Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigational drugs in clinical trials for Hidradenitis Suppurativa

ABSTRACT Introduction: Hidradenitis suppurativa is a chronic skin disease with a significant unmet need for treatment options. Randomized controlled trials are few and only a single drug (adalimumab) has Hidradenitis as a registered indication. Areas covered: The clinicaltrials.gov and the EudraCT clinical trials register for reported trials on Hidradenitis Suppurativa was searched on the 22–06-2017. Trials for upcoming new drugs for HS are reported focusing on drugs in phase I and II trials. Expert opinion: Currently, MABp1, Secukinumab, CJM112, Apremilast and IFX-1 are being investigated in Phase I and II trials and offer theoretical and promising new treatment options. A trial with the drug MEDI8968 has been terminated with disappointing results. Metformin, Botulinum Toxin B, Provodine, Benzoyl Peroxide and intralesional triamcinolone are being tested as well. Treatment of Hidradenitis remains a challenge and quality RTCs are needed. Studies indicates a range of potential targets for therapy such as interleukin-1 and interleukin-17, but ‘broad-spectrum’ immunosuppressants like phosphodiesterase-4 inhibitors are being examined as well. A range of outcomes, including Physician Global Assessment, Sartorius scores and hidradenitis suppurativa clinical response are used in these trials, making future meta-analysis of the data difficult.
Social Capital, Network Effects, and Savings in Rural Vietnam

Information failures are a major barrier to formal financial saving in low-income countries. We explore the extent to which social capital in rural Vietnam plays a role in increasing formal savings where knowledge gaps exist. Social capital is defined as information sharing and the elimination of information asymmetries through active participation in the Women's Union. We consider high- and low-quality networks in terms of the quality of information transmitted. We find that membership of high-quality networks leads to higher levels of saving in formal financial institutions and saving for productive investments. Our results support a role for social capital in facilitating savings and suggest that transmitting financial information through the branches of the Women's Union could be effective in increasing formal savings at grassroots level. We also conclude that it is important to ensure that the information disseminated is accurate given that behavioral effects are also found in networks with low-quality information.
Mitochondrial genome variability: the effect on cellular functional activity

Mitochondria are the key players in cell metabolism, calcium homeostasis, and reactive oxygen species (ROS) production. Mitochondrial genome alterations are reported to be associated with numerous human disorders affecting nearly all tissues. In this review, we discuss the available information on the involvement of mitochondrial DNA (mtDNA) mutations in cell dysfunction.
SparCML: high-performance sparse communication for machine learning

Applying machine learning techniques to the quickly growing data in science and industry requires highly-scalable algorithms. Large datasets are most commonly processed "data parallel" distributed across many nodes. Each node's contribution to the overall gradient is summed using a global allreduce. This allreduce is the single communication and thus scalability bottleneck for most machine learning workloads. We observe that frequently, many gradient values are (close to) zero, leading to sparse of sparsifyable communications. To exploit this insight, we analyze, design, and implement a set of communication-efficient protocols for sparse input data, in conjunction with efficient machine learning algorithms which can leverage these primitives. Our communication protocols generalize standard collective operations, by allowing processes to contribute arbitrary sparse input data vectors. Our generic communication library, SparCML1, extends MPI to support additional features, such as non-blocking (asynchronous) operations and low-precision data representations. As such, SparCML and its techniques will form the basis of future highly-scalable machine learning frameworks.
Differences in the Endocannabinoid System of Sperm from Fertile and Infertile Men

