients with mild-to-moderate CKD. Children (n = 15; 14.9 ± 2.4 years) with mild-to-moderate CKD (median eGFR of 95ml/min/1.73m2; range: 28-187ml/min/1.73m2) due to glomerulopathy, congenital anomalies of kidney and urinary tract (CAKUT), or haemolytic uremic syndrome (HUS) underwent a detailed ophthalmologic examination including high-resolution SD-OCT. Three OCT scans were obtained from the right eyes of all patients. Within each scan, retinal layers were separated and the mean thickness was determined at the foveal, parafoveal, and perifoveal area. The results were compared to those we obtained previously from healthy children. At the parafoveal area, thickness (median, range) of the total retina (ALL), ganglion cell layer (GCL), and inner plexiform layer (IPL) were reduced compared to healthy volunteers (339µm, (288-361µm) vs. 348µm, (320-385µm); 49.8µm (30.5-56.6µm) vs. 53.5μm (49.5-60.5µm) and 41.0µm (29.4-43.7µm) vs. 43.46µm (39.5-46.3μm); each p < 0.05). The intraretinal thickness measurements at the foveal and perifoveal areas revealed no statistically significant differences between patients and controls. Distinct changes within the parafoveal area of the total retina, GCL, and IPL are present in children with mild-to-moderate CKD. Prospective studies are required to assess the clinical significance of our findings.


Clinical practice guidelines and medical malpractice.
As clinical practice guidelines become more and more prevalent, they will define the requisite "standard of care" for medical treatment and impact medical malpractice litigation. They may even replace expert testimony.


Clinical preferences and trends of anti-vascular endothelial growth factor treatments for diabetic macular edema in Japan.
To determine the current clinical preferences of anti-vascular endothelial growth factor (VEGF) treatment protocols for diabetic macular edema (DME) in Japan. This was a descriptive cross-sectional study. Answers to a questionnaire consisting of 16 questions were obtained from 176 of 278 (63.3%) surveyed ophthalmologists. The results showed that 81.2% preferred intravitreal injections of anti-VEGF antibodies as the first-line therapy. The most important indicators for beginning anti-VEGF therapy were: the best-corrected visual acuity in 44.3% and the retinal thickness in 30.7%. In the loading phase, 53.4% preferred a single injection, and in the maintenance phase, 75.0% preferred the pro re nata regimen. Financial limitation (85.8%) was reported as the most important difficulty in the treatment. For combination therapy with anti-VEGF treatment, panretinal photocoagulation, focal photocoagulations and a sub-Tenon steroid injection were preferred. The contraindications for anti-VEGF therapy were: prior cerebral infarction (72.7%). Regarding the use of both approved anti-VEGF agents in Japan, ranibizumab and aflibercept, 39.8% doctors used them appropriately. Our results present the current clinical preferences of anti-VEGF treatment for DME in Japan. The best-corrected visual acuity and the retinal thickness are important indicators to institute this therapy. The majority of the ophthalmologists use anti-VEGF treatment as first-line therapy and prefer the 1 + pro re nata regimen.


[Intra-articular pressure in the large joints--a biomechanical variable pressure pump system].
Because of the anatomy and biomechanics intraarticular pressure modifications are caused by loading and movement of a joint. These continuous pressure alterations are examined in the hip joint of cadavers and in the shoulder-joint of cadavers and volunteers. The clinical importance is shown. The hereto hardly know changes of intraaticular pressure cause a strong synoviamovement and serve the provisioning of the joint-cartilage with the help of the changing, pressure pump-system.


Predictors and outcomes of healthcare-associated infections in COVID-19 patients.
Healthcare-associated infections (HAI) after viral illnesses are important sources of morbidity and mortality. This has not been extensively studied in hospitalized COVID-19 patients. This study included all COVID-19-positive adult patients (≥18 years) hospitalized between 01 March and 05 August 2020 at the current institution. The Centers for Disease Control and Prevention definition of HAI in the acute care setting was used. The outcomes that were studied were rates and types of infections and in-hospital mortality. Several multivariable logistic regression models were constructed to examine characteristics associated with development of HAI. Fifty-nine (3.7%) of 1565 patients developed 140 separate HAIs from 73 different organisms: 23 were Gram-positive, 39 were Gram-negative and 11 were fungal. Patients who developed HAI did not have higher odds of death (OR 0.85, 95% CI 0.40-1.81, p = 0.69). HAIs were associated with the use of tocilizumab (OR 5.04, 95% CI 2.4-10.6, p < 0.001), steroids (OR 3.8, 95% CI 1.4-10, p = 0.007), hydroxychloroquine (OR 3.0, 95% CI 1.0-8.8, p = 0.05), and acute kidney injury requiring hemodialysis (OR 3.7, 95% CI 1.1-12.8, p = 0.04). HAI were common in hospitalized Covid-19 patients. Tocilizumab and steroids were associated with increased risk of HAIs.


