bluuebunny/crossref_metadata_2025 huggingface dataset:
Equity and use of telehealth modalities among people living with HIV during the COVID-19 pandemic
Authors: Carson Hannah , Wang Karen H. , Paek Hyung , Hoffman Pamela , Arakaki Andrew , Gonzalez-Colaso Rosana , Barakat Lydia A , Villanueva Merceditas , Womack Julie A
Published: December 2023

Background

COVID-19 forced a rapid transition to telehealth. Little is known about the use of telephone versus video visits among people living with or at risk for HIV (PWH).

Setting

We studied electronic health record data from an urban HIV clinic. Our sample included visit- and person-level data. Visit-level data came from appointments scheduled from 30 March 2020 to 31 May 2020. Person-level data came from patients 18+ years of age who completed at least one telephone or video visit during the period of interest.

Methods

We performed a cross-sectional analysis. Our primary outcome was telehealth modality (telephone or video). We compared visit completion status by telehealth modality. We evaluated associations between patient characteristics and telehealth modality using logistic regression.

Results

In total, 1742 visits included information on telehealth modality: 1432 telephone (82%) and 310 (18%) video visits. 77% of telephone visits were completed compared to 75% of video visits ( p = 0.449). The clinic recorded 643 completed telehealth visits in April and 623 in May 2020. The proportion of telephone visits decreased from 84% in April to 79% in May ( p = 0.031). Most patients participated in telephone versus video visits (415 vs. 88 patients). Older age (adjusted odds ratio [AOR] 3.28; 95% confidence interval [CI], 1.37–7.82) and Black race (AOR 2.42; 95% CI, 1.20–4.49) were positively associated with telephone visits. Patient portal enrollment (AOR 0.06; 95% CI, 0.02–0.16) was negatively associated with telephone visits.

Conclusion

PWH used telephone more than video visits, suggesting that telephone visits are a vital healthcare resource for this population.
Research on user's highly sensitive privacy disclosure intention in home intelligent health service system: A perspective from trust enhancement mechanism
Authors: Li Shugang , Li Ruoxuan , Zhu Boyi , Zhang Beiyan , Li Jiayi , Liu Fang , Wei Yanfang
Published: December 2023

Objective

The aim is to investigate the determinants and mechanisms that influence user's highly sensitive privacy disclosure intention (HSPDI) in home intelligent health service system (HIHSS).

Methods

This study improves the privacy calculus theory by considering the influence of service providers’ trust enhancement mechanism besides benefit and risk factors and investigates their impact on users’ HSPDIs. This study takes perceived valence and perceived security as the trade-off result among perceived benefits, perceived risks, financial trust enhancement mechanism, and the technical trust enhancement mechanism and suggests that perceived valence and perceived security further affect users’ HSPDI in HIHSS. Moreover, the common and differential effects of the perceived justice of privacy violation compensation (PJOPVC) and the perceived effectiveness of privacy protection technologies (PEOPPTs) are studied. The structural equation model is used to analyze 204 valid samples to test the proposed model.

Results

The results show that perceived benefits and perceived risks are important predictors of perceived valence and perceived security, and further affect users’ HSPDI. We find PJOPVC has a greater impact on perceived valence while PEOPPT has a greater impact on perceived security.

Conclusions

We recommend that the HSPDI of users with low perceived valence can be improved by providing privacy violation compensation while the HSPDI of users with low perceived security can be enhanced by popularizing relevant knowledge of privacy protection technologies.
Investigating the effects of digital foot self-management program on enhancing self-efficacy and self-care behavior among community-dwelling older adults with type 2 diabetes: A randomized controlled trial
Authors: Chen Shu-Ming , (Jo) Wu Chiung-Jung
Published: December 2023

Introduction

Diabetic foot self-management intervention programs have been proven to positively influence individuals’ behaviors in preventing diabetic foot ulcers. Using digital technologies to deliver programs can facilitate compliance with diabetes self-management programs. However, few studies have focused on the effects of such digital programs on improving the self-efficacy and behaviors of older adults with type 2 diabetes in the community.

Aim

To evaluate the effects of a digital foot self-management program on self-efficacy, self-care behavior, and Hemoglobin A1c levels.

Design

A single-blinded, randomized controlled trial was conducted.

Methods

The intervention program comprised a 4-week digital foot care program with one face-to-face education session, phone calls once weekly, and LINE messages (social media) three times per research nurse and a follow-up of three months. Patients in the control group received routine care.

Results

A total of 100 participants ( n = 50 in the control and n = 50 in the intervention groups) completed the study with a mean age of 67.55 (SD = 11.17). The results showed significant improvements in self-efficacy ( F = 2187.24, p < 0.01) and self-care behavior ( F = 614.71, p < 0.01) in foot care between the groups. The Hemoglobin A1c levels showed a 0.41% reduction over time in the experimental group ( t = −3.759; p < 0.01), whereas the control group showed a 0.06% reduction ( t = −0.797, p > 0.05).

