Meta-analysis of multiple primary prevention trials of cardiovascular events using aspirin.
Several meta-analyses have focused on determination of the effectiveness of aspirin (acetylsalicylic acid) in primary prevention of cardiovascular (CV) events. Despite these data, the role of aspirin in primary prevention continues to be investigated. Nine randomized trials have evaluated the benefits of aspirin for the primary prevention of CV events: the British Doctors' Trial (BMD), the Physicians' Health Study (PHS), the Thrombosis Prevention Trial (TPT), the Hypertension Optimal Treatment (HOT) study, the Primary Prevention Project (PPP), the Women's Health Study (WHS), the Aspirin for Asymptomatic Atherosclerosis Trial (AAAT), the Prevention of Progression of Arterial Disease and Diabetes (POPADAD) trial, and the Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial. The combined sample consists of about 90,000 subjects divided approximately evenly between those taking aspirin and subjects not taking aspirin or taking placebo. A meta-analysis of these 9 trials assessed 6 CV end points: total coronary heart disease, nonfatal myocardial infarction (MI), total CV events, stroke, CV mortality, and all-cause mortality. No covariate adjustment was performed, and appropriate tests for treatment effect, heterogeneity, and study size bias were applied. The meta-analysis suggested superiority of aspirin for total CV events and nonfatal MI, (p <0.05 for each), with nonsignificant results for decreased risk for stroke, CV mortality, and all-cause mortality. There was no evidence of a statistical bias (p >0.05). In conclusion, aspirin decreased the risk for CV events and nonfatal MI in this large sample. Thus, primary prevention with aspirin decreased the risk for total CV events and nonfatal MI, but there were no significant differences in the incidences of stroke, CV mortality, all-cause mortality and total coronary heart disease.


Clinical and electroencephalographical follow-up study of early myoclonic encephalopathy.
We report a clinico-electroencephalographical follow-up study on a male patient with early myoclonic encephalopathy. Frequent massive and fragmentary myoclonic seizures, and myoclonic-clonic seizures were the initial symptoms at the age of 3 days. EEG revealed a suppression-burst pattern at the onset in which burst phases often coincided with myoclonic seizures. Subsequently, non-epileptic erratic myoclonus, various partial seizures and flexor spasms were observed. The partial seizures ceased at around 4 months of age, while the non-epileptic myoclonus and flexor spasms have persisted beyond the age of 6 months. The EEG pattern evolved into atypical hypsarhythmia at two months of age. No specific biochemical or neuroradiological findings were disclosed. His neuropsychiatric development was arrested from the onset. These observations suggest that early myoclonic encephalopathy is an independent epileptic syndrome and that it might be different from early-infantile epileptic encephalopathy described by Ohtahara.


Bithorax complex genes control alary muscle patterning along the cardiac tube of Drosophila.
Cardiac specification models are widely utilized to provide insight into the expression and function of homologous genes and structures in humans. In Drosophila, contractions of the alary muscles control hemolymph inflow and support the cardiac tube, however embryonic development of these muscles remain largely understudied. We found that alary muscles in Drosophila embryos appear as segmental pairs, attaching dorsally at the seven-up (svp) expressing pericardial cells along the cardiac dorsal vessel, and laterally to the body wall. Normal patterning of alary muscles along the dorsal vessel was found to be a function of the Bithorax Complex genes abdominal-A (abd-A) and Ultrabithorax (Ubx) but not of the orphan nuclear receptor gene svp. Ectopic expression of either abd-A or Ubx resulted in an increase in the number of alary muscle pairs from seven to 10, and also produced a general elongation of the dorsal vessel. A single knockout of Ubx resulted in a reduced number of alary muscles. Double knockouts of both Ubx and abd-A prevented alary muscles from developing normally and from attaching to the dorsal vessel. These studies demonstrate an additional facet of muscle development that depends upon the Hox genes, and define for the first time mechanisms that impact development of this important subset of muscles.


Predictors of renal function in diabetic and non-diabetic renal disease.
Forty-two patients with renal disease due to diabetic nephropathy (14 patients), tubulointerstitial disease (14 patients) and glomerular disease (14 patients) underwent measurement of glomerular filtration rate (GFR) by the 51Cr-EDTA 'one-shot' method and simultaneous serum beta 2-microglobulin, serum creatinine and creatinine clearance estimation. Serum creatinine was a significantly better predictor of GFR than serum beta 2-microglobulin in patients with diabetic nephropathy, whereas both methods were equally useful predictors of GFR in non-diabetic renal disease. Serum creatinine measurement remains the best method for detecting early reduction of GFR on a serum sample.


Immune regulation of viral infection and vice versa.
In our laboratory we study the mechanisms by which the immune system controls viral infection and by which viruses evade immune control. To study issues at this interface between virology and immunology, we work from the hypothesis that viruses manipulate the immune response as the immune response attempts to eradicate the virus. Analysis of these issues is key to understanding acute and chronic diseases caused by viruses. Two concepts drive our approach: (1) the simultaneous analysis of immune and viral mechanisms allows novel insights, and (2) genetic tests in vivo are necessary to establish mechanisms.


Vectorial capacities for malaria in eastern Amazonian Brazil depend on village, vector species, season, and parasite species.
The vector species in the Amazon River Basin are regionally and locally diverse, which makes it imperative to understand and compare their roles in malaria transmission to help select appropriate methods of intervention and evaluation. The major aim of this study was to measure the vectorial capacity of five Anopheles species in three neighbouring villages, for two Plasmodium parasite species affecting humans. From 32 consecutive months of sampling in three villages, 1.5-7.0 km apart, on the Matapi River, Amapá State, Brazil, vectorial capacities (C) were estimated as time series for An. darlingi, An. marajoara, An. nuneztovari, An. triannulatus, and An. intermedius. Monthly parity measurements for each vector species were used to estimate daily survivorship and compared to estimates of survivorship from mark-release-recapture experiments. Gonotrophic cycle lengths were estimated through a time-series analysis of parity data, and durations of sporogony at study site temperatures for the two malaria parasite species were estimated from previous literature. The absolute abundances of five vector species were strongly tracked by the spatial variation in C among villages. Temporally, C varied between wet and dry seasons, with An. darlingi, An. marajoara and An. triannulatus exhibiting higher C in the dry season from August to December, and An. nuneztovari its highest C early in the rainy season in January and February. Anopheles intermedius exhibited higher C in the rainy season from April to June than in the dry season. Significant differences in overall survival for each independent variable, and a significant difference in C between wet and dry seasons, among villages, and among vector species for both Plasmodium falciparum and Plasmodium vivax. A generalized linear mixed model (GLMM) analysis by village showed significant effects of vector species on C in only one village, but significant effects of parasite species in all three. Although the GLMM analysis detected no significant parasite x vector species interaction effects on C, effects on C of spline regressions of C dynamics x vector species interactions were significant in all villages. These detailed analyses of entomological and parasitological variables revealed hidden complexities of malaria epidemiology at local scales in neighbouring riverine villages of the Amazon Region.


Risk of 30-day Readmission After Knee or Hip Replacement in Rheumatoid Arthritis and Osteoarthritis by Non-Medicare and Medicare Payer Status.
To determine the indication and risk of 30-day rehospitalization after hip or knee replacement among patients with rheumatoid arthritis (RA) and osteoarthritis (OA) by Medicare and non-Medicare status. Using the Nationwide Readmission Database (2010-2014), we defined an index hospitalization as an elective hospitalization with a principal procedure of total hip (THR) or knee replacement (TKR) among adults aged ≥ 18 years. Primary payer was categorized as Medicare or non-Medicare. Survey logistic regression provided the odds of 30-day rehospitalization in RA relative to OA. We calculated the rates for principal diagnoses leading to rehospitalization. Overall, 3.53% of 2,190,745 index hospitalization had a 30-day rehospitalization. Patients with RA had a higher adjusted risk of rehospitalization after TKR (OR 1.11, 95% CI 1.02-1.21) and THR (OR 1.39, 95% CI 1.19-1.62). Persons with RA and OA did not differ with respect to rates of infections, cardiac events, or postoperative complications leading to the rehospitalization. After TKR, RA patients with Medicare had a lower venous thromboembolism (VTE) risk (OR 0.58, 95% CI 0.58-0.88), whereas those with RA had a greater VTE risk (OR 2.41, 95% CI 1.04-5.57) after THR. Patients with RA had a higher 30-day rehospitalization risk than OA after TKR and THR regardless of payer type. While infections, postoperative complications, and cardiac events did not differ, there was a significant difference in VTE as the principal diagnosis of rehospitalization.


Colonization factors of enterotoxigenic E. coli (ETEC) from residents of northern Egypt.
Infection caused by enterotoxigenic Escherichia coli (ETEC) poses a serious health problem to children in developing countries. Colonization of the small intestinal mucosa by ETEC strains is mediated by antigenically specific fimbriae, also known as colonization factor antigens (CFA). The importance of this study arises from reports that active and passive immunization with ETEC strains harboring CFAs induced protective immunity against diarrhea in animal models with preformed antibodies. In humans, ETEC containing CFA/I, II, III and IV have been identified. The aim of this study was to define CFAs of ETEC isolated in Alexandria, Egypt. One hundred and seven ETEC isolates from 132 human residents in Alexandria, Egypt were isolated during a birth cohort study. ETEC isolates were screened for heat labile (LT) and heat stable (ST) toxins using a 32P oligonucleotide hybridization probe and a GM1 ELISA. These isolates were examined using monoclonal antibodies against CFA/I, II, III, IV, and against the putative colonization antigens PCF0159 and PCF0166, CS 7 and CS 17. CFAs were found in 48% of ETEC strains. CFA/I was found in 18% of the strains, CFA/II in 10% and CFA/IV in 14%. CFA III was not found. All fifteen strains expressing CFA/IV expressed CS6 and produced ST. CFA/IV was not found in non-ST producing strains, while CFA/I was absent in ST-only producing strains.


