Conectar
by Caio R. Monteiro, Victor Augusto de Oliveira, Rabeche Schmith, João Pedro A. Rezende, Tales L. Resende, João A. Negrão, Marina A. C. Danés
This study aimed to evaluate the effects of rumen-protected methionine (RPM) supplementation on productive and physiological responses of primiparous Holstein cows during summer. We hypothesized that RPM supplementation would maintain or improve milk yield and composition due to beneficial physiological, redox, and inflammatory responses in cows exposed to summer heat. The trial was conducted in a randomized block design during nine weeks in Brazil using 80 primiparous cows (182 ± 64 DIM; 42.9 ± 4.7 kg/d milk). Cows were blocked by milk yield and DIM and assigned to a control diet (CON; no added RPM) or the same diet supplemented with RPM (Mepron®, Evonik) at 0.75 g/kg diet dry matter, targeting 20 g/cow/day (product contains 62% metabolizable methionine) to the average cow. Milk yield and composition, vaginal temperature, respiratory rate, and plasma samples were collected in weeks 3, 6, and 9. Data were analyzed using mixed models including treatment, week, and their interaction as fixed effects, and block and cow as random effects. Cows were maintained under naturally occurring summer conditions. Environmental monitoring during weeks 3, 6, and 9 indicated elevated temperature–humidity index (THI) values, with values remaining above the heat-stress threshold (THI > 68) for 68.3% of the monitored hours (mean THI = 70.6; range 61.0–84.4). Overall (least squares mean across weeks 3, 6, and 9), RPM increased milk yield by 2.0 kg/d (44.9 vs. 42.9 kg/d), protein yield by 50 g/d (1,464 vs. 1,414 g/d), lactose yield by 108 g/d (2,109 vs. 2,001 g/d), and total solids yield by 176 g/d (5,331 vs. 5,155 g/d). Lactose concentration was lower in RPM (4.71 vs. 4.76%). Fat yield was unaffected, but a treatment × week interaction was observed for fat content. Milk fatty acid (FA) profile was unchanged, although treatment × week interactions were observed for individual fatty acids (C16:0, C18:0, C18:1, and preformed FA). Plasma glucose was lower, and insulin was higher in RPM than in CON cows (39.3 vs. 43.2 mg/dL and 0.52 vs. 0.35 ng/mL, respectively). Antioxidant capacity improved, with RPM cows having greater ferric reducing antioxidant power (32.9 vs. 28.5 µM) and lower malondialdehyde (2.48 vs. 2.78 nmol/mL). Other biochemical, inflammatory, and immune markers were unaffected. Respiratory rate was slightly higher in RPM than in CON cows (55 vs. 50 breaths/min). Mean vaginal temperature did not differ between treatments; however, a treatment × time × hour interaction was observed. Supplementation with RPM improved milk and solids yield, and enhanced antioxidant capacity and insulin levels, supporting its use to improve metabolic resilience under warm conditions.by Naoya Nakagawa, Ami Igarashi, Hideaki Yokogawa, Akira Kobayashi, Tomomi Higashide, Satoru Yamagami, Takahiko Hayashi
The aim of this study was to identify the clinical factors associated with postoperative visual acuity following Descemet’s membrane endothelial keratoplasty (DMEK), with emphasis on the impact of macular diseases. This retrospective multicenter study included consecutive eyes that underwent DMEK between March 1, 2011, and June 30, 2022, and had available optical coherence tomography findings. Eyes with other ocular diseases causing visual loss were excluded. Overall, 77 eyes of 66 patients were included in the study. Univariable and multivariable regression analyses were performed to identify the predictors of best-corrected visual acuity (BCVA) at the final follow-up. Worse preoperative visual acuity and macular comorbidity were identified as independent predictors of poorer postoperative BCVA. Among macular pathologies, cystoid macular edema was most strongly correlated with reduced vision in the univariable analysis (β = 0.195; p = 0.016). In the subgroup analysis, worse preoperative visual acuity and macular comorbidity remained significant predictors (pby Adam V. Wisnewski, Jian Liu
A panel of hybridomas specific for different isomers of toluene diisocyanate (TDI), a cross‑linking chemical used in polyurethane production, has been previously described. These hybridomas were originally developed by researchers at the USA’s National Institute for Occupational Safety and Health (NIOSH). We sought to determine the DNA sequence encoding these TDI-specific monoclonal antibodies, enabling identification of germline gene rearrangement resulting in chemical specificity as well as production of the mAbs recombinantly. B cell receptor sequencing (BCR-seq) of hybridoma RNA readily identified productive heavy and light chain antibody sequences. The productive light chains of all 7 hybridomas showed strong identity with different genomic variable (V) and joining (J) region sequences with few changes from germline configuration. However, the productive heavy chains contained more substantial changes in their genomic V and J-region sequences consistent with antigen-driven affinity maturation, as well as N- and P- nucleotide additions comprising their complementarity-determining region 3 (CDR3). The hybridoma-defined TDI-specific mAbs were subsequently produced recombinantly in a human embryonic kidney cell line expression