bluuebunny/crossref_metadata_2025 huggingface dataset:
Hinduism and Musicology of Religion
Authors: Beck Guy
Published: January 2025

This bibliographic essay engages the theories and methods of musicology of religion as they relate to Hinduism. Applied broadly, musicology of religion focuses on the subject area of religion and music in a comparative context across cultures and time periods. The immense historical record of data collected on the relation of music and religion, along with the rising discussions of the role of music in various religious traditions, points to the growing need to identify religion and music as a singular unit of study and research. The principal object of study for the musicology of religion is thus the visible or invisible connections between religion and music in the broadest sense, with the methods necessarily geared toward finding cross-cultural patterns and insights about religion that may be concealed or less obvious. Musicology of religion is designed to rise above the empirical and culture-specific methods and findings of the social sciences and ethnomusicology to incorporate philosophical, phenomenological, theological, and cognitive dimensions. Research in the history of religions, musicology, aesthetics, and cognitive studies has identified human nature as homo religiosus (“religious human”) and homo musicus (“musical human”), that is, predisposed to act religiously and to make music. These two natures are linked together in two ways, one externally as homo ritualis (“ritual human”), covering the tendency to act ritually or liturgically, and the other internally as homo aestheticus (“aesthetic human”), the ability to experience beauty and the arts. The latter terms exemplify the application of musicology of religion to the study of Hinduism and music, for Hindu practitioners exhibit one of the most enduring senses of the primacy of religious ritual and its association with the arts and music. The approach of musicology of religion widens the scope for the study of music in Hinduism so that the educated world can benefit from placing the Hindu musical experience in conversation with religious studies, theology, phenomenology, cognitive studies, and aesthetics. It thus aims to bring Indian or Hindu music into further dialogue with many of the developing fields of discourse in the humanities and social sciences, stimulating new directions in research and teaching. Acknowledging the established field of Indian music studies, this article complements the separate Oxford Bibliographies in Hinduism article “Hinduism and Music” and the Oxford Bibliographies in Music article “Music in India.” Somewhat different from these entries, however, this article, rather than compiling descriptive sources for the study of music in Hinduism and India, draws together a variety of theories and methods from other disciplines that will hopefully provide more fertile ground for comparative studies on the role of music in Hinduism. Musicology of Religion presents the sources for the approach of musicology of religion, and Hinduism and Music identifies new sources for the study of specific Hindu traditions of music as well as important works in Indian aesthetics.
Transaction Cost Economics and Stakeholder Theory
Authors: Ketokivi Mikko , Mahoney Joseph
Published: January 2025

Transaction cost economics (TCE) combines the intellectual foundations of law, economics, and organization theory to address the governance of contractual relationships and economic transactions. TCE seeks to identify governance structures where the value-creating skills and resources are put to comparatively better uses—in short, economic efficiency by avoiding waste. How the final assembler of automobiles should organize its relationships with its component suppliers is a representative example of TCE’s domain of application. In automobile assembly, the question of which components to make internally and which to buy from external suppliers—the make-or-buy decision—is an illustrative research question. As the illustration shows, TCE takes the exchange relationship, or transaction, as its central unit of analysis. Viewed through a stakeholder lens, TCE focuses on complex, long-term contractual relationships beset with bilateral dependency, high environmental uncertainty, and behavioral risk. In the context of buyer-supplier relationships in the automotive value chain, a long-term relationship that involves various relation-specific investments is an example of such a complex relationship. For example, a seat manufacturer might geographically collocate its seat assembly plant with the automaker’s final assembly plant to supply seats efficiently for final assembly. Stakeholder relationships emerge as the contracting parties become bilaterally dependent. TCE’s logic suggests that enfranchised stakeholder relationships be adequately safeguarded by implementing the appropriate governance structures. Even though TCE initially focused on topics such as vertical integration and buyer-supplier relationships, the TCE approach to governance applies generally to any intra- or inter-organizational issue that can be framed as a contracting problem. The objective of this article is to offer a summary of the six central TCE-based research programs that are intimately related to stakeholder governance. The number of representative contributions under each research program has been limited to a maximum of ten texts (i.e., articles, books, or book chapters). Given that since the inception of TCE scholarship in the 1960s, several hundred scholars across the world have contributed several thousand articles to TCE’s research programs, the contributions in this review are unavoidably selective and illustrative, and not comprehensive.
Epidemiology of Lyme Disease as Identified Through Electronic Health Records in a Large Midwestern Health System, 2016–2019
Authors: Kugeler Kiersten J , Scotty Erica , Hinckley Alison F , Hook Sarah A , Nawrocki Courtney C , Nikolai Anne M , Linz Alexandra M , Meece Jennifer , Schotthoefer Anna M
Published: January 2025

Background

Lyme disease is the most common vector-borne disease in the United States; however, its frequency is not reliably measured through surveillance. Electronic health records (EHR) might capture the frequency and characteristics of Lyme disease cases more accurately. We queried EHR from 1 health system to describe the epidemiology of Lyme disease cases in Wisconsin during 2016–2019.

Methods

Within a cohort of persons evaluated for Lyme disease, we applied a Lyme disease case definition based on first-line antibiotics within 14 days of a Lyme disease diagnosis code or test order or on the same day as a related keyword in clinical notes. We compared characteristics of cases to those of cases reported through surveillance and reviewed medical charts to assess case definition validity.

