Miracle-dz/UniFAR-FTUs huggingface dataset:
The Influences of Illumination Regime on Egg-laying Rhythms of Honey Bee Queens

Honey bee queens show extreme fecundity, commonly laying more than a thousand eggs in a single day. It has proven challenging to study the temporal organization of egg-laying behavior because queens are typically active around the clock in the dark cavity of a densely populated nest. To contend with this challenge, we developed two novel methods allowing detailed monitoring of queen activity and egg laying. We first adapted a high-resolution, continuous, tracking system allowing to track the position of barcode-tagged queens in observation hives with colonies foraging outside. We found that the queen is active ~96% of the day with typically no diurnal rhythm. Next, we developed a new laboratory procedure to monitor egg laying at single egg resolution under different light regimes. We found that under constant darkness (DD) and temperature conditions, queens laid eggs with no circadian rhythms. Queen fecundity was severely reduced under constant light (LL). Under a 12:12 illumination regime, queen fecundity was comparable to under constant darkness, with a higher number of eggs during the light phase. These daily rhythms in egg laying continued when these queens were released to DD conditions, suggesting that egg-laying rhythms are influenced by endogenous circadian clocks. These results suggest that honey bee queens are active and lay eggs around the clock with no diurnal rhythms. Light has complex influences on these behaviors, but more studies are needed to determine whether these effects reflect the influence of light directly on the queen or indirectly by affecting workers that interact with the queen.
Antiphospholipid antibody positivity in early systemic lupus erythematosus is associated with subsequent vascular events

Abstract Objective aPL are found in the blood of 20–30% of patients with SLE. Although aPL cause vascular thrombosis in the antiphospholipid syndrome, it is not clear whether positive aPL levels in early SLE increase risk of subsequent vascular events (VE). In a previous analysis of 276 patients with SLE, we found that early positivity for ≥2 of IgG anti-cardiolipin (anti-CL), IgG anti-β2-glycoprotein I (anti-β2GPI) and anti-domain I of β2-glycoprotein I (anti-DI) showed a possible association with VE. Here we have extended that analysis. Methods Serum samples taken from 501 patients with SLE early in their disease had been tested for IgG anti-CL, anti-β2GPI and anti-DI by ELISA. Complete VE history was available for 423 patients of whom 23 were excluded because VE occurred before the diagnosis of SLE. For the remaining 400 patients we carried out Kaplan–Meier survival analysis to define groups at higher risk of VE. Results Of 400 patients, 154 (38.5%) were positive for one or more aPL, 27 (6.8%) were double/triple-positive and 127 (31.8%) were single-positive. There were 91 VE in 77 patients, of whom 42 were aPL-positive in early disease. VE were significantly increased in aPL-positive vs aPL-negative patients (P = 0.041) and in double/triple-positive vs single-positive vs aPL-negative patients (P = 0.0057). Omission of the IgG anti-DI assay would have missed 14 double/triple-positive patients of whom six had VE. Conclusion Double/triple-positivity for IgG anti-CL, anti-β2GPI and anti-DI in early SLE identifies a population at higher risk of subsequent VE.
Tinengotinib (TT-00420), a Novel Spectrum-Selective Small-Molecule Kinase Inhibitor, Is Highly Active Against Triple-Negative Breast Cancer

Abstract Triple-negative breast cancer (TNBC) is a highly heterogeneous cancer lacking actionable targets. Using a phenotypic screen of TNBC cells, we discovered a novel multiple kinase inhibitor tinengotinib (TT-00420) that strongly inhibited Aurora A/B, FGFR1/2/3, VEGFRs, JAK1/2, and CSF1R in biochemical assays. Exposure to tinengotinib specifically inhibited proliferation across all subtypes of TNBC in vitro and in vivo, while leaving luminal breast cancer cells intact. Incubation of HCC1806 with tinengotinib led to dose-dependent downregulation of genes essential for TNBC cell growth and proliferation. Studies revealed that the potential mechanism of action of tinengotinib involved, predominantly, inhibition of Aurora A or B kinase activity, while inhibition of other pathways contributed to suppression of potency and activity. In vitro treatment of TNBC cell lines or in vivo administration in a syngeneic model with tinengotinib resulted in up-regulation of CXCL10 and 11 or diminished tumor-associated macrophage (TAM) infiltration. Tinengotinib represents a novel combinatorial inhibitory mechanism to treat TNBC. The phase I trial of tinengotinib was completed (ClinicalTrials.gov identifier: NCT03654547).
The effect of different carbon sources on biofouling in membrane fouling simulators: microbial community and implications

