Miracle-dz/UniFAR-FTUs huggingface dataset:
Water‐Processable, Stretchable, Self‐Healable, Thermally Stable, and Transparent Ionic Conductors for Actuators and Sensors

For emerging biocompatible, wearable, and stretchable epidermal electronic devices, it is essential to realize novel stretchable conductors with the attributes of transparency, low‐cost and nontoxic components, green‐solvent processbility, self‐healing, and thermal stabililty. Although conducting materials–rubber composites, ionic hydrogels, organogels have been developed, no stretchable material system that meets all the outlined requirements has been reported. Here, a series of P(SPMA‐r‐MMA) polymers with different ratios of ionic side chains is designed and synthesized, and it is demonstrated that the resulting stretchable ionic conductors with glycerol are transparent, water processable, self‐healable, and thermally stable due to the chemically linked ionic side chain, satisfying all of the aforementioned requirements. Among the series of polymer gels, the P(SPMA0.75‐r‐MMA0.25) gel shows optimum conductivity (6.7 × 10−4 S cm−1), stretchability (2636% of break at elongation), and self‐healing (98.3% in 3 h) properties. Accordingly, the transparent and self‐healable P(SPMA0.75‐r‐MMA0.25) gels are used to realize thermally robust actuators up to 100 °C and deformable and self‐healable thermal sensors.
The pharmacology and therapeutic applications of monoclonal antibodies

Monoclonal antibodies (mAbs) have emerged as a major class of therapeutic agents on the market. To date, approximately 80 mAbs have been granted marketing approval. In 2018, 12 new mAbs were approved by the FDA, representing 20% of the total number of approved drugs. The majority of mAb therapeutics are for oncological and immunological/infectious diseases, but these are expanding into other disease areas. Over 100 monoclonal antibodies are in development, and their unique features ensure that these will remain a part of the therapeutic pipeline. Thus, the therapeutic value and the elucidation of their pharmacological properties supporting clinical development of these large molecules are unquestioned. However, their utilization as pharmacological tools in academic laboratories has lagged behind their small molecule counterparts. Early therapeutic mAbs targeted soluble cytokines, but now that mAbs also target membrane‐bound receptors and have increased circulating half‐life, their pharmacology is more complex. The principles of pharmacology have enabled the development of high affinity, potent and selective small molecule therapeutics with reduced off‐target effects and drug‐drug interactions. This review will discuss how the same basic principles can be applied to mAbs, with some important differences. Monoclonal antibodies have several benefits, such as fewer off‐target adverse effects, fewer drug‐drug interactions, higher specificity, and potentially increased efficacy through targeted therapy. Modifications to decrease the immunogenicity and increase the efficacy are described, with examples of optimizing their pharmacokinetic properties and enabling oral bioavailability. Increased awareness of these advances may help to increase their use in exploratory research and further understand and characterize their pharmacological properties.
Lessons from eRNAs: understanding transcriptional regulation through the lens of nascent RNAs

ABSTRACT Nascent transcription assays, such as global run-on sequencing (GRO-seq) and precision run-on sequencing (PRO-seq), have uncovered a myriad of unstable RNAs being actively produced from numerous sites genome-wide. These transcripts provide a more complete and immediate picture of the impact of regulatory events. Transcription factors recruit RNA polymerase II, effectively initiating the process of transcription; repressors inhibit polymerase recruitment. Efficiency of recruitment is dictated by sequence elements in and around the RNA polymerase loading zone. A combination of sequence elements and RNA binding proteins subsequently influence the ultimate stability of the resulting transcript. Some of these transcripts are capable of providing feedback on the process, influencing subsequent transcription. By monitoring RNA polymerase activity, nascent assays provide insights into every step of the regulated process of transcription.
Renal microvascular lesions in lupus nephritis

