bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can we revive CETP-inhibitors for the prevention of cardiovascular disease?
Authors: Nicholls Stephen J. , Ray Kausik K. , Nelson Adam J. , Kastelein John J.P. 
Published: November 2022

Purpose of review
To review recent developments in the field of cholesteryl ester transfer protein (CETP) inhibition from clinical trials and genomic analyses which have the potential to impact future clinical programs.

Recent findings
CETP plays an important role in remodelling of lipoproteins. A large body of evidence suggests that the presence of low CETP activity should have favourable effects on lipid profiles and cardiovascular risk. However, a number of clinical development programs of pharmacological CETP inhibitors have been disappointing with reports of toxicity and clinical futility. These findings have led many to consider abandoning CETP inhibition as a potential strategy for cardiovascular prevention. However, recent observations from genomic analyses and post hoc observations of prior clinical trials have given greater insights into the potential relationship between CETP inhibition and cardiovascular risk. This has highlighted the importance of lowering levels of atherogenic lipoproteins.

Summary
These findings provide a pathway for ongoing clinical development of CETP inhibitors, where the potential to play an important role in the prevention of cardiovascular disease may still be possible. The lessons learned and pathway forward for new CETP inhibitors will be reviewed.
Parasympathetic vs. sympathetic changes in heart rate variability following a multimodal integrative medicine intervention for frontline COVID-19 personnel
Authors: Vagedes Jan , Kassem Sameer , Gressel Orit , Samuels Noah , Eden Arieh , Ben-Arye Eran 
Published: November 2022

ABSTRACT

Objective
Frontline healthcare providers (HCPs) working in COVID-19 hospital departments need to deal with considerable physical and emotional stress on a daily basis. We conducted a pilot study to examine changes in heart rate variability (HRV) in frontline COVID-19 personnel following an integrative medicine (IM) intervention.

Methods
HCPs working in isolated COVID-19 in-patient departments underwent a single 30-minute individually-tailored IM sessions combining various IM modalities (acupuncture, mind-body and/or manual-movement modalities, including Anthroposophic medicine). HRV parameters were compared during the first IM session at 3-minute intervals, at the beginning of treatments and after 20 minutes. Root square of successive differences (RMSSD) was measured, as were domains of time (SDNN, pNN50) and frequency (LF/HF Ratio). Pre- and post-intervention concerns were assessed using the MYCaW (Measure Yourself Concerns and Well-being) questionnaire, with post-treatment free-text narratives analyzed for clusters of emotional and spiritual-related keywords (ESKs).

Results
A total of 114 HCPs underwent in IM treatment session and HRV measurements, of which 75 (65.8%) expressed ESKs. RMSSD increased only in the ESK-expressing group (P < 0.001). LF/HF ratios decreased in both groups, with HF power increasing in the ESK-expressing (p = 0.043) and LF power decreasing in the non-ESK-expressing groups (p = 0.004).

Conclusions
Increased parasympathetic activity was observed in all HCPs following the IM intervention, particularly among those expressing ESKs. LF/HF parameters suggest different relaxation-associated mechanisms, with increased HF (regulated predominantly by parasympathetic tone) in the ESK-expressing and decreased LF (regulated partially by sympathetic tone) in the non-expressing group. Additional research needs to explore the relationship between subjective effects of the IM intervention and physiological mechanisms of relaxation in HCPs working in stressful environments.

Trial Registration: The study was registered at ClinicalTrials.gov (NCT05104827).
“The new gay plague”: analysis of public attitudes toward monkeypox
Authors: Shah Tej 
Published: November 2022

