bluuebunny/crossref_metadata_2025 huggingface dataset:
Topographic and Structural Anatomy of the Suspensory Ligament of the Penis: Implications for Phalloplasty
Authors: Mariani Ursula Meredith , Fayman Moshe , Nkomozepi Pilani , Ihunwo Amadi Ogonda , Mazengenya Pedzisai
Published: January 2024

Background

The suspensory ligamentous system of the penis supports the penis when erect and plays a key role during coitus. These ligaments, which are prone to injury during coitus, are clinically important in penile reconstruction procedures.

Objectives

The current study investigated the macro- and microanatomy of the suspensory ligamentous system of the penis to determine the origin, course, insertion, dimensions, and tissue composition of these ligaments, knowledge of which is vital for successful penile reconstruction procedures.

Methods

The study utilized a total of 49 cadavers. Gross anatomy dissection, MRI, and histological staining were performed to elucidate the topography, dimensions, and tissue composition of the suspensory ligaments of the penis.

Results

Three ligaments were observed to form the suspensory ligamentous system of the penis. The most superficial is the fundiform ligament, which consists of superficial bundles and deep median bundles, with the former arising from the Scarpa's fascia and the latter arising from the linea alba of the anterior abdominal wall; both inserted into the superficial fascia of the penis. The suspensory ligament of the penis arose from the pubic symphysis and inserted into the deep fascia (Buck's fascia) of the penis. The arcuate ligament arose from the body of the pubis and pubic symphysis and inserted into the Buck's fascia. The ligaments were determined to consist of adipose tissue, collagen fibers, elastic fibers and reticular fibers, in varying proportions.

Conclusions

The suspensory ligaments of the penis exhibit a fan-like structure on the penis that allows the forward movement of the penis as a result of engorgement of the erectile bodies while simultaneously offering support.

Level of Evidence: 5
Temperature variability is associated with the occurrence of extrapair paternity in blue tits
Authors: Arct Aneta , Martyka Rafał , Drobniak Szymon M , Gustafsson Lars , Cichoń Mariusz
Published: January 2024

In birds, extrapair paternity (EPP) constitutes an alternative mating strategy, with potentially important fitness consequences for both males and females and their offspring. Several factors have been identified that can influence the occurrence of EPP, but the role of environmental variability has so far received relatively little attention. Using long-term data set from a wild population of the blue tit (Cyanistes cearuleus), we assess the importance of ambient temperature in modulating the levels of extrapair paternity. Here, we showed that the variability of local thermal conditions affects the occurrence of EPP. Specifically, we found that the probability of EPP increased with rising variability in ambient temperature experienced by females prior to egg laying. This pattern is consistent with an idea of plastic female responses to unpredictable environments. Our results suggest that extrapair mating may represent an adaptive behavioral strategy to compensate for the potential negative effects of unstable environmental conditions.
Improved diagnostic performance of insertable cardiac monitors by an artificial intelligence-based algorithm
Authors: Crespin Eliot , Rosier Arnaud , Ibnouhsein Issam , Gozlan Alexandre , Lazarus Arnaud , Laurent Gabriel , Menet Aymeric , Bonnet Jean-Luc , Varma Niraj
Published: January 2024

Aims

The increasing use of insertable cardiac monitors (ICM) produces a high rate of false positive (FP) diagnoses. Their verification results in a high workload for caregivers. We evaluated the performance of an artificial intelligence (AI)-based ILR-ECG Analyzer™ (ILR-ECG-A). This machine-learning algorithm reclassifies ICM-transmitted events to minimize the rate of FP diagnoses, while preserving device sensitivity.

Methods and results

We selected 546 recipients of ICM followed by the Implicity™ monitoring platform. To avoid clusterization, a single episode per ICM abnormal diagnosis (e.g. asystole, bradycardia, atrial tachycardia (AT)/atrial fibrillation (AF), ventricular tachycardia, artefact) was selected per patient, and analyzed by the ILR-ECG-A, applying the same diagnoses as the ICM. All episodes were reviewed by an adjudication committee (AC) and the results were compared. Among 879 episodes classified as abnormal by the ICM, 80 (9.1%) were adjudicated as ‘Artefacts’, 283 (32.2%) as FP, and 516 (58.7%) as ‘abnormal’ by the AC. The algorithm reclassified 215 of the 283 FP as normal (76.0%), and confirmed 509 of the 516 episodes as abnormal (98.6%). Seven undiagnosed false negatives were adjudicated as AT or non-specific abnormality. The overall diagnostic specificity was 76.0% and the sensitivity was 98.6%.

