bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating resistance of potato cultivars and breeding clones to golden cyst nematode Globodera rostochiensis in China
Authors: Jiang Ru , Wang Pengjun , Zhang Zhengyu , Liang Shumin , Li Yanshan , Yao Chunguang , Huang Wenkun , Hu Xianqi , Peng Deliang , Li Yinmei , Liu Xia , Peng Huan
Published: January 2025

The golden cyst nematode, Globodera rostochiensis, is a regulatory pathogen that can significantly reduce potato yields and hinder the international trade of potatoes. Unfortunately, this nematode has been reported in southwestern China. Nevertheless, limited information exists on the resistance levels of Chinese potato germplasm, especially primary commercial cultivars, to G. rostochiensis in southwestern China. This study evaluated the resistance of 35 potato cultivars currently grown in the southwest and northern China, along with 132 novel breeding clones, to G. rostochiensis. Our result showed that 8 cultivars and 35 clones were identified as carrying the H1 resistance gene using two established molecular markers, 57R and TG689, including the prominent cultivars ‘Atlantic’ and ‘Jizhangshu 12’, which rank among the top five in terms of cultivated area in China. Furthermore, two cultivars, ‘Yunshu 202’ and ‘Zhongshu 20’, along with 13 clones, demonstrated high resistance to G. rostochiensis, with no cysts detected in the rhizosphere soil through bioassays. The resistant cultivar ‘Yunshu 202’ stimulated G. rostochiensis hatching, yet the invading J2s failed to progress into the female stage. The results highlight the potential for developing resistant cultivars to reduce potato cyst nematode population densities for future research endeavors. This study identified resistant cultivars for immediate integration into China's comprehensive potato cyst nematode management strategy, while also facilitating the screening of breeding clones for resistance to G. rostochiensis.
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.

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.

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.
Sotatercept: A New Era in Pulmonary Arterial Hypertension
Authors: Anand Suneesh C. , Furqan Muhammad , Tonelli Adriano R. , Brady Daniela , Levine Avi , Rosenzweig Erika B. , Frishman William H. , Aronow Wilbert S. , Lanier Gregg M.
Published: January 2025

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by proliferative remodeling and obliterative narrowing of the pulmonary vasculature. While outcomes have improved with existing treatments targeting 3 main pathways, there remains a critical need for novel therapies that address different and novel mechanisms of PAH. Sotatercept, recently Food and Drug Administration (FDA) approved, is a groundbreaking fusion protein that binds to activin and growth differentiation factors, rebalancing antiproliferative and pro-proliferative signals to reverse remodeling in both the pulmonary vasculature and the right ventricle. This review highlights current evidence exploring the safety and efficacy of sotatercept in the 2 landmark trials, phase 2 Pulmonary Arterial Hypertension and Sotatercept Trial and Research and phase 3 Sotatercept Treatment in Expansion of Long-term Learning and Assessment in PAH trial, which were instrumental in securing FDA approval for adult PAH patients with WHO functional class II or III symptoms already receiving background pulmonary hypertension therapy. Overall, sotatercept represents a landmark advancement in PAH treatment, offering hope for patients and the potential to delay or avoid lung transplantation. Importantly, this marks the beginning of an era of targeted therapies aimed at reverse remodeling in PAH while improving outcomes.
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

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.
Physical activities, sedentary behavior, sleep quality, and quality of life among female medical versus nonmedical college students: A cross-sectional study
Authors: Alghamdi Abdulrhman S. , AlOyyna Nawal N. , Alhusaini Adel A.
Published: January 2025

Despite the numerous health benefits of physical activity (PA), sedentary behavior (SB) and physical inactivity remain major public health concerns. A lack of PA increases the chance of developing some noncommunicable diseases that are on the rise worldwide. Therefore, this study aimed to evaluate the level of PA, SB, sleep quality (SQ), and quality of life (QOL) among Saudi female college students. A cross-sectional study was carried out among female students enrolled in various colleges, both medical and nonmedical, at King Saud University in Riyadh during the academic year 2018 to 2019. Participation posters were sent to colleges’ departments, and survey links were shared through university social media channels. The study utilized the International Physical Activity Questionnaire and the Pittsburgh Sleep Quality Index to evaluate PA and SQ and the World Health Organization Quality of Life Assessment Instrument to evaluate QOL. In order to conduct statistical analyses, frequency counts, means, and standard deviations were calculated for PA, SQ, and QOL scores. In this study, 131 Saudi female college students were conveniently recruited from 223 who met the inclusion criteria, with a mean age of 20.4 ± 1.4. Most participants were from medical colleges (n = 86, 6, 5.6%) and the minority were nonmedical (n = 45, 34.4%). We have found that International Physical Activity Questionnaire indicated that most students had low PA (52% of the participants), about 35% had a moderate PA, and only 17% had high PA. SB was present among 22.9% of participants. Nearly 68.7% of the students scored poorly on the Pittsburgh Sleep Quality Index for SQ. The students had high QOL, with a mean WHOQOL-BREF total score of 90.76 ± 12.77. Medical and nonmedical students showed no significant differences in PA, SB, or QOL. No apparent relationship was found between PA and SQ or QOL. This study shows that a significant proportion of female college students maintain an unfavorable lifestyle characterized by insufficient PA and subpar SQ. Implementing programs that encourage students to be more physically active, reduce sedentary time, and integrate sleep education programs to improve their sleep habits are necessary.
Are YouTube videos on treatments for temporomandibular disorders reliable?: An observational study
Authors: Yüce Polat Mevlüde , Yapici Yavuz Günay , Odabaşi Onur
Published: January 2025