system, purified, and tested for their binding capacity against albumin derivatized with TDI, related diisocyanates, and control antigen. The recombinant versions of the TDI-specific mAbs demonstrated binding capacity for different isomers (2,4 and 2,6) of TDI consistent with that previously reported for the hybridoma secreted clones; one specific for 2,4-TDI, one specific for 2,6-TDI, three that bind both 2,4- and 2,6-TDI, and two that show cross-reactivity with 4,4′‑methylene diphenyl diisocyanate (MDI). None of the recombinant mAbs bound to aliphatic hexamethylene diisocyanate (HDI), its oligomer, or control antigen. Additional recombinant versions of the TDI mAbs, with identical V-regions, but different C-regions, demonstrated the dependence of antigen specificity on the V-region, but also highlighted the potential for C-region sequence to affect their detection in ELISA assays. The DNA sequences defined herein may be useful to other investigators wishing to generate recombinant TDI-specific mAbs as detection reagents for research or as standards for clinical serology tests.by Wenting Yan, Carmel L. Montgomery, Liz Dennett, Stephanie A. Chamberlain
BackgroundThe demographic landscape of Western countries has shifted to a more diverse one. Along with the trend of an aging population, a new problem has emerged, which is the increased linguistic diversity in the aging population in these countries. As people age and their care needs increase, they may not receive optimal care if they don’t speak the same language as their caregivers in long-term care facilities. Culturally and linguistically responsive long-term care services are important to ensure the best care for an aging population, but there is limited evidence in the literature on the scope and practice of these services. The objective of this scoping review is to map out the types of CLR programs in LTC settings and examine their core components and target populations.
MethodsThe Arksey and O’Malley framework, further developed by Levac and colleagues, will be employed in this scoping review. The research question was framed using the PCC framework. A comprehensive systematic search was developed with an experienced librarian and will be conducted in Scopus, CINAHL, Embase, Medline, PsycINFO, and Academic Search Complete. All primary study designs, including quantitative, qualitative, and mixed methods, will be included. Studies must focus on culturally and linguistically responsive care programs used or implemented in long-term care services. There will be no date or language limitations. Findings will be thematically synthesized to answer the research question.
ConclusionThis review protocol provides a transparent process for how it will be conducted. We aim to contribute to a better understanding of what culturally and linguistically responsive care programs exist, how cultural and linguistic responsiveness is currently addressed across diverse care environments, and what gaps remain in long-term care.
by Seong Tak Woo, Sungdae Na
Intraoral palatal plates used in electropalatography (EPG) and tongue-interface systems are designed to monitor articulatory movement with minimal disruption to speech. However, their presence may subtly influence acoustic characteristics by altering tongue mobility and intraoral airflow. This study examines the acoustic effects of a pseudo-palatal plate during the articulation of consonants and vowels. Speech samples from healthy adults were recorded with and without the plate and analyzed using spectral and phonatory measures, including Mel-frequency cepstral coefficients (MFCCs), second formant (F2) slope, jitter, shimmer, harmonics-to-noise ratio (HNR), and quadrilateral vowel space area (qVSA). MFCC-based correlation coefficients and F2 slopes remained highly consistent across conditions, indicating minimal impact on consonant articulation. Shimmer (−0.72%), HNR (+2.5 dB), and qVSA (−24.1%) exhibited directionally consistent changes, with qVSA trending toward reduction; however, overall variation was limited. Vowel formant structures and consonant production were preserved mainly, suggesting that the palatal plate did not significantly impair vocal function. These findings support the interpretation that observed acoustic shifts are more consistent with filter-level effects than with changes at the glottal source. Although palatal plates may introduce minor acoustic variations, their impact on speech production appears minimal, reinforcing their suitability for therapeutic and assistive use, provided that acoustic considerations are addressed during design and clinical implementation.by Ece Zengin, Aybuke Ucgun, Mehmet Emir Çevik, Sehnaz Evrimler, Ihsaniye Suer Dogan
BackgroundEpicardial adipose tissue (EAT) is associated with cardiometabolic disorders such as diabetes mellitus (DM), hyperlipidemia, and nonalcoholic fatty liver disease. However, its potential relationship with pancreatic steatosis and pancreatitis remains unclear, and existing studies offer inconsistent findings. Therefore, a clearer understanding of whether EAT reflects broader systemic ectopic fat burden or inflammatory processes is needed.This study evaluated the relationships between EAT thickness and DM, hyperlipidemia, hepatosteatosis, pancreatic steatosis, and pancreatitis.
