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Nevin Manimala Statistics

Effect of a Telemedicine Model on Patients With Heart Failure With Reduced Ejection Fraction in a Resource-Limited Setting in Vietnam: Cohort Study

J Med Internet Res. 2025 Mar 19;27:e67228. doi: 10.2196/67228.

ABSTRACT

BACKGROUND: Heart failure (HF) is a complex, life-threatening condition marked by high morbidity, mortality, reduced functional capacity, poor quality of life, and substantial health care costs. HF with reduced ejection fraction (HFrEF) represents the subgroup of HF with the highest risks of mortality and hospitalization, necessitating the prioritization of care and management models to optimize treatment outcomes in these patients. Currently, data on the effectiveness of telemedicine models in resource-limited settings, such as low- and middle-income countries, are scarce.

OBJECTIVE: This study aimed to evaluate the impact of telemedicine on improving prognosis in patients with HFrEF in Vietnam.

METHODS: In this prospective cohort study, we recruited patients who received either remote monitoring and management (telemedicine) or standard monitoring and management (usual care) in the outpatient department of the Vietnam National Heart Institute, Bach Mai Hospital, Hanoi, Vietnam. Eligible patients were ≥18 years old, had a diagnosis of HFrEF defined as left ventricular ejection fraction (LVEF) ≤40%, had a history of HF hospitalization within the past 12 months, and presented with clinical symptoms classified as New York Heart Association (NYHA) II or III. The primary composite outcome was defined as the time to the first unplanned HF hospitalization or all-cause mortality. The follow-up period for all outcomes extended to 12 months.

RESULTS: In total, 426 patients (298/426, 70% male; 128/426, 30% female) with a mean age of 61.3 (SD 14.6) years and a mean LVEF of 32.1% (SD 6.0%) were included in our study. Of these patients, 121 received telemedicine care, while 305 received usual care. The primary outcome occurred in 23 (23/121, 19%) patients in the telemedicine group and 82 (82/305, 26.9%) patients in the usual care group during the follow-up period, indicating a significant reduction in risk (adjusted hazard ratio [aHR] 0.57, 95% CI 0.35-0.94; P=.03). However, this effect was primarily driven by a significant reduction in unplanned HF hospital admissions (aHR 0.57, 95% CI 0.33-0.98; P=.04) rather than in all-cause mortality (aHR 0.77, 95% CI 0.36-1.63; P=.49).

CONCLUSIONS: This study demonstrates that a simplified telemedicine model, even in resource-limited settings such as Vietnam, can effectively facilitate the remote monitoring and management of patients with HFrEF, resulting in significant reductions in HF-related hospitalizations and all-cause mortality.

TRIAL REGISTRATION: National Agency for Science and Technology Information (NASATI), Vietnam CT07/01-2022-3; https://nsti.vista.gov.vn/projects/dth/xay-dung-mo-hinh-theo-doi-va-tu-van-suc-khoe-tim-mach-tu-xa-tai-thanh-pho-ha-noi-109276.html.

PMID:40106810 | DOI:10.2196/67228

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Neurobiological Mechanisms of Enhanced Pain-Relieving Transcutaneous Electrical Nerve Stimulation via Visuo-Tactile Stimulation in Immersive Virtual Reality: Randomized Controlled Trial

J Med Internet Res. 2025 Mar 19;27:e63137. doi: 10.2196/63137.

ABSTRACT

BACKGROUND: Enhancing the effectiveness of current pain relief strategies is a persistent clinical challenge. Although transcutaneous electrical nerve stimulation (TENS) is used in various painful conditions, its effectiveness may decline over time, requiring additional pain management strategies. Immersive virtual reality (VR) with personalized visuo-tactile stimulation has demonstrated analgesic properties. Nevertheless, whether visuo-tactile stimulation can enhance the pain-relieving outcomes of TENS and its underlying neurophysiological mechanisms remains largely unknown.

OBJECTIVE: The study aims to investigate whether the integration of visuo-tactile stimulation with TENS can enhance the pain-relieving outcomes of TENS alone, and we also aim to explore the brain mechanisms underlying the analgesic effect of this integrated intervention.