AbstractMonkeypox was declared a public health emergency on August 4, 2022, in the United States. The emerging isolation of the virus in the LGBTQ+ community—particularly among gay, bisexual, and men who have sex with men (GBMSM)—has led many to draw parallels between the emerging multi-country outbreak and the 1980s HIV/AIDS crisis. The purpose of this study was to investigate media framing of the monkeypox outbreak in American media through the lens of HIV social constructionist theory. Content analysis of a sample of 59 articles from the top-five most viewed U.S. media outlets was collated against quantitative trends in word frequencies in monkeypox-related tweets (n = 255,363). Results found that coverage often framed monkeypox as a product of GBMSM hypersexuality, leading to potentially stigmatizing perceptions and the drastic increase in tweet content related to sexual activity. While greater attention to stigma was observed in coverage, blame attribution to populations, governments, and practices was one of the most common frames across all media sources. Heavy reporting of systemic barriers to vaccination, testing, or diagnosis serve as continuities from HIV/AIDS and COVID-19 epidemics, underscoring fears around a second plague and influencing public attitudes. Monkeypox conspiracy theories also proliferated heavily on Twitter, with a noticeable increase in conspiracy language over time. These findings can inform the social realities of monkeypox, an understudied dimension, of which an understanding is vital to implementing services that address all elements of the ongoing outbreak.
A phenomic modeling approach for using chlorophyll-a fluorescence-based measurements on coral photosymbionts: a step towards bio-optical bleaching prediction
Authors: Hoadley Kenneth D. , Lockridge Grant , McQuagge Audrey , Pahl K. Blue , Lowry Sean , Wong Sophie , Craig Zachary , Petrik Chelsea , Klepac Courtney , Muller Erinn M. 
Published: November 2022

AbstractWe test a newly developed instrument prototype which utilizes time-resolved chlorophyll-afluorescence techniques and fluctuating light to characterize Symbiodiniaceae functional traits across seven different coral species under cultivation as part of ongoing restoration efforts in the Florida Keys. While traditional chlorophyll-afluorescence techniques only provide a handful of algal biometrics, the system and protocol we have developed generates > 1000 dynamic measurements in a short (∼11 min) time frame. Resulting ‘high-content’ algal biometric data revealed distinct phenotypes, which broadly corresponded to clade-level Symbiodiniaceae designations determined using quantitative PCR. Next, algal biometric data fromAcropora cervicornis(10 genotypes) andA. palmata(5 genotypes) coral fragments was correlated with bleaching response metrics collected after a two month-long exposure to high temperature. A network analysis identified 1973 correlations (Spearman R > 0.5) between algal biometrics and various bleaching response metrics. These identified biomarkers of thermal stress were then utilized to train a predictive model, and when tested against the sameA. cervicornisandA. palmatacoral fragments, yielded high correlation (R = 0.92) with measured thermal response (reductions in absorbance by chlorophyll-a). When applied to all seven coral species, the model ranked fragments dominated byCladocopiumorBreviolumsymbionts as more bleaching susceptible than corals harboring thermally tolerant symbionts (Durusdinium). While direct testing of bleaching predictions on novel genotypes is still needed, our device and modeling pipeline may help broaden the scalability of existing approaches for determining thermal tolerance in reef corals. Our instrument prototype and analytical pipeline aligns with recent coral restoration assessments that call for the development of novel tools for improving scalability of coral restoration programs.
Protective Role of Podocytic IL-15 / STAT5 Pathway in Experimental Focal and Segmental Glomerulosclerosis
Authors: Niasse Aïssata , Louis Kevin , Lenoir Olivia , Schwarz Chloé , Xu Xiaoli , Couturier Aymeric , Dobosziewicz Hélène , Corchia Anthony , Placier Sandrine , Vandermeersch Sophie , Hennighausen Lothar , Frere Perrine , Galichon Pierre , Surin Brigitte , Ouchelouche Souhila , Louedec Liliane , Migeon Tiffany , Verpont Marie-Christine , Buob David , Xu-Dubois Yi-Chun , Francois Hélène , Rondeau Eric , Mesnard Laurent , Hadchouel Juliette , Luque Yosu 
Published: November 2022

