bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure and Functions of Gap Junctions and Their Constituent Connexins in the Mammalian CNS
Authors: Kirichenko E. Yu. , Skatchkov S. N. , Ermakov A. M. 
Published: June 2021

Abstract—
Numerous data obtained in the last 20 years indicate that all parts of the mature central nervous system, from the retina and olfactory bulb to the spinal cord and brain, contain cells connected by gap junctions (GJs). The morphological basis of the GJs is a group of joined membrane hemichannels called connexons, the subunit of each connexon is the protein connexin. In the central nervous system, connexins show specificity and certain types of them are expressed either in neurons or in glial cells. Connexins and GJs of neurons, combining certain types of inhibitory hippocampal and neocortical neuronal ensembles, provide synchronization of local impulse and rhythmic activity, thalamocortical conduction, control of excitatory connections, which reflects their important role in the processes of perception, concentration of attention and consolidation of memory, both on the cellular and at the system level. Connexins of glial cells are ubiquitously expressed in the brain, and the GJs formed by them provide molecular signaling and metabolic cooperation and play a certain role in the processes of neuronal migration during brain development, myelination, tissue homeostasis, and apoptosis. At the same time, mutations in the genes of glial connexins, as well as a deficiency of these proteins, are associated with such diseases as congenital neuropathies, hearing loss, skin diseases, and brain tumors. This review summarizes the existing data of numerous molecular, electrophysiological, pharmacological, and morphological studies aimed at progress in the study of the physiological and pathophysiological significance of glial and neuronal connexins and GJs for the central nervous system.
Big food and the World Health Organization: a qualitative study of industry attempts to influence global-level non-communicable disease policy
Authors: Lauber Kathrin , Rutter Harry , Gilmore Anna B 
Published: June 2021

IntroductionThere is an urgent need for effective action to address the over 10 million annual deaths attributable to unhealthy diets. Food industry interference with policies aimed at reducing non-communicable diseases (NCDs) is widely documented at the national level but remains under-researched at the global level. Thus, this study explores how ultra-processed food industry actors have attempted to influence NCD policy at WHO.MethodsA combination of inductive and deductive thematic coding of internal industry documents, academic literature and interviews with key informants from international organisations and global civil society was used to identify action-based strategies ultra-processed food industry actors employ to influence global-level policy.ResultsUltra-processed food industry actors have attempted to influence WHO and its policies through three main action-based strategies: coalition management, involvement in policy formulation, and information management. Coalition management includes the creation and use of overt alliances between corporations—business associations—and more covert science-focused and policy-focused intermediaries, the hiring of former WHO staff and attempted co-option of civil society organisations. Industry involvement in policy formulation is operationalised largely through the lobbying of Member States to support industry positions, and business associations gaining access to WHO through formal consultations and hearings. Information management involves funding and disseminating research favourable to commercial interests, and challenging unfavourable evidence.ConclusionWe provide novel insights into how ultra-processed food industry actors shape global-level NCD policy and identify a clear need to guard against commercial interference to advance NCD policy. In their approach, the political behaviour of multinational food corporations bears similarities to that of the tobacco industry. Increased awareness of, and safeguarding against, commercial interference at the national as well as the global level have the potential to strengthen the crucial work of WHO.
Warwick-India-Canada (WIC) global mental health group: rationale, design and protocol
Authors: Singh Swaran P , Mohan Mohapradeep , Iyer Srividya N , Meyer Caroline , Currie Graeme , Shah Jai , Madan Jason , Birchwood Max , Sood Mamta , Ramachandran Padmavati , Chadda Rakesh K , Lilford Richard J , Rangaswamy Thara , Furtado Vivek 
Published: June 2021

