bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of early versus late remdesivir treatment in hospitalized mild to moderate COVID-19 patients in the Omicron era: A retrospective study
Authors: Ryu Byung-Han , Lee Ju Young , Lee Sun Hee
Published: July 2024

Although real-world studies have found that remdesivir is effective in preventing poor prognosis, more information is needed on the optimal timing of remdesivir administration in high-risk coronavirus disease 2019 (COVID-19) patients in the Omicron era. From February 2022 to January 2023, a single-center retrospective study was performed in Korea. We compared the clinical characteristics and treatment outcomes between early (remdesivir treatment within 0–3 days from symptom onset) and late (≥ 4 days from symptom onset) treatment groups of patients who received remdesivir monotherapy. Of 284 patients, 225 were classified into the early treatment group and 59 were classified into the late treatment group. The early treatment group had a lower rate of 28-day progression to severe disease than the late treatment group (1.4% vs 7.4%, P = .03). Delaying remdesivir treatment ≥ 4 days from symptom onset (adjusted odds ratio [aOR], 6.17; 95% CI, 1.18–32.44; P = .03) and Charlson comorbidity index ≥ 3 (aOR, 9.62; 95% CI, 1.65–56.10; P = .01) were independent risk factors for 28-day progression to severe disease. Our results suggest that early administration of remdesivir could be associated with better prognosis in COVID-19 patients with the Omicron variant, and within 3 days from symptom onset seems to be the appropriate timing.
High-grade Anaplastic Transformation of Ovarian Serous Borderline Tumor
Authors: Zhang Xiaoming , Devereaux Kelly A. , Ryan Emily , Fei Fei , Kunder Christian A. , Longacre Teri A.
Published: July 2024

Ovarian serous borderline tumors (SBTs) have a generally favorable prognosis. Although the risk of progression to low-grade serous carcinoma is well documented, progression to high-grade carcinoma is rare. We report the clinicopathologic features of seven SBTs, each associated with the presence of a morphologically unique high-grade component with an extremely dismal prognosis. All of the SBTs exhibited typical hierarchical branching and scattered eosinophilic cells, whereas the high-grade component consisted of a profuse proliferation of epithelioid cells with abundant dense, eosinophilic cytoplasm, variable nuclear pleomorphism, and evident loss of WT1, estrogen receptor, and p16 positivity. In most cases, the SBT demonstrated an abrupt transition to the high-grade component, but one patient initially presented with the usual SBT and developed a recurrent disease that was composed entirely of the high-grade component. Targeted next-generation sequencing revealed identical driver mutations in both the SBT and high-grade components (BRAF in 3, KRAS in 1), confirming clonality. Three cases, in addition, harbored telomerase reverse transcriptase promoter mutations in both components. One case, despite insufficient material for sequencing, was BRAF V600E-positive by immunohistochemistry. Most patients with available follow-up data died within 9 months of diagnosis. This study confirms prior reports of ovarian SBT transformation to high-grade carcinoma and further characterizes a distinct subset with abundant dense eosinophilic cytoplasm and an extremely dismal prognosis. The presence of BRAF mutations in a major subset of these tumors questions the notion that BRAF is associated with senescent eosinophilic cells and improved outcomes in SBT. The role of the additional telomerase reverse transcriptase promoter mutations merits further investigation.
Five centuries of genome evolution and multi-host adaptation of Campylobacter jejuni in Brazil
Authors: Buiatte Ana Beatriz Garcez , Souza Stephanie S. R. , Costa Leticia Roberta Martins , Peres Phelipe Augusto Borba Martins , de Melo Roberta Torres , Sommerfeld Simone , Fonseca Belchiolina Beatriz , Zac Soligno Nicole I. , Ikhimiukor Odion O. , Armendaris Paulo Marcel , Andam Cheryl P. , Rossi Daise Aparecida
Published: July 2024

Consumption of raw, undercooked or contaminated animal food products is a frequent cause of Campylobacter jejuni infection. Brazil is the world’s third largest producer and a major exporter of chicken meat, yet population-level genomic investigations of C. jejuni in the country remain scarce. Analysis of 221 C. jejuni genomes from Brazil shows that the overall core and accessory genomic features of C. jejuni are influenced by the identity of the human or animal source. Of the 60 sequence types detected, ST353 is the most prevalent and consists of samples from chicken and human sources. Notably, we identified the presence of diverse bla genes from the OXA-61 and OXA-184 families that confer beta-lactam resistance as well as the operon cmeABCR related to multidrug efflux pump, which contributes to resistance against tetracyclines, macrolides and quinolones. Based on limited data, we estimated the most recent common ancestor of ST353 to the late 1500s, coinciding with the time the Portuguese first arrived in Brazil and introduced domesticated chickens into the country. We identified at least two instances of ancestral chicken-to-human infections in ST353. The evolution of C. jejuni in Brazil was driven by the confluence of clinically relevant genetic elements, multi-host adaptation and clonal population growth that coincided with major socio-economic changes in poultry farming.
Effect of bio-fortification of Balanites aegyptiaca
Del seed proteins on the mineral profile and pasting property of ogi
products
Authors: Friday Ogori Akama , Tartenger Girgih Abraham , Ojotu Eke Mike , Oneh Abu Joseph
Published: July 2024

