Miracle-dz/UniFAR-FTUs huggingface dataset:
How acceptable is paternalism? A survey-based study of clinician and nonclinician opinions on paternalistic decision making

ABSTRACT We conducted an empirical study to explore clinician and lay opinions on the acceptability of physician paternalism. Respondents read a vignette describing a patient with brain hemorrhage facing urgent surgery that would be lifesaving but would result in long-term severe disability. Cases were randomized to show either low or high surrogate distress and certain or uncertain prognosis, with respondents rating the acceptability of not offering brain surgery. Clinicians (N = 169) were more likely than nonclinicians (N = 649) to find the doctor withholding surgery acceptable (30.2% vs. 11.4%, p ≤ 0.001). Among clinicians, the doctor withholding surgery was more acceptable when prognosis was certain to be poor (odds ratio [OR] 2.04, 95% confidence interval [CI] 1.04, 4.01). There was no effect of surrogate distress on clinician ratings. Responses among lay public were more variable. Given the differences in attitudes across clinicians and lay public, there is an ongoing need to engage stakeholders in the process of end-of-life decision making.
Inhibition of NMDA Receptors Prevents the Loss of BDNF Function Induced by Amyloid β

Brain-derived neurotrophic factor (BDNF) plays important functions in cell survival and differentiation, neuronal outgrowth and plasticity. In Alzheimer’s disease (AD), BDNF signaling is known to be impaired, partially because amyloid β (Aβ) induces truncation of BDNF main receptor, TrkB-full length (TrkB-FL). We have previously shown that such truncation is mediated by calpains, results in the formation of an intracellular domain (ICD) fragment and causes BDNF loss of function. Since calpains are Ca2+-dependent proteases, we hypothesized that excessive intracellular Ca2+ build-up could be due to dysfunctional N-methyl-d-aspartate receptors (NMDARs) activation. To experimentally address this hypothesis, we investigated whether TrkB-FL truncation by calpains and consequent BDNF loss of function could be prevented by NMDAR blockade. We herein demonstrate that a NMDAR antagonist, memantine, prevented excessive calpain activation and TrkB-FL truncation induced by Aβ25–35. When calpains were inhibited by calpastatin, BDNF was able to increase the dendritic spine density of neurons exposed to Aβ25135. Moreover, NMDAR inhibition by memantine also prevented Aβ-driven deleterious impact of BDNF loss of function on structural (spine density) and functional outcomes (synaptic potentiation). Collectively, these findings support NMDAR/Ca2+/calpains mechanistic involvement in Aβ-triggered BDNF signaling disruption.
Editors' note: Wrist sensor reveals sympathetic hyperactivity and hypoventilation before probable SUDEP

In “Wrist sensor reveals sympathetic hyperactivity and hypoventilation before probable SUDEP,” authors Picard et al. reported probable sudden unexpected death in epilepsy (SUDEP) in a 20-year-old man wearing a smartwatch that recorded wrist motion via 3-axis accelerometer and electrodermal activity. They suggest, based on the extremely elevated peri-ictal electrodermal response (EDR) recorded by the smartwatch at the time of death, that the reported case supports autonomic dysfunction and severe postictal cerebral dysfunction as SUDEP mechanisms.
Potent anti‐leukemia activities of humanized CD19‐targeted Chimeric antigen receptor T (CAR‐T) cells in patients with relapsed/refractory acute lymphoblastic leukemia