Evaluation of an agar gel immunodiffusion test to detect infection of cattle with bluetongue viruses in Queensland, Australia.
An agar gel immunodiffusion (AGID) test to detect group-specific antibodies to infection of cattle by bluetongue viruses was evaluated using field collected sera in Queensland, Australia. The AGID test was compared to the serum neutralisation (SN) test used to detect serotype-specific bluetongue virus antibodies. The AGID test was found to be highly sensitive (95% confidence interval, 80.7-100%) but to have moderate specificity (95% confidence interval, 59.3-79.6%), relative to the SN test. The correlation between AGID and SN test results was 0.41 (P < 0.001). Using likelihood ratio estimates the chance (posttest probability) of an AGID test positive serum sample being positive (titre > or = 1:20) in the SN test was estimated to be 87% and 90% for 2+ and 3+ AGID test reactions, respectively. A serum sample was estimated to have a probability of 40% of being positive in the SN test if it gave a 1+ reaction in the AGID test. Results suggest that the AGID test should ideally be used as a screening test in serological surveys and surveillance programs. If the test is to be used for identification of individually infected cattle, a cutoff point of > or = 2+ should be employed.


[Influence of count rate on image quality in three-dimensional PET acquisition].
In FDG-PET examinations, optimization of the injected dose and duration of acquisition are important in determining the physical performance of PET or the PET/CT scanner. This study was intended to elucidate the influence of count rate on image quality. Three PET/CT scanners (Biograph sensation 16, Discovery ST, and Aquiduo) were used in this study. Body and scatter phantoms (NEMA 2001) and a cylindrical phantom (for QC use) were also used. Data acquisition was performed repeatedly for about 6 h to achieve a fixed 15 million counts of true plus scatter. The count rate performance and image quality (signal-to-noise ratio and contrast) of each frame were analyzed after data acquisition. The relationship between the count rate and image quality was also analyzed. A positive correlation between the random fraction (ratio of random to prompt count rate) and signal-to-noise ratio was found in all PET/CT scanners, but with differing effects of the count rate's influence on image quality. Image contrast was not correlated with count rate. Acquisition parameters must be determined by considering each scanner's effect on how count rate influences image quality.


Evaluation of radiological methods of assessing cup anteversion in total hip replacement.
Prospective clinical study. In total hip replacement, the placement of the cup is critical as inaccurate placement can cause impingement, accelerated wear and dislocations. The position of the cup is assessed by abduction and anteversion. There are many radiological methods available for this purpose, while the reliability and validity of the methods have not been adequately done. Calculation by CT method is a gold standard. The aim of study was to evaluate the reliability and validity of all the methods. In 30 hips of 25 consecutive patients, 13 females and 12 males who underwent primary total hip replacement in our institution, the component version in all the five radiological methods was calculated and compared with CT evaluation of angles. The intra- and interobserver reliabilities were assessed. Average CT measurement was 23.28 for anteversion. Lewinnek, Liaw, Hassan, Widmer and Ritun methods had average deviation of 4.330, 4.390, 4.880, 6.840 and 6.220, respectively. All the radiographic and CT methods had excellent intra- and interobserver reliabilities (C.I. 0.894-0.960 and 0.861-0.953). All the methods except Widmer had a significant validity against CT. Plain X-rays (AP) are reliable for measuring cup anteversion. Lewinnek, Liaw, Riten and Hassans methods for calculation of cup anteversion are closer to CT in accuracy (p value >0.05). Widmer method varies significantly (p value <0.05) from CT.


Genomic era analyses of RNA secondary structure and RNA-binding proteins reveal their significance to post-transcriptional regulation in plants.
The eukaryotic transcriptome is regulated both transcriptionally and post-transcriptionally. Transcriptional control was the major focus of early research efforts, while more recently post-transcriptional mechanisms have gained recognition for their significant regulatory importance. At the heart of post-transcriptional regulatory pathways are cis- and trans-acting features and factors including RNA secondary structure as well as RNA-binding proteins and their recognition sites on target RNAs. Recent advances in genomic methodologies have significantly improved our understanding of both RNA secondary structure and RNA-binding proteins and their regulatory effects within the eukaryotic transcriptome. In this review, we focus specifically on the collection of these regulatory moieties in plant transcriptomes. We describe the approaches for studying RNA secondary structure and RNA-protein interaction sites, with an emphasis on recent methodological advances that produce transcriptome-wide datasets. We discuss how these methods that include genome-wide RNA secondary structure determination and RNA-protein interaction site mapping are significantly improving our understanding of the functions of these two elements in post-transcriptional regulation. Finally, we delineate the need for additional genome-wide studies of RNA secondary structure and RNA-protein interactions in plants.


