bluuebunny/crossref_metadata_2025_split huggingface dataset:
BrdU immuno-tagged G-quadruplex ligands: a new ligand-guided immunofluorescence approach for tracking G-quadruplexes in cells
Authors: Masson Thibaut , Landras Guetta Corinne , Laigre Eugénie , Cucchiarini Anne , Duchambon Patricia , Teulade-Fichou Marie-Paule , Verga Daniela 
Published: November 2021

Abstract
G-quadruplexes (G4s) are secondary structures forming in G-rich nucleic acids. G4s are assumed to play critical roles in biology, nonetheless their detection in cells is still challenging. For tracking G4s, synthetic molecules (G4 ligands) can be used as reporters and have found wide application for this purpose through chemical functionalization with a fluorescent tag. However, this approach is limited by a low-labeling degree impeding precise visualization in specific subcellular regions. Herein, we present a new visualization strategy based on the immuno-recognition of 5-bromo-2′-deoxyuridine (5-BrdU) modified G4 ligands, functionalized prior- or post-G4-target binding by CuAAC. Remarkably, recognition of the tag by antibodies leads to the detection of the modified ligands exclusively when bound to a G4 target both in vitro, as shown by ELISA, and in cells, thereby providing a highly efficient G4-ligand Guided Immunofluorescence Staining (G4-GIS) approach. The obtained signal amplification revealed well-defined fluorescent foci located in the perinuclear space and RNase treatment revealed the preferential binding to G4-RNA. Furthermore, ligand treatment affected significantly BG4 foci formation in cells. Our work headed to the development of a new imaging approach combining the advantages of immunostaining and G4-recognition by G4 ligands leading to visualization of G4/ligands species in cells with unrivaled precision and sensitivity.
WHIRLY1 of Barley and Maize Share a PRAPP Motif Conferring Nucleoid Compaction
Authors: Oetke Svenja , Scheidig Axel J , Krupinska Karin 
Published: November 2021

Abstract
WHIRLY1 in barley was shown to be a major architect of plastid nucleoids. Its accumulation in cells of Escherichia coli coincided with an induction of nucleoid compaction and growth retardation. While WHIRLY1 of maize had similar effects on E. coli cells, WHIRLY1 proteins of Arabidopsis and potato as well as WHIRLY2 proteins had no impact on nucleoid compaction in E. coli. By mutagenesis of HvWHIRLY1 the PRAPP motif at the N-terminus preceding the highly conserved WHIRLY domain was identified to be responsible for the nucleoid compacting activity of HvWHIRLY1 in bacteria. This motif is found in WHIRLY1 proteins of most members of the Poaceae family, but neither in the WHIRLY2 proteins of the family nor in any WHIRLY protein of eudicot species such as Arabidopsis thaliana. This finding indicates that a subset of the monocot WHIRLY1 proteins has acquired a specific function as nucleoid compacters by sequence variation in the N-terminal part preceding the conserved WHIRLY domain and that in different groups of higher plants the compaction of nucleoids is mediated by other proteins.
Allosteric Modulation of the Sigma-1 Receptor Elicits Antipsychotic-like Effects
Authors: Chen Jiali , Li Guangying , Qin Pingping , Chen Jiaojiao , Ye Na , Waddington John L , Zhen Xuechu 
Published: November 2021

Abstract
Allosteric modulation represents an important approach in drug discovery because of its advantages in safety and selectivity. SOMCL-668 is the first selective and potent sigma-1 receptor allosteric modulator, discovered in our laboratory. The present work investigates the potential therapeutic effects of SOMCL-668 on phencyclidine (PCP)-induced schizophrenia-related behavior in mice and further elucidates underlying mechanisms for its antipsychotic-like effects. SOMCL-668 not only attenuated acute PCP-induced hyperactivity and PPI disruption, but also ameliorated social deficits and cognitive impairment induced by chronic PCP treatment. Pretreatment with the selective sigma-1 receptor antagonist BD1047 blocked the effects of SOMCL-668, indicating sigma-1 receptor-mediated responses. This was confirmed using sigma-1 receptor knockout mice, in which SOMCL-668 failed to ameliorate PPI disruption and hyperactivity induced by acute PCP and social deficits and cognitive impairment induced by chronic PCP treatment. Additionally, in vitro SOMCL-668 exerted positive modulation of sigma-1 receptor agonist-induced intrinsic plasticity in brain slices recorded by patch-clamp. Furthermore, in vivo lower dose of SOMCL-668 exerted positive modulation of improvement in social deficits and cognitive impairment induced by the selective sigma-1 agonist PRE084. Also, SOMCL-668 reversed chronic PCP-induced down-regulation in expression of frontal cortical p-AKT/AKT, p-CREB/CREB and BDNF in wide-type but not sigma-1 knockout mice. Moreover, administration of the PI3K/AKT inhibitor LY294002 abolished amelioration by SOMCL-668 of chronic PCP-induced schizophrenia-related behaviors by inhibition of BDNF expression. The present data provide initial, proof-of-concept evidence that allosteric modulation of the sigma-1 receptor may be a novel approach for the treatment of psychotic illness.
Protected through Part-time Employment? Labor Market Status, Domestic Responsibilities, and the Life Satisfaction of German Women during the COVID-19 Pandemic
Authors: Bertogg Ariane , Kulic Nevena , Strauss Susanne 
Published: November 2021

