bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Postnatal Inflammation Alters Adult Microglial Responses to LPS that Are Sex-, Region- and Timing of Postnatal Inflammation-Dependent
Authors: Nikodemova Maria , Oberto Jose R , Berschel Mackenzie R , Michaelson Alysha L , Watters Jyoti J , Mitchell Gordon S 
Published: June 2024

Abstract

Background.
Adverse events in early life can have impact lasting into adulthood. We investigated the long-term effects of systemic inflammation during postnatal development on adult microglial responses to LPS in two CNS regions (cortex, cervical spinal cord) in male and female rats.
Methods.
Inflammation was induced in Sprague-Dawley rats by lipopolysaccharide (LPS, 1 mg/kg) administered intraperitoneally during postnatal development at P7, P12 or P18. As adults (12 weeks of age), the rats received a second LPS dose (1 mg/kg). Control rats received saline. Microglia were isolated 3 hours post-LPS from the cortex and cervical spinal cord. Gene expression was assessed via qRT-PCR for pro-inflammatory (IL-6, iNOS, Ptgs2, C/EBPb, CD14, CXCL10), anti-inflammatory (CD68, Arg-1), and homeostatic genes (P2Y12, Tmemm119). CSF-1 and CX3CL1 mRNA was analyzed in microglia-free homogenates.
Results.
Basal gene expression in adult microglia was largely unaffected by early life LPS. Changes in adult microglial pro-inflammatory genes in response to LPS were either unchanged or attenuated in rats exposed to LPS during postnatal development. Ptgs2, C/EBPb, CXCL10 and Arg-1 were the genes most affected, with expression levels significantly downregulated vs control rats without postnatal LPS exposure. Cortical microglia were affected more by postnatal inflammation than spinal microglia, and males were more impacted than females. Overall, inflammatory challenge at P18 had the greatest effect on adult microglial gene expression, whereas challenge at P7 had less impact. Microglial homeostatic genes were unaffected by postnatal LPS.
Conclusions.
Long-lasting effects of postnatal inflammation on adult microglia depend on the timing of postnatal inflammation, CNS region and sex.
BHB promotes the proliferation of neural stem cells by activating the Erk1/2- MAPK pathway and changing histone modification patterns
Authors: Wang Leilei , Zhao Tingting , Shang Sen , Lu Xiaoyun 
Published: June 2024

Abstract

Neural stem cells (NSCs) have the ability to proliferate and differentiate into neurons, astrocytes, oligodendrocytes and some other types of cells, which were used in therapies for multiple neural system disorders. However, the efficacy of NSCs is limited by their short lifespan. Therefore, promoting the proliferation of NSCs is one of the key bottlenecks in their use for transplantation and treatment. According to our research, β-hydroxybutyrate (BHB) promoted cell cycle progression, thereby enhancing the proliferation of both primary NSCs and neural progenitor cell line C17.2. The BHB receptors GPR41 and GPR109A were found to mediate this effect by activating the Erk1/2 pathway. Furthermore, the key transcription factors regulating NSC proliferation, Pax6 and Sox2, were also upregulated by BHB via increased histone trimethylation and acetylation levels in their promoters. In conclusion, BHB enhanced the proliferation of NSCs through a receptor-dependent pathway. At same time, epigenetic modification also plays a role in this process.
Inflammatory Markers Related to Medical Nutritional Therapy in Critically Ill Patients in Intensive Care Unit: Study on CRP and Procalcitonin
Authors: Syauki Andi Yasmin , Majid Nurhidayah , Bukhari Agussalim , Taslim Nurpudji A. , As'ad Suryani , Aminuddin  , Syam Nurbaya , Ashari Nur 
Published: June 2024