IntroductionThe primary aim of the National Institute of Health Research-funded global health research group, Warwick-India-Canada (WIC), is to reduce the burden of psychotic disorders in India. India has a large pool of undetected and untreated patients with psychosis and a treatment gap exceeding 75%. Evidence-based packages of care have been piloted, but delivery of treatments still remains a challenge. Even when patients access treatment, there is minimal to no continuity of care. The overarching ambition of WIC programme is to improve patient outcomes through (1) developing culturally tailored clinical interventions, (2) early identification and timely treatment of individuals with mental illness and (3) improving access to care by exploiting the potential of digital technologies.Methods and analysisThis multicentre, multicomponent research programme, comprising five work packages and two cross-cutting themes, is being conducted at two sites in India: Schizophrenia Research Foundation, Chennai (South India) and All India Institute of Medical Sciences, New Delhi (North India). WIC will (1) develop and evaluate evidence-informed interventions for early and first-episode psychosis; (2) determine pathways of care for early psychosis; (3) investigate the efficacy and cost-effectiveness of community care models, including digital and mobile technologies; (4) develop strategies to reduce the burden of mental illnesses among youth; (5) assess the economic burden of psychosis on patients and their carers; and (6) determine the feasibility of an early intervention in psychosis programme in India.Ethics and disseminationThis study was approved by the University of Warwick’s Biomedical and Scientific Research Ethics Committee (reference: REGO-2018-2208), Coventry, UK and research ethics committees of all participating organisations. Research findings will be disseminated through peer-reviewed scientific publications, presentations at learnt societies and visual media.
What risks to sustainability are identified throughout care bundle implementation and how can they be addressed? A mixed methods case study
Authors: Lennox Laura , Eftychiou Linda , Matthew Dionne , Dowell Jackie , Winn Trish 
Published: June 2021

ObjectivesDespite national guidance on how to identify and treat heart failure (HF), variation in HF care persists across UK hospitals. Care bundles have been proposed as a mechanism to deliver reliable optimal care for patients; however, specific challenges to sustain care bundles in practice have been highlighted. With few studies providing insight into how to design or implement care bundles to optimise sustainability, there is little direction for practitioners seeking to ensure long-term impact of their initiatives. This study explores the sustainability risks encountered throughout the implementation of a HF care bundle (HFCB) and describes how these challenges were addressed by a multidisciplinary team (MDT) to enhance sustainability over time.DesignA longitudinal mixed method case study examined the HFCB improvement initiative from September 2015 to August 2018. A standardised sustainability tool was used to collect perceptions of sustainability risks and actions throughout the initiative. Observations, key-informant interviews and documentary analysis were conducted to gain in-depth understanding of how the MDT influenced sustainability through specific actions. A qualitative database was developed using a consolidated sustainability framework to conduct thematic analysis. Sustainability outcomes were explored 1-year post funding to ascertain progress towards sustainment.ResultsThe MDT identified six sustainability challenges for the HFCB: infrastructure limitations, coding reliability, delivery consistency, organisational fit, resource stability and demonstrating impact. The MDT undertook multiple actions to enhance sustainability, including: (1) developing a business case to address infrastructure limitations; (2) incorporating staff feedback to increase bundle usability; (3) establishing consistent training; (4) increasing reliability of baseline data; (5) embedding monitoring and communication; and (6) integrating the bundle into current practices.ConclusionThrough the description of challenges, actions and learning from the MDT, this study provides practical lessons for practitioners and researchers seeking to embed and sustain care bundles in practice.
Phase II clinical trial using anti-CD3 × anti-HER2 bispecific antibody armed activated T cells (HER2 BATs) consolidation therapy for HER2 negative (0–2+) metastatic breast cancer
Authors: Lum Lawrence G. , Al-Kadhimi Zaid , Deol Abhinav , Kondadasula Vidya , Schalk Dana , Tomashewski Elyse , Steele Patricia , Fields Kristie , Giroux Melissa , Liu Qin , Flaherty Lawrence , Simon Michael , Thakur Archana 
Published: June 2021

