bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-separation parenting apps in the hands of family law practitioners: expectations versus experience
Authors: Irving Michelle A , Heard Genevieve , Smyth Bruce M , Payne Jason L , Althor Glenn
Published: December 2023

Post-separation parenting apps are an alternative to mainstream digital communication (e.g. text and email) for separated parents. They vary in cost and features, generally incorporating a messaging tool, shared calendar, expense tracker, and the ability to export records for legal purposes. While often recommended in the context of family law, evidence for efficacy and safety is lacking. This study sought insights from family law professionals about the value of post-separation parenting apps in high-conflict cases. Thirty family mediators, known in Australia as Family Dispute Resolution Practitioners, role-played pairs of high-conflict separated parents using one of 10 popular post-separation parenting apps. After completing a set of common co-parenting tasks, dyadic interviews and focus groups were used to discuss their observations. Overall, practitioners expressed disappointment with the apps. Key themes included potential individual differences in separated parents’ technical skills, time availability, and intentions towards app use. Usability challenges specific to the tested apps were also identified. Rather than simplifying interactions for separated parents, these combined contextual variables were thought likely to contribute to frustration and inter-parental conflict. As a result, practitioners in the study resolved to be far more cautious with app recommendations for high-conflict clients.
The Impact of Recent Demography on Functional Genetic Variation in North African Human Groups
Authors: Lucas-Sánchez Marcel , Abdeli Amine , Bekada Asmahan , Calafell Francesc , Benhassine Traki , Comas David
Published: December 2023

The strategic location of North Africa has made the region the core of a wide range of human demographic events, including migrations, bottlenecks, and admixture processes. This has led to a complex and heterogeneous genetic and cultural landscape, which remains poorly studied compared to other world regions. Whole-exome sequencing is particularly relevant to determine the effects of these demographic events on current-day North Africans’ genomes, since it allows to focus on those parts of the genome that are more likely to have direct biomedical consequences. Whole-exome sequencing can also be used to assess the effect of recent demography in functional genetic variation and the efficacy of natural selection, a long-lasting debate. In the present work, we use newly generated whole-exome sequencing and genome-wide array genotypes to investigate the effect of demography in functional variation in 7 North African populations, considering both cultural and demographic differences and with a special focus on Amazigh (plur. Imazighen) groups. We detect genetic differences among populations related to their degree of isolation and the presence of bottlenecks in their recent history. We find differences in the functional part of the genome that suggest a relaxation of purifying selection in the more isolated groups, allowing for an increase of putatively damaging variation. Our results also show a shift in mutational load coinciding with major demographic events in the region and reveal differences within and between cultural and geographic groups.
Integration of solar receiver and thermal energy storage into a single unit in concentrating solar plants
Authors: Yang Song , Wang Jun , Lund Peter D
Published: December 2023

Integrating solar receivers and thermal energy storage in a concentrating solar thermal plant helps to enhance plant efficiency and cost-effectiveness. Here, we provide an overview of the technology to unify solar receivers and thermal energy storage into a single system. We discuss the advantages, challenges, and prospects associated with this innovative approach. This emerging technology has the potential to improve overall thermal performance and facilitate operation of high-temperature dispatchable concentrating solar thermal systems.
Detailing Early Shoot Growth Arrest in Kro-0 x BG-5 Hybrids of Arabidopsis thaliana
Authors: Sageman-Furnas Katelyn , Duarte Gustavo T , Laitinen Roosa A E
Published: December 2023

Shoot growth directly impacts plant productivity. Plants adjust their shoot growth in response to varying environments to maximize resource capture and stress resilience. While several factors controlling shoot growth are known, the complexity of the regulation and the input of the environment are not fully understood. We have investigated shoot growth repression induced by low ambient temperatures in hybrids of Arabidopsis thaliana Kro-0 and BG-5 accessions. To continue our previous studies, we confirmed that the Kro-0 allele of DYNAMIN-RELATED PROTEIN 3B causes stunted shoot growth in the BG-5 background. We also found that shoot growth repression was most pronounced near the apex at a lower temperature and that the cells in the hybrid stem failed to elongate correctly. Furthermore, we observed that shoot growth repression in hybrids depended on light availability. Global gene expression analysis indicated the involvement of hormones, especially strigolactone, associated with the dwarf phenotype. Altogether, this study enhances our knowledge on the genetic, physiological and environmental factors associated with shoot growth regulation.
Particulate matter composition drives differential molecular and morphological responses in lung epithelial cells
Authors: Engels Sean M , Kamat Pratik , Pafilis G Stavros , Li Yukang , Agrawal Anshika , Haller Daniel J , Phillip Jude M , Contreras Lydia M
Published: December 2023

Particulate matter (PM) is a ubiquitous component of air pollution that is epidemiologically linked to human pulmonary diseases. PM chemical composition varies widely, and the development of high-throughput experimental techniques enables direct profiling of cellular effects using compositionally unique PM mixtures. Here, we show that in a human bronchial epithelial cell model, exposure to three chemically distinct PM mixtures drive unique cell viability patterns, transcriptional remodeling, and the emergence of distinct morphological subtypes. Specifically, PM mixtures modulate cell viability, DNA damage responses, and induce the remodeling of gene expression associated with cell morphology, extracellular matrix organization, and cellular motility. Profiling cellular responses showed that cell morphologies change in a PM composition-dependent manner. Finally, we observed that PM mixtures with higher cadmium content induced increased DNA damage and drove redistribution among morphological subtypes. Our results demonstrate that quantitative measurement of individual cellular morphologies provides a robust, high-throughput approach to gauge the effects of environmental stressors on biological systems and score cellular susceptibilities to pollution.
Just Kidding? Two Roles for the Concept of Joking in Political Speech
Authors: Walker Zoe
Published: December 2023