MethodsThis retrospective, single-center study included 200 patients who underwent abdominal CT between 2022 and 2024. EAT thickness was measured at the mid-RCA and LAD levels, and subcutaneous fat was measured at the umbilical level. Liver and pancreatic steatosis were assessed with CT or MRI. Demographic and clinical data (age, gender, LDL cholesterol, diabetes, and history of pancreatitis) were collected. Mann-Whitney U, Spearman correlation, and logistic regression were used in analyses; p Results
Of the 200 patients, 31.4% had diabetes, 42% had hepatosteatosis, and 73.5% had a history of pancreatitis. EAT and subcutaneous fat were significantly higher in women at all levels (p Conclusions
EAT thickness is significantly associated with DM, LDL cholesterol, pancreatitis history, and age, supporting its role as a potential imaging biomarker of cardiometabolic risk. These findings suggest that EAT may serve as an imaging marker of broader metabolic and inflammatory burden, supporting its relevance for cardiometabolic risk assessment.
by Orit Wonderman Bar Sela, Shay Ofir Geva, Gaby S. Pell, Yiftach Roth, Jason Friedman, Afnan Muhana, Silvi Frenkel-Toledo, Nachum Soroker
Unidirectional transcranial magnetic stimulation (udTMS; e.g., via Figure-of-8 coil) depolarizes mainly neurons whose axonal orientation aligns with the direction of the induced electric field. A novel dual H-coil (T360°) TMS system (BrainsWayTM, Israel) generates a rotational magnetic field aimed to recruit a larger neuronal population by induction of a multidirectional electric field (rfTMS). This study aimed to comparatively assess the neurophysiological properties of motor evoked potentials (MEPs) elicited from the first dorsal interosseous (FDI) muscle following udTMS (via Figure-of-8 and H7 coils) vs. multidirectional rfTMS. In this study, 10 healthy adult subjects received TMS via the three coil configurations in a random order. The results showed that rfTMS elicited larger MEPs at a lower resting motor threshold (rMT) compared to the unidirectional coils. These findings suggest that rfTMS is likely to recruit larger populations of neurons compared to conventional udTMS coil configurations. This may be advantageous in efforts to enhance motor recovery following brain damage by treatments using TMS.by Devika A. Shenoy, William C. Cruz, Shamik Bhat, Katelyn Parsons, Aaron D. Therien, Kevin A. Wu, Christian A. Pean, William C. Eward
BackgroundRadical resection of bone tumors is a clinically effective but costly procedure. Despite the implementation of federal price transparency mandates, little is known about the nationwide variation in negotiated prices for these specialized oncologic surgeries. This study aimed to quantify the variation in negotiated rates for radical resection of the humerus and femur/knee and identify associated hospital, payor, and state-policy drivers.
MethodsThis cross-sectional study analyzed hospital-negotiated payor rates from the Turquoise Health database for current procedural terminology (CPT) codes 24150 (humerus resection) and 27365 (femur/knee resection). Multivariate linear regression was used to determine the associations between hospital size and type, payor class, and state-level policies (Medicaid expansion, Certificate of Need [CoN] laws, All-Payer Claims Database [APCD] mandates, and Nurse Practitioner [NP] scope of practice) on negotiated payor rates.
ResultsA total of 285,857 negotiated rates were analyzed. Significant price variation was observed across all factors. Large hospitals (>1000 beds) and Critical Access Hospitals (for femur/knee resection only) had significantly higher rates. CoN laws were associated with higher prices for both procedures (+$348.25 and +$667.98, respectively), as were APCD mandates for femur/knee resections (+$1231.24). Medicare Advantage plans paid inconsistently compared to commercial plans, paying more for humerus but substantially less for femur/knee resections.
DiscussionNegotiated prices for radical bone tumor resection are highly variable and influenced by a complex interplay of market dynamics, challenging the assumption that price transparency alone can standardize healthcare costs for specialized care.