AbstractDuring glomerular diseases, podocyte-specific pathways can modulate the intensity of the lesions and prognosis. The therapeutic targeting of these pathways could thus improve the management and prognosis of chronic kidney diseases. The Janus Kinase/ Signal Transducer and Activator of Transcription (JAK/STAT) pathway, classically described in immune cells, has been recently described in intrinsic kidney cells. Here, we show, for the first time, that STAT5 is activated in human podocytes in focal segmental glomerulosclerosis (FSGS). Additionally,Stat5podocyte-specific inactivation aggravates the functional and structural alterations in a mouse model of FSGS. This could be due, at least in part, to an inhibition of the autophagic flux. Finally, Interleukin 15 (IL-15), a classical activator of STAT5 in immune cells, increases STAT5 phosphorylation in human podocytes and its administration alleviates glomerular injuryin vivoby maintaining the autophagy flux in podocytes. In conclusion, activating podocytic STAT5 with commercially available IL-15 represents a new therapeutic avenue with the potential for FSGS.
Genetic bases of resistance to the ricehoja blancadisease deciphered by a QTL approach
Authors: Silva Alexander , Montoya María Elker , Quintero Constanza , Cuasquer Juan , Tohme Joe , Graterol Eduardo , Cruz Maribel , Lorieux Mathias 
Published: November 2022

AbstractRicehoja blanca(RHB) is one of the most serious diseases in rice growing areas in tropical Americas. Its causal agent isRice hoja blanca virus(RHBV), transmitted by the planthopperTagosodes orizicolusMüir. Genetic resistance is the most effective and environment-friendly way of controlling the disease. So far, only one major quantitative trait locus (QTL) ofOryza sativassp.japonicaorigin,qHBV4.1, that alters incidence of the virus symptoms in two Colombian cultivars has been reported. This resistance has already started to be broken, stressing the urgent need for diversifying the resistance sources. In the present study we performed a search for new QTLs ofO. sativa indicaorigin associated with RHB resistance. We used four F2:3segregating populations derived fromindicaresistant varieties crossed with a highly susceptiblejaponicapivot parent. Beside the standard method for measuring disease incidence, we developed a new method based on computer-assisted image processing to determine the affected leaf area (ALA) as a measure of symptom severity. Based on the disease severity and incidence scores in the F3families under greenhouse conditions, and SNP genotyping of the F2individuals, we identified four newindicaQTLs for RHB resistance on rice chromosomes 4, 6 and 11, namelyqHBV4.2WAS208,qHBV6.1PTB25,qHBV11.1andqHBV11.2. We also confirmed the wide-range action ofqHBV4.1. Among the five QTLs,qHBV4.1andqHBV11.1had the largest effects on incidence and severity, respectively. These results provide a more complete understanding of the genetic bases of RHBV resistance in the cultivated rice gene pool, and can be used to develop marker-aided breeding strategies to improve RHB resistance. The power of joint-and meta-analyses allowed precise mapping and candidate gene identification, providing the basis for positional cloning of the two major QTLsqHBV4.1andqHBV11.1.
Engineering circuits of human iPSC-derived neurons and rat primary glia
Authors: Girardin Sophie , Ihle Stephan J. , Menghini Arianna , Krubner Magdalena , Tognola Leonardo , Duru Jens , Ruff Tobias , Fruh Isabelle , Müller Matthias , Vörös János 
Published: November 2022

ABSTRACTNovelin vitroplatforms based on human neurons are needed to improve early drug testing and address the stalling drug discovery in neurological disorders. Topologically controlled circuits of human induced pluripotent stem cell (iPSC)-derived neurons have the potential to become such a testing system. In this work, we buildin vitroco-cultured circuits of human iPSC-derived neurons and rat primary glial cells using microfabricated polydimethylsiloxane (PDMS) structures on microelectrode arrays (MEAs). Such circuits are created by seeding either dissociated cells or pre-aggregated spheroids at different neuron-to-glia ratios. Furthermore, an antifouling coating is developed to prevent axonal overgrowth in undesired locations of the microstructure. We assess the electrophysiological properties of different types of circuits over more than 50 days, including their stimulation-induced neural activity. Finally, we demonstrate the effect of magnesium chloride on the electrical activity of our iPSC circuits as a proof-of-concept for screening of neuroactive compounds.
The septate junction component Bark beetle is required forDrosophilaintestinal barrier function and homeostasis
Authors: Hodge R. A. , Ghannam M. , Edmond E. , de la Torre F. , D’Alterio Cecilia , Kaya N.H. , Resnik-Docampo M. , Reiff T. , Jones D. L. 
Published: November 2022

