bluuebunny/crossref_metadata_2025 huggingface dataset:
LSM14B is essential for mitochondrial clustering in the oocyte meiosis
Authors: Wan Yanling , Yang Shuang , Li Tongtong , Cai Yuling , Zhang Mingyu , Huang Tao , Lv Yue , lu Gang , Li Jingxin , Sha Qianqian , Chen Zijiang , Liu Hongbin
Published: April 2023

As oocyte meiotic maturation, they undergo two successive meiotic M phases, notably lacking an intervening interphase phase. During these M phases, oocytes remain transcriptionally quiescent, and we now know that “translational repressed mRNAs” are stored in a structure called the mitochondria associated ribonucleoprotein domain (MARDO). LSM14B is one of the abundant proteins of MARDO, and is predicted to bind mRNA, but its function(s) remain elusive. Here, we demonstrate that LSM14B functions to promote MARDO assembly in mouse oocytes. We also found that LSM14B knockout female mice are infertile, and show that the knockout oocytes fail to enter meiosis II, instead entering an aberrant interphase-like stage. Finally, we show that the failure of oocyte maturation results from decreased expression of Cyclin B1. Our study has revealed that the RNA-binding protein LSM14B modulates MARDO assembly and is essential for oocyte meiotic maturation.
Unveiling dynamics behind Glioblastoma Multiforme single-cell data heterogeneity
Authors: Vieira Junior Marcos Guilherme , de Almeida Côrtes Adriano Maurício , Gonçalves Carneiro Flávia Raquel , Carels Nicolas , da Silva Fabrício Alves Barbosa
Published: April 2023

Glioblastoma Multiforme (GBM), a brain tumor distinguished for its aggressive nature, presents heterogeneity that stems from multifaceted mechanisms, such as genetic mutations, epigenetic modifications, genomic instability, and selective pressures. We reason that the aggressiveness of GBM enables even a limited dataset to serve as a representative sample within the domain of cancer attractors, allowing our sample to reflect a representative trajectory within the attractor’s domain. Utilizing single-cell RNA sequencing data, we proceed with a detailed analysis of GBM’s cellular landscape. Rooted in characteristics observed in stochastic systems, we considered factors like genomic instability to introduce a level of noise or unpredictability, thereby characterizing the cancer dynamics through stochastic fixed points. These fixed points, derived from centroids obtained through various clustering methods, were rigorously verified for method sensitivity. This methodological foundation, wherein sample and time averages are equivalent, assigns paramount interpretative value to the data cluster centroids, aiding both in parameter fitting and subsequent stochastic simulations. This scenario is supported by the compelling correlation found between centroids of experimental and simulated datasets. The use of stochastic modeling to compute the Waddington landscape enriched our analysis of GBM’s cellular heterogeneity and provided a visual framework for validating the centroids and standard deviations as accurate characterizations of potential cancer attractors. Specifically, this approach allowed us to assess the compatibility between data dispersion and the corresponding basin of attraction, thereby bridging molecular-level variations and systems-level dynamics. We also examined the stability and transitions between these attractors, revealing a potential interplay between subtypes and potentially uncovering factors that drive cancer recurrence and progression. By connecting molecular mechanisms related to cancer heterogeneity with statistical properties of gene expression dynamics we expect to set the stage for the development of potential diagnostic tools and pave the way for personalized therapeutic interventions.
Receptor-like cytoplasmic kinases belonging to different subfamilies mediate immune responses downstream of the Cf-4 resistance protein inNicotiana benthamiana
Authors: Huang Wen R.H. , Braam Ciska , Kretschmer Carola , Liu Huan , Ferik Filiz , van der Burgh Aranka M. , Pluis Max , Hagan Agnes Omabour , Villanueva Sergio Landeo , Wu Jinbin , Loosbroek Amber van , Wang Yulu , Seidl Michael F. , Stuttmann Johannes , Joosten Matthieu H.A.J.
Published: April 2023

Cell-surface receptors, which are either receptor-like proteins (RLPs) or receptor-like kinases (RLKs), form the first layer of the plant innate immune system. The LRR-RLKs SUPPRESSOR OF BIR1-1 (SOBIR1) and BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1 (BAK1) are the common regulatory co-receptors of LRR-RLPs. The tomato LRR-RLP Cf-4, which specifically detects the apoplastic effector Avr4 that is secreted by the pathogenic intercellular fungusCladosporium fulvum, requires SOBIR1 and BAK1 to mediate resistance against this fungus. It is proposed that phosphorylation events take place between the cytoplasmic kinase domains of SOBIR1 and BAK1, which lead to the initiation of various downstream signaling outputs such as the rapid phosphorylation of receptor-like cytoplasmic kinases (RLCKs), the accumulation of reactive oxygen species (ROS), the activation of mitogen-activated protein kinase (MAPK) cascades, and in some cases, the hypersensitive response (HR). Here, by performingin vitrophosphorylation assays, we show that SOBIR1 directly phosphorylates BAK1, whereas BAK1, in its turn, directly phosphorylates SOBIR1, which results in the full activation of the Cf-4-containing immune complex. We found that threonine 522, present in the activation segment of the SOBIR1 kinase domain ofNicotiana benthamiana(Nb), is required for its intrinsic kinase activity, and is essential for the Avr4/Cf-4/SOBIR1/BAK1-triggered ROS burst, MAPK activation and the HR. Tyrosine residue Y469 was found to be crucial for the Avr4/Cf-4- triggered activation of MAPKs and the HR, but not for ROS production andNbSOBIR1 intrinsic kinase activity. RLCKs are well-recognized to act as the initial cytoplasmic transducers, bridging cell-surface receptor complexes with their downstream signaling partners. By knocking out multiple genes belonging to different RLCK-VII subfamilies inN. benthamianaplants stably expressingCf-4, we show that members of the RLCK-VII subfamilies 6, 7 and 8 are required for the Avr4/Cf-4-triggered ROS production. Typically, the Avr4 protein triggers a biphasic ROS burst in leaf discs obtained fromN. benthamiana:Cf-4plants, in which the first transitory response is followed by a second, sustained ROS burst. Interestingly, the intensities of the first and second phase of the ROS burst are affected in different ways in the variousrlck-viiknock-out plants, indicating that there are different downstream ROS regulatory mechanisms, involving different RLCKs inN. benthamiana. Further studies show that members from RLCK-VII-6, 7 and 8 also play an essential role in regulating the ROS production triggered by flg22, chitin, and the nlp20/RLP23 and the pg13/RLP42 combinations.
Raynals, an online tool for the analysis of dynamic light scattering
Authors: Burastero Osvaldo , Draper-Barr George , Raynal Bertrand , Chevreuil Maelenn , England Patrick , Garcia-Alai Maria M.
Published: April 2023

