bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Insights into Pink-eyed Dilution Protein (Oca2)
Authors: Mesdaghi Shahram , Murphy David L. , Simpkin AJ , Rigden Daniel J.
Published: December 2022

Recent innovations in computational structural biology have opened an opportunity to revise our current understanding of the structure and function of clinically important proteins. This study centres on human Oca2 which is located on mature melanosomal membranes. Mutations of Oca2 can result in a form of oculocutanous albinism which is the most prevalent and visually identifiable form of albinism. Sequence analysis predicts Oca2 to be a member of the SLC13 transporter family but it has not been classified into any existing SLC families. The modelling of Oca2 with AlphaFold2 and other advanced methods shows that, like SLC13 members, it consists of a scaffold and transport domain and displays a pseudo inverted repeat topology that includes re-entrant loops. This finding contradicts the prevailing consensus view of its topology. In addition to the scaffold and transport domains the presence of a cryptic GOLD domain is revealed that is likely responsible for its trafficking from the endoplasmic reticulum to the Golgi prior to localisation at the melanosomes and possesses known glycosylation sites. Analysis of the putative ligand binding site of the model shows the presence of highly conserved key asparagine residues that suggest Oca2 may be a Na+/dicarboxylate symporter. Known critical pathogenic mutations map to structural features present in the repeat regions that form the transport domain. Exploiting the AlphaFold2 multimeric modelling protocol in combination with conventional homology modelling allowed the building of a plausible homodimer in both an inward- and outward-facing conformation supporting an elevator-type transport mechanism.
Single Cell transcriptional analysis ofex vivomodels of cortical and hippocampal development identifies unique longitudinal trends
Authors: Krizay Daniel K. , Goldstein David B. , Boland Michael J.
Published: December 2022

Postnatal cortical and hippocampal mouse primary neuronal cultures are powerful and widely-used models of neuronal activity and neurological disease. While this model is frequently used to recapitulate what is seenin vivo, how the transcriptomic profiles of neuronal networks change over development is not fully understood. We use single-cell transcriptomics to provide a view of neuronal network establishment and maturation. Our data highlight region-specific differences and suggest how cell populations program the transcriptome in these brain regions. We demonstrate that patterns of expression markedly differ between and within neurological diseases, and explore why these differences are found and how well they compare to other models. In particular, we show significant expression differences between genes associated with epilepsy, autism spectrum disorder, and other neurological disorders. Collectively, our study provides novel insights on this popular model of development and disease that will better inform design for drug discovery and therapeutic intervention.

Abstract Figure

Graphical Abstract

(A) Schematic representing select gene expression progression through neuronal network maturation from human cortical organoids (3- and 6-Month Organoid), newborn mice (P0 Mouse), immatureex vivocortex derived cultures (DIV 3ex vivo), functionally matureex vivocortex derived cultures (DIV15-31ex vivo), and adult mice (P56 Mouse). Color represents proportion of excitatory neurons with detectable expression for selected representative genesMapk10, Igfbp2, which increase and decrease through network maturation, respectively.

(B) Schematic representing divergent expression patterns between genes associated with epilepsy and ASD through network maturation between the organoids andex vivocultures shown in (A). Color scales represent the change in the percentile, in respect to all genes, of the proportion of excitatory neurons with detectable expression.
Subcellular location defines GPCR signal transduction
Authors: Radoux-Mergault Arthur , Oberhauser Lucie , Aureli Simone , Gervasio Francesco Luigi , Stoeber Miriam
Published: December 2022

G protein-coupled receptors in intracellular organelles can be activated in response to membrane permeant ligands, which contributes to the diversity and specificity of agonist action. The opioid receptors (ORs) provide a striking example, where opioid drugs activate ORs in the Golgi apparatus within seconds of drug addition. Till date, our knowledge on the signaling of intracellular GPCRs remains incomplete and it is unknown if the downstream effects triggered by ORs in plasma membrane and Golgi apparatus differ. To address this gap, we first assess the recruitment of signal transducers to ORs in both compartments. We find that Golgi-localized ORs couple to Gαi/o probes and are phosphorylated by GPCR kinases (GRK2/3), but unlike plasma membrane receptors, do not recruit β-arrestin or a specific Gα probe. Subsequent molecular dynamics simulations with OR–transducer complexes in model bilayers mimicking plasma membrane or Golgi composition reveal that the lipid environment promotes location selective coupling. Unbiased global analyses then show that OR activation in the plasma membrane and Golgi apparatus has strikingly different downstream effects on transcription and protein phosphorylation. Taken together, the study delineates OR signal transduction with unprecedented spatial resolution and reveals that the subcellular location defines the signaling effect of opioid drugs.
Additive effects of Zamzam water in reducing fasting blood glucose and LDL-cholesterol in rats fed on a ketogenic diet
Authors: AlJuwaie Ghadeer Fouad , Latif Rabia , Alsheikh Mona Hmoud , Alsunni Ahmed , Chathoth Shahanas
Published: December 2022

Purpose

The ketogenic diet (KD) has gained popularity due to its ability to improve type 2 diabetes, weight loss, antioxidant and anti-inflammatory activity. However, long-term use of the KD might not be safe due to its adverse effects. This study examined the effects of the KD alone or in combination with Zamzam water (holy water for Muslims) on glucose homeostasis, lipid parameters and oxidant-antioxidant variables in rats.

