bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perseverance of Optimal Realignment is Associated With Improved Cost-utility in Adult Cervical Deformity Surgery
Authors: Passias Peter G. , Williamson Tyler K , Lebovic Jordan , Eck Andrew , Schoenfeld Andrew J , Bennett-Caso Claudia , Owusu-Sarpong Stephane , Koller Heiko , Tan Lee , Eastlack Robert , Buell Thomas , Lafage Renaud , Lafage Virginie 
Published: January 2025

Background:
Early-term complications may not predict long-term success after adult cervical deformity (ACD) correction.

Objective:
Evaluate whether optimal realignment results in similar rates of perioperative complications but achieves longer-term cost-utility.

Study Design:
Retrospective cohort study.

Methods:
ACD patients with 2-year data included. Outcomes: distal junctional failure (DJF), good clinical outcome (GCO):[Meeting 2 of 3: (1) NDI>20 or meeting MCID, (2) mJOA≥14, (3)NRS-Neck improved≥2]. Ideal Outcome defined as GCO without DJF or reoperation. Patient groups were stratified by correction to ‘Optimal radiographic outcome’, defined by cSVA 9 (<40 mm) AND TS-CL (<15 deg) upon correction. Cost calculated by CMS.com definitions, and cost-per-QALY was calculated by converting NDI to SF-6D. Multivariable analysis controlling for age, baseline T1-slope, cSVA, disability, and frailty, was used to assess complication rates, clinical outcomes, and cost-utility based on meeting optimal radiographic outcome.

Results:
One hundred forty-six patients included: 52 optimal radiographic realignment (O) and 94 not optimal (NO). NO group presented with higher cSVA and T1-slope. Adjusted analysis showed O group suffered similar 90-day complications (P>0.8), but less DJK, DJF (0% vs. 18%; P<0.001) and reoperations (18% vs. 35%; P=0.02). Patients meeting optimal radiographic criteria more often met Ideal outcome [odds ratio: 2.2, (1.1–4.8); P=0.03]. Despite no differences in overall cost, O group saw greater clinical improvement, translating to a better cost-utility [mean difference: $91,000, ($49,000–$132,000); P<0.001].

Conclusion:
Despite similar perioperative courses, patients optimally realigned experienced less junctional failure, leading to better cost-utility compared with those sub-optimally realigned. Perioperative complication risk should not necessarily preclude optimal surgical intervention, and policy efforts might better focus on long-term outcome measures in adult cervical deformity surgery.

Level of Evidence:
Level III.
Innate lymphoid cells in HIV pathogenesis and in the human female genital tract
Authors: Werner Alexandra , Holmes Aleah , Moldovan Genna , Rodriguez-Garcia Marta 
Published: January 2025

Purpose of review
Women are underrepresented in HIV infection and prevention research despite making up half of people living with HIV. The female genital tract (FGT) serves as a primary site of HIV acquisition, but gaps in knowledge remain regarding protective innate immune mechanisms. Innate lymphoid cells are tissue-resident cells involved in mucosal barrier maintenance and protection, and innate lymphoid cells (ILCs) are altered during chronic HIV infection. However, ILCs role in mucosal HIV pathogenesis is unclear and they are poorly characterized in the FGT.

Recent findings
Human ILCs differ from their mouse counterparts and plastically adjust to their tissue of residency. Human ILC characterization is difficult due to tissue-specific adaptations and transition between subsets. While evidence for ILC involvement in antiviral activity and barrier maintenance is provided in mouse models, human ILC role in mucosal immunity remain understudied, particularly in the FGT. In chronic HIV/simian immunodeficiency virus (SIV) infection, ILCs are altered in a tissue-specific manner, and SIV models indicate potential for antiviral responses.