Ogi production results in nutrient loss. B. aegyptiaca seeds,
rich in biomaterials, could enhance ogi’s nutritional potential. This
study aimed to fortify ogi with bioactives from B. aegyptiaca
seeds, targeting a 16% protein inclusion, compared to ogi flour as
control. Mineral profiles were analyzed, showing higher levels in the fortified
samples, particularly in DAM-ogi and PP-ogi, which are implicated in diabetes
control. Pasting profiles indicated higher values in PP-ogi, suggesting improved
rheological properties due to B. aegyptiaca bioactives.
Sst- and Vip-Cre mouse lines without age-related hearing loss
Authors: Foss Calvin T. , Olsen Timothy , Bigelow James , Hasenstaub Andrea R.
Published: July 2024

GABAergic interneurons, including somatostatin (SST) and vasoactive intestinal peptide (VIP) positive cells, play a crucial role in cortical circuit processing. Cre recombinase-mediated manipulation of these interneurons is facilitated by commercially available knock-in mouse strains such as Sst-IRES-Cre (Sst-Cre) and Vip-IRES-Cre (Vip-Cre). However, these strains are troublesome for hearing research because they are only available on the C57BL/6 genetic background, which suffer from early onset age-related hearing loss (AHL) due to a mutation of the Cdh23 gene. To overcome this limitation, we backcrossed Sst-Cre and Vip-Cre mice to CBA mice to create normal-hearing offspring with the desired Cre transgenes. We confirmed that in these “CBA Cre” lines, Cre drives appropriate expression of Cre-dependent genes, by crossing CBA Cre mice to Ai14 reporter mice. To assess the hearing capabilities of the CBA Cre mice, we measured auditory brainstem responses (ABRs) using clicks and tones. CBA Cre mice showed significantly lower ABR thresholds compared to C57 control mice at 3, 6, 9, and 12 months. In conclusion, our study successfully generated Sst-Cre and Vip-Cre mouse lines on the CBA background that will be valuable tools for investigating the roles of SST and VIP positive interneurons without the confounding effects of age-related hearing loss.
Claudin-11 regulates immunological barrier formation and spermatogonial proliferation through stem cell factor
Authors: Sugawara Taichi , Sonoda Kayoko , Chompusri Nattapran , Noguchi Kazuhiro , Okada Seiji , Furuse Mikio , Wakayama Tomohiko
Published: July 2024

Tight junctions (TJs) between adjacent Sertoli cells are believed to form immunological barriers that protect spermatogenic cells expressing autoantigens from autoimmune responses. However, there is no direct evidence that Sertoli cell TJs (SCTJs) do indeed form immunological barriers. Here, we analyzed male mice lacking claudin-11 (Cldn11), which encodes a SCTJ component, and found autoantibodies against antigens of spermatocytes/spermatids in their sera. Defective spermatogenesis was not restored inCldn11-deficient mice on a genetic background mimicking a severely impaired adaptive immune system. This suggests that defective spermatogenesis is not caused by autoimmune responses against spermatogenic cells. Further analyses showed thatCldn11knockout impaired Sertoli cell polarization, localization of stem cell factor (SCF) (a key molecule for maintaining differentiating spermatogonia) to the basal compartment of seminiferous tubules, and also proliferation of differentiating spermatogonia. We propose that CLDN11 creates a microenvironment for SCF-mediated spermatogonial proliferation at the basal compartment via Sertoli cell polarization.
Genomics-FM: Universal Foundation Model for Versatile and Data-Efficient Functional Genomic Analysis
Authors: Ye Peng , Bai Weiqiang , Ren Yuchen , Li Wenran , Qiao Lifeng , Liang Chaoqi , Wang Linxiao , Cai Yuchen , Sun Jianle , Yang Zejun , Zheng Peng , Dong Nanqing , Chen Tao , Wang Zhihui , Liu Xihui , Ma Xinzhu , Yan Hongliang , Wang Zhen , Wang Sijia , Ouyang Wanli
Published: July 2024

Artificial intelligence (AI) plays a crucial role in genomic analysis, offering great potential for comprehending biological phenomena such as heredity, development, diseases, and evolution. However, the development of AI models needs substantial labeled data, and these models are typically task-specific with limited generalizability to various applications. Here, we develop Genomics-FM, a genomic vocabulary driven foundation model that enables versatile and label-efficient functional genomic analysis. Specifically, Genomics-FM is first pretrained with ensemble genomic vocabulary on vast unlabelled data to learn comprehensive and generalizable representations and then finetuned with specific genomic vocabulary on limited labeled data to selectively activate and adapt the pretraining knowledge for specific tasks. We show that Genomics-FM significantly reduces the dependence on labeled data, and demonstrates the capability to outperform existing models across a comprehensive suite of tasks including genome annotation, epigenomic and expression profile prediction, and variant effect assessment. Remarkably, Genomics-FM even shows impressive zero-shot predictive capabilities across diverse species and tissues and exhibits noticeable adaptability to RNA-related tasks. With feasibility in data scarcity and even cross-domain biological scenarios, Genomics-FM will promote the broad application of AI and empower researchers to tackle previously insurmountable challenges, paving the way for groundbreaking research and discoveries.
Systematic Targeting of Protein Complexes with Molecular COUPLrs
Authors: Yang Diane , Harry Stefan Andrew , Chong Harrison Byron , Zhang Edwin , Nordenfelt Natalie Shannon , Chen Nicholas , Lee Christine , Kaluziak Stefan , Codd Elizabeth , Trivedi Samay , Gohar Magdy , McKnight Giovan , Mitchell Dawn R. , Ge Maolin , Gao Chengzhuo , Holmes Zavontae , Yang Wenxin , Smith Abigail Elizabeth , Carlin Alexander Daniel , Lazarov Matthew J. , Khandelwal Neha , Hara Mariko , Zhang Siwen , Leong Herman Xin Yang , Martinez Luna Hector , Chearavanont Zander , Emonds Kim , Popoola George , Barakat Idris , Onozato Maristela , Mahamdeh Mohammed , Fujino Toshio , Seo Hyuk-Soo , Dhe-Paganon Sirano , Sun Zhen-Yu Jim , Heffron Gregory J , Hata Aaron , Soberman Roy Jason , Liau Brian B. , Iafrate A. John , Bar-Peled Liron
Published: July 2024

