bluuebunny/crossref_metadata_2025 huggingface dataset:
“Oncocytoid Renal Cell Carcinomas After Neuroblastoma” Represent TSC-mutated Eosinophilic Solid and Cystic Renal Cell Carcinomas
Authors: Argani Pedram , Medeiros L. Jeffrey , Matoso Andres , Baraban Ezra , Lotan Tamara , Pawel Bruce R. , McKenney Jesse K. , Mehra Rohit , Falzarano Sara M. , Pallavajjalla Aparna , Lin Ming-Tseh , Patel Sachin , Rawwas Jawhar , Bendel Anne E. , Gagan Jeffrey , Palsgrove Doreen N.
Published: July 2023

The concept of oncocytoid renal cell carcinoma in patients who have survived neuroblastoma as a distinct biologic entity has been controversial since its original description in 1999. This is in part because similar oncocytoid renal cell carcinomas have been described in association with other pediatric cancers, and also because other renal cell carcinoma subtypes (such as MiT family translocation renal cell carcinoma) have been described in children who have survived neuroblastoma. We identified an index case of a child who survived medulloblastoma and developed multifocal bilateral oncocytoid renal cell carcinomas with morphology and immunophenotype compatible with eosinophilic solid and cystic renal cell carcinoma (ESC RCC) and demonstrated that both neoplasms harbored distinctive mutations in the TSC1/TSC2 genes. Remarkably, the child’s remaining bilateral multifocal renal neoplasms completely responded to MTOR inhibitor therapy without need for further surgery. To confirm our hypothesis that oncocytoid renal cell carcinomas after childhood cancer represent ESC RCC, we obtained formalin-fixed paraffin-embedded tissue blocks from 2 previously published cases of oncocytoid renal cell carcinoma after neuroblastoma, confirmed that the morphology and immunophenotype was consistent with ESC RCC, and demonstrated that both cases harbored somatic TSC gene mutations. Both expressed markers previously associated with neoplasms harboring TSC gene mutations, glycoprotein nonmetastatic B, and cathepsin K. Of note, one of these patients had 2 ESC RCC which harbored distinctive TSC2 mutations, while the background kidney of the other patient had multiple small cysts lined by similar oncocytoid cells which showed loss of TSC2 protein. We then reviewed 3 of 4 cases from the original 1999 report of oncocytoid renal cell carcinomas after neuroblastoma, found that all 3 demonstrated morphology (including basophilic cytoplasmic stippling) that is characteristic of ESC RCC, showed that all 3 overexpressed glycoprotein nonmetastatic B, and showed that both cases with adequate material demonstrated loss of TSC2 protein and expressed cytokeratin 20 and cathepsin K by immunohistochemistry. In summary, “oncocytoid renal cell carcinomas after neuroblastoma” represent ESC RCC which are often multifocal in patients who have survived childhood cancer, likely representing an incompletely characterized tumor predisposition syndrome. MTOR-targeted therapy represents an effective therapeutic option for such patients to preserve functional nephrons.
Extending Quality Improvement for Pancreatoduodenectomy Within the High-Volume Setting
Authors: Cannas Samuele , Casciani Fabio , Vollmer Charles M. ,   on behalf of the Pancreas Fistula Study Group
Published: July 2023

Objective:

To analyze the association of a surgeon’s experience with postoperative outcomes of pancreatoduodenectomies (PDs) when stratified by Fistula Risk Score (FRS).

Summary Background Data:

Centralization is now well-established for pancreatic surgery. Nevertheless, the benefits of individual surgeon’s experience in high-volume settings remains undefined.

Methods:

Pancreatoduodenectomies performed by 82 surgeons across 18 international, specialty institutions (median:140 PD/year) were analyzed. Surgeon cumulative PD volume was linked with postoperative outcomes through multivariable models, adjusted for patient/operative characteristics and the FRS. Then, surgeon experience was also stratified by the ten, previously defined, most clinically impactful scenarios for clinically-relevant pancreatic fistula (CR-POPF) development.

Results:

Of 8,189 PDs, 18.7% suffered severe complications (Accordion≥3), 4.8% were reoperated upon and 2.2% expired. Although the most experienced surgeons (top-quartile; >525 career PDs) more often operated on riskier cases, their experience was significantly associated with declines in CR-POPF (P<0.001), severe complications (P=0.008), reoperations (P<0.001), and length of stay (LOS) (P<0.001) - accentuated even more in the most impactful FRS scenarios (2,830 patients). Risk-adjusted models indicate male gender, increasing age, ASA class and FRS, but not surgeon experience, as being associated with severe complications, failure-to-rescue and mortality. Instead, upper-echelon experience demonstrates significant reductions in CR-POPF (OR 0.66), reoperations (OR 0.64) and LOS (OR 0.65) in moderate-to-high fistula risk circumstances (FRS≥3, 68% of cases).