METHODS: In this study, 75 healthy participants were enrolled and randomly assigned to 1 of 3 groups: congruent TENS-VR (TENS-ConVR) and 2 control groups (incongruent TENS-VR [TENS-InVR] and TENS alone). In the context of TENS-ConVR, we combined TENS and VR by connecting TENS-induced paresthesia with personalized visual bodily feedback. The visual feedback was designed to align with the spatiotemporal patterns of the paresthesia induced by TENS. A pain rating task and a 32-channel electroencephalography were applied.

RESULTS: Two-way ANOVAs showed that TENS-ConVR exhibited a statistically greater reduction in pain rating (F1,48=6.84; P=.01) and N2 amplitude (F1,48=5.69; P=.02) to high-intensity pain stimuli before and after stimulation than TENS alone. The reduction of brain activity was stronger in participants who reported stronger pain-relieving outcomes. TENS-ConVR reduced the brain oscillation in the gamma band, whereas this result was not found in TENS alone.

CONCLUSIONS: This study observed that combining TENS and visual stimulation in a single solution could enhance the pain-relieving effect of TENS, which has the potential to improve the effectiveness of current pain management treatments.

TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2500098834; https://www.chictr.org.cn/showprojEN.html?proj=254171.

PMID:40106805 | DOI:10.2196/63137

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Proximal Effects of a Just-in-Time Adaptive Intervention for Smoking Cessation With Wearable Sensors: Microrandomized Trial

JMIR Mhealth Uhealth. 2025 Mar 19;13:e55379. doi: 10.2196/55379.

ABSTRACT

BACKGROUND: Tobacco use remains the leading preventable cause of morbidity and mortality in the United States. Novel interventions are needed to improve smoking cessation rates. Mindfulness-based interventions (MBIs) for cessation address tobacco use by increasing awareness of the automatic nature of smoking and related behaviors (eg, reactivity to triggers for smoking) from a nonjudgmental stance. Delivering MBIs for smoking cessation via innovative technologies allows for flexibility in the timing of intervention delivery, which has the potential to improve the efficacy of cessation interventions. Research shows MBIs target key mechanisms in the smoking cessation process and can be used to minimize drivers of smoking lapse.

OBJECTIVE: This single-arm study investigated the impact of mindfulness-based strategies and motivational messages on proximal outcomes, collected via ecological momentary assessment (EMA), relevant to tobacco abstinence via a microrandomized trial. This approach allows for the evaluation of intervention content on proximal outcomes (eg, reduced negative affect) that are thought to impact positive distal outcomes (eg, smoking abstinence).

METHODS: All participants were motivated to quit smoking, and the intervention they received included nicotine replacement therapy, brief individual counseling, and a 2-week Just-in-Time Adaptive Intervention (JITAI) with wearable sensors. Throughout the JITAI period, a single strategy was randomly pushed (vs not) multiple times per day through the smartphone application. An EMA next assessed negative affect, positive affect, mindfulness, abstinence self-efficacy, motivation to quit, craving, and smoking motives. The primary analyses evaluated differences in EMA outcomes (proximal) for when a strategy was pushed versus not pushed. Additional analyses evaluated changes in similar outcomes collected from surveys at the baseline and end-of-treatment visits.

RESULTS: Participants (N=38) were 63% (24/38) female, 18% (7/38) Hispanic or Latino, and 29% (11/38) African American. They had an average age of 49 years and smoked an average of 15 (SD 7.9) cigarettes per day. Results indicated that receiving the JITAI significantly reduced proximal negative affect in the second (and final) week of the intervention. Self-reports provided at baseline and end of treatment showed significant decreases in perceived stress, automaticity of smoking and craving, and a significant increase in abstinence self-efficacy. Increases in abstinence self-efficacy significantly predicted abstinence.

CONCLUSIONS: To our knowledge, this is the first study to test the proximal impact of a mindfulness-based JITAI on key variables associated with smoking cessation. Our primary finding was that negative affect was lower following the completion of a strategy (vs when no strategy was delivered) in the final week of the JITAI. Among a larger sample size, future research should extend the length of the intervention to further evaluate the impact of the JITAI, as well as include a comparison condition to further evaluate how each component of the intervention uniquely impacts outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03404596; https://clinicaltrials.gov/study/NCT03404596.