[Cardiac MRI of congenital heart disease : From fetus to adult].
Cardiac magnetic resonance imaging (MRI) is an important diagnostic tool for initial diagnostic workup and follow-up of patients with congenital heart disease (CHD) of different age groups. This review provides an overview of clinically applied MRI sequences for the assessment of CHD, highlights technical developments, and demonstrates key aspects of reporting in specific heart defects. Presentation of epidemiologic data, summary of studies on MRI sequences and their clinical application, and demonstration of clinical examples. The broad spectrum of congenital heart defects requires the use of various sequences, which can be modified depending on patient age or treatment status. Cine imaging can be used to assess cardiac function and volumes, phase contrast flow measurements allow for the assessment of vessel hemodynamics, and various techniques of MR angiography allow visualization of the thoracic vessels with high spatiotemporal resolution. New developments allow high-resolution vascular imaging without the need for contrast agents, assessment of additional hemodynamic parameters, or fetal cardiac MRI. Cardiac MRI can be employed in children as well as in adults with CHD. By using different sequences and considering the treatment status and surgery-related complications, the vast majority of clinical questions can be answered.


Looking Back: Disease Modeling.
Over the past decade, the growth of stem cell-based models of human disorders has contributed to novel drug discovery and precision medicine possibilities. For our tenth anniversary, we asked authors who cited a selection of our most popular papers in this area about how these studies influenced them.


Primary ciliary dyskinesia in Amish communities.
Primary ciliary dyskinesia is an autosomal recessive multigenic disease that results in impaired mucociliary clearance. We have diagnosed 9 subjects with primary ciliary dyskinesia from geographically dispersed Amish communities, on the basis of clinical characteristics and ciliary ultrastructural defects. Despite consanguinity, affected individuals had evidence of genetic heterogeneity.


Ceramics update.
The aim of this paper is to review recent developments in dental ceramics related both to the refinement of existing materials and technologies and to the development of new techniques. The appropriate literature has been reviewed and the relevant information selected for inclusion in this article. It is concluded that the main advances are related to developments aimed to overcoming the mechanical shortcomings of ceramic materials, such as their inherent brittleness. Several new systems have been developed, some of which appear to be very promising, but there are, as yet, no data related to the long term performance of restorations by these new techniques.


Corrigendum to "Assessment of Rwandan diabetic patients' needs and expectations to develop their first diabetes self-management smartphone application (Kir'App)".
[This corrects the article DOI: 10.1177/2042018819845318.].


Ecological consequences of Australian "Black Summer" (2019-20) fires: A synthesis of Australian Commonwealth Government report findings.
During the summer of 2019-2020, more than 15 000 wildfires burned up to 19 million hectares of forest and woodland regions across Australia. These fires culminated in the worst Australian fire season on record, producing what has come to be known as the Australian "Black Summer." The fires have been described as an "ecological disaster," but the scale of the impacts is so extensive that the full ecological consequence may take years to assess. In the immediate aftermath of the Black Summer fires, two major national investigations were established by the Australian Commonwealth Government. By reviewing reports produced by these two investigations, high-level insights into the scale of the ecological consequences of the Black Summer fires have been obtained and are summarized here. Through these insights, the urgency for action to reduce the occurrence, and improve the management, of future comparable fire events is made clear. Integr Environ Assess Manag 2021;17:1136-1140. © 2021 SETAC.


Outcomes for treatment of depression in the Veterans Health Administration: Rates of response and remission calculated from clinical and survey data.
Healthcare Effectiveness Data and Information Set (HEDIS) quality measures for depression treatment aggregate Patient Health Questionnaire (PHQ)-9 data from routine clinical assessments recorded in electronic health records (EHR). To determine whether aggregated PHQ-9 data in US Veterans Health Administration (VHA) EHRs should be used to characterize the organization's performance, we compared rates for depression response and remission calculated from EHRs with rates calculated with data representing the underlying Veteran patient population estimated using Veterans Outcome Assessment (VOA) survey data. We analyzed data from initial assessments and 3-month follow-up for Veterans beginning treatment for depression. EHR data were available for only a minority of Veteran patients, and the group of Veterans with EHR data differed from the underlying Veteran patient population with respect to demographic and clinical characteristics. Aggregated rates of response and remission from EHR data were significantly different from estimates based on representative VOA data. The findings suggest that until patient-reported outcome from EHRs are available for a substantial majority of patients receiving care, aggregated measures of patient outcomes derived from these data cannot be assumed to be representative of the outcomes for the overall population, and they should not be used as outcome-based measures of quality or performance.


Solid pseudopapillary neoplasm of the pancreas: distinct patterns of onset, diagnosis, and prognosis for male versus female patients.
Solid pseudopapillary neoplasm of the pancreas is a distinctive pancreatic neoplasm with low metastatic potential. This study examines clinical differences and prognosis between male and female patients. The medical records of 34 consecutive patients with pancreatic solid pseudopapillary neoplasms between 1990 and 2006 were reviewed. Whenever feasible, organ-preserving operation was performed. Statistical analysis was performed using chi-square and Student t test. There were 27 women (79%) and seven men (21%) with median age of 23 years. Mean diameter of the tumor was 7 cm. Tumor size tended to be smaller in patients treated in more recent years. Conservative surgery was possible in 11 patients including spleen-preserving distal pancreatectomy in 3, central pancreatectomy in 5, and enucleation in 3 patients. Median hospital stay was 11 days, morbidity rate was 62%, including 17 patients with grade A pancreatic fistula, and there was no operative mortality. Mean follow-up time was 84 months. Tumor recurred in 2 patients (6%). Overall late morbidity rate was 12%. At the time of diagnosis, age was (x +/- SD) higher among male patients (25 +/- 2 years vs 37 +/- 7 years; P <.05) with no difference in tumor size. The neoplasms were more aggressive in male patients; therefore, conservative surgery was less likely. There was no correlation between tumor aggressiveness and age of the patient or size of tumor. This is the first single center study to demonstrate that solid pseudopapillary neoplasms in male patients have distinct patterns of onset and aggressiveness when compared with female patients. Although valid prognostic criteria are still lacking, it appears that male patients may be best treated by more radical operation and should be observed more closely during follow-up.


Phenytoin-induced depression of salivary IgA and gingival hyperplasia.
IgA concentrations were determined in saliva from epileptic patients taking phenytoin and in saliva from healthy controls, by single radial immunodiffusion technique. Mean salivary IgA in epileptic children was 7.23 mg/ml; in healthy children, 16.44 mg/ml. Corresponding values for adults were 13.53 and 19.48 mg/ml, respectively. In 14 out of 84 samples, salivary IgA levels were too low for quantitative analysis. Salivary IgA levels were normal in untreated patients and fell during treatment with phenytoin. Gingival inflammation was commonly accompanied by an increase of salivary IgG and serum-derived IgA, whereas compensatory increase of IgM was infrequent. Phenytoin-induced deficiency of salivary IgA can result in increased susceptibility to gingival inflammation, which is considered one of the predisposing factors for subsequent development of gingival hyperplasia.


Plasma nitrite/nitrate level is inversely correlated with plasma low-density lipoprotein cholesterol level.
Plasma nitrite/nitrate (NOx) is a stable end product of the vasodilator nitric oxide (NO). However, there are few reports about plasma NOx levels in humans. The purpose of this study was to assess the availability of plasma NOx for evaluating basal endogenously-synthesized or endothelium-derived NO, and to examine whether NOx levels are lowered in patients with coronary artery disease (CAD) or its risk factors. Plasma NOx levels were measured using an automated system based on the Griess reaction. NOx levels for a 24-h period reproducibly became lowest at 6 A.M. in restricted healthy volunteers, and became stable in inpatient volunteers at 6 A.M. within 4 days after admission. Based on these findings, NOx levels at 6 A.M. in inpatients can be considered as the basal levels. In 40 inpatients suspected of CAD (28 men, 12 women; mean age 60 +/- 11 years), the basal levels of NOx were not related to CAD and its risk factors, except for hypercholesterolemia. The NOx level of patients with hypercholesterolemia was significantly lower than that of patients with normal cholesterol (n = 16,34 +/- 16 mumol/l vs. n = 24, 49 +/- 23 mumol/l, p < 0.03). Furthermore, the NOx levels correlated negatively with the total cholesterol and low-density lipoprotein cholesterol levels (r = -0.40, p < 0.01; r = -0.47, p < 0.003, respectively), but not with other lipid fraction levels. The results suggest that the quantity of basal endothelium-derived NO synthesis may be decreased in the presence of hypercholesterolemia.


The serotonin transporter gene polymorphism is associated with the susceptibility and the pain severity in idiopathic trigeminal neuralgia patients.
To investigate the possible association between the serotonin transporter gene (5-HTTLPR) and rs 25531 polymorphism and the susceptibility and the pain severity in Trigeminal Neuralgia patients. A total of 244 TN patients and 280 age and sex matched healthy volunteer were recruited. 5-HTTLPR and rs 25531 genotyping were performed. All patients received the carbamazepine treatment and the treatment response was evaluated at 6 months. The genotype distribution of 5-HTTLPR between TN patients and controls were significantly different. The TN Patients had a higher prevalence of short-short genotype than controls. The short-short genotype carriers are also significantly associated with higher pain severity and poorer carbamazepine treatment response compared to the long-long genotype carriers. In contrast, the rs 25531 polymorphism was not associated with the susceptibility to TN, neither with the pain severity and the treat response to carbamazepine. The 5-HTTLPR polymorphism is associated with the susceptibility to TN and pain severity of TN.


[Child food refusal: when will we call a child psychiatrist?].
Food refusal is a frequent symptom in infants and toddlers. Many difficulties resolve with pediatric treatment. In some cases of feeding disorders it is necessary to involve child psychiatrist intervention. This indication depends of child characteristics (medical and psychiatric diagnosis, failure to thrive, psycho-affective development) and also of family functioning and parental psychopathology.


Tethered dimer inhibitors of NAD synthetase: parallel synthesis of an aryl-substituted SAR library.
We previously reported that tethered dimers containing indoles on one end and a permanent positive charge on the other, using a 6-9 carbon polymethylene tether, provided NAD synthetase inhibitors with impressive antibacterial activities against Gram-positives. Here, we report that the phenyl ring is a good substitute for indole, and we utilize solution-phase parallel synthesis to explore structure-activity relationships for substituents on that ring. General conclusions are that nonpolar substituents are more effective than polar ones and that different positional isomers often have very different enzyme inhibition activities. This latter observation reveals that enzyme activity is sensitive to minor structural changes and suggests that nonspecific detergent actions are not important for the observed effects.