Abstract

Background and objectives: Malnutrition is the most frequent complication in patients in an intensive care unit (ICU). CRP and Procalcitonin are used as acute phase inflammatory markers, adversely affecting patient outcomes. This study aims to determine the effect of medical nutritional therapy on the level of CRP and procalcitonin in critically ill patients.
Methods: This study was a retrospective cohort design on critically ill patients at Wahidin Sudirohusodo Teaching Hospital from 2020-2021, 250 subjects met the inclusion criteria by screening for malnutrition using the m-Nutric score, CRP assessment using Flouroscene immune assay, procalcitonin using chemiluminescent microparticle immune assay, nutrition intake by 24-hours food recall, all patients received medical nutrition therapy.
Results: This study showed patients with low grade m-Nutric score significantly decreased of CRP level (energy intake ≥ 600 kcal p=0.009) not for procalcitonin level (p=0.841), while procalcitonin tend to be significantly decreased (energy intake < 600 kcal p=0.054) not with CRP level (p=0.655). Patient with high-risk m-Nutric score showed significancy decreased procalcitonin level (energy intake ≥ 600 kcal p=0.011) while not for CRP (p=0.109) and procalciton (energy intake < 600 kcal p=0.138).
Conclusion: Medical nutritional therapy with energy intake ≥ 600 kcal incritical ill decreased CRP level in a low risk m-Nutric score, and decreased procalcitonin level in a high risk m-Nutric score.
Construction of Acenaphthylenes via C−H Activation-Based Tandem Penta- and Hexaannulation Reactions
Authors: You Jingsong , Li Jian , Liu Tao , Liu Junjie , Zhang Cheng , Yang Yudong , Tan Guangying 
Published: June 2024

Abstract

Acenaphthylene-containing polycyclic aromatic hydrocarbons (AN-PAHs) are noteworthy structural motifs for organic functional materials due to their non-alternant electronic structure, which increases electron affinity. However, the synthesis of AN-PAHs has traditionally required multiple sequential synthetic steps, limiting structural diversity. Herein, we present a novel tandem C−H penta- and hexaannulation reaction of aryl alkyl ketone with acetylenedicarboxylate. This integrated approach enhances overall efficiency and selectivity, marking a significant advancement in AN-PAH synthesis. Mechanistic studies unveil an orchestrated extension of five- and six-membered rings through C−H activation-annulation and Diels–Alder reaction. Additionally, the tandem annulation reaction can be performed stepwise, further validating the proposed mechanism and increasing the structural diversity of AN-PAHs.
Measuring Attentional Bias Using the Dot-Probe Task in Young Women: Psychometric Properties and Feasibility of Response-Based Computations, Dwell Time, and the N2pc Component
Authors: Klonteig Sandra , Roalsø Elise Solbu , Jonassen Rune , Hilland Eva , Moberget Torgeir , Mirtaheri Peyman , Kraft Brage 
Published: June 2024

Abstract

Background Attentional bias (AB) is characterized by preferential cognitive and emotional processing of mood-congruent stimuli and considered a central mechanism in mood disorders. Considerable research has focused on improving AB measures to enhance mechanistic understanding and clinical utility. The present study examines psychometric properties of a range of AB measures with a multimodal setup.
Methods A nonclinical sample of 62 women aged 20–30 years completed the facial dot-probe task while behavioral responses (reaction time), eye-gaze patterns (eye tracking), and electrical brain potentials (electroencephalography) were recorded. AB metrics from four types of AB measures – traditional, response-based, dwell time, and the N2pc component– were examined with internal consistency and short-term test-retest calculations. AB metrics with an internal consistency score over .4 were considered reliable, and their validity was explored by examining relations to depression and anxiety symptoms. In addition, the consistency between reliable metrics across trials were examined.
Results Findings show that traditional AB metrics exhibited no degree of reliability, whereas response-based and dwell time metrics overall demonstrated better internal consistencies and higher test-retest reliability. The previously reported reliability of the N2pc component was not observed. As for validity, no linear associations were found between the reliable measures, depression, and anxiety. There were no relations between metrics across trials.
Conclusions This study provides insights for future AB research, emphasizing the potential of novel metrics over traditional ones and the use of multimodal setups to develop reliable and potentially hybrid measurements for clinical assessment.
Comprehensive Role of GDF15 in Inhibiting Adipogenesis and Hyperlipidemia, Enhancing Cardiovascular Health and Alleviating Inflammation in Metabolic Disorders
Authors: Nayak Nikita , Mukherjee Tuhin , Pattnaik Ashok 
Published: June 2024