Summary
ILCs are tissue-resident plastic cells that provide barrier protection at mucosal surfaces and display antiviral capacity. Considering that HIV is primarily transmitted through mucosal exposure, more research is needed to understand ILC contribution to HIV pathogenesis in human mucosal surfaces relevant for HIV acquisition.
Elephant in the room: natural killer cells don’t forget HIV either
Authors: Jost Stephanie , Reeves R. Keith 
Published: January 2025

Purpose of review
Like elephants (and T cells), accumulating evidence suggest natural killer (NK) cells never forget. The description of adaptive or memory NK cells, which can be induced by HIV/SIV infections and vaccines and associated with protective effects in persons with HIV (PWH), has dramatically increased the interest in leveraging NK cells to prevent HIV infection or suppress HIV reservoirs. However, harnessing their full antiviral potential has been hindered by an incomplete understanding of mechanisms underlying adaptive NK cell development and infected cell recognition. Herein, we outline the main discoveries around the adaptive functions of NK cells, with a focus on their involvement in HIV infection.

Recent findings
NK cells with diverse adaptive capabilities, including antigen-specific memory, cytokine-induced and CMV-driven adaptive subsets, likely all play a role in HIV infection. Importantly, true antigen-specific memory NK cells have been identified that mediate recall responses against multiple infectious agents such as HIV, influenza, and SARS-CoV-2. The NKG2C receptor is pivotal for certain adaptive NK cell subsets, as it marks a population with enhanced antibody-dependent functions and has been described as the main receptor mediating antigen-specific responses via recognition of viral peptides presented by HLA-E.

Summary
Antiviral functions of adaptive/memory NK cells have tremendous, but as of yet, untapped potential to be harnessed for vaccine design, curative, or other therapeutic interventions against HIV.
Gafchromic Films as a Complementary In-field Dosimetric Tool to Monitor Low Photon Radiation Doses (≤50 mSv)
Authors: Nivi Nicky , Moise Helen , Pejović-Milić Ana 
Published: January 2025

Abstract
This study elucidated the radiation response characteristics of a Gafchromic radiochromic film subjected to low photon doses of ≤50 mSv, which corresponds to the annual whole body effective dose limit for radiation workers in Canada. Radiochromic films are investigated for possible use as a complementary tool for the Canadian Armed Forces that can be worn in addition to their existing personal dosimetry to quickly assess personal radiation dose received from radiological hazards without reliance on electronics. The films were exposed to varying photon energies emanating from x-ray generators and radioisotopes, specifically cesium-137, cobalt-60, and americium-241. The resultant radiation-induced film darkening was quantitatively assessed employing three analytical methodologies: net optical density analysis, UV/Visible spectroscopic analysis, and Fourier Transform Infrared spectroscopic analysis. Ideally, a film dosimeter necessitates a pronounced chromatic alteration and the capability to accurately quantify doses ≤50 mSv where net optical density analysis was identified as the optimal modality for interpreting the film darkening into a dose approximation. This new approach established a lower detection threshold of 7.6 mSv for the films when exposed to cesium-137 radiation. Notably, the film exhibited a linear dose response relationship in terms of net optical density; however, a photon energy-dependent variability was observed within the 0–100 mSv dose range. In conclusion, these Gafchromic radiochromic films present a promising candidate for military dosimetry applications. They offer a real-time, visual dose response that can be discerned by military personnel or analyzed using mobile spectroscopic instrumentation. Moreover, these films demonstrate proficiency in the accurate quantification of photon doses ≤50 mSv. Future investigations will evaluate the film's performance under heterogeneous and indeterminate radiation environments, as well as the impact of environmental conditions on the film’s performance.
Identification of target gene–microribonucleic acid–transcription factor regulatory networks in colorectal adenoma-carcinoma sequence
Authors: Li Junxing , Yan Xinmei , Jiao Huyu , Chen Jingjing , Lin Yi , Zhou Minghui , Jin Fuchang , Xu Qiuxian , Zhang Zhengang 
Published: January 2025

Abstract

Background
Many studies have examined the role of genes, proteins, and microribonucleic acids (miRNAs) in colorectal cancer (CRC). However, these studies did not establish the regulatory relationships among multi-omics, and only a few have investigated the key genes involved in the transition from colorectal adenoma to CRC. In this study, we established regulatory networks of target gene–miRNA–transcription factors (TFs) to elucidate the pathogenesis of CRC.

Methods
Data from 70 patients with CRC were obtained from the Gene Expression Omnibus database. Bioinformatics analyses were used to identify the hub genes involved in the colorectal adenoma-carcinoma sequence. We conducted prognostic evaluations, analyzed gene co-expression patterns, assessed immune cell infiltration, and performed Mendelian randomization. A gene-miRNA-TF network was constructed and further analyzed.