Results

Among 67 289 possible Lyme disease events in the cohort, 13 494 (20.1%) met our Lyme disease case definition. Cases were more common among males, children 5–9 years, older adults, White non-Hispanic persons, and in the summer months. EHR-based Lyme disease incidence was 4–8 times that reported through surveillance. The EHR definition had moderately high sensitivity (83.4%) and specificity (71.1%) for confirmed and probable Lyme disease.

Conclusions

EHR queries show promise to capture the incidence of Lyme disease more completely and provide more robust clinical information than public health surveillance. Demographic and seasonal characteristics of EHR-identified cases were comparable to those identified through surveillance. Further algorithm refinement might improve accuracy of measuring Lyme disease in EHR systems.
Brain-inspired wiring economics for artificial neural networks
Authors: Zhang Xin-Jie , Moore Jack Murdoch , Gao Ting-Ting , Zhang Xiaozhu , Yan Gang
Published: January 2025

Wiring patterns of brain networks embody a trade-off between information transmission, geometric constraints, and metabolic cost, all of which must be balanced to meet functional needs. Geometry and wiring economy are crucial in the development of brains, but their impact on artificial neural networks (ANNs) remains little understood. Here, we adopt a wiring cost-controlled training framework that simultaneously optimizes wiring efficiency and task performance during structural evolution of sparse ANNs whose nodes are located at arbitrary but fixed positions. We show that wiring cost control improves performance across a wide range of tasks, ANN architectures and training methods, and can promote task-specific structural modules. An optimal wiring cost range provides both enhanced predictive performance and high values of topological properties, such as modularity and clustering, which are observed in real brain networks and known to improve robustness, interpretability, and performance of ANNs. In addition, ANNs trained using wiring cost can emulate the connection distance distribution observed in the brains of real organisms (such as Ciona intestinalis and Caenorhabditis elegans), especially when achieving high task performance, offering insights into biological organizing principles. Our results shed light on the relationship between topology and task specialization of ANNs trained within biophysical constraints, and their geometric resemblance to real neuronal-level brain maps.
Partner (in)congruence in gender role attitudes and relationship satisfaction
Authors: Park Haeyoung Gideon , Qin Helena Yuchen , Horne Rebecca M , Impett Emily A , Yorgason Jeremy B , Cheung Felix
Published: January 2025

The societal shift toward greater gender equality has led to increased variability in people’s gender role attitudes, or the belief that men and women should occupy distinct family roles (i.e. men as breadwinners and women as homemakers). Existing evidence on the association between gender role attitudes and relationship well-being remains inconclusive with mixed findings, likely because past research has not adequately considered the direction and degree of (in)congruencies between partners within the relationship. Using longitudinal samples of 1,327 couples from the United States and 5,856 couples from Germany tracked over 2 and 13 years, respectively, we employed dyadic response surface analysis to examine how different patterns of partner (in)congruencies in gender role attitudes predict relationship well-being in mixed-gender relationships. The results showed that, for US men and German men and women, the direction of incongruence between partners’ gender role attitudes mattered: relationship satisfaction was higher when men adopted more egalitarian attitudes than women (or conversely, when women adopted more traditional attitudes than men) compared with the reverse. Relationship satisfaction was also higher when both partners showed congruence in extreme gender role attitudes (either strongly traditional or egalitarian) than when either partner endorsed more neutral attitudes. US women reported higher relationship satisfaction only when either partner endorsed more egalitarian attitudes. Although past research emphasizes the benefits of partner similarity for relationship well-being, our findings highlight the importance of both similarity and complementarity in gender role attitudes, potentially subject to cultural and contextual factors.
Effects of double data extraction on errors in evidence synthesis: a crossover, multicenter, investigator-blinded, randomized controlled trial
Authors: Tang Lijun , Wang Ruoxi , Doi Suhail A R , Furuya-Kanamori Luis , Lin Lifeng , Qin Zongshi , Tao Fangbiao , Xu Chang
Published: January 2025

Objectives

The objective was to investigate the role of double extraction in reducing data errors in evidence synthesis for pharmaceutical and non-pharmaceutical interventions.

Design

Crossover randomized controlled trial (RCT).

Setting

University and hospital with teaching programs in evidence-based medicine.

Participants

One hundred eligible participants were randomly assigned in a 1:1 ratio to perform data extraction tasks for either 10 RCTs of pharmaceutical interventions or 10 RCTs of non-pharmaceutical interventions, followed by a crossover pattern and a further cross-checking process (double extraction). Only data on binary adverse outcomes were extracted.

Intervention

Double data extraction versus single extraction.

Primary and secondary outcome measures

The primary outcome was the error rate before and after the cross-checking process. The secondary outcome was the absolute difference in error rates. Error rates were assessed at both the study level and the cell level.

Results

Error rates in the pharmaceutical and non-pharmaceutical groups were 64.65% and 59.90%, respectively, with an absolute difference of 4.75% and an odds ratio (OR) of 1.29 [95% confidence interval (CI): 1.06–1.57, P = .01] when measured at the study level. After cross-checking, error rates decreased to 44.88% and 39.54%, with the difference between the two groups remaining at 5.34%, and an OR of 1.27 (95%CI: 1.1–1.46; P < .01). Similar differences were observed when measured at the cell level.

Conclusion

Although double extraction reduced data errors, the error rate remained high after the process. Evidence synthesis research may consider triple data extraction to further minimize potential data errors.