Abstract Renal microvascular lesions, common in lupus nephritis (LN), are associated with long-term poor outcomes. There are mainly five pathological types of renal microvascular lesions in LN: (1) vascular immune complex deposits (ICD), (2) arteriosclerosis (AS), (3) thrombotic microangiopathy (TMA), (4) non-inflammatory necrotizing vasculopathy (NNV), and (5) true renal vasculitis (TRV). The pathogenesis of renal microvascular lesions in LN remains to be elucidated. The activation and dysfunction of endothelial cells, in addition to the contribution of immune system dysfunction, especially the immune complex-induced vascular inflammation and antiphospholipid antibody-associated thrombotic events, are key mechanisms in the development of vascular lesions in LN that need to be further investigated. Alteration of the microvascular environment produces an acute immunological response that recruits immune cells, such as T cells, monocytes, and macrophages, which induces platelet aggregation with microthrombus formation. There is also increased cytotoxicity caused by cytokines produced by immune cells in the kidney. Identifying the mechanism underlying the pathogenesis of renal microvascular lesions in LN might provide potential targets for the development of novel therapies.
Brain structural effects of treatments for depression and biomarkers of response: a systematic review of neuroimaging studies

Abstract Antidepressive pharmacotherapy (AD), electroconvulsive therapy (ECT) and cognitive behavioural therapy (CBT) are effective treatments for major depressive disorder. With our review, we aim to provide a systematic overview of neuroimaging studies that investigate the effects of AD, ECT and CBT on brain grey matter volume (GMV) and biomarkers associated with response. After a systematic database research on PubMed, we included 50 studies using magnetic resonance imaging and investigating (1) changes in GMV, (2) pre-treatment GMV biomarkers associated with response, or (3) the accuracy of predictions of response to AD, ECT or CBT based on baseline GMV data. The strongest evidence for brain structural changes was found for ECT, showing volume increases within the temporal lobe and subcortical structures – such as the hippocampus–amygdala complex, anterior cingulate cortex (ACC) and striatum. For AD, the evidence is heterogeneous as only 4 of 11 studies reported significant changes in GMV. The results are not sufficient in order to draw conclusions about the structural brain effects of CBT. The findings show consistently that higher pre-treatment ACC volume is associated with response to AD, ECT and CBT. An association of higher pre-treatment hippocampal volume and response has only been reported for AD. Machine learning approaches based on pre-treatment whole brain patterns reach accuracies of 64–90% for predictions of AD or ECT response on the individual patient level. The findings underline the potential of brain biomarkers for the implementation in clinical practice as an additive feature within the process of treatment selection.
Protective Effects of Bergamot (Citrus bergamia Risso & Poiteau) Juice in Rats Fed with High-Fat Diet

Abstract The bergamot (Citrus bergamia Risso & Poiteau), a small tree cultivated along the Ionian coast of the Calabria region in Southern Italy, is an ancient plant used for the production of essential oil from fruit peel, but recently evaluated also for the high content of phenolics in the fruit pulp. Indeed, the juice is rich in glycosylated flavone and flavanones, showing a wide range of pharmacological activities. Noteworthy preclinical and clinical studies reported that bergamot juice is effective in reducing plasma lipids. The aim of this study was to evaluate the beneficial effects of a C. bergamia juice using an experimental animal model of metabolic syndrome and cardiovascular risk in vivo. A significant reduction of both triglyceride levels and cardiovascular risk was observed in animals fed with a high-fat diet and bergamot juice. Daily oral treatment with bergamot juice significantly limits a high-fat-induced increase in body, visceral adipose tissue, liver, and heart weight. In addition, C. bergamia juice showed protective effects on hepatic steatosis, probably due to the reduction of oxidative stress and inflammation. Chemical constituents of administered bergamot juice, investigated by means of liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analyses were represented by a wide range of flavonoids, with neohesperidin, neoeriocitrin, and naringin being the most abundant flavonoids according to previous studies. Furthermore, a considerable amount of brutieridin, a flavanone O-glycoside having a 3-hydroxy-3-methyl-glutaryl residue, was observed.
Ondansetron use in the first trimester of pregnancy and the risk of neonatal ventricular septal defect.