AbstractThe COVID-19 lockdown measures have challenged individuals to reconcile employment, childcare, and housework. This article addresses whether these challenges have reduced life satisfaction among German women by focusing on their labor market status and drawing upon a topical online survey (Kantar) collected in Germany at two points in time: May 2020 and November 2020. We find that part-time employed women were better protected against a decline in life satisfaction, but only during the first lockdown. Economically inactive women were most likely to experience a decline in life satisfaction during the first lockdown, but least likely during the second lockdown. Life satisfaction has further decreased between the first and the second lockdown, and the likelihood of a decrease has converged for full-time, part-time, and economically inactive women.
The dark septate endophyte Phialocephala sphaeroides confers growth fitness benefits and mitigates pathogenic effects of Heterobasidion on Norway spruce
Authors: Wen Zilan , Terhonen Eeva , Asiegbu Fred O 
Published: November 2021

Abstract
Forest trees frequently interact with a diverse range of microorganisms including dark septate endophytes (DSEs) and fungal pathogens. Plant defense responses to either individual pathogens or endophytes have been widely studied, but very little is known on the effect of coinfection on host defenses. To study the impact of coinfection or tripartite interaction on plant growth and host defenses, Norway spruce (Picea abies (L.) Karst) seedlings were inoculated with a DSE Phialocephala sphaeroides or with a root pathogen Heterobasidion parviporum Niemela & Korhonen or coinfected with both fungi. The results showed that the DSE promoted the root growth of spruce seedlings. Control seedlings without any inoculum were subjected to sequencing and used as a baseline for identification of differentially expressed genes (DEGs). RNA-seq analysis of seedlings inoculated with P. sphaeroides, infected with H. parviporum or coinfected with both fungi resulted in a total of 5269 DEGs. The majority of DEGs were found in P. sphaeroides-inoculated seedlings. Lignin biosynthesis pathways were generally activated during fungal infections. The pattern was distinct with endophyte inoculation. The majority of the genes in the flavonoid biosynthesis pathway were generally suppressed during fungal infections. A specific transcriptional response to P. sphaeroides inoculation was the increased transcripts of genes involved in jasmonic acid biosynthesis, mitogen-activated protein kinases signaling pathway, plant hormone signal transduction and calcium-mediated signaling. This may have potentially contributed to promoting the root growth of seedlings. Although the coinfection suppressed the induction of numerous genes, no negative effect on the growth of the spruce seedlings occurred. We conclude that the subsequent H. parviporum infection triggered reprogramming of host metabolism. Conversely, the endophyte (P. sphaeroides), on the other hand, counteracted the negative effects of H. parviporum on the growth of the spruce seedlings.
Exploring Residents’ Well-Being and Burnout via Qualitative Ecological Momentary Assessment
Authors: Shea Judy A. , Bellini Lisa M. , Desai Sanjay V. , Barg Frances K. , Eriksen Whitney , Wietlisbach Larissa E. , Yakubu Abdul-Rakeem , Asch David A. 
Published: November 2021

Purpose
Most of what is known about resident burnout and wellness comes from cross-sectional snapshot surveys. The purpose of this study was to elicit qualitative perspectives on wellness from a cohort of internal residents over time using ecological momentary assessment.

Method
Drawing on principles of ecological momentary assessment, 13 different open-ended survey prompts were delivered between October and March during the 2019–2020 academic year. Participants were 88 randomly selected internal medicine residents from 4 internal medicine training programs in the Northeast.