Trial registration number

Chinese Clinical Trial Registry Center (Identifier: ChiCTR2200062206).
Global and regional burden of cardiovascular diseases attributable to non-optimal temperatures: findings from the global burden of disease study 2021
Authors: Jena Diptismita , Padhi Bijaya Kumar
Published: January 2025

Background

Cardiovascular diseases (CVD) are leading contributors to global morbidity and mortality, significantly influenced by non-optimal temperatures. This study projects the impact of temperature fluctuations on CVD through 2050, considering environmental and climate changes.

Methods

Using Global Burden of Disease (GBD) study data, we analysed age-standardized death rates and disability-adjusted life years (ASR DALYs) related to non-optimal temperatures. We applied Estimated Annual Percentage Change (EAPC) for trend analysis and Auto-Regressive Integrated Moving Average (ARIMA) models for forecasting CVD mortality and DALYs from 2022 to 2050.

Results

EAPC analysis revealed a decline in CVD mortality rates, with a decrease of −0.32% for males (95% CI: −0.39 to −0.24%) and −0.42% for females (95% CI: −0.48 to −0.36%), indicating reduced mortality from non-optimal temperatures. Regions with higher Socio-Demographic Index showed more significant declines. ARIMA forecasts predict a substantial increase in CVD burden with deaths projected to rise from 1.2 million in 2022 to 1.9 million by 2050, and DALYs expected to increase from 2.4 million to over 3 million during the same period.

Conclusion

The projected rise in CVD due to temperature variability highlights the need for robust health systems integrated with climate action to mitigate risks. This research underscores the importance of advancing SDG 3.4 to reduce non-communicable disease mortality and emphasizes climate considerations in health planning per SDG 13.
Expanding the genomic diversity of human anelloviruses
Authors: Modha Sejal , Hughes Joseph , Orton Richard J , Lytras Spyros
Published: January 2025

Anelloviruses are a group of small, circular, single-stranded DNA viruses that are found ubiquitously across mammalian hosts. Here, we explored a large number of publicly available human microbiome datasets and retrieved a total of 829 anellovirus genomes, substantially expanding the known diversity of these viruses. The majority of new genomes fall within the three major human anellovirus genera: Alphatorquevirus, Betatorquevirus, and Gammatorquevirus, while we also present new genomes of the under-sampled Hetorquevirus, Memtorquevirus, and Samektorquevirus genera. We performed recombination analysis and show evidence of extensive recombination across all human anelloviruses. Interestingly, more than 95% of the detected events are between members of the same genus and only 15 inter-genus recombination events were detected. The breakpoints of recombination cluster in hotspots at the ends and outside of the ORF1 gene, while a recombination coldspot was detected within the gene. Our analysis suggests that anellovirus evolution is governed by homologous recombination; however, events between distant viruses or ones producing chimaeric ORF1s likely lead to nonviable recombinants. The large number of genomes further allowed us to examine how essential genomic features vary across anelloviruses. These include functional domains in the ORF1 protein and the nucleotide motif of the replication loop region, required for the viruses’ rolling-circle replication. A subset of the genomes assembled in both this and previous studies are completely lacking these essential elements, opening up the possibility that anellovirus intracellular populations contain nonstandard viral genomes. However, low-read depth of the metagenomically assembled contigs may partly explain the lack of some features. Overall, our study highlights key features of anellovirus genomics and evolution, a largely understudied group of viruses whose potential in virus-based therapeutics is recently being explored.
The C3/C3aR pathway exacerbates acetaminophen‐induced mouse liver injury via upregulating podoplanin on the macrophage
Authors: Xie Zhanli , Jiang Jiang , Yang Fei , Han Jingjing , Ma Zhenni , Wen Tao , Bai Xia
Published: January 2025

Acute liver failure (ALF) is a life‐threatening condition that occurs when the liver sustains severe damage and rapidly loses its function. The primary cause of ALF is the overdose of acetaminophen (APAP), and its treatment is relatively limited. The involvement of the complement system in the development of ALF has been implicated. However, the related mechanisms remain poorly understood. Complement 3 (C3) knockout mice, complement 3a receptor (C3aR) knockout mice, platelet C‐type lectin‐like receptor 2 (Clec‐2)–deficient mice, and myeloid cell podoplanin (Pdpn)‐deficient mice were generated. Liver tissues were collected for histological analysis, RNA sequencing, confocal immunofluorescence, and immunoblot analyses. Our data demonstrated that APAP activated the C3/C3aR pathway, leading to intrahepatic hemorrhage, ultimately resulting in hepatocyte necrosis. Deletion of C3 or C3aR mitigated APAP‐induced liver injury (AILI). C3/C3aR signaling upregulated the expression and phosphorylation of transcription factors STAT3 and c‐Fos in hepatic Kupffer cells, which in turn increased PDPN expression, promoting platelet recruitment to the Kupffer cells via the interaction of PDPN and the CLEC‐2 on platelets. Since the activation of platelets mediated by C3/C3aR occurs irrespective of the major hemostatic pathways, blocking the C3/C3aR pathway in ALF could be a coagulopathy‐sparing and novel therapeutic approach. In summary, this study unveiled the critical roles of the C3/C3aR pathway in developing AILI, providing evidence that the C3/C3aR pathway could be an effective therapeutic target for AILI.
WISP1 inhibition of YAP phosphorylation drives breast cancer growth and chemoresistance via TEAD4 activation
Authors: Dong Tingting , Liu Li , You Yikai , Liu Jin , Wang Fuchao , Li Shimeng , Yu Zhenghong
Published: January 2025