Dynamic light scattering (DLS) is routinely employed to assess the homogeneity and size distribution profile of samples containing microscopic particles in suspension or solubilised polymers. In this work, we introduce Raynals, an user-friendly software for the analysis of single-angle DLS data that uses the Tikhonov-Phillips regularisation. Performance is evaluated on simulated and experimental data, generated by different DLS instruments, for several proteins and gold nanoparticles. DLS data can be easily misinterpreted and the simulation tools available in Raynals allow understanding of the limitations of the measurement and its resolution. It has been designed as a tool to address quality control of biological samples, during sample preparation and optimisation, and it helps in the detection of aggregates showing the influence of large particles. Last, Raynals provides flexibility in the way the data is presented, allows exporting publication-quality figures, it is free for academic use, and can be accessed online on the eSPC data analysis platform at spc.embl-hamburg.de.
The Calcium Transient Coupled to the L-Type Calcium Current Attenuates Action Potential Alternans
Authors: Warren Mark , Poelzing Steven
Published: April 2023

Background

Action potential (AP) alternans are linked to increased arrhythmogenesis. It is suggested that calcium (Ca2+) transient (CaT) alternans cause AP alternans through bi-directional coupling feedback mechanisms because CaT alternans can precede AP alternans and develop in AP alternans free conditions. However, the CaT is an emergent response to intracellular Ca2+handling, and the mechanisms linking AP and CaT alternans are still a topic of investigation. This study investigated the development of AP alternans in the absence of CaT.

Methods

AP (patch clamp) and intracellular Ca2+(Fluo-4 epifluorescence) were recorded simultaneously from isolated rabbit ventricle myocytes perfused with the intracellular Ca2+buffer BAPTA (10-20 mM) to abolish CaT and/or the L-type Ca2+ channel activator Bay K 8644 (25 nM).

Results

After a rate change, alternans were critically damped and stable, overdamped and ceased over seconds, underdamped with longer scale harmonics, or unstably underdamped progressing to 2:1 capture. Alternans in control cells were predominantly critically damped, but after CaT ablation with 10 or 20 mM BAPTA, exhibited respectively increased overdamping or increased underdamping. Alternans were easier to induce in CaT free cells as evidenced by a higher alternans threshold (ALT-TH: at least 7 pairs of alternating beats) relative to control cells. Alternans in Bay K 8644 treated cells were often underdamped, but the ALT-TH was similar to control. In CaT ablated cells, Bay K 8644 prolonged AP duration (APD) leading predominantly to unstably underdamped alternans.

Conclusions

AP alternans occur more readily in the absence of CaT suggesting that the CaT dampens the development of AP alternans. The data further demonstrate that agonizing the L-type calcium current without the negative feedback of the CaT leads to unstable alternans. This negative feedback mechanism may be important for understanding treatments aimed at reducing CaT or its dynamic response to prevent arrhythmias.
Endothelial structure contributes to heterogeneity in brain capillary diameter
Authors: Sargent Sheridan M. , Bonney Stephanie K. , Li Yuandong , Stamenkovic Stefan , Takeno Marc , Coelho-Santos Vanessa , Shih Andy Y.
Published: April 2023

The high metabolic demand of brain tissue is supported by a constant supply of blood through dense microvascular networks. Capillaries are the smallest class of vessels and vary in diameter between ∼2 to 5 μm in the brain. This diameter range plays a significant role in the optimization of blood flow resistance, blood cell distribution, and oxygen extraction. The control of capillary diameter has largely been ascribed to pericyte contractility, but it remains unclear if endothelial wall architecture also contributes to capillary diameter heterogeneity. Here, we use public, large-scale volume electron microscopy data from mouse cortex (MICrONS Explorer, Cortical MM^3) to examine how endothelial cell number, endothelial cell thickness, and pericyte coverage relates to microvascular lumen size. We find that transitional vessels near the penetrating arteriole and ascending venule are composed of 2 to 5 interlocked endothelial cells, while the numerous capillary segments intervening these zones are composed of either 1 or 2 endothelial cells, with roughly equal proportions. The luminal area and diameter is on average slightly larger with capillary segments composed of 2 interlocked endothelial cells versus 1 endothelial cell. However, this difference is insufficient to explain the full range of capillary diameters seen in vivo. This suggests that both endothelial structure and other influences, such as pericyte tone, contribute to the basal diameter and optimized perfusion of brain capillaries.
Nitric oxide suppresses cilia activity in ctenophores
Authors: Norekian Tigran P. , Moroz Leonid L.
Published: April 2023