AbstractAge-related loss of intestinal barrier function has been found across species, and the causes remain unknown. The intestinal epithelial barrier is maintained by tight junctions (TJs) in mammals and septate junctions (SJs) in insects. Specialized tricellular junctions (TCJs) are found at the nexus of three adjacent cell membranes, and we showed previously that aging results in mis-localization of the tricellular SJ (tSJ) component Gliotactin (Gli) in enterocytes (ECs) of theDrosophila melanogasterintestine. In embryonic epithelia, the tSJ protein Bark beetle (Bark) recruits Gli to tSJs, which prompted us to investigate Bark function in the intestine. Bark protein localization decreases at tSJs in aged flies. EC-specificbarkdepletion in young flies led to hallmarks of intestinal aging and shortened lifespan, whereas depletion ofbarkin progenitor cells reduced Notch activity, biasing differentiation toward the secretory lineage. Together, our data implicate Bark in EC maturation, maintenance of intestinal barrier integrity, and homeostasis. Understanding the assembly and maintenance of tSJs to ensure barrier integrity may lead to strategies to improve tissue integrity when function is compromised.
De novotranscriptome assembly and the effect of foreign RNA contamination
Authors: Alvarez Roberto Vera , Landsman David 
Published: November 2022

AbstractMultiple next-generation-sequencing (NGS)-based studies are enabled by the availability of a reference genome of the target organism. Unfortunately, several organisms remain unannotated due to the cost and complexity of generating a complete (or close to complete) reference genome. These unannotated organisms, however, can also be studied if ade novoreference transcriptome is assembled from whole transcriptome sequencing experiments. This technology is cost effective and widely used but is susceptible to off-target RNA contamination. In this manuscript, we present GTax, a taxonomy structured database of genomic sequences that can be used with BLAST to detect and remove foreign contamination in RNA sequencing samples before assembly. In addition, we investigate the effect of foreign RNA contamination on ade novotranscriptome assembly ofSolanum lycopersicum(tomato). Our study demonstrates that removing foreign contamination in sequencing samples reduces the number of assembled chimeric transcripts.
Remodeling of a tripartite substrate-binding motif in the HD domain provides the mechanism for activation of CRISPR-Cas10 DNases
Authors: Yu Zhenxiao , Wang Fang , She Qunxin 
Published: November 2022

AbstractType III CRISPR systems are endowed with multiple immune activities, including target RNA cleavage, RNA-activated DNA cleavage and the cOA synthesis among which molecular mechanism remains elusive for the DNase. Here, DNase of LdCsm is investigated. Structural modeling revealed two HD loop segments. Cas10 mutants carrying either loop truncation or amino acid substitution in the HD domain are generated and characterized. We found each HD loop contains a substrate-binding site essential for its immunity. In fact, the substrate binding requires a tripartite motif composed of the two loop binding sites and the HD catalytic site. We demonstrate cognate target RNA (CTR) remodels the tripartite motif to activate the LdCsm DNase in two consecutive events: (a) it reduces the flexibility of LD-L1 and facilitates the simultaneous substrate binding at both loops, (b) the bound substrate is then propelled into the catalytic site via LD-L2 oscillation, driving the substrate into the catalytic site for DNA cleavage.
A Scalable and Adaptive Ultra-high-density Fan-out Strategy for High-throughput Flexible Microelectrodes
Authors: Zhang Huiling , Wang Yang , Yang Xinze , Yuan Miao , Yang Xiaowei , Gui Qiang , Wang Yijun , Chen Hongda , Liu Ruping , Pei Weihua 
Published: November 2022