Burden and cost of comorbidities in patients with neuromyelitis optica spectrum disorder.
Neuromyelitis optica spectrum disorder (NMOSD) is associated with various comorbidities, including non-autoimmune and autoimmune conditions. The burden and cost of illness for NMOSD are unclear, particularly in the context of comorbidities. Claims data from IBM MarketScan Commercial and Medicare Supplemental Databases between 2014 and 2018 were analyzed. Patients with NMOSD were specified as having inpatient or outpatient claims for NMOSD diagnosis or specific NMOSD symptoms claims and no subsequent claims for multiple sclerosis (MS) or use of MS disease-modifying therapy (DMT). Continuous enrollment ≥ 6 months before and ≥ 1 year after the first claim (index date) was required for study inclusion. Total costs stratified by comorbidities within 12 months post-index date were calculated per patient and compared 1:5 with matched non-NMOSD controls. A total of 162 patients with NMOSD and 810 non-NMOSD controls were evaluated. A significantly higher proportion of NMOSD patients had comorbidities than non-NMOSD controls (66.7% vs 41.5%; P < 0.001). Concomitant autoimmune disease occurred in 19.1% vs 4.9% (P < 0.001) of patients with NMOSD vs non-NMOSD controls. NMOSD patients incurred significantly higher total median (interquartile range) healthcare costs per patient ($68,386.48 [$23,373.54-$160,862.70]) than matched non-NMOSD controls with autoimmune disease ($17,215.13 [$6715.48-$31,441.93]; P < 0.001) or patients with NMOSD without autoimmune comorbidity ($23,905.42 [$8632.82-$67,251.54]; P = 0.022). Similarly, patients with NMOSD and non-autoimmune comorbidities incurred higher median healthcare costs than matched controls. Patients with NMOSD experience significant disease burden and cost that are amplified by comorbidities. Effective therapies are needed, particularly for patients with concomitant autoimmune disease.


The Diagnostic Workup in Chronic Spontaneous Urticaria-What to Test and Why.
In chronic spontaneous urticaria (CSU), the guidelines recommend very limited diagnostic procedures during the routine workup, although additional investigations might be indicated in some patients with CSU. For physicians treating patients with CSU, it is often difficult to decide which diagnostic tests are useful. To provide recommendations on what diagnostic tests should be performed on which patients with CSU. We performed an extensive literature search on the respective topics and identified relevant questions that should prompt diagnostic procedures based on the published evidence and expert consensus among all authors. We provide questions, diagnostic testing, where appropriate, and recommendation that should be included when assessing the history of a patient with CSU, to explore and rule out differential diagnoses, to assess patients for underlying causes and modifying conditions, to explore patients for comorbid diseases and consequences of having CSU, and to assess patients for CSU components that can help to predict their disease course and response to treatment. Here, we provide physicians treating patients with CSU with information about which clues should lead to which tests and why.


Laparoscopic radioisotope-guided sentinel lymph node mapping and excision of the rectum--an experimental study.
Patients with a low-risk T1 rectal carcinoma can undergo the therapy of a local excision. In these patients the lymph node (LN) status remains unknown. There is a potential risk of up to 7% for nodal metastasis. To investigate the possibility of using the sentinel lymph node (SLN) concept, an experimental study on pigs was undertaken. The objective was to laparoscopically identify and extract SLNs from the rectum using a radioisotope (RI). The experiment was conducted in 30 pigs, since the sample size calculation indicated that with 30 animals a two-sided 95% confidence interval for a single proportion using the large sample normal approximation would extend at most 0.107 from the observed proportion of 0.9. One milliliter of a mixture of the RI Technetium 99 m (Tc99 m) and patent blue V dye was administered in the rectum endoscopically and after the lapse of 1 h, we laparoscopically identified and excised all SLNs using a laparoscopic gamma camera probe. We found in all operated pigs (n = 30) at least one SLN (lymph node with highest measured counts per second (cps)). In mean we detected 1.6 SLN (range one to three SLNs). In 28 cases, the SLN concept was successful. Sensitivity for detecting SLNs was 93% (n = 28/30), the probe count rate ranged from 600-10,000 cps with a median of 3,800. Minimal invasive mapping and excision of SLN of the rectum using a RI is feasible. The sensitivity for detecting SLN was high (93%). The application of this procedure on humans seems to be possible.


Measurement of the neutron charge radius and the role of its constituents.
The neutron is a cornerstone in our depiction of the visible universe. Despite the neutron zero-net electric charge, the asymmetric distribution of the positively- (up) and negatively-charged (down) quarks, a result of the complex quark-gluon dynamics, lead to a negative value for its squared charge radius, [Formula: see text]. The precise measurement of the neutron's charge radius thus emerges as an essential part of unraveling its structure. Here we report on a [Formula: see text] measurement, based on the extraction of the neutron electric form factor, [Formula: see text], at low four-momentum transfer squared (Q2) by exploiting the long known connection between the N → Δ quadrupole transitions and the neutron electric form factor. Our result, [Formula: see text], addresses long standing unresolved discrepancies in the [Formula: see text] determination. The dynamics of the strong nuclear force can be viewed through the precise picture of the neutron's constituent distributions that result into the non-zero [Formula: see text] value.


Comparing outcomes of nonoperative treatment for adhesive small bowel obstruction with and without antibiotics.
Some clinicians administer antibiotics in adhesive SBO treatment to prevent bacterial translocation without evidence confirming reduced sepsis and mortality. We aimed to evaluate the effectiveness of preventive antibiotic administration in nonoperative treatment of adhesive small bowel obstruction (SBO) in a retrospective study. Using a Japanese national inpatient database, we identified 114,786 eligible patients with adhesive SBO and divided patients into a group who did not receive intravenous antibiotics in the initial 2 consecutive days after admission (control group, n = 71,666) and a group who received intravenous antibiotics ≥2 days after admission (antibiotic group, n = 43,120). To compare the in-hospital mortality, occurrence of sepsis, septic shock, Clostridioides difficile colitis, length of stay, and total costs between the two groups, we performed instrumental variable analyses to adjust for measured and unmeasured confounding factors. Overall, in-hospital mortality was 2.2%, and the occurrence of sepsis was 0.8%. In the instrumental variable analyses, no significant differences were found for in-hospital mortality, occurrence of sepsis, septic shock, Clostridioides difficile colitis, or total hospitalization costs. The antibiotic group showed a longer length of stay than the control group (coefficient, 1.9 days; 95% confidence interval, 0.6-3.2). In this large nationwide cohort of patients with adhesive SBO, we found no benefit regarding preventive antibiotic administration in nonoperative treatment; however, antibiotic administration was associated with a longer hospital stay. These results did not support routine administration of antibiotics at admission to prevent bacterial translocation.


A longitudinal study of the sociosexual dynamics in a captive family group of wolves: the University of Connecticut wolf project.
An interest in the role of the social environment on the evolution of behavior led Professor Benson Ginsburg to studies of wolf social behavior. He initiated the University of Connecticut wolf project with a family group of wolves housed in a protected enclosure in an isolated area of campus. One aim of this project was to conduct a longitudinal study of a family group of wolves in order to understand the proximate behavioral mechanisms underlying mating dynamics with a degree of control and opportunistic observation that could not be achieved through field studies. The development of social relationships and the dynamics of mating were observed for 9 years. As in nature, agonistic relationships strongly influenced reproductive success, successful breeding was limited to a single pair each season, and the behavioral dynamics included status transitions with breeder rotations. Our work, when combined with the results of other captive wolf studies, has contributed valuable information to the general understanding of wolf social behavior, especially regarding the proximate behavior patterns underlying group social interactions and reproduction. This understanding has broadened perspectives on the dynamic interplay between social behavior and evolutionary processes.


Conjunctival provocation test: high clinical reproducibility but little local temperature change.
Ten atopic and five healthy individuals participated in eight conjunctival provocation tests (CPT) in an effort to improve the CPT procedure. Results were evaluated by thermography and the use of conventional criteria under various conditions. Due to considerable spontaneous variability and change in temperature already after instillation of diluent, thermography was not sensitive enough to identify positive CPT results. The precision of the CPT was within one 10-log step in all tests and in all patients. Itching appeared before erythema in 83% of subjects and within 5-8 min after instillation of the allergen. This was true also when only one eye was used for the CPT. We therefore conclude that the CPT procedure can be used in one eye every 5-8 min when indicated in clinical routine and that it is a safe, precise method.


Fixation of medial malleolar fractures with magnesium bioabsorbable headless compression screws: short-term clinical and radiological outcomes in eleven patients.
The purpose of this retrospective study was to evaluate the outcome of medial malleolar fractures treated with magnesium (MgYREZr) bioabsorbable compression screw fixation. Eleven patients with a medial malleolar fracture (either isolated or accompanied by bimalleolar or trimalleolar ankle fractures) who were treated with magnesium bioabsorbable compression screws between 2015 and 2016 in our hospital were retrospectively evaluated. Patients were monitored with a mean follow-up of 17.3 ± 4.1 months (range 12-24 months). The mechanism of injury was ground level falls in all patients. All fractures were classified as closed fractures. American Orthopedic Foot and Ankle Society's (AOFAS) scale and the visual analog scale (VAS) were used to evaluate the clinical results during the final follow-up. Bone union and a possible loss of reduction were assessed with serial radiographs. Potential complications including revision surgery and infection were recorded and reported. There were 11 patients (4 female, 7 male) with a mean age of 41 ± 21.9 years (range 20-78 years). Six patients had Herscovici type C and five patients had type B fractures. At the final follow-up the mean AOFAS score was 94.9 ± 5.7 points (range 85-100 points) and the mean VAS score was 0.4 ± 1.2 points (range 0-4 points). Radiographic solid union was achieved in all cases. No complications were seen during the follow-up. No patients required implant removal or revision surgery. This is the first study that investigates the use of bioabsorbable magnesium compression screws in medial malleolar fractures. The results of this study revealed that fixation of medial malleolar fractures with bioabsorbable magnesium compression screws provides adequate fixation with good functional results. Level IV, therapeutic, retrospective case series.


