Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report

Abstract In March 2020, the WHO declared a pandemic of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With >8.8 million cases and >450,000 deaths reported globally, a vaccine is urgently needed. We report the available safety, tolerability, and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose escalation study among healthy adults, 18-55 years of age, randomized to receive 2 doses, separated by 21 days, of 10 g, 30 g, or 100 g of BNT162b1, a lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein RBD. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titers in sera increased with dose level and after a second dose. Geometric mean neutralizing titers reached 1.8- to 2.8-fold that of a panel of COVID-19 convalescent human sera. These results support further evaluation of this mRNA vaccine candidate.
E3 ligase ZFP91 inhibits Hepatocellular Carcinoma Metabolism Reprogramming by regulating PKM splicing

Rationale: Hepatocellular carcinoma (HCC) is one of the most lethal cancers, and few molecularly targeted anticancer therapies have been developed to treat it. Thus, the identification of new therapeutic targets is urgent. Metabolic reprogramming is an important hallmark of cancer. However, how ubiquitin ligases are involved in the regulation of cancer metabolism remains poorly understood. Methods: RT-PCR, western blot and IHC were used to determine ZFP91 expression. RNAi, cell proliferation, colony formation and transwell assays were used to determine the in vitro functions of ZFP91. Mouse xenograft models were used to study the in vivo effects of ZFP91. Co-IP together with mass spectrometry or western blot was utilized to investigate protein-protein interaction. Ubiquitination was analyzed using IP together with western blot. RNA splicing was assessed by using RT-PCR followed by restriction digestion. Lactate production and glucose uptake assays were used to analyze cancer metabolism. Results: We identified that an E3 ligase zinc finger protein 91 (ZFP91) suppressed HCC metabolic reprogramming, cell proliferation and metastasis in vitro and in vivo. Mechanistically, ZFP91 promoted the Lys48-linked ubiquitination of the oncoprotein hnRNP A1 at lysine 8 and proteasomal degradation, thereby inhibiting hnRNP A1-dependent PKM splicing, subsequently resulting in higher PKM1 isoform formation and lower PKM2 isoform formation and suppressing HCC glucose metabolism reprogramming, cell proliferation and metastasis. Moreover, HCC patients with lower levels of ZFP91 have poorer prognoses, and ZFP91 is an independent prognostic factor for patients with HCC. Conclusions: Our study identifies ZFP91 as a tumor suppressor of hepatocarcinogenesis and HCC metabolism reprogramming and proposes it as a novel prognostic biomarker and therapeutic target of HCC.
Submerged Carbonate Banks Aggregate Pelagic Megafauna in Offshore Tropical Australia

The conservation of marine biodiversity is firmly embedded in national and international policy frameworks. However, the difficulties associated with conducting broad-scale surveys of oceanic environments restrict the evidence base available for applied management in pelagic waters. For example, the Oceanic Shoals Australian Marine Park (AMP) was established in 2012 in a part of Australia’s continental shelf where unique topographic features are thought to support significant levels of biodiversity, yet where our understanding of ecological processes remains limited. We deployed mid-water baited remote underwater video systems (mid-water BRUVS) in the Oceanic Shoals AMP to provide the first non-extractive baseline assessment of pelagic wildlife communities in the area. We used these observations and high-resolution multibeam swaths of the seafloor to explore potential relationships between prominent geomorphological features and the (i) composition, (ii) richness, and (iii) relative abundance of pelagic communities. We documented 32 vertebrate species across three sampling areas, ranging from small baitfish to large sharks and rays, and estimated that up to nearly twice as many taxa may occur within the region as a whole. This highlights the Oceanic Shoals AMP as a reservoir of biodiversity comparable to other documented offshore oceanic hotspots. Our results also confirm the AMP as a possible distant foraging destination for IUCN red listed sea turtles, and a potential breeding and/or nursing ground for a number of charismatic cetaceans. Model outputs indicate that both species richness and abundance increase in proximity to raised geomorphic structures such as submerged banks and pinnacles, highlighting the influence of submarine topography on megafauna distribution. By providing a foundational understanding of spatial patterns in pelagic wildlife communities throughout a little studied region, our work demonstrates how a combination of non-destructive sampling techniques and predictive models can provide new opportunities to support decision-making under data shortage.
Clinial Features, Individualized Treatment and Long-Term Surgical Outcomes of Skull Base Meningiomas With Extracranial Extensions