BACKGROUND Literature is divided regarding the risk of neonatal ventricular septal defect (VSD) associated with first trimester ondansetron use in pregnancy. METHODS We evaluated the risk of VSD associated with first trimester exposure to intravenous or oral ondansetron in 33 677 deliveries at Magee-Womens Hospital in Pittsburgh, PA (2006-2014). Using log-binomial regression, we evaluated the risk: (1) in the full cohort, (2) using propensity score designs with both matching and inverse probability weighting and (3) utilizing clustered trajectory analysis evaluating the role of dose. Sensitivity analyses assessed the association between ondansetron and all recorded birth defects in aggregate. RESULTS A total of 3733 (11%) pregnancies were exposed to ondansetron in the first trimester (dose range: 2.4-1008 mg). Ondansetron was associated with increased risk of VSD with risk ratios ranging from 1.7 [95% confidence interval (CI) 1.0-2.9] to 2.1 (95% CI 1.1-4.0) across methods. Risks correspond to one additional VSD for approximately every 330 pregnancies exposed in the first trimester. The association was dose-dependent with increased risk in women receiving highest cumulative doses compared with lowest doses [adjusted risk ratio: 3.2 (95% CI 1.0-9.9)]. The association between ondansetron and congenital malformations was diluted as the outcome included additional birth defects. CONCLUSIONS First trimester ondansetron use is associated with an increased risk of neonatal VSD potentially driven by higher doses. This risk should be viewed in the context of risks attributable to severe untreated nausea and vomiting of pregnancy.
Gene drives for schistosomiasis transmission control

Schistosomiasis is one of the most important and widespread neglected tropical diseases (NTD), with over 200 million people infected in more than 70 countries; the disease has nearly 800 million people at risk in endemic areas. Although mass drug administration is a cost-effective approach to reduce occurrence, extent, and severity of the disease, it does not provide protection to subsequent reinfection. Interventions that target the parasites’ intermediate snail hosts are a crucial part of the integrated strategy required to move toward disease elimination. The recent revolution in gene drive technology naturally leads to questions about whether gene drives could be used to efficiently spread schistosome resistance traits in a population of snails and whether gene drives have the potential to contribute to reduced disease transmission in the long run. Responsible implementation of gene drives will require solutions to complex challenges spanning multiple disciplines, from biology to policy. This Review Article presents collected perspectives from practitioners of global health, genome engineering, epidemiology, and snail/schistosome biology and outlines strategies for responsible gene drive technology development, impact measurements of gene drives for schistosomiasis control, and gene drive governance. Success in this arena is a function of many factors, including gene-editing specificity and efficiency, the level of resistance conferred by the gene drive, how fast gene drives may spread in a metapopulation over a complex landscape, ecological sustainability, social equity, and, ultimately, the reduction of infection prevalence in humans. With combined efforts from across the broad global health community, gene drives for schistosomiasis control could fortify our defenses against this devastating disease in the future.
“双打击”多发性骨髓瘤患者的临床预后分析

目的 分析并探讨“双打击”多发性骨髓瘤（MM）患者的临床特征及预后。 方法 研究对象为2010–2016年第二军医大学长征医院诊断的89例MM患者，通过FISH检测染色体变化，基因测序检测TP53基因突变情况，根据最新Walker BA学者提出的“双打击”骨髓瘤定义，分析“双打击”MM患者的临床特征及预后。 结果 “双打击”MM患者15例（16.85%），中位无进展生存（PFS）时间（8. 4个月）和中位总生存（OS）时间（22. 2个月）较非“双打击”MM患者的中位PFS时间（14. 2个月）和中位OS时间（39. 2个月）显著降低（P均<0.05）。 多因素预后风险分析显示，“双打击”是影响患者PFS（HR=2.171，95%CI 1.206~3.907，P=0.010）和OS（HR=4.106，95%CI 2.116~7.969，P<0.001）的独立预后不良因素，且“双打击”患者的中位PFS时间（8. 4个月）和中位OS时间（22. 2个月）分别较R-ISS Ⅲ期患者的中位PFS时间（11. 8个月）和中位OS时间（24. 3个月）显著缩短（P均<0.05）。 结论 “双打击”MM患者预后极差，亟待前瞻性临床研究改善此类患者预后。
Tissue Engineering and Regenerative Medicine 2019: the role of Biofabrication - A Year in Review.