Chimeric antigen receptor T (CAR‐T) cell therapy has shown promising results for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). The immune response induced by murine single‐chain variable fragment (scFv) of the CAR may limit CAR‐T cell persistence and thus increases the risk of leukemia relapse. In this study, we developed a novel humanized scFv from the murine FMC63 antibody. A total of 18 R/R ALL patients with or without prior murine CD19 CAR‐T therapy were treated with humanized CD19‐targeted CAR‐T cells (hCART19s). After lymphodepletion chemotherapy with cyclophosphamide and fludarabine, the patients received a single dose (1 × 106/kg) of autologous hCART19s infusion. Among the 14 patients without previous CAR‐T therapy, 13 (92.9%) achieved complete remission (CR) or CR with incomplete count recovery (CRi) on day 30, whereas 1 of the 3 patients who failed a second murine CAR‐T infusion achieved CR after hCART19s infusion. At day 180, the overall and leukemia‐free survival rates were 65.8% and 71.4%, respectively. The cumulative incidence of relapse was 22.6%, and the nonrelapse mortality rate was 7.1%. During treatment, 13 patients developed grade 1‐2 cytokine release syndrome (CRS), 4 patients developed grade 3‐5 CRS, and 1 patient experienced reversible neurotoxicity. These results indicated that hCART19s could induce remission in patients with R/R B‐ALL, especially in patients who received a reinfusion of murine CAR‐T.
Crab Shell Extract Improves Sperm Parameters and Antioxidant Status in Testes of Diabetic Rats

ABSTRACT Crab shell (CS), which contains antioxidant compounds, has been used as a promising nutritional and medical compound in traditional medicine. Oxidative stress plays a critical role in the development of diabetes. This study aims to investigate the effects of CS extract (CSE) on sperm parameters, antioxidant status, and histopathology changes of testes in diabetic rats. In this experimental study, 40 Wistar male rats were investigated in five groups (n = 8/group): diabetic rats treated with different CS concentrations (i.e., 100, 200, and 400 mg/kg), diabetic group, and nondiabetic control. To induce diabetes, a single dose (60 mg/kg) of streptozotocin (STZ) was injected intraperitoneally; three days later, treatment with CSE was begun and conducted for 14 days. The fasting blood glucose, testes weight, and viability, number, and motility of sperm were assessed. In addition, the levels of ferric reducing antioxidant power (FRAP) and nitric oxide (NO) were estimated in the testes. Testes were examined using histological analysis. The results of this study revealed that sperm number, motility, and serum testosterone levels of CSE-treated diabetic rats increased significantly (p = .000) compared with the untreated diabetic group in a dose-depended manner while the number of immotile sperm decreased significantly (p = .017). CS also reduced the testicular level of nitric oxide and fasting blood glucose; however, it led to significant growth in the FRAP levels of testes (p = .002). Our results suggest that CSE improves sperm parameters and protects the testicular tissue against the oxidative stress damage induced by diabetes.
Nanomaterials in the environment: Behavior, fate, bioavailability, and effects—An updated review

The present review covers developments in studies of nanomaterials (NMs) in the environment since our much cited review in 2008. We discuss novel insights into fate and behavior, metrology, transformations, bioavailability, toxicity mechanisms, and environmental impacts, with a focus on terrestrial and aquatic systems. Overall, the findings were that: 1) despite substantial developments, critical gaps remain, in large part due to the lack of analytical, modeling, and field capabilities, and also due to the breadth and complexity of the area; 2) a key knowledge gap is the lack of data on environmental concentrations and dosimetry generally; 3) substantial evidence shows that there are nanospecific effects (different from the effects of both ions and larger particles) on the environment in terms of fate, bioavailability, and toxicity, but this is not consistent for all NMs, species, and relevant processes; 4) a paradigm is emerging that NMs are less toxic than equivalent dissolved materials but more toxic than the corresponding bulk materials; and 5) translation of incompletely understood science into regulation and policy continues to be challenging. There is a developing consensus that NMs may pose a relatively low environmental risk, but because of uncertainty and lack of data in many areas, definitive conclusions cannot be drawn. In addition, this emerging consensus will likely change rapidly with qualitative changes in the technology and increased future discharges. Environ Toxicol Chem 2018;37:2029–2063. © 2018 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Elimination of urogenital schistosomiasis in Iran: past history and the current situation

