bluuebunny/crossref_metadata_2025 huggingface dataset:
Who develops chronic pain after an acute lower limb injury? A longitudinal study of children and adolescents
Authors: Fisher Emma , Monsell Fergal , Clinch Jacqui , Eccleston Christopher
Published: June 2024

Prevention of chronic pain is a major challenge in this area of clinical practice. To do this, we must be able to understand who is most at risk of developing chronic pain after an injury. In this study, we aimed to identify risk factors of chronic pain onset, disability, and pain interference after a lower limb musculoskeletal injury in children and adolescents between 8 to 16 years of age. We assessed biopsychosocial factors including age, sex, pubertal status, anxiety, depression, fear of pain, pain worry, adverse life events, and sleep in children. We also assessed risk factors in parents including parent anxiety, depression, parent pain catastrophising, and protective behaviours. Logistic and hierarchical linear regressions identified risk factors assessed immediately postinjury for outcomes assessed at 3 months postinjury. Fourteen percent (17/118 children) reported chronic pain 3 months after injury. There were significant between-group differences in children with and without chronic pain at baseline. Children with chronic pain reported higher pain intensity, disability, pain interference, child depression, fear of pain, and catastrophic thinking about their pain. Regressions showed child depression and fear of pain at baseline independently predicted chronic pain onset at 3 months, parent protectiveness predicted child pain interference at 3 months, and child depression, poor sleep, parent anxiety and pain catastrophising predicted disability. Most children recover after a lower limb injury, but a minority develop chronic pain predicted by important psychosocial risk factors, which could be addressed to prevent the onset of treatment-resistant chronic pain and disability.
Burden of chronic pain among adult pastoralists in Ethiopia: a cross-sectional household survey
Authors: Baum Eleonore , Abdi Sied , Hattendorf Jan , van Eeuwijk Peter , Tschopp Rea , Vosseler Birgit , Zinsstag Jakob , Probst-Hensch Nicole
Published: June 2024

Chronic pain is a major global health problem. Untreated pain causes particular suffering in marginalized communities. Most studies investigating chronic pain in sub-Saharan Africa stem from South Africa and Nigeria. Pastoralists are particularly underrepresented in pain research. The main objective of this study is to investigate the burden of chronic pain in adult pastoralists in the Somali Regional State of Ethiopia. We conducted a cross-sectional household survey among adult pastoralists (aged 18 years or older, N = 299) by face-to-face interviews. To randomly select households, we applied GPS-based household localization and recruitment. Chronic pain was self-reported by 17.0% (95% CI: 10.8-25.7) of male and 34.7% (95% CI: 28.4-41.5) of female adult pastoralists. The prevalence of chronic pain increased with age from 5.4% (95% CI: 0.8-30.1; 18-34 years) to 27.1% (95% CI: 15.1-43.7; 35-54 years) to 69.1% (95% CI: 53.7-81.1; 55 years and older). The body sites most commonly affected among those with chronic pain were knees (37.2%), followed by lower back (33.7%) and head (23.3%). The data for the first time provide insights into the burden of chronic pain among Somali pastoralists and reveal associated risk factors. The results support the planning of locally adapted health interventions for pastoralist-specific pain management considering the effects of chronic pain on pastoralists' daily lives.
Metabolic support for patients on extra-corporeal membrane oxygenation
Authors: Hileman Bethany Anne , Martucci Gennaro , Subramanian Harikesh
Published: June 2024

Purpose of review

The purpose of the review is to summarize recent research on metabolic support during extracorporeal membrane oxygenation. In this review, we cover the evidence on nutritional supplementation, both the route of supplementation, timing of initiation of supplementation as well as quantities of supplementation needed. In addition, we discuss the recent trend in awake extracorporeal membrane oxygenation (ECMO) and its benefits to patients.

Recent findings

As ECMO use continues to increase over the last few years, for both cardiovascular as well as respiratory failure, the need to optimize the metabolic states of patients has arisen. Increasing evidence has pointed towards this hitherto unexplored domain of patient care having a large impact on outcomes. Additionally, strategies such as awake ECMO for select patients has allowed them to preserve muscle mass which could aid in a faster recovery.

There is a role of optimal metabolic support in the early recovery of patients on ECMO that is currently under-recognized. Future directions of research that aim to improve post ECMO outcomes must focus on this area.
Light, sleep and circadian rhythm in critical illness
Authors: Perry Heather , Alight Athina , Wilcox M. Elizabeth
Published: June 2024

Purpose of review

Sleep and circadian disruption (SCD) are associated with worse outcomes in the ICU population. We discuss sleep, circadian physiology, the role of light in circadian entrainment and its possible role in treating SCD, with special attention to the use of light therapies and ICU design.

Recent findings

The American Thoracic Society recently published an official research statement highlighting key areas required to define and treat ICU SCD. Recent literature has been predominantly observational, describing how both critical illness and the ICU environment might impair normal sleep and impact circadian rhythm. Emerging consensus guidance outlines the need for standardized light metrics in clinical trials investigating effects of light therapies. A recent proof-of-concept randomized controlled trial (RCT) showed improvement in delirium incidence and circadian alignment from ICU room redesign that included a dynamic lighting system (DLS).

