Miracle-dz/UniFAR-FTUs huggingface dataset:
Hospitalized COVID-19 Patients Were Five Times More Likely to Suffer From Total Sleep Deprivation Compared to Non-COVID-19 Patients; an Observational Comparative Study

Objectives: Sleeping disorders are a common complaint in patients who suffer from an acute COVID-19 infection. Nonetheless, little is known about the severity of sleep disturbances in hospitalized COVID-19 patients, and whether these are caused by disease related symptoms, hospitalization, or the SARS-CoV-2 virus itself. Therefore, the aim of this study was to compare the quality and quantity of sleep in hospitalized patients with and without COVID-19, and to determine the main reasons for sleep disruption. Methods: This was an observational comparative study conducted between October 1, 2020 and February 1, 2021 at the pulmonary ward of an academic hospital in the Netherlands. This ward contained both COVID-19-positive and -negative tested patients. The sleep quality was assessed using the PROMIS-Sleep Disturbance Short Form and sleep quantity using the Consensus Sleep Diary. Patient-reported sleep disturbing factors were summarized. Results: A total of 79 COVID-19 patients (mean age 63.0, male 59.5%) and 50 non-COVID-19 patients (mean age 59.5, male 54.0%) participated in this study. A significantly larger proportion of patients with COVID-19 reported not to have slept at all (19% vs. 4% of non-COVID-19 patients, p = 0.011). The Sleep quality (PROMIS total score) and quantity (Total Sleep Time) did not significantly differ between both groups ((median PROMIS total score COVID-19; 26 [IQR 17-35], non-COVID-19; 23 [IQR 18-29], p = 0.104), (Mean Total Sleep Time COVID-19; 5 h 5 min, non-COVID-19 mean; 5 h 32 min, p = 0.405)). The most frequently reported disturbing factors by COVID-19 patients were; ‘dyspnea’, ‘concerns about the disease’, ‘anxiety’ and ‘noises of other patients, medical staff and medical devices’. Conclusion: This study showed that both patients with and without an acute COVID-19 infection experienced poor quality and quantity of sleep at the hospital. Although the mean scores did not significantly differ between groups, total sleep deprivation was reported five times more often by COVID-19 patients. With one in five COVID-19 patients reporting a complete absence of night sleep, poor sleep seems to be a serious problem. Sleep improving interventions should focus on physical and psychological comfort and noise reduction in the hospital environment.
Robust Tracking Control of the Euler–Lagrange System Based on Barrier Lyapunov Function and Self-Structuring Neural Networks

This article studies the robust tracking control problems of Euler–Lagrange (EL) systems with uncertainties. To enhance the robustness of the control systems, an asymmetric tan-type barrier Lyapunov function (ATBLF) is used to dynamic constraint position tracking errors. To deal with the problems of the system uncertainties, the self-structuring neural network (SSNN) is developed to estimate the unknown dynamics model and avoid the calculation burden. The robust compensator is designed to estimate and compensate neural network (NN) approximation errors and unknown disturbances. In addition, a relative threshold event-triggered strategy is introduced, which greatly saves communication resources. Under the proposed robust control scheme, tracking behavior can be implemented with disturbance and unknown dynamics of the EL systems. All signals in the closed-loop system are proved to be bounded by stability analysis, and the tracking error can converge to the neighborhood near the origin. The numerical simulation results show the effectiveness and the validity of the proposed robust control scheme.
NBER WORKING PAPER SERIES THE ECONOMIC IMPACTS OF THE US-CHINA TRADE WAR

In 2018, the US launched a trade war with China, an abrupt departure from its historical leadership in integrating global markets. By late 2019, the US had tariffed roughly $350 billion of Chinese imports, and China had retaliated on $100 billion US exports. Economists have used a diversity of data and methods to assess the impacts of the trade war on the US, China and other countries. This article reviews what we have learned to date from this work. Pablo Fajgelbaum Princeton University Department of Economics International Economics Section Room 294 Julis Romo Rabinowitz Bldg Princeton, NJ 08544 and NBER pfajgelb@princeton.edu Amit Khandelwal Graduate School of Business Columbia University Uris Hall 606, 3022 Broadway New York, NY 10027 and NBER ak2796@columbia.edu
A plant reovirus hijacks the DNAJB12–Hsc70 chaperone complex to promote viral spread in its planthopper vector