Conclusion

The new AI-based ILR-ECG-A lowered the rate of FP ICM diagnoses significantly while retaining a > 98% sensitivity. This will likely alleviate considerably the clinical burden represented by the review of ICM events.
The strongest aftershock in seismic models of epidemic type
Authors: Molchan G , Varini E
Published: January 2024

We consider an epidemic-type aftershock model, ETAS(F), for a large class of distributions F determining the number of direct aftershocks. This class includes Poisson, Geometric, Negative Binomial distributions and many other. Assuming an exponential form of the productivity and magnitude laws, we find a limiting distribution of the strongest aftershock magnitude μa when the initial cluster event m• is large. The regime can be either subcritical or critical; the initial event can be dominant in size or not. In the subcritical regime, the mode of the limiting distribution is determined by the parameters of productivity and the magnitude laws; the shape of this distribution is not universal and is effectively determined by F. For example, the Geometric F-distribution generates the logistic law, and the Poisson distribution (studied earlier) generates the Gumbel type 1 law. The accuracy of these laws for moderate initial magnitudes is tested numerically. The limit distribution of the Båth’s difference m• − μa is independent of the initial event size only if the regime is critical, and the ratio of exponents in the laws of magnitude and productivity is contained in the interval (1,2). Previous studies of the μa-distribution have dealt with the traditional Poisson F model and with arbitrary (not necessarily dominant) initial magnitude m•.
T-cell help in the germinal center: homing in on the role of IL-21
Authors: Petersone Lina , Walker Lucy S K
Published: January 2024

Interleukin 21 (IL-21) is a pleiotropic cytokine that is overproduced in multiple autoimmune settings. Provision of IL-21 from follicular helper T cells is an important component of T-cell help within germinal centers (GC), and the last few years have seen a resurgence of interest in IL-21 biology in the context of the GC environment. While it has been more than a decade since T cell-derived IL-21 was found to upregulate B-cell expression of the GC master transcription factor B-cell lymphoma 6 (Bcl-6) and to promote GC expansion, several recent studies have collectively delivered significant new insights into how this cytokine shapes GC B-cell selection, proliferation, and fate choice. It is now clear that IL-21 plays an important role in GC zonal polarization by contributing to light zone GC B-cell positive selection for dark zone entry as well as by promoting cyclin D3-dependent dark zone inertial cycling. While it has been established that IL-21 can contribute to the modulation of GC output by aiding the generation of antibody-secreting cells (ASC), recent studies have now revealed how IL-21 signal strength shapes the fate choice between GC cycle re-entry and ASC differentiation in vivo. Both provision of IL-21 and sensitivity to this cytokine are finely tuned within the GC environment, and dysregulation of this pathway in autoimmune settings could alter the threshold for germinal center B-cell selection and differentiation, potentially promoting autoreactive B-cell responses.
Psychometric Properties of Instruments That Measure Vaping Outcome Expectancies: A Systematic Review
Authors: Wall Nicole , Fox-Wasylyshyn Susan , Mirza Noeman , Ralph Jody
Published: January 2024

Introduction

Vaping is a growing public health concern. Interventions that address vaping must build upon rigorous research that uses psychometrically sound instruments to measure vaping-associated outcome expectancies.

Aims and Methods

The primary aim was to appraise the reporting of psychometric properties of instruments used to measure vaping outcome expectancies. Secondary aims were to distinguish the different types of outcome expectancies assessed across the measures, the conceptual underpinnings, and the evidence explaining e-cigarette use etiology. This systematic review was guided by an adapted version of the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline and Risk of Bias Checklist. Five electronic databases were searched for peer-reviewed studies, dissertations, and theses that psychometrically evaluated instruments that measure vaping outcome expectancies. Studies that met the inclusion criteria were appraised based on their reporting of nine psychometric properties outlined in the COSMIN checklist.

Results

The review included 11 studies that described eight instruments and reported on two to five of nine predetermined psychometric properties. Structural validity, construct validity, and internal consistency were the most commonly reported properties. No studies reported test-retest, intrarater, or interrater reliability, measurement error, or responsiveness. Content validity and measurement invariance were only reported by two and four studies, respectively. The most commonly included subscales in the instruments were affect regulation, positive sensory experience, and negative health consequences. Many of the outcome expectancy subscales were associated with e-cigarette behaviors.

Conclusions

There is limited reporting of psychometric testing of instruments that measure vaping outcome expectancies; however, utilization of the COSMIN guideline could enhance the quality of such reporting.

Implications

Appraising the reporting of psychometric properties of instruments that measure vaping outcome expectancies is a first step to ensuring valid and reliable instruments are used to support rigorous research and build evidence-based knowledge. Future research should focus on testing for responsiveness, measurement error, and reliability, and on quality appraisal of the instruments. Studying vaping outcome expectancies may improve understanding of factors that influence and deter vaping. This may contribute to the development of effective interventions aimed at vaping cessation and prevention.
Circ_0001861 facilitates trophoblast cell proliferation, migration, invasion and epithelial-mesenchymal transition via the miR-296-5p/forkhead box protein 1 pathway in preeclampsia
Authors: Liu Yanhua , Wang Shengpu , Zhang Xiaoying , Jia Xuewei , Lu Yuemei , Liu Yaping
Published: January 2024

Background:

Preeclampsia (PE) is one of the leading causes of maternal mortality and placental trophoblastic disorders. Recent studies reported that circular RNAs (circRNAs) were involved in PE pathogenesis. However, the role of circ_0001861 in PE progression is largely unknown.

Methods:

The RNA expression of circ_0001861, forkhead box protein 1 (FOXP1) and microRNA-296-5p (miR-296-5p) was detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Western blot assay was performed to examine the protein levels of FOXP1 and epithelial–mesenchymal transition (EMT) markers. Cell viability, proliferation, migration and invasion were detected by cell counting kit-8, 5-ethynyl-2’-deoxyuridine, and transwell assays. Luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation (RIP) assay were conducted to explore the interaction between miR-296-5p and circ_0001861 or FOXP1.