Further investigation is needed to define the optimal physical properties of light therapy in the ICU environment as well as timing and duration of light treatments. Work in this area will inform future circadian-promoting design, as well as multicomponent nonpharmacological protocols, to mitigate ICU SCD with the objective of improving patient outcomes.
Research of assisted housing design for the bedridden elderly and their family caregivers
Authors: Shang Tingting , Wang Yue , Yao Yanan , Wang Yu , Wang Xiaomeng
Published: June 2024

Objectives:

To explore the housing design strategies based on the needs of the bedridden elderly and their family caregivers to promote the health of the bedridden elderly and reduce the stress of family caregiving.

Methods:

A descriptive qualitative study, grounded in phenomenological principles, was undertaken to investigate the experiences of 24 bedridden elderly individuals and their respective 24 family caregivers. The interviews were semistructured and supplemented by nonparticipant observations.

Results:

The needs of the bedridden elderly and their family caregivers for the housing environment were mainly focused on safety guarantees, health promotion, and care assistance. Challenges such as spatial barriers, poor environmental quality, and insufficient adaptability in housing components and aids can greatly reduce the assisted role of housing.

Conclusion:

This paper emphasizes the importance of tailoring housing design to the specific physical characteristics, sensory needs, and behavioral habits of the bedridden elderly and their family caregivers. Effective layout and design should consider spatial flow, control and regulation of the physical environment, and the careful selection and configuration of accessories and aids.
Celecoxib enhances the response of tumor cells to cisplatin through upregulating PUMA in non–small cell lung cancer carrying wild-type p53
Authors: Xiao Yuxuan , Wang Ziyu , Gu Meng , Tan Jinjing , Li Weiying
Published: June 2024

Celecoxib, a cyclooxygenase-2 inhibitor, can enhance the efficacy of chemotherapy; however, its effect seems inconsistent. In this study, we investigated whether celecoxib would increase the antiproliferative effects of cisplatin in human lung cancer cells. Our data demonstrated the synergistic effects of celecoxib with cisplatin in wild-type p53 cells and their antagonistic effects in mutated or deleted p53 cells. Combination indices of 0.82 to 0.93 reflected a synergistic effect between celecoxib and cisplatin in lung cancer cells with wild-type p53. Combination indices of 1.63 to 3.00 reflected antagonism between celecoxib and cisplatin in lung cancer cells with mutated or deleted p53. Compared with that in cells with mutated or deleted p53, apoptosis significantly increased with the addition of celecoxib and cisplatin in wild-type p53 cells (P < 0.05). Moreover, the results in vivo were similar to those in vitro: celecoxib combined with cisplatin slowed tumor growth in wild-type p53 groups and not in mutated or deleted p53 groups. In addition, celecoxib promoted p53 translocation into the nucleus and upregulated active p53 expression in wild-type p53 cells. Celecoxib combined with cisplatin upregulated PUMA (PUMA is a downstream gene of p53) after active p53 increased in wild-type p53 cells. In summary, the combination of celecoxib and cisplatin demonstrates clear synergistic effects in wild-type p53 cells and antagonistic effects in mutated or deleted p53 cells. The synergistic effect was achieved by apoptosis, induced by upregulating PUMA. Our results will provide a new treatment strategy for patients carrying wild-type p53, insensitive to cisplatin.
Spontaneous intra-abdominal hematomas in a hepatocellular carcinoma patient treated with lenvatinib: a case report
Authors: Ma Hong , Li Jun-Feng , Wang An-Rong , Tan Yong , Yuan Guang-Jin
Published: June 2024

A 44-year-old patient was admitted with tumor rupture in the left hepatic lateral lobe, and he underwent emergent exploratory laparotomy and proceeded for hepatic left lateral lobectomy on September 19, 2021. The final diagnosis of hepatocellular carcinoma was confirmed by histopathological examination of the surgical specimen. Afterward, the patient received hepatic arterial infusion chemotherapy with FOLFOX (oxaliplatin, fluorouracil, and leucovorin) for 5 cycles. Subsequently, recurrence of the hepatocellular carcinoma was diagnosed in the abdominal cavity. The patient was then treated with lenvatinib. Within less than 1 month of the treatment with lenvatinib, the patient was admitted to the emergency room on June 2, 2022, because of acute intra-abdominal bleeding (hematomas). Percutaneous intra-abdominal angiography found that the bleeding vessels were the right gastroepiploic artery and left gastric artery. The patient was stabilized after arterial embolization using gelatin sponges. The diagnosis and management of spontaneous intra-abdominal hematomas are discussed.
BMI1 overexpression is correlated with a poor prognosis and immune infiltration in hepatocellular carcinoma
Authors: Wang Min-Cong , Yang Peng-Tao , Zhang Yang , Ma Hong-Bing
Published: June 2024

Background

Owing to the occurrence of primary or secondary tolerance, the efficacy of immunotherapy for hepatocellular carcinoma (HCC) patients is limited. Therefore, the mechanism underlying this tolerance needs to be further investigated. B cell–specific Moloney murine leukemia virus integration site 1 (BMI1) is associated with cancer stem cell tumorigenesis, progression, and the maintenance of the self-renewal. However, the effect of BMI1 expression on immune infiltration and prognosis in HCC is still unclear.