Object: Skull base meningiomas with extracranial extensions are rarely described. This study describes the clinical features, surgical management and clinical outcomes of these rare tumors and investigates risk factors associated with progression-free survival (PFS). Methods: The clinical data of 34 consecutive patients who underwent surgery for skull base meningiomas with extracranial extensions from 2007 to 2018 were retrospectively collected and analyzed. Results: The mean patient age was 47.9 ± 13.9 years; 50.0% were male. The most common symptoms on admission were ophthalmic. All patients underwent a multidisciplinary consultation before surgery, and received individualized surgical management. The gross total resection (GTR) rate was 55.9% (19/34). Twelve patients received post-operative adjuvant radiotherapy (RT). Twelve patients experienced tumor recurrence during the follow-up period. The median PFS duration was 54 months. The mean overall survival (OS) duration was 111 months. By univariate analysis, a higher histological grade (WHO grade II and III), Ki-67 LI ≥ 5 and the extent of resection (EOR) were significantly associated with tumor recurrence. Multivariate analysis revealed Ki-67 LI ≥ 5, the EOR and adjuvant RT as prognostic factor of PFS. Conclusions: These relatively rare meningiomas are difficult to resect and have a poor prognosis; they are more common in males and have a higher histological grade than intracranial meningiomas. Multidisciplinary collaboration and individualized surgical strategies are crucial for surgically managing these complex tumors. Total removal of the tumor remains challenging. Subtotal resection (STR) or partial resection (PR) followed by RT is a reasonable strategy when radical resection is infeasible. Adjuvant RT should be recommended especially for tumors with histopathological risk factors (Ki-67 LI ≥ 5 or high histological grade).
Assessing palliative care education in undergraduate medical students: translation and validation of the Self-Efficacy in Palliative Care and Thanatophobia Scales for Brazilian Portuguese

Background As the global population ages, palliative care is ever more essential to provide care for patients with incurable chronic conditions. However, in many countries, doctors are not prepared to care for dying patients. Palliative care education should be an urgent concern for all medical schools all around the world, including Latin America and Brazil. Advances in palliative care education require robust assessment tools for constant evaluation and improvement of educational programmes. Bandura’s social cognitive theory proposes that active learning processes are mediated by self-efficacy and associated outcome expectancies, both crucial elements of developing new behaviour. The Self-Efficacy in Palliative Care (SEPC) and Thanatophobia Scales were developed using Bandura’s theory to assess the outcomes of palliative care training. Objectives We aimed to translate and validate these scales for Brazilian Portuguese to generate data on how well doctors are being prepared to meet the needs of their patients. Design Cross-sectional study. Setting One Brazilian medical school. Participants Third-year medical students. Methods The authors translated the scales following the European Organisation for Research and Treatment of Cancer’s recommendations and examined their psychometric properties using data collected from a sample of 111 students in a Brazilian medical school in 2017. Results The Brazilian versions of SEPC and Thanatophobia Scales showed good psychometric properties, including confirmatory factor analysis, replicating the original factors (factor range: 0.51–0.90), and acceptable values of reliability (Cronbach’s alpha: 0.82–0.97 and composite reliability: 0.82–0.96). Additionally, the Brazilian versions of the scales showed concurrent validity, demonstrated through a significant negative correlation. Conclusions The Brazilian version of the scales may be used to assess the impact of current undergraduate training and identify areas for improvement within palliative care educational programmes. The data generated allow Brazilian researchers to join international conversations on this topic and educators to develop tailored pedagogical approaches.
Insecticidal effect of botanical oils for protection of wheat seeds against red flour beetle (Tribolium castaneum)

Botanical oil is an effective element to control stored grain pest like red flour beetle. The main purpose of this study was to determine the direct toxic effects of the different plant oils. This study used five indigenous plant’s seed oil to explore the toxicity level of the plants against red flour beetle. These used plants were Karanja (Pongamia pinnata), Mahogoni (Swietenia mahagoni), Neem (Azadirachta indica), Pithraj (Aphanamixis polystachya) and Sesame (Sesamum indicum). This study also used a germination test of wheat seed to explore the effectiveness of the botanicals. This study revealed that Sesame oil showed the most toxic and repellent effect. The result showed that all the plant oils did not show any adverse effect on germination capability of seeds up to 90 days of treatment. All these indigenous plants are available throughout the country so farmers can easily use these plants in their storage structure for management of stored grain pests.
Imaging biomarkers for predicting poor prognosis of hepatocellular carcinoma: a review

