Abstract: Aims: The diagnosis of drug-induced liver injury (DILI) is relatively complex, involving a wide variety of drugs. The purpose of this study is to use algorithms to quickly screen DILI patients, count incidence rates and find risk factors. Methods: The Adverse Drug Events Active Surveillance and Assessment System-2 was used to extract the data of hospitalized patients in 2019 according to the set standards, then the RUCAM was used to evaluate patients who meet the standards. A retrospective case-control study was conducted according to suspected drugs, length of hospital stay, height and weight matched controls, and logistic regression was used to find risk factors. Results: Among the 156,570 hospitalized patients, 480 patients (499 cases) of DILI were confirmed, and the incidence of DILI was 0.32%. Anti-infective agents, antineoplastic agents, non-steroidal anti-inflammatory drugs (NASIDs) were the major category of causative drugs causing DILI, and the highest incidence of DILI caused by agent of voriconazole. The latency period and hospital stay of patients with cholestasis was relatively long. Patients with hyperlipidemia (AOR: 1.884), cardiovascular disease (AOR: 1.465), pre-existing liver disease (AOR: 1.827) and surgical history (AOR: 1.312) were likely to be risk factors for DILI. Conclusions: The incidence of DILI in hospitalized patients was uncommon (0.32%), and its pathogenic drugs were widely distributed. LiverTox’s information could assist in the diagnosis of DILI. The incidence of DILI in many drugs was seriously underestimated. It is recommended to focus on patients with hyperlipidemia, cardiovascular disease, pre-existing liver disease, and surgical history.

Males have the ability to compete for fertilizations through both pre-copulatory and post-copulatory intrasexual competition. Pre-copulatory competition has selected for large weapons and other adaptations to maximize access to females and mating opportunities while post-copulatory competition has resulted in ejaculate adaptations to maximize fertilization success. Negative associations between these strategies support the hypothesis that there is a trade-off between success at pre- and post-copulatory mating success. Recently, this trade-off has been demonstrated with experimental manipulation. Male leaf-footed cactus bugs, Narnia femorata, that lose a weapon by autotomy during development invest instead in large testes. While evolutionary outcomes of the trade-offs between pre- and post-copulatory strategies have been identified, less work has been done to identify proximate mechanisms by which the trade-off might occur, perhaps because the systems in which the trade-offs have been investigated are not ones that have the molecular tools required for exploring mechanism. Here we applied knowledge from a related model species for which we have developmental knowledge and molecular tools, the milkweed bug Oncopeltus fasciatus, to investigate the proximate mechanism by which autotomized N. femorata males developed larger testes. Autotomized males had evidence of a higher rate of transit amplification divisions in the spermatogonia, which would result in greater sperm numbers. Identification of mechanisms underlying a trade-off can help our understanding of the direction and constraints on evolutionary trajectories and thus the evolutionary potential under multiple forms of selection.

Arthritis is a common clinical feature of systemic lupus erythematosus (SLE) and is usually non-erosive as opposed to rheumatoid arthritis (RA). While RA synovial pathology has been extensively studied, little is known about the pathophysiology of lupus arthritis. Here, we aimed to explore the cytokine and cellular compartments in synovial fluids of SLE patients with arthritic manifestations. Acellular synovial fluid and paired serum samples from SLE patients (n=17) were analyzed with cytokine bead array for T helper associated cytokines. From two SLE patients, synovial fluid mononuclear cells (SFMC) were analyzed by multiparameter flow cytometry to dissect T cell, B cell, monocyte and dendritic cell phenotypes. SLE-derived SFMC were further stimulated in vitro to measure their capacity for producing IFN and IL-17A. All patients fulfilled the ACR 1982 classification criteria for SLE. Clinical records were reviewed to exclude the presence of comorbidities such as osteoarthritis or overlap with RA. IL-17A and IL-6 levels were high in SLE synovial fluid. A clear subset of the synovial CD4+ T cells expressed CCR6+, a marker associated with Th17 cells. IL-17-production was validated amongst CD4+CCR6+ T cells following in vitro stimulation. Furthermore, a strong IFN production was observed in both CD4+ and CD8+ cells. Our study shows high IL-17A and IL-6 levels in synovial fluids of patients with lupus arthritis. The Th17 pathway have been implicated in several aspects of SLE disease pathogenesis and our data points to Th17 involvement also for lupus arthritis.