Does Opioid Use Disorder Matter for Health Care Utilization Among Lung Cancer Patients? Evidence from U.S. Hospitals During 2016-2020.
BACKGROUND AND OBJECTIVE: The number of hospitalizations due to opioid use disorders in the USA increased steadily from 62,010 in 1998-2000 to 136,240 in 2015-2016; however, no health care utilization of lung cancer patients with opioid use disorder has been reported. The purpose of this paper is to investigate health care utilization due to opioid use disorder among lung cancer patients and to investigate additional charge status due to this disorder. The National Inpatient Sample of the USA was used to identify lung cancer patients (n = 11,418, weighted n = 557,090) from 2016 to 2020. The characteristics of patient samples, temporal trend of opioid use disorder, and its association with health care utilization measured by hospital charges were thoroughly examined by the multivariate survey linear regression model. Among 557,090 lung cancer patients, 2.4% had opioid use disorder. The proportion of opioid use disorder among lung cancer patients during the study periods had continuously grown. Hospital charges also continued to increase during the study period and were higher among lung cancer patients with opioid use disorder. Survey linear results showed that opioid use disorder was associated with 12.6% higher hospital charges. Analysis of subgroups revealed that this trend was similar across p < the majority of social groups; however, it was significantly higher among Caucasian individuals (0.001) and self-pay groups (p = 0.035) than among others. Research conducted has identified gaps in care in rural and suburban areas and a lack of equal care given to minority and low-income patients. These vulnerable groups access health care less often, are charged more for the care they receive, and often face multiple barriers to treatment. Unless these issues are addressed with a focus on socioeconomic factors, race, and region, the opioid epidemic will continue to negatively decimate these populations.


Placental Histopathology and Pregnancy Outcomes in "Early" vs. "Late" Placental Abruption.
Placenta-associated pregnancy complications (fetal growth restriction and preeclampsia) are traditionally classified as "early" and "late" due to their different pathophysiology, histopathology, and pregnancy outcomes. As placental abruption (PA) represents another placenta-associated complication, we aimed to study if this categorization can be applied to PA as well. Pregnancy and placental reports of all pregnancies complicated by PA between November 2008 and January 2019 were reviewed. Maternal background, pregnancy outcomes, and placental histopathology were compared between cases of PA < 34 weeks (early PA group) vs. > 34 weeks (late PA group). Placental lesions were classified according to the "Amsterdam" criteria. The primary outcome was severe neonatal morbidity (≥ 1 severe neonatal complications: seizures, IVH, HIE, PVL, blood transfusion, NEC, or death). Included were 305 cases of PA, 71 (23.3%) in the early group and 234 (76.7%) in the late group. The early PA group was characterized by higher rates of vaginal bleeding upon presentation (p = 0.003), DIC (p = 0.018), and severe neonatal morbidity (p < 0.001). The late PA group was characterized by a higher rate of urgent Cesarean deliveries (p < 0.001). The early PA group was characterized by higher rates of placental maternal vascular malperfusion (MVM) lesions (p < 0.001), maternal inflammatory response (MIR) lesions (p < 0.001), placental hemorrhage (p < 0.001), and a lower feto-placental ratio (p < 0.001). Using regression analysis, we found that severe neonatal morbidity was independently associated with early abruption (aOR = 5.3, 95% CI = 3.9-7.6), placental MVM (aOR = 1.5, 95% CI = 1.2-1.9), placental MIR (aOR = 1.9, 95% CI = 1.4-2.3), and inversely associated with antenatal corticosteroids (aOR = 0.9, 95% CI = 0.6-0.98). "Early" and "late" PA significantly differ in their presentation, placental pathology, and pregnancy outcomes.


Scientism in Medical Education and the Improvement of Medical Care: Opioids, Competencies, and Social Accountability.
Scientism in medical education distracts educators from focusing on the content of learning; it focuses attention instead on individual achievement and validity in its measurement. I analyze the specific form that scientism takes in medicine and in medical education. The competencies movement attempts to challenge old "scientistic" views of the role of physicians, but in the end it has invited medical educators to focus on validity in the measurement of individual performance for attitudes and skills that medicine resists conceptualizing as objective. Academic medicine should focus its efforts instead on quality and relevance of care. The social accountability movement proposes to shift the focus of academic medicine to the goal of high quality and relevant care in the context of community service and partnership with the institutions that together with medicine create and cope with health and with health deficits. I make the case for this agenda through a discussion of the linked histories of the opioid prescribing crisis and the professionalism movement.