SUMMARY In recent years, through a national programme for schistosomiasis control, this infection has been eliminated from Iran. The aim of this study was to report the process of significant decrease of urogenital schistosomiasis in southwestern Iran. During national programme surveillance for urogenital schistosomiasis control which was implemented by Centres for Disease Control and Prevention (CDC) of Khuzestan province from 1975 to 2013, more than 1·3 million urine samples were taken from inhabitants of high risk foci. All urine samples were gathered between 10:00 a.m and 02:00 p.m and, after centrifuging, specimens were tested under optical microscope in order to detect Schistosoma haematobium eggs. Data analysis was performed using SPSS 18 software. In this retrospective study significant reduction was seen in number of infections between 1975 and 2013. During the years 1975–1980, 1981–1990 and 1991–2000 there were 1582, 761 and 79 cases of S. haematobium, respectively. In 2001 only one case was reported from Ahvaz and indeed this was the last case of urogenital schistosomiasis in Khuzestan and of course, in Iran. Prevalence from 1·064% between 1975 and 1980 slumped to 0% in 2012–2013. During several projects for surveillance of urogenital schistosomiasis, selective population chemotherapy, snail control, population education, environmental improvement, etc were carried out throughout the surveillance period. According to elimination of S. haematobium in Khuzestan province, the only endemic region of Iran, control of disease, especially the campaign with intermediate host snails should be continued. Iran can be a successful model for countries suffering from this disease.
Effectiveness of an online SUpport PRogramme (SUPR) for older hearing aid users: study protocol for a cluster randomised controlled trial

Background An educational SUpport PRogramme called SUPR has been developed for hearing aid users (HAUs) and their communication partners (CPs) offering care beyond hearing aid fitting. SUPR teaches its users communication strategies, hearing aid handling skills and personal adjustment to hearing impairment. Methods/design Using a cluster randomised controlled trial design, 70 Dutch hearing aid dispenser practices were randomised into hearing aid fitting (care as usual, 34 practices) and hearing aid fitting including SUPR (36 practices). The aim was to recruit a total of 569 older (aged 50+ years) first-time (n=258) and experienced (n=311) HAUs and their CPs. SUPR consists of a Practical Support Booklet and online material offered via email over a period of 6–7 months. The booklet provides practical information on hearing aids, advice on communication strategies and home exercises. The online material consists of educational videos on hearing aid functionality and usage, communication strategies and peer testimonials. Finally, noncommittal email contact with the dispenser is offered. Every HAU is asked to assign a CP who is advised to be involved intensively. Effect measurements for HAUs and their CPs will occur at baseline and at 6, 12 and 18 months follow-up via online questionnaires. The primary outcomes for HAUs will be the use of communication strategies as measured by the subscales of the Communication Profile for the Hearing Impaired. A process evaluation will be performed. Ethics and dissemination The study was approved by the Dutch Institutional Review Board of the VU Medical University Center Amsterdam. This intervention could contribute to lowering the hearing impairment burden in our ageing society. The results will be disseminated through peer-reviewed publications and scientific conferences. Trial registration number ISRCTN77340339; Pre-results.
Bondi flow from a slowly rotating hot atmosphere

A supermassive black hole in the nucleus of an elliptical galaxy at the centre of a cool-core group or cluster of galaxies is immersed in hot gas. Bondi accretion should occur at a rate determined by the properties of the gas at the Bondi radius and the mass of the black hole. X-ray observations of massive nearby elliptical galaxies, including M87 in the Virgo cluster, indicate a Bondi accretion rate u MB which roughly matches the total kinetic power of the jets, suggesting that there is a tight coupling between the jet power and the mass accretion rate. While the Bondi model considers non-rotating gas, it is likely that the external gas has some angular momentum, which previous studies have shown could decrease the accretion rate drastically. We investigate here the possibility that viscosity acts at all radii to transport angular momentum outwards so that the accretion inflow proceeds rapidly and steadily. The situation corresponds to a giant advection-dominated accretion flow (ADAF) which extends from beyond the Bondi radius down to the black hole. We find solutions of the ADAF equations in which the gas accretes at just a factor of a few less than u MB. These solutions assume that the atmosphere beyond the Bondi radius rotates with a sub-Keplerian velocity and that the viscosity parameter is large, α ≥ 0.1, both of which are reasonable for the problem at hand. The infall time of the ADAF solutions is no more than a few times the free-fall time. Thus, the accretion rate at the black hole is closely coupled to the surrounding gas, enabling tight feedback to occur. We show that jet powers of a few per cent of u MBc 2 are expected if either a fraction of the accretion power is channelled into the jet or the black hole spin energy is tapped by a strong magnetic field pressed against the black hole by the pressure of the accretion flow. We discuss the Bernoulli parameter of the flow, the role of convection and the possibility that these as well as magnetohydrodynamic effects may invalidate the model. If the latter comes to pass, it would imply that the rough agreement between observed jet powers and the Bondi accretion rate is a coincidence and jet power is determined by factors other than the mass accretion rate.
Substance P induces plasticity and synaptic tagging/capture in rat hippocampal area CA2

