bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimicrobial resistance detection methods in water environments: a scoping review
Authors: Alfahl Zina , Chueiri Alexandra , Carolan Shaunagh , Darcy Gabriel , Hussain Nadia , Cahill Niamh , O’Connor Louise 
Published: November 2024

Abstract
Antimicrobial resistance (AMR) in water environments poses a significant threat to public health, ecosystem stability, and the effectiveness of antimicrobial treatments. This review aims to provide a comprehensive overview of the methods used to detect AMR in various water environments. A literature search was conducted following the PRISMA guidelines. Original articles published in English relating to AMR in water environments were included. Reviews, protocols, and abstracts were excluded. A total of 115 publications were selected for full-text evaluation. Overall, river water samples were the most commonly assessed samples across all of the reviewed studies (49/115 studies, 42%). The top 3 countries investigating AMR genes in water samples were the USA (19 studies, 17%), China (11 studies, 10%), and Brazil (10 studies, 9%). The review revealed that polymerase chain reaction and metagenomic methods are increasingly preferred for their high sensitivity, specificity, and comprehensive detection capabilities, appearing in 65/115 (57%) and 31/115 (27%) studies, respectively. Despite higher costs and technical complexity, these methods provide valuable insights into the resistome of water environments. Culture-dependent methods, while most cost effective and straightforward, are limited by their time-consuming nature and inability to detect non-viable resistant organisms, reducing their effectiveness in comprehensive AMR surveillance. The review addresses the challenges and limitations of current detection methods and proposes directions for future research to develop more robust, cost-effective, and user-friendly detection methods. The review highlights the urgent need for integrated approaches to monitor and mitigate AMR in water environments, ensuring better public health and environmental protection.
Diacylglycerol kinase δ is required for skeletal muscle development and regeneration
Authors: Sakai Hiromichi , Murakami Chiaki , Takechi Mayumi , Urano Takeshi , Sakane Fumio 
Published: November 2024

AbstractDiacylglycerol kinase δ (DGKδ) phosphorylates diacylglycerol to produce phosphatidic acid. Previously, we demonstrated that down‐regulation of DGKδ suppresses the myogenic differentiation of C2C12 myoblasts. However, the myogenic roles of DGKδ in vivo remain unclear. In the present study, we generated DGKδ‐conditional knockout mice under the control of the myogenic factor 5 (Myf5) gene promoter, which regulates myogenesis and brown adipogenesis. The knockout mice showed a significant body weight reduction and apparent mass decrease in skeletal muscle, including the tibialis anterior (TA) muscle. Moreover, the thickness of a portion of the myofibers was reduced in DGKδ‐deficient TA muscles. However, DGKδ deficiency did not substantially affect brown adipogenesis, suggesting that Myf5‐driven DGKδ deficiency mainly affects muscle development. Notably, skeletal muscle injury induced by a cardiotoxin highly up‐regulated DGKδ protein expression, and the DGKδ deficiency significantly reduced the thickness of myofibers, the expression levels of myogenic differentiation markers such as embryonic myosin heavy chain and myogenin, and the number of newly formed myofibers containing multiple central nuclei during muscle regeneration. DGKδ was strongly expressed in myogenin‐positive satellite cells around the injured myofibers and centronucleated myofibers. These results indicate that DGKδ has important roles in muscle regeneration in activated satellite cells. Moreover, the conditional knockout mice fed with a high‐fat diet showed increased fat mass and glucose intolerance. Taken together, these results demonstrate that DGKδ plays crucial roles in skeletal muscle development, regeneration, and function.
The advent of immune checkpoint inhibition for the treatment of patients with primary advanced or recurrent dMMR/MSI high endometrial cancer in 2025
Authors: Silk Tarik , Hacker Kari E. , Growdon Whitfield , Pothuri Bhavana 
Published: November 2024

Purpose of review
The Cancer Genome Atlas identified four distinct molecular subtypes of endometrial cancer (EC): POLE mutated, mismatch repair deficient (dMMR), copy number low, and copy number high. The goal of this review is to summarize the profound clinical implications of molecular subtyping, particularly in guiding treatment decisions for dMMR and microsatellite instability high (MSI-H) EC.