Results:

Circ_0001861 and FOXP1 were downregulated but miR-296-5p was upregulated in PE placenta. Upregulation of circ_0001861 facilitated trophoblast cell proliferation, migration, invasion and EMT. Mechanistically, circ_0001861 sponged miR-296-5p to elevate FOXP1 expression, thus promoting trophoblast cell progression.

Conclusion:

The circ_0001861/miR-296-5p/FOXP1 axis plays a critical role in trophoblast cell proliferation, migration, invasion and EMT, which may provide a novel insight into developing potential therapeutic targets for PE.
Normal physiological distribution and tumor localization of 64CuCl2 in different human malignancies along with semiquantitative scoring: a comparative evaluation with 18Fluorodeoxyglucose (18FDG) PET-CT
Authors: Baberwal Parth , Sonavane Sunita , Vimalnath K. V. , Chakravarty Rubel , Chakraborty Sudipta , Basu Sandip
Published: January 2024

Objective

This study aimed to explore 64-Copper-Chloride (64CuCl2) PET-CT in various malignancies and demonstrate a head-to-head comparison of uptake on 64CuCl2 PET/computed tomography (CT) and 18fluorodeoxyglucose (18FDG)-PET/CT scans for different malignancies, with an emphasis on 18FDG nonavid malignancies.

Methods

Fifty-three patients diagnosed with various biopsy-proven malignancies (except prostate cancer) were recruited in this prospective study. All the patients underwent both 64CuCl2 PET/CT and 18FDG-PET/CT. 64CuCl2 PET/CT was acquired at 1, 3 and 24 h time points. We studied the physiological biodistribution of 64CuCl2 in the various organs, corroborated the uptake of 64CuCl2 with various types of malignancies and comparison of their uptake with 18FDG-PET/CT and their correlation with each other in various lesions.

Results

The biodistribution study showed that the liver concentrated 64CuCl2 the most out of all the organs, followed by the pancreas and large intestine. Liver and intestinal activity increased subsequently with delayed imaging, and the washout of 64CuCl2 was noted in the pancreas in delayed images and followed a hepatobiliary excretion of tracer over a period of time. In lesion-wise analysis, it was noted that the primary neuroendocrine tumor, melanoma and renal/urothelial malignancy group showed more uptake of 64CuCl2, than that in metastasis and vice-versa was noted in lung and soft tissue malignancies. Comparing it with 18FDG, it was seen that FDG showed more uptake in lesions and showed no significant correlation (Kappa value: 0.089) with the uptake of 64CuCl2 in the lesion-wise comparison.

Conclusion

64CuCl2 PET/CT did not show any added advantage over 18FDG-PET/CT in the evaluation of the studied malignancies, both primary and their metastasis. Biodistribution studies showed the liver as the organ with maximum uptake, which implies it may hinder the detection of abdominal or hepatic involvement of the disease.
Impact factors of benefiting from initial 131I ablation in patients with intermediate-risk differentiated thyroid carcinoma: a study based on a re-evaluation of therapeutic response
Authors: Ren Li , Hu Yongquan , Hu Yehuan , Xiao Da , Sun Junjie , Zhu Bo , Zhang Congli
Published: January 2024

Objective

This study was carried out to confirm whether patients with intermediate-risk differentiated thyroid cancer (DTC) could benefit from initial 131I ablation and to identify the factors that impacted the benefit.

Methods

We retrospectively assessed a cohort of 548 patients with intermediate-risk DTC who were classified into structural incomplete response (SIR), biochemical incomplete response (BIR), indeterminate response (IDR), and excellent response (ER) groups according to the ATA guidelines (version 2015). A downgrade in the classification, such as from initial SIR to final BIR, IDR, or ER, from BIR to IDR or ER, and from initial IDR to final ER, was defined as benefiting from initial 131I ablation (benefit group). Non-downgraded classification meant non-benefit.

Results

64.78% of patients benefited from the initial 131I ablation in the final re-evaluation. Gender (OR = 0.038, P = 0.002), interval time (OR = 0.038, P = 0.002) and serum ps-Tg (OR = 0.961, P = 0.001) were independent prognostic factors for benefiting from initial 131I ablation, with the cutoff value were 5 months and 19.08 ng/ml.

Conclusion

Patients with intermediate-risk DTC could benefit from initial 131I ablation. Female patients with intermediate-risk DTC whose interval time <5 months and ps-Tg <19.08 ng/ml were more likely to benefit. Early 131I ablation for such patients is beneficial for achieving a complete therapeutic response.
Transcranial direct current stimulation alters cerebrospinal fluid-interstitial fluid exchange in mouse brain
Authors: Wang Yan , Monai Hiromu
Published: January 2024

Background

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has gained prominence recently. Clinical studies have explored tDCS as an adjunct to neurologic disease rehabilitation, with evidence suggesting its potential in modulating brain clearance mechanisms. The glymphatic system, a proposed brain waste clearance system, posits that cerebrospinal fluid-interstitial fluid (CSF-ISF) exchange aids in efficient metabolic waste removal. While some studies have linked tDCS to astrocytes inositol trisphosphate (IP3)/Ca2+signaling, the impact of tDCS on CSF-ISF exchange dynamics remains unclear.

Hypothesis

tDCS influences the dynamics of CSF-ISF exchange through astrocytic IP3/Ca2+signaling.