Methods

To assess the relationship between BMI1 expression and HCC prognosis and immune infiltration, the GEPIA database, TIMER database, and K-M plotter were used. TIMER database was used to determine the levels of BMI1 in various tumor tissues and corresponding normal tissues, and examine the association between BMI1 expression and tumor-infiltrating immune cells. GEPIA database was applied to determine BMI1 expression in various tumor tissues and corresponding normal tissues. K-M Plotter was used to study the relationships among BMI1 expression, clinicopathological features, and survival rates.

Results

BMI1 expression was markedly higher in various solid tumors compared with that in the respective normal tissues, including HCC, and high expression led to poor relapse-free survival and overall survival in HCC patients. BMI1 overexpression was also correlated with the infiltration of immune cells (eg, B cells, CD8+T cells, CD4+T cells, dendritic cells, neutrophils, and macrophages) and positively associated with different subsets of T cells, monocytes, and M1 macrophages, among others.

Conclusions

This study demonstrates that high BMI1 expression is strongly correlated with immune infiltration and poor prognosis in HCC. Increased expression of BMI1 might thus be a potential mechanism of immune tolerance in this disease.
Progress and current perspectives of diagnosis and treatment of hepatoid adenocarcinoma of the stomach
Authors: Qin Kai , Zhang Jing , Gong Chen , Cheng Yi
Published: June 2024

Hepatoid adenocarcinoma of the stomach (HAS) is a rare malignant gastric tumor exhibiting both hepatocellular and adenocarcinomatous differentiation. Patients are often diagnosed at an advanced stage, and their clinical symptoms closely resemble those of gastric adenocarcinoma. Because of its rarity, misdiagnosis and missed diagnoses are prevalent. Compared with gastric adenocarcinoma, HAS typically exhibits higher invasiveness and a more unfavorable prognosis. This review aimed to elaborate on the pathological features, potential mechanisms, clinical characteristics, diagnosis, and prognosis of HAS. The insights provided aimed to contribute robust guidance for the clinical management of patients with HAS.
TROVE2 regulated invasion and migration of hepatocellular carcinoma cells via heparanase
Authors: Cheng Niangmei , Zheng Xiaoyuan , Huang Jingyun , Wang Fei , Wang Yang , Zhong Yue , Wang Yingchao , Wang Gaoxiong , Zhao Bixing
Published: June 2024

Background

The role of TROVE domain family member 2 (TROVE2) has been well-demonstrated in autoimmune diseases; however, its involvement in liver cancer remains unclear. Therefore, this study aimed to explore the biological function and clinical significance of TROVE2 in hepatocellular carcinoma (HCC).

Methods

The expression level of TROVE2 was analyzed in HCC and paired adjacent tissue samples using real-time reverse transcription-quantitative polymerase chain reaction. The impact of TROVE2 on migration and invasion in HCC cells was analyzed through Transwell assays and Western blotting. High-throughput transcriptome sequencing and bioinformatics analyses were performed to identify downstream target genes. Back-complementation experiments were employed to verify the influence of downstream proteins on TROVE2-induced invasion and migration of HCC cells.

Results

TROVE2 exhibited significant overexpression in liver cancer tissue, correlating with shorter overall survival. Overexpression of TROVE2 facilitated the invasion, metastasis, and epithelial-mesenchymal transition (EMT) process of HCC cells, whereas TROVE2 knockdown restrained migration, invasion, and EMT in these cells. Transcriptome sequencing and bioinformatics analysis identified heparanase (HPSE) as a downstream target protein of TROVE2. Subsequent back-complementation experiments provided evidence that HPSE overexpression promoted TROVE2-mediated prometastasis effects. Moreover, the study revealed that TROVE2 was capable of regulating the EMT pathway through GSK-3β phosphorylation.

Conclusions

TROVE2 facilitated the invasion, migration, and EMT process of HCC cells through phosphorylation of the HPSE/GSK-3β axis, indicating its significance as an important protein in tumor progression.
Prevalence and Correlates of SARS-CoV-2 Vaccine Uptake and Hesitancy Among People With HIV Across the United States
Authors: Spinelli Matthew A. , Johnson Mallory O. , Lisha Nadra E. , Jain Jennifer P. , Moreira Carlos V. , Glidden David V. , Burkholder Greer A. , Crane Heidi M. , Jacobson Jeffrey M. , Cachay Edward R. , Mayer Kenneth H. , Napravnik Sonia , Moore Richard D. , Gandhi Monica , Christopoulos Katerina A.
Published: June 2024

Background:

People with HIV (PWH) have higher risk of COVID-19 mortality. SARS-CoV-2 vaccination is highly effective among PWH, although vaccine hesitancy could limit the population-level impact.

Setting:

From February 2021 to April 2022, PWH from 8 sites in the Centers for AIDS Research Network of Integrated Clinical Systems completed a vaccine hesitancy instrument as part of routine care.