Wnt1-inducible signaling pathway protein 1 (WISP1) promotes breast cancer. The Hippo signaling pathway demonstrates a potential connection with WISP1, necessitating an exploration of their interaction. This study hypothesized that WISP1 boosts breast cancer by modulating the Hippo signaling pathway. The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to analyze WISP1 expression and Hippo signaling in breast cancer patients. WISP1, yes-associated protein (YAP), and domain family member 4 (TEAD4) were overexpressed or silenced in breast cancer cells. Epithelial–mesenchymal transition (EMT), and chemoresistance of breast cancer cells were evaluated. Immunofluorescence, PCR, immunoprecipitation, and western blot were used to detect the expression of WISP1 and key Hippo signaling factors and their interactions. Enrichment analysis indicated activation of WISP1 and Hippo signaling pathway and correlated with a worse prognosis in breast cancer. WISP1 overexpression facilitated EMT and chemotherapy resistance in breast cancer. Importantly, overexpression of WISP1 promoted YAP’s nuclear translocation. TEAD4 expression in YAP precipitates from nuclear of WISP1-overexpressing MCF-7 cells increased. The promoting effect of WISP1 on breast cancer was counteracted by silencing YAP or TEAD4. Moreover, in WISP1 small interfering RNA-transfected MCF-7 cells, p-YAP expression increased, while interaction between YAP and TEAD4 decreased. WISP1 silencing led to ubiquitin increase and TEAD reduction in the p-YAP precipitates. In conclusion, WISP1 promotes YAP nuclear translocation and binding with TEAD4 by inhibiting YAP phosphorylation, reducing ubiquitin recruitment, and participating in transcriptional regulation in breast cancer.
The rectal microbiome: understanding its role in HIV transmission
Authors: Català-Moll Francesc , Paredes Roger
Published: January 2025

Purpose of review

Condomless receptive anal intercourse stands out as the sexual practice with highest risk of HIV-1 infection. Recent studies have suggested that the gut microbiome influences susceptibility to HIV transmission. This review explores recent research on host risk factors, the rectal microbiome composition, local inflammation, and bacteria-derived mediators that may affect HIV transmission.

Recent findings

Constitutive host factors such as rectal mucosal structure and immune cell populations in the rectum contribute to increased susceptibility. Changes in the composition of the rectal microbiota, influenced by sexual practices and HIV infection modulate immune activation and inflammation, impacting HIV susceptibility. Bacteria-derived mediators may further influence immune responses and HIV replication in the rectal mucosa.

Understanding the role of the rectal microbiome in HIV transmission has important clinical implications. Targeted interventions that modulate the microbiome may reduce susceptibility to HIV transmission by regulating immune responses and inflammation. Further research into the host–microbiome interactions could lead to novel preventive and therapeutic strategies to mitigate HIV transmission.
Emerging role of natural killer cells in non-AIDS comorbidities during suppressive antiretroviral therapy
Authors: Alles Mario , Demberg Thorsten , Liyanage Namal P.M.
Published: January 2025

Purpose of review

Despite decades of insights about the role of natural killer (NK) cells in HIV infection, their persistent dysregulation despite antiretroviral therapy (ART) and its pathological consequences have been incompletely delineated. In this review, we highlight recent findings on the immunophenotypic and functional alterations of NK cells during virally suppressed HIV infection and explore their potential impact on promoting non-AIDS related comorbidities among people living with HIV (PLWH).

Recent findings

Of note are the apparent persistent activated profiles of NK cells and pathophysiological events such as endoplasmic reticulum (ER) stress in potentially driving NK cell derived inflammation and tissue destruction. Additionally, recent interest in trained immunity is discussed as a potential mediator of ongoing NK cell dysregulation, contributing to comorbidities such as cardiovascular disease and neurocognitive disorders, both with an inflammatory etiology.

Clinical and mechanistic evidence suggests persistent activation and dysregulation of the innate immune system are major drivers of non-AIDS comorbidities during virally suppressed HIV infection. Delineating the mechanistic role of specific components of innate immunity such as NK cells in inducing these pathologies will lead to the identification of novel therapeutic/prophylactic strategies to improve the overall health of PLWH.
Trauma history and persistent poor objective and subjective sleep quality among midlife women
Authors: Jakubowski Karen , Riedmann Carly A. , Chang Yuefang , Koenen Karestan C. , Maki Pauline M. , Thurston Rebecca C.
Published: January 2025

Objectives

Whereas some work links trauma exposure to poor subjective sleep quality, studies largely rely upon limited trauma measures and self-reported sleep at one time point. It is unknown whether trauma is related to persistent poor sleep, whether associations differ based on childhood versus adulthood trauma, and whether trauma exposure is related to poorer objectively assessed sleep. We tested whether childhood or adult trauma associated with persistent poor objectively and subjectively measured sleep at two time points in midlife women.

Methods

One hundred sixty-seven women aged 40-60 at baseline were assessed twice 5 years apart. At baseline, women reported childhood trauma (Child Trauma Questionnaire), adult trauma (Brief Trauma Questionnaire), demographics, depressive symptoms, apnea symptoms, and medical history, and provided physical measures. At both visits, women completed 3 days of actigraphy (total sleep time [TST], wake after sleep onset [WASO]) and reported sleep quality (Pittsburgh Sleep Quality Index). Relations of childhood and adult trauma exposure, respectively, with persistent poor sleep at both baseline and follow-up visits (TST [<6 hours], WASO [>30 minutes], Pittsburgh Sleep Quality Index [>5]) were assessed in logistic regression models, adjusted for age, race/ethnicity, education, body mass index, sleep medications, nightshift work, apnea, depressive symptoms, vasomotor symptoms, and alcohol use.