Molecular glues that engage protein complexes have transformed the study of cell biology and have had a direct impact on clinical oncology. However, the identification of new glue classes and their corresponding protein complexes has remained largely serendipitous. To overcome this challenge, we report the development of molecular COUPLrs, elaborated small molecules flanked by two cysteine-reactive warheads, as well as CONNECT, an integrated chemical proteomic platform for target deconvolution. By profiling a library of molecular COUPLrs across 13 cancer cell lines, we uncovered hundreds of proteins that can be coupled together, including in some cases in mutant selective fashions. We develop an advanced COUPLr for the oncogene EML4-ALK, which engages the fusion outside of its kinase domain, restricts protein dynamics, and disrupts EML4-ALK signaling. Collectively, molecular COUPLrs substantially expand the scope of proteins that can be chemically connected, providing an unbiased approach to identify small molecules that target protein complexes.
Extensive transcriptional differentiation and specialization of a parasite across its host’s metamorphosis
Authors: DuBose James G. , de Roode Jacobus C.
Published: July 2024

Foundational theory on life cycle evolution suggests that given genetic independence, the phenotypes presented by different life stages will diverge more when they occupy more dissimilar niches. When divergence between stages is significant and punctual, we typically consider the life cycle complex. In parasites, the delineation between simple and complex life cycles is usually made between those that occupy single and multiple host species. However, many parasites can experience significant niche shifts in a single host. To explore the potential for a host’s metamorphosis to shape divergence between stages across its parasite’s life cycle, we quantified the transcriptional differentiation and specialization that the protozoan parasiteOphryocystis elektroscirrhaexhibits across the metamorphosis of its host the monarch butterfly. We found evidence thatO. elektroscirrhadifferentiates in concordance with the ecological turnover imposed by monarch transitions to different stages, and that patterns of transcriptional decoupling across theO. elektroscirrhaexceeded even that of its host. However, because of its greater gene content, the monarch exhibited greater total transcriptional turnover than its parasite. These findings highlight that synthesis of evolutionary theory pertaining to free-living and parasitic life cycles could be facilitated by more nuanced and continuous descriptions of life cycle complexity.
Alzheimer’s disease neuropathologic change mediates the relationship between ambient air pollution and dementia severity
Authors: Kim Boram , Blam Kaitlin , Elser Holly , Xie Sharon X. , Van Deerlin Vivianna M. , Penning Trevor M. , Weintraub Daniel , Irwin David J. , Massimo Lauren M. , McMillan Corey T. , Mechanic-Hamilton Dawn , Wolk David A. , Lee Edward B.
Published: July 2024

Background

Exposure to fine particulate matter air pollution (PM2.5increases risk for dementia. However, it is unknown whether this relationship is mediated by dementia-related neuropathologic change found at autopsy. We aimed to examine relationships between PM2.5exposure, dementia severity, and dementia-associated neuropathologic change.

Methods

This cross-sectional study used harmonized demographic, clinical, genetic, and neuropathological data from autopsy cases collected from 1998 to 2022 at the Center for Neurodegenerative Disease Research brain bank, University of Pennsylvania. Cases who had common neuropathologic forms of dementia and complete data on neuropathologic measures,APOEgenotype, and residential address were included in this study cohort. Dementia severity was measured by Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores. Ten dementia-associated neuropathologic measures representing Alzheimer’s disease, Lewy body disease, limbic-predominant age related TDP-encephalopathy, and cerebrovascular disease were graded or staged according to the consensus criteria. One-year average PM2.5exposure prior to death was estimated using a spatiotemporal prediction model based on residential addresses as the primary exposure measure. Linear, logistic and structural equation models were used to examine the relationships between PM2.5, CDR-SB and neuropathologic measures.

Results

A total of 861 autopsy cases were included (mean age at death 76.6 years [SD 10.3]; 481 [56%] male). Each 1 μg/m3increase in one-year average PM2.5concentration prior to death was associated with significantly greater cognitive and functional impairment (increase in CDR-SB score of 0.78; 95% confidence interval [CI], 0.52-1.05), faster cognitive and functional decline (change in CDR-SB scores of 0.13; 95% CI, 0.09-0.16), more severe Alzheimer’s disease neuropathologic change (ADNC; odds ratio [OR] of 1.07; 95% CI, 1.01-1.13), and a higher prevalence of large infarcts (OR, 1.17; 95% CI, 1.05-1.30). The relationship between PM2.5exposure and CDR-SB was mediated by ADNC (change in CDR-SB score due to ADNC level of 0.36; 95% CI, 0.13-0.65).