Methods:

Participants were defined as vaccine hesitant if they had not received the SARS-CoV-2 vaccine and would probably/definitely not receive it. We assessed factors associated with SARS-CoV-2 vaccine hesitancy using logistic regression adjusted for demographics, unsuppressed viral load (VL > 200 copies/mL), month, and time on ART; using inverse probability weighting for survey nonresponse.

Results:

Overall, 3288 PWH with a median age of 55 were included; 18% were female and 94% were virally suppressed. At the time of survey, 27% reported they had not received the SARS-CoV-2 vaccine, and 9% (n = 279) reported vaccine hesitancy. Factors associated with vaccine hesitancy included female sex (adjusted odds ratio [AOR] = 2.3; 95% confidence interval (CI): 1.6–3.2), Black vs. White race (AOR 1.7; 95% CI: 1.2 to 2.4), younger age (AOR 1.4; 95% CI: 1.2 to 1.5), and unsuppressed VL (AOR 1.9; 95% CI: 1.3 to 3.0).

Conclusion:

Overall, over one-quarter of PWH in this multisite cohort were unvaccinated for SARS-CoV-2 when interviewed February 21–April 22. Vaccine hesitancy was reported by approximately 9% of PWH and was higher among women, Black PWH, younger PWH, PWH with unsuppressed VL, and those in the South/Midwest. Renewed efforts are needed to address concerns of PWH about vaccinations against COVID-19 as the pandemic evolves, and vaccines in general, given the potential for future pandemics.
Compositional Differential Abundance Testing: Defining and Finding a New Type of Health-Microbiome Associations
Authors: Ma Siyuan , Huttenhower Curtis , Janson Lucas
Published: June 2024

A major task of microbiome epidemiology is association analysis, where the goal is to identify microbial features related to host health. This is commonly performed by differential abundance (DA) analysis, which, by design, examines each microbe as isolated from the rest of the microbiome. This does not properly account for the microbiome’s compositional nature or microbe-microbe ecological interactions, and can lead to confounded findings, i.e., microbes that only appear to associate with health through their confounding association with health-related, biologically informative microbes. To remedy these issues, we present Compositional Differential Abundance (CompDA) analysis, a novel approach for health-microbiome association. CompDA provides a novel approach to identify health-related microbes by examining the microbiome holistically, which a) accounts for the data’s compositionality and ecological interactions, and b) has clear interpretations corresponding to host health as affected by microbiome-based interventions. CompDA prioritizes health-related microbes and controls false discoveries by implementing recent advances from high-dimensional statistics, and can be flexibly adapted to many common tasks in modern microbiome epidemiology, including enhancing microbiome-based machine learning by providing rigorous p-values to prioritize important features. We validate the performance of CompDA, and compare against canonical microbiome association methods including DA with extensive, real-data-informed simulation studies. Lastly, we report novel and consistent findings of CompDA in application, based on re-examination of recently reported microbial signatures of colorectal cancer in a meta-analysis.
IMMUNOTAR - Integrative prioritization of cell surface targets for cancer immunotherapy
Authors: Shraim Rawan , Mooney Brian , Conkrite Karina L. , Weiner Amber K. , Morin Gregg B. , Sorensen Poul H. , Maris John M. , Diskin Sharon J. , Sacan Ahmet
Published: June 2024

Cancer remains a leading cause of mortality globally. Recent improvements in survival have been facilitated by the development of less toxic immunotherapies; however, identifying targets for immunotherapies remains a challenge in the field. To address this challenge, we developed IMMUNOTAR, a computational tool that systematically prioritizes and identifies candidate immunotherapeutic targets. IMMUNOTAR integrates user-provided RNA-sequencing or proteomics data with quantitative features extracted from publicly available databases based on predefined optimal immunotherapeutic target criteria and quantitatively prioritizes potential surface protein targets. We demonstrate the utility and flexibility of IMMUNOTAR using three distinct datasets, validating its effectiveness in identifying both known and new potential immunotherapeutic targets within the analyzed cancer phenotypes. Overall, IMMUNOTAR enables the compilation of data from multiple sources into a unified platform, allowing users to simultaneously evaluate surface proteins across diverse criteria. By streamlining target identification, IMMUNOTAR empowers researchers to efficiently allocate resources and accelerate immunotherapy development.
Aligning Brains into a Shared Space Improves their Alignment to Large Language Models
Authors: Bhattacharjee Arnab , Zada Zaid , Wang Haocheng , Aubrey Bobbi , Doyle Werner , Dugan Patricia , Friedman Daniel , Devinsky Orrin , Flinker Adeen , Ramadge Peter J. , Hasson Uri , Goldstein Ariel , Nastase Samuel A.
Published: June 2024