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with a high mortality rate. Heterogeneity is the main biological characteristic of HCC, which manifests through the different biological behaviors of each phenotype and ultimately, affects patient prognosis and treatment efficacy. Various aggressive biological behaviors are considered to be associated with the poor prognosis of HCC patients including poor differentiation, microvascular invasion, intracellular fat accumulation, invasive growth, bile duct invasion or tumor thrombosis, and tumor spread and metastasis, and have been reported as prognostic biomarkers. In addition, HCC results from multifactor synergistic damage, and various factors related to genetics, molecular pathology and immunohistochemistry such as β-catenin, Ki67, cytokeratin-19, and epithelial cell adhesion molecule have an impact on HCC differentiation and prognosis. This article is an overview of the biological behaviors that lead to poor prognosis of HCC, and the roles of morphological and quantitative noninvasive imaging biomarkers in the evaluation and prediction of these behaviors. Some common biomarkers related to genetics, molecular pathology and immunohistochemistry are also briefly summarized. It is hoped that this review will provide clinicians and radiologists with an update on the development of liver imaging, and provide directions for the combination of radiology, genetics, molecular pathology and histopathology to better predict the prognosis of HCC patients.
Electronic Documentation in Pediatrics: The Rationale and Functionality Requirements

Clinical documentation has dramatically changed since the implementation and use of electronic health records and electronic provider documentation. The purpose of this report is to review these changes and promote the development of standards and best practices for electronic documentation for pediatric patients. In this report, we evaluate the unique aspects of clinical documentation for pediatric care, including specialized information needs and stakeholders specific to the care of children. Additionally, we explore new models of documentation, such as shared documentation, in which patients may be both authors and consumers, and among care teams while still maintaining the ability to clearly define care and services provided to patients in a given day or encounter. Finally, we describe alternative documentation techniques and newer technologies that could improve provider efficiency and the reuse of clinical data.
Toshiba’s Speech Recognition System for the CHiME 2020 Challenge

This paper summarizes the Toshiba entry for Track 1 of CHiME 2020 challenge, corresponding to the multi-array speech recognition task. The system is based on conventional acoustic modeling (AM), where phonetic targets are tied to features at the frame-level, and it consists of a combination of convolutional neural networks (CNNs) (with or without residual connections) and factorized time delay neural networks (TDNNFs). We also explored several enhancement strategies for the train and test data, speaker normalization and discriminative training. Results are reported using the provided 3-gram language model (3G LM) and after rescoring with a neural network language model (RNN LM). Following system combination, the submit-ted system achieves a performance of 35.89% and 37.54% word error rate (WER) using 3G LM on the development (DEV) and evaluation (EVAL) sets, respectively. Using the RNN LM, our system achieves a performance of 34.83% and 36.83% WER on DEV and EVAL, respectively. Proposed system was ranked 4th in both the constrained and the unconstrained language model subtracks.
Active flow network generates molecular transport by packets: case of the endoplasmic reticulum

Biological networks are characterized by their connectivity and topology but also by their ability to transport materials. In the case of random transportation, the efficacy is measured by the time it takes to travel between two nodes of the network. We study here the consequences of a unidirectional transport mechanism occurring in the endoplasmic reticulum (ER) network, a structure present in the cell cytoplasm. This unidirectional transport mechanism is an active-waiting transportation, where molecules have to wait a random time before being transported from one node to the next one. We develop here a general theory of transport in an active network and find an unusual network transportation, where molecules group together in redundant packets instead of being disperse. Finally, the mean time to travel between two nodes of the ER is of the order of 20 min, but is reduced to 30 s when we consider the fastest particles because it uses optimal paths. To conclude, the present theory shows that unidirectional transport is an efficient and robust mechanism for fast molecular redistribution inside the ER.
Danish Clinical Event Extraction Developing a clinical event extraction system for electronic health records using deep learning and active learning

Danish electronic health records contain valuable information that is not fully utilized today. Given the unstructured nature of clinical texts, natural language processing techniques are required to extract relevant entities from these records. This study develops a deep learning based system capable of recognizing clinical events in Danish electronic health records. A total of 2.090 breast cancer-related sentences are annotated, comprising 42.753 words and 5.809 events. We fine-tune a pretrained multilingual BERT model on this data, reaching an F1-score of 87.5% on recognizing event spans. An active learning system is implemented for sentence querying to explore how the cost of annotation can be reduced. We implement two active learning strategies, uncertainty sampling and diversity sampling. We find that both strategies lead to a higher F1-score than random sampling when trained on the same amount of sentences. Specifically, we see an F1-score increase of 1.3% and 2.6% compared to random sampling, corresponding to an error reduction of 7.2% and 14.5%. However, in terms of the amount of annotated words, we find random sampling to be less costly than both active learning strategies. We test our fine-tuned BERT model on sentences related to pneumonia in order to establish its cross-domain capabilities. We observe a 5.7 percentage point drop in F1-score, leading to a score of 81.8%. While the benefits of active learning in terms of annotation cost remain unclear and require more research, these findings do prove the feasibility of a Danish clinical event extraction system.
Why chimpanzees carry dead infants: an empirical assessment of existing hypotheses