AbstractFlexible neural microelectrodes demonstrate higher compliance and better biocompatibility than rigid electrodes. They have multiple microfilaments can be freely distributed across different brain regions. However, high-density fan-out of high-throughput flexible microelectrodes remains a challenge since monolithic integration between electrodes and circuits is not currently available as it is for silicon electrodes. Here, we proposed a high-density fan-out strategy for high-throughput flexible electrodes. The flexible electrodes are partially overlapped on the printed circuit board (PCB). A modified wire bonding method is used to reduce the pads area on the PCB. Both the traces and pads on the PCB are optimized to minimize the back-end package. It is significantly reducing the connection area. In addition, the vertical rather than horizontal connection between the connector and the PCB further decrease the volume of the package. 1024 channel flexible electrodes are bonded to the high-density PCB within an area of 11.8×10mm2, and the success connection rate can reach 100%. The high-density fan-out strategy proposed in this paper can effectively reduce the volume of high-throughput flexible electrodes after packaging, which facilitates the miniaturization of in vivo multichannel recording devices and contributes to long-term recording.
Do women board members affect dividend policy and cash holdings? Evidence from ASEAN emerging economies
Authors: Nadia Linda Putri , Hanafi Mamduh M. 
Published: November 2022

Purpose
This study aims to examine the influence of board gender diversity on dividend policy and cash holdings in several emerging economies. This study also investigates the nonlinear impact of women on dividend policy and cash holdings and the differences between countries with one- and two-tier board systems.

Design/methodology/approach
The sample includes 103 firms listed in the Association of South East Asian Nations (ASEAN) countries of Indonesia, Malaysia, the Philippines and Thailand. The data represent all industries except the financial industry. The sample period is the 10 financial years from 2010 to 2019. This study analyzed unbalanced panel data with fixed effect specifications for baseline model analysis.

Findings
This study finds robust evidence indicating that women’s presence negatively influences dividends and positively influences cash holdings. The findings in the additional analysis are significant and show a nonlinear relationship, supporting the substitution hypothesis.

Practical implications
The findings of this paper certainly provided a valuable contribution as a useful empirical guide for policy decision-makers in developing countries, regulators and corporate decision-makers related to board gender diversity. Developed countries have implemented a minimum quota of women boards in the composition of the board of directors. However, there are still few developing countries that implement these policies. Women can reflect or show their values in corporate governance, such as being careful in making decisions and being conservative about risk. These guides policymakers in implementing a minimum quota of women in the composition of the board of directors.

Originality/value
This study contributes to the debate on the impact of gender diversity on dividends and cash holdings, especially in ASEAN emerging economies because there is a notable empirical gap relative to developed countries. Moreover, this study contributes to the necessary nuanced understanding of the substitution hypothesis in emerging economies. The results also support the explanation of critical mass theory to account for the nonlinear relationship between the number of women board members and dividends and cash holdings.
Influencer marketing effectiveness: the mechanisms that matter
Authors: Hugh Wilkie Dean Charles , Dolan Rebecca , Harrigan Paul , Gray Harriet 
Published: November 2022

Purpose
The continued evolution of influencer marketing has created a need to better understand influencer marketing effectiveness. With brands increasingly partnering with influencers, research is yet to provide an integrated perspective examining the critical role of both parties. This study aims to draw on the source credibility model and signaling theory to explain the mechanisms that matter in influencer marketing effectiveness.

Design/methodology/approach
The proposed model of influencer marketing effectiveness is analyzed using partial least squares with data from 281 followers of social media influencers.

Findings
The authors establish influencer characteristics of popularity and attractiveness as heuristic cues that inform judgments of influencer efficacy. Further, category involvement and altruistic motives for collaboration are shown to moderate followers’ reliance on these heuristic cues. Then, a sequential mediating effect demonstrates the critical roles of the influencer and partner brand in three desired outcomes: enhanced perception of brand authenticity, enhanced brand engagement and positive attitudes toward influencer posts.

Research limitations/implications
Future research should consider other heuristic cues that could inform influencer efficacy judgments and switch the focus toward the partner brand’s impact on such judgments.

Practical implications
A step-by-step visual framework is presented to help marketers and influencers translate these findings into key responsibilities for developing more effective and collaborative partnerships.

Originality/value
Besides presenting an integrated perspective, signaling theory provides an original lens for explaining influencer marketing effectiveness, addressing the need to expand the theoretical boundaries of influencer marketing research.