Aging, lifestyle factors, hormones and bone health in Singaporean men.
The present study examined how age, bodyweight, body fat, regular exercise and some endocrine factors are associated with osteoporosis, spine bone mineral density (Sbmd) and femoral neck bone mineral density (Fnbmd) in Singaporean men. Body composition and bone scans of lumbar spine at L2-L4 and hip were carried out with duel-energy X-ray absorptiometry (DXA). Anthropometric parameters were measured and demographic data, medical history and exercise schedule were collected via a questionnaire. Osteoporosis prevalence was higher and Sbmd and Fnbmd were lower in men with high percent body fat (PBF) and conversely osteoporosis prevalence was lower and Sbmd and Fnbmd were higher in men with higher body mass index (BMI). Age was negatively associated with Fnbmd but not Sbmd. On the other hand, PBF and insulin levels were negatively associated with both Sbmd and Fnbmd. Body mass index and exercise intensity were positively associated with both Sbmd and Fnbmd. Sex hormones were significantly associated with only Sbmd but not Fnbmd. Both estradiol and DHEAS were positively, while testosterone was negatively associated with Sbmd. The study shows that the prevalence of osteoporosis and some of the determinants of bone mineral density (BMD) in Singaporean men was site-specific. Further, BMI and PBF are opposing predictors of BMD. Therefore, any strategy for improving bone health should include modalities that increase lean and bone mass and decrease fat mass. The bone health of Singaporean men is comparable to non-Hispanic whites and better than some other Asian men.


Immunological mechanisms in specific immunotherapy.
Specific immunotherapy (SIT) represents the only curative treatment of allergy and is, therefore, of particular interest for immunological and pharmacological research. The current understanding of immunological mechanisms underlying SIT focuses on regulatory T cells (T regs), which balance Th1 and Th2 effector functions. This ensures that allergens are recognized, but tolerated by the immune system. There is clear evidence that SIT restores the disturbed balance of T regs and effector cells in allergic patients. Current efforts are focused to improve SIT regimens to make them more applicable in atopy and asthma. The current review provides an overview on the mechanisms of SIT and possible adjuvant treatment strategies on the background of the T reg concept.


Odontogenic carcinoma with sarcomatous proliferation. A case report.
An unusual case of odontogenic carcinoma of the mandible showing a sarcomatous proliferation is described. The tumour had caused invasive bone destruction with extension into the soft tissues of the cheek. It was successfully treated by resection of the mandible and radical neck dissection. Although ameloblastomatous features were observed in an infrabony area, the majority of the intrabony lesion consisted of a proliferation of epithelial cells arranged in fine strands or networks which were randomly scattered in a collagenous stroma in the periphery. The tumour cells assumed a fibroblastic appearance and were intermingled with stroma cells in the extrabony lesion. The lesion could not be placed in any of the three entities of odontogenic carcinoma in the WHO classification.


Sex differences in methamphetamine pharmacokinetics in adult rats and its transfer to pups through the placental membrane and breast milk.
Methamphetamine (METH) abuse is a growing health problem worldwide, and METH use during pregnancy not only endangers the mother's health but also the developing fetus. To provide better insight into these risks, we performed the following experiments. First, we investigated how sex influences the pharmacokinetics of METH and amphetamine (AMP) in male and female rats. Subsequently, we simulated chronic exposure of prenatal infants to METH abuse by investigating brain and plasma levels of METH and AMP in dams and pups. Finally, we modeled chronic exposure of infants to METH via breast milk and investigated sex differences in pups with regard to drug levels and possible sensitization effect of chronic prenatal METH co-treatment. We observed significantly higher levels of METH and AMP in the plasma and brain of female rats compared to males. Additionally, brain concentrations of METH and AMP in pups exposed to METH prenatally were equivalent to 62.13% and 37.78% relative to dam, respectively. Plasma concentrations of AMP where equivalent to 100% of the concentration in dams, while METH was equivalent to only 36.98%. Finally, we did not observe a significant effect relative to sex with regard to METH/AMP levels or sensitization effects linked to prenatal METH exposure. We demonstrated that female rats display higher levels of METH and AMP, thus indicating a greater risk of addiction and toxicity. Furthermore, our data show that pups are exposed to both METH and AMP following dam exposure.


