Miracle-dz/UniFAR-FTUs huggingface dataset:
Natural and Recombinant SARS-CoV-2 Isolates Rapidly Evolve In Vitro to Higher Infectivity through More Efficient Binding to Heparan Sulfate and Reduced S1/S2 Cleavage

The spike protein of SARS-CoV-2 is a major determinant of viral pathogenesis. It mediates binding to the ACE2 receptor and, later, fusion of viral envelope and cellular membranes. ABSTRACT One of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virulence factors is the ability to interact with high affinity to the ACE2 receptor, which mediates viral entry into cells. The results of our study demonstrate that within a few passages in cell culture, both the natural isolate of SARS-CoV-2 and the recombinant cDNA-derived variant acquire an additional ability to bind to heparan sulfate (HS). This promotes a primary attachment of viral particles to cells before their further interactions with the ACE2. Interaction with HS is acquired through multiple mechanisms. These include (i) accumulation of point mutations in the N-terminal domain (NTD) of the S protein, which increases the positive charge of the surface of this domain, (ii) insertions into the NTD of heterologous peptides containing positively charged amino acids, and (iii) mutation of the first amino acid downstream of the furin cleavage site. This last mutation affects S protein processing, transforms the unprocessed furin cleavage site into the heparin-binding peptide, and makes viruses less capable of syncytium formation. These viral adaptations result in higher affinity of viral particles to heparin, dramatic increase in plaque sizes, more efficient viral spread, higher infectious titers, and 2 orders of magnitude higher infectivity. The detected adaptations also suggest an active role of NTD in virus attachment and entry. As in the case of other RNA-positive (RNA+) viruses, evolution to HS binding may result in virus attenuation in vivo. IMPORTANCE The spike protein of SARS-CoV-2 is a major determinant of viral pathogenesis. It mediates binding to the ACE2 receptor and, later, fusion of viral envelope and cellular membranes. The results of our study demonstrate that SARS-CoV-2 rapidly evolves during propagation in cultured cells. Its spike protein acquires mutations in the NTD and in the P1′ position of the furin cleavage site (FCS). The amino acid substitutions or insertions of short peptides in NTD are closely located on the protein surface and increase its positive charge. They strongly increase affinity of the virus to heparan sulfate, make it dramatically more infectious for the cultured cells, and decrease the genome equivalent to PFU (GE/PFU) ratio by orders of magnitude. The S686G mutation also transforms the FCS into the heparin-binding peptide. Thus, the evolved SARS-CoV-2 variants efficiently use glycosaminoglycans on the cell surface for primary attachment before the high-affinity interaction of the spikes with the ACE2 receptor.
Closed-loop automated reaching apparatus (CLARA) for interrogating complex motor behaviors

Objective. Closed-loop neuromodulation technology is a rapidly expanding category of therapeutics for a broad range of indications. Development of these innovative neurological devices requires high-throughput systems for closed-loop stimulation of model organisms, while monitoring physiological signals and complex, naturalistic behaviors. To address this need, we developed CLARA, a closed-loop automated reaching apparatus. Approach. Using breakthroughs in computer vision, CLARA integrates fully-automated, markerless kinematic tracking of multiple features to classify animal behavior and precisely deliver neural stimulation based on behavioral outcomes. CLARA is compatible with advanced neurophysiological tools, enabling the testing of neurostimulation devices and identification of novel neurological biomarkers. Results. The CLARA system tracks unconstrained skilled reach behavior in 3D at 150 Hz without physical markers. The system fully automates trial initiation and pellet delivery and is capable of accurately delivering stimulation in response to trial outcome with short latency. Kinematic data from the CLARA system provided novel insights into the dynamics of reach consistency over the course of learning, suggesting that learning selectively improves reach failures but does not alter the kinematics of successful reaches. Additionally, using the closed-loop capabilities of CLARA, we demonstrate that vagus nerve stimulation (VNS) improves skilled reach performance and increases reach trajectory consistency in healthy animals. Significance. The CLARA system is the first mouse behavior apparatus that uses markerless pose tracking to provide real-time closed-loop stimulation in response to the outcome of an unconstrained motor task. Additionally, we demonstrate that the CLARA system was essential for our investigating the role of closed-loop VNS stimulation on motor performance in healthy animals. This approach has high translational relevance for developing neurostimulation technology based on complex human behavior.
Physical Activity Patterns and Relationships With Cognitive Function in Patients With Breast Cancer Before, During, and After Chemotherapy in a Prospective, Nationwide Study