Results

Childhood trauma was related to persistent high WASO (odds ratio [95% confidence interval] = 2.16 [1.04-4.50], P = 0.039, multivariable). Adult trauma was related to persistent poor sleep quality (odds ratio [95% confidence interval] = 2.29 [1.07-4.93], P = 0.034, multivariable). Trauma was unrelated to persistent short TST.

Conclusions

Childhood and adult trauma, respectively, were related to persistent poor objective sleep continuity and subjective sleep quality in midlife women, independent of risk factors.
CD63-high macrophage-derived exosomal miR-6876-5p promotes hepatocellular carcinoma stemness via PTEN/Akt-mediated EMT pathway
Authors: Zhang Shuairan , Liu Shiqi , Dong Hang , Jin Xiuli , Sun Jing , Sun Ji , Wu Gang , Li Yiling
Published: January 2025

Objective:

Accumulating evidence suggests that microRNAs derived from macrophage exosomes can regulate the stemness and progression of cancer. However, the interaction mechanisms between HCC cells and tumor-associated macrophages remain unclear.

Methods:

Exosomes were extracted from control or CD63 overexpression macrophages and co-cultured with HCC cells. The stemness, proliferation, epithelial-mesenchymal transition, and in vivo tumorigenicity of HCC cells were assessed to determine the role of CD63-high macrophage-derived exosomal miR-6876-5p in HCC. The binding relationship between miR-6876-5p and the PTEN/Akt axis was also investigated.

Results:

Elevated CD63 expression was associated with increased tumor-associated macrophage infiltration and poorer prognosis in HCC. CD63-high macrophage-derived exosomes enhanced HCC cell proliferation, stemness, and epithelial-mesenchymal transition. miR-6876-5p within these exosomes was identified as a key mediator, promoting HCC progression by targeting PTEN and activating the Akt signaling pathway. In vivo studies confirmed that CD63-high macrophage-derived exosomal miR-6876-5p accelerated tumor growth and enhanced stemness in HCC cells.

Conclusions:

CD63-high macrophage-derived exosomes, particularly those enriched with miR-6876-5p, play a pivotal role in HCC progression by enhancing stemness and promoting epithelial-mesenchymal transition through the PTEN/Akt pathway. Targeting these exosomes and their microRNAs offers a promising therapeutic strategy forHCC.
Acid sphingomyelinase deficiency and Gaucher disease: Underdiagnosed and often treatable causes of hepatomegaly, splenomegaly, and low HDL cholesterol in lean individuals
Authors: Mistry Pramod K. , Cassiman David , Jones Simon A. , Lachmann Robin , Lukina Elena , Prada Carlos E. , Wasserstein Melissa P. , Thurberg Beth L. , Foster Meredith C. , Patel Reema M. , Underhill Lisa H. , Peterschmitt M. Judith
Published: January 2025

Background:

Acid sphingomyelinase deficiency (ASMD) and Gaucher disease type 1 (GD1) are rare inherited sphingolipid disorders with multisystemic manifestations, including liver disease and dyslipidemia. Despite effective treatments, insufficient disease awareness frequently results in diagnostic delays during which irreversible complications occur. We delineated the shared and distinctive features of hepatic, splenic, and lipoprotein phenotypes in ASMD and GD1.

Methods:

We analyzed baseline hepatic, splenic, and lipoprotein phenotypes of untreated adults in pivotal trials of ASMD (ASCEND, N=36) and GD1 (ENGAGE, N=40).

Results:

The mean cohort ages were 34.8 years in ASMD and 31.8 years in GD1. Most patients had normal or low body mass index. Moderate hepatosplenomegaly (mean volume in multiples of normal) was common in both cohorts (hepatomegaly 1.53±0.42 and 1.40±0.32, respectively; splenomegaly 11.45±4.36 and 13.20±5.91, respectively). Liver function tests were mildly elevated in ASMD but normal in GD1. In both disorders, mean HDL cholesterol (mg/dL) was profoundly low (22.23±9.14 ASMD; 26.25±8.08 GD1) and correlated inversely with liver volume (r=−0.45 ASMD, p=0.005; r=−0.50 GD1, p=0.001) and spleen volume (r=−0.60 ASMD, p=0.0001; r=−0.63 GD1, p<0.0001). Mean LDL cholesterol (mg/dL) was elevated in ASMD (145.86±49.80) but low in GD1 (68.85±22.53). HDL cholesterol correlated inversely with serum concentrations of lyso-sphingomyelin in ASMD (r=−0.48, p=0.003) and glucosylsphingosine in GD1 (r=−0.63, p<0.0001).

Conclusions:

ASMD and GD1 should be considered in differential diagnosis of patients with unexplained liver and lipid abnormalities, especially young, lean adults with very low HDL and hepatosplenomegaly. HDL emerged as a potential biomarker of disease activity in these sphingolipid disorders.
Increased MASH-associated liver cancer in younger demographics
Authors: Danpanichkul Pojsakorn , Pang Yanfang , Suparan Kanokphong , Auttapracha Thanida , Sirimangklanurak Supapitch , Attia Abdelrahman M. , Thimphitthaya Chanattha , Ni Law Michelle Shi , Yu Zhenning , Soliman Mostafa A. , Polpichai Natchaya , Kanitthamniyom Chanakarn , Kim Donghee , Noureddin Mazen , Singal Amit G. , Wijarnpreecha Karn , Yang Ju Dong
Published: January 2025

Background:

The incidence of cancer and the prevalence of metabolic disease and metabolic dysfunction–associated steatotic liver disease is increasing in young adults. However, updated global data on metabolic dysfunction–associated steatohepatitis (MASH)-associated primary liver cancer (PLC) in young adults remains scarce.