Abstract Many viruses usurp the functions of endoplasmic reticulum (ER) for virus‐encoded membrane proteins proper functional folding or assembly to promote virus spread. Southern rice black‐streaked dwarf virus (SRBSDV), a plant reovirus, exploits virus‐containing tubules composed of nonstructural membrane protein P7‐1 to spread in its planthopper vector Sogatella furcifera. Here, we report that two factors of the ER‐associated degradation (ERAD) machinery, the ER chaperone DNAJB12 and its cytosolic co‐chaperone Hsc70, are activated by SRBSDV to facilitate ER‐to‐cytosol export of P7‐1 tubules in S. furcifera. Both P7‐1 of SRBSDV and Hsc70 directly bind to the J‐domain of DNAJB12. DNAJB12 overexpression induces ER retention of P7‐1, but Hsc70 overexpression promotes the transport of P7‐1 from the ER to the cytosol to initiate tubule assembly. Thus, P7‐1 is initially retained in the ER by interaction with DNAJB12 and then delivered to Hsc70. Furthermore, the inhibitors of the ATPase activity of Hsc70 reduce P7‐1 tubule assembly, suggesting that the proper folding and assembly of P7‐1 tubules is dependent on the ATPase activity of Hsc70. The DNAJB12–Hsc70 chaperone complex is recruited to P7‐1 tubules in virus‐infected midgut epithelial cells in S. furcifera. The knockdown of DNAJB12 or Hsc70 strongly inhibits P7‐1 tubule assembly in vivo, finally suppressing effective viral spread in S. furcifera. Taken together, our results indicate that the DNAJB12–Hsc70 chaperone complex in the ERAD machinery facilitates the ER‐to‐cytosol transport of P7‐1 for proper assembly of tubules, enabling viral spread in insect vectors in a manner dependent on ATPase activity of Hsc70.
An Allogeneic Multiple Myeloma GM-CSF–Secreting Vaccine with Lenalidomide Induces Long-term Immunity and Durable Clinical Responses in Patients in Near Complete Remission

Purpose: This proof-of-principle clinical trial evaluated whether an allogeneic multiple myeloma GM-CSF–secreting vaccine (MM-GVAX) in combination with lenalidomide could deepen the clinical response in patients with multiple myeloma in sustained near complete remission (nCR). Patients and Methods: Fifteen patients on lenalidomide were treated with MM-GVAX and pneumococcal conjugate vaccine (PCV; Prevnar) at 1, 2, 3, and 6 months. Results: Eight patients (53.3%) achieved a true CR. With a median follow-up of 5 years, the median progression-free survival had not been reached, and the median overall survival was 7.8 years from enrollment. MM-GVAX induced clonal T-cell expansion and measurable cytokine responses that persisted up to 7 years in all patients. At baseline, a higher minimal residual disease was predictive of early relapse. After vaccination, a lack of both CD27−DNAM1−CD8+ T cells and antigen-presenting cells was associated with disease progression. Conclusions: MM-GVAX, along with lenalidomide, effectively primed durable immunity and resulted in long-term disease control, as suggested by the reappearance of a detectable, fluctuating M-spike without meeting the criteria for clinical relapse. For patients in a nCR, MM-GVAX administration was safe and resulted in prolonged clinical responses.
Innate Immunity and Cell Death in Alzheimer's Disease

The innate immune system plays key roles in controlling Alzheimer's disease (AD), while secreting cytokines to eliminate pathogens and regulating brain homeostasis. Recent research in the field of AD has shown that the innate immune-sensing ability of pattern recognition receptors on brain-resident macrophages, known as microglia, initiates neuroinflammation, Aβ accumulation, neuronal loss, and memory decline in patients with AD. Advancements in understanding the role of innate immunity in AD have laid a strong foundation to elucidate AD pathology and devise therapeutic strategies for AD in the future. In this review, we highlight the present understanding of innate immune responses, inflammasome activation, inflammatory cell death pathways, and cytokine secretion in AD. We also discuss how the AD pathology influences these biological processes.
Brain functional and effective connectivity based on electroencephalography recordings: A review