In this paper, I discuss two roles for the concept of joking in political speech. First, I discuss how claiming to have been joking can provide speakers with a powerful form of deniability. I argue that the aesthetic dimension of jokes makes such a denial especially well placed to undermine both a hearer's evidence for an utterance having been sincere, and, separately, their belief that it was sincere—I call the latter ‘aesthetic gaslighting’. Second, I discuss the use of jokes to influence hearers’ thinking and behaviour under the radar. I show that not only does the fact that an utterance was a joke fail to prevent it from influencing hearers, but in some cases, the fact that it was a joke actually makes it more influential than a sincere utterance would have been.
TNFAIP3 Derived from Skeletal Stem Cells Alleviated Rat Osteoarthritis by Inhibiting the Necroptosis of Subchondral Osteoblasts
Authors: Li Xiao-Tong , Li Zhi-Ling , Li Pei-Lin , Wang Fei-Yan , Zhang Xiao-Yu , Wang Yu-Xing , Zhao Zhi-Dong , Yin Bo-Feng , Hao Rui-Cong , Mao Ning , Xia Wen-Rong , Ding Li , Zhu Heng
Published: December 2023

Recent investigations have shown that the necroptosis of tissue cells in joints is important in the development of osteoarthritis (OA). This study aimed to investigate the potential effects of exogenous skeletal stem cells (SSCs) on the necroptosis of subchondral osteoblasts in OA. Human SSCs and subchondral osteoblasts isolated from human tibia plateaus were used for Western blotting, real-time PCR, RNA sequencing, gene editing, and necroptosis detection assays. In addition, the rat anterior cruciate ligament transection OA model was used to evaluate the effects of SSCs on osteoblast necroptosis in vivo. The micro-CT and pathological data showed that intra-articular injections of SSCs significantly improved the microarchitecture of subchondral trabecular bones in OA rats. Additionally, SSCs inhibited the necroptosis of subchondral osteoblasts in OA rats and necroptotic cell models. The results of bulk RNA sequencing of SSCs stimulated or not by tumor necrosis factor α suggested a correlation of SSCs-derived tumor necrosis factor α-induced protein 3 (TNFAIP3) and cell necroptosis. Furthermore, TNFAIP3-derived from SSCs contributed to the inhibition of the subchondral osteoblast necroptosis in vivo and in vitro. Moreover, the intra-articular injections of TNFAIP3-overexpressing SSCs further improved the subchondral trabecular bone remodeling of OA rats. Thus, we report that TNFAIP3 from SSCs contributed to the suppression of the subchondral osteoblast necroptosis, which suggests that necroptotic subchondral osteoblasts in joints may be possible targets to treat OA by stem cell therapy.
Dense Lichenoid Inflammation in Paget Disease: A Diagnostic Pitfall
Authors: Zayas Jacqueline , Sokumbi Olayemi
Published: December 2023

Mammary Paget disease is a rare form of breast cancer, which typically presents as an eczematous plaque on the nipple or surrounding skin. It is often a clinical diagnosis that is confirmed with skin biopsy. Histologic hallmarks of mammary Paget disease include large, pleomorphic, malignant, ductal epithelial cells within the epidermis. Chronic lichenoid inflammation may be seen in the papillary dermis but is not diagnostic. Because mammary Paget disease often overlies ductal carcinoma in situ or invasive carcinoma of the breast, prompt bilateral mammography is warranted. We report a case of Paget disease of the nipple with negative breast imaging that was originally misdiagnosed due to a dense lichenoid infiltrate obscuring the neoplasm.
Cutaneous Horn Presentation in Porokeratotic Eccrine Ostial and Dermal Duct Nevus. A Brief Review and Case Report
Authors: Cuartero-Castro Gerardo , Cid-García Anahí , Téllez-Alvarado Adriana , Gutiérrez-Quiroz Claudia Teresita
Published: December 2023

Porokeratotic eccrine ostial and dermal duct nevus is a rare adnexal hamartoma characterized by the presence of a cornoid lamella exclusively overlying eccrine acrosyringia. Different clinical presentations have been reported in the literature. Here, we report a case of a 6-year-old girl diagnosed with porokeratotic eccrine ostial and dermal duct nevus confirmed by histopathologic study. Atypical lesions are described as whitish, warty-looking neoformations located in the anterolateral region of the right hip (cutaneous horn).
The Role of Rosmarinic Acid in the Protection Against Inflammatory Factors in Rats Model With Monocrotaline-Induced Pulmonary Hypertension: Investigating the Signaling Pathway of NFκB, OPG, Runx2, and P-Selectin in Heart
Authors: Atefipour Narges , Dianat Mahin , Badavi Mohammad , Radan Maryam , Mard Seyyed Ali
Published: December 2023