Design/methodology/approach

Based on the diet given for ten weeks, three groups of adult male Wistar rats were made (12 rats/group): (1) rats which fed on a chow diet and ordinary water, (2) rats which fed on KD and ordinary water and (3) rats which were given KD along with Zamzam. Fasting blood glucose (FBG), serum insulin, insulin resistance (HOMA-IR), LDL cholesterol, HDL cholesterol, superoxide dismutase and malondialdehyde were compared by one-way ANOVA followed by post-hoc Tukey’s HSD test among groups.

Findings

Rats which fed on KD and Zamzam water had significantly reduced FBG and LDL cholesterol compared to the rats which fed on a chow diet and ordinary water (p-values 0.001), and KD and ordinary water (p-value 0.004 and 0.006, respectively). Serum insulin, insulin resistance, HDL cholesterol, superoxide dismutase and malondialdehyde did not differ significantly.

Originality/value

Consumption of KD along with Zamzam for ten weeks significantly reduces FBG and LDL cholesterol. KD alone does not decrease these parameters in ten weeks duration.
Integrating green human resource management and circular economy to enhance sustainable performance: an empirical study from the Qatari service sector
Authors: Obeidat Shatha M. , Abdalla Shahira , Al Bakri Anas Abdel Karim
Published: December 2022

Purpose

This study aims to contribute to the current Green human resource management (HRM) field by providing an empirical examination of a comprehensive model that tests the effect of green strategic intent on Green HRM implementation, the possible effect of Green HRM and green empowerment on circular economy, and the effect of circular economy on sustainable performance. It examines the mediating effect of circular economy on the link between Green HRM and sustainable performance.

Design/methodology/approach

The study is empirical in nature. It focuses on the service sector in Qatar. Managers that work in the service sector represent the study participants. 149 questionnaires were collected and 131 completed questionnaires were used in the analysis. An advanced Partial Least Squares Structural Equation Modeling (SEM-PLS) analysis was conducted to reveal the study results.

Findings

The study findings confirmed the positive effect of green strategic intent on Green HRM, the positive link between Green HRM and green empowerment on circular economy, and the positive relationship between circular economy and sustainable performance. It also confirms the indirect effect of circular economy on the link between green HRM and sustainable performance.

Research limitations/implications

Because of the chosen research approach and the focus on the service sector in Qatar only, research results may lack generalizability.

Practical implications

This study provides important implications for practice on how to improve Green HRM practices; particularly for its unique context, the Qatari service sector.

Originality/value

This study is considered original since it is one of the few to examine a conceptual framework that links Green HRM, circular economy and sustainable performance.
Employees’ helping behavior toward the victims of human trafficking in the lodging industry
Authors: Farboudi-Jahromi Melissa , Tasci Asli D.A. , Sönmez Sevil
Published: December 2022

Purpose

This study aims to examine the factors that influence hotel/motel employees’ helping behavior toward the victims of human trafficking.

Design/methodology/approach

Using a survey-based quantitative method, this study examines and compares two models of helping behavior based on egoism and altruism theories to measure the helping tendencies of lodging employees toward victims of human trafficking.

Findings

The study results show that perceived intrinsic rewards of helping and empathy with the victims are the major antecedents of employees’ likelihood to help the victims.

Research limitations/implications

The study contributed to the egoism school of thought and the Cost-Reward Model by showing that only perceived intrinsic rewards drive individuals’ intention to help in risky covert situations, such as human trafficking, while perceived extrinsic rewards may demotivate people to help in these situations.

Originality/value

Previous studies overlooked the role of the lodging industry in human trafficking. This study focuses on service employees as potential helpers of the victims as they notice in hotels/motels.
Chernobyl dreams: investigating visitors’ storytelling in the Chernobyl exclusion zone
Authors: Ojala Veera
Published: December 2022

Purpose

Little is known about the overall meaning of the Chernobyl exclusion zone (CEZ) from the visitors’ point of view. Conceptualizing the zone as a storyscape and its narratives as intangible heritage resources, this study aims to investigate the visitors’ engagement with these resources and the resulting articulations from the engagements as translated into verbal and visual storytelling.

Design/methodology/approach

Participant observation and participant generated images in combination with in-depth interviews with different types of tourists were conducted. This paper uses the photographs chosen by the interviewees themselves as a photo essay to explore the evocation of stories through narrative engagement.

Findings

Through participant-oriented research, this study identified three dominant storytelling themes through which visitors focus their understanding of the CEZ. Visitors’ narrative engagements and visual storytelling co-produce the site and entail fluid and even conflicting narrative articulations about the CEZ and its cultural significance.

Research limitations/implications

The discoveries of this study stem from a unique developing heritage site. This study provided a more nuanced understanding of the different visitor categories in the CEZ and their group-specific ways to articulate, imagine and co-produce the storyscape of Chernobyl.

Originality/value

Gaining insight into the verbal and visual storytelling of tourists will contribute to the discussion of narrative consumption of different consumption profiles in tourism sites in addition to the mediation and construction of entangled memory spaces.
The role of student peers in HE student mental health and well-being
Authors: Smith Joanne , Hughes Gareth , Spanner Leigh
Published: December 2022

Purpose

There is evidence that students’ experiences in higher education can be adversely affected by mental health issues, whilst well-being can be bolstered through a sense of belonging. This study aims to draw from Student Minds research into student mental health to consider the importance of peers to constructing a sense of belonging.