Abstract Biofouling is a problem affecting the operation of nanofiltration systems due to the complexity of the carbon matrix affecting bacteria and biofilm growth. This study used membrane fouling simulators to investigate the effects of five different carbon sources on the biofouling of nanofiltration membranes. For all the carbon sources analyzed, the increase in pressure drop was most accelerated for acetate. The use of acetate as the single carbon source produced less adenosine triphosphate but more extracellular polymers than glucose. The microbial community was analyzed using 16 s rRNA. The use of more than a single carbon source produced an increase in bacteria diversity even at similar concentrations. The relative abundance of proteobacteria was the highest at the phylum level (95%) when a single carbon source was added. Additionally, it was found that the use of different carbon sources produced a shift in the microbial community, affecting the biofouling and pressure drop on membranes. Graphical Abstract
Natural Compounds with Oxepinochromene Scaffold. Structure, Source, Biological Activity and Synthesis

Natural products containing oxepinochromene motifs were first isolated from natural sources in 1960s. Natural oxepinochromenes are relatively rare and their source is limited to several endophytic and endolichenic fungi or higher plants. The importance of natural oxepinochromene derivatives lies in their promising biological activity. They exhibit a wide range of activities such as antibacterial, anticancer, anti‐inflammatory or antifungal. Consequently, their synthesis has attracted significant interest. This review discusses the source, biosynthesis, biological activity, reactions as well as the total synthesis of oxepinochromene derivatives, belonging to the xanthone, terpenoid and flavone groups of phenolic secondary metabolites.
A framework for dynamical generation of flavor mixing

Abstract. We present a dynamical mechanism à la Nambu–Jona-Lasinio [1] for the generation of masses and mixing for two interacting fermion fields. The analysis is carried out in the framework introduced long ago by Umezawa et al. [2], in which mass generation is achieved via inequivalent representations, and that we generalize to the case of two generations. The method allows a clear identification of the vacuum structure for each physical phase, confirming previous results [3] about the distinct physical nature of the vacuum for fields with definite mass and fields with definite flavor. Implications for the leptonic sector of the Standard Model are briefly discussed.
Mobile Health Application and Hypertension Management in Rural, Middle-Aged Adults

Over 29% of the adult population in the United States are diagnosed with hypertension, and rates are significantly higher in those adults who live in rural areas. Hypertension is recognized as the most prevalent comorbidity and modifiable risk factor leading to premature death. The purpose of this quality improvement project was to determine if using a mobile phone–based health application called Medisafe could enhance medication adherence and improve blood pressure control in rural-dwelling adults. A small group (N = 14) of middle-aged (45-64 years old) patients with hypertension were recruited to download the free Medisafe phone-based health application. Patients utilized the Medisafe application between their initial visit and a 4- to 6-week follow-up. At the follow-up visit, 64% (n = 9) of participants improved their level of hypertension control by blood pressure classification and improved their scores on the medication adherence questionnaire. The findings from this quality improvement project suggest the Medisafe application is useful to enhance medication adherence and blood pressure control. Future research and quality improvement initiatives are necessary to determine the broader efficacy of phone-based health applications in the rural adult population.
Brain-derived neurotrophic factor is a regulator of synaptic transmission in the adult visual thalamus.

Brain-derived neurotrophic factor (BDNF) is an important regulator of circuit development, neuronal survival, and plasticity throughout the nervous system. In the visual system, BDNF is produced by retinal ganglion cells (RGCs) and transported along their axons to central targets. Within the dorsolateral geniculate nucleus (dLGN), a key RGC projection target for conscious vision, the BDNF receptor TrkB is present on RGC axon terminals and post-synaptic thalamocortical (TC) relay neuron dendrites. Based on this, the goal of this study was to determine how BDNF modulates the conveyance of signals through the retinogeniculate (RG) pathway of adult mice. Application of BDNF to dLGN brain slices increased TC neuron spiking evoked by optogenetic stimulation of RGC axons. There was a modest contribution to this effect from a BDNF-dependent enhancement of TC neuron intrinsic excitability including increased input resistance and membrane depolarization. BDNF also increased evoked vesicle release from RGC axon terminals, as evidenced by an increased amplitude of evoked excitatory post-synaptic currents (EPSCs), which was blocked by inhibition of TrkB or phospholipase C. High-frequency stimulation revealed that BDNF increased synaptic vesicle pool size, release probability, and replenishment rate. There was no effect of BDNF on EPSC amplitude or short-term plasticity of corticothalamic feedback synapses. Thus, BDNF regulates RG synapses by both presynaptic and postsynaptic mechanisms. These findings suggest that BNDF influences the flow of visual information through the retinogeniculate pathway.
Spike protein mediated membrane fusion during SARS‐CoV‐2 infection