Cilia are the major effectors in Ctenophores, but very little is known about their transmitter control and integration. Here, we present a simple protocol to monitor and quantify cilia activity in semi-intact preparations and provide evidence for polysynaptic control of cilia coordination in ctenophores. Next, we screen the effects of several classical bilaterian neurotransmitters (acetylcholine, dopamine, L-DOPA, serotonin, octopamine, histamine, gamma-aminobutyric acid (GABA), L-aspartate, L-glutamate, glycine), neuropeptides (FMRFamide), and nitric oxide (NO) on cilia beating inPleurobrachia bacheiandBolinopsis infundibulum. Only NO inhibited cilia beating, whereas other tested transmitters were ineffective. These findings further suggest that ctenophore-specific neuropeptides could be major candidate signaling molecules controlling cilia activity in representatives of this early-branching metazoan lineage.
Temperature and turbidity interact synergistically to alter anti-predator behaviour in the Trinidadian guppy
Authors: Zanghi Costanza , Munro Milly , Ioannou Christos C
Published: April 2023

Due to climate change, freshwater habitats are facing increasing temperatures and more extreme weather that disrupts water flow. Together with eutrophication and sedimentation from farming, quarrying and urbanisation, freshwaters are becoming more turbid as well as warmer. Predators and prey need to be able to respond to one another adaptively, yet how changes in temperature and turbidity interact to affect predator-prey behaviour remains unexplored. Using a fully factorial design, we tested the combined effects of increased temperature and turbidity on the behaviour of guppy shoals (Poecilia reticulata) in the presence of one of their natural cichlid predators, the blue acara (Andinoacara pulcher). Our results demonstrate that the prey and predator were in closest proximity in warmer, turbid water, with an interaction between these stressors showing a greater than additive effect. There was also an interaction between the stressors in the inter-individual distances between the prey, where shoal cohesion increased with temperature in clear water, but decreased when temperature increased in turbid water. The closer proximity to predators and reduction in shoaling in turbid, warmer water may increase the risk of predation for the guppy, suggesting that the combined effects of elevated temperature and turbidity may favour predators rather than prey.
Task-relevant object shape properties act as poor but viable cues for the attribution of motor errors to external objects
Authors: Modchalingam Shanaathanan , Ayala Maria N. , Henriques Denise Y. P.
Published: April 2023

When a context change is detected during motor learning, motor memories - internal models for executing movements within some context - may be created or existing motor memories may be activated and modified. Assigning credit to plausible causes of errors can allow for fast retrieval and activation of a motor memory, or a combination of motor memories, when the presence of such causes is detected. Features of the movement-context intrinsic to the movement dynamics, such as posture of the end effector, are often effective cues for detecting context change whereas features extrinsic to the movement dynamics, such as the colour of an object being moved, are often not. These extrinsic cues are typically not relevant to the motor task at hand and can be safely ignored by the motor system. We conducted two experiments testing if extrinsic but task-relevant object-shape cues during an object- transport task can act as viable contextual cues for error assignment to the object, and the creation of new, object-shape-associated motor memories. In the first experiment we find that despite the object- shape cues, errors are primarily attributed to the hand transporting the object. In a second experiment, we find that although participants can execute differing movements cued by the object shape in a dual adaptation task, they primarily use explicit strategies to do so.
Discovery of GS-5245 (Obeldesivir), an Oral Prodrug of Nucleoside GS-441524 that Exhibits Antiviral Efficacy in SARS-CoV-2 Infected African Green Monkeys
Authors: Mackman Richard L. , Kalla Rao , Babusis Darius , Pitts Jared , Barrett Kimberly T. , Chun Kwon , Du Pont Venice , Rodriguez Lauren , Moshiri Jasmine , Xu Yili , Lee Michael , Lee Gary , Bleier Blake , Nguyen Anh-Quan , O’Keefe B. Michael , Ambrosi Andrea , Cook Meredith , Yu Joy , Dempah Elodie , Bunyan Elaine , Riola Nicholas C. , Lu Xianghan , Liu Renmeng , Davie Ashley , Hsiang Tien-Ying , Gale Michael , Niedziela-Majka Anita , Feng Joy Y. , Hedskog Charlotte , Bilello John P. , Subramanian Raju , Cihlar Tomas
Published: April 2023