The level of GAD67 protein is highly sensitive to small increases in intraneuronal gamma-aminobutyric acid levels.
Increases (> 2.5-fold) in GABA levels in rat brain lead to a large decrease in the level of the 67-kDa form of glutamate decarboxylase (GAD67) through a mechanism involving either a change in GAD67 protein stability or a change in GAD67 mRNA translation. In the present study, brain levels of GABA were manipulated by treating rats with various doses of gamma-vinyl-gamma-aminobutyric acid (GVG), and the dependence of total GAD activity and levels of GAD67 and GAD65 protein on the levels of GABA was analyzed. Initial studies showed that both GABA and GAD67 protein levels reached new steady-state levels after two to four daily injections; GABA increased 1.5- (30 mg of GVG/kg) and fourfold (150 mg of GVG/kg), and GAD67 protein content decreased by 30 and 70%. To assess the sensitivity of GAD67 to GABA, rats were injected with eight different doses of GVG (15-150 mg/kg) for 5 days. With increasing doses of GVG, we observed a gradual increase in both whole-tissue and synaptosomal GABA levels and a gradual decrease in GAD67 protein and GAD activity. The levels of GAD65 remained constant at all GVG doses. GAD67 was remarkably sensitive to GABA. The synaptosomal GAD67 level decreased approximately 12% and the whole-neuron GAD67 level decreased approximately 3% for each 1% increase in nerve terminal GABA content when it was close to its physiological level. Our results clearly demonstrate that GAD67 is tightly controlled by intraneuronal GABA, and we suggest that this regulatory mechanism has important implications for the physiological regulation of GABAergic function in the mammalian brain.


Circular RNA circ-TNPO3 suppresses metastasis of GC by acting as a protein decoy for IGF2BP3 to regulate the expression of MYC and SNAIL.
Gastric cancer (GC) continues to be the most common gastrointestinal malignancy in China, and tumor metastases are a major reason for poor prognosis. Circular RNAs (circRNAs) are an intriguing type of noncoding RNAs with important regulatory roles. However, the roles of circRNAs in GC metastasis have not been fully elucidated. Here, we reported that circ-transportin 3 (TNPO3) was significantly downregulated in 103 pairs of GC tissues compared with matched noncancerous tissues. The level of circ-TNPO3 expression correlated with differentiation of GC, and plasma circ-TNPO3 could serve as a potential diagnostic biomarker. Functionally, circ-TNPO3 inhibited proliferation and migration of GC in vitro and in vivo. We further verified that circ-TNPO3 competitively interacted with insulin-like growth factor 2 binding protein 3 (IGF2BP3) protein; thus, the role of IGF2BP3 in stabilizing MYC mRNA was weakened, which inhibited the expression of MYC and its target SNAIL. Taken together, circ-TNPO3 acts as a protein decoy for IGF2BP3 to regulate the MYC-SNAIL axis, thereby suppressing the proliferation and metastasis of GC. Therefore, circ-TNPO3 has the potential to serve as a therapeutic target for GC.


[Adaptive reactions of algal populations to exposure to toxic substances].
The adaptative reactions of alga populations to the toxic effect have been investigated by the functional triad method. The role of phenotypic and genotypic adaptation and the dynamics of their correlation during the alga adaptation to the toxic media has been revealed.


Clinical correlations of auditory P200 topography and left temporo-central deficits in schizophrenia: a preliminary study.
A number of studies using nontopographic analyses have reported an amplitude decrement of the auditory P200 component in schizophrenics compared to normal controls. Here we report a topographic analysis of the auditory P200 (204-272 ms; peak to baseline) in chronic medicated schizophrenics (N = 11) and normal controls (N = 18) and the correlation between this measure and clinical symptoms in schizophrenia. Exploratory T-statistic mapping (SPM) and "protected" Hotelling's T-squared contrasts of integrated voltages over the entire scalp showed that schizophrenics' P200 component had diminished amplitude in the left temporo-central region. Furthermore, P200 amplitude in the same scalp region during the experimental condition of counting infrequent tones was highly correlated with negative symptoms in the schizophrenic group.


Beta-haemolytic group A streptococci emm75 carrying altered pyrogenic exotoxin A linked to scarlet fever in adults.
To determine the etiological cause of a food-borne outbreak of scarlet fever in adults. Swabs from the throats of the patients and asymptomatic control were cultured on blood agar plates individually. Biochemical identification of all isolates was performed with a VITEX automated system. Antibiotic susceptibility was examined by using the Kirby-Bauer disc diffusion method. emm gene and extracellular pyrogenic exotoxins of each isolate were amplified by using polymerase chain reaction and subjected to DNA sequencing. Sequence differences between the isolated and the highly similar reference sequences were compared on BLAST. Bioinformatics was used to predict protein structures. Beta-haemolytic group A streptococci (GAS) emm75 were identified from 10 of 13 available patients. The isolates were susceptible to penicillin, ampicillin, vancomycin, cefatriaxone, ofloxacin, linezolid and quinupristin. All of the isolates carried pyrogenic exotoxin A (speA) and cysteine protease (speB). Isolated speA was phylogenetically different from 30 highly similar references on BLAST. Differences in the primary sequence of the deduced protein were 14.37-20.12% between the speA and each of 11 references. Secondary protein structure of the speA was different from the references at the N-terminal. GAS emm75 encoding altered speA was responsible for the food-borne outbreak of scarlet fever in adults.