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has posed a serious threat to public health and has quickly become a global concern. The infection of SARS‐CoV‐2 begins with the binding of its spike protein to the receptor‐angiotensin‐converting enzyme 2 (ACE2), which, after a series of conformation changes, results in the fusion of viral‐cell membranes and the release of the viral RNA genome into the cytoplasm. In addition, infected host cells can express spike protein on their cell surface, which will interact with ACE2 on neighboring cells, leading to cell membrane fusion and the formation of multinucleated cells or syncytia. Both viral entry and syncytia formation are mediated by spike‐ACE2 interaction and share some common mechanisms of membrane fusion. Here in this review, we will summarize our current understanding of spike‐mediated membrane fusion, which may shed light on future broad‐spectrum antiviral development.
High risk APOL1 genotypes and kidney disease among treatment naïve HIV patients at Kano, Nigeria

Introduction Racial disparities are known in the occurrence of kidney disease with excess risks found among people of African descent. Apolipoprotein L1 (APOL1) gene variants G1 and G2 are associated with kidney disease among HIV infected individuals of African descent in the USA as well as among black population in South Africa. We set out to investigate the prevalence of these high-risk variants and their effects on kidney disease among HIV infected patients in Northern Nigeria with hitherto limited information despite earlier reports of high population frequencies of these alleles from the Southern part of the country. Methods DNA samples obtained from the whole blood of 142 participants were genotyped for APOL1 G1 and G2 variants after initial baseline investigations including assessment of kidney function. Participants comprised 50 HIV positive patients with no evidence of kidney disease, 52 HIV negative individuals with no kidney disease and 40 HIV positive patients with chronic kidney disease (CKD) evidenced by persistent proteinuria and/or reduced eGFR, who also had a kidney biopsy. All the HIV positive patients were newly diagnosed and treatment naïve. Results The distribution of the APOL1 genotypes among the study participants revealed that 24.6% had a G1 risk allele and 19.0% a G2. The frequency of the High Risk Genotype (HRG) was 12.5% among those with CKD compared to 5.8% in the HIV negative group and zero in the HIV positive no CKD group. Having the HRG was associated with a higher odds for developing HIV Associated Nephropathy (HIVAN) (2 vs 0 risk alleles: OR 10.83, 95% CI 1.38–84.52; P = 0.023; 2 vs 0 or 1 risk alleles: OR 5.5, 95% CI 0.83–36.29; P = 0.07). The HRG was also associated with higher odds for Focal Segmental Glomerulosclerosis (FSGS) (2 vs 0 risk alleles: OR 13.0, 95% CI 2.06–81.91; P = 0.006 and 2 vs 0 or 1 risk alleles: OR 9.0, 95%CI 1.62–50.12; P = 0.01) when compared to the control group. Conclusion This study showed a high population frequency of the individual risk alleles of the APOL1 gene with higher frequencies noted among HIV positive patients with kidney disease. There is high association with the presence of kidney disease and especially FSGS and HIVAN among treatment naive HIV patients carrying two copies of the HRG.
Searching for electromagnetic counterpart of LIGO gravitational waves in the Fermi GBM data with ADWO