BackgroundMetastatic human epidermal growth receptor II (HER2) negative breast cancer remains incurable. Our phase I study showed that anti-CD3 × anti-HER2 bispecific antibody armed activated T cells (HER2 BATs) may be effective against HER2-tumors. This phase II trial evaluates the efficacy and immune responses of HER2 BATs given to patients with metastatic HER2-estrogen and/or progesterone receptor positive (HR+) and triple negative breast cancer (TNBC) as immune consolidation after chemotherapy. The primary objective of this study was to increase the traditional median time to progression after failure of first-line therapy of 2–4 months with the secondary endpoints of increasing overall survival (OS) and immune responses.MethodsHER2- metastatic breast cancer (MBC) patients received 3 weekly infusions of HER2 BATs and a boost after 12 weeks.ResultsThis phase II study included 24 HER2-HR+ and 8 TNBC patients who received a mean of 3.75 and 2.4 lines of prior chemotherapy, respectively. Eight of 32 evaluable patients were stable at 4 months after the first infusion. There were no dose limiting toxicities. Tumor markers decreased in 13 of 23 (56.5%) patients who had tumor markers. The median OS was 13.1 (95% CI 8.6 to 17.4), 15.2 (95% CI 8.6 to 19.8), and 12.3 (95% CI 2.1 to 17.8) months for the entire group, HER2-HR+, and TNBC patients, respectively. Median OS for patients with chemotherapy-sensitive and chemotherapy-resistant disease after chemotherapy was 14.6 (9.6–21.8) and 8.6 (3.3–17.3) months, respectively. There were statistically significant increases in interferon-γ immunospots, Th1cytokines, Th2cytokines, and chemokines after HER2 BATs infusions.ConclusionsIn heavily pretreated HER2-patients, immune consolidation with HER2 BATs after chemotherapy appears to increase the proportion of patients who were stable at 4 months and the median OS for both groups as well as increased adaptive and innate antitumor responses. Future studies combining HER2 BATs with checkpoint inhibitors or other immunomodulators may improve clinical outcomes.
Mesoporous silica nanoparticles inflame tumors to overcome anti-PD-1 resistance through TLR4-NFκB axis
Authors: Sun Mayu , Gu Pengfei , Yang Yang , Yu Luodan , Jiang Zheshun , Li Jingquan , Le Yingying , Chen Yu , Ba Qian , Wang Hui 
Published: June 2021

BackgroundThe clinical benefits of antiprogrammed cell death protein 1 (PD-1) therapy are compromised by resistance in immunologically cold tumors. Convergence of immunotherapy and bioengineering is potential to overcome the resistance. Mesoporous silica nanoparticles (MSNs) are considered the most promising inorganic biological nanomaterials for clinical transformation, however, the fundamental influence of MSNs on immunotherapy is unclear. In this study, we aimed to investigate the role of MSNs in tumor resensitization and explore the feasibility of MSNs combined with anti-PD-1 in cancer therapy.MethodsIntrinsic and acquired resistant tumors, as well as spontaneous and secondary tumor recurrence models, were used to evaluate the influence of MSNs and the synergistical effect with anti-PD-1 therapy. The roles of CD8+ cytotoxic T-lymphocytes (CTLs) and macrophages were assessed in Rag-1-/- mice, ovalbumin/OT-1 TCR transgenic T-cell system, and other blocking mice models. Mechanistic studies were processed by transcriptomics analysis and conducted in primary cells, in vitro coculture systems, and Toll-like receptor 4 (TLR4) knockout mice.ResultsBoth granular and rod-shaped MSNs efficiently overcame tumor resistance with dependence on diameter and aspect ratio. Only once injection of MSNs in prior to anti-PD-1 markedly improved the treatment efficacy, protective immunity, and prognosis. MSNs per se boosted infiltration of CTLs as the early event (days 2–3); and synergistically with anti-PD-1 therapy, MSNs rapidly established a T cell-inflamed microenvironment with abundant high-activated (interferon-γ/tumor necrosis factor-α/Perforin/GranzymeB) and low-exhausted (PD-1/lymphocyte-activation gene 3 (LAG-3)/T-cell immunoglobulin and mucin-domain containing-3 (TIM-3)) CTLs. Chemokines Ccl5/Cxcl9/Cxcl10, which were produced predominantly by macrophages, promoted MSNs-induced CTLs infiltration. MSNs led to high Ccl5/Cxcl9/Cxcl10 production in vitro and in mice through regulating TLR4-NFκB axis. Blocking TLR4-NFκB axis in macrophages or CTLs infiltration abrogated MSNs-induced resensitization to anti-PD-1 therapy.ConclusionsMSNs efficiently and rapidly inflame immunologically cold tumors and resensitize them to anti-PD-1 therapy through TLR4-NFκB-Ccl5/Cxcl9/Cxcl10 axis. MSNs-based theranostic agents can serve as sensitizers for patients with resistant tumors to improve immunotherapy.
Swimming capability of target fish from eight hydropower stations in China relative to fishway design
Authors: Shi Xiaotao , Ke Senfan , Tu Zhiying , Wang Yongmeng , Tan Junjun , Guo Wentao 
Published: June 2021