Methods:

This study analyzed data from the Global Burden of Disease study between 2000 and 2021 to assess the age-standardized incidence, mortality, and disability-adjusted life years rates from MASH-associated PLC in young adults (15–49 y).

Results:

In 2021, there were 4300 incidence cases, 3550 deaths, and 179,340 disability-adjusted life years from MASH-associated PLC in young adults. Among various etiologies of PLC in young adults, only MASH-associated PLC had increased incidence rates (annual percent change: +0.26, 95% CI: 0.16%–0.35%), with the Eastern Mediterranean region having the largest observed increase (annual percent change: 1.46%, 95% CI: 1.40%–1.51%). In 2021, MASH-associated PLC in young adults made up 6% (+1% from 2000) incident cases, 6% (+2% from 2000) deaths, and 6% (+2% from 2000) disability-adjusted life years of all PLC in this age group. Over half of the countries exhibited an increase in age-standardized incidence rate from MASH-associated PLC in young adults from 2000 to 2021.

Conclusions:

The incidence of MASH-associated PLC in young adults is significantly increasing, signaling likely future increases in PLC incidence among older adults as this cohort ages. This trend necessitates urgent strategies worldwide to mitigate the epidemics of MASH-associated PLC in young adults.
The immunological landscape of primary biliary cholangitis: Mechanisms and therapeutic prospects
Authors: Ronca Vincenzo , Davies Scott P. , Oo Ye Htun , Lleo Ana
Published: January 2025

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by the progressive destruction of intrahepatic bile ducts, leading to fibrosis, and potentially cirrhosis. PBC has been considered a prototypical autoimmune condition, given the presence of specific autoantibodies and the immune response against well-defined mitochondrial autoantigens. Further evidence supports the interaction of immunogenetic and environmental factors in the etiology of PBC. An immunological attack on biliary epithelial cells with secondary failure of biliary transporters, eg, the anion exchange protein 2, is traditionally considered the primum movens. A recent hypothesis proposes a primary failure of biliary epithelial cells with the downregulation of anion exchange protein 2 secondary to epigenetic mechanisms (miR-506 overexpression), which then triggers the immunological storm. This highlights the secretory defect as the culprit and sustaining factor in the pathogenesis of PBC with ursodeoxycholic acid helping to restore this protective mechanism by promoting bicarbonate secretion and reducing bile acid toxicity. In this review, we aim to provide the most recent evidence on the immunopathogenesis of PBC. We will analyze the immune function of the biliary epithelium, assessing the immunomodulatory functions of the bile acids and the evidence of the immunological roles of the secretory pathways targeted by the current treatments.
Health-related Quality of Life in Children and Adolescents After Successful Treatment of Chronic Hepatitis C With Sofosbuvir/Velpatasvir: One-year Outcomes
Authors: Pokorska-Śpiewak Maria , Dobrzeniecka Anna , Talarek Ewa , Aniszewska Małgorzata , Pluta Magdalena , Marczyńska Magdalena , Indolfi Giuseppe
Published: January 2025

Background and aims:

The aim of this study was to assess the health-related quality of life (HRQL) of children with chronic hepatitis C (CHC) at 1 year after the effective treatment with sofosbuvir/velpatasvir (SOF/VEL).

Methods:

All 50 patients treated for CHC with a fixed dose SOF/VEL in the noncommercial, nonrandomized, open-label PANDAA-PED study achieved sustained virologic response at 12 weeks after the end of treatment. Evaluation of HRQL at 1-year posttreatment was compared with the baseline (before the treatment) assessment. KIDSCREEN-27 questionnaires, which included 5 dimensions of HRQL, for child self-reporting and parent proxy reporting were used. The normal range for the population was set to T values of 40–60 points. Child–parent agreement was analyzed using the intraclass correlation coefficient (ICC).

Results:

Mean T values were within the normal range for all HRQL dimensions. A significant improvement in “autonomy & parent relation” in children’s self-assessment (from 48.3 to 51.5, P = 0.03) was observed. In parent proxy assessment, a significant decrease occurred in “school” dimension (from 49.5 to 45.8, P = 0.03), which was not revealed at 3-month posttreatment. Older age was associated with worse HRQL scores in all dimensions. Evaluation of the ICC for child self-reports versus parent proxy reports revealed poor-to-moderate agreement for most single measures, lower than at 3-month posttreatment analysis.

Conclusions:

This is the first study to present the long-term influence of treatment with direct-acting antivirals on patient-reported outcomes in children. At 1 year after effective treatment with SOF/VEL, an improvement in some areas of children’s well-being was revealed, which may indicate also some patient-reported outcomes benefits of direct-acting antiviral therapy. Despite the improvement in the child self-report of “autonomy & parent relation,” there was a more pronounced discrepancy between children self-reports and parents proxy reports in all dimensions of HRQL. Older patients’ age correlated with worse HRQL assessment. If this finding is mediated by the duration of hepatitis C virus infection, it would support recommendation for the treatment of younger children.
Plasma Microbial Cell-Free DNA Sequencing for Diagnosis of Pediatric Lyme Disease
Authors: Handel Andrew S. , Ahmed Asim A. , Venkatasubrahmanyam Shivkumar , Bercovici Sivan , Mao Qing , Ho Carine , Hollemon Desiree D. , Beneri Christy
Published: January 2025