Conclusions

PM2.5exposure may increase dementia risk by increasing ADNC. Measures that improve air quality may represent a population-level intervention for the prevention of dementia.
Structure of yeast RAVE bound to a partial V1complex
Authors: Wang Hanlin , Tarsio Maureen , Kane Patricia M. , Rubinstein John L.
Published: July 2024

Vacuolar-type ATPases (V-ATPases) are membrane-embedded proton pumps that acidify intracellular compartments in almost all eukaryotic cells. Homologous with ATP synthases, these multi-subunit enzymes consist of a soluble catalytic V1subcomplex and a membrane-embedded proton-translocating VOsubcomplex. The V1and VOsubcomplexes can undergo reversible dissociation to regulate proton pumping, with reassociation of V1and VOrequiring the protein complex known as RAVE (regulator of theATPase ofvacuoles andendosomes). In the yeastSaccharomyces cerevisiae, RAVE consists of subunits Rav1p, Rav2p, and Skp1p. We used electron cryomicroscopy (cryo-EM) to determine a structure of yeast RAVE bound to V1. In the structure, RAVE is a L-shaped complex with Rav2p pointing toward the membrane and Skp1p distant from both the membrane and V1. Only Rav1p interacts with V1, binding to a region of subunit A not found in the corresponding ATP synthase subunit. When bound to RAVE, V1is in a rotational state suitable for binding the free VOcomplex, but it is partially disrupted in the structure, missing five of its 16 subunits. Other than these missing subunits and the conformation of the inhibitory subunit H, the V1complex with RAVE appears poised for reassembly with VO.
Primary bovine white blood cells support dissemination of Lumpy Skin Disease Virus while suppressing viral replication
Authors: Kumar Manoj , Frid Ohad , Sol Asaf , Rouvinski Alexander , Karniely Sharon
Published: July 2024

Lumpy skin disease (LSD) is a severe infectious, emerging transboundary disease of cattle, caused by a Pox family DNA virus. Lumpy skin disease virus (LSDV) infection is associated with a febrile response followed by emergence of widespread dermal nodules. In addition to the skin, LSDV resides in multiple internal organs and can be isolated from the blood of infected cattle. LSDV is suggested to be mechanically transmitted by biting arthropods. Live attenuated vaccines are commonly used to control disease and its spread. We have characterized the tropism, replication, and dissemination of a LSDV field isolate and of an attenuated vaccine strain usingin vitrosystems. To follow virus infection and dissemination in living cells, we have generated recombinant viruses expressing green fluorescent protein (GFP) under a synthetic viral promoter. Recombinant, GFP-expressing, LSDVs demonstrated similar replication kinetics to their corresponding parental LSDV strains in a bovine kidney cell line (MDBK). We further demonstrated that LSDV-GFP productively replicated in a bovine macrophage cell line and in primary bovine foreskin cells with no apparent differences between the field isolate and the vaccine strain. When bovine peripheral blood mononuclear cells (PBMCs) were infected with either LSDV recombinant strain, we observed specific viral driven GFP fluorescence as well as significant viral gene expression. However, infected PBMCs failed to support substantial viral DNA replication and release of infectious progeny. Subsequent analysis of the anti-viral response revealed that heat treated (HT) LSDV induced the expression of interferon- stimulated genes (ISGs) in PBMCs, but this response was suppressed by infectious viruses. Finally, we show that despite failed replication, LSDV infected PBMCs transmitted the virus to recipient co-cultured MDBK cells and produced infectious foci, suggesting a potential role of PBMCs in LSDV dissemination.

Highlights

Virulent and attenuated LSDV productively replicated in bovine kidney and bovine macrophage cell lines as well as in primary fibroblasts.

Adherent white blood cells were susceptible to LSDV field and attenuated vaccine infection.

LSDV showed active viral transcription in PBMCs yet no significant viral genome replication or production of infectious progeny.

PBMCs infected with heat-treated LSDV but not with fully infectious viruses upregulated ISGs’ RNA.

PBMCs transmitted and disseminated LSDV to contacting permissive cells.
Brain Structural Correlates of an Impending Initial Major Depressive Episode
Authors: Kraus Anna , Dohm Katharina , Borgers Tiana , Goltermann Janik , Grotegerd Dominik , Winter Alexandra , Thiel Katharina , Flinkenflügel Kira , Schürmeyer Navid , Hahn Tim , Langer Simon , Kircher Tilo , Nenadić Igor , Straube Benjamin , Jamalabadi Hamidreza , Alexander Nina , Jansen Andreas , Stein Frederike , Brosch Katharina , Usemann Paula , Teutenberg Lea , Thomas-Odenthal Florian , Meinert Susanne , Dannlowski Udo
Published: July 2024

Background

Neuroimaging research has yet to elucidate, whether reported gray matter volume (GMV) alterations in major depressive disorder (MDD) exist already before the onset of the first episode. Recruitment of presently healthy individuals with a known future transition to MDD (converters) is extremely challenging but crucial to gain insights into neurobiological vulnerability. Hence, we compared converters to patients with MDD and sustained healthy controls (HC) to distinguish pre-existing neurobiological markers from those emerging later in the course of depression.