by Clarisse Kagoyire, Albert Ndagijimana, Gilbert Nduwayezu, Jean Nepo Utumatwishima, Jean Pierre Mpatswenumugabo, Marie Anne Mukasafari, Diane Rinda, Vedaste Ndahindwa, Kristina Elfving, Gunilla Krantz, Torbjörn Lind, Ali Mansourian, Renée Båge, Ewa Wredle, Elias Nyandwi, Aline Umubyeyi, Jean Baptiste Ndahetuye, Petter Pilesjö
Despite national progress, stunting remains prevalent in specific regions of Rwanda, highlighting the limitations of coarse-resolution data for effective mapping and intervention planning. This study explored optimal spatial resolution and analytical approach to capture localised dynamics and the multifactorial nature of stunting. A cross-sectional, population-based study was conducted in the Northern Province of Rwanda, focusing on children aged 1–36 months. Data were collected using structured questionnaires covering socio-demographic, economic, health, childcare, livestock factors and anthropometric measurements. Environmental characteristics were obtained from national datasets, while household geographic coordinates were captured using a customized mobile geodata platform (emGeo). After data cleaning, predictors were analysed using univariable and multivariable logistic regression as well as geographically weighted logistic regression (GWLR) to account for spatial heterogeneity. Among 601 children, stunting prevalence was 27% (boys 33.8%; girls 20.9%). GWLR improved model fit, increasing adjusted deviance explained from 34% to 39%. Significant predictors included child age (adjusted OR = 2.46; 95% CI: 1.78–3.39), male sex (OR = 2.83; 95% CI: 1.65–4.86), birthweight (OR = 0.71; 95% CI: 0.54–0.94), maternal autonomy (ability to refuse sexual intercourse; OR = 0.48; 95% CI: 0.27–0.86), inconsistent maternal social support (OR = 2.30; 95% CI: 1.20–4.42), household electricity access (OR = 0.48; 95% CI: 0.27–0.84) and handwashing facilities (OR = 0.21; 95% CI: 0.07–0.67). GWLR revealed substantial spatial heterogeneity in these factors, delineating areas where each factor matters most. This household-level, spatially explicit analysis reveals localised risk patterns often masked by aggregated national data. Prioritising context-specific interventions (such as electrification, hygiene promotion, and enhanced maternal social support), can enhance effectiveness. The proposed analytical workflow provides a model for addressing persistent stunting in other resource-limited settings.by Jimmy Andreyvan Cainamarks-Alejandro, Liliana Cruz-Ausejo, Miguel Angel Burgos-Flores, Jaime Rosales-Rimache, Jonh Astete-Cornejo, David Villarreal-Zegarra
BackgroundThe COVID-19 pandemic marked an increase in depressive, anxiety, and post-traumatic stress disorder symptoms, more specifically among healthcare workers, teachers, and police officers. These workers face external and occupational factors which had a significant impact on mental health, significant increase in workload and direct exposure to the virus, shortage of personnel protective equipment, and instances of abuse, including discrimination. Mental health care in primary care requires a process of early identification and timely referral of complex cases. Telehealth emerges as an effective alternative for addressing challenges in mental health care, although its implementation encounters obstacles.
ObjectiveTo design a telehealth service that facilitates screening, initial management, and timely referral for mental health diagnoses in workers with prior SARS-CoV-2 infection, and to evaluate usability, acceptability, and user satisfaction.
MethodsMixed-method study with a user-centered design approach involving key external and internal service users in three sequential stages (pre-design, co-design, and post-design). The study phases lasted 6 months, involving a total of 23 participants in the pre-design phase (contextual inquiry and preparation and training), 12 participants in the co-design phase (framing the issue, generative design, and sharing design), and in the post-design phase, 4 participants were involved in service implementation, and 81 participants—drawn from the subgroup of 134 users who received psychoeducation—were included in the efficacy assessment.
ResultsThe proposal included the development and evaluation of a service model guide and a telehealth software platform. First, the participants took part in a series of workshops (Pre-design, Co-design) where they provided ideas for meeting the product requirements, based on the Design Thinking methodology framework. The telehealth service model was named TelePsico CENSOPAS. It comprised four processes: a) Service promotion; b) User pre-identification; c) Appointment management; d) Psychoeducation counseling and referral. The Telehealth platform was designed through three cycles of an iterative process and integrated a proprietary development platform with third-party service technologies for communication support and information exchange. During post-design, the pilot test involved 698 screened patients; 193 were identified with mental health risks, and 134 of them received psychoeducation sessions. In addition to user acceptance, the usability score of the platform was 86.1 ± 16.9 SD, satisfaction dimensions of the service was 45.1 ± 7.2 SD for satisfaction with care processes, and 36.7 ± 5.2 SD satisfaction with psychological care.