Male infertility is a major cause of problems for many couples in conceiving a child. Recently, lifestyle pastimes such as alcohol, tobacco and marijuana have been shown to have further negative effects on male reproduction. The endocannabinoid system (ECS), mainly through the action of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) at cannabinoid (CB1, CB2) and vanilloid (TRPV1) receptors, plays a crucial role in controlling functionality of sperm, with a clear impact on male reproductive potential. Here, sperm from fertile and infertile men were used to investigate content (through LC-ESI-MS), mRNA (through quantitative RT-PCR), protein (through Western Blotting and ELISA) expression, and functionality (through activity and binding assays) of the main metabolic enzymes of AEA and 2-AG (NAPE-PLD and FAAH, for AEA; DAGL and MAGL for 2-AG), as well as of their binding receptors CB1, CB2 and TRPV1. Our findings show a marked reduction of AEA and 2-AG content in infertile seminal plasma, paralleled by increased degradation: biosynthesis ratios of both substances in sperm from infertile versus fertile men. In addition, TRPV1 binding was detected in fertile sperm but was undetectable in infertile sperm, whereas that of CB1 and CB2 receptors was not statistically different in the two groups. In conclusion, this study identified unprecedented alterations of the ECS in infertile sperm, that might impact on capacitation and acrosome reaction, and hence fertilization outcomes. These alterations might also point to new biomarkers to determine male reproductive defects, and identify distinct ECS elements as novel targets for therapeutic exploitation of ECS-oriented drugs to treat male fertility problems.
Patient preferences and randomised clinical trials.

The child should be examined but not without the knowledge and agreement of a parent (or the order of a court). Mothers of pr? adolescent children should always be invited to be present, except in the most exceptional circumstances. Adolescent patients should be asked whether they wish a parent to be present. It is usually counterproductive to examine a resistant child, and if his or her cooperation cannot be obtained the examination should be deferred unless there are urgent medical reasons to proceed. The child should be examined as soon as optimal arrangements can be made. Few children require urgent examination. Repetitive examination is usually abusive and should be avoided. The examination should be conducted in absolute privacy and in an environment where the child can be comfortable? not behind screens in open wards or in police stations. There should be adequate equipment for any necessary diagnostic tests. Recording and photographic facilities are an advantage but their value is outweighed if they cause distress to the child or mean that another examination has to be conducted. Who should examine?
Bioeconomic modeling for a small-scale sea cucumber fishery in Yucatan, Mexico

Due to the heavy exploitation of holothurians over the last few decades, it is necessary to implement fishing regulations aimed at reversing this situation. Holothurians require specific regulations that take into account their biology and ecology. Their behavior to group and form patches as a strategy for feeding, defense and reproduction, makes them vulnerable to overfishing. The higher the population density, the higher the catchability coefficient, and because they are sedentary organisms, the catchability does not change significantly until the density is very low. Hence, the stock assessment of holothurians can be improved by analyzing their spatial distribution. This paper proposes a stock assessment technique that considers the spatial distribution pattern of the sea cucumber Isostichopus badionotus from Yucatan, Mexico. A bioeconomic spatial model was developed to explain the interactions between fishing effort allocation, quasi-profits and the population in the short term. Because of the high price of the species and the low production costs, artisanal fishers preferred to maximize short-term quasi-profits, rather than the long-term benefits they could gain with low fishing mortality rates.
Targeting tachykinin receptors in neuroblastoma

Neuroblastoma is the most common extracranial tumor in children. Despite aggressive multimodal treatment, high-risk neuroblastoma remains a clinical challenge with survival rates below 50%. Adding targeted drugs to first-line therapy regimens is a promising approach to improve survival in these patients. TACR1 activation by substance P has been reported to be mitogenic in cancer cell lines. Tachykinin receptor (TACR1) antagonists are approved for clinical use as an antiemetic remedy since 2003. Tachykinin receptor inhibition has recently been shown to effectively reduce growth of several tumor types. Here, we report that neuroblastoma cell lines express TACR1, and that targeting TACR1 activity significantly reduced cell viability and induced apoptosis in neuroblastoma cell lines. Gene expression profiling revealed that TACR1 inhibition repressed E2F2 and induced TP53 signaling. Treating mice harboring established neuroblastoma xenograft tumors with Aprepitant also significantly reduced tumor burden. Thus, we provide evidence that the targeted inhibition of tachykinin receptor signaling shows therapeutic efficacy in preclinical models for high-risk neuroblastoma.
Characterizing Adversity of Lysosomal Accumulation in Nonclinical Toxicity Studies: Results from the 5th ESTP International Expert Workshop