Today, people frequently turn to the internet to seek information about temporomandibular joint disorders and treatments, as in all other health areas. However, does the information presented online without professional evaluation truly reflect the facts, and if so, to what extent? Based on this question, our study aims to evaluate YouTube™ videos on the treatment of temporomandibular joint diseases. In this cross-sectional study, a search was conducted on YouTube using the search term “TMJ (temporomandibular joint) treatment” for YouTube videos. One hundred sixty-three videos that met the study criteria were evaluated for content usefulness by 3 researchers. The videos were categorized as having low and high content according to usefulness score. All videos were classified according to the source and type of the videos. Statistical analysis were conducted using with Chi-Square test and Mann–Whitney U test. It was found that 130 videos had low content, while 33 videos had high content. It was observed that the number of views, duration in minutes, number of comments, number of likes, number of days since uploading and the rate of views were higher in videos with high content (P < .05). However, no significant association was found between the usefulness score and the source that uploaded the video and video type (P > .05). The results of our study reveal that the vast majority of videos on the treatment of temporomandibular diseases on YouTube contain insufficient information.
Efficacy of TiRobot assistance in distal locking for femoral intramedullary nailing
Authors: Peng Yuanxiang , Cai Feng , Liu Luhua , Qu Gaoyang , Wu Pengyun , Xia Sijie , Shen Feng
Published: January 2025

This study compares the efficacy of the TiRobot with traditional external aiming frames in distal locking of femoral intramedullary nails. A cohort of 44 patients, who underwent intramedullary nailing treatment for femoral fractures between October 2020 and October 2023, was retrospectively analyzed. Participants were allocated into 2 groups. The observation group (n = 22) received TiRobot assistance for distal locking of femoral intramedullary nails, and the control group (n = 22) was managed using conventional external aiming frames. Key variables included the first-attempt success rate of distal locking, number of fluoroscopic exposures, time to achieve locking, and volume of intraoperative blood loss. The observation group, assisted by TiRobot, achieved a significantly higher first-attempt success rate of 90.9%, as compared to 54.5% in the control group. All initial failures were subsequently managed manually, with a statistically significant difference noted between the groups (P < .05). Furthermore, the observation group required fewer fluoroscopic exposures (11.00 ± 2.93) than the control group (19.68 ± 16.28) (P < .05). The time to achieve locking was significantly shorter in the observation group (14.05 ± 3.37 min) compared to the control group (24.41 ± 14.93 min) (P < .05). The volume of intraoperative blood loss was reduced in the observation group (54.55 ± 5.54 mL) versus the control group (60.45 ± 11.01 mL) (P < .05). The incorporation of TiRobot in the distal locking of femoral intramedullary nailing prominently enhances the first-attempt success rate, reduces the procedural time and intraoperative blood loss, and diminishes the radiation exposure for both healthcare providers and patients.
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

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.
Telephonic Visits Program to Link Justice-Involved Individuals Diagnosed With HIV in Jail to Community HIV Care
Authors: Agroia Harit , Walsh Kristin , Lopez Iliam , Padilla Rene
Published: January 2025