Background: To describe how parents and families of children with cancer evaluate the benefits and risks of using social media (SM) and how they navigate disagreements between oncologists’ advice and information found on SM. Procedure: Parents of children who had been previously diagnosed with cancer, and who had used SM for a purpose related to that child’s health were recruited through SM sites and nonprofit organizations across the U.S. and were invited to complete questionnaires about their experiences using SM; a subset of participants also completed a follow-up in-depth interview. Open-ended responses and interviews were analyzed using thematic analysis. Results: 90 parents completed written questionnaires; 21 completed follow-up interviews. 70% described experiencing a situation in which information shared on SM conflicted with information provided by their child’s oncologist. Although 86% discussed it with the oncologist and 70% described the response as positive, 78% retained negative feelings about the experience. Openness to discussing SM, honesty, transparency and humility regarding the limits of medicine, and shared decision-making regarding information found on SM were connected with reported trust in the oncologist. Conclusions: Parents offered valuable insights regarding their experiences navigating SM, including 8 recommendations for how pediatricians might approach discussing parental SM use. Future studies will evaluate the utility of these recommendations for pediatric clinicians.

The stability of plant biomass production in the face of environmental change is fundamental for maintaining terrestrial ecosystem functioning, as plant biomass is the ultimate source of energy for nearly all life forms. However, most studies have focused on the stabilizing effect of plant diversity, neglecting the effect of soil biodiversity, the largest reservoirs of biodiversity on Earth. Here we investigated the effects of plant and soil biodiversity on the temporal stability of biomass production under varying simulated precipitation in grassland microcosms. Soil biodiversity loss reduced temporal stability by suppressing asynchronous responses of plant functional groups. Greater plant diversity, especially in terms of functional diversity, promoted temporal stability, but this effect was independent of soil biodiversity loss. Moreover, multitrophic biodiversity, plant and soil biodiversity combined, was positively associated with temporal stability. Our study highlights the importance of maintaining the biodiversity of multiple trophic levels for sustainable biomass production.

The Vero cell line is the most used continuous cell line in viral vaccine manufacturing. This adherent cell culture platform requires the use of surfaces to support cell growth, typically roller bottles or microcarriers. We have recently compared the production of rVSV-ZEBOV on Vero cells between microcarrier and fixed-bed bioreactors. However, suspension cultures are considered superior with regards to process scalability. Therefore, we further explore the Vero suspension system for rVSV-vectored vaccine production. Previously, this suspension cell line was only able to be cultivated in a proprietary medium. Here, we expand the adaptation and bioreactor cultivation to a serum-free commercial medium. Following small scale optimization and screening studies, we demonstrate bioreactor productions of highly relevant vaccines and vaccine candidates against Ebola virus disease, HIV and COVID-19 in the Vero suspension system. rVSV-ZEBOV, rVSV-HIV and rVSVInd-msp-SF-Gtc can replicate to high titers in the bioreactor, reaching 3.87 × 107 TCID50/mL, 2.12 × 107 TCID50/mL and 3.59 × 109 TCID50/mL, respectively. Further, we compare cell specific productivities, and the quality of the produced viruses by determining the ratio of total viral particles to infectious viral particles