ConclusionThe proposal for mental health telehealth services and its supporting platform was successfully developed and accepted by both internal and external users, particularly within well-structured occupational health services in workplaces serving vulnerable occupational groups. In addition, it achieved higher satisfaction and usability scores than Peru’s outpatient care services. These findings support the replicability of user-centered design frameworks—such as design thinking—within the occupational health sphere.
by Yaosen Du, Yiyong Yang, Xiaolong Wu, Pengju Gao, Hanchen Ma
To enhance the efficiency, safety, and data accuracy of drilling engineering, this study developed an integrated business management platform for drilling engineering grassroots units based on the Business Model Driven (BMD) approach. The platform is built on a “five horizontal, three vertical” cloud computing architecture, establishing a five-layer system from the infrastructure layer to the user layer horizontally, and supported by standard specifications, safety, and maintenance systems vertically, enabling collaboration across multiple business scenarios and data integration. Currently, four major modules with over 20 functionalities have been developed, supporting applications such as task coordination, engineering supervision, data analysis, and accident handling. Operational results demonstrate that the platform effectively promotes integrated management of drilling engineering through real-time data sharing, full-process quality control, and intelligent decision-making, thereby enhancing operational quality and safety, reducing accident risks, and providing critical technological support for the digital transformation and upgrading of the drilling industry.by Oksana Kovtun, Olga Cheshun, Oksana Pashchuk, Kostyantyn Dumchev
BackgroundUkraine’s HIV epidemic remains concentrated among key populations, with sex workers (SWs) facing overlapping vulnerabilities, including a history of injection drug use. Although overall HIV prevalence has declined, prevention coverage remains below national and global targets. Accurate mapping of sex work hotspots is essential for effective outreach, yet existing data are fragmented and incomplete, especially in privatized and digitally mediated environments. This study aimed to systematically identify and characterize sex work venues across eight Ukrainian cities and assess their coverage by HIV prevention services.
MethodsIn 2021, we conducted a two-stage, multi-informant mapping study across eight Ukrainian cities, interviewing 1,212 secondary and 2,277 primary key informants, including SWs. Hotspots were characterized by type, perceived safety, access modality, operating schedule, and presence of SW subgroups. We used descriptive statistics, exploratory factor analysis, and multivariable mixed-effects regression to identify factors associated with HIV prevention service coverage.
ResultsOf 2,581 identified hotspots, 2,118 (82.1%) were validated as active. Apartments (43.2%), virtual platforms (11.7%), and street-based sites (11.1%) were the most common. Only 13.7% of hotspots were registered in the national HIV service registry, while 34.1% received prevention service delivery and 18.9% were reached by mobile vans. Coverage was highest at street-based and office-type venues and consistently lowest in private, virtual, and pimp-mediated settings. Service coverage was positively associated with 24/7 or daytime operation, higher perceived safety, open access, and the presence of SWs who inject drugs.
ConclusionsThis study provides comprehensive mapping of sex work hotspots in Ukraine, revealing persistent gaps in HIV prevention for less visible and harder-to-reach SWs. Community-led mapping achieved high validation rates (86.8%) and identified substantial unmet needs in digital and concealed hotspots. Routine hotspot mapping, combined with engagement with SW communities, is essential for data-driven, equitable, and adaptive HIV responses in rapidly changing contexts.
by Yanan Fu, YuXin Wei, ZiKun Pang, Jie Yang, XinGang Sun
PurposeThis study outlines the changes in the age- and sex-specific burden of motor neuron disease (MND) in China from 1990 to 2021, focusing on the prevalence, incidence, number of disability-adjusted life years and mortality. Additionally, these trends are evaluated in comparison to the Global Burden of Disease data.
MethodsPublic data from the Global Burden of Disease database covering the period from 1990 to 2021 were analyzed to explore the burden of motor neuron disease in China and worldwide. Trends in prevalence, incidence, disability-adjusted life years (DALYs) and mortality were examined in the analysis. The average annual percentage change was calculated using Joinpoint, and the relevant 95% confidence intervals (95% CIs) were examined to identify changes in the MND burden over time. Additionally, a thorough comparative analysis was performed to investigate the differences in the MND burden between China and other regions worldwide, considering factors such as age, sex, and time periods.
ResultsFrom 1990 to 2021, the age-standardized incidence rate (ASIR) of motor neuron disease (MND) in China declined from 0.65 per 100,000 to 0.46 per 100,000, whereas the global ASIR decreased slightly from 0.81 per 100,000 to 0.77 per 100,000. In contrast, the age-standardized prevalence rate (ASPR) in China increased from 2.131 per 100,000 to 2.298 per 100,000, whereas the global ASPR decreased slightly from 3.356 per 100,000 to 3.31 per 100,000. The age-standardized mortality rate (ASMR) in China increased from 0.151 per 100,000 to 0.181 per 100,000; the global ASMR also increased from 0.38 per 100,000 to 0.46 per 100,000 during this period. Moreover, the age-standardized disability-adjusted life year (ASDR) rate in China decreased slightly from 7.995 per 100,000 to 7.672 per 100,000, whereas the global ASDR increased from 11.221 per 100,000 to 12.167 per 100,000. The average annual percentage changes (AAPCs) for the ASPR, ASIR, ASDR, and ASMR in China were −1.10%, 0.25%, 0.57%, and −0.14%, respectively. In contrast, the global AAPCs were −0.16%, −0.04%, 0.58%, and 0.26%, respectively. Age and sex played distinct roles in shaping MND burden. The ASIR of MND decreased but then increased for both sexes, remaining higher for males. Its ASPR trends differed: a slight increase in males versus an increase then decrease in females. While the ASMR was consistently higher for males, the DALYs for males started to decrease but surpassed those for females. Global MND rates have remained stable.