Despite its relative youth, biofabrication is unceasingly expanding by assimilating the contributions from various disciplinary areas and their technological advances. Those developments have spawned the range of available options to produce structures with complex geometries while accurately manipulating and controlling cell behaviour. As it evolves, biofabrication impacts other research fields, allowing the fabrication of tissue models of increased complexity that more closely resemble the dynamics of living tissue. The recent blooming and evolutions in biofabrication has opened new windows and perspectives that could aid the translational struggle in TERM applications. Based on similar methodologies applied in past years' review, we identified the most high-impact publications and reviewed the major concepts, findings, and research outcomes in the context of advancement beyond the state-of-the-art in the field. We first aim to clarify the confusion in terminology and concepts in biofabrication to therefore introduce the striking evolutions in 3D and 4D bioprinting of tissues. We conclude with a short discussion on the future outlooks for innovation that Biofabrication could bring to TERM research.
An ethical framework for genetic counseling in the genomic era

The field of genetic counseling has grown and diversified since the profession emerged in the early 1970s. In the same period, genomic testing has become more complex, profitable, and widespread. With these developments, the scope of ethical considerations relevant to genetic counseling has expanded. In light of this, we find it helpful to revisit how ethical and relational variables are used to inform genetic counseling practice. Our specific focus is on whether, and to what extent, it is ethically acceptable for genetic counselors to make normative recommendations to patients. This article builds on prior literature that has critiqued nondirectiveness, a concept that has influenced and constrained the modern profession of genetic counseling since its origin. In it, we review scholarly efforts to move beyond nondirectiveness, which we believe privilege patient autonomy at the expense of other important values. We then argue that genetic counselors should favor a more explicit commitment to the principles of beneficence and non‐maleficence, as well as a broader understanding of autonomy and the relational variables that impact genetic counseling. Finally, to translate our arguments into practice, we present a framework of six considerations that genetic counselors should take into account when deciding whether it is ethically acceptable, or even desirable, to make recommendations to patients in certain areas of their work.
Atherosclerotic and Hypertensive Cardiovascular Disease are Associated with Death at Sublethal Carboxyhemoglobin Levels: A Postmortem Study

Residential fires are a significant cause for morbidity and mortality in the United States. Death is often the result of soot and smoke inhalation causing carbon monoxide (CO) toxicity. The approximate lethal level of carboxyhemoglobin (COHb) in healthy adults has been well described. However, a significant number of medical examiner cases involve infirmed decedents, often elderly, with complex cardiovascular disease burdens. It is well known that death in these cases will occur at sublethal levels of COHb; however, increased lethality has been largely documented via anecdotal experience and lacks quantification. Fifty‐five cases were identified where death resulted from smoke and soot inhalation suffered in a residential fire. The control group, with no cardiovascular disease, had an age‐adjusted mean COHb level of 61.6% at the time of death. Presence of hypertensive cardiovascular disease showed a 30% reduction in COHb (age‐adjusted mean 43.2%), atherosclerotic disease showed a 33% reduction (age‐adjusted mean 41.5%), and combined disease presentation accounted for 41% reduction (age‐adjusted mean 36.3%). When controlling for age, atherosclerotic and hypertensive cardiovascular diseases were each associated with statistically significant decreases in COHb (p < 0.01). Increasing age was associated with decreased COHb levels at 2.8% per 10 years of life (p < 0.01), even when modeled with hypertensive and atherosclerotic disease. These findings carry important public health significance, as well as practical significance for the medical examiner when interpreting COHb levels in cases of suspected deaths due to smoke and soot inhalation.
Adoption of protocols to improve quality of medical research