Letter to EditorTo the EditorEgg-allergic children have higher ovomucoid (OVM)-specific IgD (sIgD) levels compared to the atopic controls.1 Within the egg-allergic group, children with higher levels of OVM-sIgD have a decreased risk of anaphylactic reactions. Ovalbumin (OVA)-sIgD increases in egg-allergic children desensitized by oral immunotherapy (OIT) but not in children unresponsive to OIT or with sustained unresponsiveness to OVA challenge.2 The natural development of tolerance and the acquisition of sustained unresponsiveness by OIT in egg-allergic children are associated with an increase in OVM-specific IgG4 (sIgG4) levels and a decrease in OVM-specific IgE (sIgE) levels.3 To elucidate the potential role of IgD in the outgrowing of egg allergy, we analyzed levels of egg white (EW)-, OVM-, and OVA-sIgD and sIgG4 in sera from 57 egg-allergic children (28 avoided all forms of egg in the diet (complete avoidance of egg: CAE), 18 were able to ingest at least 1/32 cooked whole egg but not one cooked whole egg (partial avoidance of egg: PAE), and 11 outgrew egg allergy (OGE)) and 23 healthy non-egg allergic children (non-egg allergy: NEA) (Table S1). The study was approved by The Research Ethics Committee of University of Fukui (#20110052), and written informed consent was obtained from the parent or guardians.EW-, and OVM-sIgE levels measured using ImmunoCAP (Thermo-Fisher Inc., MA) were higher in the CAE group, followed by the PAE, OGE, and NEA groups (Fig 1, Fig S1). The CAE group exhibited lower serum levels of EW- and OVA-sIgD compared to the NEA group and the PAE group, respectively, and had the lowest OVM-sIgD serum levels among all groups, suggesting that OVM-sIgD levels are associated with outgrowing egg allergy. We observed the lowest serum levels of EW-, OVA-, and OVM-sIgG4 in the CAE group, followed by the PAE and OGE groups. The ratio of OVM-sIgD to OVA-sIgD increased as children outgrew egg allergy, whereas the ratio of OVM-sIgG4 to OVA-sIgG4 did not change. Thus, the production of OVM-sIgD differs from OVM-sIgG4 as children naturally outgrow egg allergy.High-affinity, but not low-affinity, IgE is known to cause anaphylaxis.4 High-affinity IgE is derived from memory IgG1+ B cells, whereas low-affinity IgE is derived from naïve IgM+IgD+ B cells. Considering class switching pathways, switching direction from IgM to IgD, and from IgG1 to IgE or IgG4, elevated OVM-sIgD levels might be associated with low-affinity OVM-sIgE levels as children outgrow egg allergy, resulting in hypo-responsiveness to OVM.A recent study found that OVM-sIgE avidity was more effective at differentiating clinically reactive egg-allergic patients from those tolerant of heated egg compared to EW-sIgE.5 The ratio of OVM-sIgE to OVM-sIgD or sIgG4 in the CAE group was significantly higher compared to the PAE, OGE, and NEA groups (Fig 2). Receiver operating analysis revealed that the ratio of OVM-sIgE to OVM-sIgD discriminated non-tolerant from partially-tolerant egg-allergic patients with the largest area under the curve (AUC = 0.965) compared with levels of OVM-sIgE or the ratio of OVM-sIgE to OVM-sIgG4. The optimal cutoff for the ratio of OVM-sIgE to OVM-sIgD had 86.5% sensitivity and 96.4% specificity to identify high-risk subjects (Table S2).There are several limitations to this study. First, there was a small number of patients. Second, all children were only challenged with heated egg and were instructed to avoid egg of any form if they tested positive with less than 1/32 cooked whole egg. Finally, there was a lack of trajectory of sIgD levels during natural tolerance development.In conclusion, the ratio of OVM-sIgE to OVM-sIgD is a useful marker to identify high-risk egg-allergic patients capable of ingesting a low-dose of cooked whole egg who might be a good candidate for low-dose OIT.

The mirid bugs Stenotus rubrovittatus and Trigonotylus caelestialium, which cause pecky rice, have become a threat to rice cultivation in Asia. Damage caused by these pests has rapidly become frequent since around 2000 in Japan. Their expansion pattern is not simple, making it difficult to manage them by prediction. Some insects with wide distributions have locally adapted variations in life-history traits. We performed laboratory rearing experiments to assess the geographical scale of intraspecific variations in life-history traits of S. rubrovittatus and T. caelestialium. These were aimed at increasing the accuracy of occurrence estimates and the number of generations per year. These results were compared with previous research, and differences in development rates were observed between populations of different latitudes, but not of the same latitude. Finally, plotting the timing of adult emergence and the potential number of generations per year on maps with a 5-km grid revealed that they differed greatly locally at the same latitude. These maps can be used for developing more efficient methods of managing mirid bugs in integrated pest management.

An adult male with alcoholic cirrhosis presented with acute blood loss anemia, hypotension and a painful bruise over his body's left side. He denied any trauma or falls. Computed tomography of the chest showed left chest wall hematoma. Emergent angiography with successful embolization of the left intercostal artery was performed.

First described in 1965 by Johnson and Wilcox, partial absence of the tricuspid valve (TV) associated with a ventricular septal defect(VSD) is a very rare malformation.(1) Heart failure secondary to severe TV regurgitation results in-utero fetal compromise. (2) We present here a fetus with partial absence of the tricuspid valve with conoventricular septal defect.

Congenital aneurysm of the ductus arteriosus is reported in 0.8% in neonatal autopsies, however true incidence is unknown because of high rate of asymptomatic cases and spontaneous regression. Possible complications in symptomatic cases are; thromboembolism, spontaneous rupture, erosion, infection, compression of airways and death. In this report we present a newborn with giant DAA diagnosed in first day of life, surgically treated after thrombosis of aneurysm.