Methods

Combining two clinical cohorts (n=1709), voxel-wise GMV ofn=45 converters,n=748 patients with MDD, andn=916 HC were analyzed in regions-of-interest approaches. By contrasting the subgroups and considering both remission state and reported recurrence at a 2-year clinical follow-up, we stepwise disentangled effects of 1) vulnerability, 2) the acute depressive state, and 3) an initial vs. a recurrent episode.

Results

Analyses revealed higher amygdala GMV in converters relative to HC (pTFCE-FWE=.037,d=0.447) and patients (pTFCE-FWE=.005,d=0.508), remaining significant when compared to remitted patients with imminent recurrence. Lower GMV in the dorsolateral prefrontal cortex (pTFCE-FWE<.001,d=0.188) and insula (pTFCE-FWE=.010,d=0.186) emerged in patients relative to HC but not to converters, driven by patients with acute MDD.

Conclusion

By examining one of the largest available converter samples in psychiatric neuroimaging, this study allowed a first determination of neural markers for an impending initial depressive episode. Our findings suggest a temporary vulnerability, which in combination with other common risk factors might facilitate prediction and in turn improve prevention of depression.
Altered Cortical Network Dynamics during Observing and Preparing Action in Patients with Corticobasal Syndrome
Authors: Krösche Marius , Hartmann Christian , Butz Markus , Schnitzler Alfons , Hirschmann Jan
Published: July 2024

Besides parkinsonism, higher order cortical dysfunctions such as apraxia are hallmarks of the corticobasal syndrome (CBS). To date, little is known about the electrophysiological underpinnings of these symptoms.

To shed more light on the pathophysiology of CBS, we recorded the magnetoencephalogram of 17 CBS patients and 20 age-matched controls engaged in an observe-to-imitate task. The task involved the display of a tool-use video in first person view (action observation), a written instruction to withhold movement until the presentation of a Go cue (movement preparation), and unilateral tool-use imitation. We investigated modulations of spectral power on the source level.

Action observation was associated with an event-related desynchronization in the beta-band (13-30Hz), which was weaker in CBS patients than in healthy controls. The group effect localized to superior parietal, primary motor, premotor and inferior frontal cortex bilaterally. While participants awaited the Go cue, beta power was again suppressed in the hemisphere contralateral to movement, and the rate of suppression correlated with reaction time. This modulation, too, was weaker in the CBS group. Immediately before movement onset, however, beta power was similar in both groups.

Our results reveal that action observation triggers beta suppression, likely reflecting motor cortical disinhibition, which is reduced in CBS patients. This pathological alteration might be a neural correlate of a selective deficit in the embedding of observed action into a motor representation (visuo-motor mapping). The suboptimal timing of the beta-power suppression to the upcoming Go cue presumably reflects a deficit in learning the trial’s temporal structure rather than a deficit in movement initialization.

Highlights

Action observation elicits a suppression of cortical beta power.

This suppression is diminished in CBS patients relative to controls.

The timing of beta desynchronization to an upcoming Go cue is impaired in CBS patients.

No evidence for an alteration of movement initialization in CBS patients.
Banking the unbanked: exploring the impact of internet penetration on accessibility to banking services in developed and developing economies
Authors: Jain Shivani , Sahu Jagadish Prasad
Published: July 2024

Purpose

The surge in internet usage has generated widespread speculation and optimism regarding its potential impact on the accessibility to financial services. The aim of this study is to investigate the effect of internet penetration on the accessibility of banking services in developed and developing countries.

Design/methodology/approach

Panel data regression methods are used to estimate the impact of internet penetration on accessibility to banking services in a sample of 74 countries from Global Findex survey waves of 2011, 2014, 2017 and 2021. To mitigate potential issues related to heteroscedasticity, autocorrelation and cross-sectional dependence, the study has implemented cluster robust standard errors testing. Furthermore, as a sensitivity check, the sample has been segregated into developed and developing country groups.

Findings

The study finds a significant positive correlation between internet penetration and banking access in full sample. Subsample analysis reveals that this relationship is statistically significant in developed countries, but not in developing ones, despite being positive. The research discusses the implications of these findings for both country groups.

Originality/value

Research to date has largely investigated the link between information and communication technology (ICT) and financial inclusion, often treating internet penetration as one component of ICT, which obscures its individual influence. This study, however, isolates internet penetration to specifically analyze its distinct effects on banking accessibility across developed and developing countries.
Knowledge fusion-driven sustainable decision-making for mega transportation infrastructure projects
Authors: Li Long , Luan Haiying , Yuan Mengqi , Zheng Ruiyan
Published: July 2024

Purpose

As the scale of mega transportation infrastructure projects (MTIs) continues to expand, the complexity of engineering construction sharply increases and decision-making sustainability faces severe challenges. Decision-making for mega transportation infrastructure projects unveils the knowledge-intensive characteristic, requiring collaborative decisions by cross-domain decision-makers. However, the exploration of heterogeneous knowledge fusion-driven decision-making problems is limited. This study aims to improve the deficiencies of existing decision-making by constructing a knowledge fusion-driven multi-attribute group decision model under fuzzy context to improve the sustainability of MTIs decision-making.