Shortness of breath and syncope are common symptoms of right ventricular failure caused by pulmonary arterial hypertension (PAH), which is the result of blockage and increased pressure in the pulmonary arteries. There is a significant amount of evidence supporting the idea that inflammation and vascular calcification (VC) are important factors in PAH pathogenesis. Therefore, we aimed to investigate the features of the inflammatory process and gene expression involved in VC in monocrotaline (MCT)-induced PAH rats. MCT (60 mg/kg, i.p.) was used to induce PAH. Animals were given normal saline or rosmarinic acid (RA) (10, 15, and 30 mg/kg, gavage) for 21 days. An increase in right ventricular systolic pressure was evaluated as confirming PAH. To determine the level of inflammation in lung tissue, pulmonary edema and the total and differential white blood cell counts in the bronchoalveolar lavage fluid were measured. Also, the expression of NFκB, OPG, Runx2, and P-selectin genes was investigated to evaluate the level of VC in the heart. Our experiment showed that RA significantly decreased right ventricular hypertrophy, inflammatory factors, NFκB, Runx2, and P-selectin gene expression, pulmonary edema, total and differential white blood cell count, and increased OPG gene expression. Therefore, our research showed that RA protects against MCT-induced PAH by reducing inflammation and VC in rats.
Resurfacing Dehiscence(s) Without Reducing Diverticulum Effectively Silences Pulsatile Tinnitus: Novel Surgical Techniques for Diverticulum and Intraoperative Microphone Monitoring
Authors: Hsieh Yue-Lin , Gao Xiuli , Chen Xi , Wang Shenjiang , Wang Wuqing
Published: December 2023

Objective

To emphasize the surgical importance of addressing dehiscence over diverticulum in resolving pulsatile tinnitus (PT) in patients with sigmoid sinus wall anomalies (SSWAs) and investigate anatomical differences.

Study Design

Retrospective data analysis.

Setting

Multi-institutional tertiary university medical centers.

Patients

Fifty participants (dehiscence/diverticulum, 29:21 cases) with SSWA-associated PT were included in the study. All 21 diverticulum participants underwent surgical intervention.

Interventions

1) Surgical intervention with novel techniques monitored by intraoperative microphone. 2) Radiologic and ophthalmologic imaging methods.

Main Outcome Measure(s)

Quantitative and qualitative preoperative and postoperative alterations of PT and anatomical differences between dehiscence and diverticulum.

Results

Addressing dehiscence overlying diverticulum and sigmoid sinus wall dehiscences significantly reduced visual analog score and Tinnitus Handicap Inventory (p < 0.01). Sinus wall reconstruction led to substantial PT sound intensity reduction in the frequency range of 20 to 1000 Hz and 20 to 500 Hz (paired-sample t test, p < 0.01). Diploic vein analysis showed a significant positive correlation in 85.7% of the diverticulum cohort compared with the dehiscence cohort (p < 0.01). Eight percent of the participants exhibited papilledema, which was limited to the dehiscence cohort.

Conclusion

1) Effective reduction of PT can be achieved by addressing all dehiscences, including those overlying the diverticulum, without the need to exclude the diverticulum. 2) Diploic vein may involve in the formation of diverticulum, and loss of dura mater and vascular wall thickness are observed at the SSWA locations.
Pre-Registration Nursing Students' Perceptions of Digital Health Technology on the Future of Nursing
Authors: Wong Pauline , Brand Gabrielle , Dix Samantha , Choo Dawn , Foley Pieternella , Lokmic-Tomkins Zerina
Published: December 2023

Background:

Health informatics competencies, digital health education, and nursing students' perceptions of technology are critical to ensure a future digitally capable health care workforce.

Purpose:

To explore preregistration students' perceptions of digital health technology impact on their role as nurses.

Methods:

Using a qualitative exploratory approach, students from 2 Australian universities were purposively sampled. Data were collected through photo-elicitation from 3 focus groups and thematically analyzed. Photo-elicitation provided reference points to encourage more in-depth exploration.

Results:

Themes included fear of the unknown and who am I? Nursing in a digital world. Human interaction was fundamental to their nursing role and digital health technology could depersonalize care, creating tension around their reason for choosing a nursing career.

Conclusions:

Educators should prepare students to redefine their nursing identity by exploring how digital health technology augments their practice and critical thinking skills, while addressing fear of a perceived threat to the future of nursing.
Knowledge Acquisition Based on Participant Role Assignment in a High-Fidelity Simulation
Authors: Hooper Barbara L. , Carlson Nancy G.
Published: December 2023

Background:

Participant roles can vary with simulation. Some roles involve providing direct care during the simulation, whereas other roles involve observing the simulation either in the simulation environment or in another room with audiovisual capabilities.

Purpose:

To determine whether learning outcomes are comparable for students regardless of role played in a simulation.

Methods:

A quasi-experimental design was used to determine whether knowledge acquisition was influenced by role assignment (primary or secondary nurse, family member, or observer) when participating in a high-fidelity simulation among 267 study participants.

Results:

There was a statistically significant increase in the mean score for knowledge acquisition for all participants (P < .001). There was no difference in knowledge acquisition based on the role assignment in the simulation (F = 0.28, P = .84).

Conclusions:

Knowledge acquisition is possible regardless of the role played in a high-fidelity simulation.
Structural Bias in the Completeness of Death Investigations for Sudden Unexpected Infant Deaths (SUIDs)
Authors: Thyden Naomi Harada , Slaughter-Acey Jaime , Widome Rachel , Warren John Robert , Osypuk Theresa L.
Published: December 2023

Objective:

To assess sudden unexpected infant death (SUID) investigations for structural inequities by race/ethnicity and geography.