Conclusions:

At specialty institutions, major morbidity, mortality and failure-to-rescue are primarily associated with baseline patient characteristics, while cumulative surgical experience impacts pancreatic fistula occurrence and its attendant effects for most, higher-risk pancreatoduodenectomies. These data also suggest an extended proficiency curve exists for this operation.
The Use of Oblique-viewing Endoscopic Ultrasound for Accessing the Afferent Limb for Endoscopic Ultrasound-guided Biliary Drainage in Patients with Severe Stenotic Hepaticojejunal Anastomosis: One Case and Literature Review
Authors: Huang Ping-Xiao , Song Qi-Long , Di Shu-Jie , Fan Yan , Zhang Heng
Published: July 2023

Background:

The treatment of hepaticojejunal anastomotic strictures in patients with surgically altered anastomosis is challenging. Endoscopic ultrasound (EUS)-guided biliary drainage is being established as a feasible biliary drainage procedure. How can oblique-viewing endoscopic ultrasound (OV-EUS) safely reach the treatment area in the afferent limb for EUS-guided hepaticojejunostomy? This is a key, meaningful, and challenging question.

Methods:

A unique case of an OV-EUS-guided hepaticojejunostomy performed in a patient with severe stenotic hepaticojejunal anastomosis was reported, and the relevant literatures were reviewed.

Results:

There are only 3 previous case reports of EUS-guided transanastomotic drainage using OV-EUS. The above 3 cases reported did not elaborate on the key treatment details of the procedure. Especially how can the OV-EUS safely reach the treatment area in the afferent limb?

Conclusions:

For patients with severe anastomotic stricture, when the retrograde or antegrade guide wire cannot pass through the stenosis to establish biliary drainage, OV-EUS can safely reach the treatment area in the afferent limb under the guidance of a fluoroscopic view and a guide wire. Thus, an OV-EUS-guided hepaticojejunostomy can be achieved.
The pharmacokinetic–pharmacodynamic modelling framework as a tool to predict drug resistance evolution
Authors: Witzany Christopher , Rolff Jens , Regoes Roland R. , Igler Claudia
Published: July 2023

Pharmacokinetic–pharmacodynamic (PKPD) models, which describe how drug concentrations change over time and how that affects pathogen growth, have proven highly valuable in designing optimal drug treatments aimed at bacterial eradication. However, the fast rise of antimicrobial resistance calls for increased focus on an additional treatment optimization criterion: avoidance of resistance evolution. We demonstrate here how coupling PKPD and population genetics models can be used to determine treatment regimens that minimize the potential for antimicrobial resistance evolution. Importantly, the resulting modelling framework enables the assessment of resistance evolution in response to dynamic selection pressures, including changes in antimicrobial concentration and the emergence of adaptive phenotypes. Using antibiotics and antimicrobial peptides as an example, we discuss the empirical evidence and intuition behind individual model parameters. We further suggest several extensions of this framework that allow a more comprehensive and realistic prediction of bacterial escape from antimicrobials through various phenotypic and genetic mechanisms.
α-Catenin Dependent E-cadherin Adhesion Dynamics as Revealed by an Accelerated Force Ramp
Authors: Bush Joshua , Cabe Jolene I. , Conway Daniel , Maruthamuthu Venkat
Published: July 2023

Tissue remodeling and shape changes often rely on force-induced cell rearrangements occurring via cell-cell contact dynamics. Epithelial cell-cell contact shape changes are particularly dependent upon E-cadherin adhesion dynamics which are directly influenced by cell-generated and external forces. While both the mobility of E-cadherin adhesions and their adhesion strength have been reported before, it is not clear how these two aspects of E-cadherin adhesion dynamics are related. Here, using magnetic pulling cytometry, we applied an accelerated force ramp on the E-cadherin adhesion between an E-cadherin-coated magnetic microbead and an epithelial cell to ascertain this relationship. Our approach enables the determination of the adhesion strength and force-dependent mobility of individual adhesions, which revealed a direct correlation between these key characteristics. Since α-catenin has previously been reported to play a role in both E-cadherin mobility and adhesion strength when studied independently, we also probed epithelial cells in which α-catenin has been knocked out. We found that, in the absence of α-catenin, E-cadherin adhesions not only had lower adhesion strength, as expected, but were also more mobile. We observed that α-catenin was required for the recovery of strained cell-cell contacts and propose that the adhesion strength and force-dependent mobility of E-cadherin adhesions act in tandem to regulate cell-cell contact homeostasis. Our approach introduces a method which relates the force-dependent adhesion mobility to adhesion strength and highlights the morphological role played by α-catenin in E-cadherin adhesion dynamics.
C. elegansAfadin is required for epidermal morphogenesis and functionally interfaces with the cadherin-catenin complex and RhoGAP PAC-1/ARHGAP21
Authors: Hall Allison E. , Klompstra Diana , Nance Jeremy
Published: July 2023

During epithelial morphogenesis, the apical junctions connecting cells must remodel as cells change shape and make new connections with their neighbors. In theC. elegansembryo, new apical junctions form when epidermal cells migrate and seal with one another to encase the embryo in skin (‘ventral enclosure’), and junctions remodel when epidermal cells change shape to squeeze the embryo into a worm shape (‘elongation’). The junctional cadherin-catenin complex (CCC), which links epithelial cells to each other and to cortical actomyosin, is essential forC. elegansepidermal morphogenesis. RNAi genetic enhancement screens have identified several proteins that interact with the CCC to promote epidermal morphogenesis, including the scaffolding protein Afadin (AFD-1), whose depletion alone results in only minor morphogenesis defects. Here, by creating a null mutation inafd-1, we show thatafd-1provides a significant contribution to ventral enclosure and elongation on its own. Unexpectedly, we find thatafd-1mutant phenotypes are strongly modified by diet, revealing a previously unappreciated maternal nutritional input to morphogenesis. We identify functional interactions between AFD-1 and the CCC by demonstrating that E-cadherin is required for the polarized distribution of AFD-1 to cell contact sites in early embryos. Finally, we show thatafd-1promotes the enrichment of polarity regulator and CCC-interacting protein PAC-1/ARHGAP21 to cell contact sites, and identify genetic interactions suggesting thatafd-1andpac-1regulate epidermal morphogenesis at least in part through parallel mechanisms. Our findings reveal thatC. elegansAFD-1 makes a significant contribution to epidermal morphogenesis and functionally interfaces with core and associated CCC proteins.
Long-term root electrotropism reveals habituation and hysteresis
Authors: Salvalaio Maddalena , Sena Giovanni
Published: July 2023