ConclusionThe prevalence, incidence, DALYs and mortality of motor neuron disease in China decreased between 1990 and 2021, suggesting a relative decrease in the total burden of MND in the country. Age influences the burden of MND, with a higher occurrence incidence in children and middle-aged individuals; the prevalence of MND is highest in the younger population, whereas MND-related mortality is the highest within the middle-aged and senior populations. Compared with females, males are more likely to be affected by MND and have a greater likelihood of death. Given the rapid population aging in China, MND is expected to remain a significant public health issue.
by Guohui Wang, Lu Liu, Hanshu Zhang, Panpan Mao, Saijuan Lu, Xiaofang Zhang, Xingde Li, Cangsang Song
BackgroundLiver transplantation (LT) is an effective treatment for patients with end-stage liver disease. In recent years, more and more evidence has supported the association between gut microbiota dysbiosis and the pathogenesis and progression of liver diseases.
MethodsThe study included 36 patients who received tacrolimus treatment after liver transplantation. Patients were stratified into subgroups according to three key variables: tacrolimus treatment duration, whole-blood tacrolimus concentration, and tacrolimus concentration-to-dose (C/D) ratio. Fecal samples and whole-blood specimens were collected from all participants. The Illumina HiSeq X platform was used to detect the gut metagenome, analyzing the composition and characteristics of the gut microbiota. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology was employed to detect metabolites of the gut microbiota, revealing their metabolic profiles.
ResultsAs the duration of tacrolimus use increased, the diversity of the gut microbiota also increased, and the abundance of Escherichia coli_D and Bacteroides stercoris rose. Additionally, the abundance of Brunovirus and Uetakevirus tended to decrease. The abundance of gene functions related to chemical carcinogenesis and bacterial invasion of epithelial cells significantly decreased. In the gut microbiota metabolites, 16 substances like Astragaloside A and Acetyl-L-carnitine significantly increased, while 108 substances like Capsaicin and TLK significantly decreased. Within a certain range, as the concentration of tacrolimus in whole blood increased, the diversity of the gut microbiota increased. The abundance of Phocaeicola and Klebsiella increased, and the abundance of Peduovirus among viruses also rose. However, excessively high concentrations may lead to a decrease in the diversity of the gut microbiota and a decrease in the abundance of Phocaeicola. With respect to the C/D ratio, increased ratios were linked to significantly higher levels of 57 fecal metabolites (e.g., PC 34:2, 5-Methyl-2’-deoxycytidine), whereas 13 metabolites (e.g., FAHFA 2:0/16:0) showed substantial declines.
ConclusionsTacrolimus treatment is associated with distinct alterations in gut microbiota and metabolites among LT recipients. These findings provide a preliminary framework for future investigations aimed at optimizing immunosuppressive regimens, although their clinical translational potential requires validation in larger-scale, prospective cohort studies.
by Jingwen Gao, Yasushige Shingu, Ryota Azuma, Satoru Wakasa
BackgroundInflammatory response plays a pivotal role in myocardial injury and post-infarction remodeling after acute myocardial infarction (AMI). Mechanical unloading (UL) of the left ventricle (LV) has been proposed as a potential therapeutic strategy to preserve cardiac function; however, its effects on myocardial inflammation remain incompletely understood.
MethodsWe employed a rat model of partial UL using heterotopic heart-lung transplantation following AMI. RNA sequencing (RNA-seq) was performed to evaluate transcriptomic changes, with a specific focus on inflammatory pathways in the non-infarcted remote area. Immune cell abundance was estimated using deconvolution analysis (QUANTISEQ). Quantitative PCR was performed to analyze some inflammatory cytokines, and macrophage polarization was evaluated by immunohistochemistry.
ResultsAMI significantly impaired cardiac function, which was mitigated by UL. RNA-seq analysis revealed marked activation of inflammatory pathways and identified several hub genes involved in cytokine signaling following AMI, while these transcriptional changes were not significantly altered in UL groups after AMI. Immune cell profiling demonstrated an increase in M2 macrophages after AMI, while UL preserved M2 macrophage levels. Histological analysis further supported UL’s modulatory effect on macrophage polarization. Pro-inflammatory cytokines TNFα and IL1β were upregulated after AMI but showed attenuation with UL.