Conclusion

The newly developed digital foot self-management program was effective in community-dwelling older adult patients with type 2 diabetes.
Confrontation and Avoidance of Uncivil Behaviors in the Workplace: Empirical Evidence From the Tourism Industry
Authors: Nasir Sobia , Roomi Muhammad Azam , Nasir Nadia , Khan Waqas , Rashid Muhammad
Published: December 2023

This study examines factors hindering employee engagement, focusing on perceived workplace incivility and its relationship with work engagement. It also presents the mediating and moderating roles of emotional responses and coping mechanisms in the workplace to determine “why” and “when” employee engagement is destabilized. The cross-sectional study used 391 samples from the hotel industry; data were collected from the crew staff via self-administered questionnaires and analyzed using Smart PLS. The study’s outcome draws attention to perceived workplace incivility and its significant negative impact on work engagement. The results also reveal that employees’ emotional responses and coping mechanisms play significant mediator and moderator roles in the relationship between workplace incivility and work engagement. In terms of theoretical background, the study makes a novel theoretical contribution by applying Affective Events Theory (AET) when employees confront incivility that triggers emotional reactions and then shows how those reactions lead to adverse work outcomes and behaviors. The study outcomes have significant implications for strategic hotel industry staff and policymakers and provide insights for future researchers. Hotel management might consider this study helpful for generating a crew-supportive work environment and stabilizing employee engagement.
Factors Influencing Early Childhood Educators’ Use of Digital Educational Aids: A Sequential Explanatory Study
Authors: Alotaibi Manar S.
Published: December 2023

Kindergarten educators play a crucial role in promoting young children’s technological awareness and ensuring that they possess the necessary skills and knowledge to integrate technology effectively into their teaching practices. This study examines the factors that influence early childhood educators’ use of digital educational aids, that is, media and technology. The study employs a sequential explanatory design, which is a mixed-methods approach consisting of two phases. The first phase is quantitative, where data is collected through surveys, and the second phase is qualitative, where semi-structured interviews are conducted among a small subsample to gain a deeper understanding of the participants’ perspectives. The survey data collected from 369 early childhood educators revealed that attitudes toward the value of technology in aiding children’s learning had the strongest influence on technology use. Additionally, semi-structured interviews conducted with 62 educators found that teacher beliefs, knowledge, and attitudes, as well as access to technology and media resources, influenced the frequency and quality of technology and media use in preschool classrooms. These findings emphasize the importance of extrinsic factors including support, resources, and policies, while intrinsic factors include confidence and beliefs. Moreover, teacher attitudes toward the value of technology for learning and confidence using technology had the strongest positive effects on actual technology use.
Mediating Effect of Creativity on How Burnout Affects Social Media Use: An Examination on Physicians
Authors: Şahin Dilek
Published: December 2023

Burnout is a state of emotional, physical, and mental exhaustion due to exposure to excessive and prolonged stress. It isn’t a medical condition. However, it negatively affects the creativity of employees. The individual with increasing burnout withdraws into his/her world by reducing his/her social ties with his/her environment. Those who are self-isolating might try to connect with the outside world by using social media more. This study primarily aims to examine the mediating effect of creativity on how burnout affects social media use among physicians through a correlational survey study design. Personal information form, Maslach Burnout Inventory, Kaufman Domains of Creativity Scale, and Social Media Disorder Scale were utilized as measures. A total of 529 physicians participated in the study. According to the results, there is a correlation between burnout and self/everyday creativity, as well as self/creativity and social media use. Moreover, there is a correlation between burnout and social media use. It was concluded in the study that creativity among physicians had a mediating effect on social media user. This study is meaningful in terms of seeing the effect of burnout on self/everyday creativity and social media usage. Directing physicians to programs that reduce/prevent burnout might positively affect their self/everyday creativity and social media usage.
Perceptual Thresholds for Threat Are Lowered in Anxiety: Evidence From Perceptual Psychophysics
Authors: Glasgow Shannon , Imbriano Gabriella , Ozturk Sekine , Jin Jingwen , Mohanty Aprajita
Published: December 2023

Anxiety is believed to be characterized by heightened sensitivity to threat. The behavioral-inhibition system (BIS), a risk factor for anxiety, is hypothesized to index this threat sensitivity. In the present study, we address a critical gap in the literature: Neither anxiety nor BIS have been clearly linked with behavioral measures of threat sensitivity indexed by lowered threat-related perceptual thresholds. We used psychophysical methods to precisely measure absolute perceptual thresholds for detection of threatening and neutral faces. We examined their relationships with self-reported BIS and anxious apprehension in individuals diagnosed with anxiety disorders and individuals not diagnosed with anxiety disorders. Irrespective of anxiety disorder diagnosis, higher self-reported BIS and anxious apprehension were associated with reduced perceptual thresholds for threatening versus neutral stimuli, but only BIS showed a specific association after controlling for anxious apprehension. Using adaptive psychometrics, in this study, we offer key empirical evidence linking specific temperamental dimensions with perceptual indices of threat sensitivity transdiagnostically across anxiety disorders.
Multiparametric MRI of Knees in Collegiate Basketball Players: Associations With Morphological Abnormalities and Functional Deficits
Authors: Nosrat Cameron , Gao Kenneth T. , Bhattacharjee Rupsa , Pedoia Valentina , Koff Matthew F. , Gold Garry E. , Potter Hollis G. , Majumdar Sharmila
Published: December 2023

Background:

Rates of cartilage degeneration in asymptomatic elite basketball players are significantly higher compared with the general population due to excessive loads on the knee. Compositional quantitative magnetic resonance imaging (qMRI) techniques can identify local biochemical changes of macromolecules observed in cartilage degeneration.

