[Cytological differential diagnostic accuracy in severe dysplasia and carcinoma in situ of the cervix and possible clinical consequences (author's transl)].
Since 1943 when Papanicolaou introduced cytology into gynecology the method has changed from a simple screening test into a sophisticated morphologic technique, the differential cytology. In Germany this development is documented by an improved cytologic classification (Münchner Nomenklatur). An own material is presented consisting of 520 cases of histologically proven severe dysplasias and in situ carcinomas. It can be shown that careful and critical use of differential cytology with due regard to its limits can improve the accuracy of the cytologic prediction of a cervical lesion. A delineation against invasive cancer is possible with a hundred percent accuracy. On the basis of these results it seems justifiable to perform a primary hysterectomy without pretherapeutic cone-biopsy. It is pointed out that this procedure is only possible in institutions were the possibilities of differential cytology are well-known and--which is more important--where the limits of the method are known and respected. In any case of doubt the procedure of diagnosis and therapy has to be discussed and planned in close cooperation between the clinicians and the morphologists.


The Rare Sides of Twin Research: Important to Remember/Twin Research Reviews: Representation of Self-Image; Twins With Kleine-Levin Syndrome; Heteropaternal Lemur Twins; Risk of Dental Caries/In the Media: High-Society Models; 'Winkelevii' Super Bowl Twins; Multiple Birth × Three; Twin Sister Surrogate; A Presidential Twin?
This article explores some rare sides of twin research. The focus of this article is the sad plight of the Dionne quintuplets, born in Canada in 1934. However, several other studies belong in this category, such as Dr Josef Mengele's horrifying twin research conducted at the Auschwitz concentration camp, Dr John Money's misguided attempt to turn an accidentally castrated male twin into a female, Russian scientists' cruel medical study of conjoined female twins and Dr Peter Neubauer's secret project that tracked the development of separated twins. Reviews of current twin research span twins' representation of self-image, twins with Kleine-Levin Syndrome, heteropaternal twinning in lemurs and factors affecting risk of dental caries. Media coverage includes a pair of high-society models, a book about the 'Winkelevii' twins, Super Bowl twin teammates, a family with three sets of fraternal twins, a twin sister surrogate and a near presidential twin.


Addiction: an underestimated problem in psoriasis health care.
Psoriasis is a disease of enormous socio-economic impact. Despite approval of numerous highly efficient and costly therapies, a minor proportion of severely affected patients actually receives sufficient treatment. To investigate whether addictions are associated with psoriasis and to develop evidence-based recommendations for dermatologists in their daily clinical practice in order to improve medical assessment of psoriasis and patients' quality of life. Psoriasis patients at the University Department of Dermatology were asked to fill out a paper-based self-reported anonymous questionnaire with 92 questions of validated screening tests for the six most common addictions in Germany (alcohol, nicotine, drugs and illegal drugs, gambling, food). Body weight and height as well as current Psoriasis Area and Severity Index (PASI) were documented as well. Between October 2015 and February 2016, 102 patients (65 males, 37 females; mean age 49.7 years (SD 13.4), range 18-83 years) participated in the study. Fifty-seven of the 102 patients showed addictive behaviour. Of these, 23.8% were high-risk drinkers, 41% regular smokers, 11% at risk of drug abuse, 4.1% at risk of food dependency and 19% compulsive gamblers. Compared with the general population, these results are significantly higher for alcohol abuse (P < 0.005), nicotine (P < 0.001) and gambling (P < 0.001). Body mass index was significantly higher in the study population (P < 0.001). Addictions and gambling are more prevalent in patients with psoriasis compared with the general population. Respective screening measures are recommended in daily practice for doctors treating psoriasis patients, and PeakPASI is suggested as a score to document patients' lifetime highest PASI. Parallel to new drug approvals and even more detailed insights into the pathomechanism of psoriasis, public health strategies and interdisciplinary approaches are essential for a general sustained psoriasis treatment.


High-performance green electronic substrate employing flexible and transparent cellulose films.
Today's widely used and rapidly updated electronic substrates are composed of petroleum-based polymers, but the resulting electronic waste (such as Dioxin, oxole, PCBs, etc.) will cause massive harm to the environment and human body. Therefore, we report an effective approach for fabricating recyclable and high-performance cellulose films as green electronic substrates by calendering. The crosslinking between CH and CHCH in cellulose modified by maleic anhydride led to the in-situ formation of a chemical crosslinking network, and hydrogen bonds acted as a sacrificial physical crosslinking network. The dual crosslinked cellulose film exhibits high strength (120.56 MPa), improved elongation (increased by 263%), and outstanding thermal stability (thermal decomposition temperature is 311 °C). Further, the film has been successfully used as a substrate for biomass sensor and realized apparent responses to changes. The scientific strategy paves the way for the large-scale fabrication of high-performance cellulose films and simultaneously promotes green electronic substrates' industrialization.


DNA sequences of yeast H3 and H4 histone genes from two non-allelic gene sets encode identical H3 and H4 proteins.
The complete DNA sequences of two loci encoding H3 and H4 histones in Saccharomyces cerevisiae have been determined. Each locus contains one H3 and one H4 gene. The genes at each locus are divergently transcribed and the coding sequences are separated by 646 base-pairs at one locus and 676 base-pairs at the other. The H3 genes code for identical histone H3 proteins and the H4 genes code for identical histone H4 proteins. The yeast proteins differ from histones H3 and H4 of calf by 15 and 8 amino acid substitutions, respectively, and these differences are largely confined to the carboxy-terminal halves of the proteins. The genes demonstrate a bias in synonymous codon usage similar to that noted for other yeast genes. This bias is confined to the coding sequences of the genes and is specific for the reading frame encoding the proteins. The coding sequence of each gene is flanked on both sides by DNA with an A + T content of 70 to 80%. Possible regulatory sequences are located relative to the 5' and 3'-termini of the histone H3 and H4 RNA transcripts.


Migraine and nosebleed in children case series and literature review.
The presence of nose bleeding during a migraine attack as a single occurrence is so far rarely reported. Therefore, we have decided to report such occurrences we have noticed to further improve and build upon possible existing knowledge of such incidences. 728 children with an average age of 11.5 years, suffering from migraine were examined for nose bleeding. All structural, trauma, coagulation and medical causes were excluded. A computer-based literature search was also conducted to identify other cases of such sort. Eight cases (1.1%) of nose bleeding during attacks of migraine with no other known causes were identified. An additional 3 cases were identified in literature, though the presenting age was 25 years or above. In our case series, nose bleeding exclusively occurred during the attacks of headaches, although it was not considerably related to aura, frequency, location or intensity of migraine attacks. The presence of nose bleeding associated with migraine is an uncommon phenomenon and its mechanism is still unknown.


Relationship between Job Satisfaction and Workload of Nurses in Adult Inpatient Units.
Among Nursing and Psychology professionals, the job satisfaction of those in Adult Inpatient Units is analyzed, with a new scale to measure nursing workloads validated. Objective: The objective of this study was to relate nursing workloads to professional job satisfaction. Methods: This is an observational, analytical, descriptive, concurrent and quantitative study, which used the Overall Job Satisfaction scale and subscales therein, to identify global satisfaction-intrinsic or related to motivational factors and extrinsic or associated with hygienic factors-in nursing professionals (n = 104) from eight Inpatient Units of Internal Medicine and Surgery, in four hospital centers, to describe job satisfaction in the professionals studied and to find statistically significant associations between job satisfaction and workload (measured with the scale MIDENF®) in the inpatient units where they work. Results: There were higher levels of satisfaction in the variables "relationship with immediate boss" and "relationship with fellow workers", and lower levels in "relationship with senior management" and "organizational system of the unit". In the inferential analysis, the scores were 75.63 for overall satisfaction, 35.28 for intrinsic satisfaction, and 40.36 for extrinsic satisfaction. Conclusions: There is a close relationship between workload and job satisfaction, showing more dissatisfaction regarding organizational aspects and professional recognition.


Fabrication and Development of Binder-Free Mn-Fe-S Mixed Metal Sulfide Loaded Ni-Foam as Electrode for the Asymmetric Coin Cell Supercapacitor Device.
Currently, the fast growth and advancement in technologies demands promising supercapacitors, which urgently require a distinctive electrode material with unique structures and excellent electrochemical properties. Herein, binder-free manganese iron sulfide (Mn-Fe-S) nanostructures were deposited directly onto Ni-foam through a facile one-step electrodeposition route in potentiodynamic mode. The deposition cycles were varied to investigate the effect of surface morphologies on Mn-Fe-S. The optimized deposition cycles result in a fragmented porous nanofibrous structure, which was confirmed using Field Emission Scanning Electron Microscopy (FE-SEM). X-ray photoelectron spectroscopy (XPS) confirmed the presence of Mn, Fe, and S elements. The energy dispersive X-ray spectroscopy and elemental mapping revealed a good distribution of Mn, Fe, and S elements across the Ni-foam. The electrochemical performance confirms a high areal capacitance of 795.7 mF cm-2 with a 24 μWh cm-2 energy density calculated at a 2 mA cm-2 current density for porous fragmented nanofiber Mn-Fe-S electrodes. The enhancement in capacitance is due to diffusive-controlled behavior dominating the capacitator, as shown by the charge-storage kinetics. Moreover, the assembled asymmetric coin cell device exhibited superior electrochemical performance with an acceptable cyclic performance of 78.7% for up to 95,000 consecutive cycles.


An analysis of the graph processing landscape.
The value of graph-based big data can be unlocked by exploring the topology and metrics of the networks they represent, and the computational approaches to this exploration take on many forms. For the use-case of performing global computations over a graph, it is first ingested into a graph processing system from one of many digital representations. Extracting information from graphs involves processing all their elements globally, which can be done with single-machine systems (with varying approaches to hardware usage), distributed systems (either homogeneous or heterogeneous groups of machines) and systems dedicated to high-performance computing (HPC). For these systems focused on processing the bulk of graph elements, common use-cases consist in executing for example algorithms for vertex ranking or community detection, which produce insights on graph structure and relevance of their elements. Many distributed systems (such as Flink, Spark) and libraries (e.g. Gelly, GraphX) have been built to enable these tasks and improve performance. This is achieved with techniques ranging from classic load balancing (often geared to reduce communication overhead) to exploring trade-offs between delaying computation and relaxing accuracy. In this survey we firstly familiarize the reader with common graph datasets and applications in the world of today. We provide an overview of different aspects of the graph processing landscape and describe classes of systems based on a set of dimensions we describe. The dimensions we detail encompass paradigms to express graph processing, different types of systems to use, coordination and communication models in distributed graph processing, partitioning techniques and different definitions related to the potential for a graph to be updated. This survey is aimed at both the experienced software engineer or researcher as well as the graduate student looking for an understanding of the landscape of solutions (and their limitations) for graph processing.