Aims. The Fermi collaboration identified a possible electromagnetic counterpart of the gravitational wave event of September 14, 2015. Our goal is to provide an unsupervised data analysis algorithm to identify similar events in Fermi ’s Gamma-ray Burst Monitor CTTE data stream. Methods. We are looking for signals that are typically weak. Therefore, they can only be found by a careful analysis of count rates of all detectors and energy channels simultaneously. Our Automatized Detector Weight Optimization (ADWO) method consists of a search for the signal, and a test of its significance. Results. We developed ADWO, a virtual detector analysis tool for multi-channel multi-detector signals, and performed successful searches for short transients in the data-streams. We have identified GRB150522B, as well as possible electromagnetic candidates of the transients GW150914 and LVT151012. Conclusions. ADWO is an independently developed, unsupervised data analysis tool that only relies on the raw data of the Fermi satellite. It can therefore provide a strong, independent test to any electromagnetic signal accompanying future gravitational wave observations.
Cross-sectional and longitudinal relationships between cardiorespiratory fitness and health-related quality of life in primary school children in England: the mediating role of psychological correlates of physical activity.

AIMS The aims were (1) to analyse the cross-sectional and longitudinal associations between children's cardiorespiratory fitness (CRF) and health-related quality of life (HRQoL) and (2) to examine whether these associations were mediated by physical activity self-efficacy and physical activity enjoyment. METHODS This study involved 383 children (10.0 ± 0.5 years) recruited from 20 primary schools in northwest England. Data were collected on two occasions 12 weeks apart. The number of laps completed in the 20-m Shuttle Run Test was used as the CRF indicator. HRQoL was assessed using the KIDSCREEN-10 questionnaire. Physical activity self-efficacy and enjoyment were assessed with the social-cognitive and Physical Activity Enjoyment Scale questionnaires, respectively. Linear mixed models with random intercepts (schools) assessed associations between CRF and HRQoL cross-sectionally, and longitudinally. Boot-strapped mediation procedures were performed, and indirect effects (IE) with 95% confidence intervals (CI) not including zero considered as statistically significant. Analyses were adjusted for sex, time of the year, socioeconomic status, waist-to-height ratio, maturation, and physical activity. RESULTS CRF was cross-sectionally associated with HRQoL (β = 0.09, 95% CI = 0.02, 0.16; p = .015). In the longitudinal analysis, CRF at baseline was associated with HRQoL at 12 weeks after additionally controlling for baseline HRQoL (β = 0.08, 95% CI = 0.002; p = .15, p = .045). Cross-sectionally, physical activity self-efficacy and enjoyment acted individually as mediators in the relationship between CRF and HRQoL (IE = 0.069, 95% CI = 0.038; p = .105 and IE = 0.045, 95% CI = 0.016; p = .080, respectively). In the longitudinal analysis, physical activity self-efficacy showed a significant mediating effect (IE = 0.025, 95% CI = 0.004; p = .054). CONCLUSION Our findings highlight the influence of CRF on children's psychological correlates of physical activity and their overall HRQoL.
Medical Cannabis Use Patterns and Adverse Effects in Inflammatory Bowel Disease

Goals: To investigate medical cannabis (MC) use patterns and adverse effects in patients with inflammatory bowel disease (IBD). Background: MC is now legal in many states. Although previous studies suggest improvement in disease activity among IBD patients using MC, use patterns and adverse effects are unclear. Study: A cross-sectional anonymous survey was conducted (October 23, 2020 to January 24, 2021) among patients accessing MC dispensaries in New York and Minnesota. Eligibility criteria: age 18 years or older, selfreported IBD diagnosis, MC dispensary purchase. Survey questions included IBD characteristics, MC and healthcare utilization, and MC effects/adverse events. Participant characteristics were analyzed with descriptive statistics. Utilization patterns and symptoms before and after MC use were compared using the Stuart Maxwell test. Results: Of 236 respondents, overall IBD disease activity was mild-to-moderate. Most respondents (61.0%) took a biological. Median frequency of MC use was at least once within the past week. Most respondents used products with high Δ9-tetrahydrocannabinol content (87.5%) through vape pens/cartridges (78.6%). Respondents reported fewer emergency room visits in the 12 months after versus before MC use (35.2 vs 41.5%, P<0.01) and less impact of symptoms on daily life. Most respondents reported euphoria with MC use (75.4%). The other common side effects were feeling drowsy, groggy, or with memory lapses (4.2%), dry mouth/eyes (3.4%), and anxiety/depression or paranoia (3.4%). Few respondents reported MC diversion (1.3%). Conclusions: MC users with IBD perceive symptom benefits and report decreased emergency room visits without serious adverse effects. Further studies are needed to confirm these results with objective measures of healthcare utilization and disease activity.
Secondary donor-derived CD19 CAR-T therapy is safe and efficacious in acute lymphoblastic leukemia with extramedullary relapse after first autologous CAR-T therapy