Recent findings
Clinical trials have demonstrated the remarkable efficacy of immunotherapy in dMMR/MSI-H EC tumors. Trials including GARNET, KEYNOTE-158, NRG GY-018, and RUBY have shown significant improvements in clinical outcomes for patients with advanced and recurrent disease, leading to FDA approvals for immunotherapy in both frontline and recurrent EC treatment settings.
Building on these successes, recent studies, including DUO-E, are exploring combination therapies to enhance the efficacy of immunotherapy in EC. Simultaneously, trials including NRG GY-020, are investigating the potential benefits of immunotherapy in early-stage disease.

Summary
Immunotherapy therapy has revolutionized the treatment of endometrial cancer in both upfront and recurrent settings, with molecular subtyping identifying patients most likely to benefit, especially those with dMMR/MSI-H tumors.
Quantitative assessment of the associations between ABCA1 gene polymorphism and glaucoma risk, evidence from a meta-analysis
Authors: Wang Fabin , Gou Xin , Wu Fan , Qiao Hong , Zhao Dengli 
Published: November 2024

Background:
The association between polymorphisms in the ATP-binding cassette transporter A1 (ABCA1) gene and the risk of developing glaucoma has yielded conflicting results across various studies. This meta-analysis aims to comprehensively assess whether genetic variations in ABCA1 significantly contribute to the susceptibility to glaucoma.

Methods:
An extensive search was conducted across major databases, including PubMed, EMBASE, and the China National Knowledge Infrastructure (CNKI), covering all publications from the inception of each database through December 2023. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to quantify the strength of the association between ABCA1 polymorphisms and glaucoma risk.

Results:
A significant association was observed between ABCA1 gene polymorphisms and glaucoma risk in the overall analysis, as demonstrated by allele contrast (P < .001), homozygote comparison (P < .001), heterozygote comparison (P < .001), recessive genetic model (P = .017), and dominant genetic model (P < .001). Notably, these associations were particularly pronounced in the Asian population, with all models showing statistical significance (P < .05). However, no significant association was detected in Caucasian or mixed populations, suggesting a potential ethnic specificity in the genetic susceptibility to glaucoma conferred by ABCA1 polymorphisms.

Conclusions:
Our findings indicate that ABCA1 polymorphisms may play a role in increasing the risk of glaucoma, specifically within Asian populations. This contrast highlights the importance of considering ethnic background in genetic association studies.
Two case reports of breast cancer combined with synchronous primary intrahepatic cholangiocarcinoma/mixed liver cancer
Authors: Tan Miduo , Luo Liu , Wang Taoli , Zhang Zhiyong , Wei Yuqin , Long Chenyan 
Published: November 2024

Rationale:
This case report discusses multiple primary malignant tumors, which refer to the occurrence of 2 or more different histological types of malignant tumors simultaneously or successively in the same individual.

Patient concerns:
We present 2 female patients who were admitted to the hospital due to a “left breast mass” and were found to have multiple solid masses in the liver upon imaging.

Diagnoses:
Postoperative pathology revealed that one patient had breast invasive ductal carcinoma was complicated with primary intrahepatic cholangiocarcinoma and mixed hepatocellular carcinoma with intrahepatic cholangiocarcinoma.

Interventions:
Both patients underwent extensive resection of the lesion.

Outcomes:
Regular postoperative checkups and follow-ups have been conducted, and both patient’s current conditions are stable.

Lessons:
The treatment approach adopted in this case report may serve as a favorable reference for the management of similar cases. However, further extensive biological studies are still needed to investigate the biological mechanisms of multiple primary malignant tumors and to discover specific therapeutic approaches to achieve more clinical benefits for patients.
A comprehensive review of biomarker research in diabetic nephropathy from a global bibliometric and visualization perspective
Authors: Li Qin , Xie Yafei , Zuo Meiying , Li Fang 
Published: November 2024