Significance The hippocampal area Cornu Ammonis (CA) CA2 is a small region interposed between CA1 and CA3. For a long time, there has been a lack of information on the CA2 area’s role in memory formation. This area is innervated by supramammillary axonal fibers that are rich with Substance P (SP), which acts as a neurotransmitter and neuromodulator. We show that SP induces an NMDA receptor- and protein synthesis-dependent potentiation of CA2 synapses that requires kinases such as CaMKIV and PKMζ. The SP-induced effects on Schaffer collateral-CA2 synapses transform entorhinal cortical-CA2 short-term potentiation into long-term potentiation, thereby expressing synaptic tagging and capture, an associative property of neuronal populations that engage in consolidation. The hippocampal area Cornu Ammonis (CA) CA2 is important for social interaction and is innervated by Substance P (SP)-expressing supramammillary (SuM) nucleus neurons. SP exerts neuromodulatory effects on pain processing and central synaptic transmission. Here we provide evidence that SP can induce a slowly developing NMDA receptor- and protein synthesis-dependent potentiation of synaptic transmission that can be induced not only at entorhinal cortical (EC)-CA2 synapses but also at long-term potentiation (LTP)-resistant Schaffer collateral (SC)-CA2 synapses. In addition, SP-induced potentiation of SC-CA2 synapses transforms a short-term potentiation of EC-CA2 synaptic transmission into LTP, consistent with the synaptic tagging and capture hypothesis. Interestingly, this SP-induced potentiation and associative interaction between the EC and SC inputs of CA2 neurons is independent of the GABAergic system. In addition, CaMKIV and PKMζ play a critical role in the SP-induced effects on SC-CA2 and EC-CA2 synapses. Thus, afferents from SuM neurons are ideally situated to prime CA2 synapses for the formation of long-lasting plasticity and associativity.
Thermal and mechanical stability of retained austenite in 1%C bearing steels with varying Si contents

The present study is concerned with thermal and mechanical stability of retained austenite (RA) obtained in high-carbon, high-silicon steels after quenching and tempering. Through the investigation of three different alloy compositions with Si content of ∼0.3, 0.6 and 1.2 wt-%, it is shown that increasing silicon dramatically increases thermal stability. Compression tests on quenched and tempered specimens indicate that RA was also mechanically more stable when present in higher silicon steels. This paper is part of a Themed Issue on Recent developments in bearing steels.
Understanding Humans in Crowded Scenes: Deep Nested Adversarial Learning and A New Benchmark for Multi-Human Parsing

Despite the noticeable progress in perceptual tasks like detection, instance segmentation and human parsing, computers still perform unsatisfactorily on visually understanding humans in crowded scenes, such as group behavior analysis, person re-identification and autonomous driving, etc. To this end, models need to comprehensively perceive the semantic information and the differences between instances in a multi-human image, which is recently defined as the multi-human parsing task. In this paper, we present a new large-scale database "Multi-Human Parsing (MHP)" for algorithm development and evaluation, and advances the state-of-the-art in understanding humans in crowded scenes. MHP contains 25,403 elaborately annotated images with 58 fine-grained semantic category labels, involving 2-26 persons per image and captured in real-world scenes from various viewpoints, poses, occlusion, interactions and background. We further propose a novel deep Nested Adversarial Network (NAN) model for multi-human parsing. NAN consists of three Generative Adversarial Network (GAN)-like sub-nets, respectively performing semantic saliency prediction, instance-agnostic parsing and instance-aware clustering. These sub-nets form a nested structure and are carefully designed to learn jointly in an end-to-end way. NAN consistently outperforms existing state-of-the-art solutions on our MHP and several other datasets, and serves as a strong baseline to drive the future research for multi-human parsing.
Clinical features and survival of gastric cancer patients with DNA mismatch repair deficiency