PURPOSE Physical activity (PA) is a promising intervention for cancer-related cognitive decline, yet research assessing its use during chemotherapy is limited. This study evaluated patterns of PA before, during, and after chemotherapy in patients with breast cancer and the association between PA and cognitive function. METHODS In a nationwide, prospective cohort study, we assessed PA (Aerobics Center Longitudinal Study PA measure) and perceived and objectively measured cognitive functioning (Functional Assessment of Cancer Therapy–Cognitive, Delayed Match to Sample, and Rapid Visual Processing measures) at prechemotherapy (T1), postchemotherapy (T2), and 6 months postchemotherapy (T3) in patients with breast cancer and cancer-free, age-matched controls at equivalent time points. Longitudinal linear mixed-effects models (LMMs) characterized PA changes over time between patients and controls, adjusting for demographic and clinical factors. LMMs further estimated the role of prechemotherapy PA and changes in PA during chemotherapy on cognitive changes over time. RESULTS Patients with stage I-IIIC breast cancer (n = 580; age M [standard deviation] = 53.4 [10.6] years) and controls (n = 363; age M [standard deviation] = 52.6 [10.3] years) were included. One third of patients met national PA guidelines at T1, dropping to 21% at T2 before rising to 37% at T3. LMMs revealed declines in PA from T1 to T2 in patients compared with controls (all P < .001). Patients meeting guidelines at T1 demonstrated better cognitive scores over time on the Functional Assessment of Cancer Therapy–Cognitive and Rapid Visual Processing (all P < .05), with similar patterns of objectively-measured cognitive function as controls. In patients, greater moderate-to-vigorous PA at the previous time point was significantly associated with better cognitive trajectories (all P < .05), and adherence to PA guidelines throughout chemotherapy was associated with better self-reported cognition (P < .01). CONCLUSION This nationwide study demonstrates that PA maintenance before and during chemotherapy is associated with better cognitive function immediately and 6 months after chemotherapy completion. More physical activity before and during chemotherapy was associated with better cognition in pts w/ breast cancer.
Social inequalities in protective behaviour uptake at the start of the COVID-19 pandemic: results from a national survey

We aimed to assess social patterns of handwashing, social distancing, and working from home at the start of the COVID-19 pandemic in Canada, and determine what proportions of the overall prevalence and social inequalities in handwashing and social distancing are related to inequalities in the opportunity to work from home, to guide pandemic preparedness and response. Using cross-sectional data from the Canadian Perspectives Survey Series, collected between March 29 and April 3, 2020, among Canadian adults (N=4455), we assessed prevalence of not working from home, social distancing in public, or practicing frequent handwashing, according to age, sex, marital status, immigration, education, chronic disease presence, and source of COVID-19 information. Multivariate regression, population attributable fraction estimation, and generalized product mediation analysis were applied. Absence of frequent handwashing and distancing was more common among those working outside than within the home (prevalence differences of 7% (95% CI: 4, 10) and 7% (95% CI: 3, 10), respectively). Inequalities in handwashing and distancing were observed across education and immigration status. Over 40% of the prevalence of non-uptake of handwashing and distancing was attributable to populations not being able to work from home. If all worked from home, over 40% (95% CI: 8, 70) of education-based inequalities in handwashing and distancing could be eliminated, but differences by immigration status would likely remain. For pandemic response, both workplace safety initiatives and mechanisms to address the inequitable distribution of health risks across socio-economic groups are needed to reduce broader inequalities in transmission risk.
Exercise hyperthermia induces greater changes in gastrointestinal permeability than equivalent passive hyperthermia