Evaluating Behavioral and Linguistic Changes During Drug Treatment for Depression Using Tweets in Spanish: Pairwise Comparison Study.
Depressive disorders are the most common mental illnesses, and they constitute the leading cause of disability worldwide. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed drugs for the treatment of depressive disorders. Some people share information about their experiences with antidepressants on social media platforms such as Twitter. Analysis of the messages posted by Twitter users under SSRI treatment can yield useful information on how these antidepressants affect users' behavior. This study aims to compare the behavioral and linguistic characteristics of the tweets posted while users were likely to be under SSRI treatment, in comparison to the tweets posted by the same users when they were less likely to be taking this medication. In the first step, the timelines of Twitter users mentioning SSRI antidepressants in their tweets were selected using a list of 128 generic and brand names of SSRIs. In the second step, two datasets of tweets were created, the in-treatment dataset (made up of the tweets posted throughout the 30 days after mentioning an SSRI) and the unknown-treatment dataset (made up of tweets posted more than 90 days before or more than 90 days after any tweet mentioning an SSRI). For each user, the changes in behavioral and linguistic features between the tweets classified in these two datasets were analyzed. 186 users and their timelines with 668,842 tweets were finally included in the study. The number of tweets generated per day by the users when they were in treatment was higher than it was when they were in the unknown-treatment period (P=.001). When the users were in treatment, the mean percentage of tweets posted during the daytime (from 8 AM to midnight) increased in comparison to the unknown-treatment period (P=.002). The number of characters and words per tweet was higher when the users were in treatment (P=.03 and P=.02, respectively). Regarding linguistic features, the percentage of pronouns that were first-person singular was higher when users were in treatment (P=.008). Behavioral and linguistic changes have been detected when users with depression are taking antidepressant medication. These features can provide interesting insights for monitoring the evolution of this disease, as well as offering additional information related to treatment adherence. This information may be especially useful in patients who are receiving long-term treatments such as people suffering from depression.


A meta-analysis of ozone effect on tooth bleaching.
This systematic review assessed the effectiveness of ozone (O3) in the color change of in-office tooth bleaching in vital teeth (TB) and the sensitivity control. Only randomized controlled clinical trials were included. Seven databases were used as primary search sources, and three additional sources were searched to capture the "grey literature" partially. The JBI tool was used to assess the risk of bias. TB was assessed using the ΔELab color change metric comparing tooth color pre- and post-bleaching. We meta-analyzed the ΔELab estimates per method and calculated the absolute standardized mean difference using random-effect models. The GRADE approach assessed the certainty of the evidence. The ΔELab estimates ranged from 1.28 when the O3 was used alone to 6.93 when combined with hydrogen peroxide (HP). Two studies compared O3 and HP alone, but their TB was similar (SMD = - 0.02; 95%CI: - 0.54; 0.49). The bleaching effectiveness for the combination of O3 + HP compared to HP was similar (SMD = 0.38; 95%CI: - 0.04; 0.81). Thus, based on the available literature, our findings suggest that O3 is not superior to the conventional technique using HP on the change of tooth color. The O3 did not present sensitivity when used alone. When O3 was used in combination with HP, patients reported hypersensitivity only when O3 was applied before HP, i.e., no sensitivity was perceived when O3 was applied after HP.


Kinetics of Microcystin-LR Removal in a Real Lake Water by UV/H2O2 Treatment and Analysis of Specific Energy Consumption.
The hepatotoxin microcystin-LR (MC-LR) represents one of the most toxic cyanotoxins for human health. Considering its harmful effect, the World Health Organization recommended a limit in drinking water (DW) of 1 µg L-1. Due to the ineffectiveness of conventional treatments present in DW treatment plants against MC-LR, advanced oxidation processes (AOPs) are gaining interest due to the high redox potential of the OH• radicals. In this work UV/H2O2 was applied to a real lake water to remove MC-LR. The kinetics of the UV/H2O2 were compared with those of UV and H2O2 showing the following result: UV/H2O2 > UV > H2O2. Within the range of H2O2 tested (0-0.9 mM), the results showed that H2O2 concentration and the removal kinetics followed an increasing quadratic relation. By increasing the initial concentration of H2O2, the consumption of oxidant also increased but, in terms of MC-LR degraded for H2O2 dosed, the removal efficiency decreased. As the initial MC-LR initial concentration increased, the removal kinetics increased up to a limit concentration (80 µg L-1) in which the presence of high amounts of the toxin slowed down the process. Operating with UV fluence lower than 950 mJ cm-2, UV alone minimized the specific energy consumption required. UV/H2O2 (0.3 mM) and UV/H2O2 (0.9 mM) were the most advantageous combination when operating with UV fluence of 950-1400 mJ cm-2 and higher than 1400 mJ cm-2, respectively.


Comparison of antithrombotic agents during urgent percutaneous coronary intervention following thrombolytic therapy: A retrospective cohort study.
The optimal antithrombotic regimen for urgent percutaneous coronary interventions (PCI) following thrombolytic therapy for ST segment myocardial infarction (STEMI) is currently unknown. We performed a retrospective analysis of all patients referred to our institution from January 2005 to July 2014 who underwent urgent PCI within 24 hr after receiving thrombolytic therapy. The patients were divided into three cohorts based on the anticoagulation strategy during PCI-bivalirudin, heparin alone or heparin plus Glycoprotein IIb/IIIa inhibitor (GPI). The primary end point of major adverse cardiovascular events (MACE) was defined as a composite of inpatient death, myocardial infarction (MI) and stroke. Net adverse clinical events (NACE) were defined as a combination of MACE plus major bleeding complications. Univariable, multivariable and propensity-weighted modeling were used to compare MACE and NACE between the three treatment groups. A total of 695 patients met the inclusion criteria during the study period. In the univariable analysis, there was no significant difference treatment in MACE between the three groups (Bivalirudin: 1.2% vs. Heparin + GPI: 4.4%; Heparin alone: 2.7%, P = 0.11). In the reduced logistic regression model, compared to bivalirudin, the odds of NACE was significantly higher with heparin alone (OR: 3.58, 95% CI: 1.21, 10.54, P = 0.02) or with heparin plus GPI (OR: 9.0, 95% CI: 2.83, 28.64, P <0.001). In STEMI patients undergoing PCI within 24 hr after thrombolytic therapy, bivalirudin was associated with a strong trend toward reduced bleeding complications as compared to heparin alone or heparin plus GPI. The optimal antithrombotic regiment for urgent PCI following thrombolytic therapy is currently unknown. Our study demonstrated that use of bivalirudin during PCI following thrombolytic therapy is associated with a trend toward reduced bleeding complications compared to heparin alone or heparin plus GPI. Large randomized trials of adjunctive anticoagulation during PCI in this complex post-thrombolytic population are warranted. © 2017 Wiley Periodicals, Inc.


Primary cutaneous nocardiosis caused by Nocardia nova with possible Apremilast contribution.
Primary cutaneous nocardiosis accounts for 5-8 % of all nocardiosis cases and represents a diagnostic dilemma among immunocompetent and immunocompromised hosts. Herein, we present a case of a 30-year-old male with history of psoriasis with recent addition of Apremilast. Patient received intralesional triamcinolone injections for psoriatic plaques on the hands and abdomen prior to traveling to warm climate vacation. While on vacation, patient developed hand swelling and painful, red nodules on the dorsal hands and abdomen, sites where he received intralesional injections. Patient was empirically given doxycycline, but continued to develop new nodules. An abdominal lesion was biopsied for H&E and tissue culture. Tissue culture revealed beaded gram-positive rods identified as Nocardia nova by MALDI-TOF. Patient was switched to trimethoprim-sulfamethoxazole with significant improvement. This case represents an atypical primary cutaneous nocardiosis with Nocardia nova most likely in the setting of intralesional steroid injections and possible contribution of Apremilast.


Neuronal responses to ethylenediamine: preferential blockade by bicuculline.
The effects of ethylenediamine have been compared with GABA using two systems: microiontophoretic application to rat neurones in vivo, and superfusion of rat sympathetic ganglia in vitro. Using both techniques ethylenediamine mimicked closely the responses to GABA, showing a potency of 0.044 relative to GABA = 1.0 in the ganglion. Bicuculline, but not strychnine, blocked ethylenediamine and GABA without affecting glycine, and strychnine blocked only glycine, in vivo. It was particularly clear from the in vitro experiments that bicuculline is about twice as effective an antagonist of ethylenediamine than of GABA.


Improving MHC class I antigen-processing predictions using representation learning and cleavage site-specific kernels.
In this work, we propose a new deep-learning model, MHCrank, to predict the probability that a peptide will be processed for presentation by MHC class I molecules. We find that the performance of our model is significantly higher than that of two previously published baseline methods: MHCflurry and netMHCpan. This improvement arises from utilizing both cleavage site-specific kernels and learned embeddings for amino acids. By visualizing site-specific amino acid enrichment patterns, we observe that MHCrank's top-ranked peptides exhibit enrichments at biologically relevant positions and are consistent with previous work. Furthermore, the cosine similarity matrix derived from MHCrank's learned embeddings for amino acids correlates highly with physiochemical properties that have been experimentally demonstrated to be instrumental in determining a peptide's favorability for processing. Altogether, the results reported in this work indicate that MHCrank demonstrates strong performance compared with existing methods and could have vast applicability in aiding drug and vaccine development.


Erratum: Perception, beliefs, and causal attribution of autism early signs in Ecuadorian general population.
[This corrects the article DOI: 10.3389/fpsyg.2022.915817.].


Joint-based description of protein structure: its application to the geometric characterization of membrane proteins.
A macroscopic description of a protein structure allows an understanding of the protein conformations in a more simplistic manner. Here, a new macroscopic approach that utilizes the joints of the protein secondary structures as a basic descriptor for the protein structure is proposed and applied to study the arrangement of secondary structures in helical membrane proteins. Two types of dihedral angle, Ω and λ, were defined based on the joint points of the transmembrane (TM) helices and loops, and employed to analyze 103 non-homologous membrane proteins with 3 to 14 TM helices. The Ω-λ plot, which is a distribution plot of the dihedral angles of the joint points, identified the allowed and disallowed regions of helical arrangement. Analyses of consecutive dihedral angle patterns indicated that there are preferred patterns in the helical alignment and extension of TM proteins, and helical extension pattern in TM proteins is varied as the size of TM proteins increases. Finally, we could identify some symmetric protein pairs in TM proteins under the joint-based coordinate and 3-dimensional coordinates. The joint-based approach is expected to help better understand and model the overall conformational features of complicated large-scale proteins, such as membrane proteins.