Remdesivir1is an amidate prodrug that releases the monophosphate of nucleoside GS-441524 (2) into lung cells thereby forming the bioactive triphosphate2-NTP.2-NTP, an analog of ATP, inhibits the SARS-CoV-2 RNA-dependent RNA polymerase replication and transcription of viral RNA. Strong clinical results for1have prompted interest in oral approaches to generate2-NTP. Here we describe the discovery of a 5’-isobutyryl ester prodrug of2 (GS-5245, Obeldesivir,3) that has low cellular cytotoxicity and three to seven-fold improved oral delivery of2in monkeys. Prodrug3is cleaved pre-systemically to provide high systemic exposures of2that overcome its less efficient metabolism to2-NTPleading to strong SARS-CoV-2 antiviral efficacy in an African green monkey infection model. Exposure-based SARS-CoV-2 efficacy relationships resulted in an estimated clinical dose of 350-400 mg twice-daily. Importantly, all SARS-CoV-2 variants remain susceptible to2which supports development of3as a promising COVID-19 treatment.
A von Hámos spectrometer for diamond anvil cell experiments at the High Energy Density Instrument of the European X-ray Free-Electron Laser
Authors: Kaa Johannes M. , Konôpková Zuzana , Preston Thomas R. , Cerantola Valerio , Sahle Christoph J. , Förster Mirko , Albers Christian , Libon Lélia , Sakrowski Robin , Wollenweber Lennart , Buakor Khachiwan , Dwivedi Anand , Mishchenko Mikhail , Nakatsutsumi Motoaki , Plückthun Christian , Schwinkendorf Jan-Patrick , Spiekermann Georg , Thiering Nicola , Petitgirard Sylvain , Tolan Metin , Wilke Max , Zastrau Ulf , Appel Karen , Sternemann Christian
Published: April 2023

A von Hámos spectrometer has been implemented in the vacuum interaction chamber 1 of the High Energy Density instrument at the European X-ray Free-Electron Laser facility. This setup is dedicated, but not necessarily limited, to X-ray spectroscopy measurements of samples exposed to static compression using a diamond anvil cell. Si and Ge analyser crystals with different orientations are available for this setup, covering the hard X-ray energy regime with a sub-eV energy resolution. The setup was commissioned by measuring various emission spectra of free-standing metal foils and oxide samples in the energy range between 6 and 11 keV as well as low momentum-transfer inelastic X-ray scattering from a diamond sample. Its capabilities to study samples at extreme pressures and temperatures have been demonstrated by measuring the electronic spin-state changes of (Fe0.5Mg0.5)O, contained in a diamond anvil cell and pressurized to 100 GPa, via monitoring the Fe Kβ fluorescence with a set of four Si(531) analyser crystals at close to melting temperatures. The efficiency and signal-to-noise ratio of the spectrometer enables valence-to-core emission signals to be studied and single pulse X-ray emission from samples in a diamond anvil cell to be measured, opening new perspectives for spectroscopy in extreme conditions research.
Soft X-ray spectro-ptychography of boron nitride nanobamboos, carbon nanotubes and permalloy nanorods
Authors: Vijayakumar Jaianth , Yuan Hao , Mille Nicolas , Stanescu Stefan , Swaraj Sufal , Favre-Nicolin Vincent , Najafi Ebrahim , Hitchcock Adam P. , Belkhou Rachid
Published: April 2023

Spectro-ptychography offers improved spatial resolution and additional phase spectral information relative to that provided by scanning transmission X-ray microscopes. However, carrying out ptychography at the lower range of soft X-ray energies (e.g. below 200 eV to 600 eV) on samples with weakly scattering signals can be challenging. Here, results of soft X-ray spectro-ptychography at energies as low as 180 eV are presented, and its capabilities are illustrated with results from permalloy nanorods (Fe 2p), carbon nanotubes (C 1s) and boron nitride bamboo nanostructures (B 1s, N 1s). The optimization of low-energy X-ray spectro-ptychography is described and important challenges associated with measurement approaches, reconstruction algorithms and their effects on the reconstructed images are discussed. A method for evaluating the increase in radiation dose when using overlapping sampling is presented.
The emergence of digital learning in higher education: a lesson from the COVID-19 pandemic
Authors: Al Masud Abdullah , Hossain Md. Alamgir , Biswas Sukanta , Ruma Afroza Parvin , Rahman Kazi Shoyebur , Tagore Saurabh
Published: April 2023

Purpose

The coronavirus disease 2019 (COVID-19) has a significant influence on many aspects of life, including education. As a result, the education system in emerging nations such as Bangladesh needs a rapid transition from conventional to technology-based distance learning. This study looks at the current state of higher education and how well online courses that use technology work.

Design/methodology/approach

This study used a structural equation model (SEM) to analyze the 392 student records taken from several universities in Bangladesh.

Findings

This research showed that students are more likely to use a digital higher education system if faculty are willing, students are eager and the economy is stable. Students who have had a bad experience with digital learning should know that a virtual evaluation system is needed. The willingness of students to use technology also plays a significant role in whether or not the students will take online classes. The research shows that combining traditional classroom and online learning is the best way to create a long-term learning system.

Originality/value

The model suggested in this study has a big effect, and Bangladesh policymakers should consider this model when planning a new kind of technology-based education.
Ownership structure and firm sustainable investments: evidence from emerging markets
Authors: Qasem Ameen , Mohammed Abdulalem , Battisti Enrico , Ferraris Alberto
Published: April 2023

Purpose

The aim of this study is to examine the ownership impact on firm sustainable investments (FSIs). In particular, this research examines the link between institutional investor ownership (IIO), managerial ownership (MOWN) and FSIs in the tourism industry in Malaysia.

Design/methodology/approach

This study uses a data set of 346 firm-year observations from 2008 to 2020 and applies feasible generalized least squares (FGLS) regression analysis. The study sample is based on tourism firms listed on Bursa Malaysia (the Malaysian Stock Exchange).

Findings

There is a significant positive association between IIO and FSIs. When IIO is classified into foreign (FIIO) and local (LIIO), this significant association is mainly driven by FIIO. In addition, there is a significant, positive association between managerial ownership (MOWN) and firm sustainable investments (FSIs). These findings imply that firm ownership has an influence on FSIs in the tourism industry.