PMID:40106803 | DOI:10.2196/55379

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Loss of Tbx4 Affects Postnatal Lung Development and Predisposes to Pulmonary Hypertension

Am J Respir Cell Mol Biol. 2025 Mar 19. doi: 10.1165/rcmb.2024-0459OC. Online ahead of print.

ABSTRACT

Pulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by remodeling of the precapillary pulmonary arteries. Genomic variation within the T-box 4 (TBX4) transcription factor is the second most common genetic cause of PAH, and can also cause severe lung developmental disorders with neonatal PH. Currently, the effect of TBX4 loss-of-function on later stages of lung development and predisposition to lung disease, including PH, is not well understood. Therefore, we have generated Tbx4 conditional knockout (Tbx4-CKO) mice in which Cre recombinase deletes exon 5 of Tbx4 within the embryonic lung mesenchyme to create a null allele. We harvested lungs from these mice at various timepoints to examine alveologenesis, vascularization, vascular remodeling, lung cellular composition, and disruption of transcriptional activity compared with control lungs. Right ventricular systolic pressure (RVSP) was measured in six-month-old mice to evaluate for PH. Tbx4-CKO lungs show enlargement of airspaces, as confirmed by an increase in mean linear intercept at P14 (24.9%), P36 (31.5%), and P180 (49.6%). These lungs also show a 39.3% decrease in von Willebrand Factor-positive vessels and a 14.2% increase in vessel wall thickness. Consistent with these results, Tbx4-CKO mice show a statistically significant increase of 15.7% in RVSP and 16.3% in the Fulton index. Bulk-RNA sequencing analysis revealed enrichment of pathways and genes relevant to lung alveologenesis, angiogenesis, and PH. Our results show that disruption of Tbx4 expression during early lung development is sufficient to disrupt postnatal lung development and circulation.

PMID:40106779 | DOI:10.1165/rcmb.2024-0459OC

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A new marker for predicting sentinel lymph node metastasis in early (cT1-2N0) breast cancer: Tumor-infiltrating lymphocytes (TILs)

PLoS One. 2025 Mar 19;20(3):e0320487. doi: 10.1371/journal.pone.0320487. eCollection 2025.

ABSTRACT

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are associated with lymph node metastasis and prognosis in breast cancer. Therefore, we explored the value of TILs in predicting sentinel lymph node metastasis (SLNM) in patients with early-stage (cT1-2N0) breast cancer and provided a new method for preoperative assessment of SLNM status.

METHODS: This study included 337 patients with early-stage breast cancer who underwent surgery at our hospital from January 2022 to December 2023. The expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 in the patients was assessed using immunohistochemistry (IHC). TILs in the core needle biopsy samples were evaluated histopathologically, and patients were divided into high and low TILs groups based on the density of TILs. Statistical analysis was conducted, and a predictive model was established.

RESULTS: The study found that patients with high TILs had a significantly lower rate of SLNM compared to those with low TILs (P < 0.001). The cT stage and the level of TILs were identified as independent predictive factors for SLNM. The ROC curve analysis indicated that the density of TILs has good predictive efficacy for SLNM. Based on the results of the multivariate regression analysis, a nomogram predictive model for SLNM was constructed.

CONCLUSIONS: Our study showed that the density of TILs and cT stage are independent predictive factors for SLNM in early-stage (cT1-2N0) breast cancer, and the predictive effect of TILs density on SLNM is significant in Luminal and triple-negative breast cancers.

PMID:40106761 | DOI:10.1371/journal.pone.0320487

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Increased Incidence of Asteroid Hyalosis in Bilaterial Macular Telangiectasia Type II Patients

Retina. 2025 Mar 10. doi: 10.1097/IAE.0000000000004467. Online ahead of print.

ABSTRACT

PURPOSE: Investigate the relationship between Bilateral Macular Telangiectasia Type II (MacTel) and Asteroid Hyalosis (AH) and identify the factors that influence this correlation.