Patients with germline DNA mismatch repair deficiency (dMMR) have an increased risk of gastric cancer. From our institutional database, we identified 12 patients with germline dMMR gastric cancer. Ten patients (83%) underwent surgical resection, with a 5‐year overall survival rate of 88%. None of the three patients who received preoperative therapy and five patients with recurrent or metastatic disease experienced a significant response to 5‐fluorouracil–based chemotherapy.
Toxicity of chemotherapy regimens in advanced and metastatic pancreatic cancer therapy: A network meta‐analysis

This network meta‐analysis is adopted in order to compare the toxicity of different chemotherapy regimens in the treatment of advanced/metastatic pancreatic cancer (PC). Randomized controlled trials (RCTs) about different chemotherapy regimens for advanced/metastatic PC were included in this network meta‐analysis using Cochrane Library and PubMed electronic databases. The network meta‐analysis was performed to combine direct and indirect evidence in order to calculate the odd ratios (OR) and draw a surface under the cumulative ranking (SUCRA) curve. A total of 19 RCTs were enrolled in this network meta‐analysis including 12 chemotherapy regimens (Gemcitabine, Gemcitabine + S‐1 [tegafur], Gemcitabine + nab‐paclitaxel, Gemcitabine + Capecitabine, Gemcitabine + Cisplatin, FOLFIRINOX [oxaliplatin + irinotecan + fluorouracil + leucovorin], Gemcitabine + oxaliplatin, Gemcitabine + irinotecan, Gemcitabine + Exatecan, Gemcitabine + pemetrexed, Gemcitabine + 5‐FU, S‐1). The incidence of anemia of Gemcitabine + Capecitabine regimen was higher compared with Gemcitabine regimen, Gemcitabine + pemetrexed regimen exhibited the highest incidence rates of anemia and neutropenia; while Gemcitabine + S‐1, Gemcitabine + Cisplatin and FOLFIRINOX regimens exhibited the highest incidence rates of neutropenia. However, S‐1 regimen exhibited lower incidence rates of leukopenia and thrombocytopenia. Moreover, the incidence rates of nausea/vomiting and rash of Gemcitabine + S‐1 regimen were higher compared with Gemcitabine regimen, while Gemcitabine + Cisplatin regimen had the highest incidence rate of nausea/vomiting. This study demonstrated that the hematologic toxicity of S‐1 regimen was the lowest, while Gemcitabine regimen exhibited the lowest incidence rate of non‐hematologic toxicity, providing guidance for the treatment of advanced/metastatic PC.
Liability Dollarization , Sudden Stops & Optimal Financial Policy

Banks in emerging markets intermediate capital inflows denominated in hard currencies (i.e. tradable goods) to fund loans denominated in domestic currency (i.e. domestic consumption units). This “liability dollarization” affects borrowing decisions via three effects absent from standard Sudden Stops models, in which domestic loans are in units of tradables. First, real depreciations reduce ex-post real interest rates, and hence the burden of repaying outstanding debt. Second, expected real appreciations reduce ex-ante real interest rates and increase the resources generated by issuing new debt. Third, the positive co-movement of consumption and real interest rates reduces the expected marginal cost of borrowing. These effects add an “intermediation externality” to the macroprudential externality of the standard models. Optimal policy under commitment is time-inconsistent, tightens access to debt when expectations of real appreciation rise, and does not require capital controls. In contrast, an optimal, time-consistent policy requires both domestic credit regulation and capital controls. Quantitatively, the model predicts higher debt ratios with milder Sudden Stops than the standard models, but it fits observed Sudden Stops better. The optimal policy is very effective but also complex, while simple rules optimized to maximize welfare are much less effective, and implemented with ad-hoc values can reduce welfare significantly. Welfare-improving policies favor taxing domestic debt more than capital inflows, and subsidizing inflows is part of the optimal policy.