Abstract

Recent studies have shown that large language models (LLMs) can accurately predict neural activity measured using electrocorticography (ECoG) during natural language processing. To predict word-by-word neural activity, most prior work has estimated and evaluated encoding models within each electrode and subject—without evaluating how these models generalize across individual brains. In this paper, we analyze neural responses in 8 subjects while they listened to the same 30-minute podcast episode. We use a shared response model (SRM) to estimate a shared information space across subjects. We show that SRM significantly improves LLM-based encoding model performance. We also show that we can use this shared space to denoise the individual brain responses by projecting back into the individualized electrode space, and this process achieves a mean 38% improvement in encoding performance. The strongest improvement was observed for brain areas specialized for language comprehension, specifically in the superior temporal gyrus (STG) and inferior frontal gyrus (IFG). Critically, estimating a shared space allows us to construct encoding models that better generalize across individuals.
Passive droplet microfluidic platform for high-throughput screening of microbial proteolytic activity
Authors: Potenza Luca , Kozon Łukasz , Drewniak Lukasz , Kaminski Tomasz S.
Published: June 2024

Traditional bacterial isolation methods are often costly, have limited throughput, and may not accurately reflect the true microbial community composition. Consequently, identifying rare or slow-growing taxa becomes challenging. Over the last decade, a new approach has been proposed to replace traditional flasks or multi-well plates with ultrahigh-throughput droplet microfluidic screening assays. In this study, we present a novel passive droplet-based method designed for isolating proteolytic microorganisms, which are crucial in various biotechnology industries. Following the encapsulation of single cells in gelatin microgel compartments and their subsequent clonal cultivation, microcultures are passively sorted at high throughput based on the deformability of droplets. Our novel chip design offers a 50-fold improvement in throughput compared to previously developed deformability-based droplet sorter. This method expands an array of droplet-based microbial enrichment assays and significantly reduces the time and resources required to isolate proteolytic bacteria strains.
GLARE: Discovering hidden patterns in spaceflight transcriptome using representation learning
Authors: Seo DongHyeon , Strickland Hunter F. , Zhou Mingqi , Barker Richard , Ferl Robert J , Paul Anna-Lisa , Gilroy Simon
Published: June 2024

Spaceflight studies present novel insights into biological processes through exposure to stressors outside the evolutionary path of terrestrial organisms. Despite limited access to space environments, numerous transcriptomic datasets from spaceflight experiments are now available through NASA’s GeneLab data repository, which allows public access to these datasets, encouraging further analysis. While various computational pipelines and methods have been used to process these transcriptomic datasets, learning-model-driven analyses have yet to be applied to a broad array of such spaceflight-related datasets. In this study, we propose an open-source framework, GLARE: GeneLAb Representation learning pipelinE, which consists of training different representation learning approaches from manifold learning to self-supervised learning that enhances the performance of downstream analytical tasks such as pattern recognition. We illustrate the utility of GLARE by applying it to gene-level transcriptional values from the results of the CARA spaceflight experiment, an Arabidopsis root tip transcriptome dataset that spanned light, dark, and microgravity treatments. We show that GLARE not only substantiated the findings of the original study concerning cell wall remodeling but also revealed additional patterns of gene expression affected by the treatments, including evidence of hypoxia. This work suggests there is great potential to supplement the insights drawn from initial studies on spaceflight omics-level data through further machine-learning-enabled analyses.
Directionality bias underpins divergent spatiotemporal progression of Alzheimer-related tauopathy in mouse models
Authors: Torok Justin , Mezias Christopher , Raj Ashish
Published: June 2024

Mounting evidence implicates trans-synaptic connectome-based spread as a shared mechanism behind different tauopathic conditions, yet also suggests there is divergent spatiotemporal progression between them. A potential parsimonious explanation for this apparent contradiction could be that different conditions incur differential rates and directional biases in tau transmission along fiber tracts. In this meta-analysis we closely examined this hypothesis and quantitatively tested it using spatiotemporal tau pathology patterns from 11 distinct models across 4 experimental studies. For this purpose, we extended a network-based spread model by incorporating net directionality along the connectome. Our data unambiguously supports the directional transmission hypothesis. First, retrograde bias is an unambiguously better predictor of tau progression than anterograde bias. Second, while spread exhibits retrograde character, our best-fitting biophysical models incorporate the mixed effects of both retrograde- and anterograde-directed spread, with notable tau-strain-specific differences. We also found a nontrivial association between directionality bias and tau strain aggressiveness, with more virulent strains exhibiting less retrograde character. Taken together, our study implicates directional transmission bias in tau transmission along fiber tracts as a general feature of tauopathy spread and a strong candidate explanation for the diversity of spatiotemporal tau progression between conditions. This simple and parsimonious mechanism may potentially fill a critical gap in our knowledge of the spatiotemporal ramification of divergent tauopathies.
RADIP technology comprehensively identifies H3K27me3-mediated RNA-chromatin interactions
Authors: Shu Xufeng , Kato Masaki , Takizawa Satoshi , Suzuki Yutaka , Carninci Piero
Published: June 2024

Many RNAs associate with chromatin, either directly or indirectly. Several technologies for mapping regions where RNAs interact across the genome have been developed to investigate the function of these RNAs. Obtaining information on the proteins involved in these RNA–chromatin interactions is critical for further analysis. Here, we developed RADIP (RNA and DNA interacting complexes ligated and sequenced (RADICL-seq) with immunoprecipitation), a novel technology that combines RADICL-seq technology with chromatin immunoprecipitation to characterize RNA–chromatin interactions mediated by individual proteins. Building upon the foundational principles of RADICL-seq, RADIP extends its advantages by increasing genomic coverage and unique mapping rate efficiency compared to existing methods. To demonstrate its effectiveness, we applied an anti-H3K27me3 antibody to the RADIP technology and generated libraries from mouse embryonic stem cells (mESCs). We identified a multitude of RNAs, including RNAs from protein-coding genes and non-coding RNAs, that are associated with chromatin via H3K27me3 and that likely facilitate the spread of Polycomb repressive complexes over broad regions of the mammalian genome, thereby affecting gene expression, chromatin structures and pluripotency of mESCs. Our study demonstrates the applicability of RADIP to investigations of the functions of chromatin-associated RNAs.

