Category: Nevin Manimala

J Med Internet Res. 2025 Feb 7;27:e64069. doi: 10.2196/64069.

ABSTRACT

BACKGROUND: Data sharing plays a crucial role in health informatics, contributing to improving health information systems, enhancing operational efficiency, informing policy and decision-making, and advancing public health surveillance including disease tracking. Sharing individual participant data in public, environmental, and occupational health trials can help improve public trust and support by enhancing transparent reporting and reproducibility of research findings. The International Committee of Medical Journal Editors (ICMJE) requires all papers to include a data-sharing statement. However, it is unclear whether journals in the field of public, environmental, and occupational health adhere to this requirement.

OBJECTIVE: This study aims to investigate whether public, environmental, and occupational health journals requested data-sharing statements from clinical trials submitted for publication.

METHODS: In this bibliometric survey of “Public, Environmental, and Occupational Health” journals, defined by the Journal Citation Reports (as of June 2023), we included 202 journals with clinical trial reports published between 2019 and 2022. The primary outcome was a journal request for a data-sharing statement, as identified in the paper submission instructions. Multivariable logistic regression analysis was conducted to evaluate the relationship between journal characteristics and journal requests for data-sharing statements, with results presented as odds ratios (ORs) and corresponding 95% CIs. We also investigated whether the journals included a data-sharing statement in their published trial reports.

RESULTS: Among the 202 public, environmental, and occupational health journals included, there were 68 (33.7%) journals that did not request data-sharing statements. Factors significantly associated with journal requests for data-sharing statements included open access status (OR 0.43, 95% CI 0.19-0.97), high journal impact factor (OR 2.31, 95% CI 1.15-4.78), endorsement of Consolidated Standards of Reporting Trials (OR 2.43, 95% CI 1.25-4.79), and publication in the United Kingdom (OR 7.18, 95% CI 2.61-23.4). Among the 134 journals requesting data-sharing statements, 26.9% (36/134) did not have statements in their published trial reports.

CONCLUSIONS: Over one-third of the public, environmental, and occupational health journals did not request data-sharing statements in clinical trial reports. Among those journals that requested data-sharing statements in their submission guidance pages, more than one quarter published trial reports with no data-sharing statements. These results revealed an inadequate practice of requesting data-sharing statements by public, environmental, and occupational health journals, requiring more effort at the journal level to implement ICJME recommendations on data-sharing statements.

PMID:39919275 | DOI:10.2196/64069

Hum Reprod. 2025 Feb 7:deaf009. doi: 10.1093/humrep/deaf009. Online ahead of print.

ABSTRACT

STUDY QUESTION: Does the slow-freezing and thawing process have a negative impact on the transcriptome of oocytes isolated from early-stage human follicles compared to fresh controls?

SUMMARY ANSWER: The transcriptional profiles of fresh and frozen/thawed oocytes did not cluster separately, indicating undetectable differences between the two groups when compared to within-donor heterogeneity.

WHAT IS KNOWN ALREADY: Previous studies using histological analysis of follicle morphology, density, and stage distribution in slow-frozen/thawed human ovarian cortex compared to fresh controls showed no differences between the two groups. Clinical cases reported in the past 10 years have demonstrated that transplanted slow-frozen/thawed and fresh ovarian cortex restored normal serum FSH levels and regular menstrual cycles by 5 months. However, the slow-frozen and thawed tissue resulted in lower rates of pregnancies and live births, albeit not statistically significant.

STUDY DESIGN, SIZE, DURATION: We utilized single-cell RNA-sequencing (scRNAseq) of 144 human oocytes isolated from cadaver ovaries obtained from three donors.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Human ovarian cortex from three healthy premenopausal donors 16, 18, and 27 years old was cut into squares measuring 10 × 10 × 1 mm3 and either slow-frozen and thawed or processed fresh. First, using a novel method for isolating live oocytes from primordial and primary follicles, the ovarian cortex squares were fragmented with a McIlwain tissue chopper and enzymatically digested. Next, oocytes were mechanically denuded under a dissection microscope and placed individually into wells containing lysis buffer for scRNAseq. Lysed single oocytes were subjected to library prep using the seqWell PlexWell rapid single-cell RNA protocol. Pooled libraries were subjected to 150-bp paired-end sequencing on the NovaSeq6000 Illumina platform. In total, we sequenced 144 oocytes-24 oocytes isolated fresh and 24 oocytes isolated after slow-freezing and thawing from each of the three donors. Additionally, we performed histological analysis of fresh and frozen/thawed ovarian cortex tissue from all three donors using hematoxylin and eosin staining and analyzed morphology, follicle density, and follicle stage distribution differences between fresh and cryopreserved ovarian cortex.