Results
Periostin (POSTN), thrombospondin 2 (THBS2), collagen alpha-2 type I (COL1A2), and other molecules were found to interact and play key roles in the colorectal adenoma-carcinoma sequence. The 3 genes–11 miRNAs–6 TFs regulatory network we constructed was involved in this process through various pathways and interactions with immune cells. Several molecules in this network affected the final prognosis of patients with CRC. THBS2 showed a causal genetic relationship with neutrophils (p = 0.035, odds ratio = 1.020 [95% confidence interval = 1.001–1.039]). Therefore, bleomycin and other drugs may potentially improve the prognosis of patients with CRC.

Conclusion
The 3 genes–11 miRNAs–6 TFs regulatory network may provide valuable insights into the pathogenesis of CRC. Additionally, some of these molecules may affect patient prognosis, serving as biomarkers or therapeutic targets. THBS2 may promote neutrophil infiltration into CRC tissues by increasing neutrophil levels in the blood.
The Impact of the COVID-19 Pandemic on Medical-Legal Partnership Services and Cases
Authors: Ramos Athena K. , Sanchez Roman Maria Jose , Soto Prado Priscila , Schmeits Karen , Rodabaugh Kerry 
Published: January 2025

Context:
Medical-legal partnerships (MLPs) are innovative, promising models that integrate legal service providers and medical professionals to prevent, detect, and address legal, social, and economic needs arising from social inequities that may negatively impact health. The COVID-19 pandemic impacted health care systems across the United States. MLP workflows and legal services were also interrupted by COVID-19 infection prevention and control measures such as no-visitor policies, social distancing, and the cancellation of non-emergent or routine health care services.

Objective:
We sought to describe the impact of COVID-19 on legal services provided by an MLP by exploring case types and services provided prior to the COVID-19 pandemic and during the pandemic.

Design:
This is an examination of MLP services provided at a Midwestern academic medical center comparing data from three years prior to the pandemic (2017-2019) to three years during the pandemic (2020-2022).

Setting:
The MLP is a collaboration between the University of Nebraska Medical Center/Nebraska Medicine (an academic medical center) and Legal Aid of Nebraska and Iowa Legal Aid (legal service providers).

Participants:
Case data was drawn from individuals who were MLP patient-clients between 2017 and 2022.

Main Outcome Measures:
The main outcome measures were the number of cases and categories and types of legal services provided by the MLP.

Results:
Consistent across time, we found that on average 494 cases were closed each year. Consumer/finance cases decreased significantly from pre-COVID-19 to during the pandemic, while family cases increased significantly during the pandemic. Cases related to income maintenance increased across time.

Conclusions:
Through the COVID-19 pandemic experience and understanding the case mix, MLPs and health care champions can be better prepared to understand some of the challenges that may occur and changes that may be necessary to better serve patient-clients during a public health emergency.
Regulation of Phosphatidylinositol-(4,5)-bisphosphate and Active-Rho1p Levels and Distribution is Crucial for Correct Spatio-temporal Cytokinesis and Echinocandin Responses inCandida albicans
Authors: Badrane Hassan , Nguyen M. Hong , Clancy Cornelius J. 
Published: January 2025