Hyperthermia and exertional heat illness increase gastrointestinal (GI) permeability, although whether the latter is only via hyperthermia is unclear. The aim of this pilot study was to determine whether different changes in GI permeability, characterized by an increased plasma lactulose:rhamnose concentration ratio ([L:R]), occurred in exercise hyperthermia in comparison to equivalent passive hyperthermia. Six healthy adult male participants (age 25 ± 5 years, mass 77.0 ± 6.7 kg, height 181 ± 6 cm, peak oxygen uptake [ V·O2peak ] 48 ± 8 ml.kg−1.min−1) underwent exercise under hot conditions (Ex‐Heat) and passive heating during hot water immersion (HWI). Heart rate (HR), rectal temperature (TCORE), rating of perceived exertion (RPE), and whole‐body sweat loss (WBSL) were recorded throughout the trials. The L:R ratio, peak HR, change in HR, and change in RPE were higher in Ex‐Heat than HWI, despite no differences in trial duration, peak core temperature or WBSL. L:R was strongly correlated (p < 0.05) with HR peak (r = 0.626) and change in HR (r = 0.615) but no other variable. The greater L:R in Ex‐Heat, despite equal TCORE responses to HWI, indicates that increased cardiovascular strain occurred during exercise, and exacerbates hyperthermia‐induced GI permeability at the same absolute temperature.
Behavioral Response of the Tropical Bed Bug, Cimex hemipterus (Hemiptera: Cimicidae) to Carbon Dioxide

Abstract Bed bugs (Cimex spp.) (Hemiptera: Cimicidae) are obligatory blood-sucking insects. Research on their behavioral response to host-derived olfactory cues will be helpful for designing more effective management tools. However, previous studies mainly focused on Cimex lectularius L. , while the related studies on Cimex hemipterus (F.) have been rarely reported. In this study, we evaluated the behavioral responses of C. hemipterus to one of the crucial host-derived cues – carbon dioxide (CO2), at various concentrations. Pitfall traps baited with CO2 captured significantly more C. hemipterus (72%) than unbaited ones (28%). In the Y-tube test, bed bugs' exploratory activity (response rate) gradually decreased (from 70 to 27%) as the CO2 concentration increased (from 0.9 to 14.5%); and bed bugs exhibited a significant attraction to CO2 when the tested CO2 concentrations were between 0.9 and 7.3%. Cimex hemipterus were no longer attracted to CO2 after their antennae or mouthparts or both antennae and mouthparts were removed. In conclusion, C. hemipterus are attracted to CO2, and both antennae and mouthparts are important for CO2 perception.
Simultaneous 2D and 3D cell culture array for multicellular geometry, drug discovery and tumor microenvironment reconstruction

Cell culture systems are indispensable in vitro tools for biomedical research. Although conventional two-dimensional (2D) cell cultures are still used for most biomedical and biological studies, the three-dimensional (3D) cell culture technology attracts increasing attention from researchers, especially in cancer and stem cell research. Due to the different spatial structures, cells in 2D and 3D cultures exhibit different biochemical and biophysical phenotypes. Therefore, a new platform with both 2D and 3D cell cultures is needed to bridge the gap between 2D and 3D cell-based assays. Here, a simultaneous 2D and 3D cell culture array system was constructed by microprinting technology, in which cancer cells exhibited heterozygous geometry structures with both 2D monolayers and 3D spheroids. Cells grown in 3D spheroids showed higher proliferation ability and stronger cell-cell adhesion. Spheroids derived from various types of cancer cell lines exhibited distinct morphologies through a geometrical confinement stimulated biomechanical transduction. Z-projected images of cancer cell aggregates were used to analyze 3D multicellular architecture features. Notably, by using a support vector machine classifier, we distinguished tumor cells from normal cells with an accuracy greater than 95%, according to the geometrical features of multicellular spheroids in phase contrast microscopy images. Cancer cells in multicellular spheroid arrays exhibited higher drug resistance of anticancer drug cisplatin than cells grown in 2D cultures. Finally, we developed a co-culture system composed of tumor spheroid arrays, fibroblast cells and photo-crosslinkable gelatin methacryloyl hydrogel to mimic tumor microenvironment which consisted of solid tumor massed, surrounding stromal cells and extracellular matrix. Together, our newly developed simultaneous 2D and 3D cell culture array has great potential in comprehensive evaluation of cellular events in both 2D and 3D, rapid production of spheroid arrays and multicellular geometry-based tumor cell detection.
Bacterial Diversity of Water and Sediment Samples from Gull Point State Park (West Okoboji, Iowa) Determined Using 16S rRNA Gene Amplicon Sequencing