Pathophysiology, Diagnosis, and New Therapeutic Approaches for Ischemic Mitral Regurgitation.
Ischemic mitral regurgitation (MR) is a valvular complication frequently seen in patients with coronary artery disease and is associated with increased mortality and morbidity. Ischemic mitral regurgitation has a complex, heterogeneous, and still incompletely understood pathophysiology involving both the mitral valve and the left ventricle. The occurrence of valve regurgitation in patients with ischemic cardiomyopathy in return accelerates left ventricular remodelling and dysfunction, ultimately leading to irreversible heart failure. Diagnostic evaluation of ischemic MR is unique and different from the other causes of MR. The severity thresholds associated with outcomes are different from primary MR, and specific imaging characteristics are potentially useful to guide therapy. The use of imaging modalities such as 3-dimensional echocardiography and cardiac magnetic resonance imaging can refine the diagnostic evaluation and help in choosing the correct management. Although multiple treatments are available to improve ischemic MR, each therapeutic option is associated with limitations and incomplete success. Therapy has therefore to be individualised for each patient. Current options include optimal medical therapy, cardiac resynchronisation therapy, percutaneous or surgical revascularisation, surgical mitral repair or replacement, and new percutaneous interventions. This review aims to discuss the latest insights regarding the pathophysiology, diagnosis, and treatment of ischemic MR.


Case-control study to evaluate predictors of lymphedema after breast cancer surgery.
To identify risk factors for lymphedema after breast cancer surgery. Multisite case-control study. Lymphedema clinics in the upper midwestern region of the United States. 94 patients with lymphedema and 94 controls without lymphedema, matched on type of axillary surgery and surgery date. The Measure of Arm Symptom Survey, a patient-completed tool, assessed potential risk factors for lymphedema. Severity of lymphedema was measured by arm circumference, and disease and treatment factors were collected via chart review. Risk factors for lymphedema after breast cancer surgery. On univariate analysis, patients with lymphedema were more likely than controls to be overweight (body mass index >or= 25) (p = 0.009). They also were more likely to have had axillary radiation (p = 0.011), mastectomy (p = 0.008), chemotherapy (p = 0.033), more positive nodes (p = 0.009), fluid aspirations after surgery (p = 0.005), and active cancer status (p = 0.008). Strength training (p = 0.014) and air travel (p = 0.0005) were associated with less lymphedema occurrence. On multivariate analysis, the only factor significantly associated with lymphedema was being overweight (p = 0.022). Being overweight is an important modifiable risk factor for lymphedema. Axillary radiation, more extensive surgery, chemotherapy, and active cancer status also were predictive of lymphedema. This study provides evidence that excess weight contributes to lymphedema; strength training and airline travel did not contribute to lymphedema.


Synthesis of N6-alkyl(aryl)-2-alkyl(aryl)thioadenosines as antiplatelet agents.
A series of novel N(6)-alkyl(aryl)-2-alkyl(aryl)thioadenosines were synthesized, and their human antiplatelet aggregation activities were evaluated by the stimulation of adenosine 5'-diphosphate (ADP). Some of these compounds showed strong activity, among which compound 5b(11) displayed the highest activity with an IC(50) value of 29 ± 3 μM. Furthermore, five compounds were tested against arachidonic acid (AA)-induced human platelet aggregation. The results showed that compound 5b(10) exhibited the highest activity with an IC(50) value of 3 ± 2 μM. The adenosine derivatives substituted with a phenethyl group at the N(6) position and a methylthio or ethylthio group at the C-2 position displayed high antiplatelet aggregation activity.


A comparative analysis of intrusion of incisor teeth achieved in adults and children according to facial type.
A comparison was made of incisor intrusion achieved in adults and children with deep bite. Facial type was also examined for effect upon intrusion achieved. Fifty-five cases treated with bioprogressive mechanics were studied cephalometrically; subjects included twenty-four adults and thirty-one children. Neither age nor facial type was found to be statistically related to the amount of incisor intrusion achieved in this sample. A method of measuring intrusion at the root apices was devised and was thought to give a more accurate indication of actual bodily intrusion. More external root changes during treatment were observed for adults than for growing children. There was a wide latitude in the amount of intrusion observed in both groups and in all three facial types. Considerable overbite reduction was noted for the sample, and intrusion was found to be but one factor in this.


[Treating, negotiating and referring. Perspective of the dentist and specialist].
Dentists and dental specialists are in general well aware of the professional treatment standards. Nevertheless, it is occasionally necessary or unavoidable to adjust or even to ignore these standards in the management of an individual patient.


Handedness switching as a presenting sign for pediatric low-grade gliomas: An insight into brain plasticity from a short case series.
To describe clinical data, rehabilitation services, and outcomes of children with handedness switching as their presenting symptom before low-grade glioma (LGG) diagnosis. A retrospective chart review was performed for five patients (four female and four white) with LGG and confirmed handedness switching before LGG diagnosis. All children were less than 8 years at diagnosis, and two patients were less than 3 years. All children were initially right-handed and experienced loss of motor function, ranging from weakness to paresis, in their dominant hand. The median time from switching handedness to diagnosis was 1 month (range: 0.75-60 months). Rehabilitation was offered for three patients, and motor function deficits in the initial dominant hand were resolved in two of the total cohort. At long-term follow-up, hand dominance returned to the initial hand in three patients. Handedness switching should be acknowledged as a potential sign of LGG in children, and early long-term rehabilitation services should be offered for these children.


Cardiomegaly secondary to patent ductus arteriosus causing extrinsic compression of left pulmonary vein.
Primary pulmonary vein (PV) stenosis is a challenging condition to manage. Recently, extrinsic compression of the PV is being detected has cause of narrowing and subsequent turbulence. This can be managed without direct intervention on the PV, reducing the risk of recurrence. We report a case of extrinsic compression of the PV due to cardiomegaly, relieved after patent ductus arteriosus ligation.


Immunohistochemical detection of early myocardial damage in two sudden deaths due to intentional butane inhalation. Two case reports with review of literature.
The abuse of household and other commercially available products containing volatile organic solvents is underrecognized. Not infrequently intentional butane inhalation results in high morbidity and mortality. A fatal outcome of butane abuse can be caused by asphyxia, cardiac arrhythmia or trauma. The reported number of cases in which death was the consequence of pure butane inhalation is limited, and in most cases a mixture of propellants was involved. This report covers two cases of sudden death due to the sniffing of a cigarette lighter refill containing butane. Autopsy was followed by toxicological, pathohistological and immunohistochemical analysis. Butane gas was confirmed in samples of blood, urine, brain and lungs by the gas chromatography method - "headspace" technique. Histology showed almost identical changes in the lungs and heart in both cases. The morphology of heart damage on standard H/E stains was of special interest because it displayed all the characteristics of chronic and acute myocardial hypoxia found in the absence of atherosclerotic heart disease. In order to confirm early cardiac death caused by asphyxia due to butane inhalation a panel of immunohistochemical agents was used: Myoglobin, Desmin, Fibronectin, Fibrinogen and CC9.


The cellular uptake and cytotoxic effect of curcuminoids on breast cancer cells.
Curcuminoids (including curcumin) are natural antioxidants demonstrating potent chemopreventive properties against several forms of cancer. This study investigated the antiproliferative and induced apoptotic effects of curcuminoids on three cell lines isolated from human breast adenocarcinoma and ductal carcinoma (MDA-MB-231, MDA-MB-435S, and MCF-7). This study developed a highly sensitive, reproducible assay method using high-pressure liquid chromatography to quantify the cellular uptake of curcuminoids by breast cancer cells and quantitate its effect on inhibition of proliferation and activation of apoptosis in breast cancer cells. Results indicate that curcuminoids inhibited cell proliferation and activation of apoptosis in the cell lines in this study. Both effects were observed to increase in proportion to the cellular uptake of curcuminoids; cellular uptake increased following an increase in the dosage of curcuminoids. The inhibition of proliferation and increased apoptosis of breast cancer cells appears to be associated with the uptake of curcuminoids by cancer cells.


The crystal structure of sulfamethoxazole, interaction with DNA, DFT calculation, and molecular docking studies.
Sulfamethoxazole (SMX) [4-amino-N-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide] is structurally established by single crystal X-ray diffraction measurement. The crystal packing shows H-bonded 2D polymer through N(7)-H(7A)-O(2), N(7)-H(7B)-O(3), N(1)-H(1)-N(2), C(5)-H(5)-O(3)-S(1) and N(7)-(H7A)-O(2)-S(1). Density Functional Theory (DFT) and Time Dependent-DFT (TD-DFT) computations of optimized structure of SMX determine the electronic structure and has explained the electronic spectral transitions. The interaction of SMX with CT-DNA has been studied by absorption spectroscopy and the binding constant (Kb) is 4.37×10(4)M(-1). The in silico test of SMX with DHPS from Escherichia coli and Streptococcus pneumoniae helps to understand drug metabolism and accounts the drug-molecule interactions. The molecular docking of SMX-DNA also helps to predict the interaction feature.


Basal cell carcinoma: 10-year experience with electrochemotherapy.
Electrochemotherapy (ECT), by combining manageable cytotoxic agents with short electric pulses, represents an effective palliative skin-directed therapy. The accumulated evidence indicates that ECT stands out as a safe and well-tolerated alternative treatment for patients with multiple or large basal cell carcinoma (BCC), who are not suitable for conventional treatments. However, long-term data and shared indications are lacking. In this observational study, we retrospectively analyzed 84 prospectively collected patients with multiple, recurrent or locally advanced BCC who were not candidate for standard therapies and received bleomycin-based ECT according to the European Standard Operative Procedures of ECT, from 2006 to 2016. Disease extent was local, locally advanced and metastatic in 40 (48%), 41 (49%) and 3 (3%), respectively. Forty-four (52%) individuals had multiple BCCs. Grade 3 skin toxicity after ECT was observed in 6% of cases. Clearance rate was 50% (95% CI 39-61%). Primary presentation (p = 0.004), tumor size <3 cm (p < 0.001), well-defined borders (p = 0.021), absence of tumor ulceration (p = 0.001), non-aggressive BCC histology (p = 0.046) and age ≤69 years were associated with higher complete response rate. In patients with local BCC, the clearance rate was 72.5 and 85% after one or two ECT cycles, respectively. In the laBCC group, 32 patients (78%) achieved an objective response. Five-year recurrence rate for local and laBCC was 20 and 38%, respectively (p ≤ 0.001). One or two ECT cycles with bleomycin may be a valuable palliative treatment in well-selected patients with multiple BCCs and favorable tumor features. Validation of predictive factors will be imperative to match patients with optimal ECT treatment modalities. Management of laBCC with ECT warrants further investigation. Trial registration ISRCTN14633165 Registered 24 March 2017 (retrospectively registered).