Results
The response rate was 95%. Three main themes regarding wellness were self, program/education environment, and medical/structural system. A fourth theme, the desire to provide quality patient care, cut across all other themes. The patient care theme repeatedly stressed residents’ desire to spend more time with patients. The self theme primarily reflected messages about personal emotions and the need for work–life balance and wellness. The program/education environment theme reflected the value of learning, teamwork and community, and program culture. The medical/structural system theme showed that residents’ experiences were shaped by the efficiency of their days and largely a product of their schedules and administrative support. Closing advice to future trainees was optimistic and reassuring.

Conclusions
While findings support much of what has been learned via single-occasion survey snapshots, an ecological momentary assessment design allowed a deeper dive into contextual associations. The results affirm the primacy of patient care and also highlight the value of teamwork and culture. Peers and program leaders are heavily influential in setting the tone for the learning experience, whether for the day or with a more enduring message of respect and support. There is opportunity to maximize high- or higher-value learning experiences for residents and find solutions to reduce and reframe the perceived “low-value administrative work” that is part of care coordination.
Selective Microvascular Tissue Transfection Using Minicircle DNA for Systemic Delivery of Human Coagulation Factor IX in a Rat Model Using a Therapeutic Flap
Authors: Than Peter A. , Davis Christopher R. , Rennert Robert C. , Morrison Shane D. , Findlay Michael W. , Kay Mark A. , Gurtner Geoffrey C. 
Published: November 2021

Background:
Gene therapy is a promising treatment for protein deficiency disorders such as hemophilia B. However, low tissue selectivity and efficacy are limitations of systemic vector delivery. The authors hypothesized that selective transfection of rat superficial inferior epigastric artery flaps could provide systemic delivery of coagulation factor IX, preventing the need for systemic vector administration.

Methods:
Minicircle DNA containing green fluorescent protein, firefly luciferase, and human coagulation factor IX was created. Vector constructs were validated by transfecting adipose-derived stromal cells isolated from Wistar rat superficial inferior epigastric artery flaps and evaluating transgene expression by fluorescence microscopy, bioluminescence, and enzyme-linked immunosorbent assay. Minicircle DNA luciferase (10 and 30 μg) was injected into murine (wild-type, C57/BL/6) inguinal fat pads (n = 3) and followed by in vivo bioluminescence imaging for 60 days. Wistar rat superficial inferior epigastric artery flaps were transfected with minicircle DNA human coagulation factor IX (n = 9) with plasma and tissue transgene expression measured by enzyme-linked immunosorbent assay at 2 and 4 weeks.

Results:
Transfected adipose-derived stromal cells expressed green fluorescent protein for 30 days, luciferase for 43 days, and human coagulation factor IX (21.9 ± 1.2 ng/ml) for 28 days in vitro. In vivo murine studies demonstrated dose-dependence between minicircle DNA delivery and protein expression. Ex vivo rat superficial inferior epigastric artery flap transfection with minicircle DNA human coagulation factor IX showed systemic transgene expression at 2 (266.6 ± 23.4 ng/ml) and 4 weeks (290.1 ± 17.1 ng/ml) compared to control tissue (p < 0.0001).

Conclusions:
Rat superficial inferior epigastric artery flap transfection using minicircle DNA human coagulation factor IX resulted in systemic transgene detection, suggesting that selective flap or angiosome-based tissue transfection may be explored as a treatment for systemic protein deficiency disorders such as hemophilia B.
Uptake, Retention, and Adherence to Pre-exposure Prophylaxis (PrEP) in TRIUMPH: A Peer-Led PrEP Demonstration Project for Transgender Communities in Oakland and Sacramento, California
Authors: Sevelius Jae M. , Glidden David V. , Deutsch Madeline , Welborn Layla , Contreras Alejandro , Salinas Arianna , Venegas Luz , Grant Robert M. 
Published: November 2021

Background:
TRIUMPH (Trans Research–Informed communities United in Mobilization for the Prevention of HIV) was a community-led, transgender-specific pre-exposure prophylaxis (PrEP) demonstration project at 2 community-based clinical sites in California. TRIUMPH used peer health education, community mobilization, and clinical integration of PrEP with hormone therapy to promote PrEP knowledge and acceptability. The goal of this study was to evaluate PrEP uptake, retention, and adherence among TRIUMPH participants and examine site-based differences.