Design/methodology/approach

This study utilizes intuitionistic fuzzy information to handle uncertain information; calculates decision-makers and indicators weights by hesitation, fuzziness and intuitionistic fuzzy entropy; applies the intuitionistic fuzzy weighted averaging (IFWA) operator to fuse knowledge and uses consensus to measure the level of knowledge fusion. Finally, a calculation example is given to verify the rationality and effectiveness of the model.

Findings

This research finally constructs a two-level decision model driven by knowledge fusion, which alleviates the uncertainty and fuzziness of decision knowledge, promotes knowledge fusion among cross-domain decision-makers and can be effectively applied in practical applications.

Originality/value

This study provides an effective decision-making model for mega transportation infrastructure projects and guides policymakers.
EnglishHelper: funding options for social enterprises
Authors: Batra Neetika , Nihar K. Lubza , Iyer S. Veena
Published: July 2024

Learning outcomes

This case aims to introduce students to the social sector financing (internal and external) landscape, and its nuances. It specifically provides material to enable critical evaluation and decision-making around financing a for-profit social enterprise and its associated challenges.

Case overview/synopsis

The case highlights the fundraising options available to a social enterprise in an emerging economy like India. EnglishHelper Technologies Private Ltd. (EH) commenced operations in 2011 as a subsidiary of its parent Boston-based company, to provide technology-based learning solutions primarily to the underserved segments of the country’s population. Sanjay Gupta, co-founder and CEO, EH Inc., wanted to explore funding options suitable for the company’s next growth stage. The existing funding sources of equity from its parent company, grants and revenues (mainly from product sales to government schools) had worked well for EH in the initial years of its growth. But its financial performance was being impacted, and, additionally, further scaling up would require sources that could give a much larger quantum of funds and add support to EH’s operations. EH would also need to revisit its revenue model to strengthen its financial sustainability, by drawing lessons from the other prevalent ones in the ed-tech sector and make it more effective. The case encourages students to assess the various funding alternatives, internal and external, for a social sector private company with a for-profit model like EH, to enable it to achieve its scaling-up plans while serving its social mission.

Complexity academic level

The case is relevant for both undergraduate and postgraduate students and can be used in business administration programs.

Subject code

CSS 1: Accounting and finance.

Supplementary materials

Teaching notes are available for educators only.
A teaching-learning sequence to develop epistemic thinking in engineering students at master’s educational level
Authors: Cascarosa Salillas Esther , Sánchez-Azqueta Carlos , Gimeno Cecilia , Aldea C.
Published: July 2024

Purpose

This research work had been a double objective, to help the students achieve the learning outcomes, scientific skills and on the other hand, to develop specific scientific sub-competences, all of these related not only with the conceptual knowledge but also with the knowledge of procedurals and epistemology.

Design/methodology/approach

A didactic sequence has been designed and applied with students of the University Catholique of Louvain (Belgium) in collaboration with teachers from the University of Zaragoza (also researchers in the knowledge areas of Electronics, Applied Physics and the Didactics of Experimental Sciences). Several methodologies were applied thorough the teaching-learning sequence as the flipped classroom is. A varied sample of assessment instruments was used.

Findings

The results suggest this sequence produces a more significant learning than a more conventional teaching, however there is no increase in the number of students who passed. The students explaining phenomena scientifically, evaluating and designing experiments and making researchable questions and interpreting data and scientific evidence, which are a consequence of the development of scientific knowledge (content, procedural and epistemic). In addition, the students kept motivated by this methodological change and maintained the perception of having achieved the expected learning according to the objectives of the course.

Originality/value

Until a few years ago, research in the didactics of experimental sciences, and the application in the classroom of the results obtained, was limited to education in non-university stages. The opportunity of this work is to expand knowledge in relation to the application of didactic strategies in physics education at a higher level.
Sustainable development, economic policy uncertainty and tax risk
Authors: Chen Wanyi , Meng Fanli
Published: July 2024

Purpose

Unpredictable economic landscapes have led to a continuous escalation in global economic policy uncertainty (EPU). Improving risk management and sustainability in an environment with high macro risk is critical for business development. This study aims to explore the impact of corporate sustainable development on corporate tax risk.

Design/methodology/approach

After using a sample of companies that were A-share listed on the Shanghai and Shenzhen stock exchanges from 2011 to 2021, this paper applies ordinary least squares and a moderate effect model.

Findings

Better environmental, social and governance (ESG) performance can weaken corporate tax risk by improving green innovation capability, reputation and information transparency. Meanwhile, the restraining effect of ESG on tax risk was more significant amid high EPU. These impacts were amplified amid higher market competition, lower tax supervision and a lower degree of corporate digital transformation.

Practical implications

The findings emphasize the need for the government to establish a healthy business and tax environment so that enterprises can improve sustainable development and increase their risk management abilities, especially post-COVID-19.

Social implications

This study guides enterprises and the entirety of society to in paying attention to and promoting ESG practices, which can enhance enterprise tax management.