Background:Diabetic nephropathy (DN) is a common complication of diabetes, which is prone to develop into end-stage renal disease, and early diagnosis and treatment is the key to effective management of DN. Biomarkers have important clinical significance in the diagnosis and treatment of DN and have attracted extensive attention from researchers in recent years. The aim of this study was to visualize the field of biomarker research in DN through bibliometric analysis, to summarize the current status and predict future trends of this field, with a view to providing valuable insights for scholars and policy makers.Methods:Literature search and data collection from Web of Science Core Collection. Calculations and visualizations were performed using Microsoft Excel, VOSviewer, Bibliometrix R-package, and CiteSpace.Results:We identified 1274 publications about biomarker research in DN from 1995 to November 01, 2023, with a steady increase in annual publications. China, Steno Diabetes Center in Denmark, andFrontiers in Endocrinologywere the most productive country, institution, and journal, respectively; Mischak, Harald was both the most productive and highly cited author, andKidney Internationalwas the most cited journal. The high frequency keywords were “albuminuria,” “chronic kidney disease” and “expression.” In addition, “macrophage,” “fibrosis” and “omics” are potentially promising topics.Conclusion:Our study comprehensively and visually summarized the important findings of global biomarker research in DN and revealed the structure, hotspots, and evolutionary trends in this field. It would inspire subsequent studies from a macroscopic perspective and provide a basis for rational allocation of resources and identification of collaborations among researchers.
Functional variability of Nef in antagonizing SERINC5 during acute to chronic HIV-1 infection
Authors: Li Weiting , Li Guoqing , Liu Yuyang , Meng Lina , Zhang Tianxin , Wang Libian , Li Haochen , Yu Bin , Wu Jiaxin , Wang Chu , Yu Xianghui 
Published: November 2024

Objective:
The ability of HIV-1 Nef to counteract the host restriction factor SERINC5 and enhance virion infectivity has been well established. However, the impact of long-term within-host Nef evolution on this antagonistic capability remains unclear.

Design:
Analysis of longitudinal activity of Nef in antagonizing SERINC5.

Methods:
We investigated the downregulation activity of Nef against SERINC5 at different stages of infection by analyzing the cognate transmitted/founder, set point, and/or chronic Nef isolates from a cohort of 19 people with either subtype B or C HIV-1.

Results:
The Nef isolates from different stages exhibited varying abilities to antagonize SERINC5. Long-term evolution resulted in mutations accumulated in Nef and a decline of Nef-mediated SERINC5 downregulation function in subtype B, but not in subtype C viruses, leading to a rapid reduction in viral load from peak viremia. Furthermore, we identified four polymorphisms of both subtype B and C Nef that are associated with variations in the SERINC5 antagonistic function and viral infectivity. HIV-1NL4–3 variants encoding Nef E63G, A83G, R105K, or D108E mutants exhibited reduced replication capacity through a SERINC5-dependent mechanism. However, among different subjects, only a small part of naturally occurring mutations at these sites were selected by host T-cell responses, suggesting a limited impact of host T-cell responses on influencing Nef's ability to antagonize SERINC5.

Conclusion:
These results highlight the potential contribution of functional variation in Nef to differences in HIV-1 pathogenesis and provide significant implications for understanding the evolutionary interaction between Nef and SERINC5 in vivo.
Cognitive functions supporting learning over time in naming treatment for aphasia
Authors: Goldberg Emily B. , Hula William D. , Cavanaugh Robert , Swiderski Alexander M. , Autenreith Alyssa , Dickey Michael Walsh 
Published: November 2024

AbstractPurposeAphasia rehabilitation is a learning process that unfolds over time. Previous work has examined aphasia treatment response using pre- to post-treatment comparison, largely ignoring the unfolding learning response that occurs session-to-session. We aimed to: (1) characterize the shape of learning while individuals with aphasia received intensive anomia intervention, and (2) identify the cognitive predictors of this learning response.MethodIndividuals (n=39) with chronic post-stroke aphasia received intensive semantic feature analysis (SFA). Naming accuracy for trained and semantically-related, untrained words was probed daily. We used Bayesian generalized linear mixed effects models to estimate the shape of learning during SFA treatment, and to measure the influence of key cognitive functions on treatment response.ResultsMost treatment gains appeared early during treatment, after the first four hours of intervention. Verbal recognition and visuospatial memory were associated with the magnitude of those early treatment gains, favoring strong cognitive performers. Treatment generalization to untrained targets was present but modest, with some evidence suggesting that visuospatial recall performance may be associated with treatment generalization.ConclusionsMonitoring SFA treatment response early could help inform clinicians whether patients will respond optimally to intervention. Verbal recognition and visuospatial recall support learning during treatment, helping elucidate cognitive underpinnings of learning during aphasia rehabilitation.
Synergistic Multi-Pronged Interactions Mediate the Effective Inhibition of Alpha-Synuclein Aggregation by the Chaperone HtrA1
Authors: Chinchilla Priscilla , Wang Baifan , Lubin Joseph H. , Yang Xue , Roth Jonathan , Khare Sagar D. , Baum Jean 
Published: November 2024