Purpose/Hypothesis:

The purpose of this study was to utilize multiparametric qMRI to (1) quantify how T1ρ and T2 relaxation times differ based on the presence of anatomic abnormalities and (2) correlate T1ρ and T2 with self-reported functional deficits. It was hypothesized that prolonged relaxation times will be associated with knees with MRI-graded abnormalities and knees belonging to basketball players with greater self-reported functional deficits.

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

A total of 75 knees from National Collegiate Athletic Association Division I basketball players (40 female, 35 male) were included in this multicenter study. All players completed the Knee injury and Osteoarthritis Outcome Score (KOOS) and had bilateral knee MRI scans taken. T1ρ and T2 were calculated on a voxel-by-voxel basis. The cartilage surfaces were segmented into 6 compartments: lateral femoral condyle, lateral tibia, medial femoral condyle, medial tibia (MT), patella (PAT), and trochlea (TRO). Lesions from the MRI scans were graded for imaging abnormalities, and statistical parametric mapping was performed to study cross-sectional differences based on MRI scan grading of anatomic knee abnormalities. Pearson partial correlations between relaxation times and KOOS subscore values were computed, obtaining r value statistical parametric mappings and P value clusters.

Results:

Knees without patellar tendinosis displayed significantly higher T1ρ in the PAT compared with those with patellar tendinosis (average percentage difference, 10.4%; P = .02). Significant prolongation of T1ρ was observed in the MT, TRO, and PAT of knees without compared with those with quadriceps tendinosis (average percentage difference, 12.7%, 13.3%, and 13.4%, respectively; P ≤ .05). A weak correlation was found between the KOOS-Symptoms subscale values and T1ρ/T2.

Conclusion:

Certain tissues that bear the brunt of impact developed tendinosis but spared cartilage degeneration. Whereas participants reported minimal functional deficits, their high-impact activities resulted in structural damage that may lead to osteoarthritis after their collegiate careers.
The Short-Term Effects of the Shift From Prior-Year to Current-Year Enrollment on School Inputs in Arizona
Authors: Nguyen-Hoang Phuong , Nga Le Angie
Published: December 2023

Arizona shifted to using current-year enrollment, instead of prior-year enrollment, as the basis for determining state aid for school districts following the passage of Arizona Education Finance Amendment (AEFA) in 2017. This study examines the short-term effects of AEFA implementation on school inputs—namely, expenditures and district personnel, particularly teachers. We find that the average district does not seem to respond to AEFA. However, our heterogeneity analyses reveal that the highest-income districts significantly reduce more inputs than the lowest-income districts in response to AEFA. The differential impact between these two groups is most evident in instructional expenditures, administration expenditures, total full-time equivalent teachers, and particularly teachers with 1–5 years of experience.
The Content and Methodological Features of Professionally Oriented Training of Engineering Students in Higher Mathematics
Authors: Yermaganbetova Saule K. , Abylkasymova Alma E. , Baishagirov Khairulla Zh.
Published: December 2023

This study reveals the content and methodological features of professionally oriented training of engineering students in higher mathematics. The authors provide examples of applied tasks for students of different technical specialities. The relevance of this article is determined by the fact that a modern higher educational institution sets itself the task of providing graduates with a certain set of competencies, as well as a set of acquired knowledge and skills. Thus, young people in their future life can easily navigate in terms of professional development. Nothing prevents them from easily adapting to the constantly changing social and economic conditions, meeting the current needs of the personnel market. All this allows building a competent process of training future specialists. Young engineers can build mutual understanding, cooperate with representatives of other industries, since solving complex problems and conducting joint research requires, first of all, the presence of a solid foundation consisting of natural science and mathematical disciplines, the establishment of which should take place within the framework of a higher educational institution. It is for this reason that one of the most significant problems should be identified related to the mathematical training of students of technical higher educational institutions. The purpose of the study is to identify and clarify the content and methodological features of professional training of engineering students in higher mathematics. Mathematics has a special and priority place among other sciences studied at the university. The modern course of mathematics is based on a highly developed logical and computational apparatus. Without the current achievements in the field of mathematics, there would be no high technologies that are everywhere today and are found in all areas of human activity without exception. The methods and ideas of mathematics are widely used in the cycle of technical disciplines. Mathematics, due to its inherent applied capabilities, is used in natural science and engineering research.
Reading Comprehension and Constructive Learning: Policy Considerations in the Age of Artificial Intelligence
Authors: McCarthy Kathryn S. , Yan Eleanor F.
Published: December 2023