Functional connectivity and effective connectivity of the human brain, representing statistical dependence and directed information flow between cortical regions, significantly contribute to the study of the intrinsic brain network and its functional mechanism. Many recent studies on electroencephalography (EEG) have been focusing on modeling and estimating brain connectivity due to increasing evidence that it can help better understand various brain neurological conditions. However, there is a lack of a comprehensive updated review on studies of EEG‐based brain connectivity, particularly on visualization options and associated machine learning applications, aiming to translate those techniques into useful clinical tools. This article reviews EEG‐based functional and effective connectivity studies undertaken over the last few years, in terms of estimation, visualization, and applications associated with machine learning classifiers. Methods are explored and discussed from various dimensions, such as either linear or nonlinear, parametric or nonparametric, time‐based, and frequency‐based or time‐frequency‐based. Then it is followed by a novel review of brain connectivity visualization methods, grouped by Heat Map, data statistics, and Head Map, aiming to explore the variation of connectivity across different brain regions. Finally, the current challenges of related research and a roadmap for future related research are presented.
Screening of prototype antiseizure and anti‐inflammatory compounds in the Theiler's murine encephalomyelitis virus model of epilepsy

Infection with Theiler's murine encephalomyelitis virus (TMEV) in C57Bl/6J mice results in handling‐induced seizures and is useful for evaluating compounds effective against infection‐induced seizures. However, to date only a few compounds have been evaluated in this model, and a comprehensive study of antiseizure medications (ASMs) has not yet been performed. Furthermore, as the TMEV infection produces marked neuroinflammation, an evaluation of prototype anti‐inflammatory compounds is needed as well.
The Road to Personalized Myeloma Medicine: Patient-specific Single-domain Antibodies for Anti-idiotypic Radionuclide Therapy

To this day, multiple myeloma remains an incurable cancer. For many patients, recurrence is unavoidably a result of lacking treatment options in the minimal residual disease stage. This is due to residual and treatment-resistant myeloma cells that can cause disease relapse. However, patient-specific membrane-expressed paraproteins could hold the key to target these residual cells responsible for disease recurrence. Here, we describe the therapeutic potential of radiolabeled, anti-idiotypic camelid single-domain antibody fragments (sdAbs) as tumor-restrictive vehicles against a membrane-bound paraprotein in the syngeneic mouse 5T33 myeloma model and analogously assess the feasibility of sdAb-based personalized medicine for patients with multiple myeloma. Llamas were immunized using extracts containing paraprotein from either murine or human sera, and selective sdAbs were retrieved using competitive phage display selections of immune libraries. An anti-5T33 idiotype sdAb was selected for targeted radionuclide therapy with the β−-particle emitter 177Lu and the α-particle emitter 225Ac. sdAb-based radionuclide therapy in syngeneic mice with a low 5T33 myeloma lesion load significantly delayed tumor progression. In five of seven patients with newly diagnosed myeloma, membrane expression of the paraprotein was confirmed. Starting from serum-isolated paraprotein, for two of three selected patients anti-idiotype sdAbs were successfully generated.
ILIVE Project Volunteer study. Developing international consensus for a European Core Curriculum for hospital end-of-life-care volunteer services, to train volunteers to support patients in the last weeks of life: A Delphi study

Background: Volunteers make a huge contribution to the health and wellbeing of the population and can improve satisfaction with care especially in the hospice setting. However, palliative and end-of-life-care volunteer services in the hospital setting are relatively uncommon. The iLIVE Volunteer Study, one of eight work-packages within the iLIVE Project, was tasked with developing a European Core Curriculum for End-of-Life-Care Volunteers in hospital. Aim: Establish an international consensus on the content of a European Core Curriculum for hospital end-of-life-care volunteer services which support patients in the last weeks of life. Design: Delphi Process comprising the following three stages: 1. Scoping review of literature into palliative care volunteers. 2. Two rounds of Delphi Questionnaire. 3. Nominal Group Meeting. Setting/participants: Sixty-six participants completed the Round 1 Delphi questionnaire; 75% (50/66) took part in Round 2. Seventeen participants attended the Nominal Group Meeting representing an international and multi-professional group including, clinicians, researchers and volunteer coordinators from the participating countries. Results: The scoping review identified 88 items for the Delphi questionnaire. Items encompassed organisational issues for implementation and topics for volunteer training. Three items were combined and one item added in Round 2. Following the Nominal Group Meeting 53/87 items reached consensus. Conclusion: Key items for volunteer training were agreed alongside items for implementation to embed the end-of-life-care volunteer service within the hospital. Recommendations for further research included in-depth assessment of the implementation and experiences of end-of-life-care volunteer services. The developed European Core Curriculum can be adapted to fit local cultural and organisational contexts.
Balancing life and death: BCL‐2 family members at diverse ER–mitochondrial contact sites