MAIN RESULTS AND THE ROLE OF CHANCE: The histological analysis revealed no differences in follicle stage distribution or follicle morphology between conditions, with the percentage of normal follicles in fresh and frozen/thawed tissue, respectively, as 86.7% and 91.0% for Donor 1, 91.7% and 92.5% for Donor 2, and 96.1% and 91.1% for Donor 3. The follicle density per mm3 in fresh and frozen/thawed tissue, respectively, was 279.4 and 235.8 for Donor 1, 662.2 and 553.5 for Donor 2, and 55.8 and 71.4 for Donor 3. The difference in follicle density was not statistically significant between fresh and frozen/thawed conditions for Donors 2 and 3, and significant (P = 0.017) for Donor 1. The stromal cell densities in fresh and frozen/thawed tissue, respectively, were 0.014 in both conditions for Donor 1, 0.014 and 0.016 for Donor 2, and 0.013 and 0.014 for Donor 3. There was no statistically significant difference in stromal cell density between conditions in Donor 1 and Donor 3, though it was statistically significant (P ≤ 0.001) for Donor 2. The transcriptional profiles of fresh and frozen/thawed oocytes did not cluster separately, suggesting insignificant differences between the two groups. However, at the group mean level, there was a small shift between the fresh and frozen/thawed oocytes and the shifts were parallel across the three donors. In this comparison, fresh oocytes were enriched for gene ontology terms related to chromosome segregation and mitosis, whereas frozen/thawed oocytes were enriched for terms related to wound response, cAMP signaling, and extracellular matrix organization.

LARGE SCALE DATA: Datasets available on Zenodo.org. DOI: https://zenodo.org/records/13224872.

LIMITATIONS, REASONS FOR CAUTION: In this study, we only sequenced the oocytes isolated from early-stage follicles due to technical challenges collecting and sequencing the somatic cells surrounding the oocytes. Investigating the transcriptomic changes after freezing and thawing in the somatic cells would need to be studied in the future. Additionally, we built RNAseq libraries immediately after thawing focusing on the immediate changes. Investigation of the effects that manifest at later timepoints, either in culture or upon implantation in an animal model, may reveal additional effects of the freeze/thaw process on the transcriptome.

WIDER IMPLICATIONS OF THE FINDINGS: The only clinically approved method of fertility preservation for prepubertal cancer patients and adult patients who cannot delay cancer treatment is ovarian tissue cryopreservation. Investigation of cryopreservation-induced changes in follicles at all stages is critical to further our understanding of the safety and efficacy of using these tissues for fertility preservation in the clinic. Our study is the first to analyze transcriptomic changes between individual fresh and slow-frozen/thawed human oocytes collected from early-stage follicles. To accomplish this, we developed a novel method for dissociating both fresh and frozen/thawed human ovarian cortex to obtain live denuded oocytes from early-stage follicles. Our findings provide insights into the use of cryopreserved tissue and follicles for fertility preservation efforts.

STUDY FUNDING/COMPETING INTEREST(S): This work was funded by National Institutes of Health (NIH) R01HD099402, Career Training in Reproductive Biology (CTRB) Training Grant National Institutes of Health (NIH) T32 to Jordan Machlin, National Institutes of Health (NIH) F31-HD106626 and National Institutes of Health (NIH) T31H-D079342 to Andrea Jones, National Institutes of Health (NIH) T32-GM70449 to D. Ford Hannum, and The Chan Zuckerberg Initiative Grant CZF2019-002428. We have no conflicts of interest to declare.

PMID:39919251 | DOI:10.1093/humrep/deaf009

J Head Trauma Rehabil. 2025 Feb 7. doi: 10.1097/HTR.0000000000001016. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine the relationship between neighborhood disadvantage and severity of vestibular, sensory, mood-behavioral, and cognitive neurobehavioral symptoms among Veterans with a mild traumatic brain injury (mTBI); and whether Veterans in underrepresented racial/ethnic groups with high neighborhood disadvantage experience the most severe symptoms.