Recurrent seizures in metachromatic leukodystrophy.
The unusual presentation of juvenile onset metachromatic leukodystrophy (MLD) and frequent complex partial seizures in a patient led us to perform a retrospective study of 18 patients with MLD to identify the prevalence and type of recurrent seizures during the first 2 years of the disease. Five of 17 patients (29%) had developed recurrent seizures within 12 months of the onset of symptoms, and one patient was lost to follow-up. By 24 months after onset of symptoms, 5 patients were lost to follow-up, and 6 of the remaining 13 patients (46%) had developed recurrent seizures. In all, 7 patients, 4 with late infantile-onset and 3 with juvenile-onset disease, developed recurrent seizures. Four patients, including 3 with juvenile-onset disease had complex partial seizures. We conclude that recurrent seizures are common in MLD and may occur at any stage of the disease, particularly in patients with juvenile onset. Generalized seizures are more frequent in patients with late infantile-onset, whereas partial seizures are more common in those with juvenile-onset disease.


Of cancer and cave fish.
We propose that the drivers of carcinogenesis lie more in the adaptive changes that are enabled by local or systemic alterations of tissue architecture than in the genetic changes observed in cancer cells. A full understanding of cancer biology and therapy through a cataloguing of the cancer genome is unlikely unless it is integrated into an evolutionary and ecological context.


Loss of JAK2 regulation via a heterodimeric VHL-SOCS1 E3 ubiquitin ligase underlies Chuvash polycythemia.
Chuvash polycythemia is a rare congenital form of polycythemia caused by homozygous R200W and H191D mutations in the VHL (von Hippel-Lindau) gene, whose gene product is the principal negative regulator of hypoxia-inducible factor. However, the molecular mechanisms underlying some of the hallmark abnormalities of Chuvash polycythemia, such as hypersensitivity to erythropoietin, are unclear. Here we show that VHL directly binds suppressor of cytokine signaling 1 (SOCS1) to form a heterodimeric E3 ligase that targets phosphorylated JAK2 (pJAK2) for ubiquitin-mediated destruction. In contrast, Chuvash polycythemia-associated VHL mutants have altered affinity for SOCS1 and do not engage with and degrade pJAK2. Systemic administration of a highly selective JAK2 inhibitor, TG101209, reversed the disease phenotype in Vhl(R200W/R200W) knock-in mice, an experimental model that recapitulates human Chuvash polycythemia. These results show that VHL is a SOCS1-cooperative negative regulator of JAK2 and provide biochemical and preclinical support for JAK2-targeted therapy in individuals with Chuvash polycythemia.


A prospective evaluation of leak point pressure, bladder compliance and clinical status in myelodysplasia patients with tethered spinal cords.
We evaluated prospectively 26 patients with myelodysplasia and a tethered spinal cord to determine whether surgical release of the tethered cord positively influenced leak point pressure, bladder compliance, upper tract status and/or clinical management. Urodynamics were performed immediately before and after the neurosurgical procedure, and at 3 and 6 months postoperatively. Mean patient age was 7.8 years (range 2 days to 34 years) and median interval from onset of symptoms to surgery was 60 days (range 2 days to 4 years). Patient presentation included a combination of orthopedic, neurological and urological symptoms. Of 26 patients 9 (35%) had new hydronephrosis, urinary tract infections or urinary incontinence. Leak point pressure and bladder compliance did not change significantly by 6 months postoperatively. Of the 4 patients who presented with hydronephrosis 1 worsened in status, 2 stabilized and 1 improved. Clinical status was unchanged in 16 patients, improved in 4 and worsened in 6. There was no significant relationship between patient age and urodynamic or clinical outcome. Among patients followed for at least 6 months radiographic and clinical improvement occurred in 25% and 15%, respectively. Urodynamic improvements were transient. Surgical release of a tethered cord improved the urological status in less than a quarter of the patients in this series.


A comprehensive review of topical hemostatic agents: The good, the bad, and the novel.
Uncontrolled exsanguination remains the leading cause of death for trauma patients, many of whom die in the pre-hospital setting. Without expedient intervention, trauma-associated hemorrhage induces a host of systemic responses and acute coagulopathy of trauma. For this reason, health care providers and prehospital personal face the challenge of swift and effective hemorrhage control. The utilization of adjuncts to facilitate hemostasis was first recorded in 1886. Commercially available products haves since expanded to include topical hemostats, surgical sealants, and adhesives. The ideal product balances efficacy, with safety practicality and cost-effectiveness. This review of hemostasis provides a guide for successful implementation and simultaneously highlights future opportunities.


Divergent synthesis of complex polyketide-like macrolides from a simple polyol fragment.
[structure: see text] Three stereochemically and structurally complex non-natural polyketide macrolides have been synthesized from the same simple polyol precursor. That this polyol fragment is rapidly available in quantity is key to the practicality of these syntheses and allows the targeting of more highly complex and "natural product-like" macrolides.


The in vivo measurement of replication fork velocity and pausing by lag-time analysis.
An important step towards understanding the mechanistic basis of the central dogma is the quantitative characterization of the dynamics of nucleic-acid-bound molecular motors in the context of the living cell. To capture these dynamics, we develop lag-time analysis, a method for measuring in vivo dynamics. Using this approach, we provide quantitative locus-specific measurements of fork velocity, in units of kilobases per second, as well as replisome pause durations, some with the precision of seconds. The measured fork velocity is observed to be both locus and time dependent, even in wild-type cells. In this work, we quantitatively characterize known phenomena, detect brief, locus-specific pauses at ribosomal DNA loci in wild-type cells, and observe temporal fork velocity oscillations in three highly-divergent bacterial species.


HLA study in Iranian desert Yazd province inhabitants.
Yazd City (1,200,000 inhabitants) is placed in the middle of its Iran desert province and it was constructed on a oasis in ancient times.However,it was a central point on the Silk Road and merchants from both Asia and Mediterranean/European areas crossed through Yazd City.We have studied HLA-A,-B,-DRB1 and DQB1 alleles in Yazd population.Analysys of nine most frequent extended class I and class II haplotypes shows that four of them are specific of this population.The other six haplotypes are also found in Asian and Mediterranean populations in significant frequency. This supports that the nowadays relatively isolated in desert Yazd area also contains people that may bear HLA genes probably originated because of long lasting merchants route between Europe and Asia through the European/Asian Silk Road in addition to other HLA genes close to other Iranian populations, including Kurds.


The moral barrier effect: Real and imagined barriers can reduce cheating.
This research presents a nudge-based approach to promoting honest behavior. Specifically, we introduce the moral barrier hypothesis, which posits that moral violations can be inhibited by the introduction of spatial boundaries, including ones that do not physically impede the act of transgressing. We found that, as compared to a no barrier condition, children cheated significantly less often when a barrier was strategically placed to divide the space where children were seated from a place that was associated with cheating. This effect was seen both when the barrier took a physical form and when it was purely symbolic. However, the mere presence of a barrier did not reduce cheating: if it failed to separate children from a space that was associated with cheating, children cheated as much as when there was no barrier at all. Taken together, these findings support the moral barrier hypothesis and show that even seemingly unremarkable features of children's environments can nudge them to act honestly.


How do neonatal units within the Australian and New Zealand Neonatal Network manage ex-preterm infants with severe chronic lung disease still requiring major respiratory support at term?
The aim was to survey the Australian and New Zealand Neonatal Network (ANZNN) member units regarding current services and management guidelines for the ex-premature infant with severe chronic lung disease (CLD) still requiring significant respiratory support at term. A 16-question survey was sent to clinical directors of all Level 3 units in Australia and New Zealand via the network. Reminder emails were sent, as required, to prompt a satisfactory response rate. Survey responses were received from 26 of the 29 (90%) ANZNN Level 3 units. At 37 weeks' corrected gestation, over 90% of the units provide ongoing respiratory support in the neonatal intensive care unit (NICU). However, by 50 weeks, ongoing care is provided in several settings, including NICU, high dependency unit (HDU)/paediatric intensive care unit or respiratory wards. The majority (76%) of units arrange transfer on an ad hoc basis, but six units (24%) have set criteria for transfer based on gestation, workload and respiratory requirement. Three units declared a maximum age in NICU (44, 46 or 48 weeks). A variety of approaches were used to identify infants who were likely to require transfer, and 78% of units had a staff member assigned to assist transition. Three units stated that they had a home ventilation programme suitable for these infants. No unit supplied a guideline on tracheostomy or specific respiratory management post-term. Despite a significant number of babies requiring ongoing support for severe CLD, the location of the service appears very variable, and there is a lack of specific written guidelines.


LiverNet: efficient and robust deep learning model for automatic diagnosis of sub-types of liver hepatocellular carcinoma cancer from H&E stained liver histopathology images.
Liver cancer is one of the most common types of cancers in Asia with a high mortality rate. A common method for liver cancer diagnosis is the manual examination of histopathology images. Due to its laborious nature, we focus on alternate deep learning methods for automatic diagnosis, providing significant advantages over manual methods. In this paper, we propose a novel deep learning framework to perform multi-class cancer classification of liver hepatocellular carcinoma (HCC) tumor histopathology images which shows improvements in inference speed and classification quality over other competitive methods. The BreastNet architecture proposed by Togacar et al. shows great promise in using convolutional block attention modules (CBAM) for effective cancer classification in H&E stained breast histopathology images. As part of our experiments with this framework, we have studied the addition of atrous spatial pyramid pooling (ASPP) blocks to effectively capture multi-scale features in H&E stained liver histopathology data. We classify liver histopathology data into four classes, namely the non-cancerous class, low sub-type liver HCC tumor, medium sub-type liver HCC tumor, and high sub-type liver HCC tumor. To prove the robustness and efficacy of our models, we have shown results for two liver histopathology datasets-a novel KMC dataset and the TCGA dataset. Our proposed architecture outperforms state-of-the-art architectures for multi-class cancer classification of HCC histopathology images, not just in terms of quality of classification, but also in computational efficiency on the novel proposed KMC liver data and the publicly available TCGA-LIHC dataset. We have considered precision, recall, F1-score, intersection over union (IoU), accuracy, number of parameters, and FLOPs as metrics for comparison. The results of our meticulous experiments have shown improved classification performance along with added efficiency. LiverNet has been observed to outperform all other frameworks in all metrics under comparison with an approximate improvement of [Formula: see text] in accuracy and F1-score on the KMC and TCGA-LIHC datasets. To the best of our knowledge, our work is among the first to provide concrete proof and demonstrate results for a successful deep learning architecture to handle multi-class HCC histopathology image classification among various sub-types of liver HCC tumor. Our method shows a high accuracy of [Formula: see text] on the proposed KMC liver dataset requiring only 0.5739 million parameters and 1.1934 million floating point operations per second.