METHODS: A retrospective review utilizing the Retina Consultants of Alabama database from January 2016 to February 28, 2024 was conducted. The charts of 321 patients with retinal telangiectasias were assessed, and 143 were excluded. They were further partitioned into those with AH+MacTel (n=16) versus MacTel only (n=162). The incidence was determined and compared to population-based AH studies with similar patient demographics. Demographic and ocular data were collected and compared between the AH+MacTel and MacTel only groups.

RESULTS: AH was more prevalent in our MacTel cohort (9.88%) compared to Beaver Dam (1.20%, p<.001), Blue Mountains (1.01%, p<0.001), UCLA Autopsy (1.96%, p<.001), and Gutenberg Health studies (0.477%, p<0.001). An inverse link was found between AH+MacTel patients and posterior vitreous detachments (p<0.045 univariate, p<0.025 multivariate). AH+MacTel patients presented fewer ocular conditions (1.79±1.12) than MacTel only patients (2.31±1.11) and significantly lower OCT Central Subfield Thickness (224±43.0 μm) versus MacTel alone (249±49.6 μm; unadjusted mean difference: -25 μm, 95% CI: -45.3 to -4.76).

CONCLUSION: There was a statistically significantly higher prevalence of patients with AH who also had a diagnosis of MacTel compared to the general population.

PMID:40106717 | DOI:10.1097/IAE.0000000000004467

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MAFin: Motif Detection in Multiple Alignment Files

Bioinformatics. 2025 Mar 19:btaf125. doi: 10.1093/bioinformatics/btaf125. Online ahead of print.

ABSTRACT

MOTIVATION: Whole Genome and Proteome Alignments, represented by the Multiple Alignment File (MAF) format, have become a standard approach in comparative genomics and proteomics. These often require identifying conserved motifs, which is crucial for understanding functional and evolutionary relationships. However, current approaches lack a direct method for motif detection within MAF files. We present MAFin, a novel tool that enables efficient motif detection and conservation analysis in MAF files to address this gap, streamlining genomic and proteomic research.

RESULTS: We developed MAFin, the first motif detection tool for Multiple Alignment Format files. MAFin enables the multithreaded search of conserved motifs using three approaches: 1) using user-specified k-mers to search the sequences. 2) with regular expressions, in which case one or more patterns are searched, and 3) with predefined Position Weight Matrices. Once the motif has been found, MAFin detects the motif instances and calculates the conservation across the aligned sequences. MAFin also calculates a conservation percentage, which provides information about the conservation levels of each motif across the aligned sequences, based on the number of matches relative to the length of the motif. A set of statistics enables the interpretation of each motif’s conservation level, and the detected motifs are exported in JSON and CSV files for downstream analyses.

AVAILABILITY: MAFin is offered as a Python package under the GPL license as a multi-platform application and is available at: https://github.com/Georgakopoulos-Soares-lab/MAFin.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:40106711 | DOI:10.1093/bioinformatics/btaf125

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Unfolding the nutraceutical potentials of Dendrobium nobile Lindl orchid flowers based on their color variation: a high-resolution mass spectrometry-based untargeted metabolomics study

J AOAC Int. 2025 Mar 19:qsaf025. doi: 10.1093/jaoacint/qsaf025. Online ahead of print.

ABSTRACT

BACKGROUND: Dendrobium nobile is an edible orchid with diverse therapeutic properties. In north-eastern Himalayan states of India, the extract of this flower is consumed by tribal populations for the treatment of diabetes, cancer, and cardiovascular diseases. However, the profile of biologically active compounds in the colored varieties of D. nobile orchid flowers cultivated in the north-eastern Himalayan region is not well-established, necessitating a thorough investigation.

OBJECTIVE: This study aims to establish and compare the metabolite profile of three types of D. nobile flowers (white, light-pink, and dark pink) using liquid chromatography-high resolution mass spectrometry (LC-HRMS).

METHODS: The homogenized and cryoground flower samples were extracted with aqueous methanol. After LC-MS data acquisition through full-scan (untargeted) and MS/MS (targeted) modes, data processing involved peak alignment, adduct identification, and integration. Results were compared by multivariate statistics using Independent Component Analysis.