Methods

In this study, we administered tDCS (0.1mA for 10 minutes) to C57BL/6 mice anesthetized with ketamine-xylazine (KX). The anode was positioned on the cranial bone above the cortex, and the cathode was inserted into the neck. Following tDCS, we directly assessed brain fluid dynamics by injecting biotinylated dextran amine (BDA) as a CSF tracer into the cisterna magna (CM). The brain was then extracted after either 30 or 60 minutes and fixed. After 24 hours, the sectioned brain slices were stained with Alexa 594-conjugated streptavidin (SA) to visualize BDA using immunohistochemistry. We conducted Electroencephalography (EEG) recordings and aquaporin 4 (AQP4)/CD31 immunostaining to investigate the underlying mechanisms of tDCS. Additionally, we monitored the efflux of Evans blue, injected into the cisterna magna, using cervical lymph node imaging. The experiments were subsequently repeated with inositol trisphosphate receptor type 2 (IP3R2)-knockout mice.

Results

Post-tDCS, we observed an increased CSF tracer influx, indicating a modulation of CSF-ISF exchange by tDCS. Additionally, tDCS appeared to enhance the brain’s metabolic waste efflux. EEG recordings showed an increase in delta wave post-tDCS. But no significant change in AQP4 expression was detected 30 minutes post-tDCS.

Conclusion

Our findings suggest that tDCS augments the glymphatic system’s influx and efflux. Through astrocyte IP3/Ca2+signaling, tDCS was found to modify the delta wave, which correlates positively with brain clearance. This study underscores the potential of tDCS in modulating brain metabolic waste clearance.
Genomic background sequences systematically outperform synthetic ones in de novo motif discovery for ChIP-seq data
Authors: Raditsa Vladimir V. , Tsukanov Anton V. , Bogomolov Anton G. , Levitsky Victor G.
Published: January 2024

Efficientde novomotif discovery from the results of wide-genome mapping of transcription factor binding sites (ChIP-seq) is dependent on the choice of background nucleotide sequences. The foreground sequences (peaks) represent not only specific motifs of target transcription factors, but also the motifs overrepresented throughout the genome, such as simple sequence repeats. We performed a massive comparison of the ‘synthetic’ and ‘genomic’ approaches to generate background sequences forde novomotif discovery. The ‘synthetic’ approach shuffled nucleotides in peaks, while in the ‘genomic’ approach randomly selected sequences from the reference genome or only from gene promoters according to the fraction of A/T nucleotides in each sequence. We compiled the benchmark collections of ChIP-seq datasets for mammalian and Arabidopsis, and performedde novomotif discovery. We showed that the genomic approach has both more robust detection of the known motifs of target transcription factors and more stringent exclusion of the simple sequence repeats as possible non-specific motifs. The advantage of the genomic approach over the synthetic one was greater in plants compared to mammals. We developed the AntiNoise web service (https://denovosea.icgbio.ru/antinoise/) which implements a genomic approach to extract genomic background sequences for twelve eukaryotic genomes.
Genomic signatures associated with the evolutionary loss of egg yolk in parasitoid wasps
Authors: Zhao Xianxin , Liu Yuanyuan , Yang Yi , He Chun , Chan Kevin C. , Lin Haiwei , Fang Qi , Ye Gongyin , Ye Xinhai
Published: January 2024

Trait regression and loss have occurred repeatedly in numerous lineages throughout evolutionary history in response to changing environments. In parasitoid wasps, a mega-diverse group of hymenopteran insects, loss or reduction of yolk in the egg has been reported in many species. This phenotypic change likely evolved as a response to the shift from ectoparasitism to endoparasitism. However, the genetic basis of this trait and the impact of its loss on genome evolution remain poorly understood. Here, we performed a comparative genomic analysis of 64 hymenopteran insects. The conserved insect yolk protein genevitellogenin(Vg) underwent five independent loss events in four families, involving 23 of the analyzed endoparasitoid species. Whole-genome alignment suggested thatVgloss occurred during genome rearrangement events. Analysis ofVgreceptor gene (VgR) loss, selection, and structural variation in lineages lackingVgdemonstrated functional biases in the patterns of gene loss. The ectoparasitism to endoparasitism transition did not appear to be the primary driver ofVgloss or the subsequentVgRevolution. A number of parallel and convergent genomic changes were observed betweenVg-loss lineages, including gene family evolution and selection of genes related to transport, development, and metabolism. These changes may have facilitated embryonic development without the yolk in these lineages. Together, these findings reveal the genomic basis underlying a unique trait loss in parasitoid wasps. More broadly, this study enhances our understanding of yolk loss evolution outside the class Mammalia, highlighting a potential evolutionary trend arising from the availability of an alternative nutrient source for embryonic development.
Piggybacking functionalized DNA nanostructures into live cell nuclei
Authors: Roozbahani Golbarg M. , Colosi Patricia , Oravecz Attila , Sorokina Elena M. , Pfeifer Wolfgang , Shokri Siamak , Wei Yin , Didier Pascal , DeLuca Marcello , Arya Gaurav , Tora László , Lakadamyali Melike , Poirier Michael G. , Castro Carlos E.
Published: January 2024