:
Growth Differentiation Factor 15 (GDF15) has emerged as a pivotal signaling molecule implicated
in diverse physiological processes, spanning metabolic regulation, inflammation, and cardiovascular health.
This study provides a comprehensive exploration of GDF15's multifaceted role, primarily focusing on its association
with obesity-related complications and therapeutic potential. GDF15's involvement in energy homeostasis,
specifically its regulation of body weight and appetite through hindbrain neuron activation and the
GFRAL-RET signaling pathway, underscores its significance as an appetite-regulating hormone. GDF15's intricate
modulation within adipose tissue dynamics in response to dietary changes and obesity, coupled with its
influence on insulin sensitivity, highlights its critical role in metabolic health. The manuscript delves into the
intricate crosstalk between GDF15 and pathways related to insulin sensitivity, macrophage polarization, and
adipose tissue function, elucidating its potential as a therapeutic target for metabolic disorders associated with
obesity. GDF15's association with chronic low-grade inflammation and its impact on cardiovascular health,
particularly during hyperlipidemia and ischemic events, are explored. The intricate relationship between GDF15
and cardiovascular diseases, including its effects on endothelial function, cardiac hypertrophy, and heart
failure, emphasizes its multifaceted nature in maintaining overall cardiovascular well-being. Challenges regarding
the therapeutic application of GDF15, such as long-term safety concerns and ongoing clinical investigations,
are discussed. Lastly, future research directions exploring GDF15's potential in addressing obesity-related
complications and cardiovascular risks are proposed, highlighting its promising role as a therapeutic target
in reshaping treatment strategies for obesity and associated health conditions.
Gamma-tocotrienol Inhibits Proliferation and Growth of HSD17B4 Overexpressing HepG2 Liver Cancer Cells
Authors: Wang Xiaoming , Liang Xijia , Zhang Nan , Wang Yaqi , Hu Meng , Shi Yun , Yao Min , Hou Lianguo , Jiang Lingling 
Published: June 2024

Introduction:
Hydroxysteroid 17-beta dehydrogenase 4 (HSD17B4) is involved in the
progression of hepatocellular carcinoma (HCC).

Aims:
This study aimed to investigate the inhibitory effect of gamma-tocotrienol (γ-T3) on the proliferation
and growth of HSD17B4-overexpressing HepG2 cells.

Methods:
HepG2 cells were transfected with empty or HSD17B4-overexpressing plasmids, followed
by vitamin E (VE) or γ-T3 treatment. MTS assay, Western blotting, qRT-PCR, and flow cytometry
were employed to assess cell proliferation, protein expression, mRNA levels, and apoptosis.
HSD17B4 interaction with γ-T3 was assessed by quantifying γ-T3 in the collected precipitate
of HSD17B4 using anti-flag magnetic beads. Tumor xenografts were established in NSG mice,
and tumor growth was monitored.

Results:
HSD17B4 overexpression significantly promoted HepG2 cell proliferation, which was effectively
counteracted by VE or γ-T3 treatment in a dose-dependent manner. VE and γ-T3 did not
exert their effects through direct regulation of HSD17B4 expression. Instead, γ-T3 was found to interact
with HSD17B4, inhibiting its activity in catalyzing the conversion of estradiol (E2) into estrone.
Moreover, γ-T3 treatment led to a reduction in cyclin D1 expression and suppressed key proliferation
signaling pathways, such as ERK, MEK, AKT, and STAT3. Additionally, γ-T3 promoted
apoptosis in HSD17B4-overexpressing HepG2 cells. In an in vivo model, γ-T3 effectively reduced
the growth of HepG2 xenograft tumors.

Conclusion:
In conclusion, our study demonstrates that γ-T3 exhibits potent anti-proliferative and
anti-tumor effects against HepG2 cells overexpressing HSD17B4. These findings highlight the
therapeutic potential of γ-T3 in HCC treatment and suggest its role in targeting HSD17B4-associated
pathways to inhibit tumor growth and enhance apoptosis.
The Therapeutic Potential of Targeting the Connexin43 as a New Approach to Reducing Post-surgical Adhesion
Authors: Moslem Alireza , Khodashahi Rozita , Ferns Gordon A. , Aliakbarian Mohsen , Arjmand Mohammad-Hassan 
Published: June 2024