Plant roots sense many physical and chemical cues in soil, such as gravity, humidity, light and chemical gradients, and respond by redirecting their growth towards or away from the source of the stimulus. This process is called tropism. While gravitropism is the tendency to follow the gravitational field downwards, electrotropism is the alignment of growth with external electric fields and the induced ionic currents. Although root tropisms are at the core of their ability to explore large volumes of soil in search of water and nutrients, the molecular and physical mechanisms underlying most of them remain poorly understood. We have previously provided a quantitative characterization of root electrotropism in Arabidopsis (Arabidopsis thaliana) primary roots exposed for 5 hours to weak electric fields, showing that auxin asymmetric distribution is not necessary but that cytokinin biosynthesis is. Here, we extend that study showing that long-term electrotropism is characterized by a complex behavior. We describe overshoot and habituation as key traits of long-term root electrotropism in Arabidopsis and provide quantitative data about the role of past exposures in the response to electric fields (hysteresis). On the molecular side, we show that cytokinin, although necessary for root electrotropism, is not asymmetrically distributed during the bending.

Overall, the data presented here represent a significant step forward towards the understanding of the molecular mechanisms regulating electrotropism in plants and provide a quantitative platform for future studies on the genetics of this and other tropisms.
A gel-coated air-liquid-interface culture system with tunable substrate stiffness matching healthy and diseased lung tissues
Authors: He Zhi-Jian , Chu Catherine , Dickson Riley , Cai Li-Heng
Published: July 2023

Since its invention in the late 1980s, the air-liquid-interface (ALI) culture system has been the standardin vitromodel for studying human airway biology and pulmonary diseases. However, in a conventional ALI system, cells are cultured on a porous plastic membrane that is much stiffer than human airway tissues. Here, we develop a gel-ALI culture system by simply coating the plastic membrane with a thin layer of hydrogel with tunable stiffness matching that of healthy and fibrotic airway tissues. We determine the optimum gel thickness that does not impair the transport of nutrients and biomolecules essential to cell growth. We show that the gel-ALI system allows human bronchial epithelial cells (HBECs) to proliferate and differentiate into a pseudostratified epithelium. Further, we discover that HBECs migrate significantly faster on hydrogel substrates with stiffness matching that of fibrotic lung tissues, highlighting the importance of mechanical cues to human airway remodeling. The developed gel-ALI system provides a facile approach to studying the effects of mechanical cues on human airway biology and in modeling pulmonary diseases.

New and Noteworthy

In a conventional air-liquid-interface (ALI) system, cells are cultured on a plastic membrane that is much stiffer than human airway tissues. We develop a gel-ALI system by coating the plastic membrane with a thin layer of hydrogel with tunable stiffness matching that of healthy and fibrotic airway tissues. We discover that human bronchial epithelial cells migrate significantly faster on hydrogel substrates with pathological stiffness, highlighting the importance of mechanical cues to human airway remodeling.
Conformational Properties of Polymers at Droplet Interfaces as Model Systems for Disordered Proteins
Authors: Wang Jiahui , Devarajan Dinesh Sundaravadivelu , Nikoubashman Arash , Mittal Jeetain
Published: July 2023

Polymer models serve as useful tools for studying the formation and physical properties of biomolecular condensates. In recent years, the interface dividing the dense and dilute phases of condensates has been discovered to be closely related to their functionality, but the conformational preferences of the constituent proteins remain unclear. To elucidate this, we perform molecular simulations of a droplet formed by liquid–liquid phase separation of homopolymers, as a surrogate model for the prion-like low-complexity domains. By systematically analyzing the polymer conformations at different locations in the droplet, we find that the chains become compact at the droplet interface compared to the droplet interior. Further, segmental analysis revealed that the end sections of the chains are enriched at the interface to maximize conformational entropy, and are more expanded than the middle sections of the chains. We find that the majority of chain segments lie tangential to the droplet surface and only the chain ends tend to align perpendicular to the interface. These trends also hold for the natural proteins FUC LC and LAF-1 RGG, which exhibit more compact chain conformations at the interface compared with the droplet interior. Our findings provide important insights into the interfacial properties of biomolecular condensates and highlight the value of using simple polymer physics models to understand the underlying mechanisms.
A Small-Molecule Approach to Bypass In Vitro Selection of New Aptamers: Designer Pre-Ligands Turn Baby Spinach into Sensors for Reactive Inorganic Targets
Authors: Aggarwal Tushar , Wang Liming , Gutierrez Bryan , Guven Hakan , Erguven Huseyin , Izgu Enver Cagri
Published: July 2023