The study of non-human primate thanatology has expanded dramatically in recent years as scientists seek to understand the evolutionary roots of human death concepts and practices. However, observations of how conspecifics respond to dead individuals are rare and highly variable. Mothers of several species of primate have been reported to carry and continue to interact with dead infants. Such interactions have been proposed to be related to maternal condition, attachment, environmental conditions or reflect a lack of awareness that the infant has died. Here, we tested these hypotheses using a dataset of cases of infant corpse carrying by chimpanzees in Gombe National Park, Tanzania (n = 33), the largest dataset of such cases in chimpanzees. We found that mothers carried infant corpses at high rates, despite behavioural evidence that they recognize that death has occurred. Median duration of carriage was 1.83 days (interquartile range = 1.03–3.59). Using an information theoretic approach, we found no support for any of the leading hypotheses for duration of continued carriage. We interpret these data in the context of recent discussions regarding what non-human primates understand about death.
The contribution of non-coding regulatory elements to cardiovascular disease

Cardiovascular disease collectively accounts for a quarter of deaths worldwide. Genome-wide association studies across a range of cardiovascular traits and pathologies have highlighted the prevalence of common non-coding genetic variants within candidate loci. Here, we review genetic, epigenomic and molecular approaches to investigate the contribution of non-coding regulatory elements in cardiovascular biology. We then discuss recent insights on the emerging role of non-coding variation in predisposition to cardiovascular disease, with a focus on novel mechanistic examples from functional genomics studies. Lastly, we consider the clinical significance of these findings at present, and some of the current challenges facing the field.
A simulation study to examine the information content in phylogenomic datasets under the multispecies coalescent model.

We use computer simulation to examine the information content in multilocus datasets for inference under the multispecies coalescent (MSC) model. Inference problems considered include estimation of evolutionary parameters (such as species divergence times, population sizes, and cross-species introgression probabilities), species tree estimation, and species delimitation based on Bayesian comparison of delimitation models. We found that the number of loci is the most influential factor for almost all inference problems examined. While the number of sequences per species does not appear to be important to species tree estimation, it is very influential to species delimitation. Increasing the number of sites and the per-site mutation rate both increase the mutation rate for the whole locus and these have the same effect on estimation of parameters, but the sequence length has a greater effect than the per-site mutation rate for species tree estimation. We discuss the computational costs when the datasize increases, and provide guidelines concerning the subsampling of genomic data to enable the application of full-likelihood methods of inference.
What Are We Measuring? Convergence of Leadership with Interpersonal and Non-interpersonal Personality

Since leadership styles have been most commonly defined in terms of interpersonal influence, one would assume that they have their main projections on the interpersonal circumplex. In this study, the relations between leadership styles from the Multifactor Leadership Questionnaire and Leader Behaviour Description Questionnaire and both interpersonal and HEXACO personality scales are investigated. As expected, charismatic leadership and leader's consideration have strong projections on the interpersonal circumplex, with main projections on the warm-agreeable octant. Transactional leadership, passive leadership, and task-oriented leadership have considerably weaker or no projections on the circumplex. Leader's consideration is most strongly related to interpersonal personality while both transactional and passive leadership are most strongly related to non-interpersonal personality. It is concluded that especially charismatic leadership and leader's consideration are captured almost fully by the HEXACO personality inventory.
BCR ABL Kinase Inhibitors for Cancer Therapy

BCR-ABL tyrosine kinase inhibitors have started era of molecular targeted therapy and marked a greatest milestone in cancer drug discovery. Despite of impressive cytogenetic response rates achieved with several agents in patients with chronic myelogenous leukemia (CML) in chronic phase, those with advanced stage CML frequently obtain more modest responses that are in many instances of short duration. Several mechanisms of resistance to imatinib are also observed among patients that develop clinical resistance to imatinib. Some approaches are being pursued to overcome these mutations. Deregulated tyrosine kinase activity of the BCR-ABL fusion protein has been established as the causative molecular event in CML. BCR-ABL tyrosine kinase is an ideal target for pharmacological inhibition. Following the initial success of imatinib as frontline therapy for CML, several second generation therapeutic inhibitors have been developed with increased potency and the ability to inhibit the majority of imatinib resistant mutations. In addition, many other protein kinases implicated in signaling transduction downstream BCR-ABL play critical roles in the pathogenesis of CML, thus representing potential therapeutic targets revealed from several clinical studies. The objective of present article is on current developments of potential existing and new innovative BCR-ABL kinase inhibitors for tumor therapy and specificity of several new inhibitors.