GRAPHICAL ABSTRACT
An Updated Structure of Oxybutynin Hydrochloride
Authors: Lin Jieye , Bu Guanhong , Unge Johan , Gonen Tamir
Published: June 2024

Oxybutynin (Ditropan), a widely distributed muscarinic antagonist for treating the overactive bladder, has been awaiting a definitive crystal structure for nearly 50 years due to the sample and technique limitations. Past reports used powder X-ray diffraction (PCRD) to shed light on the possible packing of the molecule however a 3D structure remained elusive. Here we used Microcrystal Electron Diffraction (MicroED) to successfully unveil the 3D structure of oxybutynin hydrochloride. We identify several inconsistencies between the reported PXRD analyses and the experimental structure. Using the improved model, molecular docking was applied to investigate the binding mechanism between M3muscarinic receptor (M3R) and (R)-oxybutynin, revealing essential contacts/residues and conformational changes within the protein pocket. A possible universal conformation was proposed for M3R antagonists, which is valuable for future drug development and optimization. This study underscores the immense potential of MicroED as a complementary technique for elucidating the unknown pharmaceutical crystal structures, as well as for the protein-drug interactions.
A DNA-based molecular clamp for probing protein interactions and structure under force
Authors: Chung Minhwan , Zhou Kun , Powell John , Lin Chenxiang , Schwartz Martin A.
Published: June 2024

Cellular mechanotransduction, a process central to cell biology, embryogenesis, adult physiology and multiple diseases, is thought to be mediated by force-driven changes in protein conformation that control protein function. However, methods to study proteins under defined mechanical loads on a biochemical scale are lacking. We report the development of a DNA based device in which the transition between single-stranded and double-stranded DNA applies tension to an attached protein. Using a fragment of the talin rod domain as a test case, negative-stain electron microscopy reveals programmable extension while pull down assays show tension-induced binding to two ligands, ARPC5L and vinculin, known to bind to cryptic sites inside the talin structure. These results demonstrate the utility of the DNA clamp for biochemical studies and potential structural analysis.
Exact Quantum Sensing Limits for Bosonic Dephasing Channels
Authors: Huang Zixin , Lami Ludovico , Wilde Mark M.
Published: June 2024

Dephasing is a prominent noise mechanism that afflicts quantum information carriers, and it is one of the main challenges toward realizing useful quantum computation, communication, and sensing. Here, we consider discrimination and estimation of bosonic dephasing channels, when using the most general adaptive strategies allowed by quantum mechanics. We reduce these difficult quantum problems to simple classical ones based on the probability densities defining the bosonic dephasing channels. By doing so, we rigorously establish the optimal performance of various distinguishability and estimation tasks and construct explicit strategies to achieve this performance. To the best of our knowledge, this is the first example of a non-Gaussian bosonic channel for which there are exact solutions for these tasks.

Published by the American Physical Society
2024
The effect of transport apertures on relay-imaged, sharp-edged laser profiles in photoinjectors and the impact on electron beam properties
Authors: Roper Mark , Percival Suzanna , Morrow Katherine
Published: June 2024

In a photoinjector electron source, the initial transverse electron bunch properties are determined by the spatial properties of the laser beam on the photocathode. Spatial shaping of the laser is commonly achieved by relay imaging an illuminated circular mask onto the photocathode. However, the Gibbs phenomenon shows that recreating the sharp edge and discontinuity of the cut profile at the mask on the cathode is not possible with an optical relay of finite aperture. Furthermore, the practical injection of the laser into the photoinjector results in the beam passing through small or asymmetrically positioned apertures. This work uses wavefront propagation to show how the transport apertures cause ripple structures to appear in the transverse laser profile even when effectively the full laser power is transmitted. The impact of these structures on the propagated electron bunch has also been studied with electron bunches of high and low charge density. With high charge density, the ripples in the initial charge distribution rapidly wash-out through space charge effects. However, for bunches with low charge density, the ripples can persist through the bunch transport. Although statistical properties of the electron bunch in the cases studied are not greatly affected, there is the potential for the distorted electron bunch to negatively impact machine performance. Therefore, these effects should be considered in the design phase of accelerators using photoinjectors.
Military-experienced directors, CEO busyness and financial statement footnotes readability: evidence from Indonesia
Authors: Abdul Wahab Effiezal Aswadi , Harymawan Iman , Wardani Damara Ardelia Kusuma , Nasih Mohammad
Published: June 2024

Purpose

This study examines the relationship between the characteristics of militarily experienced directors and financial statement footnote readability. The second research question considers whether CEO busyness impacts the relationship between military-experienced directors and financial statement footnotes readability.