Correctional facilities serve as a key location to identify and treat those with HIV given high rates of HIV seen in justice-involved individuals; however, substantial barriers exist to accessing HIV care in the community upon release. In response to restricted in-person activities due to COVID-19, the County of Santa Clara (SCC) Jail launched a telephonic visits program in January 2021 to link justice-involved individuals diagnosed with HIV to community HIV care following release. Telephonic visits were conducted by social workers from SCC Public Health Department; these visits entailed conducting an HIV needs assessment, providing education, and offering support services. Following release, individuals were contacted by phone to assist with scheduling appointments, refilling medications, and transportation to clinic appointments. Telephonic visits offered a new opportunity to support HIV linkage to care; connecting with individuals prior to release from jail may mitigate barriers in receiving ongoing HIV care in the community.
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.
Leptospira gorisiae sp. nov, L. cinconiae sp. nov, L. mgodei sp. nov, L. milleri sp. nov and L. iowaensis sp. nov: five new species isolated from water sources in the Midwestern United States
Authors: Hamond Camila , Tibbs-Cortes Bienvenido , Fernandes Luis G. V. , LeCount Karen , Putz Ellie J. , Anderson Tammy , Camp Patrick , Stuber Tod , Hicks Jessica , van der Linden Hans , dos Santos Ribeiro Priscyla , Bayles Darrell O. , Schlater Linda K. , Nally Jarlath E.
Published: January 2025

Isolates of Leptospira spp. were cultured from water sources at five different sites in central Iowa in the Midwestern United States and characterized by whole-genome sequencing. Isolates were helix-shaped and motile. Genome sequence analyses determined that the isolates could be clearly distinguished from other species described in the genus Leptospira and included one species that belonged to the pathogen subclade P1, one species that belonged to the pathogen subclade P2 and three species that belonged to the saprophyte subclade S1. The names Leptospira gorisiae sp. nov. (type strain WS92.C1T=NVSL-WS92.C1T=KIT0303T), Leptospira cinconiae sp. nov. (type strain WS58.C1T=NVSL-WS58.C1T=KIT0304T), Leptospira mgodei sp. nov. (type strain WS4.C2T=NVSL.WS4.C2T=KIT0305T), Leptospira iowaensis sp. nov. (type strain WS39.C2T=NVSL-WS39.C2T=KIT0306T) and Leptospira milleri sp. nov. (type strain WS60.C2T=NVSL-WS60.C2T=KIT0307T) are proposed.
Single molecule imaging of RecBin vivoreveals dynamics of DNA Double Strand Break repair inEscherichia coli
Authors: Thédié Daniel , Lepore Alessia , McLaren Lorna , El Karoui Meriem
Published: January 2025

Repairing DNA damage is of primary importance for all living organisms. DNA double-strand breaks (DSBs) are one of the most serious types of DNA damage, as they lead to loss of genetic information and death when not repaired. InE. coli, they are recognised and processed by the RecBCD complex, which initiates repair by homologous recombination. Although the repair dynamics downstream of RecBCD has been well characterised, it is still unclear how long this complex stays attached to DNA and what triggers its dissociationin vivo. To answer these questions, we imaged RecB at the single-molecule level, and quantified its dynamic behaviour in bacterial cells exposed to ciprofloxacin, an antibiotic that induces DSBs. Our results show that RecB forms long-lived complexes with DSBs (10 seconds), and that its dissociation from DNA is an intrinsic property of the complex, that does not depend on the amount of DNA damage, nor the following steps in the repair pathway. More-over, we show that we can use RecB binding to DSBs as a marker to estimate the rate of damage formation. This study provides a detailed quantitative insight into the interaction of RecBCD with DNA double-strand ends inE. coli in vivo, and into the bacterial response to DSBs induced by ciprofloxacin.
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

Candidaspecies 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

Thiocyanate (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.

Importance

While 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

Various 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

Background

Anemia 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.

Objective

The 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.

Methods

This 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.

Results

In 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).

Conclusions

Inflammation 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

Myalgic 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
Comparative immuno-biology at clinical recognition of early multiple organ dysfunction syndrome in pediatric and adult patients using single-cell transcriptomics
Authors: Shankar Rama , Goodyke Austin W. , Koirala Shubham , Paithankar Shreya , Chen Ruoqiao , Hartog Nicholas L. , Chesla Dave , Rajasekaran Surender , Chen Bin
Published: January 2025