The outer mitochondrial membrane is a busy place. One essential activity for cellular survival is the regulation of membrane integrity by the BCL‐2 family of proteins. Another critical facet of the outer mitochondrial membrane is its close approximation with the endoplasmic reticulum. These mitochondrial‐associated membranes (MAMs) occupy a significant fraction of the mitochondrial surface and serve as key signaling hubs for multiple cellular processes. Each of these pathways may be considered as forming their own specialized MAM subtype. Interestingly, like membrane permeabilization, most of these pathways play critical roles in regulating cellular survival and death. Recently, the pro‐apoptotic BCL‐2 family member BOK has been found within MAMs where it plays important roles in their structure and function. This has led to a greater appreciation that multiple BCL‐2 family proteins, which are known to participate in numerous functions throughout the cell, also have roles within MAMs. In this review, we evaluate several MAM subsets, their role in cellular homeostasis, and the contribution of BCL‐2 family members to their functions.
A Mutual Attention Model for Drug Target Binding Affinity Prediction

Vrious machine learning approaches have been developed for drug-target interaction (DTI) prediction. One class of these approaches, DTBA, is interested in Drug-Target Binding Affinity strength, rather than focusing merely on the presence or absence of interaction. Several machine learning methods have been developed for this purpose. However, almost all depend heavily on the use of increasingly sophisticated inputs to improve their performance. In addition, these methods do not allow any analysis or interpretation due to their black-box characteristic. This work is an attempt to overcome these limitations by taking advantage of the use of attention mechanisms with convolution models. In this paper, we define a new mutual attention based model for DTBA prediction. We represent both compounds and targets by sequences. Our model starts by aligning the drug-target pairs, then a learned masking is performed to retain the most promising regions, of both sequences, and amplify them with a learned factor in such a way to make the learning focus more on them. We evaluate the performance of our method on two benchmark datasets, KIBA and Davis. The results show that our mutual attention approach is very effective. Compared to other well-known approaches, it achieved excellent results regarding the considered performance metrics.
Tunable 3D Hydrogel Microchannel Networks to Study Confined Mammalian Cell Migration

Cells adapt and move due to chemical, physical, and mechanical cues from their microenvironment. It is therefore important to create materials that mimic human tissue physiology by surface chemistry, architecture, and dimensionality to control cells in biomedical settings. The impact of the environmental architecture is particularly relevant in the context of cancer cell metastasis, where cells migrate through small constrictions in their microenvironment to invade surrounding tissues. Here, a synthetic hydrogel scaffold with an interconnected, random, 3D microchannel network is presented that is functionalized with collagen to promote cell adhesion. It is shown that cancer cells can invade such scaffolds within days, and both the microarchitecture and stiffness of the hydrogel modulate cell invasion and nuclear dynamics of the cells. Specifically, it is found that cell migration through the microchannels is a function of hydrogel stiffness. In addition to this, it is shown that the hydrogel stiffness and confinement, influence the occurrence of nuclear envelope ruptures of cells. The tunable hydrogel microarchitecture and stiffness thus provide a novel tool to investigate cancer cell invasion as a function of the 3D microenvironment. Furthermore, the material provides a promising strategy to control cell positioning, migration, and cellular function in biological applications, such as tissue engineering.
Subunit exchange among endolysosomal tethering complexes is linked to contact site formation at the vacuole