Although reading in the digital age looks different than in the past (e.g., on a screen, shorter texts spread across multiple sources), reading continues to be a central part of everyday life. Research in reading comprehension shows that this type of modern reading requires more complex knowledge building inference processes that are difficult for many adolescents and adults. Constructive and personalized learning activities can support readers’ knowledge building. Researchers have been using artificial intelligence (AI) to make these types of activities more effective and accessible. Emerging directions and considerations also result from the introduction of generative AI. Increased collaboration across researchers, developers, educators, and policymakers would afford empirically supported research, development, and implementation that can keep pace with the quickly evolving technological landscape.
No Simple Solutions to Complex Problems: Cognitive Science Principles Can Guide but Not Prescribe Educational Decisions
Authors: Yan Veronica X. , Sana Faria , Carvalho Paulo F.
Published: December 2023

Cognitive science of learning points to solutions for making use of existing study and instruction time more effectively and efficiently. However, solutions are not and cannot be one-size-fits-all. This paper outlines the danger of overreliance on specific strategies as one-size-fits-all recommendations and highlights instead the cognitive learning processes that facilitate meaningful and long-lasting learning. Three of the most commonly recommended strategies from cognitive science provide a starting point; understanding the underlying processes allows us to tailor these recommendations to implement at the right time, in the right way, for the right content, and for the right students. Recommendations regard teacher training, the funding and incentivizing of educational interventions, guidelines for the development of educational technologies, and policies that focus on using existing instructional time more wisely.
Exploratory clinical subgroup clustering in systemic sclerosis: Results from the Indian Progressive Systemic Sclerosis Registry
Authors: Philip Shery Susan , Janardana Ramya , Shenoy Padmanabha , Kavadichanda Chengappa , Bairwa Devender , Sircar Geetabali , Ghosh Parasar , Wakhlu Anupam , Selvam Sumithra , Khanna Dinesh , Shobha Vineeta
Published: December 2023

Objective:

To conduct an exploratory cluster analysis of systemic sclerosis patients from the baseline data of the Indian systemic sclerosis registry.

Methods:

Patients satisfying American College of Rheumatology-European League Against Rheumatism classification criteria for systemic sclerosis were included. The clusters formed using clinical and immunological parameters were compared.

Results:

Of the 564 systemic sclerosis registry participants, 404 patients were included. We derived four clusters of which three were anti-topoisomerase I predominant and one was anti-centromere antibody 2 dominant. Cluster 1 ( n-82 (20.3%)) had diffuse cutaneous systemic sclerosis patients with the most severe skin disease, anti-topoisomerase I positivity, males, younger age of onset and high prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 2 ( n-141 (34.9%)) was also diffuse cutaneous systemic sclerosis and anti-topoisomerase I predominant but with less severe skin phenotype than cluster 1 and a lesser prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 3 ( n-119 (29.5%)) had limited cutaneous systemic sclerosis patients with anti-topoisomerase I positivity along with other antibodies. The proximal muscle weakness was higher and digital pitting scars were lower, while other organ involvement was similar between clusters 2 and 3. Cluster 4 ( n-62 (15.30%)) was the least severe group with limited cutaneous systemic sclerosis and anti-centromere antibody predominance. Age of onset was higher with low musculoskeletal disease and a higher presence of upper gastrointestinal features. The prevalence of interstitial lung disease was similar in the three anti-topoisomerase I predominant clusters.

Conclusion:

With exploratory cluster analysis, we confirmed the possibility of subclassification of systemic sclerosis along a spectrum based on clinical and immunological characteristics. We also corroborated the presence of anti-topoisomerase I in limited cutaneous systemic sclerosis and the association of interstitial lung disease with anti-topoisomerase I.
Virtual Reality in Heritage Management: A Case Study of the Virtual Tour of ‘Back to the Future’ Exhibition of Godrej Archives, Mumbai
Authors: Jadhav Shweta , Nayak Bismita
Published: December 2023

In today’s digital era, organizations are increasingly embracing new and innovative technologies to enhance their communication strategies and reach a wider audience. By examining the case of the virtual tour of Godrej Archives’ permanent exhibition ‘Back to the Future’ housed in Godrej’s Vikhroli campus, this article demonstrates how organizations can leverage digital technologies to enhance storytelling, effectively communicate their history, vision and values and engage a diverse audience. As a part of the digital strategy, Godrej Archives has adopted digital technology for effective data management since 2015, and in 2020–2021, it started exploring the potential of digital avenues such as virtual tour for disseminating corporate heritage. The findings emphasize the potential of digital platforms in transforming traditional approaches to corporate storytelling and heritage marketing.
“Honor” killings and customary laws: A case study of Khap Panchayats in Haryana, India
Authors: Bhattacharya Priyadarshini
Published: December 2023