Design/methodology/approach

We use nonfinancial listed firms on the Indonesian Stock Exchange from 2010 to 2018, which amounted to 1,002 firm-year observations. We test the hypotheses and use fixed effects and Heckman's two-stage regression.

Findings

This study documents a negative relationship between military directors and financial statement footnote readability. We extend this relationship by factoring board busyness into the equation. We find that the presence of military-connected and busy CEOs negatively impacts the readability of financial statement footnotes. The results remain robust after additional analyses.

Research limitations/implications

Future research should consider a more robust measure of military-experienced directors. A broader context of directors' busyness should be considered, such as including multiple directorships.

Originality/value

We revisit the literature on military-experienced directors by considering political connections as one of the proxies for military connections in Indonesia. The findings largely support the convergence of the political connections literature in which rent-seeking activities are prevalent and prevent sound financial reporting.
Bank financial distress and earnings management strategies: evidence from MENA countries
Authors: Ben Rejeb Mouna , Alzyadat Safwan , Merzki Nozha
Published: June 2024

Purpose

This study investigates and compares the earnings management strategies of financially distressed and non-distressed banks.

Design/methodology/approach

Using a regression analysis, this study examines a sample of banks operating in the MENA region. We focus on real earnings management strategies via commission and fee income (CF) and accrual-based earnings management strategies via loan loss provisions (LLP). A subsample analysis was performed, lagged dependent variables and additional control variables were included as a robustness check.

Findings

The findings consistently reveal a more extensive use of real earnings management strategies via CF among distressed banks than among non-distressed ones. Specifically, banks smooth their income via CF under distress conditions. However, LLP-based earnings management strategies are only implemented in healthy banks. These behaviors persist in banks that operate under different monitoring systems and institutional settings.

Research limitations/implications

This study marks its entry into the literature debate on accounting and non-accounting decisions that influence bank financial reporting. It argues that, in the presence of financial difficulties, bank managers define earnings management strategies based on the probability of being detected, rather than looking at their costs.

Practical implications

From a prudential perspective, the findings suggest the need for prudential rules to supervise the reporting of CF income associated with high fees or discount incentives used intentionally by bank managers to convince clients to delay or accelerate payments and, consequently, affect reported earnings.

Originality/value

This study adds to the literature by investigating the effect of bank financial distress on both real and accrual-based earnings management to provide a comprehensive analysis of bank earnings management strategies in the presence of financial difficulties.
The mediating role of organizational culture between transformational leadership and organizational performance in SMEs
Authors: Peña Jorge , Caruajulca Percy
Published: June 2024

Purpose

Considering the entrepreneurship nature and the high number of small and medium enterprises (SMEs) in the Latin American region, this study seeks to empirically test the relationship between organizational culture (OC), transformational leadership (TF) and organizational performance (OP) to support their long-term survival.

Design/methodology/approach

Under a post-positivism paradigm, quantitative approach and correlational scope, this research analyzed the interrelationship between OC, TF and OP across Peruvian SMEs. Confirmatory factor analysis (CFA) and structural equation modeling (SEM) were used to test the hypotheses based on the responses of 276 SMEs’ top executives from the commerce, services, manufacturing, construction and agriculture industries.

Findings

OC fully mediates the relationship between TL and OP. Although TF solely does not drive OP, the mediating effect of OC is crucial for SMEs’ long-term survival, especially considering their contribution to employment, poverty reduction and GDP in developing countries. Entrepreneurial transformational leaders inspire their followers to achieve goals, strive to develop individual skills, transmit confidence and leave aside their own interests to focus on the common goal of growing their entrepreneurship competitively.

Originality/value

The three variables under analysis have been applied to large companies and SMEs. However, this research enriches previous findings, highlighting the necessity for an adequate OC derived from an entrepreneur with TL, contributing to the survival of SMEs, whose results are critical for developing countries’ economies.
Sustainable water management in construction: life-cycle embodied water assessment of residential buildings
Authors: Rauf Abdul , Shafiq Muhammad Tariq , Khalfan Malik Mansoor Ali , Ulhaq Irfan
Published: June 2024

Purpose

This study aims to enhance our understanding of sustainable water management in construction through a life-cycle embodied water assessment of a villa in the United Arab Emirates (UAE). It provides insights and recommendations for improving the water efficiency by identifying areas for potential embodied water saving and reduction in environmental impacts in the construction industry.

Design/methodology/approach

This study uses a life-cycle assessment (LCA) approach and focuses on a UAE villa as a case study. It analyses the embodied water consumption during construction (initial embodied water) and maintenance (recurrent embodied water) using an input–output-based hybrid analysis. Additionally, it compares the embodied water observations with the operational water usage and comprehensively evaluates the water consumption in the villa’s life-cycle.

Findings

The initial (28%) and recurrent embodied water (42%) represent significant proportions of a building’s life-cycle water demand. The structural elements, predominantly concrete and steel, contribute 40% of the initial embodied water consumption. This emphasises the importance of minimising the water usage in these materials. Similarly, internal finishes account for 47% of the recurrent embodied water. This emphasises the importance of evaluating the material service life.