ABSTRACTCandidaspecies cause severe infections like invasive candidiasis, which annually affect 1.5 million people worldwide and cause close to 1 million deaths.Candida albicansis the predominant cause of candidiasis. We previously showed that EH domain-containing protein Irs4p binds 5-phosphatase enzyme Inp51p to regulate plasma membrane levels of phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2) inC. albicans. Indeed, deletion ofIRS4orINP51led to elevated levels of PI(4,5)P2and presence of abnormal intracellular membranous PI(4,5)P2patches. We demonstrated an interplay between PI(4,5)P2and septins to regulate the PKC-Mkc1 cell wall integrity pathway, echinocandin and cell wall stress responses, and virulence during candidiasis. In the current investigation, we used fluorescent protein tagging and live cell imaging to follow the nascency of PI(4,5)P2patches. We show that these abnormal patches tightly correlate with cytokinesis, as they predominantly arise close to the site and time of cell division. We further demonstrate these patches colocalize PI(4,5)P2with actomyosin ring components Act1p and Myo1p, which form its core, and active Rho1p, a small GTPase that plays a regulatory role. Additionally, activation of Rho1p was altered inirs4andinp51mutants compared to wild-type strain, with over-activation or down-activation during early exponential or stationary phase, respectively. Wild-type cells exposed to 4xMIC of the echinocandin caspofungin show abnormal PI(4,5)P2patches colocalizing the same cytokinesis components as above, except that they were transient. Taken together, our results support a model in which PI(4,5)P2plays a pivotal role, along with Rho1p, in the correct execution of cytokinesis and response to caspofungin.
Stable isotope probing of carbonyl sulfide and cyanate pathways in microbial thiocyanate biodegradation
Authors: Ling Yu-Chen , Watts Mathew P. , Moreau John W. 
Published: January 2025

AbstractThiocyanate (SCN−) is toxic to many aquatic organisms at elevated concentrations. Historically, large amounts of SCN−were released to the environment by gold mining and coal coking. Microbial SCN−degradation provides a cost-effective approach to remediation; however, knowledge is still limited about the relative roles of the two known enzymatic SCN−biodegradation pathways. Here we applied stable carbon and nitrogen isotope probing of SCN−-degrading microbial cultures to assess quantitatively the relative contributions of the cyanate (OCN−) and carbonyl sulfide (COS) pathways over a 24-hour experiment. In contrast to common assumptions, our results demonstrate that the OCN−pathway initiatesbeforethe COS pathway and can contribute up to 70% of early SCN−biodegradation. These results yield new insights into the dynamics of SCN−biodegradation, and also show that microorganisms can incorporate carbon and nitrogen from the SCN−into biomass, resolving the question of nitrogen mass balance. Our study holds implications for improving bioreactor design for SCN−bioremediation and for understanding the dynamics for sulfur, carbon and nitrogen flows from SCN−in natural environments into their respective biogeochemical cycles.ImportanceWhile the process of SCN−biodegradation has been well studied, relative contributions from the two known enzymatic pathways are still poorly resolved, hindering our ability to optimize bioremediation systems treating SCN−-contaminated wastewater. Also, as SCN−biodegradation in nature impacts the biogeochemical cycling of sulfur (as well as carbon and nitrogen), a more quantitative understanding of enzymatic SCN−biodegradation pathways will yield insights into how the reactivity of this environmentally ubiquitous compound influences marine, terrestrial and atmospheric sulfur chemistry. Here we used carbon and nitrogen stable isotope probing to assess contributions to SCN−biodegradation from known enzymatic pathways in a microbial consortium grown from SCN−-contaminated mine tailings. We found that the cyanate pathway dominates SCN−biodegradation initially, before activation of the carbonyl sulfide pathway. We attribute this ordering to the greater amount of bioenergy conservable via the cyanate pathway during the earliest stages of bioremediation.
ENTAgents: AI Agents for Complex Knowledge Otolaryngology
Authors: Chan Tsz Kin , Dinh Ngoc-Duy 
Published: January 2025

AbstractVarious healthcare applications based on large language models (LLMs) have emerged as LLMs show improved efficiency and error reduction. Recently, retrieval augmented generation (RAG) has been adopted frequently for LLM applications to solve the problem of hallucinations. Despite the success of RAG, it has its drawbacks, including incomplete semantic meanings, and large-scale dataset requirements. AI Agents have shown great potential in medicine and healthcare applications by leveraging their rich background knowledge and reasoning capabilities. In this paper, we introduce ENTAgents, a framework that utilizes both the RAG and multi-agent systems. To achieve better decision-making and enhanced explainability, we use the verbal reinforcement learning framework, Reflexion, as a reference for the task planning of ENTAgents. With the verbal feedback received from the last agent node, the agentic system can decide the best agent to utilize to improve the response of ENTAgents. We tested ENTAgents with various types of questions, including short questions, essay questions, and multiple-choice questions. ENTAgents improve accuracy by over 11.3% in handling short questions, with 2.78 folds in the length of the text and explaining clearly. ENTAgents shows higher accuracy and is more comprehensive in its answer compared to other LLM models. ENTAgents also demonstrates its ability to refine its answer with additional information to make it more thorough and educational. It also presents the capability to change its response to the correct answer in multiple-choice questions according to its self-reflection. Overall, ENTAgents is easy to use, can self-correct, and can provide detailed information in complex knowledge to users. We look forward to integrating ENTAgents into various healthcare scenarios, such as medical education and clinical decision support, particularly otolaryngology.
Role of Inflammation in the Pathogenesis of Anemia in Chronic Kidney Disease: Exploring the Impact of Inflammatory Biomarkers on Erythropoiesis and Erythropoietin Response
Authors: Ogolla Collince Odiwuor , Karani Lucy W. , Musyoki Stanslaus 
Published: January 2025