This paper examines the resilience of feudal customary councils and their links with modern local state agencies in perpetuating crimes of “honor” in the State of Haryana, India. This peculiar dynamic has been approached by tapping the experiences and direct involvement of women activists and third sector organizations. The paper asks questions that help move beyond popular polarizations constructed between the Indian State and customary caste councils by revealing their complex interface. These women’s organizations interviewed, engage in an “anthropology of state,” dissociating the state as a formal technical entity from its actual functioning. Their feminist paradigms encourage new conceptualizations of a “weak patriarchal” state. This notion draws attention to the subversion of state rules by patriarchal cultural inclinations of state agents who together join forces in complex ways with community/caste councils or Khap Panchayats in exacerbating violence against women.
Migration and migrants in Chinese cities: New trends, challenges and opportunities to theorise with urban China
Authors: Wang Zheng , Lin Liyue , Tang Shuangshuang , Xiao Yang
Published: December 2023

This introductory article to the special issue discusses some of the latest trends in migration research in urban China and focuses on three areas which have generated new understandings on migration and migrants in Chinese cities. Firstly, it identifies the various similarities and intersections between urban resettlement and migration studies by drawing on the case of China where the livelihoods and experience of migrants and resettled residents have been affected by China’s rapid urbanisation. Secondly, the paper discusses the enduring significance of the residential neighbourhood in influencing the place attachment, social relationships and career development of migrant residents. Finally, it delves deeper into the various ways studies have sought to categorise and differentiate between different migrant sub-groups in urban China and reveals that more fine-grained migration studies have helped better understand China’s large and ever more diverse migrant population and their variegated living experiences and challenges.
Mezigdomide is effective alone and in combination with menin inhibition in preclinical models of KMT2A-r and NPM1c AML
Authors: Bourgeois Wallace , Cutler Jevon A. , Aubrey Brandon J. , Wenge Daniela V. , Perner Florian , Martucci Cynthia , Henrich Jill A. , Klega Kelly , Nowak Radosław P. , Donovan Katherine A. , Boileau Meaghan , Wen Yanhe , Hatton Charlie , Apazidis Athina A. , Olsen Sarah Naomi , Kirmani Nadia , Pikman Yana , Pollard Jessica A. , Perry Jennifer A. , Sperling Adam S. , Ebert Benjamin L. , McGeehan Gerard M. , Crompton Brian D. , Fischer Eric S. , Armstrong Scott A.
Published: December 2023

Small molecules that target the menin-KMT2A protein-protein interaction (menin inhibitors) have recently entered clinical trials in lysine methyltransferase 2A (KMT2A or MLL1)–rearranged (KMT2A-r) and nucleophosmin-mutant (NPM1c) acute myeloid leukemia (AML) and are demonstrating encouraging results. However, rationally chosen combination therapy is needed to improve responses and prevent resistance. We have previously identified IKZF1/IKAROS as a target in KMT2A-r AML and shown in preclinical models that IKAROS protein degradation with lenalidomide or iberdomide has modest single-agent activity yet can synergize with menin inhibitors. Recently, the novel IKAROS degrader mezigdomide was developed with greatly enhanced IKAROS protein degradation. In this study, we show that mezigdomide has increased preclinical activity in vitro as a single-agent in KMT2A-r and NPM1c AML cell lines, including sensitivity in cell lines resistant to lenalidomide and iberdomide. Further, we demonstrate that mezigdomide has the greatest capacity to synergize with and induce apoptosis in combination with menin inhibitors, including in MEN1 mutant models. We show that the superior activity of mezigdomide compared with lenalidomide or iberdomide is due to its increased depth, rate, and duration of IKAROS protein degradation. Single-agent mezigdomide was efficacious in 5 patient-derived xenograft models of KMT2A-r and 1 NPM1c AML. The combination of mezigdomide with the menin inhibitor VTP-50469 increased survival and prevented and overcame MEN1 mutations that mediate resistance in patients receiving menin inhibitor monotherapy. These results support prioritization of mezigdomide for early phase clinical trials in KMT2A-r and NPM1c AML, either as a single agent or in combination with menin inhibitors.
Nucleic acid sensing promotes inflammatory monocyte migration through biased coagulation factor VIIa signaling
Authors: Zelaya Hortensia , Grunz Kristin , Nguyen T. Son , Habibi Anxhela , Witzler Claudius , Reyda Sabine , Gonzalez-Menendez Irene , Quintanilla-Martinez Leticia , Bosmann Markus , Weiler Hartmut , Ruf Wolfram
Published: December 2023