The four major Chinese carp (MC), Schizothorax fish species (SF), and Cobitidae fish species (CF) are the most important target fish species in China. The swimming behaviour study of three target fish groups is the key to Chinese fishway designs. The 20 min critical swimming speed (Ucrit-20 min) and endurance of the target fish species in relation to body length, swimming speed, and water temperature were estimated using multiple linear regression. The results indicated that both fish body length and water temperature had a significant effect on swimming capability. Performance comparisons indicated that SF were remarkably strong swimmer. CF possess slightly greater swimming capability than MC. The entrance velocity of the upstream fishway should be greater than Ucrit-20 min, but less than maximum swimming speed to make the flow out of the fishway noticeable. The maximum swimming distance could be estimated using endurance model at flow velocity of 1.2 m·s–1. For the downstream-migrating juvenile fish, it was suggested that the flow velocity of turbine intake should be less than maximum sustained speed avoiding entering turbine.
Electronic wavefunction with maximally entangled MPS representation
Authors: Graswald Benedikt R. , Friesecke Gero 
Published: June 2021

AbstractWe present an example of an electronic wavefunction with maximally entangled MPS representation, in the sense that the bond dimension is maximal and cannot be lowered by any re-ordering of the underlying one-body basis. Our construction works for any number of electrons and orbitals.
The breakthrough of a quantum chemist by classical dynamics: Martin Karplus and the birth of computer simulations of chemical reactions
Authors: Macuglia Daniele , Roux Benoît , Ciccotti Giovanni 
Published: June 2021

Abstract1964–1965 was an early, crucial period in Martin Karplus’ research—a time when, rather unexpectedly, he approached the problem of reactive collisions using a quasiclassical approximation with the aid of computer technologies. This marked a substantial departure from the quantum-chemical studies of nuclear magnetic resonance that had, until then, dominated his work. The historical perspective outlined by George Schatz, as well Karplus’ own biography, partly frames the contours of this remarkable period in the history of theoretical chemistry. Yet, the available historical literature is not sufficiently complete to allow us to understand Karplus’ transition from nuclear magnetic resonance to reaction dynamics. In this article, we discuss the intellectual ground on which Karplus operated around 1964, further commenting on the relevance of his quantum and quasiclassical studies and pondering how Karplus’ approach eventually led to his interest in the simulation of complex biomolecules.
Coupled network analysis revealing global monthly scale co-variability patterns between sea-surface temperatures and precipitation in dependence on the ENSO state
Authors: Ekhtiari Nikoo , Ciemer Catrin , Kirsch Catrin , Donner Reik V. 
Published: June 2021