Originality/value

This is the first attempt to consider IIO and MOWN simultaneously in a single model estimation. The findings contribute to emerging capital markets where the involvement of ownership concentration in the governance of publicly listed firms is a common practice.
Dialect connectedness and tunneling: evidence from China
Authors: Song Chen
Published: April 2023

Purpose

This study aims to examine the effects of dialect connectedness between the chairman and the chief executive officer (CEO) (DCCC) on the tunneling activities of controlling shareholders.

Design/methodology/approach

This study uses abnormal related-party transactions (ARPT) as a proxy for tunneling activities and traces dialects of chairmen and CEOs based on the respective birthplace information. Baseline results are examined using a fixed-effects model. The results remain robust when using the instrumental variable approach, propensity score matching (PSM) technique, changing the measurement of tunneling and Heckman two-step selection model.

Findings

The results show that DCCC reduces tunneling activities. This negative association is more pronounced for non-state-owned enterprises and firms whose chairmen and CEOs work in the respective hometowns. DCCC restrains tunneling activities through mechanisms by establishing an informal supervisory effect on CEOs because the CEOs fear reputational damage and strengthening cooperation between chairmen and CEOs. Further analyses suggest that this negative association is more significant when chairmen and CEOs are non-controlling shareholders, but the association is weakened during the coronavirus disease 2019 (COVID-19) crisis.

Originality/value

As dialect is a carrier of culture, this study's results imply that cultural proximity can replace formal mechanisms to enhance corporate governance.
Incidence and outcomes of uterine rupture in women with unscarred, preterm or prelabour uteri: data from the international network of obstetric survey systems
Authors: Vandenberghe Griet , Vierin Anne , Bloemenkamp Kitty , Berlage Sylvia , Colmorn Lotte , Deneux‐Tharaux Catherine , Donati Serena , Gissler Mika , Knight M. , Langhoff‐Roos Jens , Lindqvist Pelle G. , Maier Barbara , van Roosmalen Jos , Zwart Joost , Roelens Kristien ,   INOSS (the International Network of Obstetrics Survey Systems)
Published: April 2023

Objective

Analysis of atypical cases of uterine rupture, namely, uterine rupture occurring in unscarred, preterm or prelabour uteri.

Design

Descriptive multi‐country population‐based study.

Setting

Ten high‐income countries within the International Network of Obstetric Survey Systems.

Population

Women with unscarred, preterm or prelabour ruptured uteri.

Methods

We merged prospectively collected individual patient data in ten population‐based studies of women with complete uterine rupture. In this analysis, we focused on women with uterine rupture of unscarred, preterm or prelabour ruptured uteri.

Main Outcome Measures

Incidence, women's characteristics, presentation and maternal and perinatal outcome.

Results

We identified 357 atypical uterine ruptures in 3 064 923 women giving birth. Estimated incidence was 0.2 per 10 000 women (95% CI 0.2–0.3) in the unscarred uteri, 0.5 (95% CI 0.5–0.6) in the preterm uteri, 0.7 (95% CI 0.6–0.8) in the prelabour uteri, and 0.5 (95% CI 0.4–0.5) in the group with no previous caesarean. Atypical uterine rupture resulted in peripartum hysterectomy in 66 women (18.5%, 95% CI 14.3–23.5%), three maternal deaths (0.84%, 95% CI 0.17–2.5%) and perinatal death in 62 infants (19.7%, 95% CI 15.1–25.3%).

Conclusions

Uterine rupture in preterm, prelabour or unscarred uteri are extremely uncommon but were associated with severe maternal and perinatal outcome. We found a mix of risk factors in unscarred uteri, most preterm uterine ruptures occurred in caesarean‐scarred uteri and most prelabour uterine ruptures in ‘otherwise’ scarred uteri. This study may increase awareness among clinicians and raise suspicion of the possibility of uterine rupture under these less expected conditions.
Analysis of the impact of peritoneal dialysis catheter tail‐end design on catheter‐related complications
Authors: Zou Hong‐chang , Gao Ming‐ming , Chen Yan‐xia , Xu Cheng‐yun , Tu Wei‐ping , Qin Xiao‐hua
Published: April 2023

Objective

Evaluate the impact of peritoneal dialysis catheter (PDC) tail‐end design variations on PDC‐related complications.

Method

Effective data were extracted from databases. The literature was evaluated according to the Cochrane Handbook for Systematic Reviews of Interventions, and a meta‐analysis was conducted.

Results

Analysis revealed that the straight‐tailed catheter was superior to the curled‐tailed catheter in minimizing catheter displacement and complication‐induced catheter removal (RR = 1.73, 95%CI:1.18–2.53, p = 0.005). In terms of complication‐induced PDC removal, the straight‐tailed catheter was superior to the curled‐tailed catheter (RR = 1.55, 95%CI: 1.15–2.08, p = 0.004).

Conclusion

Curled‐tail design of the catheter increased the risk of catheter displacement and complication‐induced catheter removal, whereas the straight‐tailed catheter was superior to the curled‐tailed catheter in terms of reducing catheter displacement and complication‐induced catheter removal. However, the analysis and comparison of factors such as leakage, peritonitis, exit‐site infection, and tunnel infection did not reveal a statistically significant difference between the two designs.
Evidence for an alcohol‐related “harm paradox” in individuals with internalizing disorders: Test and replication in two independent community samples
Authors: Anker Justin J. , Thuras Paul , Shuai Ruichong , Hogarth Lee , Kushner Matt G.
Published: April 2023

Background

Internalizing (anxiety and mood) disorders (INTD) commonly co‐occur (are “comorbid”) with alcohol use disorder (AUD). The literature suggests that excessive alcohol use aimed at coping with INTD symptoms is, at best, a partial explanation for the high comorbidity rates observed. We hypothesized that individuals with INTD experience greater susceptibility to developing AUD symptoms due to the partially shared neurobiological dysfunctions underlying both conditions. We probe this hypothesis by testing the prediction that, after accounting for the volume of alcohol intake, individuals with INTD experience higher levels of alcohol‐related symptoms.