Methods:
Eligible participants were adult transgender and gender diverse people interested in PrEP. Participants were seen at baseline and at 1, 3, 6, 9, and 12 months for PrEP provision, clinical visits, and HIV testing. PrEP uptake was defined as dispensation of PrEP, PrEP retention was defined as proportion of expected visits completed among those who initiated PrEP, and PrEP adherence was assessed by measuring tenofovir diphosphate concentrations in dried blood spots. Logistic regression models quantified the association of variables with PrEP outcomes.

Results:
TRIUMPH enrolled 185 participants; the median age was 28 years (interquartile range: 23–35), 7% was Black, and 58% was Latinx. PrEP uptake was as follows: 78% in Oakland and 98% in Sacramento; 91% among trans women, 96% among trans men, and 70% among nonbinary participants. Almost half (47%) rarely/never believed about HIV, and 42% reported condomless sex act in the past 3 months. Participants who reported higher numbers of sex partners were more likely to be retained and adherent; other predictors of adherence included not having a primary partner and not experiencing violence in the past 3 months.

Conclusions:
This community-led, trans-specific PrEP demonstration project documents high levels of PrEP initiation in a young transgender and gender diverse cohort at risk of HIV acquisition.
Pro-Resolving Mediator Resolvin E1 Restores Alveolar Fluid Clearance in Acute Respiratory Distress Syndrome
Authors: Luo Jun , Zhang Wen-Yan , Li Hui , Zhang Pu-Hong , Tian Chao , Wu Cheng-Hua , Zhao An-Ning , Chen Man-Ling , Guo Yi-Fan , Cho Young-Chang , Jin Sheng-Wei , Hao Yu 
Published: November 2021

ABSTRACT
Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by increased permeability of the alveolar-capillary barrier and impaired alveolar fluid clearance. Resolvin E1 (RvE1) is a specialized pro-resolving mediator derived endogenously from omega-3-polyunsaturated fatty acids. RvE1 (10 μg/kg i.v.) was injected to rats 6 h post-lipopolysaccharide (LPS) (14 mg/kg) induction. After another 3 h, alveolar fluid clearance was measured in live rats (n = 8–9). The primary Type II alveolar epithelial cell was isolated and treated by LPS (1 μg/mL) with or without RvE1 (250 nM). The expression of epithelial sodium channel (ENaC), Na+/K+-ATPase (NKA), AKT, serum- and glucocorticoid-induced kinase 1 (SGK1), and Nedd4-2 were detected. RvE1 improved survival rate (30% vs. 70%, P = 0.048), increased the clearance of alveolar fluid (13.34% vs. 18.73%, P
< 0.001), reduced lung wet-dry weight ratio (5.01 vs. 4.63, P
< 0.001), mitigated lung injury scores (13.38 vs. 7.0, P
< 0.05) and inflammation in LPS-induced ARDS in rats. RvE1 upregulated alveolar ENaC and NKA expression in vivo and in vitro. In addition, RvE1 significantly increased the expression of phosphorylated AKT, SGK1, and phosphorylated Nedd4-2 in LPS-stimulated primary alveolar type II cells. The effects of RvE1 were abrogated by blocking phosphatidylinositide3’-kinase (PI3K) and SGK1 with LY294002 and GSK650394, respectively. In summary, RvE1 upregulated ENaC and NKA expression by activating PI3K/AKT/SGK1 pathway to promote alveolar fluid clearance, suggesting that RvE1 may be a potentially effective drug for ARDS treatment.
A Flexible Data-Driven Framework for COVID-19 Case Forecasting Deployed in a Developing-world Public Health Setting
Authors: Jain Sansiddh , Tiwari Avtansh , Bannur Nayana , Deva Ayush , Shingi Siddhant , Shah Vishwa , Kulkarni Mihir , Deka Namrata , Ramaswami Keshav , Khare Vasudha , Maheshwari Harsh , Dhavala Soma , Sreedharan Jithin , White Jerome , Merugu Srujana , Raval Alpan 
Published: November 2021