Detection of TIMI-3 flow before mechanical reperfusion with ultrasonic tissue characterization in patients with anterior wall acute myocardial infarction.
Spontaneous coronary reperfusion with TIMI-3 flow is associated with favorable clinical outcomes in patients with acute myocardial infarction (AMI). We investigated the ability of analyzing cardiac cycle-dependent variation of myocardial integrated backscatter (IBS) for predicting spontaneous reperfusion in anterior AMI. We recorded IBS images on admission in 104 patients with first anterior wall AMI and subsequently performed coronary angiography and coronary intervention. We measured the cyclic variation of IBS within the infarct zone and expressed its magnitude as phase-corrected magnitude (PCM) by giving positive and negative values when it showed synchronous and asynchronous contraction, respectively. Twenty-three patients showing TIMI-3 flow at the initial coronary angiography had smaller peak creatine kinase value than 57 patients with initial TIMI-0/1 flow (864+/-961 versus 2358+/-1757 IU/L; P=0.0002) and better percent wall thickening within risk area (36.1+/-15.1%) than those with TIMI-2 (16.7+/-12.8%, P<0.0001) or TIMI-0/1 (5.1+/-11.6, P<0.0001). The patients with initial TIMI-3 had higher PCM (2.7+/-1.3 dB) than those with TIMI-2 (-0.3+/-2.2 dB, P<0.0001) or those with TIMI-0/1 (-1.1+/-2.4 dB, P<0.0001). Using PCM=1.0 dB as the cutoff point, PCM detected TIMI-3 flow with 95.7% sensitivity and 90.1% specificity. Multivariable logistic regression analysis revealed that only PCM is an independent predictor for spontaneous reperfusion among the hemodynamic, echocardiographic, and electrocardiographic variables. Analysis of myocardial IBS could detect spontaneous reperfusion noninvasively in the emergent stage of anterior AMI.


Implementation of new ECMO centers during the COVID-19 pandemic: experience and results from the Middle East and India.
Extracorporeal membrane oxygenation (ECMO) use for severe coronavirus disease 2019 (COVID-19) patients has increased during the course of the pandemic. As uncertainty existed regarding patient's outcomes, early guidelines recommended against establishing new ECMO centers. We aimed to explore the epidemiology and outcomes of ECMO for COVID-19 related cardiopulmonary failure in five countries in the Middle East and India and to evaluate the results of ECMO in 5 new centers. This is a retrospective, multicenter international, observational study conducted in 19 ECMO centers in five countries in the Middle East and India from March 1, 2020, to September 30, 2020. We included patients with COVID-19 who received ECMO for refractory hypoxemia and severe respiratory acidosis with or without circulatory failure. Data collection included demographic data, ECMO-related specific data, pre-ECMO patient condition, 24 h post-ECMO initiation data, and outcome. The primary outcome was survival to home discharge. Secondary outcomes included mortality during ECMO, survival to decannulation, and outcomes stratified by center type. Three hundred and seven COVID-19 patients received ECMO support during the study period, of whom 78 (25%) were treated in the new ECMO centers. The median age was 45 years (interquartile range IQR 37-52), and 81% were men. New center patients were younger, were less frequently male, had received higher PEEP, more frequently inotropes and prone positioning before ECMO and were less frequently retrieved from a peripheral center on ECMO. Survival to home discharge was 45%. In patients treated in new and established centers, survival was 55 and 41% (p = 0.03), respectively. Multivariable analysis retained only a SOFA score < 12 at ECMO initiation as associated with survival (odds ratio, OR 1.93 (95% CI 1.05-3.58), p = 0.034), but not treatment in a new center (OR 1.65 (95% CI 0.75-3.67)). During pandemics, ECMO may provide favorable outcomes in highly selected patients as resources allow. Newly formed ECMO centers with appropriate supervision of regional experts may have satisfactory results.


Serial electrical impedance tomography course in different treatment groups; The MaastrICCht cohort.
To describe the effect of dexamethasone and tocilizumab on regional lung mechanics over admission in all mechanically ventilated COVID-19 patients. Dynamic compliance, alveolar overdistension and collapse were serially determined using electric impedance tomography (EIT). Patients were categorized into three groups; no anti-inflammatory therapy, dexamethasone therapy, dexamethasone + tocilizumab therapy. The EIT variables were (I) visualized using polynomial regression, (II) evaluated throughout admission using linear mixed-effects models, and (III) average respiratory variables were compared. Visual inspection of EIT variables showed a pattern of decreasing dynamic compliance. Overall, optimal set PEEP was lower in the dexamethasone group (-1.4 cmH2O, -2.6; -0.2). Clinically applied PEEP was lower in the dexamethasone and dexamethasone + tocilizumab group (-1.5 cmH2O, -2.6; -0.2; -2.2 cmH2O, -5.1; 0.6). Dynamic compliance, alveolar overdistension, and alveolar collapse at optimal set PEEP did not significantly differ between the three groups. Optimal and clinically applied PEEP were lower in the dexamethasone and dexamethasone + tocilizumab groups. The results suggest that the potential beneficial effects of these therapies do not affect lung mechanics favorably. However, this study cannot fully rule out any beneficial effect of anti-inflammatory treatment on pulmonary function due to its observational nature.


Transcriptional mechanism of differential sugar accumulation in pulp of two contrasting mango (Mangifera indica L.) cultivars.
Temporal transcriptome analysis combined with targeted metabolomics was employed to investigate the mechanisms of high sugar accumulation in fruit pulp of two contrasting mango cultivars. Ten sugar metabolites were identified in mango pulp with the most dominant being d-glucose. Analysis of the gene expression patterns revealed that the high-sugar cultivar prioritized the conversion of sucrose to d-glucose by up-regulating invertases and β-glucosidases and increased other genes directly contributing to the synthesis of sucrose and d-glucose. In contrast, it repressed the expression of genes converting sucrose, d-glucose and other sugars into intermediates compounds for downstream processes. It also strongly increased the expression of alpha-amylases which may promote high degradation of starch into d-glucose. Besides, ¾ of the sugar transporters was strongly up-regulated, indicative of their preponderant role in sugar accumulation in mango fruit. Overall, this study provides a good insight into the regulation pattern of high sugar accumulation in mango pulp.


Inducible epitope imprinting: 'generating' the required binding site in membrane receptors for targeted drug delivery.
We report an inducible epitope imprinting strategy that as a template, a flexible peptide chain can have a disordered-to-ordered conformational change by suitable inducement through a molecular imprinting procedure, and the formed nanoparticles can, in turn, remold the original peptide into the expected conformation and specifically bind to the corresponding protein.


Suicides committed by minors.
The bodies of 76 minors, below 18 years of age, who died as a consequence of committing suicide during the years 1960 to 1974 were examined in the Institute of Forensic Medicine in Cracow. The youngest victim was a boy 8 1/2 years of age. The majority of cases (63) referred to minors aged 16-18. The deaths were due to: hanging (41 cases), poisoning (17 cases), leaping from a height (7 cases), and others (11 cases including one case of self shooting). Among the motives for suicide the first place is taken by personal troubles, mostly school failures, then bad health and family conflicts. Prior suicidal attempts were noted in 13 cases and in 10 others oral declarations of suicide were made. Motives for suicide essentially differ from those found in earlier studies from the years 1881-1939, where ill luck in love and undesired pregnancy were treated as one of the important factors leading to suicide.


Minority Stress and Cardiovascular Disease Risk Among Sexual Minorities: Mediating Effects of Sense of Mastery.
Sexual minority adults are at greater risk for cardiovascular disease (CVD) risk factors than heterosexual adults. There is a dearth of research identifying factors that are associated with CVD risk among sexual minorities. This study examined the associations between distal and proximal minority stressors and CVD risk. We also tested a sense of mastery as one mechanism that might explain the link between minority stressors and CVD risk. Participants were 670 sexual minority adults (53.6% male; 76% White), ages 18 to 76 years (M = 41.19, SD = 14.73), obtained from a non-probability sample. Using an online survey, participants self-reported family history of CVD risk, physiological conditions (diabetes mellitus, high cholesterol, hypertension), and health behaviors (e.g., tobacco use, diet, exercise) that confer or protect against CVD risk. A weighted CVD risk index was computed. Linear and logistic regressions were conducted to test the effects of minority stressors on the CVD risk index and its specific indicators and to examine mediation. Minority stressors were associated with a sense of mastery, and mastery was associated with lower CVD risk index scores. Proximal and distal minority stressors were not directly associated with the overall CVD risk index but were associated with some specific risk indicators. Mediation analyses revealed that both distal and proximal minority stressors were indirectly associated with the CVD risk index through mastery. Research and interventions should aim to reduce CVD risk factors and target minority stressors and mastery to improve the cardiovascular health of sexual minorities.


Sexually transmitted diseases update.
STDs have worldwide distribution and result in immense social and economic cost. Knowledge of the clinical signs, symptoms, current clinical tests, and treatment recommendations is important for all health care professionals.


Re-pitching the tent sign: A case report.
The tent sign is a subtle mammographic finding that is not well delineated in current literature. It refers to localized retraction of the breast parenchyma causing a characteristic inverted "V" shape, or tent sign. It can often be the only indication that an underlying malignancy exists. We present the case of a 50 year-old female who presented on screening mammogram with a tent sign with pathology yielding invasive carcinoma.


Trace elements repartition in body fluids, hair and organs in an autopsied population evaluated by ICP-MS high resolution.
Exposure to metals and trace elements (TE) is universal and can cause toxicity in case of excessive exposure. We evaluated the concentrations and tissue distribution of 39 TE using high-resolution ICP-MS after total mineralization by microwave in twenty autopsied French subjects. We found a globally homogeneous distribution of TE in the body, with some accumulations in agents, involved in respiratory pathologies and classified as carcinogens, in the lungs. The liver, an organ of metabolism, appeared to concentrate Co, Fe, La, Mn, Mo, Pb and Zn. Fe seemed to accumulate in the spleen, the organ of hematopoiesis. The kidney showed high concentrations of some TE, which can cause nephrotoxicity. The use of microwave mineralization and high-resolution ICP-MS allowed accurate quantification and a very high sensitivity, without spectral interferences. The results obtained in this study could be used to support the interpretation of post-mortem metal concentrations in tissues.