ConclusionPartial UL potentially attenuates cardiac functional deterioration after AMI while exerting substantial effects on inflammatory gene expression and macrophage polarization. These findings suggest that the cardioprotective effects of UL may be correlated with the modulation of inflammatory pathways in the remote area after AMI.
by Anas Ismail, Moatasem Salah, Mads Gilbert, Yousef H. Abu Alreesh, Craig Jones
BackgroundGaza has faced numerous military attacks that resulted in mass casualty incidents (MCIs). The ongoing genocide in Gaza has destroyed much of the health system, including killing and injuring of hundreds of health care workers (HCWs). Current thinking on the health system reconstruction lacks empirical data and local HCWs’ perspectives. The study analyses locally driven innovations and lessons learned by HCWs who responded to MCIs between 2018 and 2021 to guide current and future planning of the reconstruction of the health system in Gaza.
MethodsThis was a qualitative study using online and face-to-face interviews with HCWs who responded to the Great March of Return and the 2021 Israeli military attacks. Transcripts and extensive notes from the interviews were recorded and analyzed on NVivo using thematic content analysis. We used the health system building blocks as themes for deductive analysis with a seventh place-based theme (Gaza-specific) to account for the context of Gaza and the MCIs.
ResultsProblems faced by HCWs mostly related to the nature and complexity of traumatic injuries, shortages in HCWs, particularly specialist doctors, poor coordination among actors, duplication of services, and shortages of supplies and equipment. Locally driven innovations and solutions included establishing new services centers, opening and expanding training programs, starting new coordination bodies, and task shifting of staff and facilities. Lessons learned included strengthening training and employment opportunities for staff, enhancing emergency preparedness and capacities, maintaining coordination bodies, enhancing community engagement and strengthening the governance of the Ministry of Health.
ConclusionReconstruction of Gaza’s health system needs to be grounded in its political context and in the experiences of HCWs who have worked in and managed the system. Locally driven solutions and lessons learned can ensure that reconstruction serves as a vehicle for self-determination and sovereignty, rather than entrenching dependency.
by Zijing Wang, Liyuan Ma, Zhanyuan Sun, Hengyi Lv, Ruxue Ma, Mengqi Ding, Hai Li, Tao Jiang
BackgroundDiethyl phthalate (DEP), a widely used plasticizer with endocrine-disrupting properties, has raised concerns regarding its potential carcinogenic effects. However, its precise role in colorectal cancer (CRC) development remains poorly understood.
MethodsThe chemical structure of DEP was obtained from the PubChem database. Potential targets of DEP were identified through ChEMBL and STITCH databases and intersected with known CRC-related genes to screen for candidate biomarkers. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the biological functions and signaling pathways involved. Molecular docking was conducted to predict the binding affinities between DEP and core targets. Finally, 200-ns molecular dynamics (MD) simulations using GROMACS were employed to evaluate the binding stability and dynamic behavior of the DEP–target complexes.
ResultsA total of 62 overlapping genes were identified between DEP targets and CRC-associated genes. GO and KEGG enrichment analyses indicated enrichment in epigenetic regulation, chromatin remodeling, and cancer-related signaling pathways, including Notch, TGF-β, and FoxO. Protein–protein interaction analysis identified EP300, EZH2, HDAC1, HDAC2, and KDM1A as key epigenetic regulators. Molecular docking predicted moderate binding affinities between DEP and these targets (−6.6 to −5.7 kcal·mol ⁻ ¹). Subsequent 200-ns MD simulations suggested that DEP formed stable complexes with HDAC1, KDM1A, and EZH2, moderate stability with EP300, and partial dissociation with HDAC2, consistent with hydrophobic and hydrogen-bonding interactions at the binding interfaces.
ConclusionThis study provides a theoretical framework for exploring the molecular mechanisms through which DEP may contribute to CRC development, emphasizing the value of network toxicology in cancer research. These findings may inform future investigations into the risks of DEP exposure and support public health policy and the development of targeted therapeutic strategies.
by Peiling Zuo, Huanhuan Zhu, Chunying Sun, Xiaohan Ma, Sheng Chen, Rong Tang, Tong Wu, Ding Zhang, Xiao Tang, Wenquan Lv, Wenzhong Chen, Xiawei Wei, Encun Hou, Minsheng Wu, Minghe Jiang
BackgroundEvidence indicates that the Endothelial Activation and Stress Index (EASIX) is a predictor of mortality in endothelium-related conditions; however, its association with mortality risk in atrial fibrillation (AF) remains uncertain. Accordingly, this study examines the relationship between EASIX and mortality risk among patients with AF.