Lysosomes have a central role in cellular catabolism, trafficking, and processing of foreign particles. Accumulation of endogenous and exogenous materials in lysosomes represents a common finding in nonclinical toxicity studies. Histologically, these accumulations often lack distinctive features indicative of lysosomal or cellular dysfunction, making it difficult to consistently interpret and assign adverse dose levels. To help address this issue, the European Society of Toxicologic Pathology organized a workshop where representative types of lysosomal accumulation induced by pharmaceuticals and environmental chemicals were presented and discussed. The expert working group agreed that the diversity of lysosomal accumulations requires a case-by-case weight-of-evidence approach and outlined several factors to consider in the adversity assessment, including location and type of cell affected, lysosomal contents, severity of the accumulation, and related pathological effects as evidence of cellular or organ dysfunction. Lysosomal accumulations associated with cytotoxicity, inflammation, or fibrosis were generally considered to be adverse, while those found in isolation (without morphologic or functional consequences) were not. Workshop examples highlighted the importance of thoroughly characterizing the biological context of lysosomal effects, including mechanistic data and functional in vitro readouts if available. The information provided here should facilitate greater consistency and transparency in the interpretation of lysosomal effects.
Morphological Characterization of Electrospun Nano‐Fibrous Membranes of Biodegradable Poly(L‐lactide) and Poly(lactide‐co‐glycolide)

Hydrophobic biodegradable polyesters, poly(L-lactide) (PLLA) and poly(lactide-co-glycolide) (PLGA), were electrospun on different types of collectors to induce morphological changes in the nanofibrous membrane. On the metal collector smooth nonwoven membranes were obtained for both PLLA and PLGA, while on the water reservoir the surface of the membranes became rough due to shrinkage and slow charge dissipation. When NaCl was added to water to enhance the conductivity, the roughness of the membrane surface was changed, yet the shrinkage remained relatively unchanged. The crystallization of PLLA electospun material on the metal plate was suppressed because of the rapid solvent evaporation, however, upon annealing above the glass transition temperature for 24 hr the PLLA membrane became crystallized. When electrospun on the water reservoir, the PLLA membrane remained amorphous. Crystalline PLLA was obtained by electrospinning on the methanol reservoir due to the swelling of nanofibers by methanol.
Detection of Stress Levels from Biosignals Measured in Virtual Reality Environments Using a Kernel-Based Extreme Learning Machine

Virtual reality (VR) is a computer technique that creates an artificial environment composed of realistic images, sounds, and other sensations. Many researchers have used VR devices to generate various stimuli, and have utilized them to perform experiments or to provide treatment. In this study, the participants performed mental tasks using a VR device while physiological signals were measured: a photoplethysmogram (PPG), electrodermal activity (EDA), and skin temperature (SKT). In general, stress is an important factor that can influence the autonomic nervous system (ANS). Heart-rate variability (HRV) is known to be related to ANS activity, so we used an HRV derived from the PPG peak interval. In addition, the peak characteristics of the skin conductance (SC) from EDA and SKT variation can also reflect ANS activity; we utilized them as well. Then, we applied a kernel-based extreme-learning machine (K-ELM) to correctly classify the stress levels induced by the VR task to reflect five different levels of stress situations: baseline, mild stress, moderate stress, severe stress, and recovery. Twelve healthy subjects voluntarily participated in the study. Three physiological signals were measured in stress environment generated by VR device. As a result, the average classification accuracy was over 95% using K-ELM and the integrated feature (IT = HRV + SC + SKT). In addition, the proposed algorithm can embed a microcontroller chip since K-ELM algorithm have very short computation time. Therefore, a compact wearable device classifying stress levels using physiological signals can be developed.
Precise integrin-targeting near-infrared imaging-guided surgical method increases surgical qualification of peritoneal carcinomatosis from gastric cancer in mice