AbstractThe Earth’s climate is a complex system characterized by multi-scale nonlinear interrelationships between different subsystems like atmosphere and ocean. Among others, the mutual interdependence between sea surface temperatures (SST) and precipitation (PCP) has important implications for ecosystems and societies in vast parts of the globe but is still far from being completely understood. In this context, the globally most relevant coupled ocean–atmosphere phenomenon is the El Niño–Southern Oscillation (ENSO), which strongly affects large-scale SST variability as well as PCP patterns all around the globe. Although significant achievements have been made to foster our understanding of ENSO’s global teleconnections and climate impacts, there are many processes associated with ocean–atmosphere interactions in the tropics and extratropics, as well as remote effects of SST changes on PCP patterns that have not yet been unveiled or fully understood. In this work, we employ coupled climate network analysis for characterizing dominating global co-variability patterns between SST and PCP at monthly timescales. Our analysis uncovers characteristic seasonal patterns associated with both local and remote statistical linkages and demonstrates their dependence on the type of the current ENSO phase (El Niño, La Niña or neutral phase). Thereby, our results allow identifying local interactions as well as teleconnections between SST variations and global precipitation patterns.
CORRELATES AND PREDICTORS OF DISABILITY RELATED TO CHRONIC LOW-BACK PAIN IN A NIGERIAN POPULATION
Authors: Maruf Fatai Adesina , Ani Kenneth , Akosile Christopher Olusanjo , Nwodo Obinna Dickson , Okonkwo Prosper Uchenna , Awhen Peter Agba 
Published: June 2021

Purpose: Identifying factors related to low-back pain (LBP) can facilitate its management. However, information on how physical activity (PA) level, health-related quality of life (HRQoL) and anthropometric characteristics are related to LBP-associated health indices in individuals with chronic LBP (CLBP) is scarce. This study explored how PA level, HRQoL and anthropometric indices are related to CLBP-related disability in a Nigerian population. Methods: This cross-sectional study involved 100 individuals with CLBP who were receiving treatment in physiotherapy out-patient clinics of selected tertiary hospitals, and 95 apparently healthy individuals. PA level, disability level and HRQoL were measured using standardized procedures. Results: Disability level inversely correlated with physical component score (PCS) of HRQoL ([Formula: see text]; [Formula: see text]), mental component score (MCS) of HRQoL ([Formula: see text]; [Formula: see text]), pain intensity ([Formula: see text]; [Formula: see text]) and PA level ([Formula: see text]; [Formula: see text]), but positively correlated with duration of pain ([Formula: see text]; [Formula: see text]) among individuals with CLBP. PCS of HRQoL ([Formula: see text]; [Formula: see text]) solely accounted for 71% of the prediction of disability level. Conclusion: PA level and HRQoL decrease with increasing CLBP-related disability with the PCS of HRQoL being mostly affected. Individuals with CLBP may need to be motivated against their health problem, and be encouraged to participate in PA.
Observational Constraints on Black Hole Spin
Authors: Reynolds Christopher S. 
Published: June 2021

The spin of a black hole is an important quantity to study, providing a window into the processes by which a black hole was born and grew. Furthermore, spin can be a potent energy source for powering relativistic jets and energetic particle acceleration. In this review, I describe the techniques currently used to detect and measure the spins of black holes. It is shown that: ▪  Two well-understood techniques, X-ray reflection spectroscopy and thermal continuum fitting, can be used to measure the spins of black holes that are accreting at moderate rates. There is a rich set of other electromagnetic techniques allowing us to extend spin measurements to lower accretion rates. ▪  Many accreting supermassive black holes are found to be rapidly spinning, although a population of more slowly spinning black holes emerges at masses above [Formula: see text] as expected from recent structure formation models. ▪  Many accreting stellar-mass black holes in X-ray binary systems are rapidly spinning and must have been born in this state. ▪  The advent of gravitational wave astronomy has enabled the detection of spin effects in merging binary black holes. Most of the premerger black holes are found to be slowly spinning, a notable exception being an object that may itself be a merger product. ▪  The stark difference in spins between the black hole X-ray binary and the binary black hole populations shows that there is a diversity of formation mechanisms.Given the array of new electromagnetic and gravitational wave capabilities currently being planned, the future of black hole spin studies is bright.