:
Post-surgical peritoneal adhesions are a serious problem causing complications, such as bowel obstruction, infertility, and pain. There are currently
no effective ways of preventing post-surgical adhesions. Excess secretion of proinflammatory cytokines and profibrotic molecules by immune cells
and adherent fibroblasts are the main mechanism that promotes post-operative fibrotic scars. Although many studies have been conducted on the
pathological causes of this disorder, there are still many unknown facts in this matter, so assessment of the role of different molecules in causing
inflammation and adhesion can lead to the creation of new treatment methods. Connexins are a group of proteins related to gap junctions that have
a role in cell communication and transmitted signaling between adjacent cells. Between different types of connexin protein isoforms, connexin43 is
known to be involved in pathological conditions related to inflammation and fibrosis. Recent studies have reported that inhibition of connexin43
has the potential to reduce inflammation and fibrosis by reducing the expression of molecules like α-SMA and plasminogen activator inhibitor
(PAI) that are involved in the early stages of adhesion formation. As well as, inhibition of connexin43 may have therapeutic potential as a target to
prevent post-surgical peritoneal adhesions.
Gamification in Mobile Apps for Children With Disabilities: Scoping Review
Authors: Mahmoudi Ebrahim , Yejong Yoo Paul , Chandra Ananya , Cardoso Roberta , Denner Dos Santos Carlos , Majnemer Annette , Shikako Keiko 
Published: June 2024

Background
Children with disabilities face numerous challenges in accessing health services. Mobile health is an emerging field that could significantly reduce health inequities by providing more accessible services. Many mobile apps incorporate gamification elements such as feedback, points, and stories to increase engagement and motivation; however, little is known about how gamification has been incorporated in mobile apps for children with disabilities.

Objective
This scoping review aims to identify and synthesize the existing research evidence on the use of gamification in mobile apps for children with disabilities. Specifically, the objectives were to (1) identify the categories of these mobile apps (eg, treatment and educational) (2), describe the health-related outcomes they target, (3) assess the types and levels of gamification elements used within these apps, and (4) determine the reasons for incorporating gamification elements into mobile apps.

Methods
We searched MEDLINE, PsycINFO, CINAHL, Embase, the ACM Digital Library, and IEEE Xplore databases to identify papers published between 2008 and 2023. Original empirical research studies reporting on gamified mobile apps for children with disabilities that implemented at least 1 gamification strategy or tactic were included. Studies investigating serious games or full-fledged games were excluded.

Results
A total of 38 studies reporting on 32 unique gamified mobile apps were included. Findings showed that gamified apps focus on communication skills and oral health in children with autism spectrum disorder while also addressing self-management and academic skills for other disability groups. Gamified mobile apps have demonstrated potential benefits across different populations and conditions; however, there were mixed results regarding their impact. The gamification strategies included fun and playfulness (23/32, 72%), feedback on performance (17/32, 53%), and reinforcement (17/32, 53%) in more than half of apps, whereas social connectivity was used as a gamification strategy in only 4 (12%) mobile apps. There were 2 main reasons for integrating gamification elements into mobile apps described in 16 (42%) studies: increasing user engagement and motivation and enhancing intervention effects.

Conclusions
This scoping review offers researchers a comprehensive review of the gamification elements currently used in mobile apps for the purposes of treatment, education, symptom management, and assessment for children with disabilities. In addition, it indicates that studies on certain disability groups and examinations of health-related outcomes have been neglected, highlighting the need for further investigations in these areas. Furthermore, research is needed to investigate the effectiveness of mobile-based gamification elements on health and health behavior outcomes, as well as the healthy development of children with disabilities.
The Digital Determinants of Health: A Guide for Competency Development in Digital Care Delivery for Health Professions Trainees
Authors: Lawrence Katharine , Levine Defne L 
Published: June 2024

Abstract
Health care delivery is undergoing an accelerated period of digital transformation, spurred in part by the COVID-19 pandemic and the use of “virtual-first” care delivery models such as telemedicine. Medical education has responded to this shift with calls for improved digital health training, but there is as yet no universal understanding of the needed competencies, domains, and best practices for teaching these skills. In this paper, we argue that a “digital determinants of health” (DDoH) framework for understanding the intersections of health outcomes, technology, and training is critical to the development of comprehensive digital health competencies in medical education. Much like current social determinants of health models, the DDoH framework can be integrated into undergraduate, graduate, and professional education to guide training interventions as well as competency development and evaluation. We provide possible approaches to integrating this framework into training programs and explore priorities for future research in digitally-competent medical education.
Assessing Generative Pretrained Transformers (GPT) in Clinical Decision-Making: Comparative Analysis of GPT-3.5 and GPT-4
Authors: Lahat Adi , Sharif Kassem , Zoabi Narmin , Shneor Patt Yonatan , Sharif Yousra , Fisher Lior , Shani Uria , Arow Mohamad , Levin Roni , Klang Eyal 
Published: June 2024

Background
Artificial intelligence, particularly chatbot systems, is becoming an instrumental tool in health care, aiding clinical decision-making and patient engagement.