Gull Point State Park is located on a peninsula on the west shore of West Okoboji Lake (Iowa, USA). It is the primary state park in the Iowa Great Lakes region. Sediment and water samples from three locations at the Gull Point pond were analyzed for their microbial composition. ABSTRACT Gull Point State Park is located on a peninsula on the west shore of West Okoboji Lake (Iowa, USA). It is the primary state park in the Iowa Great Lakes region. Sediment and water samples from three locations at the Gull Point pond were analyzed for their microbial composition.
The recycling-oriented material characterization of hard disk drives with special emphasis on NdFeB magnets

Hard disk drives (HDDs) consist of many components made from various materials: e.g. aluminum, steel, copper and rare earth elements (REEs). Recycling and reuse of these materials is desirable for economic and environmental reasons. Developing of potential HDDs recycling methods requires knowledge about HDDs material characteristic. The study aims to explore knowledge about structure and chemical composition of HDDs main components with special emphasis on NdFeB magnets. HDDs collected for the experiments came from Desktop PCs and Notebooks. The dependence between the average mass of HDDs components and such parameters as producer, year and country of production and disk capacity was analyzed. Chemical composition of NdFeB magnets and the heaviest components (i.e. top cover, mounting chassis, platters and metallic plates from magnet assembly of actuator) was analyzed by various analytical methods. The heaviest HDDs main components: top cover and mounting chassis, with the highest recycling potential, are made of aluminum and steel respectively. The majority of HDDs components showed also the existence of different alloy additions: C, Mg, Si, P, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, Sn and Pb. NdFeB magnets constitute 2.2 ± 1.1% of the average HDD from Desktop PC (517.3 ± 64.2 g) and 3.2 ± 1.2% from Notebook (108.2 ± 24.3 g). The chemical composition of NdFeB magnets from collected HDDs changes in the wide range: Fe (53–62%), Nd (25–29%), Pr (2–13%), Dy (0.1– 1.4%), Ni (2–6%), Co (0.5–3.6%), B (0.8–1.0%). Recycling of permanent magnets based on NdFeB alloys is potential remedy to fill the gap in the supply of rare earth elements on the global REEs market.
Align and Pool for EEG Headset Domain Adaptation (ALPHA) to Facilitate Dry Electrode Based SSVEP-BCI

Objective: The steady-state visual evoked potential based brain-computer interface (SSVEP-BCI) implemented in dry electrodes is a promising paradigm for alternative and augmentative communication in real-world applications. To improve its performance and reduce the calibration effort for dry-electrode systems, we utilize cross-device transfer learning by exploiting auxiliary individual wet-electrode electroencephalogram (EEG). Methods: We proposed a novel transfer learning framework named ALign and Pool for EEG Headset domain Adaptation (ALPHA), which aligns the spatial pattern and the covariance for domain adaptation. To evaluate its efficacy, 75 subjects performed an experiment of 2 sessions involving a 12-target SSVEP-BCI task. Results: ALPHA significantly outperformed a baseline approach (canonical correlation analysis, CCA) and two competing transfer learning approaches (transfer template CCA, ttCCA and least square transformation, LST) in two transfer directions. When transferring from wet to dry EEG headsets, ALPHA significantly outperformed the fully-calibrated approach of task-related component analysis (TRCA). Conclusion: ALPHA advances the frontier of recalibration-free cross-device transfer learning for SSVEP-BCIs and boosts the performance of dry electrode based systems. Significance: ALPHA has methodological and practical implications and pushes the boundary of dry electrode based SSVEP-BCI toward real-world applications.
Comparing quality of life outcomes of JAK inhibitors and biological treatments for atopic dermatitis: a systematic review and network meta-analysis