Design/methodology/approach

This paper draws from a thematic review of 12 focus groups – involving student services staff in six UK universities (69 participants) – conducted as part of the consultation and creation of the Student Minds University Mental Health Charter. The schedule considered student support, service structures and developments to enhance student well-being and manage mental health risks.

Findings

A significant theme explored here is the positionality of student peers in terms of relatability, and the importance of orientation and belonging for student mental health and well-being. The findings also consider types of peer involvement (formal/informal) and the influence of structure, training and boundaries in interventions.

Research limitations/implications

Findings reveal the importance of feeling a sense of belonging in the university community to achieve well-being and good mental health. Peer support is an important contributor that supports transitions into university and creates a sense of belonging, which is important to all students, but more so to those less familiar with university, who lack role models and more easily feel isolated.

Practical implications

The research has implications for higher education providers, which should inform the promotion of peer support within student services, based on the recognised contribution to well-being and mental health. This is important for student success and related opportunities.

Social implications

Success in higher education will open opportunities and create improved future prospects for individuals. This will not be realised for individuals who face boundaries and barriers to successful transition through university. The importance of belonging and role of peer support has implications for those who find themselves excluded in society.

Originality/value

This is a qualitative study which gives voice to individuals in universities across the UK. The theme of peer support within this context and linked with mental health and well-being is underexplored.
Application of predetermined motion and time system in sewing automat to enhance the productivity and operator utilisation
Authors: Mondal Priyabrata , Jana Prabir
Published: December 2022

Purpose

Automation and the new buzzword, “Industry 4.0”, have dominated the media headlines in recent months. In this scenario, apparel manufacturers should not only install automatic machines but also standardise them based on specific industry requirements, and precise measures are required for daily target demands.

Design/methodology/approach

This study demonstrates the application of Predetermined Motion and Time System (PMTS) tools in various automatic and semiautomatic machines to obtain higher productivity and the highest utilisation percentage of operator and automats between the 1:1 and 1:2 man vs machine configuration models. In this study, timeSSD® was used to calculate the micro motions of humans. In addition, a video annotation and modelling software Tracker was used to calculate high-speed machine movements with loading frames of 30 FPS.

Findings

After the implementation of PMTS tools, it was found that for a 1:1 man vs machine configuration, the operator utilisation is 75% per shift and the operator idle time is 50% per cycle time, and the operator is sitting idle for 2 h per 8 h of shift. So, there is scope to improve the utilisation and idle time of operator.

Research limitations/implications

With the PMTS software, an industrial engineer professional with knowledge of the micromotion economy can only calculate micromotion.

Originality/value

Exploring the first time in the world to establish standard allowed minute (SAM) of a partly automated single-unit sewing machine with partial human intervention and a semiautomatic machine. Theoretical underpinnings indicate that manufacturers use the experience to determine the SAM of any operation over time, necessitating this work to calculate standard minutes automatically.
Tourism towards the well-being of Small Island Developing States: Tourism Agenda 2030
Authors: Puig-Cabrera Miguel , Martínez-del Vas Ginesa , Beltrán-Bueno Miguel Ángel , Nuevo-López Abraham
Published: December 2022

Purpose

The purpose of this study is to contrast the capacity of tourism-specialized and non-tourism-specialized systems in small developing insular societies to achieve a well-being model aligned with the Agenda 2030.

Design/methodology/approach

The empirical method of this work consists of a panel-corrected standard errors analysis for a total of seven Caribbean Small Island Developing States (SIDS) to measure the contribution of both economic diversification and tourism specialization to well-being in the Agenda 2030 framework. Time period considered in the analysis include 2005–2019.

Findings

Linear and nonlinear relationships reveal the need to conjugate both tourism specialization and economic diversification in the 2030-development agendas of small developing insular societies as both represent a means to achieve a well-being model aligned with the Agenda 2030.

Originality/value

One of the main novelties of this work is that development is analyzed from a multidimensional point of view (standard of living, access to education and health services), as an integrated thinking that considers any tourism development model that defines a route with Sustainable Development Goals (SDGs) and Agenda 2030 as main destination in SIDS. Specifically, practical implications are given combining recommendations to foster development and face poverty (SDG-1), while inequalities situations are reduced (SDG-10) and decent jobs are generated (SDG-8). These implications also focus on strengthening local suppliers of goods and services from other sectors to be integrated into the destination value chain (SDG-2), ensuring access to education (SDG-4) and contributing to gender equality (SDG-5).
COVID‐19 antibody positivity over time and pregnancy outcomes in seven low‐and‐middle‐income countries: A prospective, observational study of the Global Network for Women's and Children's Health Research
Authors: Goldenberg Robert L. , Saleem Sarah , Billah Sk Masum , Kim Jean , Moore Janet L. , Ghanchi Najia Karim , Haque Rashidul , Figueroa Lester , Ayala Alejandra , Lokangaka Adrien , Tshefu Antoinette , Goudar Shivaprasad S. , Kavi Avinash , Somannavar Manjunath , Esamai Fabian , Mwenechanya Musaku , Chomba Elwyn , Patel Archana , Das Prabir , Emonyi Wilfred Injera , Edidi Samuel , Deshmukh Madhavi , Hossain Biplob , Siraj Shahjahan , Mazariegos Manolo , Garces Ana L. , Bauserman Melissa , Bose Carl L. , Petri William A. , Krebs Nancy F. , Derman Richard J. , Carlo Waldemar A. , Liechty Edward A. , Hibberd Patricia L. , Koso‐Thomas Marion , Peres‐da‐Silva Nalini , Nolen Tracy L. , McClure Elizabeth M.
Published: December 2022

Objectives

To determine COVID‐19 antibody positivity rates over time and relationships to pregnancy outcomes in low‐ and middle‐income countries (LMICs).