[Retracted] CCL26 regulates the proportion of CD4+CD25+FOXP3+ Tregs and the production of inflammatory factors in peripheral blood mononuclear cells following acute ischemic stroke via the STAT5 pathway.
[This retracts the article DOI: 10.3892/etm.2020.9046.].


Maternal peripartum bacteremia caused by intrauterine infection with Comamonas kerstersii: A case report.
Comamonas kerstersii (C. kerstersii) infections have considered as non-pathogenic to humans, however due to new techniques such as matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS), more cases have been identified. This is the first report of a maternal patient with a C. kerstersii bacteremia following caesarean section. Due to the severity of the patient's condition; high fever and rapidly progressing organ damage, the patient was transferred to the intensive care unit. C. kerstersii was detected by metagenomic next-generation sequencing testing. Based on the drug sensitivity test, appropriate antibiotic treatment was given and the patient recovered fully. This case report confirms that the detection via MALDI-TOF-MS and metagenomic next-generation sequencing testing provides a reliable basis for the diagnosis of this rare bacterial infection.


Functional analysis of neutrophil granulocytes from healthy, infected, and stressed neonates.
Neutrophil granulocyte function was assessed in 17 well term infants, 14 stressed infants, and eight infants with group B streptococcal infection. Chemiluminescence production elicited by opsonized zymosan or by a wild strain of type III group B streptococci, as well as phagocytosis and killing of streptococci, were measured. Chemiluminescence production by PMNs of term neonates in response to opsonized zymosan or group B streptococci was equal to that of adult controls. In contrast, six of nine stressed or infected neonates had depressed CL responses upon zymosan challenge. When opsonized type III group B streptococci were used to elicit CL, seven of ten stressed or infected infants had markedly depressed responses. Phagocytosis, as determined by a radiolabeled bacterial uptake technique, was normal in the healthy and stressed neonates. Depressed CL production by the PMNs of stressed or infected neonates was associated with impaired intracellular bactericidal activity, however. These studies indicate that stressed or infected neonates have impaired leukocyte metabolic activation that may be associated with depressed bactericidal activity. Such impairment may contribute to the morbidity and mortality observed in serious neonatal infections.


A transcription stimulatory factor binds to the upstream region of Xenopus 5 S RNA and tRNA genes.
Upstream sequence elements modulate transcription efficiency and competition strength of eucaryotic 5 S rRNA and tRNA genes transcribed by RNA polymerase III. We report on the chromatographic separation and functional characterization of at least two components involved in this process: one has a DNA binding activity and interacts with the immediate upstream region of Xenopus tRNA and 5 S rRNA genes, and a second component, which by itself does not interact with the upstream region of these genes, is required together with the DNA binding activity for transcription stimulation in vitro.


VanabinP, a novel vanadium-binding protein in the blood plasma of an ascidian, Ascidia sydneiensis samea.
Some ascidians accumulate high levels of the transition metal vanadium in their blood cells. The process of vanadium accumulation has not yet been elucidated. In this report, we describe the isolation and cDNA cloning of a novel vanadium-binding protein, designated as VanabinP, from the blood plasma of the vanadium-rich ascidian, Ascidia sydneiensis samea. The predicted amino acid sequence of VanabinP was highly conserved and similar to those of other Vanabins. The N-terminus of the mature form of VanabinP was rich in basic amino acid residues. VanabinP cDNA was originally isolated from blood cells, as were the other four Vanabins. However, Western blot analysis revealed that the VanabinP protein was localized to the blood plasma and was not detectable in blood cells. RT-PCR analysis and in situ hybridization indicated that the VanabinP gene was transcribed in some cell types localized to peripheral connective tissues of the alimentary canal, muscle, blood cells, and a portion of the branchial sac. Recombinant VanabinP bound a maximum of 13 vanadium(IV) ions per molecule with a Kd of 2.8 x 10(-5) M. These results suggest that VanabinP is produced in several types of cell, including blood cells, and is immediately secreted into the blood plasma where it functions as a vanadium(IV) carrier.


Can subunit-specific phenotypes guide surveillance imaging decisions in asymptomatic SDH mutation carriers?
With the discovery that familial phaeochromocytoma and paraganglioma syndrome can be caused by mutations in each subunit of the succinate dehydrogenase enzyme (SDH), has come the recognition that mutations in the individual subunits have their own distinct natural histories. Increased genetic screening is leading to the identification of increasing numbers of, mostly asymptomatic, gene mutation carriers and the implementation of screening strategies for these individuals. Yet there is, to date, no international consensus regarding screening strategies for asymptomatic carriers. A comprehensive PubMed search from 1/1/2000 to 28/2/2018 was undertaken using multiple search terms and subsequently a manual review of references in identified papers to identify all clinically relevant cases and cohorts. In this review, the accumulated, published experience of phenotype and malignancy risks of individual SDH subunits is analysed. Where possible screening results for asymptomatic SDH mutation carriers have been analysed separately to define the penetrance in asymptomatic carriers (asymptomatic penetrance). The combined data confirms that "asymptomatic penetrance" is highest for SDHD and when there is penetrance, the most likely site to develop a PGL is head and neck (SDHD) and extra-adrenal abdominal (SDHB). However, the risk in SDHB carriers of developing HNPGL is also high (35.5%) and a PCC is low (15.1%), and in SDHD carriers there is a high risk of developing a PCC (35.8%) or abdominal PGL (9.4%) and a small, but significant risk at other sympathetic sites. The data suggest that the risk of malignant transformation is the same for both PCC and extra-adrenal abdominal PGLs (30%-35%) in SDHB carriers. In SDHD carriers, the risk of malignant transformation was highest in HNPGLs (7.5%) and similar for sympathetic sites (3.8%-5.2%). Using this data, we suggest surveillance screening of asymptomatic carriers can be tailored to the underlying SDH subunit and review possible surveillance programmes.


A new deletion in 5'-end of dystrophin gene removing M and P promoters and dystrophin muscle enhancers.
We describe a 3-year-old boy who, at age of 8 months, during investigations for upper respiratory tract infection was found to have an incidental grossly elevated CK of 20,000 UI/l. Investigations showed only mild calf hypertrophy and absent Gower's sign, normal cognitive function. Electromyography (EMG) showed myopathic features. Electrocardiography and echocardiography were normal. His muscle biopsy revealed myopathic features indicating Duchenne-type dystrophy. Immunohistochemistry for dystrophin N-terminal, C-terminal and mid-rod antibodies analysis showed the complete absence of dystrophin in the muscle fibers. Genetic studies showed a 141.1 Kb deletion removing muscle promoter, muscle exon 1, Purkinje promoter, Purkinje exon 1, dystrophin muscle enhancers similar to one previously reported in a DMD patient who exhibited some residual expression of dystrophin. The difference in dystrophin expression between these two patients might be due to the extension of deletions. The precise delimitation of the macrodeletion here described provides a better understanding of functional organization of the 5' end of the DMD gene.


Immunological and Clinical Benefits of Maternal Immunization Against Pertussis: A Systematic Review.
Infants are vulnerable to pertussis infection particularly before initiation of pertussis vaccination. Maternal pertussis vaccination during pregnancy has been introduced in a number of countries in order to confer on young infants indirect protection from the disease through transplacental transfer of maternal antibodies. We reviewed the evidence on the immunogenicity and efficacy of maternal pertussis vaccination during pregnancy. A systematic search of PubMed/MEDLINE, EMBASE, Scopus, Cochrane Database of Systematic Reviews, ProQuest, and Science Direct was undertaken to identify studies published between January 1995 and December 2018. This review was not specific to any particular pertussis vaccine but included applicable data on available pertussis vaccines administered to pregnant women. The search identified 40 publications for inclusion in this review. Vaccination during pregnancy elicited robust maternal immune responses against all vaccine antigens and resulted in high placental transfer of pertussis antibodies to the infant that persisted well beyond delivery. Vaccination during the second or early third trimesters was considered ideal for antibody quantity and functionality. Although blunting of immune responses to some antigens in the primary immunization series was documented in neonates born to women vaccinated during pregnancy, there was no apparent adverse effect on vaccine efficacy. Multiple studies conducted in diverse settings have confirmed the effectiveness of maternal pertussis vaccination during pregnancy in preventing pertussis in infants prior to receipt of their first primary vaccine dose and beyond. These findings collectively underscore the value of maternal pertussis vaccination during pregnancy in protecting vulnerable infants too young to be vaccinated.Funding Sanofi Pasteur.Plain Language Summary Plain language summary available for this article.


Patterns of expression of the six alternatively spliced exons affecting the structures of the COL1 and NC2 domains of the alpha 1(XIII) collagen chain in human tissues and cell lines.
Reverse transcription-polymerase chain reactions and RNA protection experiments were used to examine alternative splicing of the six exons 3B-5, 12, and 13 affecting the COL1 and NC2 domains of type XIII collagen in seven human tissues and four cell lines. Distinct differences in the proportions of the variant mRNAs were found. With respect to the COL1 domain, all studied samples contained mRNAs corresponding to the shortest COL1 variants of 57 and 66 residues, with the former variant being prominent in most samples. Most of the samples also contained notable amounts of mRNAs that corresponded to the longest COL1 variants, mainly those of 104 and 95 residues. Particularly the extent of inclusion of exon 12 and 13 sequences, encoding most of the NC2 domain, varied according to the type of tissue or cell analyzed. Bone, cartilage, and colon adenocarcinoma samples contained little or none of the mRNAs corresponding to the long NC2 variants, whereas in fibroblast, lung, muscle, and osteosarcoma cells, those mRNAs were the major variants. The relative proportions of the various combinations of exons 3B-5, 12, and 13 were evaluated in four of the RNA samples. Interestingly, each of these samples appeared to contain only one to three major combinations of the six exons, representing about 40% to nearly 100% of all variants.