Fluorescent light-up aptamer (FLAP) systems are promising biosensing platforms that can be genetically encoded. Here, we describe how a single FLAP that works with specific organic ligands can detect multiple, structurally unique, non-fluorogenic, and reactive inorganic targets. We developed 4-O-functionalized benzylidene imidazolinones as pre-ligands with suppressed fluorescent binding interactions with the RNA aptamer Baby Spinach. Inorganic targets, hydrogen sulfide (H2S) or hydrogen peroxide (H2O2), can specifically convert these pre-ligands into the native benzylidene imidazolinones, and thus be detected with Baby Spinach. Adaptation of this approach to live cells opened a new opportunity for top-down construction of whole-cell sensors:Escherichia colitransformed with a Baby Spinach-encoding plasmid and incubated with pre-ligands generated fluorescence in response to exogenous H2S or H2O2. Our approach eliminates the requirement of in vitro selection of a new aptamer sequence for molecular target detection, allows for the detection of short-lived targets, thereby advancing FLAP systems beyond their current capabilities. Leveraging the functional group reactivity of small molecules can lead to cell-based sensors for inorganic molecular targets, exploiting a new synergism between synthetic organic chemistry and synthetic biology.
HDX-MS reveals concealed conformations of ISWI during different stages of nucleosome sliding
Authors: Bhat Younus A , Bhat Javaid Y , Amin Shajrul , Udgaonkar Jayant B , Wani Ajazul H
Published: July 2023

Nucleosome spacing across the genome is regulated by the adenosine 5’-triphosphate (ATP)- dependent nucleosome sliding activity of Imitation Switch, ISWI. ISWI is believed to be auto-inhibited in the resting-state by the binding of its N-and C-terminal regulatory regions to its central ATPase-domain, attaining a “closed” conformation. To slide nucleosomes ISWI must i) transition to the state competent for nucleosome binding, ii) bind to nucleosome and iii) carry the ATP-dependent nucleosome sliding. The conformations attained by full-length ISWI (FL-ISWI) during the entire sliding process have remained inaccessible by the methods used so far. Using Hydrogen/Deuterium-exchange coupled to Mass-Spectrometry (HDX-MS), we monitored conformational dynamics of theDrosophilaFL-ISWI at all the stages of sliding process. HDX-MS data show that in the resting state, ISWI samples an ensemble of conformations showing varying levels of deuterium uptake in many regions including N-and C-terminal regulatory regions, suggesting ISWI intrinsically samples relatively “open-states”. In addition to substantiating previous nucleosome binding studies, HDX-MS reveals that during actual sliding-step, regions of ATPase-domain which bind to the nucleosomal DNA undergo major conformational change. The C-terminal HSS domain switches from the solvent protected stable state to a more dynamic state, implying several interactions established by ISWI with the nucleosome upon binding are relieved during sliding. In sum, this study provides mechanistic insights into how ISWI can switch from an auto-inhibited “closed-state” to an “open-state” competent for nucleosome binding, and reveals the conformation attained by ISWI during the actual nucleosome sliding step. We propose that, like ISWI, intrinsic dynamics may be involved in functioning of other Rec-like ATPase-domain containing protein families.
Melatonin alleviates valproic acid-induced neural tube defects by modulating Src/PI3K/ERK signaling and oxidative stress
Authors: Liang Yuxiang , Wang Ying , Zhang Xiao , Jin Shanshan , Guo Yuqian , Yu Zhaowei , Xu Xinrui , Shuai Qizhi , Feng Zihan , Chen Binghong , Liang Ting , Ao Ruifang , Li Jianting , Zhang Juan , Cao Rui , Zhao Hong , Chen Zhaoyang , Liu Zhizhen , Xie Jun
Published: July 2023

Neural tube defects (NTDs) represent a developmental disorder of the nervous system that can lead to significant disability in children and impose substantial social burdens. Valproic acid (VPA), a widely prescribed first-line antiepileptic drug for epilepsy and various neurological conditions, has been associated with a fourfold increase in the risk of NTDs when used during pregnancy. Consequently, urgent efforts are required to identify innovative prevention and treatment approaches for VPA-induced NTDs. Studies have demonstrated that the disruption in the delicate balance between cell proliferation and apoptosis is a crucial factor contributing to NTDs induced by VPA. Encouragingly, our current data reveal that melatonin (MT) exerts significant inhibition on apoptosis while promoting the restoration of neuroepithelial cells proliferation impaired by VPA. Moreover, further investigations demonstrate that MT substantially reduces the incidence of neural tube malformations resulting from VPA exposure, primarily achieved by suppressing apoptosis through the modulation of intracellular reactive oxygen species levels. In addition, the Src/PI3K/ERK signaling pathway appears to play a pivotal role in VPA-induced NTDs, with a significant inhibition observed in the affected samples. Notably, MT treatment successfully reinstates the Src/PI3K/ERK signals, thereby offering a potential underlying mechanism for MT’s protective effects against VPA-induced NTDs. In summary, our current study substantiates the considerable protective potential of MT in mitigating VPA-triggered NTDs, thereby offering valuable strategies for the clinical management of VPA-related birth defects.
Vitamin B12conveys a protective advantage to phycosphere-associated bacteria at high temperatures
Authors: Brisbin Margaret Mars , Schofield Alese , McIlvin Matthew , Krinos Arianna I. , Alexander Harriet , Saito Mak
Published: July 2023