Background and aim of the study: We report our one-year single-center experience of a new technique of aortic valve replacement using a rapid-deployment valve (RD-AVR) to avoid postoperative complications. We also report the unexpected pitfalls and handling techniques that we have seen in past cases. Methods: We performed aortic valve replacement on 38 patients between May 2019 and April 2020. Their mean age was 74 years. The primary outcomes were in-hospital mortality and short-term results during a one-year follow-up period, while the secondary outcomes were related to prosthetic valve function, especially paravalvular leakage (PVL). We further analyzed the relationship between the new technique and its outcomes. Results: The mean operative time was 196 min. There were no in-hospital deaths, and the mean duration of postoperative hospital stay was 11.8 days. Valvular measurements using 3-dimensional computed tomography (3D-CT) were larger and more accurate than those measured using ultrasonic echocardiography Postoperative RD-AVR prosthetic valve function was excellent. However, PVL occurred in 4 cases one week and one year postoperatively and regurgitation did not improve. A gap associated with PVL was identified below the right-noncoronary commissure. To prevent PVL, we additionally stitched this gap in the later 18 cases; there was no case of PVL and no new pacemaker implantation in these cases. Conclusions: PVL is more likely to occur if there is a gap below the R-N commissure, especially in cases with a large annulus; therefore, applying an additional stitch to the R-N commissure is extremely useful.

Purpose: The FDA-issued PLATO trial dataset revealed that some primary deaths causes (PDC) were inaccurately reported favoring ticagrelor. However, the PLATO Investigators operated the shorter death list of uncertain quality. We compared if PDC match when trial fatalities were reported to the FDA and by the PLATO investigators. Method: The FDA list contains precisely detailed 938 PLATO deaths, while shorter investigators dataset consists of 905 deaths. We matched 4 vascular (sudden, post-MI, heart failure and stroke), and 3 non-vascular (cancer, sepsis and suicide) PDC between death lists. Results: There were more sudden deaths in the shorter list than in the FDA dataset (161 vs.138; p<0.03), post-AMI (373 vs.178; p<0.001) but fewer heart failure deaths (73 vs.109; p=0.02). Stroke numbers match well (39 vs. 37; p=NS) with only 2 ticagrelor cases removed. Cancer matched well (32 vs.31; p=NS), and sepsis cases were identical (30 vs. 30; P=NS). However, 2 extra clopidogrel suicides in the shorter list are impossible to comprehend. Conclusions: The PLATO trial PDC were mismatched between FDA and Investigators sets. We are kindly asking the ticagrelor sponsor or/and concerned PLATO Investigators to clarify the PDC dataset match.

IntroductionGraft-versus-host disease (GVHD) is a potentially serious complication of allogenic stem cell transplantation (allo-SCT), but patients who develop GVHD also have a low incidence rate of leukemia recurrence, suggesting a graft-versus-leukemia effect due to the donor lymphocytes.1 This effect has also been suggested in solid tumors. In the case here, cervical cytology transformed from squamous cell carcinoma to negative for intraepithelial lesion or malignancy (NILM), possibly due to a graft-versus-tumor (GVT) effect following allo-SCT. The cervical cytology has continued changing, although the dose of immunosuppressant likely also has an effect. Here we describe our experience in this case and review the literature.

Polynomial interpolation with equidistant nodes is notoriously unreliable due to the Runge phenomenon, and is also numerically ill-conditioned. By taking advantage of the optimality of the interpolation processes on Chebyshev nodes, one of the best strategies to defeat the Runge phenomenon is to use the mock-Chebyshev points, which are selected from a satisfactory uniform grid, for polynomial interpolation. Yet, little literature exists on the computation of these points. In this study, we investigate the properties of the mock-Chebyshev nodes and propose a subsetting method for constructing mock-Chebyshev grids. Moreover, we provide a precise formula for the cardinality of a satisfactory uniform grid. Some numerical experiments using the points obtained by the method are given to show the effectiveness of the proposed method and numerical results are also provided.

Abdominal pregnancy is a very rare, life-threatening form of ectopic pregnancy, in which implantation occurs within the peritoneal cavity. The advantages of a laparoscopic approach over a laparotomy in this setting include a reduced estimated blood loss, a shorter operating time, reduced analgesic requirements, shorter hospital stay and convalescence.

A case of a 42-year-old woman, Para 3 who had an unplanned pregnancy despite bilateral tubal ligation for contraception, and Novasure® endometrial ablation for persistent Heavy Menstrual Bleeding (HMB). The pregnancy was complicated by missed miscarriage at 14 weeks and placenta accreta. This is an uncommon event.

Plasmapheresis for the management of acute cyanide poisoning : A case report and review of literatureNavid Namakizadeh EsfahaniIsfahan University of Medical Sciences, Isfahan, [email protected] ZoofaghariDepartment of Clinical Toxicology, Isfahan Clinical Toxicology Research Center, Khorshid hospital, Isfahan, [email protected] Akhavan Sigari (corresponding author)Isfahan University of Medical Sciences, Isfahan, [email protected]: +989132151729PO: 8174673461Gholamali DorooshiDepartment of Clinical Toxicology, Isfahan Clinical Toxicology Research Center, Khorshid hospital, Isfahan, [email protected]