The hexameric HOPS (homotypic fusion and protein sorting) complex is a conserved tethering complex at the lysosome-like vacuole, where it mediates tethering and promotes all fusion events involving this organelle. The Vps39 subunit of this complex also engages in a membrane contact site between the vacuole and the mitochondria, called vCLAMP. Additionally, four subunits of HOPS are also part of the endosomal CORVET tethering complex. Here, we analyzed the partition of HOPS and CORVET subunits between the different complexes by tracing their localization and function. We find that Vps39 has a specific role in vCLAMP formation beyond tethering, and that vCLAMPs and HOPS compete for the same pool of Vps39. In agreement, we find that the CORVET subunit Vps3 can take the position of Vps39 in HOPS. This endogenous pool of a Vps3-hybrid complex is affected by Vps3 or Vps39 levels, suggesting that HOPS and CORVET assembly is dynamic. Our data shed light on how individual subunits of tethering complexes such as Vps39 can participate in other functions, while maintaining the remaining subcomplex available for its function in tethering and fusion.
Thiolated Chitosan-Centella asiatica Nanocomposite: A Potential Brain Targeting Strategy Through Nasal Route

The major challenge associated with the treatment of neurological disorders is the inefficiency of drugs to enter the Central Nervous System (CNS). Polymer-drug conjugates are now being tailored to overcome this hindrance associated with conventional drugs. The study aimed at developing polymer hybrid nasal nanocomposite for enhanced delivery of Centella to the CNS. Thiolated chitosan was complexed with Centella to form a composite using EDAC hydrochloride. The composite was characterized by FTIR, XRD, NMR, and MS. Further, this composite was converted into a nanoformulation by the ionic-gelation method, characterized, and subjected to ex vivo permeation studies. Additionally, MTT assay was performed using Human Uumbilical cord Vein Endothelial Cells (HUVECs) mimicking Blood–Brain Barrier (BBB) to establish the safety of nanocomposite. The targeting efficacy was predicted by molecular docking studies against receptors associated with BBB. The FTIR, XRD, NMR, and MS studies confirmed the chemical conjugation of thiolated chitosan with Centella. Nanocomposite characterization through SEM, AFM, and DLS confirmed the size and stability of the developed nanocomposite having a zeta potential of − 14.5 mV and PDI of 0.260. The nanocomposite showed no signs of nasal ciliotoxicity and good permeation of 89.44 ± 1.75% (mean ± SD, n = 3) at 8 h across the nasal mucosa. MTT assay showed that the nanocomposite had lesser toxicity compared to the free drug (IC50 of Centella—269.1 μg/mL and IC50 of CTC nanocomposite—485.375 μg/mL). The affinity of polymer to the BBB receptors as proved by docking studies suggests the ability of polymer-based nanocomposite to concentrate in the brain post nasal administration.
Altered dietary ratio of folic acid and vitamin B12 during pregnancy influences the expression of imprinted H19/IGF2 locus in C57BL/6 mice

Abstract Maternal folic acid and vitamin B12 (B12) status during pregnancy influence fetal growth. This study elucidated the effect of altered dietary ratio of folic acid and B12 on the regulation of H19/IGF2 locus in C57BL/6 mice. Female mice were fed diets with nine combinations of folic acid and B12 for 4 weeks. They were mated and the offspring born (F1) were continued on the same diet for 6 weeks post-weaning and were allowed to mate. The placenta and fetal (F2) tissues were collected at day 20 of gestation. H19 overexpression observed under dietary deficiency of folate combined with normal B12 (B12 normal folic acid-deficient, BNFD) was associated with an increased expression of microRNA-675 (miR-675) in maternal and fetal tissues. Insulin-like growth factor 2 (IGF2) expression was decreased under folic acid-deficient conditions combined with normal, deficient or over-supplemented state of B12 (BNFD, BDFD and BOFD) in fetal tissues along with B12 deficiency combined with normal folic acid (BDFN) in the placenta. The altered expression of imprinted genes under folic acid-deficient conditions was related to decreased serum levels of folate and body weight (F1). Hypermethylation observed at the H19 differentially methylated region (DMR) (in BNFD) might be responsible for the decreased expression of IGF2 in female fetal tissues. IGF2 DMR2 was found to be hypomethylated and associated with low serum B12 levels with B12 deficiency in fetal tissues. Results suggest that the altered dietary ratio of folic acid and B12 affects the in utero development of the fetus in association with altered epigenetic regulation of H19/IGF2 locus.