DNA origami (DO) are promising tools forin vitroorin vivoapplications including drug delivery; biosensing, detecting biomolecules; and probing chromatin sub-structures. Targeting these nanodevices to mammalian cell nuclei could provide impactful approaches for probing visualizing and controlling important biological processes in live cells. Here we present an approach to deliver DO strucures into live cell nuclei. We show that labelled DOs do not undergo detectable structural degradation in cell culture media or human cell extracts for 24 hr. To deliver DO platforms into the nuclei of human U2OS cells, we conjugated 30 nm long DO nanorods with an antibody raised against the largest subunit of RNA Polymerase II (Pol II), a key enzyme involved in gene transcription. We find that DOs remain structurally intact in cells for 24hr, including within the nucleus. Using fluorescence microscopy we demonstrate that the electroporated anti-Pol II antibody conjugated DOs are efficiently piggybacked into nuclei and exihibit sub-diffusive motion inside the nucleus. Our results reveal that functionalizing DOs with an antibody raised against a nuclear factor is a highly effective method for the delivery of nanodevices into live cell nuclei.
Beyond Basic Characterization and Omics: Immunomodulatory Roles of Platelet-Derived Extracellular Vesicles Unveiled by Functional Testing
Authors: Palviainen Mari , Puutio Johanna , Østergaard Rikke Halse , Eble Johannes A. , Maaninka Katariina , Ndika Joseph , Kari Otto K. , Kamali-Moghaddam Masood , Kjaer-Sorensen Kasper , Oxvig Claus , Aransay Ana M , Falcon-Perez Juan , Federico Antonio , Greco Dario , Laitinen Saara , Hayashi Yuya , Siljander Pia RM
Published: January 2024

Renowned for their role in hemostasis and thrombosis, platelets are also increasingly recognized for their contribution in innate immunity, immunothrombosis and inflammatory diseases. Platelets express a wide range of receptors, which allows them to reach a variety of activation endpoints and grants them immunomodulatory functions. Activated platelets release extracellular vesicles (PEVs), whose formation and molecular cargo has been shown to depend on receptor-mediated activation and environmental cues.

This study compares the immunomodulatory profiles of PEVs generated via activation of platelets by different receptors, glycoprotein VI, C-type lectin-like receptor 2, and combining all thrombin-collagen receptors. Functional assaysin vivoin zebrafish andin vitroin human macrophages respectively highlighted distinct homing and secretory responses triggered by the PEVs. In contrast, omics analyses of protein and miRNA cargo combined with physicochemical particle characterization found only subtle differences between the PEV types, which were insufficient to explain their different functional immunomodulatory profiles. Constitutively released PEVs, formed in the absence of an exogenous activator, displayed a disparate activation profile from the receptor induced PEVs.

Our findings underscore that PEVs are tunable through receptor-mediated activation. To truly comprehend their role(s) in mediating platelet functions among immune cells, conducting functional assays is imperative.

Graphical Abstract
Cryo-EM images of phase separated lipid bilayer vesicles analyzed with a machine learning approach
Authors: Sharma Karan D. , Doktorova Milka , Waxham M. Neal , Heberle Frederick A.
Published: January 2024

Lateral lipid heterogeneity (i.e., raft formation) in biomembranes plays a functional role in living cells. Three-component mixtures of low- and high-melting lipids plus cholesterol offer a simplified experimental model for raft domains in which a liquid-disordered (Ld) phase coexists with a liquid-ordered (Lo) phase. Using such models, we recently showed that cryogenic electron microscopy (cryo-EM) can detect phase separation in lipid vesicles based on differences in bilayer thickness. However, the considerable noise within cryo-EM data poses a significant challenge for accurately determining the membrane phase state at high spatial resolution. To this end, we have developed an image processing pipeline that utilizes machine learning (ML) to predict the bilayer phase in projection images of lipid vesicles. Importantly, the ML method exploits differences in both the thickness and molecular density of Lo compared to Ld, which leads to improved phase identification. To assess accuracy, we used artificial images of phase-separated lipid vesicles generated from all-atom molecular dynamics simulations of Lo and Ld phases. Synthetic ground truth datasets mimicking a series of compositions along a tieline of Ld+Lo coexistence were created and then analyzed with various ML models. For all tieline compositions, we find that the ML approach can correctly identify the bilayer phase at 5 nm lateral resolution with > 90% accuracy, thus providing a means to isolate the intensity profiles of coexisting Ld and Lo phases, as well as accurately determine domain size distributions, number of domains, and phase area fractions. The method described here provides a framework for characterizing nanoscopic lateral heterogeneities in membranes and paves the way for a more detailed understanding of raft properties in biological contexts.

Significance

Lipid rafts are important for cell function, but in most cases cannot be detected with conventional optical microscopy because of their extremely small size. Cryogenic electron microscopy (cryo-EM), because of its much greater spatial resolution, is capable of imaging domains as small as 5-10 nm. In this report, we show how machine learning techniques can be used to automatically and accurately identify raft-like domains in simulated cryo-EM images, a powerful approach that could ultimately lead to a better understanding of raft properties.
Development of deaminase-free T-to-S base editor and C-to-G base editor by engineered human uracil DNA glycosylase
Authors: Tong Huawei , Wang Haoqiang , Liu Nana , Li Guoling , Zhou Yingsi , Wu Danni , Li Yun , Jin Ming , Wang Xuchen , Li Hengbin , Wei Yinghui , Yuan Yuan , Shi Linyu , Yao Xuan , Yang Hui
Published: January 2024