Mortality after exposure to polychlorinated biphenyls and dibenzofurans: 30 years after the "Yucheng accident".
In 1979, approximately 2,000 people in central Taiwan were accidentally exposed to polychlorinated biphenyls and dibenzofurans due to ingestion of contaminated cooking oil. This event was called Yucheng, "oil-syndrome" in Chinese. We followed the exposed persons and compared their cause-specific mortality with that of neighborhood referents 30 years after the accident. We obtained age- and gender-matched referents from the 1979 neighborhoods of the exposed people. Cause-specific mortality was compared between exposed subjects (N=1803) and their neighborhood referents (N=5170) using standardized mortality ratios (SMR). Total person-years for the Yucheng subjects and neighborhood referents were 48,751 and 141,774, respectively. The SMR for all causes (SMR=1.2, 95% CI: 1.1-1.3), diseases of the circulatory system (SMR=1.3, 95% CI: 1.0-1.6), and diseases of the musculoskeletal system and connective tissue (SMR=6.4, 95% CI: 2.8-12.7) were elevated in Yucheng subjects. Among Yucheng males, the SMRs for diseases of the digestive system (SMR=1.9, 95% CI: 1.2-2.8), malignant neoplasm of stomach (SMR=3.5, 95% CI: 1.5-7.0), and malignant neoplasm of lymphatic and hematopoietic tissue (SMR=3.0, 95% CI: 1.1-6.6) were increased. The SMR for total neoplasms was increased (SMR=1.3, 95% CI: 0.9-1.7). We conclude that exposure to PCBs/PCDFs at levels that produced symptoms in many affects mortality patterns 3 decades after exposure.


Ancient gene transfer as a tool in phylogenetic reconstruction.
Although horizontal gene transfer (HGT) is often considered as a disruptive force in reconstructing organismal phylogeny, it can also be a valuable phylogenetic tool. A gene in the net of life is often horizontally transferred to the ancestor of a major lineage. If the gene is retained in the recipient and its descendants, it will constitute a shared derived character and mark the recipient and all descendants as a monophyletic group. Additionally, phylogenetically informative HGTs also provide information about the sequence of emergence of involved taxa, because the donor organism must have emerged at least as early as the recipient. Here we review the recent applications of ancient HGT events in reconstructing organismal phylogeny as well as the promise and potential pitfalls of this approach.


Therapeutic potential of targeted-gold nanospheres on collagen-induced arthritis in rats.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes functional disability due to bone destruction and severe joint pain. Current anti-rheumatic treatments develop severe complications and do not provide complete remission. Gold nanoparticles (AuNPs) have garnered attention because of their unique physical and chemical properties. In this study, we have evaluated the therapeutic effects of gold nanospheres (AuNSs) with two different ligands (targeted-nanoparticles) against collagen-induced arthritis (CIA) and compared the outcomes with conventional methotrexate (MTX) and biological (infliximab) treatments. Clinical evaluation was performed by radiographic and histological examinations. The bioaccumulation of AuNSs in vital organs was assessed. The mechanistic studies targeting pro-inflammatory/anti-inflammatory and angiogenic mediators' expressions were performed. Radiographic examination showed that the targeted AuNSs reduced joint space narrowing and bone erosion. Moreover, histopathological examination of rat ankle joints demonstrated that targeted AuNSs reduce bone and cartilage degeneration/inflammation. Gold nanospheres-conjugated with nucleus localized peptide (nuclear membrane-targeted) (AuNSs@NLS) has resolved bone destruction and inflammation compared to gold nanospheres-conjugated at polyethylene glycol (AuNSs@PEG). Although the AuNSs accumulated in different organs in both cases, they did not induce any toxicity or tissue damage. The two different targeted AuNSs significantly suppress inflammatory and angiogenic mediators' expression and induced anti-inflammatory cytokine production, but the AuNSs@NLS had superior therapeutic efficacy. In conclusion, these results suggested that nuclear membrane-targeted AuNSs effectively attenuated arthritis progression without systemic side effects.


The effects of large, small, and thinning magnitudes of alternative reinforcement on resurgence.
Resurgence refers to an increase of a previously reinforced target behavior following the worsening of conditions for a more recently reinforced alternative behavior. There is evidence to suggest that alternative reinforcers of greater magnitude are more effective at reducing target responding but may also result in more resurgence when removed. Similar effects have been observed with high rates of alternative reinforcement. However, in clinical settings, reinforcement rate thinning is used to reduce the likelihood of resurgence associated with higher rates of alternative reinforcement. Given the clinical importance of alternative reinforcer magnitude, it is necessary to evaluate how reinforcer magnitude thinning may impact resurgence as well. Following Phase 1 in which target responding was reinforced, rats earned either large (six pellets), small (one pellet), or thinned (reduced from six pellets to one across sessions) magnitude reinforcement for alternative responding during target-response extinction in Phase 2. Then, alternative responding was placed on extinction for all groups in Phase 3. Target responding was comparably elevated at the end of Phase 2 for groups Small and Thin compared to group Large. In Phase 3, resurgence was evident only in group Large but target responding remained relatively elevated in groups Small and Thin. These results provide additional evidence of the important interplay between conditions of alternative reinforcement and the persistence and resurgence of target responding.


Hemodynamic effects of naloxone in anaphylactic shock.
Recent reports suggest that endorphins may contribute to hemodynamic depression in septic and hemorrhagic shock. There is also evidence that reversal of endorphin effects with high dose naloxone may improve hemodynamic function and improve survival in shock states. The purpose of this study was to examine the effects of naloxone on hemodynamic parameters in anaphylactic shock. Anaphylactic shock was induced in sensitized rabbits with horse serum. Three minutes after serum challenge, rabbits were treated with a 3 mg/kg bolus of naloxone followed by a 3 mg/kg per h infusion (group I, n = 8), or by injection with an equal volume of saline (group II, n = 8). Cardiac output, blood pressure, heart rate and body temperature were monitored continuously for 60 min and the experiment was terminated. There was a significant increase in cardiac index in group I animals at 10 min (P less than 0.01) and 15 min (P less than 0.01). Stroke volume index was also higher in naloxone treated animals at 10 min and 15 min (P less than 0.05). Although mean blood pressure was higher in group I animals at all time intervals after naloxone was begun, the difference was statistically significant only at 60 min (P less than 0.05). Peripheral vascular resistance index was not significantly different for the two groups.


Shedding of anti-IgM from antibody-coated human lymphoma lines: differences between Epstein-Barr virus-negative lines and their virus-converted sublines.
In vitro converted, Epstein-Barr (EBV) genome-carrying cell lines showed a reduced ability to shed surface-bound antibodies, compared to their EBV-free parental B lymphoma lines. On the other hand, antibody degradation was higher with EBV-positive cells. Analysis of antibody-coated single cells revealed that cells which failed to redistribute or cap their ligand-bound surface components at 37 degrees C, were also capable of shedding bound antibody. This suggests that capping and shedding are essentially independent phenomena, although both may be influenced by the same virally induced change in the lateral mobility of membrane constituents.


Effect of serum zinc and copper levels on insulin secretion, insulin resistance and pancreatic β cell dysfunction in US adults: Findings from the National Health and Nutrition Examination Survey (NHANES) 2011-2012.
To compare zinc (Zn) and copper (Cu) levels in US adults with normoglycemia, prediabetes and diabetes, and study the association of serum Zn and Cu levels with pancreatic β cell insulin secretion, pancreatic dysfunction and insulin resistance in US adults with normoglycemia and prediabetes. Homeostatic Model Assessment (HOMA2) calculator was used to compute estimates of steady state β cell insulin secretion (HOMA2-B), peripheral insulin sensitivity (HOMA2-S), insulin resistance (HOMA-IR), and disposition index (HOMA-DI) in 804 adult individuals from the National Health and Nutrition Examination Survey (NHANES 2011-2012). There was no significant difference between serum Zn and Cu levels among subjects with normoglycemia, prediabetes, and diabetes. After adjusting for multiple possible confounders, higher serum Zn concentrations were associated with lower β cell insulin secretion (HOMA2-B; p = 0.01) and lower insulin resistance (HOMA-IR; p = 0.04) in the prediabetic subjects. In normoglycemic group, higher serum Zn levels were associated with improved pancreatic function (HOMA-DI; P = 0.02). On the other hand, higher serum Cu levels were associated with increased β cell insulin secretion (HOMA2-B, P = 0.03) only in the subjects with prediabetes. These findings support the need for further studies to investigate the role of trace elements in diabetes pathogenesis.


Occurrence of triatomines in public spaces: An atypical case in the Southwestern Brazilian Amazon.
Triatomines infest atypical public spaces in the Western Amazon. Frequent visitors to these spaces captured the insects in the state of Acre, Brazil (Rio Branco and Cruzeiro do Sul). Six insects were found in a penitentiary, a church, a school, a university, a hospital, and a health center. Five of the insects were adults (three positive for Trypanosoma cruzi) and one was a nymph. This is the first report of triatomine occurrence in schools or churches. These data are important for implementing surveillance strategies and alerting individuals about possible changes in Chagas disease transmission dynamics.


An immunohistochemical study of the distribution of intermediate filaments in the ovary of the emu (Dromaius novaehollandiae).
The immunohistochemical localization of the intermediate filaments desmin, vimentin and smooth muscle actin (SMA) in the ovary of the emu was described in the present study. The cortical region of the ovary contained developing and atretic primordial, pre-vitellogenic and vitellogenic follicles. Vimentin immunostaining was demonstrated in the granulosa cell layer of primordial, pre-vitellogenic and vitellogenic developing and atretic follicles. An interesting finding of the present study was the localization of SMA in fibroblasts located in the theca externa of late vitellogenic follicles. The presence of SMA in these fibroblasts suggests that they possess characteristics of smooth muscle cells.


Systemic treatments in MDM2 positive intimal sarcoma: A multicentre experience with anthracycline, gemcitabine, and pazopanib within the World Sarcoma Network.
Intimal sarcoma (InS) is an exceedingly rare neoplasm with an unfavorable prognosis, for which new potentially active treatments are under development. We report on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in patients with InS. Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis. Patients with MDM2-positive InS who were treated with anthracycline-based regimens, gemcitabine-based regimens, or pazopanib between October 2001 and January 2018 were selected. Local pathological review was performed to confirm diagnosis. Response was assessed by RECIST1.1. Recurrence-free survival (RFS), progression-free survival (PFS) and overall survival were computed by Kaplan-Meier method. Seventy-two patients were included (66 anthracycline-based regimens; 26 gemcitabine-based regimens; 12 pazopanib). In the anthracycline-based group, 24 (36%) patients were treated for localized disease, and 42 (64%) patients were treated for advanced disease. The real-world overall response rate (rwORR) was 38%. For patients with localized disease, the median RFS was 14.6 months. For patients with advanced disease, the median PFS was 7.7 months. No anthracycline-related cardiac toxicity was reported in patients with cardiac InS (n = 26). For gemcitabine and pazopanib, the rwORR was 8%, and the median PFS was 3.2 and 3.7 months, respectively. This retrospective series shows the activity of anthracycline-based regimens in InS. Of note, anthracyclines were used in patients with cardiac InS with no significant cardiac toxicity. The prognosis in patients with InS remains poor, and new active drugs and treatment strategies are needed.