Peritoneal carcinomatosis from gastric cancer represents a common recurrent gastric cancer that seriously affects the survival, prognosis, and quality of life of patients at its advanced stage. In recent years, complete cytoreduction surgery in combination with hyperthermic intraperitoneal chemotherapy has been demonstrated to improve the survival and prognosis of patients with malignant tumors including peritoneal carcinomatosis from gastric cancer. Establishing viable methods of accurately assessing the tumor burden in patients with peritoneal carcinoma and correctly selecting suitable patients in order to improve cytoreduction surgical outcomes and reduce the risk of postoperative complications has become a challenge in the field of peritoneal carcinoma research. Here, we investigated peritoneal carcinomatosis from gastric cancer in a mouse model by using our self-developed surgical navigation system that combines optical molecular imaging with an integrin-targeting Arg-Gly-Asp-indocyanine green (RGD-ICG) molecular probe. The results showed that our diagnostic method could achieve a sensitivity and specificity of up to 93.93% and 100%, respectively, with a diagnostic index (DI) of 193.93% and diagnostic accuracy rate of 93.93%. Furthermore, the minimum tumor diameter measured during the surgery was 1.8 mm and the operative time was shortened by 3.26-fold when compared with the conventionally-treated control group. Therefore, our surgical navigation system that combines optical molecular imaging with an RGD-ICG molecular probe, could improve the diagnostic accuracy rate for peritoneal carcinomatosis from gastric cancer, shorten the operative time, and improve the quality of the cytoreduction surgery for peritoneal carcinomatosis from gastric cancer, thus providing a solid foundation for its future clinical development and application.
Asymptotic formulae for implied volatility in the Heston model

In this paper, we prove an approximate formula expressed in terms of elementary functions for the implied volatility in the Heston model. The formula consists of the constant and first-order terms in the large maturity expansion of the implied volatility function. The proof is based on saddlepoint methods and classical properties of holomorphic functions.
Innovative Self-Regulation Strategies to Reduce Weight Gain in Young Adults: The Study of Novel Approaches to Weight Gain Prevention (SNAP) Randomized Clinical Trial.

IMPORTANCE Weight gain occurs commonly in young adults and has adverse effects on health. OBJECTIVE To compare 2 self-regulation interventions vs control in reducing weight gain in young adults over a mean follow-up of 3 years. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial in 2 academic settings of 599 participants aged 18 to 35 years with body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) of 21.0 to 30.0, recruited via mailings and emails from August 2010 to February 2012. Data were analyzed from January 2015 to January 2016. INTERVENTIONS Participants were randomized to control, self-regulation plus small changes, or self-regulation plus large changes. Both interventions focused on frequent self-weighing to cue behavior changes. "Small changes" taught participants to reduce intake and increase activity, both by approximately 100 calories per day. "Large changes" focused on losing 2.3 to 4.5 kg initially to buffer against expected weight gain. MAIN OUTCOMES AND MEASURES Changes in weight from baseline over mean follow-up of 3 years. Secondary outcomes included proportion gaining at least 0.45 kg from baseline, proportion developing obesity (BMI, ≥30.0), and weight change baseline to 2 years. RESULTS Among the 599 participants (22% men; 27% minority; mean [SD] age, 27.7 [4.4] years; mean [SD] BMI, 25.4 [2.6]), mean (SE) weight changes over a mean follow-up of 3 years were 0.26 (0.22), -0.56 (0.22), and -2.37 (0.22) kg in the control, small-changes, and large-changes groups, respectively (P < .001). Differences among all 3 groups were significant (large changes vs control, P < .001; small changes vs control, P = .02; large changes vs small changes, P < .001). On secondary outcomes, both interventions significantly reduced incidence of obesity relative to control (mean [SE], 8.6% [2.0%], 7.9% [2.0%], and 16.9% [2.7%] in the large-changes, small-changes, and control groups, respectively; P = .02 for large changes vs control and P = .002 for small changes vs control); a smaller percentage of participants in the large-changes group gained 0.45 kg or more (mean [SE], 23.6% [2.8%], 32.5% [3.8%], and 40.8% [4.4%], respectively; P < .001 vs control and P = .02 vs small changes) and weight change from baseline to 2 years was greater in control than in small or large changes (mean [SE], 0.54 [0.33], -0.77 [0.33], and -1.50 [0.34] kg, respectively; P = .02 vs small changes and P < .001 vs large changes). CONCLUSIONS AND RELEVANCE Self-regulation with large or small changes both reduced weight gain in young adults over 3 years relative to control, but the large-changes intervention was more effective. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01183689.
Entorhinal fast-spiking speed cells project to the hippocampus