Methods:

The SUID Case Registry compiles data on death investigations. We analyzed cases from 2015 to 2018 (N = 3847) to examine likelihood of an incomplete death investigation, defined as missing autopsy, missing scene investigation, or missing detailed information about where and how the body was found. We also analyzed which specific components of death investigations led to the greatest number of incomplete investigations.

Results:

Twenty-four percent of SUIDs had incomplete death investigations. Death scenes in rural places had 1.51 times the odds of incomplete death investigations (95% confidence interval [CI], 1.19-1.92) compared with urban areas. Scene investigations led by law enforcement were more likely to result in incomplete death investigations (odds ratio [OR] = 1.49; 95% CI, 1.18-1.88) than those led by medical examiners. American Indian/Alaska Native SUIDs were more likely than other racial groups to have an incomplete investigation (OR = 1.49; 95% CI, 0.92-2.42), more likely to occur in rural places (P = .055), and more likely to be investigated by law enforcement (P < .001). If doll reenactments had been performed, 358 additional cases would have had complete investigations, and if SUID investigation forms had been performed, 243 additional cases would have had complete investigations. American Indian/Alaska Native SUIDs were also more likely to be missing specific components of death investigations.

Conclusion:

To produce equitable public health surveillance data used in prevention efforts, it is crucial to improve SUID investigations, especially in rural areas and among American Indian/Alaska Native babies.
Benefits and Challenges of Sealing Deceased Individual Immunization Records in Immunization Information Systems (IIS): An Overview of Iowa's Process
Authors: Loper Ona R. , Schultz Jessica M. , King Tory L. , Tichy Kimberly J. , Kintigh Bethany F. , Callaghan Donald J.
Published: December 2023

Data cleansing practices aimed to improve data quality in immunization information systems (IIS) continue to be identified and evaluated by immunization programs to generate accurate and reliable immunization coverage rates. The Iowa Immunization Program has implemented several automated, daily data cleansing practices to improve the quality of records in Iowa's Immunization Registry Information System (IRIS), including the process of sealing records of deceased individuals through vital records matching. This process removes deceased individual records from the active IIS population, which helps reduce denominator inflation and improve the accuracy of immunization rate calculations. Other benefits to this process include decreasing record fragmentation, increasing completeness and accuracy of IIS data, improving reminder/recall functionality, and supporting better clinical decision-making for providers. This process is one of multiple practices implemented in IIS to improve data quality and is limited by several factors, including the inability to capture deaths for out-of-state records.
Mpox Management: A Holistic Local Response to a Global Threat
Authors: Crouch Simon , Jalil Edura , Pierce Anna B. , Baptista Mohana , Wong Evelyn , Stuart Rhonda
Published: December 2023

Newly formed local public health units in Victoria have been established to support a place-based approach that tailors and delivers public health initiatives and responds to public health incidents and issues. Initially, post-establishment of these units, public health activities focused on the prevention and control of communicable diseases. In 2022, mpox emerged as a global public health threat. As case numbers rose across Australia, local public health units in Victoria were engaged by the Department of Health to support a localized response to this new threat. The South East Public Health Unit, Monash Health, developed a number of targeted initiatives to control the local spread of mpox, ranging from capacity building of health professionals to increase early diagnosis, contact tracing, facilitating vaccine delivery, and community engagement. This contributed to effective local elimination within 6 months, demonstrating how LPHUs are well placed to engage with local communities and health care providers to respond rapidly to newly emerging public health threats.
Development of the FlagIt Report and Response System for Concerning or Harassing Messages Related to Public Health Work
Authors: Sell Tara Kirk , Resnick Beth A.
Published: December 2023

In response to growing reports of concerning/harassing messages and backlash related to public health work, the Johns Hopkins Bloomberg School of Public Health established the FlagIt report and response system. The system uses a dedicated FlagIt email inbox for faculty and staff to report harassing or concerning messages related to public-facing work and has an autoreply message sharing available institutional resources. The Johns Hopkins University public safety investigators review, inventory, and investigate the reported messages and share their findings with the reporter within 2 business days. In addition, the Johns Hopkins Bloomberg School of Public Health faculty FlagIt team volunteers reach out to the reporter to check in on how they are doing and offer additional supports if needed The FlagIt system was developed with existing institutional resources and did not require additional funding. Given the continued backlash against public health, other public health institutions and agencies may consider implementing similar report and response systems.
Evaluating Mediastinal Lymph Node Metastasis of Non–Small Cell Lung Cancer Using Mono-exponential, Bi-exponential, and Stretched-exponential Models of Diffusion-weighted Imaging
Authors: Zheng Yu , Han Na , Huang Wenjing , Jiang Yanli , Zhang Jing
Published: December 2023

Purpose:

To explore and compare the diagnostic values of mono-exponential, bi-exponential, and stretched-exponential diffusion-weighted imaging (DWI) parameters of primary lesions and lymph nodes (LNs) to predict mediastinal LN metastasis in patients with non–small cell lung cancer.