DNA base editors could enable direct editing of adenine (A), cytosine (C), or guanine (G), but there is no base editor for direct thymine (T) editing currently. Here, by fusing Cas9 nickase (nCas9) with engineered human uracil DNA glycosylase (UNG) variants, we developed a deaminase-free glycosylase-based thymine base editor (gTBE) with the ability of direct T editing. By several rounds of UNG mutagenesis via rational screening, we demonstrated that gTBE with engineered UNG variants could achieve T editing efficiency by up to 81.5%. Furthermore, the gTBE exhibited high T-to-S (i.e., T-to-C or T-to-G) conversion ratio with up to 0.97 in cultured human cells. Using similar strategy, we developed a deaminase-free cytosine base editor (gCBE) facilitating specifically direct C editing by engineered UNG with mutations different from gTBE. Thus, we provide two novel base editors, gTBE and gCBE, with corresponding engineered UNG variants, broadening the targeting scope of base editors.
Activation and depression of neural and hemodynamic responses induced by the intracortical microstimulation and visual stimulation in the mouse visual cortex
Authors: Suematsu Naofumi , Vazquez Alberto L , Kozai Takashi DY
Published: January 2024

Objective. Intracortical microstimulation can be an effective method for restoring sensory perception in contemporary brain-machine interfaces. However, the mechanisms underlying better control of neuronal responses remain poorly understood, as well as the relationship between neuronal activity and other concomitant phenomena occurring around the stimulation site.Approach. Different microstimulation frequencies were investigatedin vivoon Thy1-GCaMP6s mice using widefield and two-photon imaging to evaluate the evoked excitatory neural responses across multiple spatial scales as well as the induced hemodynamic responses. Specifically, we quantified stimulation-induced neuronal activation and depression in the mouse visual cortex and measured hemodynamic oxyhemoglobin and deoxyhemoglobin signals using mesoscopic-scale widefield imaging.Main results. Our calcium imaging findings revealed a preference for lower-frequency stimulation in driving stronger neuronal activation. A depressive response following the neural activation preferred a slightly higher frequency stimulation compared to the activation. Hemodynamic signals exhibited a comparable spatial spread to neural calcium signals. Oxyhemoglobin concentration around the stimulation site remained elevated during the post-activation (depression) period. Somatic and neuropil calcium responses measured by two-photon microscopy showed similar dependence on stimulation parameters, although the magnitudes measured in soma was greater than in neuropil. Furthermore, higher-frequency stimulation induced a more pronounced activation in soma compared to neuropil, while depression was predominantly induced in soma irrespective of stimulation frequencies.Significance. These results suggest that the mechanism underlying depression differs from activation, requiring ample oxygen supply, and affecting neurons. Our findings provide a novel understanding of evoked excitatory neuronal activity induced by intracortical microstimulation and offer insights into neuro-devices that utilize both activation and depression phenomena to achieve desired neural responses.
Hints of a new leptophilic Higgs sector?
Authors: Afik Yoav , Dev P. S. Bhupal , Thapa Anil
Published: January 2024

We show that a new leptophilic Higgs sector can resolve some intriguing anomalies in current experimental data across multiple energy ranges. Motivated by the recent CMS excess in the resonant eμ channel at 146 GeV, we consider a leptophilic two-Higgs-doublet model, and propose a novel resonant production mechanism for the neutral components of the second Higgs doublet at the LHC using the lepton content of the proton. Interestingly, the same Yukawa coupling Yeμ∼0.65–0.81 that explains the CMS excess also addresses the muon (g−2) anomaly. Moreover, the new Higgs doublet also resolves the recent CDF W-boson mass anomaly. The relevant model parameter space will be completely probed by future LHC data.

Published by the American Physical Society
2024
Q
-balls in the sky
Authors: Ansari Arhum , Bhandari Lalit Singh , Thalapillil Arun M.
Published: January 2024

There may exist extended configurations in the dark matter sector that are analogs of structures in the visible sector. In this work, we explore nontopological solitonic configurations, specifically Q-balls, and study when they may form macroscopic astrophysical structures and what their distinct characteristics might be. We study in some detail theoretical bounds on their sizes and constraints on the underlying parameters, based on criteria for an astrophysical Q-ball’s existence, gravitational stability and viability of solutions. Following this path, one is able to obtain novel limits on astrophysical Q-ball sizes and their underlying parameters. We also explore the gravitational lensing features of different astrophysical Q-ball profiles, which are more general than the simple thin-wall limit. It is seen that the magnification characteristics may be very distinct, depending on the actual details of the solution, even for astrophysical Q-balls having the same size and mass. Assuming that such astrophysical Q-balls may form a small component of the dark matter in the Universe, we place limits on this fraction from the gravitational microlensing surveys EROS-2, OGLE-IV, HSC-Subaru and the proposed future survey WFIRST. Exploring various astrophysical Q-ball profiles and sizes, it is found that while for most intermediate masses that we consider, the dark matter fraction comprising astrophysical Q-balls is at most subpercent, for other masses it may be significantly higher.

Published by the American Physical Society
2024
Amr Allam: outgrowing a family business
Authors: Apaydin Marina , Sand Martin Johannes Løkse , Hoogendoorn Rebecca A , Eshak Maha
Published: January 2024

Learning outcomes

The expected learning outcomes are to understand key frameworks and tools for global leaders through the application of widely used theoretical frameworks on a written business case, understand the role of the leader in a team, apply theories of change to situations to anticipate courses of events and evaluate and apply relevant theory to assess a leader’s character and personality.