We conducted an exploratory study of plasma microbial cell-free DNA sequencing for the diagnosis of Lyme disease among pediatric patients. Low levels of Borrelia burgdorferi microbial cell-free DNA (<3–5 molecules per microliter) were observed in 6/9 serologically confirmed participants, including 4/5 with arthritis and 2/3 with multiple erythema migrans.
ACTIVE POST-MARKETING SAFETY SURVEILLANCE OF NIRSEVIMAB ADMINISTERED TO CHILDREN IN WESTERN AUSTRALIA, APRIL–JULY 2024
Authors: Carcione Dale , Spencer Phoebe , Pettigrew Grace , Leeb Alan , Drake-Brockman Carla , Ford Timothy , Effler Paul
Published: January 2025

Children receiving nirsevimab were texted a link to an online survey to monitor adverse events following immunization. Total of 4340 parents received the link, which 1195 (27.5%) responded. Forty-seven (11.4%) of 410 children who received nirsevimab alone and 230 (29.3%) of 785 children who received nirsevimab coadministered reported any reaction. No adverse events required in-patient care or had ongoing sequelae.
Surgical treatment of congenital pseudarthrosis of the tibia in children: CPAM-LRC consensus and guidelines
Authors: Song Wenqi , Zhou Runhua , Liu Pei , Guo Yanjie , Shao Lei , Liu Delin , Xu Jia , Wu Tianyi , Bai Zhong , Su Chi , Liu Fuyun , Liu Jun , Kang Qinglin , Lu Shengdi
Published: January 2025

Purpose:

Congenital pseudarthrosis of the tibia (CPT) is a rare condition typically manifesting within the first decade of life. The primary objectives of surgical intervention for CPT include achieving long-term bony union of the tibia, preventing or minimizing limb length discrepancies (LLD), avoiding mechanical axis deviations of the tibia and adjacent joints, and preventing refracture. This study aims to conduct a systematic review of current treatment methods for CPT to determine the most effective non-surgical and surgical management strategies for pediatric patients with this condition.

Methods:

A review of the literature was performed according to the PRISMA guidelines. A comprehensive search of PubMed, Medline, CINAHL, Cochrane, Embase, and Google Scholar databases was performed over the years 1989 to 2024. Randomized controlled trials, cohort studies and case-control studies on the surgical treatments of CPT in children were included. Random-effects models were used to estimate the pooled primary union rate, primary union time and refracture rate. Then a consensus statement of surgical treatment of CPT in children was achieved based on Delphi methodology which included 2 rounds of electronic questionnaires and 1 round of virtual consensus meeting.

Results:

Seventy-four studies were included, 23 of which on intramedullary rods (IMR) involving 364 patients, 15 on Ilizarov methods with 230 patients, and 23 studies combining IMR with Ilizarov involving 458 patients. The pooled primary union rate for IMR, Ilizarov method, and Ilizarov combined with IMR was 69% (95% CI: 0.55–0.82), 89% (95% CI: 0.77–0.98) and 85% (95% CI: 0.74–0.94), respectively. The pooled primary union time for IMR, Ilizarov method, and Ilizarov combined with IMR was 8.95 months (95% CI: 6.53–11.37), 7.14 months (95% CI: 5.53–8.74), and 5.62 months (95% CI: 4.89–6.35), respectively. The pooled refracture rate among primary unions for IMR, Ilizarov method, and Ilizarov combined with IMR was 85% (95% CI: 0.60–1.00), 81% (95% CI: 0.56–0.98), and 60% (95% CI: 0.26–0.90), respectively. After 2 rounds of electronic questionnaires and 1 round of virtual consensus meeting, a consensus statement and guidelines of surgical treatment of CPT in children was provided.

Conclusion:

The CPAM-LRC consensus panel provided recommendations to improve management of pediatric patients with CPT in clinical practice. Combined techniques for pediatric patients after fracture or the formation of pseudarthrosis commonly include excision of the pseudarthrosis site, external fixation, intramedullary fixation, and autogenous bone grafting. Vascularized fibular graft and cross-union can be considered a viable alternative to corticocancellous autograft. Use of recombinant bone morphogenic protein (rhBMP) is not currently conclusive.
Artificial Intelligence Predicts Multiclass Molecular Signatures and Subtypes Directly From Breast Cancer Histology: a Multicenter Retrospective Study
Authors: Zhang Xiangyang , Chen Yang , Cai Changjing , Wang Yifeng , Tan Jun , Fang Zijie , Wei Le , Shao Zhuchen , Wang Liwen , Qi Tiezheng , Liu Yihan , Jiang Zhaohui , Li Yin , Han Ying , Rugambwa Tibera Kagemulo , Zeng Shan , Wang Haoqian , Shen Hong , Zhang Yongbing
Published: January 2025

Detection of biomarkers of breast cancer incurs additional costs and tissue burden. We propose a deep learning-based algorithm (BBMIL) to predict classical biomarkers, immunotherapy-associated gene signatures, and prognosis-associated subtypes directly from hematoxylin and eosin stained histopathology images. BBMIL showed the best performance among comparative algorithms on the prediction of classical biomarkers, immunotherapy related gene signatures, and subtypes.
Changes in Self-Directed Learning Among Doctor of Physical Therapy Students Across Didactic Curriculum: A Mixed-Methods Analysis
Authors: Getz Emily N. , Langerwerf Leigh , Young Jodi L. , Bliss Rebecca
Published: January 2025

Introduction.