Methods

Data from the National Epidemiological Survey on Alcohol‐Related Conditions (NESARC) Wave 3 were used for the primary analyses, and NESARC Wave 1 data were used for independent replication analyses. Individuals who reported any alcohol use in the prior year were categorized as: (1) never having had an INTD diagnosis (“INTD‐Never”); (2) having a remitted INTD diagnosis only (“INTD‐Remitted”); or (3) having current INTD diagnosis (“INTD‐Current”). Between‐group contrasts of alcohol‐related symptoms controlled for total alcohol intake (past year), drinking pattern (e.g., binging) and variables previously shown to mark exaggerated AUD symptoms relative to drinking amount (e.g., SES, gender, and family history).

Results

With all covariates in the model, individuals in the INTD‐Current group and the INTD‐Remitted group reported significantly greater alcohol‐related symptoms than those in the INTD‐Never group but did not themselves differ in level of alcohol‐related symptoms. These results were replicated in the NESARC 1 dataset.

Conclusions

Individuals with INTD experience more alcohol‐related symptoms than those who drink at the same level. While considering other explanations, we argue that this “harm paradox” is best explained by the view that INTD confers a neurobiologically mediated susceptibility to the development of AUD symptoms.
Non‐GAAP earnings and executive compensation: An experiment
Authors: Brosnan Mark , Duncan Keith , Hasso Tim , Hollindale Janice
Published: April 2023

Literature suggests investors react to the presence, presentation and prominence of non‐GAAP earnings disclosures. We extend this literature by considering the purpose of non‐GAAP earnings disclosures and their effect on investors' judgements and decisions. We find when non‐GAAP earnings are used to determine executive compensation, investors assign a higher evaluation of financial performance and invest more capital. Consistent with attribution theory, our mediation model finds that using non‐GAAP earnings to remunerate executives strengthens the informative perception of non‐GAAP earnings disclosures, influencing their evaluation and investment decision. Contrary to prior literature, we find investors intentionally rely on non‐GAAP earnings in decision‐making.
Association between childhood maltreatment and social functioning in individuals with affective disorders: A systematic review and meta‐analysis
Authors: Fares‐Otero Natalia E. , De Prisco Michele , Oliva Vincenzo , Radua Joaquim , Halligan Sarah L. , Vieta Eduard , Martinez‐Aran Anabel
Published: April 2023

Objective

Childhood maltreatment has been linked to impairments in social functioning and social cognition in adults with affective disorders. However, conclusions have been limited by inconsistent findings across different maltreatment subtypes and social domains. We conducted a systematic review and meta‐analysis to quantify associations between childhood maltreatment (overall and subtypes ‐ physical, emotional and/or sexual abuse, and/or physical and/or emotional neglect) and different domains of social functioning and social cognition in adults with affective disorders (bipolar disorder or major depressive disorder). We also examined effect moderators and mediators of these associations.

Methods

A systematic search was performed on 12.12.2022 which identified 29 studies included in qualitative synthesis (n = 3022 individuals with affective disorders), of which 27 (n = 2957) were pooled in meta‐analyses. Across studies, five social functioning and five social cognition domains were examined, of which four domains of social functioning and two domains of social cognition had sufficient data for meta‐analysis (PROSPERO CRD42022288976).

Results

Social functioning: childhood maltreatment was associated with lower global social functioning (r = −0.11 to −0.20), poorer interpersonal relations (r = −0.18 to −0.33), and with aggressive behaviour (r = 0.20–0.29) but was unrelated to vocational functioning. Emotional abuse and emotional neglect showed the largest magnitudes of effect. Social cognition: there was no meta‐analytic evidence of associations between maltreatment and social cognition domains. Exploratory moderation analyses did not identify any consistent moderators. Narrative synthesis identified attachment style as possible moderator, and sensory patterns, anxiety, and depressive symptoms as possible mediators between childhood maltreatment and social outcomes. Overall, the available evidence was limited, particularly in relation to social cognition.

Conclusions

Adults with affective disorders are at risk of social functioning difficulties after childhood maltreatment exposure, an effect observed across multiple maltreatment subtypes, social functioning domains, and diagnoses. Addressing social functioning problems may benefit maltreated adults with both bipolar disorder and major depressive disorder.
An uncommon case of Wellen's syndrome
Authors: Hu Haoran , Wang Chunfang , Gao Ning , Zhang Xiaofei , Wang Jian
Published: April 2023

Wellen's syndrome, a STEMI equivalent, is associated with severe stenosis of the proximal left anterior descending (LAD) in a patient with chest pain who needs emergency coronary angiography with the possibility of intervention. Due to only T wave changes in the electrocardiograph (ECG), Wellen's syndrome was easily ignored. Moreover, it may progress to acute myocardial infarction or even cardiac arrest. Therefore, clinicians should improve their understanding of this ECG pattern and appropriately dilate the coronary angiography indication. In addition, more dangerous narrowing of a coronary artery, as in our case, the left main artery stenosis, should also be considered.
Single cell G‐protein coupled receptor profiling of activated kidney fibroblasts expressing transcription factor 21
Authors: Kaur Harmandeep , Yerra Veera Ganesh , Batchu Sri Nagarjun , Tran Duc Tin , Kabir M. D. Golam , Liu Youan , Advani Suzanne L. , Sedrak Phelopater , Geldenhuys Laurette , Tennankore Karthik K. , Poyah Penelope , Siddiqi Ferhan S. , Advani Andrew
Published: April 2023