Originality/value

This study expands the research on the economic consequences of sustainable development and the factors influencing corporate tax risk and EPU.
A double‐blind pilot study of oral baricitinib in adult patients with lupus erythematosus panniculitis
Authors: Chen Jingjing , Luo Yijin , Duan Yuanyuan , Wang Liangchun , Long Hai , Liu Yi , Yao Xu , Lu Qianjin
Published: July 2024

Lupus erythematosus panniculitis (LEP) is a chronic inflammatory skin disease with a significant impact on the overall well‐being of patients. The safety and efficacy of oral baricitinib for the treatment of LEP have not been studied. This study aimed to explore the efficacy of oral baricitinib in patients with LEP who are recalcitrant or intolerant to conventional therapies. Patients (aged ≥18 years) with active LEP (with a revised cutaneous lupus erythematosus disease area and severity index [RCLASI]‐active score ≥4] were randomly assigned 2:1 to baricitinib (4 mg) or placebo (once daily for 20 weeks). The placebo group was switched to baricitinib (4 mg) at week 13, and the final evaluation was conducted at week 24. The primary endpoint was the proportion of patients with an RCLASI‐A score decreased by 20% at week 12. The secondary endpoints included the changes in the Cutaneous Lupus Erythematosus Disease Area and Severity Index active‐(CLASI‐A) score, the Dermatology Life Quality Index (DLQI), the Physician's Global Assessment (PGA) score, and safety. Five patients were enrolled. Three patients received baricitinib (4 mg), and two patients were treated with placebo. Two patients in the baricitinib treatment group showed a significant RCLASI‐A decrease at week 12 and week 24. Two patients in the placebo group had no change in RCLASI‐A at week 12 and a significant decrease at week 24. No new safety events were observed. Treatment with baricitinib was effective and well tolerated in patients with LEP.
Working knowledge, uncertainty and ontological politics: An ethnography of UK long covid clinics
Authors: Greenhalgh Trisha , Darbyshire Julie , Ladds Emma , Van Dael Jackie , Rayner Clare
Published: July 2024

Long covid (persistent COVID‐19) is a new disease with contested aetiology and variable prognosis. We report a 2‐year ethnography of UK long covid clinics. Using a preformative lens, we show that multidisciplinary teams (MDTs) built working knowledge based on shared practices, mutual trust, distributed cognition (e.g. emails, record entries), relational knowledge of what was at stake for the patient, and harnessing uncertainty to open new discursive spaces. Most long covid MDTs performed the working knowledge of ‘rehabilitation’, a linked set of practices oriented to ensuring that the patient understood and strove to ‘correct’ maladaptive physiological responses (e.g. through breathing exercises) and pursued recovery goals, supported by physiotherapists, psychologists and generalist clinicians. Some MDTs with a higher proportion of doctors (e.g. cardiologists, neurologists, immunologists) enacted the working knowledge of ‘microscopic damage’, seeking to elucidate and rectify long covid’s underlying molecular and cellular pathology. They justified non‐standard investigations and medication in selected patients by co‐constructing an evidentiary narrative based on biological mechanisms. Working knowledge was ontologically concordant within MDTs but sometimes discordant between MDTs. Overt ontological conflict occurred mostly when patients attending ‘rehabilitation’ clinics invoked the working knowledge of microscopic damage that had been generated and circulated in online support communities.
Symptom flares in women with chronic pelvic pain: Questionnaire study within a cohort study (translational research in pelvic pain (TRiPP))
Authors: Coxon Lydia , Lugt Celia , Horne Andrew W. , Evans Emma , Abreu‐Mendes Pedro , Arendt‐Nielsen Lars , Aziz Qasim , Becker Christian M. , Birch Judy , Charrua Ana , Demetriou Lysia , Ferreira‐Gomes Joana , Hoffman Anja , Hummelshoj Lone , Krassowski Michal , Lunde Claire E. , Meijlink Jane , Missmer Stacey A. , Perro Danielle , Zondervan Krina T. , Sieberg Christine B. , Cruz Francisco , Nagel Jens , Vincent Katy
Published: July 2024

Objective

To quantify the variation, triggers and impact on quality of life of symptom flares in women with chronic pelvic pain (CPP).

Design

Cross‐sectional questionnaire within the Translational Research in Pelvic Pain clinical cohort study.

Setting

Women with CPP, with subgroups of women with endometriosis (EAP), interstitial cystitis/bladder pain syndrome (BPS), comorbid endometriosis and interstitial cystitis/bladder pain syndrome (EABP), and those with pelvic pain without endometriosis or interstitial cystitis/bladder pain syndrome (PP).

Population or Sample

A total of 100 participants.

Methods

Descriptive and comparative analysis from flares questionnaire.

Main Outcome Measures

The prevalence, characteristics and triggers of short, medium and long symptom flares in CPP.

Results

We received 100 responses of 104 questionnaires sent. Seventy‐six per cent of women with CPP have ever experienced symptom flares of at least one length (short, medium and/or long). Flares are associated with painful and non‐painful symptoms. There is large variation for the frequency, duration, symptoms and triggers for flares. Over 60% of participants reported flares as stopping them from doing things they would usually do, >80% reported thinking about symptoms of flares and >80% reported flares being bothersome.