Patients and Methods:

Sixty-one patients with non–small cell lung cancer underwent preoperative magnetic resonance imaging, including multiple b-value DWI. The DWI parameters, including apparent diffusion coefficient (ADC) from a mono-exponential model, true diffusion (D) coefficient, pseudo-diffusion (D*) coefficient, and perfusion fraction (f) from a bi-exponential model, distributed diffusion coefficient (DDC) and intravoxel diffusion heterogeneity index (α) from a stretched-exponential model of primary tumors and LNs and the size characteristics of LNs, were measured and compared. Multivariate logistic regression analysis was used to establish models for predicting mediastinal LN metastasis. Receiver operating characteristic analysis was applied to evaluate diagnostic performances.

Results:

The DWI parameters of primary tumors showed no statistical significance between LN metastasis-positive and LN metastasis-negative groups. Nonmetastatic LNs had significantly higher ADC, D, DDC, and α values compared with metastatic LNs (all P < 0.05). The short-dimension, long-dimension, and short-long dimension ratio of metastatic LNs was significantly larger than those of nonmetastatic ones (all P < 0.05). The D value showed the best diagnostic performance among all DWI-derived single parameters, and the short dimension of LNs performed the same among all the size variables. Furthermore, the combination of DWI parameters (ADC and D) and the short dimension of LNs can significantly improve diagnostic efficiency.

Conclusions:

The ADC, D, DDC, and α from the mono-exponential, bi-exponential, and stretched-exponential models were demonstrated efficient in differentiating benign from metastatic LNs, and the combination of ADC, D, and short dimension of LNs may have a better diagnostic performance than DWI or size-derived parameters either in combination or individually.
Exosomal microRNA following severe trauma: Role in bone marrow dysfunction
Authors: Munley Jennifer A. , Willis Micah L. , Gillies Gwendolyn S. , Kannan Kolenkode B. , Polcz Valerie E. , Balch Jeremy A. , Barrios Evan L. , Wallet Shannon M. , Bible Letitia E. , Efron Philip A. , Maile Robert , Mohr Alicia M.
Published: December 2023

INTRODUCTION

Severe trauma disrupts bone marrow function and is associated with persistent anemia and altered hematopoiesis. Previously, plasma-derived exosomes isolated after trauma have been shown to suppress in vitro bone marrow function. However, the cargo contained in these vesicles has not been examined. We hypothesized that trauma plasma–derived exosomes exhibit microRNA (miRNA) changes that impact bone marrow function after severe injury.

METHODS

Plasma was collected from a prospective cohort study of trauma patients (n = 15; 7 males, 8 females) with hip and/or femur fractures and an Injury Severity Score of ≥15; elective total hip arthroplasty (THA) patients (n = 8; 4 males, 4 females) served as operative controls. Exosomes were isolated from plasma with the Invitrogen Total Exosome Isolation Kit (Thermo Fisher Scientific, Waltham, MA), and RNA was isolated using a miRNeasy Mini Kit (Qiagen, Hilden, Germany). Direct quantification of miRNA was performed by NanoString Technologies on a human miRNA gene panel and analyzed with nSolver with significance defined as p < 0.05.

RESULTS

There were no differences in age or sex distribution between trauma and THA groups; the average Injury Severity Score was 23. Trauma plasma–derived exosomes had 60 miRNA identities that were significantly downregulated and 3 miRNAs that were upregulated when compared with THA (p < 0.05). Twelve of the downregulated miRNAs have a direct role in hematopoiesis regulation. Furthermore, male trauma plasma–derived exosomes demonstrated downregulation of 150 miRNAs compared with male THA (p < 0.05). Female trauma plasma–derived exosomes demonstrated downregulation of only four miRNAs and upregulation of two miRNAs compared with female THA (p < 0.05).

CONCLUSION

We observed downregulation of 12 miRNAs linked to hematopoiesis along with sexual dimorphism in miRNA expression from plasma-derived exosomes following severe trauma. Understanding sexually dimorphic miRNA expression provides new insight into sex-based changes in postinjury systemic inflammation, immune system dysregulation, and bone marrow dysfunction and will aid us in more precise future potential therapeutic strategies.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
Comparison of Lasmiditan 200 mg Versus 100 mg for Migraine Patients: A Meta-analysis of Randomized Controlled Studies
Authors: Zhong Chuan , Zhang Xuanqin , Qin Guoyong , Wu Jixiang , Tian Yongpan
Published: December 2023

Introduction

The ideal dose of lasmiditan for migraine is not clear. This meta-analysis aims to compare the efficacy of lasmiditan 200 mg versus 100 mg for migraine patients.

Methods

We have searched several databases including PubMed, Embase, Web of Science, EBSCO, and Cochrane Library Databases and selected the randomized controlled trials comparing the efficacy of lasmiditan 200 mg versus 100 mg for migraine patients. This meta-analysis was conducted using the random-effect model.

Results

Five randomized controlled trials were included in this meta-analysis. Compared with lasmiditan 100-mg group in migraine patients, lasmiditan 200-mg group was associated with substantially increased pain free at 2 hours (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.12–1.44; P = 0.0002) and pain free at 24 hours (OR, 1.31; 95% CI, 1.08–1.60; P = 0.007) but demonstrated no obvious impact on pain relief at 2 hours (OR, 1.02; 95% CI, 0.91–1.16; P = 0.72) or MBS free at 2 hours (OR, 0.94; 95% CI, 0.77–1.14; P = 0.52). In addition, the incidence of adverse events was higher in lasmiditan 200-mg group than that in lasmiditan 100-mg group (OR, 1.29; 95% CI, 1.15–1.45; P < 0.0001).