ABSTRACT Introduction:Several novel biological agents and janus kinase (JAK) inhibitors are being investigated for efficacy in the management of atopic dermatitis (AD). However, there is a paucity of head-to-head trials comparing agents and their effect on quality of life (QoL). Methods:A systematic review of existing studies was performed, and data was pooled for meta-analysis from eligible studies of novel systemic agents for AD which reported QoL outcomes. Sixteen week least square means differences (LSM) were pooled and compared using network meta-analysis to synthesize direct and indirect comparisons, with 95% credible intervals (Crl) provided. Results:At 16 weeks, Dermatology Life Quality Index outcomes showed dupilumab 300 mg once weekly had the highest improvement versus placebo (LSM −4.63, 95% Crl −5.46,3.79). At 16 weeks, the improvement in Patient Oriented Eczema Measure scores ranked abrocitinib 200 mg daily the highest (LSM −7.62, 95% Crl −10.26; −4.98) and improvement in Hospital Anxiety and Depression Scale ranked dupilumab 300 mg once weekly highest (LSM −2.98, 95% Crl −4.48; −1.47) The improvement in peak pruritus scores ranked lebrikizumab 250 mg fortnightly (LSM −64.90, 95% Crl-84.58; −45.22) highest. Conclusion:The present study suggests that there are various systemic options for AD for which all seem to demonstrate a degree of QoL-related efficacy.
Increases in extreme heat stress in domesticated livestock species during the twenty‐first century

Anthropogenic climate change is expected to have major impacts on domesticated livestock, including increased heat stress in animals in both intensive and extensive livestock systems. We estimate the changes in the number of extreme heat stress days per year for animals raised outdoors that can be expected in the major domesticated animal species (cattle, sheep, goats, poultry, and pigs) across the globe during this century. We used the temperature humidity index as a proxy for heat stress, calculated using temperature and relative humidity data collated from an ensemble of CMIP6 climate model output for mid and end century. We estimate changes in the proportions of different livestock species that may be at increased risk of extreme heat stress under two contrasting greenhouse gas emission scenarios. Results are discussed in relation to changes in the suitability of different climate conditions for domesticated livestock during the current century. We find that by end century, extreme heat stress risk is projected to increase for all livestock species in many parts of the tropics and some of the temperate zones, and to become climatically more widespread, compared to 2000. Although adaptation options exist for both intensive and extensive livestock production systems, the increasing pervasiveness of extreme heat stress risk in the future will seriously challenge the viability of outdoor livestock keeping, particularly in the lower latitudes in lower and middle‐income countries where the costs of adaptation may be challenging to address.
Ethnic variation in outcome of people hospitalised during the first COVID-19 epidemic wave in Wales (UK): an analysis of national surveillance data using Onomap, a name-based ethnicity classification tool

Objective To identify ethnic differences in proportion positive for SARS-CoV-2, and proportion hospitalised, proportion admitted to intensive care and proportion died in hospital with COVID-19 during the first epidemic wave in Wales. Design Descriptive analysis of 76 503 SARS-CoV-2 tests carried out in Wales to 31 May 2020. Cohort study of 4046 individuals hospitalised with confirmed COVID-19 between 1 March and 31 May. In both analyses, ethnicity was assigned using a name-based classifier. Setting Wales (UK). Primary and secondary outcomes Admission to an intensive care unit following hospitalisation with a positive SARS-CoV-2 PCR test. Death within 28 days of a positive SARS-CoV-2 PCR test. Results Using a name-based ethnicity classifier, we found a higher proportion of black, Asian and ethnic minority people tested for SARS-CoV-2 by PCR tested positive, compared with those classified as white. Hospitalised black, Asian and minority ethnic cases were younger (median age 53 compared with 76 years; p<0.01) and more likely to be admitted to intensive care. Bangladeshi (adjusted OR (aOR): 9.80, 95% CI 1.21 to 79.40) and ‘white – other than British or Irish’ (aOR: 1.99, 95% CI 1.15 to 3.44) ethnic groups were most likely to be admitted to intensive care unit. In Wales, older age (aOR for over 70 years: 10.29, 95% CI 6.78 to 15.64) and male gender (aOR: 1.38, 95% CI 1.19 to 1.59), but not ethnicity, were associated with death in hospitalised patients. Conclusions This study adds to the growing evidence that ethnic minorities are disproportionately affected by COVID-19. During the first COVID-19 epidemic wave in Wales, although ethnic minority populations were less likely to be tested and less likely to be hospitalised, those that did attend hospital were younger and more likely to be admitted to intensive care. Primary, secondary and tertiary COVID-19 prevention should target ethnic minority communities in Wales.