Many marine microbes require vitamin B12(cobalamin) but are unable to synthesize it, necessitating reliance on other B12-producing microbes. Thus, phytoplankton and bacterioplankton community dynamics can partially depend on the production and release of a limiting resource by members of the same community. We tested the impact of temperature and B12availability on the growth of two bacterial taxa commonly associated with phytoplankton:Ruegeria pomeroyi, which produces B12and fulfills the B12requirements of some phytoplankton, andAlteromonas macleodii, which does not produce B12but also does not strictly require it for growth. For B12-producingR. pomeroyi, we further tested how temperature influences B12production and release. Access to B12significantly increased growth rates of both species at the highest temperatures tested (38ºC forR. pomeroyi, 40ºC forA. macleodii) andA. macleodiibiomass was significantly reduced when grown at high temperatures without B12, indicating that B12is protective at high temperatures. Moreover,R. pomeroyiproduced more B12at warmer temperatures but did not release detectable amounts of B12at any temperature tested. Results imply that increasing temperatures and more frequent marine heatwaves with climate change will influence microbial B12dynamics and could interrupt symbiotic resource sharing.
Immunometabolic cues recompose and reprogram the microenvironment around biomaterials
Authors: Maduka Chima V. , Schmitter-Sánchez Axel D. , Makela Ashley V. , Ural Evran , Stivers Katlin B. , Pope Hunter , Kuhnert Maxwell M. , Habeeb Oluwatosin M. , Tundo Anthony , Alhaj Mohammed , Kiselev Artem , Chen Shoue , Olive Andrew J. , Hankenson Kurt D. , Narayan Ramani , Park Sangbum , Elisseeff Jennifer H. , Contag Christopher H.
Published: July 2023

Circulating monocytes infiltrate and coordinate immune responses in various inflamed tissues, such as those surrounding implanted biomaterials, affecting therapeutic, diagnostic, tissue engineering and regenerative applications. Here, we show that immunometabolic cues in the biomaterial microenvironment govern CCR2- and CX3CR1-dependent trafficking of immune cells, including neutrophils and monocytes; ultimately, this affects the composition and activation states of macrophage and dendritic cell populations. Furthermore, immunometabolic cues around implants orchestrate the relative composition of proinflammatory, transitory and anti-inflammatory CCR2+, CX3CR1+and CCR2+CX3CR1+immune cell populations. Consequently, modifying immunometabolism by glycolytic inhibition drives a pro-regenerative microenvironment in part by myeloid cells around amorphous polylactide implants. In addition to, Arginase 1-expressing myeloid cells, T helper 2 cells and γδ+T-cells producing IL-4 significantly contribute to shaping the metabolically reprogramed, pro-regenerative microenvironment around crystalline polylactide biomaterials. Taken together, we find that local metabolic states regulate inflammatory processes in the biomaterial microenvironment, with implications for translational medicine.
A versatile approach to high-density microcrystals in lipidic cubic phase for room-temperature serial crystallography
Authors: Birch James , Kwan Tristan O. C. , Judge Peter J. , Axford Danny , Aller Pierre , Butryn Agata , Reis Rosana I. , Bada Juarez Juan F. , Vinals Javier , Owen Robin L. , Nango Eriko , Tanaka Rie , Tono Kensuke , Joti Yasumasa , Tanaka Tomoyuki , Owada Shigeki , Sugahara Michihiro , Iwata So , Orville Allen M. , Watts Anthony , Moraes Isabel
Published: July 2023

Serial crystallography has emerged as an important tool for structural studies of integral membrane proteins. The ability to collect data from micrometre-sized weakly diffracting crystals at room temperature with minimal radiation damage has opened many new opportunities in time-resolved studies and drug discovery. However, the production of integral membrane protein microcrystals in lipidic cubic phase at the desired crystal density and quantity is challenging. This paper introduces VIALS (versatile approach to high-density microcrystals in lipidic cubic phase for serial crystallography), a simple, fast and efficient method for preparing hundreds of microlitres of high-density microcrystals suitable for serial X-ray diffraction experiments at both synchrotron and free-electron laser sources. The method is also of great benefit for rational structure-based drug design as it facilitates in situ crystal soaking and rapid determination of many co-crystal structures. Using the VIALS approach, room-temperature structures are reported of (i) the archaerhodopsin-3 protein in its dark-adapted state and 110 ns photocycle intermediate, determined to 2.2 and 1.7 Å, respectively, and (ii) the human A2A adenosine receptor in complex with two different ligands determined to a resolution of 3.5 Å.
Analysis of public health-care facilities in rural India
Authors: Sahoo Pragyan Monalisa , Rout Himanshu Sekhar
Published: July 2023

Purpose

This paper aims to analyze the status of infrastructure, workforce and basic amenities at public health-care facilities in rural India and draw a comparison with its urban counterparts.

Design/methodology/approach

Rural Health Statistics data and National Sample Survey Office Report for the period 2019–10 were used to analyze lower-level public health facilities, namely, subcenters, primary health centers and community health centers (CHCs). Selected tracer indicators under World Health Organization’s (WHO) Service Availability and Readiness Assessment (SARA) mechanism such as health center density, core health workforce density and basic amenities were used to carry out the analysis. The extent of facility coverage was measured using the National Rural Health Mission (NRHM) guidelines and the proportion of facilities satisfying the Indian Public Health Standards (IPHS) was measured to assess the service provision quality in rural public health-care facilities.

Findings

Results indicated that the density of public health centers is higher in rural areas than in urban areas. Almost all public health-care facilities lack basic amenities in rural areas. Working positions for health specialists in CHCs barely meet the total requirement. Almost all of the public health facilities functioning in rural areas do not meet the IPHS norms.