Significance Our location in space is represented by a spectrum of space and direction-responsive cell types in medial entorhinal cortex and hippocampus. Many cells in these areas respond also to running speed. The presence of local speed-tuned cells is considered a requirement for position to be encoded in a self-motion–dependent manner; however, whether and how speed-responsive cells in entorhinal cortex and hippocampus are functionally connected have not been determined. The present study shows that a large proportion of entorhinal speed cells are fast-spiking with properties similar to those of GABAergic interneurons and that outputs from a subset of these cells, particularly the parvalbumin-expressing subset, form a component of the medial entorhinal input to the hippocampus. The mammalian positioning system contains a variety of functionally specialized cells in the medial entorhinal cortex (MEC) and the hippocampus. In order for cells in these systems to dynamically update representations in a way that reflects ongoing movement in the environment, they must be able to read out the current speed of the animal. Speed is encoded by speed-responsive cells in both MEC and hippocampus, but the relationship between the two populations has not been determined. We show here that many entorhinal speed cells are fast-spiking putative GABAergic neurons. Using retrograde viral labeling from the hippocampus, we find that a subset of these fast-spiking MEC speed cells project directly to hippocampal areas. This projection contains parvalbumin (PV) but not somatostatin (SOM)-immunopositive cells. The data point to PV-expressing GABAergic projection neurons in MEC as a source for widespread speed modulation and temporal synchronization in entorhinal–hippocampal circuits for place representation.
High‐dose melphalan‐based sequential conditioning chemotherapy followed by allogeneic haematopoietic stem cell transplantation in adult patients with relapsed or refractory acute myeloid leukaemia

Considering the unsatisfactory results of salvage therapies for patients with relapsed/refractory acute myeloid leukaemia (R/R‐AML), their value before allogeneic haematopoietic stem cell transplantation (HSCT) remains questionable. However, direct allogeneic HSCT following established conditioning regimens applied in patients with R/R‐AML during active disease has been equally disappointing. In this retrospective observational study, high‐dose melphalan, as part of a sequential preparative regimen, followed by a total body irradiation (4 × 2 Gy)‐based or a treosulfan‐based dose‐adapted conditioning therapy for allogeneic HSCT was administered to 292 adult patients (median age 56 years, range 17–74) with primary refractory (144 patients), secondary refractory (97 patients) or relapsed AML (51 patients). Overall survival rates at 3 years were 34%, 29% and 41%, respectively. Risk factors associated with an inferior survival were higher age, transplantation from a human leucocyte antigen‐mismatched donor and high disease burden. Patients transplanted with blast infiltration <20% showed a notable survival rate of 51% at 3 years. In particular, patients with primary refractory AML showed a more favourable outcome when transplanted early during their disease course. Thus, high‐dose melphalan‐based sequential conditioning chemotherapy followed by an allogeneic HSCT is feasible and enables long‐term remission to be achieved in a substantial proportion of patients with active R/R‐AML.
In Small We Trust

Day-to-day interactions often involve individuals interacting with groups, but little is known about the criteria that people use to decide which groups to approach or trust and which to avoid or distrust. Seven studies provide evidence for a “small = trustworthy” heuristic, such that people perceive numerically smaller groups as more benevolent in their character and intentions. As a result of this, individuals in trust-sensitive contexts are more likely to approach and engage with groups that are relatively small than those that are relatively large. We provide evidence for this notion across a range of contexts, including analyses of social categories (Studies 1 and 2), ad hoc collections of individuals (Study 3), interacting panels (Studies 4-6), and generalized, abstract judgments (Study 7). Findings suggest the existence of a general lay theory of group size that may influence how individuals interact with groups.