Background and Purpose

Activated fibroblasts deposit fibrotic matrix in chronic kidney disease (CKD) and G‐protein coupled receptors (GPCRs) are the most druggable therapeutic targets. Here, we set out to establish a transcriptional profile that identifies activated kidney fibroblasts and the GPCRs that they express.

Experimental Approach

RNA sequencing and single cell qRT‐PCR were performed on mouse kidneys after unilateral ureteral obstruction (UUO). Candidate expression was evaluated in mice with UUO or diabetes or injected with adriamycin or folic acid. Intervention studies were conducted in mice with diabetes or UUO. Correlative histology was performed in human kidney tissue.

Key Results

Transcription factor 21 (Tcf21)+ cells that expressed 2 or 3 of Postn, Acta2 and Pdgfra were highly enriched for fibrogenic genes and were defined as activated kidney fibroblasts. Tcf21+ α‐smooth muscle actin (α‐SMA)+ interstitial cells accumulated in kidneys of mice with UUO or diabetes or injected with adriamycin or folic acid, whereas renin‐angiotensin system blockade attenuated increases in Tcf21 in diabetic mice. Fifty‐six GPCRs were up‐regulated in single Tcf21+ kidney fibroblasts, the most up‐regulated being Adgra2 and S1pr3. Adenosine receptors, Adora2a/2b, were up‐regulated in Tcf21+ fibroblasts and the adenosine receptor antagonist, caffeine decreased Tcf21 upregulation and kidney fibrosis in UUO mice. TCF21, ADGRA2, S1PR3 and ADORA2A/2B were each detectable in α‐SMA+ interstitial cells in human kidney samples.

Conclusion and Implications

Tcf21 is a marker of kidney fibroblasts that are enriched for fibrogenic genes in CKD. Further analysis of the GPCRs expressed by these cells may identify new targets for treating CKD.

LINKED ARTICLES

This article is part of a themed issue on Translational Advances in Fibrosis as a Therapeutic Target. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.22/issuetoc
Family play, reading, and other stimulation and early childhood development in five low‐and‐middle‐income countries
Authors: Cuartas Jorge , McCoy Dana , Sánchez Juliana , Behrman Jere , Cappa Claudia , Donati Georgina , Heymann Jody , Lu Chunling , Raikes Abbie , Rao Nirmala , Richter Linda , Stein Alan , Yoshikawa Hirokazu
Published: April 2023

This paper used longitudinal data from five studies conducted in Bangladesh, Bhutan, Cambodia, Ethiopia, and Rwanda to examine the links between family stimulation and early childhood development outcomes (N = 4904; Mage = 51.5; 49% girls). Results from random‐effects and more conservative child‐fixed effects models indicate that across these studies, family stimulation, measured by caregivers’ engagement in nine activities (e.g., reading, playing, singing), predicted increments in children's early numeracy, literacy, social‐emotional, motor, and executive function skills (standardized associations ranged from 0.05 to 0.11 SD). Study‐specific models showed variability in the estimates, with null associations in two out of the five studies. These findings indicate the need for additional research on culturally specific ways in which caregivers may support early development and highlight the importance of promoting family stimulation to catalyze positive developmental trajectories in global contexts.

Research Highlights

Research on the links between family stimulation and early childhood development in low‐and‐middle‐income countries (LMICs) is limited.

We used longitudinal data from studies conducted in five LMICs to examine the links between family stimulation and early childhood development outcomes.

Results suggest that family stimulation predicted increments in children's numeracy, literacy, social‐emotional, motor, and executive function skills.

We found variability in the observed estimates, with null associations in two out of the five studies, suggesting the need for additional research in LMICs.
Information dissemination during public health emergencies: analysing the international flow of COVID‐19‐related news
Authors: Guo Hua , Zhang Jiandong , Feng Shihui , Zhou Yanli , Fan Anrong , Wang Minhong
Published: April 2023

A large‐scale exchange of information between media across national borders is frequently observed when a worldwide public health emergency occurs. This study investigated the global news citation network in the early stage of the COVID‐19 pandemic by analysing the network structure at different levels to identify important nodes and the relationships among news organisations. The results show that COVID‐19‐related international news flow had a complex and unequal pattern, with a few countries and media outlets occupying a prominent place in the network and three media groups played key but different roles in disseminating the news. It was jointly influenced by national traits, the relatedness between countries, and the pandemic emergency with public health risks. From a global perspective, the media of the United States, mainland China, and the United Kingdom played the most important parts in collaboration within the world media system in the early stage of the COVID‐19 pandemic.
Epileptic spasms in CDKL5 deficiency disorder: Delayed treatment and poor response to first‐line therapies
Authors: Olson Heather E. , Demarest Scott , Pestana‐Knight Elia , Moosa Ahsan N. , Zhang Xiaoming , Pérez‐Pérez José R. , Weisenberg Judy , O’Connor Prange Erin , Marsh Eric D. , Rajaraman Rajsekar R. , Suter Bernhard , Katyayan Akshat , Haviland Isabel , Daniels Carolyn , Zhang Bo , Greene Caitlin , DeLeo Michelle , Swanson Lindsay , Love‐Nichols Jamie , Benke Timothy , Harini Chellamani , Poduri Annapurna
Published: April 2023

Objective

We aimed to assess the treatment response of infantile‐onset epileptic spasms (ES) in CDKL5 deficiency disorder (CDD) vs other etiologies.