Sentinel lymph node detection in patients with vulvar carcinoma; Feasibility of intra-operative mapping with technetium-99m-labeled nanocolloid.
Sentinel lymph node (SLN) mapping appears to be feasible in patients with primary vulvar cancer. Previous protocols describe the injection of the technetium-99m-nanocolloid at least 3 h before surgery which involves two invasive procedures for the patient. In this study, we assessed the feasibility, safety, and accuracy of an intra-operative rather than preoperative SLN mapping in patients with primary vulvar cancer. Patients with histologically confirmed squamous cell vulvar cancer and clinically FIGO stage Ib disease underwent intra-operative SLN mapping by intradermal injection of the nanocolloid around the tumor. SLN were identified and removed before a complete inguinofemoral lymphnode dissection was performed. Surgical and pathologic data on all patients were prospectively entered into a database. An SLN procedure was performed in 16 patients; 3 patients received unilateral lymphadenectomy, and 13 women underwent surgery on both groins. In all groins but 4 at least one SLN was clearly identified (detection rate 25/29, 86%). A median number of 2 SLN and 4 non-SLN per groin were removed. 3 of 16 patients (19%) had metastatic disease in the lymph nodes. There was no false negative SLN result. Intra-operative SLN detection seems feasible in patients with early stage vulvar cancer. More patients need to be enrolled in this ongoing study before this more convenient technique can be considered safe.


[Controversial issues in colorectal screening in Hungary: conflict of clinical and public health viewpoints].
In Hungary, mortality rates from colorectal cancer are dramatically high, therefore the reduction by population screening as a public health measure is considered as one of the priorities of National Public Health Program. In the beginning, a human-specific immunological test was applied in the "model programs", as a screening tool, to detect the occult blood in the stool; compliance was 32% in average. However, the objectives of the model programs have not been achieved, because, among other reasons, a debate on the method of choice and the strategy to follow have divided the professional public opinion. In this study the debated issues are critically discussed, being convinced that, at present, population screening seems to be the most promising way to alleviate the burden of colorectal cancer.


Attenuation of polychlorinated biphenyl induced uroporphyria by iron deprivation.
A toxic sequel to polyhalogenated aromatic hydrocarbon exposure in humans is the development of porphyria cutanea tarda. In a mouse model (experimental uroporphyria) utilizing an environmentally relevant polychlorinated biphenyl (PCB) mixture, we show that the toxicity can be markedly influenced by nutritional status. In mice made susceptible to uroporphyria through a targeted deletion of one allele of uroporphyrinogen decarboxylase (Uro-D+/-), an iron deficient diet prevented the development of the uroporphyria and the changes in associated parameters normally seen within three weeks following a single exposure to Aroclor 1254. Iron deprivation also completely prevented PCB-induced uroporphyria in mice wild-type at the Uro-D locus (Uro-D+/+), a model that requires δ-aminolevulinic acid administration for the development of uroporphyria. In Uro-D+/- mice consuming δ-aminolevulinic acid, PCB exposure produced a severe uroporphyria that was attenuated, not prevented, by iron deficiency. This attenuation moderated hepatic uroporphyrin and uroporphyrinogen decarboxylase inhibitor levels, but not the depression of cytosolic uroporphyrinogen decarboxylase activity.


Heterologous expression of mlrA gene originated from Novosphingobium sp. THN1 to degrade microcystin-RR and identify the first step involved in degradation pathway.
Information on the catalytic role of mlrA gene-encoded enzyme (MlrA) in microcystin-RR (MC-RR) biodegradation was limited. This study succeeded in expressing mlrA homolog of Novosphingobium sp. THN1 in heterologous host for the first time, by constructing a recombinant bacterium. Mass spectrometric analysis showed that the recombinant MlrA hydrolyzed MC-RR into linear intermediate product by cleaving the peptide bond between Adda and arginine residue, greatly detoxifying MC-RR. This finding clearly manifested that the MlrA homolog of THN1 strain possesses its original catalytic function, and ring-opening constituted the first step in MC-RR biodegradation pathway of THN1 strain. Moreover, MC-RR degradation by intact recombinant cells and cell-free crude enzyme (CE) from recombinant was compared. Results exhibited that intact recombinant was able to degrade 20 μg mL-1 MC-RR more quickly than CE, with the maximum rate of 9.22 μg mL-1 h-1 in the first 8 h. Thus, this study provided new insights on the catalytic activity and roles of MlrA originated from THN1 strain in MC-RR biodegradation process, which lay a foundation for efficiently removing and detoxifying MC-RR, and exploring downstream steps in MC-RR biodegradation pathway of THN1 strain.


Relationship between long noncoding RNAs and physiological risk factors of cardiovascular disease.
Long noncoding ribonucleic acids (lncRNAs) are an important category of noncoding RNAs that play crucial roles in controlling the expression of genes in health and in a range of illnesses including cardiovascular disease. A large body of genetic, experimental, and epidemiologic evidence suggests roles for an increasing number of lncRNAs in the regulation of metabolism, lipid profile, inflammation, and glucose metabolism in type II diabetes. Importantly, it has been suggested that lncRNAs can regulate chromatin alteration, messenger RNA stability, microRNA action, and can control transcription factors. We aimed to highlight emerging concepts, based on the most current knowledge, regarding the roles of lncRNA in the regulation of cardiovascular risk factors such as lipid profile, glucose homeostasis, and inflammation.


Evidence-based medicine and problem based learning a critical re-evaluation.
Evidence-based medicine (EBM) has been the subject of controversy since it was introduced in 1992. However, it has yet to be critically examined as an alternative paradigm for medical education, which is how it was proposed. This commentary examines EBM on the terms on which it was originally advanced and within the context that gave rise to it, the problem-based learning (PBL) environment at McMaster University in the 1970s and 80s. The EBM educational prescription is revealed to be aligned with the information processing psychology (IPP) model of learning through acquisition of general problem solving skills that characterized the early McMaster version of PBL. The IPP model has been identified in the literature as discordant with an alternative, constructivist, model that emerged at Maastricht University in the Netherlands over the subsequent period. Strengths and weaknesses of EBM are identified from the standpoint of the underlying cognitive theories. Principles are proposed with which to guide an educationally viable approach to learning and teaching the valuable skills included within the original EBM formula.


Medial orbitofrontal cortex and nucleus accumbens mediation in risk assessment behaviors in adolescents and adults.
Risk assessment behaviors are necessary for gathering risk information and guiding decision-making. Risky decision-making heightens during adolescence, possibly as a result of low risk awareness and an increase in sensitivity to reward-associated cues and experiences. Higher adolescent engagement in high-risk behaviors may be, in part, due to developing circuits that contribute to risk assessment behaviors. Nucleus accumbens (NAc) activity is linked to risky decision-making and receives inputs carrying sensory and emotional information. Namely, the medial orbitofrontal cortex (MO) contributes to behavior guided by reward probability and sends direct projections to the NAc (MO→NAc), which may permit risk assessment in a mature circuit. Here, we evaluated risk assessment behaviors in adult and adolescent rats during elevated plus maze (EPM) exploration, including stretch and attend postures, head dips, and rears. We found that adolescents exhibited fewer EPM risk assessment behaviors than adults. We also quantified MO→NAc projections using a fluorescent anterograde tracer, Fluoro-Ruby, in both age groups. Labeled MO→NAc pathways exhibited greater total fluorescence in adults than in adolescents, indicating MO→NAc fibers increase over development. Using a disconnection approach to measure the contribution of the MO-NAc pathway in adults, we found that ipsilateral inactivation of the MO-NAc did not alter risk assessment behavior; however, MO-NAc disconnection reduced the number of stretch-and-attend postures. Together, this work suggests that the development of MO-NAc pathways can contribute to age-dependent differences in risk assessment.


Comparison of spatial encodings for ultrasound imaging.
Ultrasound pulse sequencing and receive signal focusing work hand-in-hand to determine image quality. These are commonly linked by geometry, for example using focused beams or planewaves in transmission paired with appropriate time-of-flight calculations for focusing. Spatial encoding allows a broader class of array transmissions but requires decoding of the recorded echoes before geometric focusing can be applied. Recent work has expanded spatial encoding to include not only element apodizations but also element time delays. This powerful technique allows for a unified beamforming strategy across different pulse sequences and increased flexibility in array signal processing given access to estimates of individual transmit element signals, but trade-offs in image quality between these encodings has not been previously studied. We evaluate in simulation several commonly used time delay and amplitude encodings and investigate optimization of the parameter space for each. Using signal-to-noise ratio, point resolution, and lesion detectability we found trade-offs between focused beams, planewaves, and Hadamard weight encodings. Beams with broader geometries maintained a wider field-of-view after decoding at the cost of signal-to-noise ratio (SNR) and lesion detectability. Focused beams and planewaves showed slightly reduced resolution compared to Hadamard weights in some cases, especially close to the array. We also found overall degraded image quality using random weight or random delay encodings. We validate these findings with experimental phantom imaging for select cases. We believe that these findings provide a starting point for sequence optimization and for improved image quality using the spatial encoding approach for imaging.


Loss of RUNX3 is significantly associated with advanced tumor grade and stage in endometrial cancers.
Loss of runt‑related transcription factor 3 (RUNX3) has been reported in various cancers, and one of the mechanisms mediating loss of RUNX3 expression is DNA methylation. However, the role of RUNX3 expression and its DNA methylation status as prognostic factors in endometrial cancer remain unclear. In the present study, the expression and promoter methylation of RUNX3 was examined in endometrial cancer tissues and cell lines, as well as their association with endometrial cancer prognosis. Fifty‑five endometrial cancer tissues and two endometrial cancer cell lines (HEC1‑α and Ishikawa) were studied. RUNX3 expression and promoter methylation were examined using reverse transcription‑polymerase chain reaction (RT‑PCR), methylation specific PCR (MS‑PCR), and immunohistochemical staining. The demethylating agent 5‑aza‑2'‑deoxycytidine (ADC) was used to reverse the methylation of the RUNX3 promoter. Loss of RUNX3 expression was observed in 50.9% (27/53) of endometrial cancer tissues and in the HEC1‑α cell line by immunohistochemistry and RT‑PCR, respectively. Methylation of the RUNX3 promoter was observed in 62.2% (33/53) of endometrial cancer tissues, 12.5% (1/8) of normal endometrial tissues, and the HEC1‑α cell line by MS‑PCR. Tumor grade and stage were significantly correlated with loss of RUNX3 expression. The expression of RUNX3 was restored by treatment with ADC and resulted in growth inhibition in HEC1‑α cells. The present results suggested that methylation may serve a critical role in the silencing of RUNX3 and loss of RUNX3 expression may serve as a prognostic marker in endometrial cancer.