Bi-allelic variants in MTMR5/SBF1 cause Charcot-Marie-Tooth type 4B3 featuring mitochondrial dysfunction.
Charcot-Marie-Tooth disease (CMT) type 4B3 (CMT4B3) is a rare form of genetic neuropathy associated with variants in the MTMR5/SBF1 gene. MTMR5/SBF1 is a pseudophosphatase predicted to regulate endo-lysosomal trafficking in tandem with other MTMRs. Although almost ubiquitously expressed, pathogenic variants primarily impact on the peripheral nervous system, corroborating the involvement of MTMR5/SBF1 and its molecular partners in Schwann cells-mediated myelinization. We report a case of severe CMT4B3 characterized by early-onset motor and axonal polyneuropathy in an Italian child in absence of any evidence of brain and spine MRI abnormalities or intellectual disability and with a biochemical profile suggestive of mitochondrial disease. Using an integrated approach combining both NGS gene panels and WES analysis, we identified two novel compound heterozygous missense variants in MTMR5/SBF1 gene, p.R763H (c.2291G > A) and p.G1064E (c.3194G > A). Studies in muscle identified partial defects of oxidative metabolism. We describe the first case of an early onset severe polyneuropathy with motor and axonal involvement, due to recessive variants in the MTMR5/SBF1 gene, with no evidence of brain and spine MRI abnormalities, intellectual disability, no clinical and neurophysiological evidences of distal sensory impairment, and rapid neuromuscular deterioration. This report suggests that MTMR5/SBF1 should be considered in cases of infantile-onset CMT with secondary mitochondrial dysfunction.


New perspectives on substituted relational autonomy for shared decision-making in critical care.
In critical care when unconscious patients are assisted by machines, humanity is mainly ensured by respect for autonomy, realised through advance directives or, mostly, reconstructed by cooperation with relatives. Whereas patient-centred approaches are widely discussed and fostered, managing communication in complex, especially end-of-life, situations in open intensive care units is still a point of debate and a possible source of conflict and moral distress. In particular, healthcare teams are often sceptical about the growing role of families in shared decision-making and their ability to represent patients' preferences. New perspectives on substituted relational autonomy are needed for overcoming this climate of suspicion and are discussed through recent literature in the field of medical ethics.


Outcomes of the RAFT trial: robotic surgery after focal therapy.
To report toxicity of treatment observed in men participating in the Robotic surgery After Focal Therapy (RAFT) clinical trial. Men were eligible for this prospective single group interventional study if they had histologically confirmed recurrent/residual prostate adenocarcinoma following primary FT. The short-form Expanded Prostate Cancer Index Composite (EPIC-26) measured prior to salvage robotic prostatectomy (S-RARP) and 3-monthly post-operatively together with Clavien-Dindo complications (I-IV). Secondary outcomes included biochemical recurrence-free survival (BCFS) following surgery and need for salvage treatment after surgery. This study is registered with ClinicalTrials.gov NCT03011606. Twenty-four men were recruited between February 2016 and September 2018. 1 patient withdrew from the trial after consenting and before S-RARP. 23 men completed 12-month post S-RARP follow-up. Median EPIC-26 urinary continence scores initially deteriorated after 3 months (82.4 vs 100) but there was no statistically significant difference from baseline at 12 months (100 vs 100, P = 0.31). Median lower urinary tract symptom scores improved after 12 months compared to baseline (93.8 vs 87.5, P = 0.01). At 12 months, 19/23 (83%) were pad-free and 22/23 (96%) required 0/1 pads. Median sexual function subscale scores deteriorated and remained low at 12 months (22.2 vs 58.3, P < 0.001). Utilising a minimally important difference of nine points, at 12 months after surgery 17/23 (74%) reported urinary continence to be 'better' or 'not different' to pre-operative baseline. The corresponding figure for sexual function (utilising a minimally important difference of 12 points) was 7/23 (30%). There was no statistically significant difference on median bowel/hormonal subscale scores. Only a single patient had a post-operative complication (Clavien-Dindo Grade I). BCFS at 12 months after surgery was 82.6% (95% confidence interval [CI]: 60.1-93.1%) while 4/23 (17%) received salvage radiation. The RAFT clinical trial suggests toxicity of surgery after FT is low, with good urinary function outcomes, albeit sexual function deteriorated overall. Oncological outcomes at 12 months appear acceptable.


Empathy in Medical Education: Its Nature and Nurture - a Qualitative Study of the Views of Students and Tutors.
Medical education is committed to teaching patient centred communication and empathy. However, quantitative research suggests empathy scores tend to decline as students progress through medical school. In qualitative terms, there is a need to better understand how students and tutors view the practice and teaching of clinical empathy and the phenomenon of empathic erosion. Working within a constructivist paradigm, researchers thematically analysed the individual interview data from a purposive sample of 13 senior students and 9 tutors. The four major themes were as follows: (1) 'the nature of empathy', including the concept of the innate empathy that students already possess at the beginning of medical school; (2) 'beyond the formal curriculum' and the central importance of role modelling; (3) 'the formal curriculum and the tick-box influence of assessments'; and (4) the 'durability of empathy', including ethical erosion and resilience. A garden model of empathy development is proposed - beginning with the innate seeds of empathy that students bring to medical school, the flowering of empathy is a fragile process, subject to both enablers and barriers in the formal, informal, and hidden curricula. This study provides insights into empathic erosion in medical school, including the problems of negative role modelling and the limitations of an assessment system that rewards 'tick-box' representations of empathy, rather than true acts of compassion. It also identifies factors that should enable the flowering of empathy, such as new pedagogical approaches to resilience and a role for the arts and humanities.


Chemical instability of octadecylammonium monolayers.
Octadecylammonium in monolayers transforms into a carbamate derivative, as observed by attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and 13C nuclear magnetic resonance (NMR) spectroscopy.


Correction to: Insights into the mechanism(s) of digestion of crystalline cellulose by plant class C GH9 endoglucanases.
The article Insights into the mechanism(s) of digestion of crystalline cellulose by plant class C GH9 endoglucanases, written by Siddhartha Kundu, was originally published Online First without Open Access.


Rapid up- and down-regulation of hexokinase II in rat skeletal muscle in response to altered contractile activity.
An up to 14-fold increase in total hexokinase activity induced by low-frequency stimulation in rat fast-twitch muscle was followed by a rapid decay in enzyme activity after cessation of stimulation. In vivo labeling revealed that these alterations were related to rapid changes in [35S]methionine incorporation into hexokinase II. A recovery period of 15 h after cessation of stimulation was sufficient to normalize the approximately 30-fold elevated [35S]methionine incorporation.


A study of Cisplatin-radiosensitization through inhibition of repair of sublethal radiation-damage in ovarian-carcinoma cells sensitive and resistant to Cisplatin.
Human ovarian carcinoma parental cells and cisplatin resistant variants were evaluated for the effect of cisplatin on radiosensitization and repair of sublethal radiation damage. The data showed that for 1 h cisplatin treatment (2 mu g/ml), radiosensitization was achieved only if the drug was given after irradiation. Cisplatin treatment was also able to inhibit repair of sublethal radiation damage (SLDR). The degree of inhibition was about the same in the resistant and the sensitive cell lines. In the parental line 4 mu g/ml cisplatin was required to inhibit SLDR while in the resistant line both 2 and 4 mu g/ml produced inhibition of SLDR and in the resistant cell line the degree of SLDR inhibition was greater for cisplatin after irradiation compared to cisplatin before irradiation.


Preparation of V-type cold water-swelling starch by ethanolic extrusion.
Ethanolic extrusion was used to prepare V-type cold water-swelling starch (VCWSS). Effects of extrusion temperature, ratio of starch to ethanol, and ratio of starch to water on the properties of VCWSS were investigated. It was found that when the extrusion temperature was 100 °C, the ratio of starch to ethanol was 1:0.30, and the ratio of starch to water was 1:0.60, the resulting VCWSS could quickly swell into paste in cold water with the highest V-type relative crystallinity (12.90%) and cold paste viscosity (3058 cP). Then the formation mechanism of cold paste viscosity of VCWSS was evaluated. The cold paste viscosity of VCWSS was positively related to its V-type relative crystallinity. Extrusion destroyed the granular morphology of native starch, and VCWSS particles exhibited rock-like morphology that is much larger than the granules of native starch. Formation of the V-amylose-ethanol complex during extrusion was the direct cause of rapid hydration of VCWSS.


The amino-terminus of the E2F-1 transcription factor inhibits DNA replication of autonomously replicating plasmids in mammalian cells.
The E2F1 transcription factor plays a pivotal role in driving cells out of a quiescent state and into the S phase of the cell cycle, in part by transactivating genes needed for DNA replication including DHFR, thymidine kinase, and DNA Polymerase alpha. E2F1 has also been implicated in regulating an S phase checkpoint, however its role in this checkpoint is not well defined. To determine how E2F1 affects such a checkpoint, we utilized an in vivo replication assay employing a plasmid based SV40 origin of replication, transfected into cells expressing SV40 large T antigen. Here we show that expression of full length E2F1, or only its N terminus, represses replication from plasmids containing the SV40 origin, while N terminal deletions of E2F1 do not. E2F1 appears to inhibit the elongation phase of replication and not the initiation phase since it does not affect the replication of other cotransfected plasmids containing only the SV40 origin. Further, inhibition of replication is dependent on both the amino-terminus of the E2F1 protein and on a DNA sequence that is contained within the 3' end of the E2F1 cDNA. Additionally, both full-length E2F1, or just its N-terminus, form protein complexes with two portions of the 3' end of the E2F1 cDNA. These data provide a clue to the mechanism by which E2F1 regulates transit through the S phase checkpoint, by acting on a specific DNA sequence via its amino-terminal region, to inhibit elongation of DNA replication.