Urinary phosphate and cyclic AMP excretion following citrate-induced hypocalcemic stimulation of the neonatal parathyroid glands.
Sixteen neonates, ranging in gestational age from 27 to 41 weeks and in postnatal age from birth to 8 days, were evaluated for their renal response to an endogenous PTH stimulus in 22 separate experiments. The PTH stimulus was generated by the decreased serum ionized Ca that accompanies exchange transfusion with citrated blood. The neonates increased their serum PTH from 95.8 +/- 13.1 to 133.9 +/- 15.4 microliterEq/ml (mean +/- SEM) during the transfusion, while increasing their urinary cAMP from 0.77 +/- 0.11 to 1.45 +/- 0.22 nmol/ml, and their urinary P from 12.9 +/- 2.6 to 30.6 +/- 6.1 mg/dl in the four hours following the exchange transfusion. This response was not related to postnatal or gestational age. We speculate that lack of renal responsiveness to PTH does not play a major role in the pathogenesis of early neonatal hypocalcemia.


IgA1 glycosylation in IgA nephropathy: as sweet as it can be.
Abnormally O-glycosylated IgA1 is likely to be involved in the pathogenesis of IgA nephropathy (IgAN). Buck et al. show that the enzyme activity and gene expression of specific glycosyltransferases, in purified B cells isolated from peripheral blood and bone marrow, is not reduced in IgAN patients. As only a small fraction of IgA in IgAN patients is abnormally glycosylated, it is probable that a more detailed molecular analysis at the single cell level is required to unravel the cause of this abnormality.


Betulin induces reactive oxygen species-dependent apoptosis in human gastric cancer SGC7901 cells.
Betulin, an abundant natural compound, significantly inhibited the cell viability of advanced human gastric cancer SGC7901 cells. Mechanism study demonstrated that betulin induced apoptosis through mitochondrial Bax and Bak accumulation-mediated intrinsic apoptosis pathway. Downregulation of the anti-apoptosis proteins Bcl-2 and XIAP was involved during betulin-induced cell apoptosis. Reactive oxygen species (ROS) was generated in cells after betulin treatment in a time- and dose-dependent manner. Addition of antioxidant N-acetyl-L-cysteine (NAC) significantly attenuated betulin-induced ROS generation as well as Bcl-2 and XIAP downregulation. The mitochondrial accumulation of Bax and Bak, as well as caspase activity, was also remarkably inhibited by NAC treatment, indicating that ROS are important signaling intermediates that lead to betulin-induced apoptosis by modulating multiple apoptosis-regulating proteins in SGC7901 cells.


Cell adhesion on a polymerized peptide-amphiphile monolayer.
We report the synthesis and characterization of a stable polymerized monolayer of peptide-amphihiles on a planar solid support that promotes mouse fibroblast cell adhesion and spreading. Peptide-amphiphiles consisting of a polymerizable fatty acid attached to a short RGD containing peptide sequence are self-assembled and polymerized at the water-air interface by means of the Langmuir- Blodgett technique. The surface concentration of the peptide-amphiphile is varied by co-spreading the peptide-amphiphile with an analogous non-modified polymerizable amphiphile at the water/air interface, prior to UV light-induced polymerization. The polymerized monolayer is transferred onto a hydrophobized smooth mica surface and the resulting surfaces have been investigated with respect to directing the cell adhesion and spreading of mouse fibroblast cells in a serum-free medium. Fibroblast cells adhere and spread on surfaces exposing the bioactive ligand but do not spread on reference surfaces without peptide. We find a maximum number of adherent cells at rather high peptide surface concentrations of about 10 mol% in the mixed monolayer, equivalent to more than 50 pmol/cm2 peptide on the surface of the film. We attribute this finding to a limited accessibility of the ligands by the integrins. Because of the stability of the polymerized peptide-amphiphile monolayer, these surfaces can be re-seeded multiple times with cells, i.e. adherent cells can be removed from the surface, the surface can be sterilized and cells can be re-attached.