Protease activated receptors (PARs) are cleaved by coagulation proteases and thereby connect hemostasis with innate immune responses. Signaling of the tissue factor (TF) complex with factor VIIa (FVIIa) via PAR2 stimulates extracellular signal-regulated kinase (ERK) activation and cancer cell migration, but functions of cell autonomous TF-FVIIa signaling in immune cells are unknown. Here, we show that myeloid cell expression of FVII but not of FX is crucial for inflammatory cell recruitment to the alveolar space after challenge with the double-stranded viral RNA mimic polyinosinic:polycytidylic acid [Poly(I:C)]. In line with these data, genetically modified mice completely resistant to PAR2 cleavage but not FXa-resistant PAR2–mutant mice are protected from lung inflammation. Poly(I:C)-stimulated migration of monocytes/macrophages is dependent on ERK activation and mitochondrial antiviral signaling (MAVS) but independent of toll-like receptor 3 (TLR3). Monocyte/macrophage-synthesized FVIIa cleaving PAR2 is required for integrin αMβ2-dependent migration on fibrinogen but not for integrin β1-dependent migration on fibronectin. To further dissect the downstream signaling pathway, we generated PAR2S365/T368A-mutant mice deficient in β-arrestin recruitment and ERK scaffolding. This mutation reduces cytosolic, but not nuclear ERK phosphorylation by Poly(I:C) stimulation, and prevents macrophage migration on fibrinogen but not fibronectin after stimulation with Poly(I:C) or CpG-B, a single-stranded DNA TLR9 agonist. In addition, PAR2S365/T368A-mutant mice display markedly reduced immune cell recruitment to the alveolar space after Poly(I:C) challenge. These results identify TF-FVIIa-PAR2-β-arrestin–biased signaling as a driver for lung infiltration in response to viral nucleic acids and suggest potential therapeutic interventions specifically targeting TF-VIIa signaling in thrombo-inflammation.
Low-frequency inherited complement receptor variants are associated with purpura fulminans
Authors: Bendapudi Pavan K. , Nazeen Sumaiya , Ryu Justine , Söylemez Onuralp , Robbins Alissa , Rouaisnel Betty , O’Neil Jillian K. , Pokhriyal Ruchika , Yang Moua , Colling Meaghan , Pasko Bryce , Bouzinier Michael , Tomczak Lindsay , Collier Lindsay , Barrios David , Ram Sanjay , Toth-Petroczy Agnes , Krier Joel , Fieg Elizabeth , Dzik Walter H. , Hudspeth James C. , Pozdnyakova Olga , Nardi Valentina , Knight James , Maas Richard , Sunyaev Shamil , Losman Julie-Aurore
Published: December 2023

Extreme disease phenotypes can provide key insights into the pathophysiology of common conditions, but studying such cases is challenging due to their rarity and the limited statistical power of existing methods. Herein, we used a novel approach to pathway–based mutational burden testing, the rare variant trend test (RVTT), to investigate genetic risk factors for an extreme form of sepsis-induced coagulopathy, infectious purpura fulminans (PF). In addition to prospective patient sample collection, we electronically screened over 10.4 million medical records from 4 large hospital systems and identified historical cases of PF for which archived specimens were available to perform germline whole-exome sequencing. We found a significantly increased burden of low-frequency, putatively function-altering variants in the complement system in patients with PF compared with unselected patients with sepsis (P = .01). A multivariable logistic regression analysis found that the number of complement system variants per patient was independently associated with PF after controlling for age, sex, and disease acuity (P = .01). Functional characterization of PF-associated variants in the immunomodulatory complement receptors CR3 and CR4 revealed that they result in partial or complete loss of anti-inflammatory CR3 function and/or gain of proinflammatory CR4 function. Taken together, these findings suggest that inherited defects in CR3 and CR4 predispose to the maladaptive hyperinflammation that characterizes severe sepsis with coagulopathy.
PhyloSophos: a high-throughput scientific name mapping algorithm augmented with explicit consideration of taxonomic science, and its application on natural product (NP) occurrence database processing
Authors: Cho Min Hyung , Cho Kwang-Hwi , No Kyoung Tai
Published: December 2023

Background

The standardization of biological data using unique identifiers is vital for seamless data integration, comprehensive interpretation, and reproducibility of research findings, contributing to advancements in bioinformatics and systems biology. Despite being widely accepted as a universal identifier, scientific names for biological species have inherent limitations, including lack of stability, uniqueness, and convertibility, hindering their effective use as identifiers in databases, particularly in natural product (NP) occurrence databases, posing a substantial obstacle to utilizing this valuable data for large-scale research applications.

Result

To address these challenges and facilitate high-throughput analysis of biological data involving scientific names, we developed PhyloSophos, a Python package that considers the properties of scientific names and taxonomic systems to accurately map name inputs to entries within a chosen reference database. We illustrate the importance of assessing multiple taxonomic databases and considering taxonomic syntax-based pre-processing using NP occurrence databases as an example, with the ultimate goal of integrating heterogeneous information into a single, unified dataset.