Design

With COVID‐19 antibody positivity at delivery as the exposure, we performed a prospective, observational cohort study in seven LMICs during the early COVID‐19 pandemic.

Setting

The study was conducted among women in the Global Network for Women's and Children's Health's Maternal and Newborn Health Registry (MNHR), a prospective, population‐based study in Kenya, Zambia, the Democratic Republic of the Congo (DRC), Bangladesh, Pakistan, India (two sites), and Guatemala.

Population

Pregnant women enrolled in an ongoing pregnancy registry at study sites.

Methods

From October 2020 to October 2021, standardised COVID‐19 antibody testing was performed at delivery among women enrolled in MNHR. Trained staff masked to COVID‐19 status obtained pregnancy outcomes, which were then compared with COVID‐19 antibody results.

Main Outcome Measures

Antibody status, stillbirth, neonatal mortality, maternal mortality and morbidity.

Results

At delivery, 26.0% of women were COVID‐19 antibody positive. Positivity increased over the four time periods across all sites: 13.8%, 15.4%, 21.0% and 40.9%. In the final period, positivity rates were: DRC 27.0%, Kenya 33.1%, Pakistan 32.8%, Guatemala 37.0%, Zambia 37.8%, Bangladesh 47.2%, Nagpur, India 57.4% and Belagavi, India 62.4%. Adjusting for site and maternal characteristics, stillbirth, neonatal mortality, low birthweight and preterm birth were not significantly associated with COVID‐19. The adjusted relative risk (aRR) for stillbirth was 1.27 (95% CI 0.95–1.69). Postpartum haemorrhage was associated with antibody positivity (aRR 1.44; 95% CI 1.01–2.07).

Conclusions

In pregnant populations in LMICs, COVID‐19 antibody positivity has increased. However, most adverse pregnancy outcomes were not significantly associated with antibody positivity.
‘We work in silos’: Exploring clinicians' perspectives on the dietary management of coronary heart disease and type 2 diabetes in an Australian public hospital and community health service
Authors: Mayr Hannah L. , Savill Holly , Law Lynette , Campbell Katrina L. , Hill Jan , Palmer Michelle , Hickman Ingrid J. , Kelly Jaimon T.
Published: December 2022

Aims

This study explored clinicians' perspectives on roles, practices and service delivery in the dietary management of coronary heart disease and type 2 diabetes in a public health service.

Methods

Semi‐structured individual interviews were conducted with 57 clinicians (21 nurses, 19 doctors, 13 dietitians and 4 physiotherapists) involved in the care of relevant patients across hospital and post‐acute community settings in a metropolitan health service in Australia. Interviews were audio‐recorded, transcribed verbatim and analysed using inductive thematic analysis.

Results

A total of 3 themes with 10 subthemes were identified. (a) ‘Treatment prioritisation’: important role of nutrition in risk factor management; competing priorities with complex patients; weight loss as a priority; and dietitians individualise. (b) ‘Diverse roles in providing diet advice’: a tension between nutrients, restrictions and diet quality; patients seek and trust advice from non‐dietitians; and providing nutrition information materials crosses professions. (c) ‘Dietitian access’: variable integration and resourcing; access governed by clinician discretion and perceived patient interest; and bespoke application of referral pathways.

Conclusions

Time and resource constraints, variable access and referral to dietitians, and inconsistent advice were key challenges in the dietary management of coronary heart disease and type 2 diabetes. Models of care may be improved with greater investment and integration of dietitians, including to provide professional support across disciplines and disease specialties.
Verification of delay time and image compression thresholds for telesurgery
Authors: Takahashi Yoshiya , Hakamada Kenichi , Morohashi Hajime , Akasaka Harue , Ebihara Yuma , Oki Eiji , Hirano Satoshi , Mori Masaki
Published: December 2022

Introduction

Telerobotic surgery relies on communication lines, causing delays, and video information requires pre‐transmission compression. Such delays and video degradation will continue to be unavoidable making communication conditions verification essential. Understanding the network specification values required for telerobotic surgery entails determining acceptable levels of delay and degradation due to the video compression and restoration processes during surgery.

Methods

The hinotori™ surgical robot from Medicaroid was used. Eight surgeons, skilled in robotic surgery, performed gastrectomy or rectal resection on pigs. Image compression (bitrate: 120, 60, 30, 20, 10 Mbps) was random, changing encoder settings during surgery, and delay times (30, 50, 100, 150 milliseconds) were pseudo‐randomly inserted, changing emulator settings. Acceptable video levels were evaluated. Subjective evaluations by surgeons and evaluators regarding image degradation and operability, and objective evaluations of image degradation and operability were given five‐point ratings.