Conclusions

Lasmiditan 200 mg is better for the treatment of migraine patients than lasmiditan 100 mg.
Identification of Hypertrophic Cardiomyopathy on Electrocardiographic Images with Deep Learning
Authors: Sangha Veer , Dhingra Lovedeep Singh , Oikonomou Evangelos , Aminorroaya Arya , Sikand Nikhil V , Sen Sounok , Krumholz Harlan M , Khera Rohan
Published: December 2023

Background

Hypertrophic cardiomyopathy (HCM) affects 1 in every 200 individuals and is the leading cause of sudden cardiac death in young adults. HCM can be identified using an electrocardiogram (ECG) raw voltage data and deep learning approaches, but their point-of-care application is limited by the inaccessibility of these signal data. We developed a deep learning-based approach that overcomes this limitation and detects HCM from images of 12-lead ECGs across layouts.

Methods

We identified ECGs from patients with HCM features present on cardiac magnetic resonance imaging (CMR) or those within 30 days of an echocardiogram documenting thickened interventricular septum (end-diastolic interventricular septum thickness > 15mm). Patients with CMR-confirmed HCM were considered as cases during the final model evaluation. The model was validated within clinical settings at YNHH and externally on ECG images from the prospective, population-based UK Biobank cohort. We localized class-discriminating signals in ECG images using gradient-weighted class activation mapping.

Results

Overall, 124,553 ECGs from 66,987 individuals (HCM cases and controls) were used for model development. The model demonstrated high discrimination for HCM across various ECG image formats and calibrations in internal validation (area under receiving operation characteristics [AUROC] 0.96) and external sets of ECG images from UK Biobank (AUROC 0.94). A positive screen for HCM was associated with a 100-fold higher odds of CMR-confirmed HCM (OR 102.4, 95% Confidence Interval, 57.4 – 182.6) in the held-out set. Class-discriminative patterns localized to the anterior and lateral leads (V4-V5).

Conclusions

We developed and externally validated a deep learning model that identifies HCM from ECG images with excellent discrimination. This approach represents an automated, efficient, and accessible screening strategy for HCM.
Mapping inherited genetic variation with opposite effects on autoimmune disease and cancer identifies candidate drug targets associated with the anti-tumor immune response
Authors: Chen Junyu , Epstein Michael P. , Schildkraut Joellen M. , Kar Siddhartha P.
Published: December 2023

Background

Germline alleles near genes that encode certain immune checkpoints (CTLA4,CD200) are associated with autoimmune/autoinflammatory disease and cancer but in opposite directions. This motivates a systematic search for additional germline alleles which demonstrate this pattern with the aim of identifying potential cancer immunotherapeutic targets using human genetic evidence.

Methods

Pairwise fixed effect cross-disorder meta-analyses combining genome-wide association studies (GWAS) for breast, prostate, ovarian and endometrial cancers (240,540 cases/317,000 controls) and seven autoimmune/autoinflammatory diseases (112,631 cases/895,386 controls) coupled within silicofollow-up. To ensure detection of alleles with opposite effects on cancer and autoimmune/autoinflammatory disease, the signs on the beta coefficients in the autoimmune/autoinflammatory GWAS were reversed prior to meta-analyses.

Results

Meta-analyses followed by linkage disequilibrium clumping identified 312 unique, independent lead variants with Pmeta<5×10-8associated with at least one of the cancer types at Pcancer<10-3and one of the autoimmune/autoinflammatory diseases at Pauto<10-3. At each lead variant, the allele that conferred autoimmune/autoinflammatory disease risk was protective for cancer. Mapping each lead variant to its nearest gene as its putative functional target and focusing on genes with established immunological effects implicated 32 of the nearest genes. Tumor bulk RNA-Seq data highlighted that the tumor expression of 5/32 genes (IRF1,IKZF1,SPI1,SH2B3,LAT) were each strongly correlated (Spearman’s ρ>0.5) with at least one intra-tumor T/myeloid cell infiltration marker (CD4,CD8A,CD11B,CD45) in every one of the cancer types. Tumor single-cell RNA-Seq data from all cancer types showed that the five genes were more likely to be expressed in intra-tumor immune versus malignant cells. The five lead SNPs corresponding to these genes were linked to them via expression quantitative trait locus mechanisms and at least one additional line of functional evidence. Proteins encoded by the genes were predicted to be druggable.

Conclusion

We provide population-scale germline genetic and functional genomic evidence to support further evaluation of the proteins encoded byIRF1,IKZF1,SPI1,SH2B3, andLATas possible targets for cancer immunotherapy.
The Pattern of rpoB gene mutation ofMycobacterium tuberculosisand predictors of rifampicin resistance detected by gene Xpert MTB/Rif in Tanzania
Authors: Torokaa Peter Richard , Kileo Heledy , Urio Loveness , Mbwana Mariam R. , Monah Mariam C. , Ntibabara Sephord Saul , Kimambo Jasper , Seleman Paschal , Franklin Collins , Balama Robert , Kisonga Riziki M. , Majigo Mtebe V. , Joachim Agricola
Published: December 2023

Introduction

Antimicrobial resistance associated withMycobacterium tuberculosis (MTB)is the challenge facing Tuberculosis (TB) management worldwide. Rifampicin resistance (RR) has been associated with the rpoB gene mutation. No study was conducted in Tanzania to determine the commonest mutation. The inconsistent findings from various studies support the need to determine whether reported mutation patterns are applicable in our setting. We determined the frequency of rpoB gene mutation and factors associated with RR detected using GeneXpert MTB/Rif.