Objective
This study aims to analyze the performance of ChatGPT-3.5 and ChatGPT-4 in addressing complex clinical and ethical dilemmas, and to illustrate their potential role in health care decision-making while comparing seniors’ and residents’ ratings, and specific question types.

Methods
A total of 4 specialized physicians formulated 176 real-world clinical questions. A total of 8 senior physicians and residents assessed responses from GPT-3.5 and GPT-4 on a 1-5 scale across 5 categories: accuracy, relevance, clarity, utility, and comprehensiveness. Evaluations were conducted within internal medicine, emergency medicine, and ethics. Comparisons were made globally, between seniors and residents, and across classifications.

Results
Both GPT models received high mean scores (4.4, SD 0.8 for GPT-4 and 4.1, SD 1.0 for GPT-3.5). GPT-4 outperformed GPT-3.5 across all rating dimensions, with seniors consistently rating responses higher than residents for both models. Specifically, seniors rated GPT-4 as more beneficial and complete (mean 4.6 vs 4.0 and 4.6 vs 4.1, respectively; P<.001), and GPT-3.5 similarly (mean 4.1 vs 3.7 and 3.9 vs 3.5, respectively; P<.001). Ethical queries received the highest ratings for both models, with mean scores reflecting consistency across accuracy and completeness criteria. Distinctions among question types were significant, particularly for the GPT-4 mean scores in completeness across emergency, internal, and ethical questions (4.2, SD 1.0; 4.3, SD 0.8; and 4.5, SD 0.7, respectively; P<.001), and for GPT-3.5’s accuracy, beneficial, and completeness dimensions.

Conclusions
ChatGPT’s potential to assist physicians with medical issues is promising, with prospects to enhance diagnostics, treatments, and ethics. While integration into clinical workflows may be valuable, it must complement, not replace, human expertise. Continued research is essential to ensure safe and effective implementation in clinical environments.
Integrating Social Determinants of Health in Machine Learning–Driven Decision Support for Diabetes Case Management: Protocol for a Sequential Mixed Methods Study
Authors: Lee Seung-Yup , Hayes Leslie W , Ozaydin Bunyamin , Howard Steven , Garretson Alison M , Bradley Heather M , Land Andrew M , DeLaney Erin W , Pritchett Amy O , Furr Amanda L , Allgood Ashleigh , Wyatt Matthew C , Hall Allyson G , Banaszak-Holl Jane C 
Published: June 2024

Background
The use of both clinical factors and social determinants of health (SDoH) in referral decision-making for case management may improve optimal use of resources and reduce outcome disparities among patients with diabetes.

Objective
This study proposes the development of a data-driven decision-support system incorporating interactions between clinical factors and SDoH into an algorithm for prioritizing who receives case management services. The paper presents a design for prediction validation and preimplementation assessment that uses a mixed methods approach to guide the implementation of the system.

Methods
Our study setting is a large, tertiary care academic medical center in the Deep South of the United States, where SDoH contribute to disparities in diabetes-specific hospitalizations and emergency department (ED) visits. This project will develop an interpretable artificial intelligence model for a population with diabetes using SDoH and clinical data to identify which posthospitalization cases have a higher likelihood of subsequent ED use. The electronic health record data collected for the study include demographics, SDoH, comorbidities, hospitalization-related factors, laboratory test results, and medication use to predict posthospitalization ED visits. Subsequently, a mixed methods approach will be used to validate prediction outcomes and develop an implementation strategy from insights into patient outcomes from case managers, clinicians, and quality and patient safety experts.

Results
As of December 2023, we had abstracted data on 174,871 inpatient encounters between January 2018 and September 2023, involving 89,355 unique inpatients meeting inclusion criteria. Both clinical and SDoH data items were included for these patient encounters. In total, 85% of the inpatient visits (N=148,640) will be used for training (learning from the data) and the remaining 26,231 inpatient visits will be used for mixed-methods validation (testing).

Conclusions
By integrating a critical suite of SDoH with clinical data related to diabetes, the proposed data-driven risk stratification model can enable individualized risk estimation and inform health professionals (eg, case managers) about the risk of patients’ upcoming ED use. The prediction outcome could potentially automate case management referrals, helping to better prioritize services. By taking a mixed methods approach, we aim to align the model with the hospital’s specific quality and patient safety considerations for the quality of patient care and the optimization of case management resource allocation.

International Registered Report Identifier (IRRID)
DERR1-10.2196/56049