Results

Regarding delay time, 30 and 50 millisecond periods garnered average ratings of 3.6 and 4.0, respectively, signifying that surgery was feasible. However, at 100 and 150 millisecond, average ratings were 2.9 and 2.3, respectively, indicating surgery was not feasible for the most part in these cases. The average rating for image compression was 4.0 or higher for bitrates of 20, 30, 60, and 120 Mbps, suggesting that surgery is possible even at bitrates as low as 10 Mbps, with an average rating of 4.0.

Conclusion

In remote robotic surgery using the hinotori™, image compression and delay time are largely acceptable, so surgery can be safely performed.
Don't forget cord blood in non‐remission acute myeloid leukaemia!
Authors: Castagna Luca , Patti Katia , Mulè Antonino
Published: December 2022

Transplantation from haploidentical donors is widely used, with progressive reduction of cord blood (CB) as alternative donor. The paper by Matsuda and colleagues, the largest analysing the outcome in non‐remission acute myeloid leukaemia (AML) transplanted with haploidentical donor or CB, suggests that CB is still a viable option when considering allogeneic transplantation for advanced AML.

Commentary on: Matsuda et al. Comparison of transplant outcomes between haploidentical transplantation and single cord blood transplantation in non‐remission acute myeloid leukaemia: A nationwide retrospective study. Br J Haematol. 2023;201:106–113.
Distributive justice criteria and social categorization processes predict healthcare allocation bias
Authors: Madeira Filipa , Do Bú Emerson Araújo , Freitas Gonçalo , Pereira Cicero Roberto
Published: December 2022

Objectives

Drawing on theories of distributive justice and intergroup discrimination, we examined how much distributive justice criterion and racial group membership contribute to bias in healthcare allocation decisions, by testing a theoretical model that specifies perceived stereotypicality and individual responsibility as a serial mediation process in the relationship between disease's contraction controllability (controllable vs. non‐controllable) and bias in medical decision‐making.

Method

White Portuguese medical students (N = 213) participated in an online experimental study conducted in two phases. In phase 1, we manipulated the cause of disease contagion and the salience of patient's racial categorization, and measured the stereotypicality of behaviour. In phase 2, we assessed perceived responsibility and likelihood of recommending medical treatment.

Results

Controllable (vs. non‐controllable) contraction behaviours in phase 1 were perceived as more stereotypic. As a spillover effect, more stereotypical behaviours in phase 1 predicted more patient's responsibility for their disease in phase 2. Importantly, controllable behaviours of disease contraction in phase 1 negatively affected recommendations for medical treatment in phase 2; and this negative effect was serially mediated by the stereotypicality of behaviour and patient responsibility. Furthermore, patients' skin colour moderated this process, meaning that perceptions of controllable behaviour as more stereotypic were stronger for Black than for White patients.

Conclusions

This research shows how stereotyping and social categorization bias allocation decisions through the patient's level of responsibility in decision‐making processes. The findings are discussed in light of principles of distributive justice and the literature on intergroup relations with respect to racial disparities in health care.
Chytrid prevalence and infection intensity in treefrogs from three environments with different degrees of conservation in Mexico
Authors: Bolom‐Huet René , Pineda Eduardo , Andrade‐Torres Antonio , Díaz‐Fleischer Francisco , Muñoz Antonio L. , Galindo‐González Jorge
Published: December 2022

Chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), has been related to rapid population declines and extinction in amphibians around the world. Bd has been associated with a severe decline in amphibian populations in southern Mexico. We compare the prevalence and intensity of Bd infection in two tree frogs in southern Mexico with similar life habits (Plectrohyla matudai and Ptychohyla euthysanota), inquiring if they differ across habitat types with different degrees of disturbance: preserved cloud forest, secondary cloud forest and anthropized riparian vegetation, and across three seasons. We examine the relationship between infection prevalence and intensity with biotic and abiotic variables. Infection prevalence differed between the two species, but not among environments, despite their similar life habits. Among seasons, prevalence decreased significantly at the end of the rainy season. There was no indication of significant changes in infection intensity between species, environments, and seasons. Moreover, the interaction among extrinsic factors (canopy cover, temperature, relative humidity) and factors intrinsic factors (body condition) explains the dynamics of Bd infection in the region. In our sample, we found no disease‐affected individuals, which may indicate that both species are resistant to the effects of the pathogen under field conditions. Finally, our results found no evidence to indicate that open canopies and anthropized habitats of the Sierra Madre de Chiapas are a refuge that prevents high prevalence or infection of Bd in stream breeders' amphibians.

Abstract in Spanish is available with online material.
The value of concentration of alveolar nitric oxide in diagnosing small airway dysfunction in patients with stable asthma
Authors: Wang Jing , Wu Ke , Cheng Xianliang , Chen Xiangsong , Qi Yanan , Zhao Limin
Published: December 2022

Background

Exhaled nitric oxide (FeNO) is a simple, noninvasive, and reproducible test, and FeNO (50 ml/s) is often used to reflect airway inflammation. The peripheral small airway/alveolar nitric oxide (NO) concentration is derived from the output of NO at multiple flow rates. Concentration of alveolar NO (CANO), which has been reported to reflect peripheral small airway inflammation, may be related to parameters that reflect abnormal small airway function.