Originality/value

To the best of the authors’ knowledge, the present paper is the first initiative to assess the status of rural public health-care facilities on the national level using WHO’s SARA indicators as well as NRHM and IPHS guidelines. The study is significant in terms of policy input for achieving universal health coverage in India.
The illusion of reality in the gaming world: implications for libraries
Authors: Ajani Yusuf Ayodeji , Ahmed Abdulganiy Okanla , Muhammed Rihanat Bukola
Published: July 2023

Purpose

The main purpose of this paper is to explore implications of the illusion of reality in the gaming world for libraries, aiming to uncover the challenges and opportunities they face in adapting their services to the gaming context.

Design/methodology/approach

Through a comprehensive exploration of the topic, various sources, such as Scopus, Google Scholar and ResearchGate were used. This study draws upon existing literature to analyze the impact of the illusion of reality in gaming on libraries and their offerings.

Findings

The findings emphasize the crucial role of libraries in comprehending the illusion of reality in gaming to remain relevant and effectively meet the evolving needs of patrons. It also emphasize the impact of the illusion of reality on user engagement, information-seeking behaviors, digital literacy challenges and the evolving gaming landscape. The findings highlight opportunities for libraries to leverage the illusion of reality, thereby enhancing user experiences, fostering community engagement, promoting information literacy and creating immersive learning environments.

Originality/value

This paper contributes a unique investigation into the impact of the illusion of reality in gaming on libraries, underscoring its significance. It offers practical recommendations to enhance library services, user experiences and community engagement within the gaming domain. The study provides valuable insights for library professionals, researchers and policymakers seeking to understand and adapt to the changing dynamics of the gaming world.
Resilience of small retailers in facing the Covid-19 pandemic – a qualitative study
Authors: Samanta Tamal , Aithal Rajesh
Published: July 2023

Purpose

This study aims to understand the impact of the Covid-19 pandemic on small retailers, and their response to it, using the crisis management model. The research documents the impact and responses and attempts to identify the factors contributing to and hindering retailers’ attempts to achieve resilience.

Design/methodology/approach

Semi-structured interviews were used to collect qualitative data from small retailers. The interview transcripts were analysed using MAXQDA 2020 Analytics Pro data analysis software. The heterogeneity in responses to the challenges posed by the pandemic is explained using self-determination theory and diffusion of innovation theory.

Findings

One of the most significant impacts of the crisis was the disruption in the regular supply chain network on which the studied retailers relied for their traditional buying. The retailers increased customer services such as free home delivery and enhanced the use of technology in their shops. However, and worryingly, although the retailers faced two waves of the pandemic, the urge to plan and prepare was missing. The overall crisis can, therefore, be seen as an opportunity for small retailers to improve their responses when facing similar situations.

Social implications

Small retailers are part of the social fabric in many emerging economies and function as a source of employment. They have been facing challenges from organised retail and e-commerce. The Covid-19 crisis pushed them to respond, and the authors hope that they will take some cues from this disruption and become more efficient and competitive in the future.

Originality/value

To the best of the authors’ knowledge, this is among the first studies to map the impact of the crisis on small retailers and their response to it, drawing implications for retailers and companies and analysing the efforts made by small retailers to achieve resilience.
A story-net approach to qualitative research: having tea with stories!
Authors: Price Shelley Teresa , Hartt Christopher Michael
Published: July 2023

Purpose

The purpose of this paper is to share the story-net approach and to situate it as one that benefits from blending story as Indigenous methodology with non-corporeal actant theory (NCAT). The authors hope it will serve useful in building storytelling communities where Indigenous and non-Indigenous scholars are working to heal together from colonial trauma, reveal the inner workings of historical and ongoing colonial projects, dismantle the agency of colonial projects, and welcome heartful dialogue into the centre of MOS discourse.

Design/methodology/approach

The authors employ a storytelling approach which includes mapping the story-net territory and identifying the plot points along the journey. The authors use the story-net approach to story the approach.

Findings

This approach served helpful when engaging within story archives and with storytelling collectives comprised of both Indigenous and non-Indigenous persons, peoples and knowledges. The authors found four key premises, which help to narrate the ontology, epistemology, methodology and axiology of the story-net approach and six plot points, which help in mapping the lessons learned from engaging with stories, storytellers, story listeners and the socio-discursive contexts surrounding story-net work.

Originality/value

The authors story an approach that can be useful to support emerging Indigenous scholars while engaging with their non-Indigenous colleagues to do story-net work. This approach may be useful to navigate the tensions to create safer, more humane, inclusive, relational, strengths-based and trauma-informed spaces for engaging with Indigenous stories, storytellers, story listeners and discourses, as well as, to plot the points of contention so as to set the stage for deepening respectful research relations.
Hyperhidrosis: A targeted literature review of the disease burden
Authors: Oshima Yuichiro , Fujimoto Tomoko , Nomoto Mariko , Fukui Junko , Ikoma Akihiko
Published: July 2023