TREAT: Therapeutic RNAs exploration inspired by artificial intelligence technology.
Recent advances in RNA engineering have enabled the development of RNA-based therapeutics for a broad spectrum of applications. Developing RNA therapeutics start with targeted RNA screening and move to the drug design and optimization. However, existing target screening tools ignore noncoding RNAs and their disease-relevant regulatory relationships. And designing therapeutic RNAs encounters high computational complexity of multi-objective optimization to overcome the immunogenicity, instability and inefficient translational production. To unlock the therapeutic potential of noncoding RNAs and enable one-stop screening and design of therapeutic RNAs, we have built the platform TREAT. It incorporates 43,087,953 regulatory relationships between coding and noncoding genes from 81 biological networks under different physiological conditions. TREAT introduces graph representation learning with Random Walk Diffusions to perform disease-relevant target screening, in addition to the commonly utilized Topological Degree and PageRank algorithms. Design and optimization of large RNAs or interfering RNAs are both available. To reduce the computational complexity of multi-objective optimization for large RNA, we stratified the features into local and global features. The local features are evaluated on the fixed-length or dynamic-length local bins, whereas the latter are inspired by AI language models of protein sequence. Then the global assessment is performed on refined candidates, thus reducing the enormous search space. Overall, TREAT is a one-stop platform for the screening and designing of therapeutic RNAs, with particular attention to noncoding RNAs and cutting-edge AI technology embedded, leading the progress of innovative therapeutics for challenging diseases. TREAT is freely accessible at https://rna.org.cn/treat.


Forecasting Future Monthly Patient Volume using Deep Learning and Statistical Models.
The variety of diseases is increasing day by day, and the demand for hospitals, especially for emergency and radiology units, is also increasing. As in other units, it is necessary to prepare the radiology unit for the future, to take into account the needs and to plan for the future. Due to the radiation emitted by the devices in the radiology unit, minimizing the time spent by the patients for the radiological image is of vital importance both for the unit staff and the patient. In order to solve the aforementioned problem, in this study, it is desired to estimate the monthly number of images in the radiology unit by using deep learning models and statistical-based models, and thus to be prepared for the future in a more planned way. For prediction processes, both deep learning models such as LSTM, MLP, NNAR and ELM, as well as statistical based prediction models such as ARIMA, SES, TBATS, HOLT and THETAF were used. In order to evaluate the performance of the models, the symmetric mean absolute percentage error (sMAPE) and mean absolute scaled error (MASE) metrics, which have been in demand recently, were preferred. The results showed that the LSTM model outperformed the deep learning group in estimating the monthly number of radiological case images, while the AUTO.ARIMA model performed better in the statistical-based group. It is believed that the findings obtained will speed up the procedures of the patients who come to the hospital and are referred to the radiology unit, and will facilitate the hospital managers in managing the patient flow more efficiently, increasing both the service quality and patient satisfaction, and making important contributions to the future planning of the hospital.


Pyrolysis and copyrolysis of three lignocellulosic biomass residues from the agro-food industry: A comparative study.
In this study, pyrolysis of residual biomass from the agro-alimentary industry of Argentina was investigated. The studied biomasses were rice husk, peanut shell and wheat straw. The effect of pyrolysis temperature over solid (bio-char), liquid (bio-oil) and gas (bio-gas) fractions weight yields were evaluated for each biomass, in the range of 350-650 °C. The maximum yield of bio-oil was obtained at 550 °C for rice husk (45 wt%) and wheat straw (58 wt%), and at 500 °C for peanut shells (51 wt%). At those temperatures, the data recorded the smallest spread around the mean. Different characterization techniques of raw biomass were reported, namely, thermal behavior; proximate and ultimate analysis; content of Ca, Al, K, Si and Fe; and hemicellulose, cellulose and lignin composition. Bio-oils characterization included water content and chemical compounds identification. Furthermore, bio-char HHV and BET surface area were measured. Rice husk bio-oil showed 21% selectivity towards furans of which 75% corresponded to furfural and 5-HMF. Peanut shell bio-char presented the highest Higher Heating Value (7250 kcal/kg) and BET surface area (215 m2/g). In addition, co-pyrolysis reactions and the synergistic effects over obtained products completed this study. Co-pyrolysis bio-oils yields varied between 41 and 46 wt%, for all the mixtures. Bio-oil water content decreased up to 15% for rice husk mixed with peanut shell or wheat straw. Moreover, 5-HMF was detected in all bio-oils, and furfural selectivity was higher than 5% in the three mixtures investigated.


Expression of codon-optimized PDCoV-RBD protein in baculovirus expression system and immunogenicity evaluation in mice.
Porcine deltacoronavirus (PDCoV) is a global epidemic enteropathogenic coronavirus that mainly infects piglets, and causes huge losses to the pig industry. However, there are still no commercial vaccines available for PDCoV prevention and controlment. Receptor-binding domain (RBD) is located at the S1 subunit of PDCoV and is the major target for developing viral inhibitor and vaccine. In this study, the characteristics of the RBD were analyzed by bioinformatic tools, and codon optimization was performed to efficiently express the PDCoV-RBD protein in the insect baculovirus expression system. The purified PDCoV-RBD protein was obtained and fully emulsified with CPG2395 adjuvant, aqueous adjuvant and Al(OH)3 adjuvant, respectively, to develop vaccines. The humoral and cellular immune responses were assessed on mice. The results showed that both the RBD/CPG2395 and RBD/aqueous adjuvant could induce stronger immune responses in mice than that of RBD/Al(OH)3. In addition, the PDCoV challenge infection was conducted and the RBD/CPG2395 could provide better protection against PDCoV in mice. Our study showed that the RBD protein has good antigenicity and can be used as a protective antigen, which provided a basis for the development of the PDCoV vaccine.