Aim

This study aims to investigate the relationship among CANO levels, clinical features, and small airway function‐related indicators in patients with stable asthma and to provide a simple method for monitoring small airway function in asthma.

Design and Methods

We recruited 144 patients with well‐controlled, stable asthma, including 69 patients with normal small airway function (normal group) and 75 patients with small airway dysfunction (abnormal group). CANO and pulmonary function were measured.

Results

CANO was significantly higher in the abnormal group ([7.28 ± 3.25] ppb) than the normal group CANO ([2.87 ± 1.50] ppb). FEF25–75%pred ([55.0 ± 16.5]%), FEF50%pred ([46.4 ± 13.2]%), and FEF75%pred ([41.9 ± 13.1]%) in abnormal group were significantly lower compared with normal group ([89.9 ± 7.5]%), ([80.9 ± 6.8]%), and ([73.8 ± 5.0]%). CANO was negatively correlated and FEF25–75%pred, FEF50%pred, and FEF75%pred (r = −0.87, P < 0.001; r = −0.82, P < 0.001; r = −0.78, P < 0.001). CANO was positively correlated with age (r = 0.27, P = 0.001). The area under the ROC curve was 0.875 for CANO. The optimal cutoff point of 5.3 ppb had sensitivity and specificity values of 72% and 92% in diagnosing small airway dysfunction.

Conclusion

CANO has diagnostic value for small airway dysfunction, and the optimal cutoff value is 5.3 ppb. However, the diagnostic evidence is still insufficient, so it still needs further exploration for its value in detecting small airway dysfunction.
Impact of kidney transplant on post‐operative morbidity and mortality in patients with pre‐operative cardiac dysfunction
Authors: Kumar Aman , Naso Caroline , Bacon Daniel , Agala Chris B , Gerber David A.
Published: December 2022

Background

Several studies show an increase in complications, both cardiac and non‐cardiac, and a higher mortality in patients with preexisting cardiac disease when they undergo elective surgery. Due to the high incidence of cardiac dysfunction in patients with concomitant chronic kidney disease, we wanted to determine if the same negative impact is demonstrated in patients undergoing kidney transplantation.

Methods

A retrospective analysis was done on 582 patients who underwent kidney transplant from a single transplant center between 2014 and 2019. Participants for this study were divided into two groups based on cardiac ejection fraction: normal EF (≥40%) (n = 540) and low EF (<40%) (n = 33); exclusion criteria included patients undergoing multi‐organ transplants (n = 9). Characteristics and outcomes of patients were compared before and after transplant using chi‐square tests for categorical measures, and either Kruskal–Wallis or paired Student's t tests for continuous measures. Overall survival (OS) between groups was assessed using the Kaplan–Meier test. We compared outcomes between the normal EF and low EF groups using logistic regression in raw data, and propensity score matched sample and inverse‐probability‐weighting to mitigate selection bias.

Results

There was no significant difference in survival between patients in the low EF and normal EF groups (p = .33). Among patients with low EF, mean EF after transplant significantly improved (mean: 55.83% ± 5.75%) compared to mean EF before transplant (38.28% ± 7.35%), (p = < .0001). Of the patients with a low EF before transplant, 1 in 5 had a history of CAD, compared to only 1 in 10 among those patients with a normal EF, p = .0657. Post‐transplant complications were comparable between the groups.

Conclusion

Patients undergoing kidney transplantation with a low ejection fraction do not demonstrate an increased incidence of morbidity or mortality in the peri‐ and post‐transplant follow‐up compared with patients with a normal ejection fraction. Cardiac events post‐transplantation is also comparable between the two groups. Of note, patients with a low EF have a significantly improved EF after kidney transplant which is likely a function of improvement in their physiologic state after the kidney transplant.
GABAergic synaptic transmission and cortical oscillation patterns in the primary somatosensory area of a valproic acid rat model of autism spectrum disorder
Authors: Fontes‐Dutra Mellanie , Righes Marafiga Joseane , Santos‐Terra Júlio , Deckmann Iohanna , Brum Schwingel Gustavo , Rabelo Bruna , Kazmierzak de Moraes Rafael , Rockenbach Marília , Vendramin Pasquetti Mayara , Gottfried Carmem , Calcagnotto Maria Elisa
Published: December 2022

Autism spectrum disorder (ASD) is characterized by impaired social communication and interaction associated with repetitive or stereotyped behaviour. Prenatal valproic acid (VPA) exposure in rodents is a commonly used model of ASD. Resveratrol (RSV) has been shown to prevent interneuronal and behavioural impairments in the VPA model. We investigated the effects of prenatal VPA exposure and RSV on the GABAergic synaptic transmission, brain oscillations and on the genic expression of interneuron‐associated transcription factor LHX6 in the primary somatosensory area (PSSA). Prenatal VPA exposure decreased the sIPSC and mIPSC frequencies and the sIPSC decay kinetics onto layers 4/5 pyramidal cells of PSSA. About 40% of VPA animals exhibited absence‐like spike–wave discharge (SWD) events associated with behaviour arrest and increased power spectrum density of delta, beta and gamma cortical oscillations. VPA animals had reduced LHX6 expression in PSSA, but VPA animals treated with RSV had no changes on synaptic inhibition or LHX6 expression in the PSSA. SWD events associated with behaviour arrest and the abnormal increment of cortical oscillations were also absent in VPA animals treated with RSV. These findings provide new venues to investigate the role of both RSV and VPA in the pathophysiology of ASD and highlight the VPA animal model as an interesting tool to investigate pathways related to the aetiology and possible future therapies to this neuropsychiatric disorder.
RSPO4 is a potential risk gene of stages III–IV, grade C periodontitis through effects on innate immune response and oral barrier integrity
Authors: Chopra Avneesh , Song Jiahui , Weiner January , Keceli Huseyin G. , Dincer Pervin R. , Cruz Raquel , Carracedo Angel , Blanco Juan , Dommisch Henrik , Schaefer Arne S.
Published: December 2022