Practical implications

These findings indicate the efficacy of using durable materials with low embodiment and water-efficient construction methods. Additionally, collaborative research between academia, industry, and the government is recommended in conjunction with advocating for policies promoting low embodied-water materials and transparency in the construction sector through embodied water footprint reporting.

Originality/value

Previous studies focused on the operational water and marginally addressed the initial embodied water. Meanwhile, this study highlights the significance of the initial and recurrent embodied water in the life-cycle water demand. It emphasises on the need for adaptable buildings with reduced embodied water and more durable materials to minimise the requirement for frequent material replacements.
Chinese consumers’ lived experiences of flexitarianism
Authors: Zou Stella , Bremer Phil , Mirosa Miranda
Published: June 2024

Purpose

This was an explorative study, the purpose of which was to understand how Chinese flexitarians were motivated to reduce their animal-based food consumption and specifically to explore why and what was behind these changes. Further, this study provides insights into how a transition towards a more plant-based diet might occur.

Design/methodology/approach

This study conducted 30 in-depth online interviews with Chinese flexitarians from two major Chinese cities. Interview transcripts were analysed through the lens of the Food Choice Process Model.

Findings

Participants adopted flexitarian diets due to health (n = 22), sustainability (n = 5) or ethical (n = 3) concerns. Many participants stated that they still enjoyed animal-sourced foods, were uncomfortable talking about their dietary transition and needed more social support. Consequently, most participants were unlikely to progress to vegetarian or vegan diets. While there are some commonalities between these findings and the results of similar studies with Western consumers, the many culturally and context-specific results revealed herein make an important contribution to the sustainability literature.

Originality/value

This is the first study exploring Chinese consumers’ flexitarianism experiences. These findings can be used by the food industry and interested business actors to improve communication and promotional strategies that encourage consumers to make healthier and more sustainable food choices.
Generic business strategies and competitiveness of SMEs in Nigeria
Authors: Isichei Ejikeme Emmanuel , Isichei Maria Onyejeche , Moruku Robert Kemepade
Published: June 2024

Purpose

This paper aims to investigate the mediating effect of employee engagement on the relationship between generic business strategies and the competitiveness of Small and Medium-Scale Enterprises (SMEs) in the Federal Capital Territory, Abuja (FCT).

Design/methodology/approach

The research design used a cross-sectional survey approach, focusing on SMEs registered with the SMEDAN in FCT-Abuja. A total of 349 SMEs were used. Data collection relied on a questionnaire-based survey instrument. The data were analysed using Partial Least Square Structural Equation Model (SmartPLSv3.1).

Findings

The results revealed several significant findings. Firstly, the study confirmed a direct and positive relationship between the cost leadership strategy and SME competitiveness, indicating that cost leadership significantly enhances competitiveness. Secondly, a significant and positive relationship was identified between the focus strategy and SME competitiveness, suggesting its significant contribution. However, the relationship between the differentiation strategy and SME competitiveness was found to be non-significant. Moreover, the research established that employee engagement has a significant positive effect on SME competitiveness. The study also confirmed the mediating effect of employee engagement on the relationship between cost leadership strategy and competitiveness, as well as between focus strategy and competitiveness. Lastly, employee engagement significantly mediated the relationship between differentiation strategy and SME competitiveness.

Originality/value

The paper advances a new perspective by linking internal resource’s role in strategic management effort towards ensuring increased firm competitiveness especially in SMEs. The paper offers scholars a new area of research, as it draws scholarly attention to internal behaviour mechanisms that drives top managements activities through lower-level employee participation towards ensuring improved competitiveness.
Navigating turbulence in the UK: how gender shapes self-employed social engagement during crises?
Authors: Haj Youssef Moustafa , Nolan Steve , Hussein Hiba
Published: June 2024

Purpose

This study examines the dynamic relationship between UK entrepreneurs' engagement with society and the economic climate surrounding the 2008 financial crisis – before, during and after it. We investigate whether such crises strengthen or weaken the connections between entrepreneurship and society, considering gender differences.

Design/methodology/approach

We employ individual-level data from the British Household Panel Survey (BHPS) and the UK Longitudinal Study (UKLS) to assess changes in entrepreneurs' social engagement during crises. We use panel logit and Poisson regressions to estimate trends in social engagement over time and in response to economic turmoil.

Findings

We discover that entrepreneurs are more likely to join social organisations during economic turmoil. This engagement varies by gender, with female entrepreneurs more inclined to engage with social organisations than males. This suggests that female entrepreneurs perceive crisis risks differently, seeking support to navigate uncertainty. Additionally, we find evidence supporting the idea that female entrepreneurs take longer to recover from major economic shocks than their male counterparts.

Originality/value

Entrepreneur behaviour during crises remains understudied. The role of social ties and networks in aiding entrepreneurs during systemic crises is particularly unexplored. This study addresses this gap, highlighting gender-based behavioural differences during crises and paving the way for further research. It represents a crucial step in integrating crisis literature into entrepreneurship studies.