Latency estimation for chronic disease risk: a damped exponential weighting model.
Identifying the susceptible period when environmental factors affect disease risk is essential for understanding disease etiology. Most existing epidemiologic studies use oversimplified summaries of time-dependent exposures such as baseline or most current exposure, or the cumulative average of exposure over available follow-up periods. In this paper, we introduce a damped exponential weighting model for estimating optimal exposure weights for different time intervals. This model can accommodate flexible patterns of weights and can be fit using standard software. We applied the model to assess the latency of BMI and alcohol for post-menopausal breast cancer based on 30-year exposure history in the Nurses' Health Study. We have also performed a simulation study to assess the validity of the proposed hypothesis testing and estimation procedures in realistic conditions. We found that the type I error is close to 0.05; the bias in our parameter estimates is low and the coverage probability of interval estimates is close to 0.95. For ER+/PR+ breast cancer we found that recent BMI was a more important predictor of risk than more distant BMI; for ER-/PR- breast cancer, no latency was found and risk was characterized by cumulative high levels of BMI over a long period of time. For alcohol intake, we saw a strong positive association with cumulative intake for ER+/PR+ breast cancer; no significant association was found for cumulative intake or for any latency measure of risk for ER-/PR- breast cancer. Our results underscore the value of an easy-to-implement approach to latency analysis of exposure profiles for chronic disease.


Early visual perceptual processing is altered in obsessive-compulsive disorder.
Existing studies have shown changes in attention and emotion processing of disorder-relevant visual stimuli in those with obsessive compulsive disorder (OCD). However, early visual processing in OCD has not been assessed, as previous studies did not examine the entire time course of visual processing but instead assessed potential differences in pre-determined visual evoked potentials (VEPs). This study investigates the entire visual processing stream in OCD compared to healthy age-matched controls (HC) using emotionally-neutral visual stimuli and a data-driven rather than hypothesis-driven approach. 35 HC and 26 participants with OCD underwent EEG recording while completing a modified Eriksen flanker task. Permutation-controlled t-tests were used to identify group differences in the data's full time course of visual evoked potentials. Baseline-corrected amplitudes at time points where the groups were significantly different were analyzed using ANCOVAs with BDI, BAI, and SNAP-inattentiveness scores included as covariates. This analysis identified enhanced P1 amplitudes to two visual stimuli (the initial flanker and the stimulus), corresponding to time windows of 65-93 ms and 157-187 ms post-flanker presentation in the OCD group compared to controls. Group (OCD vs. HC) was the strongest predictor of VEP amplitude during both time windows, with no significant influences of any covariates. This study showed an enhanced P1 component in people with OCD to neutral visual stimuli, potentially reflecting either inefficient or excessive early visual processing in this population. Additional inquiry is necessary to determine whether altered visual processing is associated with the sensory hypervigilance observed in those with OCD. This work identifies early visual processing alterations in OCD using neutral stimuli and a data-driven approach.


MIL-100(Fe) Supported Pt-Co Nanoparticles as Active and Selective Heterogeneous Catalysts for Hydrogenation of 1,3-Butadiene.
Superior catalytic performance for selective 1,3-butadiene (1,3-BD) hydrogenation can usually be achieved with supported bimetallic catalysts. In this work, Pt-Co nanoparticles and Pt nanoparticles supported on metal-organic framework MIL-100(Fe) catalysts (MIL=Materials of Institut Lavoisier, PtCo/MIL-100(Fe) and Pt/MIL-100(Fe)) were synthesized via a simple impregnation reduction method, and their catalytic performance was investigated for the hydrogenation of 1,3-BD. Pt1Co1/MIL-100(Fe) presented better catalytic performance than Pt/MIL-100(Fe), with significantly enhanced total butene selectivity. Moreover, the secondary hydrogenation of butenes was effectively inhibited after doping with Co. The Pt1Co1/MIL-100(Fe) catalyst displayed good stability in the 1,3-BD hydrogenation reaction. No significant catalyst deactivation was observed during 9 h of hydrogenation, but its catalytic activity gradually reduces for the next 17 h. Carbon deposition on Pt1Co1/MIL-100(Fe) is the reason for its deactivation in 1,3-BD hydrogenation reaction. The spent Pt1Co1/MIL-100(Fe) catalyst could be regenerated at 200 °C, and regenerated catalysts displayed the similar 1,3-BD conversion and butene selectivity with fresh catalysts. Moreover, the rate-determining step of this reaction was hydrogen dissociation. The outstanding activity and total butene selectivity of the Pt1Co1/MIL-100(Fe) catalyst illustrate that Pt-Co bimetallic catalysts are an ideal alternative for replacing mono-noble-metal-based catalysts in selective 1,3-BD hydrogenation reactions.


Sesquiterpene glucosides from Shenzhou honey peach fruit showed the anti-aging activity in the evaluation system using yeasts.
One new (1, SZMT01) and one known (2) anti-aging substances were isolated from Shenzhou honey peach fruit. Their structures were elucidated by spectroscopic methods and chemical derivatization, and the result reveals that these two compounds are sesquiterpene glucosides. SZMT01 possesses a new glycosylation with an ester linkage at one terminal in an acyclic sesquiterpenoid which is the end of a double bond at another terminal. Both compounds extend the replicative lifespan of K6001 yeast strain at doses of 7.5 and 25 μM. Then, to understand the action mechanism involved, we performed an anti-oxidative experiment on SZMT01. The result revealed that treatment with SZMT01 increased the survival rate of yeast under oxidative stress. Moreover, the lifespans of sod1 and sod2 mutant yeast strains with a K6001 background were not affected by SZMT01. These results demonstrate that anti-oxidative stress performs important roles in anti-aging effects of SZMT01.


Lyme disease: a rigorous review of diagnostic criteria and treatment.
Lyme disease was originally identified in Lyme, Connecticut, based upon an unusual cluster of what appeared to be patients with juvenile rheumatoid arthritis. It was subsequently identified as a new clinical entity originally called Lyme arthritis based on the observation that arthritis was a major clinical feature. However, Lyme arthritis is now called Lyme disease based upon the understanding that the clinical features include not only arthritis, but also potential cardiac, dermatologic and neurologic findings. Lyme disease typically begins with an erythematous rash called erythema migrans (EM). Approximately 4-8% of patients develop cardiac, 11% develop neurologic and 45-60% of patients manifest arthritis. The disease is transmitted following exposure to a tick bite containing a spirochete in a genetically susceptible host. There is considerable data on spirochetes, including Borrelia burgdorferi (Bb), the original bacteria identified in this disease. Lyme disease, if an organism had not been identified, would be considered as a classic autoimmune disease and indeed the effector mechanisms are similar to many human diseases manifest as loss of tolerance. The clinical diagnosis is highly likely based upon appropriate serology and clinical manifestations. However, the serologic features are often misinterpreted and may have false positives if confirmatory laboratory testing is not performed. Antibiotics are routinely and typically used to treat patients with Lyme disease, but there is no evidence that prolonged or recurrent treatment with antibiotics change the natural history of Lyme disease. Although there are animal models of Lyme disease, there is no system that faithfully recapitulates the human disease. Further research on the effector mechanisms that lead to pathology in some individuals should be further explored to develop more specific therapy.


Phosphoproteomic analysis of metformin signaling in colorectal cancer cells elucidates mechanism of action and potential therapeutic opportunities.
The biguanide drug metformin is a safe and widely prescribed drug for type 2 diabetes. Interestingly, hundreds of clinical trials have been set to evaluate the potential role of metformin in the prevention and treatment of cancer including colorectal cancer (CRC). However, the "metformin signaling" remains controversial. To interrogate cell signaling induced by metformin in CRC and explore the druggability of the metformin-rewired phosphorylation network, we performed integrative analysis of phosphoproteomics, bioinformatics, and cell proliferation assays on a panel of 12 molecularly heterogeneous CRC cell lines. Using the high-resolute data-independent analysis mass spectrometry (DIA-MS), we monitored a total of 10,142 proteins and 56,080 phosphosites (P-sites) in CRC cells upon a short- and a long-term metformin treatment. We found that metformin tended to primarily remodel cell signaling in the long-term and only minimally regulated the total proteome expression levels. Strikingly, the phosphorylation signaling response to metformin was highly heterogeneous in the CRC panel, based on a network analysis inferring kinase/phosphatase activities and cell signaling reconstruction. A "MetScore" was determined to assign the metformin relevance of each P-site, revealing new and robust phosphorylation nodes and pathways in metformin signaling. Finally, we leveraged the metformin P-site signature to identify pharmacodynamic interactions and confirmed a number of candidate metformin-interacting drugs, including navitoclax, a BCL-2/BCL-xL inhibitor. Together, we provide a comprehensive phosphoproteomic resource to explore the metformin-induced cell signaling for potential cancer therapeutics. This resource can be accessed at https://yslproteomics.shinyapps.io/Metformin/.


ApoE genotypes are associated with age at natural menopause in Chinese females.
Ages at natural menarche and menopause are influenced by several genetic factors. This study aimed to investigate the possible relationship between the apolipoprotein E (ApoE) genotype and the age at menarche and natural menopause in Chinese females. In the current study, 398 (elderly group, aged 47-80 years) and 825 (young group, aged 15-25 years) Chinese females were enrolled under informed content. Ages at natural menarche and menopause were obtained by questionnaires. ApoE genotypes were identified by restriction fragment length polymorphism analysis. In the elderly group, the number of pregnancies and live births and breastfeeding were associated with the age at menopause (P = 0.008, P = 0.002, and P = 0.023, respectively). One-way ANOVA analysis revealed that the ApoE genotype was significantly associated with age at natural menopause (ANM; P = 0.010). Compared with ApoE ε3/3 carriers, ApoE ε3/4 females showed a 1.8-year delay in ANM (P = 0.002). Single ApoE allele-positive/allele-negative analysis also showed that the age at menopause of ApoE ε4 carriers was delayed compared with those who were not carriers (P = 0.023). In the young group, no statistical difference was found in the age of menarche between the carriers of ApoE ε3/3 and ε3/4. Single ApoE allele-positive/allele-negative analysis showed that the age at menarche in ApoE ε4 carriers was slightly earlier than in those who were not carriers (P = 0.048). Meanwhile, univariate association analysis revealed that the ApoE genotypes were not significantly associated with the age at menarche using age as a covariate in the pooled group (young + elderly) (P = 0.143). We demonstrated that the ApoE genotype is significantly linked to the age at natural menopause.