Hyperhidrosis is a chronic skin condition characterized by excessive sweating. It poses a burden on affected people, reducing their quality of life and productivity. We undertook a targeted literature review (TLR) to gather current evidence on the epidemiology as well as the human and economic burden posed on patients with hyperhidrosis. Searches were performed in Medline database (access via OVID interface) and ICHUSHI database. Articles published between January 2000 and September 2020 that analyzed at least 50 patients were included. Sixty‐four publications were identified and 38 publications covering a unique domain were selected to inform this TLR. The incidence of hyperhidrosis ranged from 0.13% in the UK to 0.28% in the USA, with a higher rate in females. The prevalence of hyperhidrosis varied from 2.8%–4.8% in the US general population to 18.40% in Chinese inpatients, while the prevalence of axillary hyperhidrosis varied from 1.4% in the US general population to 5.75% in Japanese employees/students. Due to excessive sweating, hyperhidrosis was reported to be a moderate‐to‐extreme limitation at work for the US patients, with 33.5% feeling unhappy. Patients' satisfaction was high post‐treatment. Considerable costs were related to the treatment with botulinum toxin and surgery. Hospital stays for surgery lasted from 10 h to 3 days. The percentage of patients who sought a medical consultation varied from 6.3% for Japanese patients with primary focal hyperhidrosis to 51% for the US general population with any type of hyperhidrosis. There is limited evidence of the hyperhidrosis burden, particularly among Japanese patients; however, the burden was high and limited patients' daily functioning. Future actions should include implementation of educational programs to raise awareness of the condition, conduct of larger studies, and generation of more evidence. Understanding the nature of hyperhidrosis and the burden it poses is of utmost importance.
Association between pregnancy affected by vaginal bleeding and women's mortality: A cohort study
Authors: Dudukina Elena , Horváth‐Puhó Erzsébet , Sørensen Henrik Toft , Ehrenstein Vera
Published: July 2023

Objective

To investigate the association between vaginal bleeding (VB) in pregnancy and women's mortality, using VB‐unaffected pregnancies, terminations and miscarriages as comparators.

Design

Observational cohort study.

Setting

Nationwide registries of Denmark linked at an individual level.

Population or Sample

1 354 181 women and their 3 162 317 pregnancies (1979–2017), including 70 835 VB‐affected pregnancies and comparators: 2 236 359 VB‐unaffected pregnancies ending in childbirth; 589 697 terminations; and 265 426 miscarriages.

Methods

We followed pregnancies until the earliest date of woman's death, emigration or end of data.

Main outcome measures

All‐cause and cause‐specific mortality rates per 10 000 person‐years (PY) and hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted using Cox proportional hazards regression for age, calendar year, pre‐existing chronic conditions and socio‐economic factors.

Results

There were 2320 deaths from any cause among women following VB‐affected pregnancy (mortality rate 15.2, 95% CI 14.6–15.9 per 10 000 PY); 55 030 deaths following VB‐unaffected pregnancy (mortality rate 12.7, 95% CI 12.6–12.8); 27 500 deaths following a termination (mortality rate 21.9, 95% CI 21.6–22.1), and 10 865 deaths following a miscarriage (mortality rate 19.2, 95% CI 18.8–19.6). For comparison of VB‐affected versus VB‐unaffected pregnancies, associations with all‐cause (HR 1.14, 95% CI 1.09–1.19), natural causes (HR 1.15, 95% CI 1.09–1.22) and non‐natural causes (HR 1.27, 95% CI 1.08–1.48) mortality were attenuated in a sensitivity analysis of pregnancies recorded in 1994–2017 (HR 1.00, 95% CI 0.90–1.12, HR 0.98, 95% CI 0.85–1.14 and HR 1.04, 95% CI 0.72–1.51, respectively). Contrasts with remaining comparators did not suggest increased risks of all‐cause, natural or non‐natural mortality causes.

Conclusion

We found no evidence of an increased risk of women's mortality following VB‐affected versus VB‐unaffected pregnancy, termination or miscarriage.
Financial regulatory conundrums in the North Atlantic
Authors: POSNER ELLIOT , QUAGLIA LUCIA
Published: July 2023

This article explains a dominant, curious and important pattern that emerges from our original data on 11 areas of financial regulation in the United States and the European Union from the Great Financial Crisis to 2020: sustained regulatory stringency in both jurisdictions. Our novel explanation, rooted in theories about international economic interdependence, temporal process and market power, emphasizes cross‐border interactions that arose from a build‐up of ‘border‐policing’ capacities. Our medium‐n study, which combines congruence analysis and process tracing, reveals a causal mechanism – ‘joint reinforcement’ – whereby the potential penalties imposed by one of the two jurisdictions prevent or temper the other from watering down‐regulation. The study pushes the boundaries of qualitative research, advances theory and speaks to debates about global public goods.
Exploring the roles of natural resources on sustainability blueprint in G7 countries amidst green energy, technological innovation, and carbon‐tax intervention
Authors: Dong Xinhui , Ibrahim Ridwan Lanre , Ozturk Ilhan , Al‐Faryan Mamdouh Abdulaziz Saleh
Published: July 2023