SETTING: Outpatient Veterans Health Administration (VHA).

PARTICIPANTS: Veterans with the following data available in the electronic health record (2014-2020): (1) clinician-confirmed mTBI and complete neurobehavioral symptom inventory (NSI) as part of their comprehensive traumatic brain injury evaluation (CTBIE) and (2) area deprivation index (ADI) scores assessing neighborhood disadvantage from the same quarter as their CTBIE.

DESIGN: Retrospective cohort study. Latent variable regression was used to examine unique and interactive relationships between neighborhood disadvantage, race/ethnicity, and neurobehavioral symptoms.

MAIN MEASURES: NSI and ADI national percentile rank.

RESULTS: The study included 58 698 eligible Veterans. Relative to Veterans in the first quintile of ADI national percentile rank, representing those with the least neighborhood disadvantage, Veterans in the ADI quintiles indicating greater neighborhood disadvantage reported more severe vestibular, sensory, mood-behavioral, and cognitive symptoms. The strongest associations between neighborhood disadvantage and neurobehavioral symptoms were observed within the sensory (β = 0.07-0.16) and mood-behavioral domains (β = 0.06-0.15). Statistical interactions indicated that the association between underrepresented racial/ethnic group status (vs. identifying as white, non-Hispanic) and the severity of neurobehavioral symptoms did not differ among those with severe neighborhood disadvantage versus those without.

CONCLUSION: Veterans with mTBI living in more disadvantaged neighborhoods reported more severe neurobehavioral symptoms relative to those in the most advantaged neighborhoods, with the strongest relationships detected within the sensory and mood-behavioral domains. While neighborhood disadvantage and underrepresented race/ethnicity were both independently associated with symptoms, these factors did not interact to produce more severe symptoms. Findings suggest that addressing factors driving socioeconomic disadvantage may assist in mitigating symptoms in this population.

PMID:39919249 | DOI:10.1097/HTR.0000000000001016

Environ Toxicol Chem. 2025 Feb 1;44(2):484-496. doi: 10.1093/etojnl/vgae039.

ABSTRACT

The pH of freshwater ecosystems affects bioavailability of various metals to various organisms, including daphnids. Although it is well known that daphnid species show interclonal variation of metal sensitivity, knowledge about interclonal variation of bioavailability effects, such as the pH effect, is scarce. Here, we compared the effect of pH on chronic copper toxicity between two clones of Ceriodaphnia dubia, within its natural pH niche, which we determined to be approximately pH 6.5-8.5 based on existing experimental and biological monitoring data. Using a Bayesian modeling approach, we found that the effect of pH was not statistically significantly different between the two clones (with a credibility > 95%). Overall, we found an approximately threefold decrease in chronic Cu toxicity with increasing pH between pH 6.5 and 8.5, with 7-day 20% effect concentration (EC20) values ranging between 11.0 and 30.9 µg/L dissolved Cu. We then calibrated a preliminary generalized bioavailability model (gBAM) using these data and found a pH-effect slope parameter SpH = -0.247, which is within the range of previously reported values for Daphnia magna (-0.056 to -0.361) and similar to the SpH value of -0.220 used in the “invertebrate gBAM” for bioavailability-based Cu risk assessment under the Registration, Evaluation, Authorisation and Restriction of Chemicals. The preliminary C. dubia gBAM captured the magnitude of the observed pH effect well (mean of 1.3-fold EC20 prediction error, n = 9). It was also able to accurately predict chronic Cu toxicity in natural waters reported in an independent dataset (mean of 1.4-fold prediction error, n = 6). Also, two D. magna gBAMs (for two clones) and the invertebrate gBAM showed comparable predictive capabilities. Collectively, our work highlights the importance of studying relations between pH and metal bioavailability within the species’ natural niche. It also confirms earlier findings that biological variation of pH-bioavailability relations typically does not have a large impact on predictive capacity of bioavailability models, which is important for regulatory applications.

PMID:39919235 | DOI:10.1093/etojnl/vgae039

Prim Care Companion CNS Disord. 2025 Jan 28;27(1):24m03723. doi: 10.4088/PCC.24m03723.