Aim

R‐spondin 4 (RSPO4) is a suggestive risk gene of stage III–IV, grade C periodontitis and upregulated in gingiva of mice resistant to bacteria‐induced alveolar bone loss. We aimed to replicate the association, identify and characterize the putative causal variant(s) and molecular effects, and understand the downstream effects of RSPO4 upregulation.

Materials and Methods

We performed a two‐step association study for RSPO4 with imputed genotypes of a German–Dutch (896 stage III–IV, grade C periodontitis cases, 7104 controls) and Spanish sample (441 cases and 1141 controls). We analysed the allelic effects on transcription factor binding sites with reporter gene and antibody electrophoretic mobility shift assays. We used CRISPR/dCas9 activation and RNA sequencing to pinpoint RSPO4 as the target gene and to analyse downstream effects.

Results

RSPO4 was associated with periodontitis (rs6056178, pmeta = 4.6 × 10−5). rs6056178 contains a GATA‐binding motif. The rs6056178 T‐allele abolished reporter activity (p = .004) and reduced GATA binding (−14.5%). CRISPRa of the associated region increased RSPO4 expression (25.8 ± 6.5‐fold, p = .003). RSPO4 activation showed strongest induction of Gliomedin (439‐fold) and Mucin 21 (178‐fold) and of the gene set “response to interferon‐alpha” (area under the curve [AUC] = 0.8, p < 5 × 10−6). The most repressed gene set was “extracellular matrix interactions” (AUC = 0.8, padj = .00016).

Conclusion

RSPO4 is a potential periodontitis risk gene and modifies host defence and barrier integrity.
Pain trajectories of nursing home residents
Authors: Cole Connie S. , Carpenter Janet S. , Blackburn Justin , Chen Chen X. , Jones Bobby L. , Hickman Susan E.
Published: December 2022

Background

Understanding changes in nursing home (NH) resident pain over time would provide a more informed perspective, allowing opportunities to alter the course of illness, plan care, and set priorities. Therefore, the purpose of this analysis was to identify and characterize clinically meaningful, dynamic pain trajectories in NH residents.

Methods

Retrospective longitudinal analysis of NH resident pain scores with a length of stay >100 days (N = 4864). Group‐based trajectory modeling was applied to Minimum Data Set 3.0 assessments to identify pain trajectories. Trajectories were then characterized using unadjusted and adjusted cross‐sectional associations between residents' demographic and clinical characteristics and their pain trajectory.

Results

We identified four distinct trajectories: (1) consistent pain absence (48.9%), (2) decreasing‐increasing pain presence (21.8%), (3) increasing‐decreasing pain presence (15.3%), and (4) persistent pain presence (14.0%). Demographics of younger age and living in a rural area were associated with the persistent pain presence trajectory. Clinical variables of obesity and intact cognition were associated with being in the persistent pain presence trajectory. A smaller proportion of residents with moderately or severely impaired cognition were in any of the trajectory groups with pain.

Conclusions

We identified and characterized four pain trajectories among NH residents, including persistent pain presence which was associated with demographic characteristics (younger, female, rural) and clinical factors (obese, fracture, contracture). Moreover, residents with a diagnosis of Alzheimer's disease or dementia were less likely to be in any of the three trajectories with pain, likely representing the difficulty in evaluating pain in these residents. It is important that NH staff understand, recognize, and respond to the factors associated with the identified pain trajectories to improve mitigation of potentially persistent pain (e.g., hip fracture, contracture) or improve proxy pain assessment skills for residents at risk for under reporting of pain (e.g., Alzheimer's Disease).
How Risky Are U.S. Corporate Assets?
Authors: DAVYDIUK TETIANA , RICHARD SCOTT , SHALIASTOVICH IVAN , YARON AMIR
Published: December 2022

We use market data on corporate bonds and equities to measure the value of U.S. corporate assets and their payouts to investors. In contrast to equity dividends, total corporate payouts are highly volatile, turn negative when corporations raise capital, and are acyclical. At the same time, corporate asset returns are similar to returns on equity, and both are exposed to fluctuations in economic growth. To reconcile this evidence, we argue that acyclical but volatile net repurchases mask the exposure of total payouts' cash components to economic growth risks. We develop an asset pricing framework to quantitatively illustrate this economic channel.
Identification of distinct immunophenotypes in chronic pulmonary aspergillosis using cluster analysis
Authors: Sehgal Inderpaul S. , Dhooria Sahajal , Muthu Valliappan , Rudramurthy Shivaprakash M. , Prasad Kuruswamy T. , Chakrabarti Arunaloke , Aggarwal Ashutosh N. , Agarwal Ritesh
Published: December 2022

Background

Whether chronic pulmonary aspergillosis (CPA) has different immunophenotypes remains unknown.