Today's global economy faces the most devastating challenges of global warming occasioned by overdependence on natural resources. Besides, the dilemma of choosing between economic benefits and environmental costs emanating from natural resources heightens the empirical relevance of green energy in recent times. To solve this developmental puzzle, the current study presents extends the knowledge frontier by evaluating the impacts of natural resource dependence, green energy (captured by biofuels and renewable energy), carbon tax, and technological innovation on environmental sustainability in G7 economies. The empirical model endogenizes environmental policy stringency and financial development from 1996 to 2019. The empirical verification anchors on second‐generation estimators entailing Cross‐Sectional Autoregressive Distributed Lag (CS‐ARDL), Common Correlated Effects Mean Group (CCEMG), augmented mean group (AMG), and novel Method of Moment Quantile Regression (MMQR). The fallouts from the analyses uncover that natural resource dependence militates against the attainment of the sustainability blueprint by escalating the surge in CO2 emissions in G7 countries. Similarly, the feedbacks from financial development support the surge in emissions. On the flip side, green energy, technological innovation, carbon tax, and environmental policy appear as effective tools for mitigating the surge. The Fully Modified Ordinary Least Square (FMOLS) estimator for the country‐specific analysis corroborates the panel findings. Additionally, two channels of causalities, including unidirectional and bidirectional nexuses, are apparent from the estimated model. Policy measures are suggested based on empirical findings.
Bone mineral density and its influential factors in Chinese patients with newly diagnosed Crohn's disease
Authors: Zhao Yuan , Li Xiao Xuan , Li Fan , Yao Ling Ya , Liu Jing , Cao Qian
Published: July 2023

Objectives

Bone loss is a common morbidity in patients with inflammatory bowel disease (IBD). Bone mineral density (BMD) measurement is recommended for IBD patients at a high risk of osteoporosis. However, there is a lack of evidence in the need of BMD measurement in patients who are young at the first disease onset. In this study we aimed to investigate the prevalence of low BMD in patients with newly diagnosed Crohn's disease (CD) at 20–50 years of age and the potential risk factors.

Methods

A single‐center, retrospective cross‐sectional study was conducted. Medical records of the patients were reviewed and their demographics, clinical characteristics and laboratory test results were collected. Dual energy X‐ray absorptiometry (DEXA) scan was performed for BMD measurements; low BMD was defined as Z‐score or T‐score <−1.0 standard deviation (SD). Univariate and multivariate logistic regression analyses were used to determine the risk factors for low BMD.

Results

A total of 221 patients with CD were included; osteopenia and osteoporosis were identified in 23.1% and 8.6%, and 39.4% and 7.2% of the patients using Z‐score and T‐score, respectively. Female gender and a higher BMI at diagnosis were protective factors for low BMD.

Conclusions

Low BMD is common in patients with newly diagnosed CD aged 20–50 years. Female gender and a higher BMI at diagnosis might protect CD patients from bone loss. Therefore, BMD measurement and early intervention with calcium and vitamin D are recommended for these patients.
Beta‐cell function in type 2 diabetes (T2DM): Can it be preserved or enhanced?
Authors: Sayyed Kassem Laure , Rajpal Aman , Barreiro Margarita Victoria , Ismail‐Beigi Faramarz
Published: July 2023

Type 2 diabetes (T2DM) is a complex metabolic disorder manifested by hyperglycemia, insulin resistance, and deteriorating beta‐cell function. A way to prevent progression of the disease might be to enhance beta‐cell function and insulin secretion. However, most previous studies examined beta‐cell function while patients were using glycemia‐lowering agents without an adequate period off medications (washout). In the present review we focus on studies with a washout period. We performed a literature search (2010 to June 2021) using beta‐cell function and enhancement. The evidence shows that beta‐cell function can be enhanced. Bariatric surgery and very low calorie diets show improvement in beta‐cell function in many individuals. In addition, use of glucagon‐like peptide‐1 receptor agonists for prolonged periods (3 years or more) can also lead to improvement of beta‐cell function. Further research is needed to understand the mechanisms leading to improved beta‐cell function and identify agents that could enhance beta‐cell function in patients with T2DM.
Antibody response to inactivated COVID‐19 vaccine in patients with type 2 diabetes mellitus after the booster immunization
Authors: Li Haolong , Wang Yao , Li Xiaomeng , Wang Siyu , Feng Xinxin , Xiao Xinhua , Li Yongzhe
Published: July 2023

Background

The immunogenicity of booster inactivated COVID‐19 vaccines in patients with type 2 diabetes mellitus (T2DM) has remained unclear. Our study aims to investigate the antibody response to inactivated COVID‐19 vaccine following booster vaccination in patients with T2DM.

Methods

A total of 201 patients with T2DM and 102 healthy controls (HCs) were enrolled. The levels of anti‐SARS‐CoV‐2 total antibodies, anti‐receptor‐binding domain (RBD)‐specific IgG, neutralizing antibody (NAb) toward SARS‐CoV‐2 wild type (WT), and NAb toward SARS‐CoV‐2 Omicron BA.4/5 subvariant were measured to evaluate the vaccine‐induced immunological responses.

Results

The titers of anti‐RBD‐specific IgG (p = 0.018) and inhibition rates of NAb toward WT (p = 0.007) were significantly decreased in patients with T2DM compared to HCs after booster vaccination for more than 6 months. Both HCs and patients with T2DM showed poor resistance against BA.4/5 due to the detected inhibition rates being lower than the positive threshold. The levels of anti‐RBD‐specific IgG were positively associated with the proportions of CD3+CD4−CD8− T cells (p = 0.045), and patients with T2DM who had anti‐RBD‐specific IgG positivity showed higher proportions of CD3+CD4−CD8− T cells compared to those negative (p = 0.005).

Conclusions

Patients with T2DM showed impaired antibody responses after booster vaccination for more than 6 months. Decreased anti‐BA.4/5 responses give rise to the possibility of breakthrough infections for both patients with T2DM and HCs.