AbstractThe misfolding, aggregation, and the seeded spread of alpha synuclein (α-Syn) aggregates are linked to the pathogenesis of various neurodegenerative diseases, including Parkinson’s disease (PD). Understanding the mechanisms by which chaperone proteins prevent the production and seeding of α-Syn aggregates is crucial for developing effective therapeutic leads for tackling neurodegenerative diseases. We show that a catalytically inactive variant of the chaperone HtrA1 (HtrA1*) effectively inhibits both α-Syn monomer aggregation and templated fibril seeding, and demonstrate that this inhibition is mediated by synergistic interactions between its PDZ and Protease domains and α-Syn. Using biomolecular NMR, AFM and Rosetta-based computational analyses, we propose that the PDZ domain interacts with the C-terminal end of the monomer and the intrinsically disordered C-terminal domain of the α-Syn fibril. Furthermore, in agreement with sequence specificity calculations, the Protease domain cleaves in the aggregation-prone NAC domain at site T92/A93 in the monomer. Thus, through multi-pronged interactions and multi-site recognition of α-Syn, HtrA1* can effectively intervene at different stages along the α-Syn aggregation pathway, making it a robust inhibitor of α-Syn aggregation and templated seeding. Our studies illustrate, at high resolution, the crucial role of HtrA1 interactions with both the intrinsically disordered α-Syn monomers and with the dynamic flanking regions around the fibril core for inhibition of aggregation. This inhibition mechanism of the HtrA1 chaperone may provide a natural mechanistic blueprint for highly effective therapeutic agents against protein aggregation.Significance StatementPD and other synucleinopathies are marked by misfolding and aggregation of α-Syn, forming higher-order species that propagate aggregation in a prion-like manner. Understanding how chaperone proteins inhibit α-Syn aggregation and spread is essential for therapeutic development against neurodegeneration. Through an integrative approach of solution-based NMR, AFM, aggregation kinetics, and computational analysis, we reveal how a catalytically inactive variant of the chaperone HtrA1 effectively disrupts aggregation pathways. We find that the inactive Protease and PDZ domains of HtrA1 synergistically bind to key intrinsically disordered sites on both α-Syn monomers and fibrils, thereby effectively inhibiting both aggregation and templated seeding. Our work provides a natural and unique blueprint for designing inhibitors to prevent the formation and seeding of aggregates in neurodegenerative diseases.
Effects of Uni- and Bi-directional Interaction During Dyadic Ankle and Wrist Tracking
Authors: Short Matthew R. , Ludvig Daniel , Di Tommaso Francesco , Vianello Lorenzo , Perreault Eric J. , Küçüktabak Emek Barış , Hargrove Levi , Lynch Kevin , Burdet Etienne , Pons Jose L. 
Published: November 2024