Violence Against Psychiatric Trainees: Findings of a European Survey.
Violence by patients against health care professionals has been widely described. Although psychiatric trainees are particularly exposed, little is known about the extent, context, and impact of violence toward them in Europe. A cross-sectional online survey was distributed between June 2018 and December 2019 among European psychiatric trainees through professional networks, using a snowball approach. The questionnaire asked about experiences of verbal abuse and physical and sexual assaults, as well as their context and impact. Descriptive analyses of the obtained data were conducted. The survey was completed by 827 trainees from 39 countries (68.4% females). Most (83.6%) reported having been abused/assaulted at least once (of these, 92% verbally, 44.1% physically, and 9.3% sexually). Emergency rooms and inpatient units were the most frequent settings. Psychological impact of these events was commonly reported. Most respondents did not report abuses and assaults to their supervisors. They also described a lack of training for staff and aggression management plans at their institutions or of being unaware of their existence. Violence from patients is reported by many psychiatric trainees across countries in Europe, with very frequent verbal abuse and worrisome figures of physical and sexual assaults. Particularly concerning are the low proportion of trainees reporting to authorities, the lack of staff training and management protocols, and trainees' lack of awareness about those resources. Despite the study limitation of a small response rate, these results support a call for urgent efforts to address this problem in Europe, and possibly beyond.


A probable case of Legg-Calvé-Perthes disease in Warring States-era China.
Reports of Legg-Calvé-Perthes disease (LCPD) in the paleopathological literature are rare. Here, the authors present a probable case of LCPD, which presents as abnormal morphology of the proximal femur. The condition was observed in an individual of the Warring States period in Shaanxi Province, China, and the morphology involves a "mushroom head" deformity of the proximal right femur and an enlarged acetabulum, along with a contralateral tibia, talus, and navicular that are enlarged and demonstrate periosteal new bone formation. The authors consider tuberculosis, septic arthritis, trauma, slipped capital femoral epiphysis, and Legg-Calvé-Perthes disease in a differential diagnosis. The authors conclude that the most likely diagnosis for the deformity is Legg-Calvé-Perthes disease. Bony changes in the hip joint and contralateral lower leg suggest that the individual had an altered gait because of the condition.


Association between broadly defined bulimia nervosa and drug use disorders: common genetic and environmental influences.
Previous research has shown an association between bulimia (BN) and drug use disorders (DUD). The purpose of the present study was to investigate possible influences on the comorbidity between BN and DUD. Participants included 490 monozygotic and 354 dizygotic female twins and 930 females from opposite sex pairs. Multiple logistic regression analyses were used to test shared correlates and mediators. Bivariate twin analyses were used to investigate the contribution of genes and environment to the correlation between BN and DUD. Depression, neuroticism, and childhood sexual abuse (CSA) mediated the association between BN and DUD regardless of which disorder was used as the dependent variable. Analyses also indicated genetic and nonshared environmental overlap between BN and DUD. The association between BN and DUD is due mostly to overlapping genetic influences with a smaller contribution from nonshared environment. Depression, neuroticism, and CSA are likely important shared correlates.


The Superior Laryngeal Nerve and Its Vulnerability in Surgeries of the Neck.
Anatomical considerations of the superior laryngeal nerve (SLN), a branch of the vagus, provides information to minimize the potential for iatrogenic intraoperative injury, thereby preventing motor and sensory dysfunctions of the larynx. The present study aims to assess the variation of the SLN and its relationship to the superior thyroid artery (STA) and superior laryngeal artery (SLA). The study was done on 35 formalin-fixed cadavers at Oakland University in 2018-2019. In our study, we found that out of 21 cadavers, 52.4% of the external laryngeal branches (ebSLN) are related posteromedial to the STA, while 47.6% are related anteromedial to it. Out of 14 cadavers, 64.3% of the internal laryngeal branches (ibSLN) are related superoposterior to the SLA, while 35.7% are inferoposterior to it. In most cases, the SLA crosses above the ebSLN while traveling to pierce the thyrohyoid membrane to reach the larynx. The data demonstrate that both the ebSLN and ibSLN display variation in their relationship with the STA and the SLA, respectively. Awareness of these variable relationships is critical for identification and isolation of these structures in order to prevent consequences of nerve injury, primarily a reduction in the highest attainable frequency of the voice and aspiration pneumonia.


Gate reflectometry of single-electron box arrays using calibrated low temperature matching networks.
Sensitive dispersive readouts of single-electron devices ("gate reflectometry") rely on one-port radio-frequency (RF) reflectometry to read out the state of the sensor. A standard practice in reflectometry measurements is to design an impedance transformer to match the impedance of the load to the characteristic impedance of the transmission line and thus obtain the best sensitivity and signal-to-noise ratio. This is particularly important for measuring large impedances, typical for dispersive readouts of single-electron devices because even a small mismatch will cause a strong signal degradation. When performing RF measurements, a calibration and error correction of the measurement apparatus must be performed in order to remove errors caused by unavoidable non-idealities of the measurement system. Lack of calibration makes optimizing a matching network difficult and ambiguous, and it also prevents a direct quantitative comparison between measurements taken of different devices or on different systems. We propose and demonstrate a simple straightforward method to design and optimize a pi matching network for readouts of devices with large impedance, [Formula: see text]. It is based on a single low temperature calibrated measurement of an unadjusted network composed of a single L-section followed by a simple calculation to determine a value of the "balancing" capacitor needed to achieve matching conditions for a pi network. We demonstrate that the proposed calibration/error correction technique can be directly applied at low temperature using inexpensive calibration standards. Using proper modeling of the matching networks adjusted for low temperature operation the measurement system can be easily optimized to achieve the best conditions for energy transfer and targeted bandwidth, and can be used for quantitative measurements of the device impedance. In this work we use gate reflectometry to readout the signal generated by arrays of parallel-connected Al-AlOx single-electron boxes. Such arrays can be used as a fast nanoscale voltage sensor for scanning probe applications. We perform measurements of sensitivity and bandwidth for various settings of the matching network connected to arrays and obtain strong agreement with the simulations.


Persistent expression of interleukin-17 and downstream effector cytokines in recalcitrant psoriatic lesions after ustekinumab treatment.
The interleukin (IL)-23/T-helper (Th)17 axis is considered central to the pathogenesis of psoriasis, with IL-36γ considered a marker for histological differential diagnosis. However, expression data regarding key cytokines in the pathogenesis of psoriasis, as well as data on the effects of IL-23 inhibition on downstream cytokines in human psoriatic skin, are limited. We investigated the expression profile of key cytokines and the effect of ustekinumab (UST) on cytokine expression in human psoriatic tissue. Tumor necrosis factor (TNF)-α, IL-23, IL-17A, and IL-22 were highly expressed in the epidermis, dermal papillae, and upper dermis in patients with psoriasis compared with controls; IL-36γ was strongly expressed in the upper epidermis. Compared with the untreated group, expression intensity and area of IL-23 were significantly decreased in the UST group; expression areas of TNF-α, IL-17A, IL-22, and IL-36γ did not differ. This study identified the distribution and quantitative expression levels of key cytokines in psoriatic lesions and demonstrated that only IL-23 was downregulated without blocking downstream effector cytokines in recalcitrant psoriatic lesions during UST treatment. Our results suggest that, although IL-23 is inhibited, the persistent expression of IL-17 through an alternative pathway maintains the vicious cycle of the TNF-α/IL-23/IL-17 axis with IL-36γ, inducing refractory psoriatic lesions in patients with well-controlled psoriasis.


Viscous Fingering as a Rapid 3D Pattering Technique for Engineering Cell-Laden Vascular-Like Constructs.
Tissues are much larger than the diffusion limit distance, so rapidly providing blood vessels to supply embedded cells inside tissues with sufficient nutrients and oxygen is regarded as a major strategy for the success of bioengineered large and thick tissue constructs. Here, a patterning technique, viscous fingering, is developed to bioengineer vascularized-like tissues within a few minutes. By controlling viscosity, flow rate, and the volume of photo-cross-linkable prepolymer, macro- and microscale vascular network structures can be precisely engineered using the Hele-Shaw cell that is designed in this study. After cross-linking, a vascular-like gel with fingering structures is formed between the bottom and top base gels, creating a sandwich-like structure. Cells can be incorporated into the fingers, bases, or both gels. The spreading and growth direction of the embedded cells are successfully controlled and guided by manipulating the physical properties of the fingering and base gels individually. Moreover, fingering is generated, connected, and surrounded prepared cell-laden microgels in base prepolymers to form prevascularized tissue-like constructs. Taken together, the 3D cell patterning technique extends the potential for modeling and fabricating large and stackable vascularized tissue-like constructs for both ex vivo and in vivo applications.


The transformation of cancer-associated fibroblasts: Current perspectives on the role of TGF-β in CAF mediated tumor progression and therapeutic resistance.
Over the last few years, the Transforming growth factor- β (TGF-β) has been significantly considered as an effective and ubiquitous mediator of cell growth. The cytokine, TGF-β is being increasingly recognized as the most potent inducer of cancer cell initiation, differentiation, migration as well as progression through both the SMAD-dependent and independent pathways. There is growing evidence that supports the role of secretory cytokine TGF-β as a crucial mediator of tumor-stroma crosstalk. Contextually, the CAFs are the prominent component of tumor stroma that helps in tumor progression and onset of chemoresistance. The interplay between the CAFs and the tumor cells through the paracrine signals is facilitated by cytokine TGF-β to induce the malignant progression. Here in this review, we have dissected the most recent advancements in understanding the mechanisms of TGF-β induced CAF activation, their multiple origins, and most importantly their role in conferring chemoresistance. Considering the pivotal role of TGF-β in tumor perogression and associated stemness, it is one the proven clinical targets We have also included the clinical trials going on, targeting the TGF-β and CAFs crosstalk with the tumor cells. Ultimately, we have underscored some of the outstanding issues that must be deciphered with utmost importance to unravel the successful strategies of anti-cancer therapies.