Influence of the curvature of deformed graphene nanoribbons on their electronic and adsorptive properties: theoretical investigation based on the analysis of the local stress field for an atomic grid.
Electronic and adsorptive properties of deformed graphene are investigated in the current work. Armchair and zigzag nanoribbons are the subject of the study. The axial compression was a deforming load. A calculation method for the local stress field was developed. This method was based on the quantum model of the finite graphene nanoribbon and empirical calculation method of the single atom energy. The stress field of the deformed ribbon was calculated by means of the suggested methodology. The effects of the atomic grid curvature on the adsorptive capacity of graphene and the hydrogenation process was investigated by means of the developed method. The prediction of the appearance of defects on covalent C-C bond breakdown is also performed.


Association of balance control mechanisms with brain structural integrity in older adults with mild cognitive impairment.
Older adults with mild cognitive impairment (OAwMCI) exhibit subtle balance control and gait deficits which are predominantly associated with structural brain pathologies such as impaired white matter integrity and reduced gray matter volume. However, the relationship between balance recovery mechanisms and neural substrates in OAwMCI remains unknown. This study thus aimed to explore the associations of volitional (self-initiated) and reactive balance (in response to an external perturbation) control with structural brain integrity. Ten OAwMCI (MoCA 18-25/30; greater than 55 years) were examined on the limits of stability test (volitional balance via Equitest), stance perturbation test (reactive balance via ActiveStep treadmill) and underwent magnetic resonance imaging. Forward movement (frequently performed functional activity of daily living) was quantified by maximum excursion (maximum ability to shift one's center of gravity toward the theoretical limit [MXE-%])and directional control (amount of movement exhibited towards the target proportional to the movement away from the target [DCL-%]) on the limits of stability test. Slip-like (prevalent type of accidental falls) perturbations were quantified by postural stability (shortest distance of the COM motion state, i.e., its position and velocity, to the theoretical boundary) on the ActiveStep treadmill. White matter integrity was quantified by fractional anisotropy (FA, movement of water molecules directionality) and gray matter volume measured in mm3. For volitional balance control, reduced forward MXE was significantly (p < 0.05) associated with lower FA in left (R2 = 0.56) and right (R2 = 0.60) corticospinal tract, left (R2 = 0.49) and right (R2 = 0.51) corticothalamic tract, left (R2 = 0.70) and right (R2 = 0.57) frontopontine tract, right (R2 = 0.67) cingulum, anterior commissure (R2 = 0.82), and corpus callosum (R2 = 0.62). Reduced forward DCL was significantly (p < 0.05) associated with reduced gray matter volume in the left (R2 = 0.75) and right (R2 = 0.81) cerebellum, brainstem (R2 = 0.64), right (R2 = 0.49) thalamus. For reactive balance control, reduced postural stability (p < 0.05) was significantly associated with reduced FA in the left (R2 = 0.75) and right (R2 = 0.64) corticospinal tract, left (R2 = 0.67) and right (R2 = 0.65) frontopontine tract. Reduced postural stability was significantly (p < 0.05) associated with reduced gray matter volume in the brainstem (R2 = 0.72) and right cerebellum (R2 = 0.70). Our results indicate that structural brain integrity influences stability control in OAwMCI for both volitional and reactive balance tasks, which may share some common cortico-subcortical motor pathways and relay centers. Results also show that the integrity of descending pathways from cortical attentional centers could influence stability control for both tasks.


A first exploration of a Robertsonian translocation heterozygote in the mouse for its usefulness in cytological evaluation of radiation-induced meiotic autosomal non-disjunction.
In this report some data concerning the male meiotic system of mice heterozygous for Rb(11.13)4Bnr are presented and compared with those of a chromosomally normal Swiss random-bred stock. Change of the genetic background from a C3H/Swiss hybrid situation to the fourth backcross generation (to the Swiss random-bred stock), did not alter the average frequency of aneuploid secondary spermatocytes. This was confirmed by studies on post-implantation loss. Spermatogenic characteristics of Rb4/+ mice, such as testis weight, sperm production and the number of diplotene-metaphase-I figures found in stage XII of the seminiferous epithelium, suggest delay and cell death during this period. These data support our working hypothesis that such an aberrant chromosome system may be more prone to radiation effects and therefore is promising in our cytological studies into the causes of spontaneous and in our cytological studies into the causes of spontaneous and induced autosomal non-disjunction during meiosis in the mouse.