Objective

To identify different CPA immunophenotypes using cluster analysis.

Methods

We used a subject‐centred multivariate clustering approach without prior assumptions to identify CPA phenotypes. We retrospectively included the data of treatment‐naïve subjects with CPA and excluded subjects with asthma and allergic bronchopulmonary aspergillosis (ABPA). We performed a scalable two‐step cluster analysis using the log‐likelihood distance measures to identify CPA phenotypes based on the blood immunological profile (total IgE, eosinophil count and Aspergillus‐specific IgE and IgG).

Results

We included 351 CPA subjects and found two clusters. Cluster 2 (n = 118) had significantly higher serum total IgE, peripheral blood eosinophil count, and serum A. fumigatus‐specific IgE and IgG than cluster 1 (n = 233). Cluster 2 subjects had a lower FEV1:FVC ratio on spirometry and were more likely to have a fungal ball (88 [74.6%] vs. 145 (62.2%), p = .023) on the CT thorax than cluster 1. After treatment discontinuation, cluster 2 had a longer median (interquartile range) time to relapse than cluster 1 (11.5 [7.3–27.4] vs. 4 [1.1–8.9] months, p = .005).

Conclusion

We identified two distinct CPA phenotypes, type‐2 dominant and non‐type‐2, with different clinical and radiological findings and treatment outcomes. Future studies should confirm our findings and investigate different treatment strategies based on CPA phenotypes.
Risk factors for failing a repeat oral food challenge in preschool children with hen's egg allergy
Authors: Nishino Makoto , Yanagida Noriyuki , Sato Sakura , Nagakura Ken‐ichi , Takahashi Kyohei , Ogura Kiyotake , Ebisawa Motohiro
Published: December 2022

Background

Children with hen's egg (HE) allergy and a positive initial oral food challenge (OFC) require rechallenge to assess for tolerance. However, the risk factors for a positive repeat OFC remain unclear.

Methods

We retrospectively analyzed data from 243 preschool children who failed an initial OFC with half a heated HE and repeated the same OFC after 6–24 months. Logistic regression models were used to determine risk factors for a positive repeat OFC, including factors that were ascertainable immediately after the initial OFC and at the repeat OFC as variables.

Results

The median age, egg white‐, and ovomucoid‐specific IgE (sIgE) were 3.5 years, 12.7, and 7.2 kUA/L, respectively. The median interval between OFCs was 12.4 months and repeat OFCs were positive in 132 (54%) patients. One multivariate analysis model indicated that risk factors for a positive repeat OFC included cumulative dose (adjusted odds ratio [aOR]:0.58), anaphylaxis (aOR: 3.09), total serum IgE (aOR: 0.41), ovomucoid‐sIgE (aOR: 3.21), and age (aOR: 1.68) at the initial OFC. Another model indicated that the risk factors were cumulative dose (aOR: 0.59) and anaphylaxis (aOR: 3.41) at initial OFC and total serum IgE (aOR: 0.36), ovomucoid‐sIgE (aOR: 4.93), and age (aOR: 1.30) at repeat OFC.

Conclusion

Low threshold dose and severe symptoms at initial OFC, and low total serum IgE, high ovomucoid‐sIgE and higher age at initial and repeat OFCs are risk factors for the persistence of HE allergy and they may be useful when deciding the rechallenge interval for heated HE in preschool children.
Aortic dissection diagnosed with the aortic dissection detection risk score of 2 without D-dimer elevation
Authors: Saito Kanako , Soma Shunsuke
Published: December 2022

Acute aortic dissection can be fatal if overlooked, and the absence of D-dimer elevation can be used to exclude acute aortic dissection. However, we report a case of acute aortic dissection without D-dimer elevation. A man in his 70s presented to the emergency department with lumbar back pain. D-dimer was <1.0 µg/mL; however, acute aortic dissection was strongly suspected because of the sudden onset of lumbar back pain with a shifting location. Because of a difference in systolic blood pressure in both upper extremities, we performed a thorough examination using contrast-enhanced CT, leading to a diagnosis of acute aortic dissection. The patient was immediately referred to cardiovascular surgery and treated conservatively with antihypertensive management. The aortic dissection detection risk score (ADD-RS) classified the patient as high risk. This suggests the importance of using the D-dimer with the ADD-RS rather than solely relying on the D-dimer results to diagnose acute aortic dissection.
Adipophilin: roles in physiology and pathology
Authors: Li Feng-Zeng , Fang Sheng
Published: December 2022

Adipophilin (ADRP/ADPH/PLIN2), an adipocyte differentiation-related protein, is highly expressed at a very early time during the differentiation of adipocytes. It assists in the formation and maintenance of intracellular lipid droplets and plays a role in regulating the physiological functions of the body. More and more studies indicate that it is involved in the occurrence and development of a variety of glycolipid metabolic diseases and tumours. In this review, we comprehensively stated the expression and functions of adipophilin and introduced its roles in physiology and pathology.