Conclusions

Flares are prevalent and clinically very important in CPP. More research is needed to elucidate the mechanisms and characteristics underlying flares. Clinical practice should include an enquiry into flares with the aim of finding strategies to lessen their burden.
Membranous nephropathy with Kimura's disease: A case report and review of literature
Authors: Loganathan Sathish Kumar , Mondal Sanjib , Basu Suprit , Thangaraj Abarna , Vignesh Pandiarajan , Nada Ritambhra , Suri Deepti
Published: July 2024

Kimura's disease (KD) is a chronic inflammatory disorder characterized by nontender lymphadenopathy involving the head and neck region. Renal involvement in KD is rare, especially in children. We report a 12‐year‐old boy who had been previously treated for classical KD and had presented with anasarca and oliguria after 4 years. There were no swellings or lymphadenopathy. The kidney biopsy revealed membranous nephropathy. Remission was achieved with oral prednisolone and tacrolimus therapy. This patient highlights the need to regularly monitor patients with KD for the evolution of renal diseases, even if lymphadenopathy regresses. Serial monitoring for eosinophilia, inflammatory markers, and urine examination is needed to help identify subclinical disease early and prompt initiation of specific therapy.
Computed tomography imaging‐based radiologic evaluation of pulmonary artery thrombosis in a series of patients with Behcet's disease
Authors: Germe Serife Asya , Ozsoy Zehra , Bulat Bugu , Durhan Gamze , Fırlatan Büşra , Kilic Levent , Akdogan Ali
Published: July 2024

Aim

Pulmonary artery involvement is a severe complication of Behcet's disease (BD). Although venous thrombosis is common in BD, pulmonary embolism is considered to be rare because the inflammatory nature makes the thrombi strongly adherent to the venous walls. This study aimed to define the radiological characteristics of pulmonary artery thrombosis (PAT) on computed tomography (CT) imaging in BD patients.

Methods

We retrospectively evaluated 165 BD patients with vascular involvement. Among the patients with venous involvement (n = 146), we identified 65 patients who had undergone thorax CT imaging previously. Fourteen patients who were diagnosed with PAT were included in the study. Expert radiologists re‐evaluated the patients' initial and control thorax CT scans, classified the PAT as acute or chronic based on their radiological features.

Results

The patients' median age was 35 (min–max: 15–60) years at the time of the initial CT scan, and nine were male. Twelve (85.7%) patients were symptomatic at the time of CT evaluation. Upon re‐evaluating the thorax CTs, acute PAT was diagnosed in six (42.8%); chronic PAT was detected in eight (57.1%) patients. Two patients with chronic PAT also had acute PAT. Pulmonary artery aneurysms were present in three (21.4%) patients, and intracardiac thrombus was found in three (21.4%) patients.

Conclusion

A significant number of BD patients with venous involvement had radiological findings consistent with acute PAT potentially due to pulmonary emboli in this study. The clinical importance of these lesions has to be defined with future studies.
New blockholder and investor limited attention: Evidence from private acquisitions
Authors: Akbulut Mehmet E. , Huang Emily Jian , Ma Qingzhong , Zhang Athena Wei
Published: July 2024

In acquisitions of private firms, new blockholders (NewBs) are expected to form when substantial stocks are paid. Investors react strongly to a NewB signal, given the perceived monitoring and certification benefits. However, they largely ignore value‐relevant but less salient signals, such as the true quality of the acquisition. Investors' limited attention allows financially weak firms to adopt the NewB strategy and take speculative deals. Our results support this inattention hypothesis: NewB acquirers are financially weaker and earn higher announcement‐period returns, but lower long‐run returns; moreover, acquirers' financial weakness negatively predicts long‐run performance.
Unravelling the intricacies of Porphyromonas gingivalis: virulence factors, lifecycle dynamics and phytochemical interventions for periodontal disease management
Authors: Nadaf Rubeen , Kumbar Vijay M. , Ghagane Shridhar
Published: July 2024

Porphyromonas gingivalis is a gram‐negative anaerobic bacterium recognized for its pivotal role in the pathogenesis of periodontal diseases. This review covers an overview of the virulence factors and lifecycle stages of P. gingivalis, with a specific focus on attachment and colonization, biofilm formation, growth and multiplication, dormancy survival and dissemination. Additionally, we explore the significance of inter‐bacterial cross‐feeding within biofilms. Furthermore, we discuss potential phytochemical‐based strategies to target P. gingivalis, including the use of curcumin, apigenin, quercetin and resveratrol. Understanding the virulence factors and lifecycle stages of P. gingivalis, along with the promising phytochemical‐based interventions, holds promise for advancing strategies in periodontal disease management and oral health promotion.
Microangiopathic thrombocytopenia caused by vitamin B12 deficiency responding to plasma exchange
Authors: Dwyre Denis M. , Reddy Jyotsna , Fernando Leonor P. , Donnelly Jacob M. , Miller Joshua W. , Green Ralph
Published: July 2024

A young adult African American female presented with normocytic microangiopathic haemolytic anaemia, elevated lactate dehydrogenase and thrombocytopenia. The patient responded to therapeutic plasma exchanges (TPE) for presumed thrombotic microangiopathy caused by thrombotic thrombocytopenic purpura (TTP). After relapsing, the patient was found to have pancytopenia, megaloblastic bone marrow and low vitamin B12 consistent with pernicious anaemia, which improved with intramuscular B12 and discontinuation of TPE. B12‐deficient macrocytosis was not seen at presentation due to concomitant alpha‐thalassaemia. Initial clinical/laboratory improvement is attributed to B12 present in TPE plasma. B12 deficiency can mimic TTP. Vigilance is needed regarding atypical presentations of pernicious anaemia.