Despite the advancement of treatments, adults with relapsed/refractory (R/R) B-lineage acute lymphoblastic leukemia (B-ALL) have poor prognosis, with an expected five-year overall survival (OS) rate of 10%‒20% (Nguyen et al., 2008; Oriol et al., 2010). Extramedullary relapse of B-ALL is regarded as a high-risk factor generally associated with poor survival, occurring in about 15% to 20% of all relapsed patients (Ding et al., 2017; Sun et al., 2018). The central nervous system (CNS) and the testes are the most common sites of extramedullary relapse of B-ALL. In addition, extramedullary leukemia can appear in the skin, eyes, breasts, bones, muscles, and abdominal organs. The prognosis of relapsed extramedullary B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is extremely poor (Spyridonidis et al., 2012; Dahlberg et al., 2019). Conventional chemotherapy or radiation is often ineffective in such patients. At present, there are no optimal treatment strategies for treating extramedullary leukemia after allo-HSCT.
Representation of gaussian small ball probabilities in $l_2$

Let z = P +∞ i=1 x2i /a 2 i where the xi’s are i.d. d centered with unit variance gaussian random variables and (ai)i∈N an increasing sequence such that P +∞ i=1 a i < +∞. We propose an exponential-integral representation theorem for the gaussian small ball probability P (z < ε) when ε ↓ 0. We start from a result by Meyer-Wolf, Zeitouni (1993) and Dembo, MeyerWolf, Zeitouni (1995) who computed this probability by means of series. We prove that P (z < ε) belongs to a class of functions introduced by de Haan, well-known in extreme value theory, the class Gamma, for which an explicit exponential-integral representation is available. The converse implication holds under a mild additional assumption. Some applications are underlined in connection with statistical inference for random functions.
A Conductive Bioengineered Cardiac Patch for Myocardial Infarction Treatment by Improving Tissue Electrical Integrity

Conductive scaffolds are of great value for constructing functional myocardial tissues and promoting tissue reconstruction in the treatment of myocardial infarction (MI). Here, a novel scaffold composed of silk fibroin and polypyrrole (SP50) with a typical sponge‐like porous structure and electrical conductivity similar to the native myocardium is developed. An electroactive engineered cardiac patch (SP50 ECP) with a certain thickness is constructed by applying electrical stimulation (ES) to the cardiomyocytes (CMs) on the scaffold. SP50 ECP can significantly express cardiac marker protein (α‐actinin, Cx‐43, and cTnT) and has better contractility and electrical coupling performance. Following in vivo transplantation, SP50 ECP shows a notable therapeutic effect in repairing infarcted myocardium. Not only can SP50 ECP effectively improves left ventricular remodeling and restore cardiac functions, such as ejection function (EF), but more importantly, improves the propagation of electrical pulses and promote the synchronous contraction of CMs in the scar area with normal myocardium, effectively reducing the susceptibility of MI rats to arrhythmias. In conclusion, this study demonstrates a facile approach to constructing electroactive ECPs based on porous conductive scaffolds and proves the therapeutic effects of ECPs in repairing the infarcted heart, which may represent a promising strategy for MI treatment.
Calibrating spatiotemporal models of microbial communities to microscopy data: A review

Spatiotemporal models that account for heterogeneity within microbial communities rely on single-cell data for calibration and validation. Such data, commonly collected via microscopy and flow cytometry, have been made more accessible by recent advances in microfluidics platforms and data processing pipelines. However, validating models against such data poses significant challenges. Validation practices vary widely between modelling studies; systematic and rigorous methods have not been widely adopted. Similar challenges are faced by the (macrobial) ecology community, in which systematic calibration approaches are often employed to improve quantitative predictions from computational models. Here, we review single-cell observation techniques that are being applied to study microbial communities and the calibration strategies that are being employed for accompanying spatiotemporal models. To facilitate future calibration efforts, we have compiled a list of summary statistics relevant for quantifying spatiotemporal patterns in microbial communities. Finally, we highlight some recently developed techniques that hold promise for improved model calibration, including algorithmic guidance of summary statistic selection and machine learning approaches for efficient model simulation.