Methods

We conducted a retrospective cross-sectional study involving data from the National Tuberculosis and Leprosy Program database from 2020 to 2022 for cases investigated using GeneXpert. Descriptive analysis was performed as the frequency for categorical variables. The chi-square test and regression analysis assessed the relationship between the independent variables and outcome. The 95% confidence interval and a significance level of p<0.05 were used to assess the association strength.

Results

A total of 56,004 participants had status of MTB and RR. Most, 38,705/56,004 (69.11%) were male. Probe E, 89/219 (40.64%) was the predominant. Human immunodeficiency virus (HIV)-positive patients had a higher gene mutation, 134/10601 (1.26%) than HIV-negative, 306/45016 (0.68%) (p<0.001). Patients with both pulmonary and extra-pulmonary TB had about four times greater odds of developing rifampicin resistance (AOR 3.88, 95%CI: 1.80 – 8.32). RR was nearly nine times higher in previously treated patients than new patients (AOR 8.66, 95%CI: 6.97–10.76). HIV-positive individuals had nearly twice the odds of developing RR than HIV-negative individuals (AOR 1.91, 95%CI: 1.51 – 2.42).

Conclusion

The rate of RR was low compared to other studies in Tanzania, with probe E mutations the most prevalent. Patients with disseminated TB, HIV co-infection and those with prior exposure to anti-TB had more risk of RR. The findings highlight the need to strengthen surveillance of multidrug-resistant-TB among patients with a higher risk of RR.
Polygenic prediction of major depressive disorder and related traits in African ancestries UK Biobank participants
Authors: Kanjira SC , Adams MJ , Jiang Yunxuan , Tian Chao ,   23andMe Research Team, Lewis CM , Kuchenbaecker K , McIntosh AM
Published: December 2023

Introduction

Genome-Wide Association Studies (GWAS) over-represent European ancestries compared to the global population, neglecting all other ancestry groups and low-income nations. Consequently, polygenic risk scores (PRS) more accurately predict complex traits in Europeans than African Ancestries groups. Very few studies have looked at the transferability of European-derived PRS for behavioural and mental health phenotypes to non-Europeans. We assessed the comparative accuracy of PRS for Major Depressive Disorder (MDD) trained on European and African Ancestries GWAS studies to predict MDD and related traits in African Ancestries participants from the UK Biobank.

Methods

UK Biobank participants were selected based on Principal component analysis (PCA) clustering with an African genetic similarity reference population and MDD was assessed with the Composite International Diagnostic Interview (CIDI). Polygenic Risk Scores (PRS) were computed using PRSice2 using either European or African Ancestries GWAS summary statistics.

Results

PRS trained on European ancestry samples (246,363 cases) predicted case control status in Africans of the UK Biobank with similar accuracies (190 cases, R2=2%) to PRS trained on far much smaller samples of African Ancestries participants from 23andMe, Inc. (5045 cases, R2=1.8%). This suggests that prediction of MDD status from Africans to Africans had greater efficiency per unit increase in the discovery sample size than prediction of MDD from Europeans to Africans. Prediction of MDD status in African UK Biobank participants using GWAS findings of causal risk factors from European ancestries was non-significant.

Conclusion

GWAS studies of MDD in European ancestries are an inefficient means of improving polygenic prediction accuracy in African samples.
Multimodal Diverse Granularity Fusion Network based on US and CT Images for Lymph Node Metastasis Prediction of Thyroid Carcinoma
Authors: Li Guojun , Yao Jincao , Peng Chanjuan , Hu Yinjie , Zhao Shanshan , Feng Xuhan , Yang Jianfeng , Xu Dong , Li Xiaolin , Sha Chulin , He Min
Published: December 2023

Accurately predicting the risk of cervical lymph node metastasis (LNM) is crucial for surgical decision-making in thyroid cancer patients, and the difficulty in it often leads to over-treatment. Ultrasound (US) and computed tomography (CT) are two primary non-invasive methods applied in clinical practice, but both contain limitations and provide unsatisfactory results. To address this, we developed a robust and explainable multimodal deep-learning model by integrating the above two examinations. Using 3522 US and 7649 CT images from 1138 patients with biopsy-confirmed LNM status, we showed that multimodal methods outperformed unimodal counterparts at both central and lateral cervical sites. By incorporating a diverse granularity fusion module, we further enhanced the area under the curve (AUC) to 0.875 and 0.859 at central and lateral cervical sites respectively. This performance was also validated in an external cohort. Additionally, we quantified the modality-specific contributions for each nodule and systematically evaluated the applicability across various clinical characteristics, aiding in identifying individuals who can benefit most from the multimodal method.
Empowering Transformers for Evidence-Based Medicine
Authors: Mohammed Sabah , Fiaidhi Jinan , Shaik Hashmath
Published: December 2023