RESULTS: A total of 73 metabolites was identified, each with mass error of less than 5 ppm for both precursor and fragment ions. From anthocyanin classes, the chemometric analysis revealed 11 distinguishing biomarker metabolites, with variable influence on projection values above 1. Across the test accessions, three compounds, viz. cyanidin-3-diglucoside, delphinidin-3-sophoroside, and delphinidin-3-gentiobioside revealed their discriminatory presence.

CONCLUSION: The study identified the therapeutically important anthocyanins for metabolomic discrimination of three different D. nobile flower accessions. The study will be useful for authenticating D. nobile accessions, derived products, and selecting candidate traits for future breeding programs for varietal improvements.

HIGHLIGHTS: This study identified and profiled the bioactive anthocyanin compounds in D. nobile orchid flowers grown in the north-eastern Himalayan region of India, based on color variations using a non-target metabolomics approach.

PMID:40106708 | DOI:10.1093/jaoacint/qsaf025

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Teleconnection from Arctic warming suppresses long-term warming in central Eurasia

Sci Adv. 2025 Mar 21;11(12):eadq9461. doi: 10.1126/sciadv.adq9461. Epub 2025 Mar 19.

ABSTRACT

Whether the rapid warming of the Arctic, particularly the Barents-Kara Sea (BKS), substantially affects the Eurasian winter climate has been debated for over a decade. Here, we use an extended dynamical adjustment method to separate the effects of internal dynamics and thermodynamically forced BKS warming on atmospheric circulation, relying solely on observations. Evidence shows that the observed link between BKS warming and Eurasian cooling is influenced by both atmospheric internal variability and forced BKS warming. Internal variability, particularly the Arctic Oscillation, predominantly contributed to the observed Eurasian cooling from 1991 to 2012. While BKS warming has a weaker impact on Eurasian cooling on interannual to interdecadal timescales, it notably affects multidecadal scales, contributing to the observed “warming hole” in central Eurasia during 1980-2022. Our findings suggest a weak but non-negligible Eurasian cooling response to BKS warming on multidecadal timescales. These findings advance the understanding of the complex causal relationships between Arctic and mid-latitude climates.

PMID:40106553 | DOI:10.1126/sciadv.adq9461

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Vibrational exercise for Crohn’s to observe response (VECTOR): Protocol for a randomized controlled trial

PLoS One. 2025 Mar 19;20(3):e0319685. doi: 10.1371/journal.pone.0319685. eCollection 2025.

ABSTRACT

Crohn’s disease (CD) is a long-term inflammatory gastrointestinal disorder, often adversely affecting physical, emotional, and psychological well-being. Pharmaceutical management is habitually adopted; although medicinal therapies require continuous administration, and are often associated with significant side effects and low adherence rates. Whole body vibration (WBV) represents a non-invasive technique, that provides vibration stimulation to the entire body. As WBV appears to target the physiological pathways and symptoms pertinent to CD epidemiology, it may have significant potential as a novel non-pharmaceutical intervention therapy in CD. This paper presents the study protocol for a randomised controlled trial investigating the impact of WBV on health outcomes in individuals with CD. This 6-week, parallel randomised controlled trial will recruit 168 individuals, assigned to receive WBV and lifestyle education 3 times per week compared to control, receiving lifestyle education only. The primary outcome of the trial will be the difference from baseline to post-intervention in health-related quality of life between the groups, assessed with the Inflammatory Bowel Disease Quality of Life Questionnaire. Secondary outcomes will include between-group differences in other questionnaires assessing fatigue, anxiety and pain, measures of physical fitness, and biological markers for disease activity and inflammation. Statistical analyses will follow an intention-to-treat approach, using linear mixed-effects models to compare changes between time points and both trial groups. Ethical approval was granted by the Nottingham Research Ethics Committee (REC: 24/EM/0106) and the study has been registered prospectively as a clinical trial (NTC06211400).

PMID:40106525 | DOI:10.1371/journal.pone.0319685