ABSTRACTForecasting infection case counts and estimating accurate epidemiological parameters are critical components of managing the response to a pandemic. This paper describes a modular, extensible framework for a COVID-19 forecasting system, primarily deployed during the first Covid wave in Mumbai and Jharkhand, India. We employ a variant of the SEIR compartmental model motivated by the nature of the available data and operational constraints. We estimate best fit parameters using Sequential Model-Based Optimization (SMBO), and describe the use of a novel, fast and approximate Bayesian model averaging method (ABMA) for parameter uncertainty estimation that compares well with a more rigorous Markov Chain Monte Carlo (MCMC) approach in practice. We address on-the-ground deployment challenges such as spikes in the reported input data using a novel weighted smoothing method. We describe extensive empirical analyses to evaluate the accuracy of our method on ground truth as well as against other state-of-the-art approaches. Finally, we outline deployment lessons and describe how inferred model parameters were used by government partners to interpret the state of the epidemic and how model forecasts were used to estimate staffing and planning needs essential for addressing COVID-19 hospital burden.CCS CONCEPTSApplied computing → Health care information systems; Forecasting;Computing methodologies → Modeling methodologies.
Effect of electroMagnetic Interference from smartPHone On cardiac implaNtable Electronic device (EMI-PHONE study)
Authors: Apakuppakul Sanatcha , Methachittiphan Nilubon , Apiyasawat Sirin 
Published: November 2021

AbstractBackgroundSmartphone can emit two types of electromagnetic waves, static field from magnet and dynamic field from calling. Previous evidence showed the interference effects from old generation of mobile phones to cardiac implantable electronic device (CIEDs). The current generation of smartphones and CIEDS are reportedly better designed to reduce electromagnetic interference (EMI). We seek to find the presence and the magnitude of EMI from the current generation of smartphones.MethodsA total of 80 consecutive subjects with CIEDs (Included pacemaker, ICD, CRT-D, CRT-P) were recruited from our CIEDs clinic and were tested for EMI. Each subject was tested with three different smartphones (Nokia 3310, Iphone 7, and Samsung 9S). Each phone was attached to chest wall at 0 cm at pulse generator site, at atrial lead, and at ventricular lead site. During the tests, real-time interrogations were performed to detect any EMI from smartphone in stand-by mode, and during calling-in and out for 30 seconds. After the tests, post-test interrogation was performed to detect any parameters changes. Adverse events including pacemaker inhibition, false ICD shock, CIEDs device malfunction, and urgent electrophysiologist consultations were recorded.ResultsOf all 80 subjects (Mean age 70.5±12.9 year-old, 50% male) recruited in the study, all completed the tests according to our protocol. The most common type of CIEDs tested was pacemaker (N=56, 70%), followed by ICD (N=16, 20%), and CRT (N=8, 10%). Most patients (N=62, 77.5%) had more than one lead implanted. The mean year of implantation was 5.2±2.8 (Devices were implanted since 2008-2019). Of all the tests performed, there was no EMI or adverse events observed.ConclusionCurrent generation of smartphones have no EMI effect to CIEDs and can be used safely without any adverse events including pacemaker inhibition, false ICD shock and CIEDs device malfunction.
Likelihood of being Physically Inactive from a Nationally Representative sample of Autistic Children
Authors: Vasudevan Vijay 
Published: November 2021

ABSTRACTDespite the many health risks of physical inactivity, studies have demonstrated individual, family, and environmental determinants of inactivity for autistic children. However, these studies never examined these correlates at the same time. Therefore, the purpose of this study was to explore these ecological domains concurrently when examining physical inactivity correlates for autistic children. This study used data from the 2016-2020 National Survey of Children’s Health. The authors predicted physical inactivity while controlling for child, parental/household, and neighborhood correlates with autism status as the comparison group. When controlling for covariates, children with co-occurring autism and intellectual and developmental disability (IDD) (adjusted odds ratio (aOR)= 1.91, 95% confidence interval (CI): 1.36-2.68) or ASD only (aOR = 1.91, CI: 1.48-2.48) were significantly more likely to be inactive when compared to children without autism or IDD. However, autism medicine and autism severity were not predictors for obese autistic children. These findings indicate that it is important to take a holistic, ecological approach when exploring the correlates of inactivity for autistic children.
Modeling COVID-19 epidemic trends and health system needs leading to projections for developing countries: a case study of Thailand
Authors: Metchanun Nawaphan , Borgemeister Christian , Bever Caitlin , Galick David 
Published: November 2021

AbstractThailand was the first country outside China to report a COVID-19 case but had a mild impact from the outbreak especially at the beginning of the pandemic. This study systematically investigates the evolution of the COVID-19 epidemic in Thailand from January 2020 to March 2021 to uncover the COVID-19 situation in the country. By modeling all health districts throughout the country, the study found that COVID-19 contributed to an increase in excess deaths and that COVID-19 deaths might be underreported. There was a lag time in ramping up testing although testing is key to control the disease. The estimated total number of beds required by COVID-19 seems low, but it may not ensure the capacity to take care of critical cases that required ICU beds, specific medical equipment, and trained medical staff.