AbstractHaptic human-robot-human interaction allows users to feel and respond to one another’s forces while interfacing with separate robotic devices, providing customizable infrastructure for studying physical interaction during motor tasks (i.e., physical rehabilitation). For both upper- and lower-limb tasks, previous work has shown that virtual interactions with a partner can improve motor performance and enhance individual learning. However, whether the mechanism of these improvements generalizes across different human systems is an open question. In this work, we investigate the effects of haptic interaction between healthy individuals during a trajectory tracking task involving single-joint movements at the wrist and ankle. We compare tracking performance and muscle activation during haptic conditions where pairs of participants were uni- and bidirectionally connected, in order to investigate the contribution of real-time responses from a partner during the interaction. Findings indicate similar improvements in tracking performance during the bidirectional interaction for both the wrist and ankle, despite significant differences in how individuals modulated co-contraction. For each joint, bidirectional and unidirectional interaction resulted in similar improvements for the worse partner in the dyad. For the better partner, bidirectional interaction outperformed unidirectional interaction, likely due to changes in movement planning that were not observed in the unidirectional condition. While these results suggest that unidirectional interaction is sufficient for error correction of less skilled individuals during simple motor tasks, they also highlight the mutual benefits of bidirectional interaction which are consistent across the upper and lower limbs.
An annotated biobank of triple negative breast cancer patient-derived xenografts featuring treatment-naïve and longitudinal samples throughout neoadjuvant chemotherapy
Authors: Rinkenbaugh Amanda L. , Qi Yuan , Cai Shirong , Shao Jiansu , Hancock Faiza , Jeter-Jones Sabrina , Zhang Xiaomei , Powell Emily , Huo Lei , Lau Rosanna , Fu Chunxiao , Gould Rebekah , den Hollander Petra , Ravenberg Elizabeth E. , White Jason B. , Rauch Gaiane M. , Arun Banu , Yam Clinton , Thompson Alastair M. , Echeverria Gloria V. , Moulder Stacy L. , Symmans W. Fraser , Chang Jeffrey T. , Piwnica-Worms Helen 
Published: November 2024

SUMMARYTriple negative breast cancer (TNBC) that fails to respond to neoadjuvant chemotherapy (NACT) can be lethal. Developing effective strategies to eradicate chemoresistant disease requires experimental models that recapitulate the heterogeneity characteristic of TNBC. To that end, we established a biobank of 92 orthotopic patient-derived xenograft (PDX) models of TNBC from the tumors of 75 patients enrolled in the ARTEMIS clinical trial (NCT02276443) at MD Anderson Cancer Center, including 12 longitudinal sets generated from serial patient biopsies collected throughout NACT and from metastatic disease. Models were established from both chemosensitive and chemoresistant tumors, and nearly 30% of PDX models were capable of lung metastasis. Comprehensive molecular profiling demonstrated conservation of genomes and transcriptomes between patient and corresponding PDX tumors, with representation of all major transcriptional subtypes. Transcriptional changes observed in the longitudinal PDX models highlight dysregulation in pathways associated with DNA integrity, extracellular matrix interactions, the ubiquitin-proteasome system, epigenetics, and inflammatory signaling. These alterations reveal a complex network of adaptations associated with chemoresistance. This PDX biobank provides a valuable resource for tackling the most pressing issues facing the clinical management of TNBC, namely chemoresistance and metastasis.
Cell competition confers anchorage plasticity of disseminated tumor cells
Authors: Huh Hyunbin D. , Sub Yujin , Kim Jee Hung , Lee Hannah , Oh Jongwook , Lee Dong Ki , Byun Jong Hwa , Pyun Woo Yang , Pak Sehyung , Choi Junjeong , Jeong Joon , Gee Heon Yung , Park Hyun Woo 
Published: November 2024

AbstractCell competition within the primary tumor drives tumor growth by promoting the uncontrolled proliferation of winner cells and eliminating loser cells by sensing cell fitness. However, the mechanism how cell competition confers loser cells with the metastatic potential of circulating tumor cells (CTCs) remains elusive. Unexpectedly, we found cell competition-induced less fit but viable cells transformed into CTCs via adherent-to-suspension transition (AST) mechanisms in dissemination assay. The induction of AST factors, hematopoietic transcription factors hijacked by solid tumor cells, rendered CTCs competent to lose anchorage dependency and disseminate into the bloodstream, while subsequent suppression of these factors in CTCs was critical to regain adhesion and colonize metastatic lesions. Disrupting the oscillatory dynamics of AST factors blocked the adherent-suspension plasticity (ASP) of breast cancer CTCs and suppressed lung metastasis. Furthermore, multiregional single-cell transcriptomic analyses of matched primary tumors, CTCs, and metastatic lesions fromde novometastatic breast cancer patients identified the critical role of ASP in metastasis.SignificanceWe demonstrate that cell competition-mediated displacement of CTCs manifests dynamic oscillation of AST factors that confer anchorage plasticity of solid tumor cells critical for the dissemination and colonization of CTCs. These findings highlight the potential of targeting AST factors to develop effective anti-metastatic therapies.