Case overview/synopsis

Hassan Allam Holding (HAH) was a family-owned Egyptian engineering, construction and infrastructure company managed by co-Chief Executive Officers and brothers Amr and Hassan Allam. HAH experienced significant growth and success, but eventually, it reached a point where its family governance structure could no longer sustain further growth. Amr and Hassan realized this and started planning to transition toward a corporate governance structure. In 2016, they managed to get the International Finance Corporation on board as an equity partner, and this helped propel the governance transition, but they still needed to find a way to convince the family to step back. This case study can help students understand the issues that may occur during a change within an established organization of any size. The case study considers the implications the change may have on the leader, his personality and his character and how it shapes the leader in question as an outcome. This case study has been designed to be used in one or two sessions and can be offered in management or leadership courses at an undergraduate or graduate level.

Complexity academic level

This case study is intended for graduate and undergraduate students studying a leadership or management course. It can help students comprehend the challenges of a family-owned business and how change is associated with such businesses. The case also considers how leaders are shaped by effectively managing conflict. This case can be considered as Level 1 on a 1–3 scale, as the full description of the situation is given in the case and the task of the students is to analyze the leader and his decisions using various academic concepts and theories (Erskin et al., 2003).

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 3: Entrepreneurship
Beyond the stethoscope: a COVID-19 lens on the halal, business and ethical dimensions of hospitals in a Muslim majority country
Authors: Gayatri Gita , Kamarulzaman Yusniza , Balqiah Tengku Ezni , Chalid Dony Abdul , Safira Anya , Hati Sri Rahayu Hijrah
Published: January 2024

Purpose

This study aims to examine the perceptions and evaluations of Muslim COVID-19 survivors and health workers regarding the halal, business and ethical attributes of hospitals during their interactions related to COVID-19 treatment.

Design/methodology/approach

Descriptive qualitative research with semi-structured online interviews was used to gather insights from COVID-19 survivors and health workers who treated COVID-19 patients. The findings were then compared with existing literature on hospital services and Sharia attributes.

Findings

The study found that patients and health-care workers in hospitals are concerned about whether the hospital follows Sharia law, the quality of health-care and hospital services and the ethical conduct of hospital staff. This is especially true during the COVID-19 pandemic, when patients are more anxious about religious conduct and the afterlife.

Research limitations/implications

Hospitals need to address halal attributes in all aspects of their services for Muslim patients and business attributes such as standard health-care quality, service quality and ethical attributes. Participants indicated that when these needs are met, they are more likely to revisit the hospital and recommend it to others.

Originality/value

This study contributes to understanding the expectations of Muslim patients regarding hospital services that meet Islamic ethical and business requirements. Using the COVID-19 pandemic as a case study broadens the understanding of how to better serve Muslim customers.
A comparison of analysts’ and investors’ information efficiency of corporate social responsibility activities
Authors: Kang Grace Il Joo , Heo Kyongsun , Jeon Sungmin
Published: January 2024

Purpose

This paper aims to examine the extent to which sell-side analysts efficiently incorporate firms’ corporate social responsibility (CSR) activities into their earnings forecasts. In addition, this paper also investigate the CSR information efficiency of analysts vis-à-vis that of investors.

Design/methodology/approach

This paper measures CSR activities by using CSR strength and CSR concern scores from the Morgan Stanley Capital International Environmental, Social and Governance database. This paper uses analysts’ earnings forecast errors and dispersion as proxies for their information efficiency. To compare the CSR information efficiency of analysts to that of investors, this paper uses the Vt/Pt ratio, which is the equity value estimates inferred from analysts’ earnings forecasts (a proxy for analysts’ CSR information efficiency) to the stock price of the focal company (a proxy for investors’ CSR information efficiency).

Findings

The regression analysis indicates that analysts’ earnings forecasts are optimistically biased and more dispersed for firms with positive CSR activities. The paper also finds that analysts’ forecasts are more optimistically biased than investors in interpreting CSR activities.

Practical implications

The lack of standardized protocols in CSR reporting and activities has raised the risk of mispricing by analysts, threatening the stability of sustainable investments. This paper suggests that regulators and standard-setters should establish a uniform framework governing firms’ CSR activities, along with their reporting and measurement, to ensure more consistent and reliable evaluations of CSR practices.

Social implications

Analysts’ mispricing of CSR activities may distort sustainable investing, as it can overly focus on the positive impacts of stakeholder theory, overlooking agency theory’s warnings about managerial self-interest. Investors need to assess CSR efforts with a dual perspective, acknowledging their societal value but also examining their alignment with shareholder interests.