Breaking the barrier for practicing evidence-based medicine rely on effective methods for rapidly identifying relevant evidences from the body of biomedical literature. An important challenge confronted by the medical practitioners is the long time needed to browse, filter, summarize and compile information from different medical resources. Deep learning can help in solving this based on the automatic question answering (Q&A) and transformers. However, Q&A and transformers technologies are not trained to answer clinical queries that can be used for evidence-based practice nor it can respond to structured clinical questioning protocol like PICO (Patient/Problem, Intervention, Comparison and Outcome). This article describes the use of deep learning techniques for Q&A that is based on transformer models like BERT and GPT to answer PICO clinical questions that can be used for evidence-based practice extracted from sound medical research resources like PubMed. We are reporting acceptable clinical answers that are supported by findings from PubMed. Our transformer methods are reaching an acceptable state of the art performance based on two staged bootstrapping process involving filtering relevant articles followed by identifying articles that support the requested outcome expressed by the PICO question. Moreover, we are also reporting experimentations to empower our bootstrapping techniques with patch attentions to the most important keywords in the clinical case and the PICO questions. Our bootstrapped patched with attention is showing relevancy of the evidences collected based on an entropy metrics.
Integrated Systems Analysis Deciphers Transcriptome and Glycoproteome Links in Alzheimer’s Disease
Authors: Matsui Yusuke , Togayachi Akira , Sakamoto Kazuma , Angata Kiyohiko , Kadomatsu Kenji , Nishihara Shoko
Published: December 2023

Glycosylation is increasingly recognized as a potential therapeutic target in Alzheimer’s disease. In recent years, evidence of Alzheimer’s disease-specific glycoproteins has been established. However, the mechanisms underlying their dysregulation, including tissue- and cell-type specificity, are not fully understood. We aimed to explore the upstream regulators of aberrant glycosylation by integrating multiple data sources using a glycogenomics approach. We identified dysregulation of the glycosyltransferase PLOD3 in oligodendrocytes as an upstream regulator of cerebral vessels and found that it is involved in COL4A5 synthesis, which is strongly correlated with amyloid fiber formation. Furthermore, COL4A5 has been suggested to interact with astrocytes via extracellular matrix receptors as a ligand. This study suggests directions for new therapeutic strategies for Alzheimer’s disease targeting glycosyltransferases.

Graphical Abstract
The long-term effect of bariatric/metabolic surgery versus pharmacologic therapy in type 2 diabetes mellitus patients: A systematic review and meta-analysis
Authors: Yang Yumeng , Miao Chuhan , Wang Yingli , He Jianxun , Bo Yan
Published: December 2023

Background

Metabolic/bariatric surgery as a treatment for obesity and related diseases, such as type 2 diabetes mellitus (T2DM), has been increasingly recognized. However, the long-term effect (≥ five years) of metabolic surgery in T2D patients is still unclear compared with conventional pharmacologic therapy. This study aims to evaluate the diabetes remission rate, diabetic microvascular complications incidence, macrovascular complications incidence, and mortality in T2D patients who received metabolic surgery versus pharmacologic therapy more than five years after the surgery.

Methods

Searching the database, including PubMed, Embase, Web of Science, and Cochrane Library from the inception to recent (2022), for randomized clinical trials (RCTs) or cohort studies comparing T2D patients treated with metabolic surgery versus pharmacologic therapy reporting on the outcomes of the diabetes remission rate, diabetic microvascular complications, macrovascular complications, or mortality over five years or more.

Results

A total of 13 articles with a total of 68,280 patients with T2D were eligible for review and meta-analysis in this study. There is a significant long-term increase in diabetes remission for metabolic surgery compared with conventional medical therapy in the overall pooled estimation and RCT studies or cohort studies separately (overall: OR = 8.39, 95%CI: 3.58-19.67, P<0.001). Significant long-term decreases showed in the pooled results of microvascular complications incidence (HR = 0.43, 95%CI: 0.37-0.49, P<0.001), macrovascular complications incidence (HR = 0.60, 95%CI: 0.48-0.75, P<0.001) and mortality (HR = 0.44, 95%CI: 0.37-0.49, P<0.001).

Conclusion

Metabolic surgery showed more significant long-term effects than pharmacologic therapy on diabetes remission, macrovascular complications, microvascular complications incidence, and all-cause mortality in patients with T2D using currently available evidence. More high-quality evidence is needed to validate the long-term effects of metabolic surgery versus conventional treatment in the management of diabetes.
Distributed evidence accumulation across macaque large-scale neocortical networks during perceptual decision making
Authors: Zou Licheng , Palomero-Gallagher Nicola , Zhou Douglas , Li Songting , Mejias Jorge F
Published: December 2023

Despite the traditional view of parietal cortex as an important region for perceptual decision-making, recent evidence suggests that sensory accumulation occurs simultaneously across many cortical regions. We explored this hypothesis by integrating connectivity, cellular and receptor density datasets and building a large-scale macaque cortical model able to integrate conflicting sensory signals and perform a decision-making task. Our results reveal sensory evidence accumulation supported by a distributed network of temporal, parietal and frontal regions, with flexible sequential bottom-up or top-down modulation pathways depending on task difficulty. The model replicates experimental lesioning effects and reveals that the causal irrelevance of parietal areas like LIP for decision performance is explained by compensatory mechanisms within a distributed integration process. The model also reproduces observed temporal gating effects of distractor timing during and after the integration process. Overall, our work hints at perceptual integration during decision-making as a broad distributed phenomenon, providing multiple testable predictions.