Conclusions

We anticipate PhyloSophos to significantly aid in the systematic processing of poorly digitized and curated biological data, such as biodiversity information and ethnopharmacological resources, enabling full-scale bioinformatics analysis using these valuable data resources.
DL-PPI: a method on prediction of sequenced protein–protein interaction based on deep learning
Authors: Wu Jiahui , Liu Bo , Zhang Jidong , Wang Zhihan , Li Jianqiang
Published: December 2023

Purpose

Sequenced Protein–Protein Interaction (PPI) prediction represents a pivotal area of study in biology, playing a crucial role in elucidating the mechanistic underpinnings of diseases and facilitating the design of novel therapeutic interventions. Conventional methods for extracting features through experimental processes have proven to be both costly and exceedingly complex. In light of these challenges, the scientific community has turned to computational approaches, particularly those grounded in deep learning methodologies. Despite the progress achieved by current deep learning technologies, their effectiveness diminishes when applied to larger, unfamiliar datasets.

Results

In this study, the paper introduces a novel deep learning framework, termed DL-PPI, for predicting PPIs based on sequence data. The proposed framework comprises two key components aimed at improving the accuracy of feature extraction from individual protein sequences and capturing relationships between proteins in unfamiliar datasets. 1. Protein Node Feature Extraction Module: To enhance the accuracy of feature extraction from individual protein sequences and facilitate the understanding of relationships between proteins in unknown datasets, the paper devised a novel protein node feature extraction module utilizing the Inception method. This module efficiently captures relevant patterns and representations within protein sequences, enabling more informative feature extraction. 2. Feature-Relational Reasoning Network (FRN): In the Global Feature Extraction module of our model, the paper developed a novel FRN that leveraged Graph Neural Networks to determine interactions between pairs of input proteins. The FRN effectively captures the underlying relational information between proteins, contributing to improved PPI predictions. DL-PPI framework demonstrates state-of-the-art performance in the realm of sequence-based PPI prediction.
The forgotten variable? Does the euthanasia method and sample storage condition influence an organisms transcriptome – a gene expression analysis on multiple tissues in pigs
Authors: Chakkingal Bhaskaran B. , Meyermans R. , Gorssen W. , Maes G. E. , Buyse J. , Janssens S. , Buys N.
Published: December 2023

Background

Transcriptomic studies often require collection of fresh tissues post euthanasia. The chosen euthanasia method might have the potential to induce variations in gene expressions that are unlinked with the experimental design. The present study compared the suitability of ‘nitrogen gas in foam’ (ANOXIA) in comparison to a non-barbiturate anaesthetic, T-61® (T61), for euthanizing piglets used in transcriptome research. Further, the effect of common tissue storage conditions, RNAlater™ (RL) and snap freezing in liquid nitrogen (LN2), on gene expression profiles were also analysed.

Results

On comparison of the 3’mRNA-Seq data generated from pituitary, hypothalamus, liver and lung tissues, no significant differential expression in the protein coding genes were detected between the euthanasia methods. This implies that the nitrogen anoxia method could be a suitable alternative for euthanasia of piglets used in transcriptomic research. However, small nuclear RNAs (snRNAs) that constitute the eukaryotic spliceosomal machinery were found to be significantly higher (log2fold change ≥ 2.0, and adjusted p value ≤ 0.1) in pituitary samples collected using ANOXIA. Non-protein coding genes like snRNAs that play an important role in pre-mRNA splicing can subsequently modify gene expression. Storage in RL was found to be superior in preserving RNA compared to LN2storage, as evidenced by the significantly higher RIN values in representative samples. However, storage in RL as opposed to LN2, also influenced differential gene expression in multiple tissues, perhaps as a result of its inability to inhibit biological activity during storage. Hence such external sources of variations should be carefully considered before arriving at research conclusions.

Conclusions

Source of biological variations like euthanasia method and storage condition can confound research findings. Even if we are unable to prevent the effect of these external factors, it will be useful to identify the impact of these variables on the parameter under observation and thereby prevent misinterpretation of our results.
The association between systemic inflammation markers and the prevalence of hypertension
Authors: Jin Nake , Huang Lei , Hong Jun , Zhao Xuechen , Hu Jianan , Wang Shanshan , Chen Xudong , Rong Jiacheng , Lu Yingjie
Published: December 2023

Background

We conducted a large-scale epidemiological analysis to investigate the associations between systemic inflammation markers and hypertension prevalence. Our aim is to identify potential biomarkers for early detection of hypertension.

Methods

A cross-sectional study with 119664 individuals from the National Health and Nutrition Examination Survey was performed. We investigated the associations between three systemic inflammation markers, namely the systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), and the prevalence of hypertension.

Results

The prevalence rates of hypertension gradually increased with increasing logSII, logSIRI, and logAISI quartiles. In continuous analyses, each unit increase in logSII, logSIRI, and logAISI was associated with a 20.3%, 20.1%, and 23.7% increased risk of hypertension. Compared to those in the lowest quartiles, the hypertension risks for subjects in the highest logSII, logSIRI, and logAISI quartiles were 1.114-fold,1.143-fold, and 1.186-fold. The restricted cubic splines (RCS) analysis revealed a non-linear relationship between the elevation of systemic inflammation markers and hypertension prevalence. Specifically, a per standard deviation increase in any of these variables is associated with a respective 9%, 16%, and 11% increase in hypertension prevalence.