Originality/value

To the best of the authors’ knowledge, this research is the first to assess the efficiency of analysts versus investors in processing CSR information amidst growing sustainable investment interests. Furthermore, building on Dhaliwal et al. (2012), which found that voluntary CSR disclosures correlate with more accurate analyst forecasts, this research provides fresh perspectives on the evolving nature of how analysts assimilate CSR information over time.
Taking empirical evidence seriously v.2.01
Authors: Tilden Terje , Solem May‐Britt , Thuen Frode , Lorås Lennart , Stokkebekk Jan , Whittaker Kristoffer
Published: January 2024

This article discusses the status and challenges related to the basic perspective of knowledge and science in systemic practice. This article points out that some parts of the field (i.e. collaborative dialogical practice) have a preference for knowledge obtained through qualitative rather than quantitative studies. This is problematised, partly based on methodology and partly on the bias this entails in the provision of knowledge to students and systemic practitioners. The consequences of such a preference may be that systemic practitioners will lack significant knowledge, and that they are not encouraged to conduct or participate in quantitative studies. This issue highlights a stronger focus on the field's basic perspectives, as well as key political, ethical and professional policies. In response, the article presents the theories of interactive constructivism and critical realism and proposes that these become the guiding paradigm for systemic practice.
Examining the asymmetric effects of energy intensity in low‐ versus high‐income economies: New evidence using common correlated effects approach
Authors: Sim Khang Yi , Sek Siok Kun
Published: January 2024

This study aims to investigate the symmetric and asymmetric effects of total and renewable energy intensity on economic growth (GDP) in two panel groups classified by their income levels, namely, low‐ and lower‐middle‐income economies versus high‐income economies over 1990–2021. Heterogeneous estimators are adopted in the common correlated effects models, covering slope heterogeneity, cross‐sectional dependence and nonstationarity or cointegration (long‐run effect). New evidence is obtainable from this study because energy intensity is decomposed into its positive and negative series and incorporated into the model estimations so that the effect of its increases and decreases can be observed. Hence, our innovative models are improved and better mimic real economic situations. The results demonstrate that energy intensity and GDP are negatively correlated, and the causal effect is nonlinear or asymmetric. The effect also differs across the two panel groups. The decreases in total energy intensity (LTEI–) have a greater adverse impact on GDP than energy intensity increases (LTEI+) for low‐ and lower‐middle‐income economies. For high‐income economies, the detrimental influence of LTEI+ is more prominent than that of LTEI–. Moreover, the increases in renewable energy intensity (LREI+) also impede the GDP of high‐income economies, but with a relatively smaller impact compared to LTEI+ and LTEI–. On the contrary, the gain in GDP for both groups is driven by gross fixed capital formation although the conducive impact is rather small compared to the unfavourable effect of total energy intensity on the GDP. Besides, the labour force participation rate promotes a higher GDP in the high‐income group. Therefore, critical attention and proper energy policy formulation should be stipulated in achieving sustainable development and contributing to the Sustainable Development Goals.
Euthanasia, consensual homicide, and refusal of treatment
Authors: Rivera‐López Eduardo
Published: January 2024

Consensual homicide remains a crime in jurisdictions where active voluntary euthanasia has been legalized. At the same time, both jurisdictions, in which euthanasia is legal and those in which it is not, recognize that all patients (whether severely ill or not) have the right to refuse or withdraw medical treatment (including life‐saving treatment). In this paper, I focus on the tensions between these three norms (the permission of active euthanasia, the permission to reject life‐saving treatment, and the prohibition of consensual homicide), assuming a justification of euthanasia based on the right to (personal) autonomy. I argue that the best way to provide a coherent account of these norms is to claim that patients have two distinct rights: the right to autonomy and the right to bodily integrity. This solution has some relevant implications for the discussion of the legalization of active euthanasia.
Cerebrovascular and cardiovascular autonomic regulation in sickle cell patients with white matter lesions
Authors: Ferreira De Matos Christophe , Cougoul Pierre , Zaharie Oana Maria , Kermorgant Marc , Pavy‐Le Traon Anne , Gales Celine , Senard Jean‐Michel , Strumia Mathilde , Bonneville Fabrice , Nasr Nathalie
Published: January 2024

Background and purpose

White matter lesions (WMLs) are frequent in sickle cell disease (SCD), with a prevalence described to be as high as 53% by age 30. Cerebrovascular regulation and cardiovascular autonomic regulation, more specifically the sympatho‐vagal balance, can be altered in SCD. In this study the association between WMLs, cerebrovascular regulation and sympatho‐vagal balance was assessed in SCD patients.

Methods and results

Sickle cell disease patients with no history of stroke were prospectively evaluated for cerebrovascular reactivity using the breath‐holding test (BHT), the sympatho‐vagal balance (ratio low frequency/high frequency [HF]) using heart rate variability parameters and cerebral autoregulation in the time domain using correlation index Mx, and arterial cerebral compliance based on continuous assessment of cerebral blood flow velocities using transcranial Doppler ultrasound and arterial blood pressure with photo‐plethysmography. WMLs were assessed with magnetic resonance imaging using Fazekas score grading and the presence of lacunes. Forty‐one patients (F/M 25/16) were included. Median age was 37.5 years (19–65). Twenty‐nine (70.7%) patients had SS genotype. Eleven patients had WMLs (26.8%). Patients with WMLs were significantly older (p < 0.001), had a lower HF (p < 0.005) and an impaired cerebral arterial compliance (p < 0.014). The receiver operating curve for the regression model including age and HF showed a higher area under the curve compared to age alone (0.946 vs. 0.876). BHT and Mx did not significantly differ between the two groups.

Conclusions

Lower parasympathetic activity and impaired cerebral arterial compliance were associated with WMLs in adults with SCD. This could potentially yield to a better understanding of pathophysiological parameters leading to premature cerebrovascular ageing in SCD.