Physical therapy education best practice includes the development of adaptive lifelong learners because of a constantly changing health care landscape. The purpose of this study was to identify how self-directed learning (SDL) changes in traditional Doctor of Physical Therapy (DPT) students over the course of the didactic curriculum.

Review of literature.

The Master Adaptive Learning (MAL) framework has been proposed as a framework that physical therapy educators adopt to create and educate physical therapists who embrace continuous change and build a culture of creativity and innovation.

Subjects.

Fifty students from a midwestern DPT program participated in the quantitative portion, and 14 participated in the qualitative portion of the study.

Methods.

A mixed-methods approach was used to assess students’ SDL using the Motivated Strategies of Learning Questionnaire (MSLQ) and the Short Grit scale across the 3-year curriculum. Focus group interviews were conducted following quantitative data collection to develop themes and determine relationships of these themes with existing learning paradigms.

Results.

There was a statistically significant decrease in students' MSLQ scores from the students’ first semester to third and sixth semesters. In the sixth and eighth semester, scores stabilized or had limited improvement. Grit scores remained consistent. Themes that emerged from focus group interviews included deep learning, habits of the heart, and vulnerability. Multiple subthemes were also found that overlap with the MAL framework.

Discussion and Conclusion.

This study provides preliminary data to understand DPT students’ SDL journey in a traditional DPT program and highlights the need for continued research and efforts toward improving SDL strategies in DPT students. Providing students with necessary resources and support to transition to more self-directed behaviors aligns with the recent call to action to infuse the MAL framework into the PT educational continuum.
A Collaborative Model for Pediatric Clinical Education: From Design to Implementation
Authors: Ardolino Elizabeth M. , Flores Megan B , Sawyer Kathryn
Published: January 2025

Background and Purpose.

Collaborative clinical education models where 2 or more students are supervised by one clinical instructor in a clinical setting effectively support student learning and self-confidence. Use of collaborative models in specialized clinical education settings has not been widely adopted. This paper explores using Kern's 6-step approach to develop and implement a collaborative clinical education model.

Method/Model Description and Evaluation.

The process began with a general needs assessment focused on the scarcity of clinical placements in specialized fields, culminating with a decision to pilot a collaborative clinical education model. In step 2, a targeted needs assessment identified a specific pediatric clinic in which to implement the model. During steps 3 and 4, the faculty and clinical partner developed overarching goals and educational strategies for the clinical education experience. Step 5 focused on implementation, including securing institutional support, preparing students, and addressing logistical challenges. The final step of the model was assessment through review of objective data.

Outcomes.

All overarching goals and objectives of the program were met. Evaluation using interviews with students, clinical instructors, and patient caregivers indicated high satisfaction and achievement of clinical competence.

Discussion and Conclusions.

The collaborative model successfully met educational requirements and improved patient outcomes. This paper underscores the necessity of innovative clinical education strategies to meet growing demands and suggests that such models can effectively prepare students for specialized practice areas. This approach demonstrates the feasibility and value of using a framework to implement a clinical education model.
Prevalence of locomotive syndrome and associated factors in patients receiving hemodialysis
Authors: Hirota Keisuke , Matsuse Hiroo , Hashida Ryuki , Fukushima Masato , Imai Teturo , Baba Eriko , Tagima Hiroshi , Hazama Takuma , Fukami Kei , Hiraoka Koji
Published: January 2025

Muscle strength and joint and nervous system functions decline with age and in patients undergoing hemodialysis. The Japanese Orthopaedic Association has defined locomotive syndrome (LoS) as a musculoskeletal disorder primarily caused by aging. Therefore, this study aimed to investigate the prevalence of LoS and identify factors associated with its development in patients undergoing hemodialysis. Patients receiving outpatient hemodialysis at Kurume University Hospital were categorized into LoS and non-LoS groups using the cutoff value of 25-question Geriatric Locomotive Function Scale (GLFS-25). We analyzed differences in malnutrition, biochemical examinations, and Kt/V (a measure of dialysis adequacy) between the 2 groups using Wilcoxon rank-sum tests. Additionally, we evaluated factors that correlated with GLFS-25 through pairwise correlations. Multivariate analysis was performed to determine the independent factors associated with LoS. Nineteen patients were included. The median GLFS-25 score was 18. The LoS group (n = 11) had a significantly higher age (P = .0056) and chloride levels than the non-LoS group (n = 8) (P = .0175). Furthermore, the Nutritional Risk Index for Japanese Hemodialysis patients, creatinine levels, and Kt/V were significantly lower in the LoS group than in the non-LoS group (P = .0156, .0026, and .0163, respectively). The GLFS-25 showed significant correlations with age, total protein levels, C-reactive protein, chloride, creatinine, Nutritional Risk Index for Japanese Hemodialysis patients, and Kt/V (with correlation coefficients of −0.6133, −0.4779, 0.4738, 0.5381, −0.7923, 0.6508, and 0.5747, respectively). Multivariate analysis identified life-space assessment (odds ratio [OR], 3.06; 95% confidence interval [CI], −676 to 674; P < .0001) and age (OR, 31.29; 95% CI, −2061 to 2067; P = .0007) as risk factors for LoS. Age and physical activity were found to be associated with the development of LoS in patients with end-stage renal disease undergoing outpatient hemodialysis at our hospital. This emphasizes the importance of implementing preventative measures for LoS, especially for older and less physically active patients.