MethodsThis retrospective analysis utilized data from the Medical Information Marketplace in Intensive Care IV (MIMIC-IV) database, which includes critically ill patients diagnosed with AF. To examine the association between EASIX scores and mortality, Kaplan–Meier survival analysis, Cox proportional hazards models, and restricted cubic spline regression were applied to evaluate the relationship between EASIX and all-cause mortality. Subgroup analyses were conducted to explore potential interactions with key patient characteristics, and sensitivity analyses were performed to further confirm the robustness of the results.
ResultsA total of 3,193 patients were included in the analysis. KM survival analysis showed that elevated EASIX levels were associated with a higher risk of both in-hospital and ICU mortality. After adjusting for potential confounders, increased EASIX levels remained significantly associated with in-hospital mortality [HR, 1.09 (95% CI 1.03, 1.15), P = 0.0002] and ICU mortality [HR, 1.10 (95% CI 1.04, 1.17), P = 0.0002]. Stratified analyses revealed a significant interaction between sepsis, respiratory failure, and EASIX in relation to both in-hospital and ICU mortality. To evaluate the robustness of the findings, a sensitivity analysis was performed. After additionally adjusting for metoprolol and heparin as covariates, patients in the highest EASIX group continued to demonstrate the greatest mortality risk: the HR for in-hospital death was 2.08 (95% CI: 1.51–2.85), and the HR for ICU death was 1.83 (95% CI: 1.21–2.65).
ConclusionElevated EASIX levels correlate with higher mortality rates, underscoring its potential as an accessible tool for identifying high-risk patients and informing clinical decisions. However, further studies are needed to explore the underlying mechanisms and validate its applicability across diverse patient populations.
by Viral D. Oza, Colin S. Williams, Jessica S. Blackburn
The Genetically Encoded Death Indicator (GEDI) is a ratiometric, dual-fluorescence biosensor that enables real-time detection of cell death through calcium influx. Originally developed for use in neurodegeneration models, GEDI can be applied to cancer cells to quantify therapy-induced death at single-cell resolution. This protocol details how to generate GEDI-expressing cancer cell lines, empirically determine stress-induced GEDI thresholds using radiation or chemotherapeutic agents, and perform time-resolved imaging and image analysis to track cell fate. This workflow is optimized for high-throughput drug and radiation screening in heterogeneous populations and is especially useful for identifying chemo- and radio-resistant subclones. Key limitations include the need for empirical GEDI threshold calibration for each treatment condition and careful standardization of imaging parameters. The protocol outputs include GEDI ratio values, single-cell time-of-death annotations, and whole-cell morphological data in parallel, which can be linked to downstream applications such as FACS-based isolation of live or dying subpopulations, transcriptomic profiling of resistant clones, or in vivo validation using xenografts or organotypic slice culture.by Renata dos Santos Guarnieri, Guilherme Sá de Oliveira, Kaylaine Marques Ferreira, Aline Penna-de-Carvalho, Vanessa Souza-Mello, Sandra Barbosa-da-Silva
High-intensity interval training (HIIT) is an effective intervention for improving metabolic health and mitigating metabolic dysfunction-associated steatotic liver disease (MASLD). Nonetheless, the stability of these benefits throughout detraining periods and upon weight regain remains inadequately characterized. This study aimed to evaluate whether hepatic improvements induced by HIIT are sustained during detraining, even after body weight regain. Eighty male C57BL/6 mice were fed either a control (10% fat) or a high-fat (HF) diet (50% fat) for 12 weeks. Following this period, the animals were allocated to groups subjected to continuous HIIT or intermittent training cycles (each lasting 3 weeks). The outcomes assessed included body mass (BM), glucose tolerance, lipid profiles, liver enzyme levels (aspartate aminotransferase and alanine aminotransferase), hepatic steatosis, and the expression profiles of genes associated with lipogenesis (Srebf1, Mlxpl, and Fas), β-oxidation (Ppara and Cpt1a), and endoplasmic reticulum (ER) stress (Atf4, Ddit3, and Gadd45). Compared with the sedentary HF-NT condition, continuous HIIT reduced BM and improved glucose tolerance. Intermittent training (HF-TNT, HF-NTN) preserved metabolic benefits and reduced triglyceride and cholesterol levels. Notably, hepatic steatosis was significantly alleviated in all training groups but persisted even after detraining. Additionally, HIIT downregulated the expression of lipogenic genes and upregulated the expression of genes involved in β-oxidation. The levels of markers indicating ER stress were attenuated by HIIT, with a sustained reduction during periods of detraining. HIIT-induced metabolic and hepatic improvements persist partially during detraining, despite weight regain. These findings underscore the therapeutic value of continued or periodically repeated physical training in mitigating the adverse effects of an HF diet and preventing the progression of metabolic disorders such as MASLD.
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