O principal meio de divulgacao e compartilhamento dos resultados da pesquisa cientifica sao as publicacoes em periodicos especializados. A qualidade e a relevância da pesquisa sao avaliadas, dentre outros, pelo material que foi publicado, que e quase sempre o unico registro publico da pesquisa realizada. Defeitos nessa comunicacao dificultam a correta avaliacao de um estudo e acabam por limitar sua efetividade. Tal situacao torna-se critica na pesquisa em saude, por permitir decisoes equivocadas por profissionais e, consequentemente, com potencial real [. ]
Environmental and field characteristics associated with lameness in sheep: a study using a smartphone lameness app for data recording

Background Sheep lameness is a major concern among farmers and policymakers with significant impacts on animal welfare standards as well as financial and production performance. The present study attempts to identify the relative importance of environmental and farm-level management characteristics on sheep lameness. Method To address this objective, data were derived from the SPiLaMM project from 18 farms that used smartphone app to collect data, the British Geological Survey and the Meteorological Office over 2016–2018. Data were analysed using a multilevel Poisson regression model. Results Temperature and higher length of pasture had a positive relationship with lameness while concentration of Selenium in soil and flock size had a negative relationship with lameness. In addition, results showed lower lameness levels for the bedrock class mudstone, siltstone, limestone and sandstone in comparison to sandstone and finally, lambs and ewes younger than 1year old had lower levels of lameness than older ewes. Conclusion Findings of the present approach show the potential use of data collected via a smartphone app to study the epidemiology of disease. Furthermore, factors identified could be validated in intervention studies and generate data-driven disease predictive models.
Loganin alleviates LPS‐activated intestinal epithelial inflammation by regulating TLR4/NF‐κB and JAK/STAT3 signaling pathways

Inflammatory bowel disease (IBD) is a chronic, recurrent gastrointestinal inflammation that affects millions of people around the world. Loganin, an iridoid glycoside, has shown the anti‐inflammatory effects. However, the effect of loganin on IBD and its underlying molecular mechanism are not clear. The present study aimed to investigate whether loganin could alleviate IBD and its mechanisms. The intestinal epithelial Caco‐2 cell line was treated with lipopolysaccharide (LPS) to establish an in vitro IBD model. MTT assay was used to detect cell viability. The expression and release level of inflammatory factors were determined by both real‐time‐PCR and ELISA. Western blotting was used to assess the NF‐κB and JAK/STAT3 pathway‐related protein levels. The results showed that loganin repressed the expression and release of IL‐6, TNF‐α, and IL‐1β, and inhibited TLR4/NF‐κB and JAK/STAT3 signaling pathways in a concentration‐dependent manner. Overexpression of TLR4 could reverse the effect of loganin, leading to activation of NF‐κB signaling and production of inflammatory factors. Meanwhile, IGF‐1, a JAK/STAT3 signaling activator, could also reverse the anti‐inflammation effect of loganin. In conclusion, loganin inhibited LPS‐activated intestinal epithelial inflammation by repressing TLR4/NF‐κB and JAK/STAT3 signaling pathway.
A Palliative Care Program for Volunteers in a Community Setting: A Mixed-Methods Pilot Study

Background: The objective of community-based palliative care is to improve the quality of life of patients and their families and to share the responsibility of caregiving. However, the evidence of the efficacy of volunteer services in community-based palliative care is insufficient. Purpose: This pilot study sought to uncover the feasibility and efficacy of a volunteer program in palliative care. Methods: The study used a sequential mixed-methods design. A total of 19 volunteers participated in the training program, and 6 trained volunteers provided services for a period of 10 weeks to 5 families. Quantitative data were collected on death anxiety, coping with death, and meaning in life for volunteers before and after the training and after completing their services. Qualitative data were collected about volunteering experiences. Results: Significant increases in coping with death and meaning in life after training and in meaning in life after providing services were observed among volunteers. Three categories (“Volunteer’s growing influence at home,” “Discovering meaning-in-life through volunteering,” and “Death as the final journey in life”) emerged from the qualitative findings. The caregivers’ satisfaction score was high. Conclusions: A palliative care program was found to be useful for volunteers in finding meaning in life, motivating continued volunteering. Moreover, caregivers were satisfied with the palliative care service of volunteers.