Globally, sepsis remains a major health issue, with Multiple Organ Dysfunction Syndrome (MODS) being a leading cause of mortality. MODS, a severe condition often seen in intensive care units, typically results from infections or trauma and involves complex pathophysiological processes requiring various clinical interventions. Although infections are the main triggers, the mechanisms driving MODS remain unclear. To investigate the transition of sepsis to MODS, we generated a single cell RNA sequencing dataset comprising 86,839 immune cells from pediatric sepsis patients at the clinical onset of MODS patients and age-matched controls, identifying 22 distinct cell types. A cluster ofS100genes, located in the same genomic region, was highly expressed in neutrophils in MODS patients, demonstrating strong diagnostic potential across cohorts (AUC=0.94– 0.99) and potential as therapeutic targets. We found that many B and T cells showed heightened inflammation and increased apoptotic activity during early MODS. Additionally, specific transcription regulators and surface proteins associated with inflammation andS100regulations were uniquely expressed in MODS. Pseudotime analysis revealed distinctS100gene expression patterns between controls and MODS. Cell-cell interaction analysis highlighted dendritic cells as key mediators, enhancing communication between plasma cells and Vδ T cells while activating inflammatory and immunosuppressive pathways. We also analyzed 116,803 immune cells from adult MODS patients, revealing stronger immune dysregulation compared to pediatric MODS, including alteredS100gene expression, and enhanced cell-cell interactions. These findings suggest thatS100genes may serve as a marker for MODS. Furthermore, insights gained from adult MODS could improve our understanding of rare pediatric MODS and contribute to the development of better therapeutics for all MODS patients.
CD38 expression by neonatal human naïve CD4+T cells shapes their distinct metabolic state and high regulatory T cell potential
Authors: Dwyer Laura R. , Clancy Sean , Gouirand Victoire , Chien Charles , Rogers Elizabeth E. , Oltman Scott P. , Jelliffe-Pawlowski Laura L. , Lynch Susan V. , Wagner Allon , Combes Alexis J. , Scharschmidt Tiffany C.
Published: January 2025

Neonatal life is marked by rapid antigen exposure, necessitating establishment of peripheral immune tolerance via conversion of naïve CD4+T cells into regulatory T cells (Tregs). Here, we demonstrate that increased Treg differentiation by naive CD4+T cells from human cord blood versus adult blood is integrally linked to their unique metabolic profile and their elevated expression of the NADase, CD38. Early life naïve CD4+T cells demonstrate a metabolic preference for glycolysis, which directly facilitates their Treg generation. We reveal an age-dependent gradient in CD38 levels on naïve CD4+T cells and show that high CD38 expression contributes to both the glycolytic state and high Treg potential of neonatal CD4+T cells, effects that are mediated at least in part via the NAD-dependent deacetylase SIRT1. Thus, the early life window for peripheral tolerance in humans is critically enabled by the immunometabolic state of the naïve CD4+compartment.
Real-time fMRI neurofeedback reduces default mode network and auditory cortex functional connectivity in schizophrenia
Authors: Zhang Jiahe , Bauer Clemens C.C. , Morfini Francesca , Lee Yoonji , Stone Lena , Awad Angelina , Okano Kana , Hwang Melissa , Shinn Ann K. , Niznikiewicz Margaret A. , Whitfield-Gabrieli Susan
Published: January 2025

Background and Hypothesis

Auditory verbal hallucinations (AHs) are a cardinal symptom of schizophrenia that can cause distress but are not always responsive to antipsychotic medications. There is a critical need to develop novel interventions that target neural mechanisms underlying AHs. We developed a real-time fMRI neurofeedback (NFB) paradigm for AHs that aims at modulating default mode network (DMN) functional connectivity.

Study Design

Patients with schizophrenia or schizoaffective disorders who were experiencing AHs (N= 25) attempted to decrease brain activation while listening to sentences recorded in another person’s voice and increase brain activation while listening to sentences recorded in their own voice. Participants randomly assigned to the ‘real’ group (n= 12) received neurofeedback based on signals from their auditory cortex in the superior temporal gyrus (STG) and those assigned to the ‘sham’ group (n= 13) received neurofeedback based on motor cortex signals.

Study Results

Analyzing resting state fMRI data collected pre- and post-NFB, we found that: (1) at baseline, stronger within-DMN connectivity between the medial prefrontal cortex (MPFC) and posterior cingulate cortex was associated with higher AHs severity; (2) after NFB, participants in the real group, compared to those in the sham group, showed greater reduction in functional connectivity between the MPFC and auditory cortices in the STG and middle temporal gyrus (MTG). Notably, the reduction in MPFC-STG/MTG connectivity was found in all participants in the real group.