Studies in sporotrichosis: fungal morphogenesis and pathogenicity in differing environments.
Sporothrix schenckii exhibits different morphology and pathogenic properties according to the source and circumstances of its growth. The present study considers the morphology and experimental pathogenicity in relation to - the 'wild' strains; the possible circumstances enhancing pathogenicity in strains recovered from the soil; the rate and nature of the transformational steps in morphology, in human and experimental infections by established pathogenic strains; the elimination of pathogenic strains to the surface of clinical lesions, enabling a simplified diagnostic proof of infection; the rate and nature of the reversion of pathogenic forms to the 'wild' type when the constraints of the host are lessened; the plasticity of conidium-pigmentation as a sign of pathogenicity; the morphological conversions on moist wattle-wood as occur in the Gold Mines; and a note on the therapeutic value of itraconazole. Host resistance is seen to play a larger part in morphology of the pathogenic phase, and exhaustion of natural food resources as the generator of potentially pathogenic forms.


Antitumour necrosis factor therapy is associated with de novo Crohn's disease after ileal pouch-anal anastomosis.
Tumour necrosis factor inhibitors (TNFi) have revolutionized the management of moderate to severe ulcerative colitis (UC) since their approval for UC in 2005. However, many patients ultimately require surgery with ileal pouch-anal anastomosis (IPAA). Development of de novo Crohn's disease (CD) following IPAA is an increasingly common and devastating complication, sometimes progressing to pouch failure. The aim of this study was to evaluate the association of preoperative TNFi exposure and the development of de novo CD after IPAA. A prospective single-centre inflammatory bowel disease (IBD) registry was searched for consecutive patients with UC undergoing IPAA during a 25-year period ending July 2018. Patients with preoperative CD or IBD-unclassified were excluded. De novo CD was diagnosed upon endoscopic evidence of five or more mucosal ulcers proximal to the ileal pouch any time after surgery and/or pouch fistula occurring more than three months after ileostomy closure. The study cohort consisted of 400 patients with a median follow-up of 44.0 (IQR 11-113) months. Sixty-two (16%) patients developed de novo CD 28.0 (IQR 6-67) months following ileostomy closure. Survival analysis of TNFi era patients revealed a significant increase in de novo CD risk in those with preoperative TNFi exposure. Multivariable proportional hazards modelling revealed two independent predictors for de novo CD development: older age was protective (HR 0.89 per 5-year increase; P = 0.009) and preoperative TNFi exposure was hazardous (HR 2.10; P = 0.011). This prospective study is the first to suggest an association between preoperative TNFi exposure and the development of de novo CD.


Bacterial cellulose biopolymers: The sustainable solution to water-polluting microplastics.
Microplastics (MPs) pollution has become one of our time's most consequential issue. These micropolymeric particles are ubiquitously distributed across all natural and urban ecosystems. Current filtration systems in wastewater treatment plants (WWTPs) rely on non-biodegradable fossil-based polymeric filters whose maintenance procedures are environmentally damaging and unsustainable. Following the need to develop sustainable filtration frameworks for MPs water removal, years of R&D lead to the conception of bacterial cellulose (BC) biopolymers. These bacterial-based naturally secreted polymers display unique features for biotechnological applications, such as straightforward production, large surface areas, nanoporous structures, biodegradability, and utilitarian circularity. Diligently, techniques such as flow cytometry, scanning electron microscopy and fluorescence microscopy were used to evaluate the feasibility and characterise the removal dynamics of highly concentrated MPs-polluted water by BC biopolymers. Results show that BC biopolymers display removal efficiencies of MPs of up to 99%, maintaining high performance for several continuous cycles. The polymer's characterisation showed that MPs were both adsorbed and incorporated in the 3D nanofibrillar network. The use of more economically- and logistics-favourable dried BC biopolymers preserves their physicochemical properties while maintaining high efficiency (93-96%). These polymers exhibited exceptional structural preservation, conserving a high water uptake capacity which drives microparticle retention. In sum, this study provides clear evidence that BC biopolymers are high performing, multifaceted and genuinely sustainable/circular alternatives to synthetic water treatment MPs-removal technologies.


Racial Disparity in Potential Occupational Exposure to COVID-19.
Nationwide, as of 20 June 2021, COVID-19 has claimed more than 599,000 lives and infected nearly 33 million people. Studies have shown that COVID-19 disproportionately affects some racial and ethnic minority groups. This study examined whether certain racial and ethnic groups were overrepresented in occupations with potentially high COVID-19 exposure risks, relative to their share in the total workforce. The study incorporates white collar workers, who to date have not gotten as much attention in terms of workers safety. Using the March and April 2020 Current Population Survey and O*Net data, this study examined whether certain racial and ethnic groups were overrepresented in occupations with potentially high risk of exposure to COVID-19 (exposure to disease and infection at work, inability to maintain physical distancing at work, and inability to work from home) relative to their share in the total workforce. The results showed that Black workers were overrepresented in occupations with high potential risk of exposure to disease and infection at work and inability to maintain physical distancing at work. Hispanic workers were overrepresented in occupations where potential risk of inability to work from home was the highest. Occupation can be one of the risk factors for the current disproportionately high COVID-19 infection rates among Black and Hispanic workers. COVID-19-related prevention measures at high risk occupations, including providing adequate personal protective equipment, training, working space, and vaccinations, could help to reduce not only the spread of COVID-19 and infectious diseases but also their disproportionately high impact in certain minority racial and ethnic groups.


Molecular chirality mediated amyloid formation on phospholipid surfaces.
One of the neuropathological features of Alzheimer's disease (AD) is the misfolding of amyloid-β to form amyloid aggregates, a process highly associated with biological membranes. However, how molecular chirality affects the amyloid formation on phospholipid surfaces has seldom been reported. Here, l- and d-aspartic acid-modified 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (l-/d-Asp-DPPE) is synthesized to construct chiral phospholipid bilayers. We discover that the l-Asp-DPPE liposomes slightly inhibit the Aβ(1-40) nucleation process but cannot affect the oligomer elongation process. By contrast, the d-Asp-DPPE liposomes strongly inhibit both nucleation and elongation of the peptide. Notably, l- and d-Asp-DPPE liposomes not only have good biocompatibility but can also rescue Aβ(1-40)-aggregation induced cytotoxicity with significant chiral discrimination, in which the cell viability is higher in the presence of d-Asp-DPPE liposomes. Mechanism analysis and molecular dynamics simulation clearly demonstrate that differential electrostatic interactions of Lys16 in Aβ(1-40) with l- or d-Asp on the phospholipid contribute to the remarkable chiral discrimination. This study provides a deeper understanding of the crucial amyloidosis process from the perspective of the chiral interface and reveals that the convergence of d-amino acids with the liposomes might be a feasible route for AD prevention.


Comparative safety and effectiveness of rivaroxaban versus VKAs in patients with venous thromboembolism. A Danish nationwide registry-based study.
The approval of rivaroxaban has changed the landscape of treatment of venous thromboembolism (VTE). Little is known about the effect of rivaroxaban compared with vitamin K antagonists (VKA), when used in the everyday clinical practice. The aim of this study was to investigate the safety and effectiveness of rivaroxaban compared with VKAs among patients with VTE, using the Danish nationwide registries. All patients diagnosed with VTE and treated with either rivaroxaban or VKAs between 2013 and 2015 were included. A total of 12,318 patients were diagnosed with VTE and treated with VKAs [n=6,907] or rivaroxaban [n=5,411.]. Combined Cox regression analyses showed that the standardised absolute six-month risk of recurrent VTE was 3.03 % [95 % CI: 2.57 % to 3.48 %] in the rivaroxaban group and 3.13 % [95 % CI: 2.70 % to 3.56 %] in the VKA group (absolute risk difference of -0.11 % [95 % CI: -0.76 % to 0.54 %]). The standardised absolute six-months risk of bleeding was 2.28 % [95 % CI: 1.87 % to 2.67 %] for patients in the rivaroxaban group and 2.10 % [95 % CI: 1.78 % to 2.43 %] in the VKA group (absolute risk difference of 0.18 % [95 % CI: -0.34 % to 0.67]). In conclusion, rivaroxaban was associated with similar risk of recurrent VTE and bleeding compared with VKA.


Impaired ATP-binding cassette transporter A1-mediated sterol efflux from oxidized LDL-loaded macrophages.
We investigated the interaction of oxidized low density lipoprotein (OxLDL) with the ATP-binding cassette A1 (ABCA1) pathway in J774 macrophages. Cellular efflux to apolipoprotein AI (apo-AI) of OxLDL-derived cholesterol was lower than efflux of cholesterol derived from acetylated low density lipoprotein (AcLDL). ABCA1 upregulation by 8-(4-chlorophenylthio)adenosine 3':5'-cyclic monophosphate (cpt-cAMP) or 22 (R)-hydroxycholesterol (22-OH) and 9-cis retinoic acid (9cRA) increased the efflux to apo-AI of cellular sterols derived from AcLDL, but not of those from OxLDL. AcLDL, but not OxLDL, induced ABCA1 protein content and activity in J774. However, OxLDL did not influence J774 ABCA1 upregulation by cpt-cAMP or 22-OH/9cRA. We conclude that sterols released to cells by OxLDL are available neither as substrate nor as modulator of ABCA1.


Tuberculosis incidence inequalities and its social determinants in Manaus from 2007 to 2016.
Brazil is among the 30 countries with high-burden of tuberculosis worldwide, and Manaus is the capital with the highest tuberculosis incidence. The accelerated economic and population growth in Manaus in the last 30 years has strengthened the process of social stratification that may result in population groups that are less favored in terms of healthcare and are vulnerable to infection and illness due to tuberculosis. This study aimed to characterize inequalities associated with tuberculosis incidence in relation to the socioeconomic and demographic characteristics of the resident population of Manaus and to identify their determinants from 2007 to 2016. An ecological study was conducted using the data from the Diseases Notification Information System. Tuberculosis incidence rates by population characteristics (gender, ethnicity, and socioeconomic level) were calculated for each year, studied, and represented in equiplot charts. To measure the disparity of tuberculosis incidence in the resident population in Manaus, the Gini index of tuberculosis in each neighborhood was calculated based on the incidence rates of the census sectors. A thematic map was constructed to represent the spatial distribution of tuberculosis incidence inequality. Linear regression models were used to identify the relationship between the tuberculosis incidence inequality and its social determinants. From 2007 to 2016, there was an increase in the tuberculosis incidence in Manaus, together with an increase in incident inequality among genders, ethnic groups, and socioeconomic level. The incidence of tuberculosis inequality was associated with the inequalities of its possible determinants (Gini of the proportion of male population, Gini of the proportion of indigenous population, Gini of the proportion of illiteracy, Gini of income, Gini of the proportion of households connected to the water network, and Gini of the mean number of bathrooms per inhabitant), the per capita income, and the proportion of cases with laboratory confirmation. Disparities in tuberculosis incidence in the resident population in neighborhoods can be explained by the sociodemographic and economic heterogeneity. Our findings recommend that public policies and tuberculosis control strategies consider differences in the determinants of tuberculosis inequality for the development of specific actions for each population group.