AbstractBackgroundAnemia is one of the very common complications in Chronic Kidney Disease (CKD) and often included among patients who undergo hemodialysis. A very important aspect of anemia is that erythropoietin (EPO) resistance plays a very major role, whereas the role of inflammation to EPO resistance and impaired erythropoiesis is still poorly understood.ObjectiveThe objective of this study research therefore was to measure the effects of inflammation assessed by C-reactive protein (CRP) on anemia and in response to EPO in CKD patients undergoing hemodialysis here.MethodsThis is a cross-sectional study involving 120 CKD patients undergoing maintenance hemodialysis. Based on their CRP levels, participants were divided into two groups: High Inflammation (CRP ≥ 10 mg/L) and Low Inflammation (CRP < 10 mg/L). The hematological parameters such as hematocrit, serum ferritin, transferrin saturation, and EPO dose are evaluated. Statistical Analysis: Group comparisons and correlation analysis to study the relationships between CRP levels, iron status, and EPO resistance.ResultsIn the high inflammation group, hematocrit levels (29.6 ± 4.8%) were significantly lower than in the low inflammation group in a comparison of (34.2 ± 5.2%, p < 0.001). The EPO dose was higher in the high inflammation group (3,200 ± 800 IU/week vs. 2,200 ± 700 IU/week, p < 0.001). Different parameters regarding iron, like serum ferritin and transferrin saturation, were significantly lesser in the high inflammation group. CRP levels had a negative correlation with hematocrit (r = -0.42, p < 0.001) and transferrin saturation (r = -0.36, p < 0.001), while they were found to have a positive correlation with the EPO dose administered (r = 0.48, p < 0.001).ConclusionsInflammation as measured by CRP has an important effect on anemia management in CKD patients undergoing hemodialysis.
Abnormal T-Cell Activation And Cytotoxic T-Cell Frequency Discriminates Symptom Severity In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Authors: Lee Ji-Sook , Lacerda Eliana , Kingdon Caroline , Susannini Giada , Dockrell Hazel M , Nacul Luis , Cliff Jacqueline M 
Published: January 2025

AbstractMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating but poorly-understood disease. ME/CFS symptoms can range from mild to severe, and include immune system effects alongside incapacitating fatigue and post-exertional disease exacerbation. In this study, we examined immunological profiles of people living with ME/CFS by flow cytometry, focusing on cytotoxic cells, to determine whether people with mild/moderate (n= 43) or severe ME/CFS (n=53) expressed different immunological markers. We found that people with mild/moderate ME/CFS had increased expression of cytotoxic effector molecules alongside enhanced proportions of early-immunosenescence cells, determined by the CD28-CD57-phenotype, indicative of persistent viral infection. In contrast, people with severe ME/CFS had higher proportions of activated circulating lymphocytes, determined by CD69+and CD38+expression, and expressed more pro-inflammatory cytokines, including IFNγ, TNF and IL-17, following stimulationin vitro, indicative of prolonged non-specific inflammation. These changes were consistent across different cell types including CD8+T cells, mucosal associated invariant T cells and Natural Killer cells, indicating generalised altered cytotoxic responses across the innate and adaptive immune system. These immunological differences likely reflect different disease pathogenesis mechanisms occurring in the two clinical groups, opening up opportunities for the development of prognostic markers and stratified treatments.Graphical Abstract