Conclusions

These findings suggest that NFB can effectively and non-invasively modulate functional connectivity in regions associated with AHs in psychosis.
Independent regulation of memory and emotion by selective retrieval
Authors: Wang Yingying , Zhu Zijian , Subbulakshmi S. , Li Yao , Fang Fang , Anderson Michael C.
Published: January 2025

Selective retrieval of a target memory often triggers inhibitory control to reduce competition from related traces, a process that induces forgetting of the competing content. It is unknown, however, whether inhibition during selective retrieval specifically targets a competitor’s episodic representation or instead extends to its affective components. Here we report evidence in humans that selective retrieval of a neutral memory not only diminishes access to the mnemonic content of unpleasant competing memories, but also alters their emotional character. Memory and emotion suppression effects were accompanied by reduced neural activation and weakened representational patterns unique to competing memories in the VTC and amygdala respectively, in an independent fashion. Selective retrieval engaged the left VLPFC, which decreased in activity over repeated retrievals of the same memory, as competition from the unpleasant scene was resolved. This left VLPFC region colocalizes with key prefrontal regions engaged during cognitive reappraisal, suggesting that selective retrieval’s impact on affective responses may contribute to reappraisal’s benefits. These findings indicate that inhibitory control during selective retrieval affects both mnemonic and affective representations, providing a novel mechanistic basis for a well-known emotion regulation practice.
Separation measurement of two freely rotating dipole emitters at near optimal precision
Authors: Liu Sheng , Pani Sujeet , Khan Sajjad A. , Becerra Francisco E. , Lidke Keith A.
Published: January 2025

According to Rayleigh’s criterion, two incoherent emitters with a separation below the diffraction limit are not resolvable with a conventional fluorescence microscope. One method of Super-Resolution Microscopy (SRM) breaks the diffraction-limited resolution by precisely estimating the centroid position of spatiotemporally independent emitters. However, conventional detection methods of SRM techniques are not optimal for estimating the separation of two simultaneously excited emitters. Recently, a number of detection methods based on modal imaging were developed to achieve the quantum Cramér-Rao lower bound (QCRB) for estimating separations between two nearby emitters. The QCRB determines the minimum achievable precision across all possible detection methods. Current modal imaging techniques assume a scalar field generated from a point source, such as an optical fiber or a pinhole. However, for fluorescently labeled samples, point emitters are single fluorophores that can be modeled as dipole emitters, and in practice are often freely rotating. Dipole radiation must be expressed in vectorial theory and the assumption of a scalar field no longer holds. Here we propose a detection scheme based on one of the modal imaging techniques, super-localization by image inversion interferometry (SLIVER), for separation estimation of two freely rotating dipoles. We introduce a vortex wave plate before the SLIVER detection to separate the radial and azimuthal components of the dipole radiation. We demonstrated that our method achieves near constant precision independent of the separation between two dipole emitters. We also quantified the effect of numerical aperture, detection bandwidth, number of estimation parameters, background and misalignment on separation estimation. Our method provides a near optimal detection scheme for measuring the separation of two freely-rotating dipole emitters such as fluorescently tagged molecules.
A NovelXACTlncRNA Transcript with Functions Transcending X-Chromosome Inactivation
Authors: Zhang Peifen , Angles Paula Haro , Zhang Hong , Li Tingyue , Mulet-Lazaro Roger , van IJcken Wilfred F.J. , Philipsen Sjaak , Delwel Ruud , Gribnau Joost , Huylebroeck Danny , Grosveld Frank , Rougeulle Claire , Mulugeta Eskeatnaf
Published: January 2025

X-chromosome inactivation (XCI) is initiated during early mammalian embryogenesis by a long non-coding RNA (lncRNA)XIST, which coats one of the two X-chromosomes and facilitates epigenetic transcriptional silencing. A second, evolutionarily recent primate-specific lncRNAXACTwas proposed to antagonizeXIST’s ability to induce XCI.XACTexpression is restricted to pluripotent states and early embryonic stages and coats the active X-chromosome in both females and males. Here, we report a novelXACTtranscript expressed in normal and cancerous somatic cells from both the inactive (Xi) and active (Xa) X chromosomes. It coexists withXISTon the Xi without affectingXISTexpression or (re)activating X-linked genes inactivated by XCI. During hematopoietic stem cell (HSC) differentiation,XACTis primarily expressed in myeloid progenitors in both sexes.XACTexpression is activated in HSCs and peaks in megakaryocyte-erythrocyte progenitor cells (MEPs) before rapidly declining as the MEPs differentiate into megakaryocytes or erythrocytes. By combining CRISPR-basedXACTperturbation with epigenomic and transcriptional studies, we revealed the key role ofXACTin the self-renewal and differentiation of erythroid progenitors into erythrocytes, by recruiting cis-regulatory proteins and regulating transcription through ETS and AP-1 transcription factors. Furthermore,XACTis expressed in a subset of acute myeloid leukemia (AML) patients, with high levels found in erythroid-megakaryocytic blast cells; suggestingXACT’s potential as a marker for AML subtypes. Thus, we identified a novelXACTtranscript with a unique expression profile and important roles in normal and cancer cells, revealingXACTlncRNA functions beyond its previously proposed role in XCI during embryogenesis.