Methods

We evaluated patients with ES from the CDKL5 Centers of Excellence and the National Infantile Spasms Consortium (NISC), with onset from 2 months to 2 years, treated with adrenocorticotropic hormone (ACTH), oral corticosteroids, vigabatrin, and/or the ketogenic diet. We excluded children with tuberous sclerosis complex, trisomy 21, or unknown etiology with normal development because of known differential treatment responses. We compared the two cohorts for time to treatment and ES remission at 14 days and 3 months.

Results

We evaluated 59 individuals with CDD (79% female, median ES onset 6 months) and 232 individuals from the NISC database (46% female, median onset 7 months). In the CDD cohort, seizures prior to ES were common (88%), and hypsarrhythmia and its variants were present at ES onset in 34%. Initial treatment with ACTH, oral corticosteroids, or vigabatrin started within 1 month of ES onset in 27 of 59 (46%) of the CDD cohort and 182 of 232 (78%) of the NISC cohort (p < .0001). Fourteen‐day clinical remission of ES was lower for the CDD group (26%, 7/27) than for the NISC cohort (58%, 106/182, p = .0002). Sustained ES remission at 3 months occurred in 1 of 27 (4%) of CDD patients vs 96 of 182 (53%) of the NISC cohort (p < .0001). Comparable results were observed with longer lead time (≥1 month) or prior treatment. Ketogenic diet, used within 3 months of ES onset, resulted in ES remission at 1 month, sustained at 3 months, in at least 2 of 13 (15%) individuals with CDD.

Significance

Compared to the broad group of infants with ES, children with ES in the setting of CDD often experience longer lead time to treatment and respond poorly to standard treatments. Development of alternative treatments for ES in CDD is needed.
Project ABC: Unanticipated affinities and affect in hospital health care
Authors: Conceição Ana , Major Maria , Clegg Stewart
Published: April 2023

In this paper, we present an analysis of how activity‐based costing (ABC) was included among austerity policy prescriptions within the healthcare sector. Relying on the proposition that an increasing quality of outcomes is achievable simultaneously with a reduction in costs, ABC straddled tensions between the logics of care and business for clinicians but not for administrators. We draw on case study research and use institutional logics and related approaches to analyze how the introduction of ABC became a device that improved communication by clinicians with administrators. When actors’ interests and motivations were aligned, ABC was able to offer professional clinicians value in the hospital in question. The study demonstrates how and why competing logics can coexist where there is ability to affect decision‐making.
Does fishing dismantle fish culture and ecosystem structure? Questions about the implications of social learning among fish and fishers
Authors: Wilson James A. , Giske Jarl
Published: April 2023

Scientific awareness of social learning, especially among vertebrates, has expanded rapidly in recent decades. That literature suggests that social learning may be a second adaptive mechanism that interacts with and refines genetic adaptation. For an individual fish, learning from others reduces the costs of acquiring experience‐based behaviours and minimizes the hazards that arise from imperfect knowledge of local regularities. For a group of fish, social learning facilitates the evolution of time and place behaviours that work in its locality. It spreads those behaviours within the group and to subsequent generations. Thus, social learning enables persistent adaptation at a finer scale than might be possible through genetic processes alone. Strong evidence of genetic differentiation at less than a panmictic scale and persistent local depletions suggests regular, fine‐scale system structure. Social learning may play an important role in creating and maintaining this finer‐scale structure. Fishers' learned adaptations to the market and natural system usually lead them to target larger/older fish and fish aggregations at familiar times and places. However, older fish are likely to be the principal repository of the time‐and‐place experience required for local growth, survival, and reproduction, while social aggregations are important schools in which younger fish acquire the experience of older fish. Consequently, if adaptation through social learning is important among fish, there is reason to be concerned that heavy fishing of social learners reduces their abundance, as usually assumed, and impairs the inheritance of the socially learned experience required for persistent local adaptation.
Lineage tracing identifies in vitro microglia‐to‐neuron conversion by NeuroD1 expression
Authors: Irie Takashi , Matsuda‐Ito Kanae , Matsuda Taito , Masuda Takahiro , Prinz Marco , Isobe Noriko , Nakashima Kinichi
Published: April 2023

Neuronal regeneration to replenish lost neurons after injury is critical for brain repair. Microglia, brain‐resident macrophages that have the propensity to accumulate at the site of injury, can be a potential source for replenishing lost neurons through fate conversion into neurons, induced by forced expression of neuronal lineage‐specific transcription factors. However, it has not been strictly demonstrated that microglia, rather than central nervous system‐associated macrophages, such as meningeal macrophages, convert into neurons. Here, we show that NeuroD1‐transduced microglia can be successfully converted into neurons in vitro using lineage‐mapping strategies. We also found that a chemical cocktail treatment further promoted NeuroD1‐induced microglia‐to‐neuron conversion. NeuroD1 with loss‐of‐function mutation, on the other hand, failed to induce the neuronal conversion. Our results indicate that microglia are indeed reprogrammed into neurons by NeuroD1 with neurogenic transcriptional activity.