Conclusion

Our cross-sectional study reveals significant positive correlations between SII, SIRI, and AISI with the prevalence of hypertension.
Dementia and comorbidities in primary care: a scoping review
Authors: Bergman Howard , Borson Soo , Jessen Frank , Krolak-Salmon Pierre , Pirani Alessandro , Rasmussen Jill , Rodrigo Jesus , Taddeo Daiana
Published: December 2023

Background

People with dementia (PwD) are known to have more chronic conditions compared to those without dementia, which can impact the clinical presentation of dementia, complicate clinical management and reduce overall quality of life. While primary care providers (PCPs) are integral to dementia care, it is currently unclear how PCPs adapt dementia care practices to account for comorbidities. This scoping review maps recent literature that describes the role for PCPs in the prevention, detection/diagnosis and management of dementia in the context of comorbidities, identifies critical knowledge gaps and proposes potential avenues for future research.

Methods

We searched for peer-reviewed literature published between 2017–2022 in MEDLINE, Cochrane Library, and Scopus using key terms related to dementia, primary care, and comorbidity. The literature was screened for relevance by title-abstract screening and subsequent full-text screening. The prioritized papers were categorized as either ‘Risk Assessment and Prevention’, ‘Screening, Detection, and Diagnosis’ or ‘Management’ and were further labelled as either ‘Tools and Technologies’, ‘Recommendations for Clinical Practice’ or ‘Programs and Initiatives’.

Results

We identified 1,058 unique records in our search and respectively excluded 800 and 230 publications during title-abstract and full-text screening. Twenty-eight articles were included in our review, where ~ 50% describe the development and testing of tools and technologies that use pre-existing conditions to assess dementia risk. Only one publication provides official dementia screening guidelines for PCPs in people with pre-existing conditions. About 30% of the articles discuss managing the care of PwD, where most were anchored around models of multidisciplinary care and mitigating potentially inappropriate prescribing.

Conclusion

To our knowledge, this is the first scoping review that examines the role for PCPs in the prevention, detection/diagnosis and management of dementia in the context of comorbidities. Given our findings, we recommend that future studies: 1) further validate tools for risk assessment, timely detection and diagnosis that incorporate other health conditions; 2) provide additional guidance into how comorbidities could impact dementia care (including prescribing medication) in primary care settings; 3) incorporate comorbidities into primary care quality indicators for dementia; and 4) explore how to best incorporate dementia and comorbidities into models/frameworks of holistic, person-centred care.
The association between satisfaction with life and anxiety symptoms among Chinese elderly: a moderated mediation analysis
Authors: Lai Cynthia Y. Y. , Chen Lu Hua , Lai Frank H. Y. , Fung Ada W. T. , Ng Shamay S. M.
Published: December 2023

Background

Previous studies have suggested that certain personal psychological variables (e.g., life satisfaction and cognitive function) and physical variables (e.g., body mass index [BMI]) are significantly associated with individuals’ anxiety symptoms. However, relevant research on elderly is lagging and no studies have yet investigated the combined impact of these variables on anxiety. Thus, we conducted the present study to investigate the potential moderator role of BMI and the potential mediator role of cognitive function underlying the relationship between life satisfaction and anxiety symptoms in Chinese elderly based in Hong Kong.

Methods

Sixty-seven elderly aged 65 years old and above were recruited from the local elderly community centres in this pilot study. Each participant underwent a systematic evaluation using the Satisfaction with Life Scale (SWLS), Hong Kong Version of the Montreal Cognitive Assessment (HK-MoCA), and the Hamilton Anxiety Rating Scale (HAM-A) and were measured for their body weight and height. Regression analysis using the bootstrapping method was employed to test the hypothesized moderated mediation model.

Results

Our findings demonstrated the overall model accounted for 23.05% of the variance in scores of HAM-A (F (8, 57) = 2.134, p = 0.047) in Chinese elderly. There was a significant association between life satisfaction and anxiety symptoms (p = 0.031), indicating that individuals with higher life satisfaction were associated with less anxiety symptoms. Moreover, this relationship was positively moderated by BMI (b = 0.066, 95% CI [0.004, 0.128]), especially in Chinese elderly with BMI at a lower level (b = -0.571, 95% CI [-0.919, -0.224]) and an average level (b = -0.242, 95% CI [-0.460, -0.023]). No significant mediator role was detected for cognitive function (b = -0.006, 95% CI [-0.047, 0.044]) in our model.

Conclusions

Our findings suggest that increased life satisfaction can reduce anxiety symptoms among Chinese elderly as their BMI decreases (when BMI ranged between “mean - 1SD” and “mean” of the population). The significant interaction between psychological and physical factors underlying anxiety symptoms found in this study, presents a promising opportunity for translation into multi-level psychological and physical interventions for the management of anxiety in ageing patients during clinical practice.