Preferential nucleosome placement on pBR322 restriction fragments.
Two restriction fragments of DNA containing the regulatory feature GTG/CAC were experimentally associated with core histones. The reconstituted DNA-histone complexes consisted of different forms of mononucleosomes. Lambda exonuclease and Fnu4HI were used to probe the structure of each distinct nucleoprotein complex. For each of the DNA fragments, one form of particle was produced that showed preferred placement of the core octamer on the DNA. The GTG/CAC base triplets may play some role in determining the final histone core positions in these reconstitutes.


A Practical Risk Classification of Early Recurrence in Hepatocellular Carcinoma Patients with Microvascular invasion after Hepatectomy: A Decision Tree Analysis.
This study was designed to establish risk classifications for early recurrence in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) after hepatectomy. The data of 563 HCC patients with MVI after hepatectomy from two hospitals were retrospectively reviewed. Kaplan-Meier curves and Cox proportional hazards regression models were used to analyse early recurrence. The risk classification for early recurrence was established by using classification and regression tree (CART) analysis and validated by using two independent validation cohorts from two hospitals. Multivariate analysis revealed that four indices, namely, infection of chronic viral hepatitis, MVI classification, tumour size, and serum alpha-fetoprotein (AFP), were independent prognostic factors for early recurrence in HCC patients with MVI. By CART analysis, MVI classification and serum AFP became the nodes of a decision tree and 3-stratification classifications that satisfactorily determined the risk of early recurrence were established. The area under the time-dependent receiver operating characteristic curve (AUC) values of the classification for early recurrence at 0.5, 1.0, and 2.0 years were 0.75, 0.73, and 0.71, respectively, which were all significantly higher than three common classic HCC stages (BCLC stage, Chinese stage, and TNM stage). The calibration curves showed good agreement between predictions by classification for early recurrence and actual survival outcomes. These prediction results also were confirmed in the independent internal and external validation cohorts. The 3 stratification classifications enabled satisfactory risk evaluation of early recurrence in HCC patients with MVI after hepatectomy.


Chidamide in FLT3-ITD positive acute myeloid leukemia and the synergistic effect in combination with cytarabine.
Chidamide, a novel histone deacetylase inhibitor (HDACi), has been approved for treatment of T-cell lymphomas in multiple clinical trials. It has been demonstrated that chidamide can inhibit cell cycle, promote apoptosis and induce differentiation in leukemia cells, whereas its effect on acute myeloid leukemia (AML) patients with FLT3-ITD mutation has not been clarified. In this study, we found that chidamide specifically induced G0/G1 arrest and apoptosis in FLT3-ITD positive AML cells in a concentration and time-dependent manner. We also found chidamide had the cytotoxicity effect on FLT3-ITD positive and negative AML cells. Moreover, with respect to relapsed/refractory patients, chidamide showed the same effectiveness as that in de novo AML patients. Notably, chidamide synergistically enhanced apoptosis caused by cytarabine. Our results support chidamide alone or combine with cytarabine may be used as an alternative therapeutic choice for AML patients especially those with FLT3-ITD mutation or relapsed/refractory ones.


Diagnostic accuracy of Panbio rapid antigen tests on oropharyngeal swabs for detection of SARS-CoV-2.
Antigen-detecting rapid diagnostic tests (Ag-RDTs) for the detection of SARS-CoV-2 offer new opportunities for testing in the context of the COVID-19 pandemic. Nasopharyngeal swabs (NPS) are the reference sample type, but oropharyngeal swabs (OPS) may be a more acceptable sample type in some patients. We conducted a prospective study in a single screening center to assess the diagnostic performance of the Panbio™ COVID-19 Ag Rapid Test (Abbott) on OPS compared with reverse-transcription quantitative PCR (RT-qPCR) using NPS during the second pandemic wave in Switzerland. 402 outpatients were enrolled in a COVID-19 screening center, of whom 168 (41.8%) had a positive RT-qPCR test. The oropharyngeal Ag-RDT clinical sensitivity compared to nasopharyngeal RT-qPCR was 81% (95%CI: 74.2-86.6). Two false positives were noted out of the 234 RT-qPCR negative individuals, which resulted in a clinical specificity of 99.1% (95%CI: 96.9-99.9) for the Ag-RDT. For cycle threshold values ≤ 26.7 (≥ 1E6 SARS-CoV-2 genomes copies/mL, a presumed cut-off for infectious virus), 96.3% sensitivity (95%CI: 90.7-99.0%) was obtained with the Ag-RDT using OPS. Based on our findings, the diagnostic performance of the Panbio™ Covid-19 RDT with OPS samples, if taken by a trained person and high requirements regarding quality of the specimen, meet the criteria required by the WHO for Ag-RDTs (sensitivity ≥80% and specificity ≥97%) in a high incidence setting in symptomatic individuals.


Event-related-potential (ERP) reflections of mental resources: a review and synthesis.
In this review studies are evaluated that have utilized middle-latency and late components of the event-related potential (ERP) as indices of the activation of processing resources. Processing resources are defined as energetical systems that modulate cognitive processes or data processing systems. An essential element of the resource conceptualization is the idea that processing structures receive not only information input but also input from these energetical systems. It is argued further that the principal role of these systems is to provide the 'gain' for the data processing systems. In reviewing these studies special attention is paid to factors affecting the amplitude of ERP components in single- and dual-task studies, and to the inferences that can be drawn about which particular types of processing resources are reflected in these changes in component amplitudes. Finally, a working model is presented relating middle-latency and late ERP components to specific perceptual, perceptual-central and central processing resources.


Lipid raft dynamics linked to sperm competency for fertilization in mice.
It is well known that mammalian sperm acquires fertilization ability after several maturation processes, particularly within the female reproductive tract. In a previous study, we found that both glycosylphosphatidylinositol (GPI)-anchored protein (GPI-AP) release and lipid raft movement occur during the sperm maturation process. In several genetic studies, release of GPI-AP is a crucial step for sperm fertilization ability in the mouse. Here, we show that lipid raft movement is also fundamental for sperm to be competent for fertilization by comparing the sperm maturation process of two mouse inbred strains, C57BL/6 and BALB/c. We found that ganglioside GM1 movement was exclusively reduced in BALB/c compared with C57BL/6 among other examined sperm maturation parameters, such as GPI-AP release, sperm migration to the oviduct, cholesterol efflux, protein tyrosine phosphorylation and acrosome reaction, and was strongly linked to sperm fertility phenotype. The relationship between GM1 movement and in vitro fertilization ability was confirmed in other mouse strains, suggesting that lipid raft movement is one of the important steps for completing the sperm maturation process.


Intra-abdominal mesenteric desmoid tumor.
We have presented a case of mesenteric desmoid tumor, with analysis of 21 such cases previously reported in Japan.


A Strong-Acid-Resistant [Th6 ] Cluster-Based Framework for Effectively and Size-Selectively Catalyzing Reductive Amination of Aldehydes with N,N-Dimethylformamide.
Utilization of N,N-dimethylformamide (DMF) as an amine source and reductant for synthesizing tertiary amines is a promising way to replace the substrates formaldehyde and dimethylamine, and it is desirable to seek porous acid-resistant catalysts for heterogeneous catalysis of this reaction. Herein, a robust metal-organic framework (MOF) {[Th6 O4 (OH)4 (H2 O)6 (BCP)3 ]⋅10 DMF}n (1) containing stacked nanocages with a diameter of 1.55 nm was constructed. Compound 1 can maintain its single-crystal structure even kept in air at 400 °C for 3 h, and in DMF or water at 200 °C for 7 days. Density functional theory (DFT) calculations suggested that the high interaction energy between the [Th6 O4 (OH)4 (H2 O)6 ]12+ clusters and ligands was responsible for the excellent stability of 1. Catalytic investigations revealed that 1 can effectively and size-selectively catalyze the reductive amination of aldehydes with DMF, and it can be reused at least five times without obvious loss in catalytic activity.


Comprehensive smoke-free legislation and displacement of smoking into the homes of young children in Hong Kong.
To investigate the effect of comprehensive smoke-free legislation in 2007 on the exposure of children to secondhand smoke (SHS) in Hong Kong. Two cross-sectional questionnaire surveys were conducted, before (2006) and after (2008) the implementation of smoke-free legislation, among primary 2-4 students (equivalent to US grades 2-4) from 19 and 24 randomly selected schools, respectively. Adjusted ORs for SHS exposure at home and outside home post-legislation compared with pre-legislation were calculated. The strength of the association between SHS exposure and respiratory symptoms in each survey was used as an indirect indicator of the intensity of exposure. Among 3243 and 4965 never smoking students in the 2006 and 2008 surveys, the prevalence of SHS exposure in the past 7 days increased both at home (from 10.2% to 14.1%) and outside home (from 19.8% to 27.2%). Post-legislation, students were 56% more likely (p<0.01) to report SHS exposure at home coupled with an insignificantly stronger association between SHS exposure and respiratory symptoms. Similarly, students were 60% more likely (p<0.001) to report SHS exposure outside home in 2008, but the association between SHS exposure and respiratory symptoms became insignificantly weaker. Parental smoking rates were similar before and after legislation. The prevalence of exposure to SHS at home and outside home have both increased among primary school students in Hong Kong post-legislation. Comprehensive smoke-free legislation without strong support for smoking cessation might have displaced smoking into the homes of young children.


Effect of L-thyroxine on ovarian development and gestation in the viviparous guppy, Poecilia reticulata.
Treatment of female guppies from 1 day postpartum with L-thyroxine-sodium salt (Eltroxin, Glaxo) by immersion (0.5 ppm in 25% seawater renewed daily) significantly shortened the brood interval without affecting the brood size or the weight of the brood. This suggests an acceleration of early development of the fish by thyroxine. The thyroxine treatment also accelerated the development of the next batch of oocytes, particularly exogenous vitellogenesis (yolk-globule stages). The evidence suggests a role of the thyroid in vitellogenesis and gestation in the guppy.