ABSTRACT

Introduction: Mental health of health care workers (HCWs) was affected during the COVID-19 pandemic due to direct handling of suspected and confirmed cases. While neurobiological mechanisms that mediate stress, depression, and anxiety are well established, psychological mechanisms are not.

Objective: To assess (1) the prevalence of anxiety, depression, insomnia, and perceived stress among accredited social health activists, multipurpose health workers, auxiliary nurse midwives, and other certified HCWs of rural areas of Telangana, India and (2) the factors that mediate stress with depression and anxiety.

Methods: A total of 300 HCWs from across 10 primary health centers across 5 districts were selected. All participants self-reported their anxiety, depression, sleep problems, and perceived stress related to the pandemic. Sociodemographic and other relevant data pertinent to the context of stress and the pandemic were also obtained. The survey used translated and validated self report instruments and was conducted during August and September 2021.

Results: The mean (SD) scores on the Insomnia Severity Index, 7-item Generalized Anxiety Disorder scale, Pandemic-Related Perceived Stress Scale of COVID-19, and 9-item Patient Health Questionnaire were 5.94 (5.6), 4.21 (4.5), 21.94 (5.8), and 3.89 (4.8), respectively. Age <35 years and family members being COVID-19 positive were significant predictors of depression and anxiety, respectively. Greater number of family members and COVID-19-positive status were significant predictors of insomnia. While the effect of stress on anxiety was indirect through the mediation of insomnia and depression, the effect of stress on depression was direct as well as through the mediation of anxiety.

Conclusion: The study results highlight the importance of measures to address sleep-related issues in individuals who are experiencing psychosocial stressors to prevent the development of depression and anxiety.

Prim Care Companion CNS Disord 2025;27(1):24m03723.

Author affiliations are listed at the end of this article.

PMID:39919227 | DOI:10.4088/PCC.24m03723

Nurs Res. 2025 Feb 6. doi: 10.1097/NNR.0000000000000810. Online ahead of print.

ABSTRACT

BACKGROUND: The analysis of health diary data has long relied on inferential statistical methods focusing on sample means and ad hoc methods to calculate each individual’s variation in health outcomes.

OBJECTIVES: In this paper, an advanced statistical model is applied to daily diary self-reported health outcomes to simultaneously study an individual’s likeliness to report an outcome, daily mean intensity level, and variability in daily measures.

METHODS: Using observational, secondary data from 782 adults, we analyzed self-report daily fatigue symptoms, distinguishing between whether an individual reported fatigue and its severity when reported. Self-reported depressed affect and participant characteristics were used as predictors of daily fatigue symptoms.

RESULTS: A higher likeliness to report fatigue correlated with higher mean fatigue severity and greater stability in severity ratings. Higher mean severity correlated with greater stability in severity ratings. Females and those with high depressed affect were more likely to report fatigue. Females and those with high depressed affect reported greater mean severity.

DISCUSSION: The model applied to daily measures allowed for the simultaneous study of an individual’s likeliness to report a symptom, daily mean symptom severity, and variability in severity across days. An individual’s daily variation in symptom severity was represented as a model parameter that did not contain measurement error that is present in ad hoc methods.

PMID:39919218 | DOI:10.1097/NNR.0000000000000810

J Craniofac Surg. 2025 Feb 7. doi: 10.1097/SCS.0000000000011127. Online ahead of print.

ABSTRACT

INTRODUCTION: Alveolar cleft grafting plays a vital role in the treatment of individuals with cleft lip and palate. Vitamin D plays a crucial role in bone healing.

METHODOLOGY: The study involved 40 patients with cleft alveolus who were seeking alveolar cleft grafting (ACG). Participants were categorized into 2 groups-study and control-based on their vitamin D levels: those with levels below 20 were placed in the control group, while those with levels above 20 were assigned to the study group.

RESULTS: Assessment of alveolar cleft grafting success rate was done by Bergland Scale assessment. The assessment using χ2 showed that the bone level in the study group was better than the control. However, the improvement was not statistically significant (P=0.2). Assessment of volumetric bone fill was done on the CBCT. The results were statistically checked by independent t-test and showed that the bone fill in the study group (224±78.4 mm3) was better than the control (176±135 mm3). However, the improvement was not statistically significant (P=0.17). Assessment of the incidence of fistula recurrence was done using the χ2 test. In the study group, the incidence of fistula was 5%, while in the control group, it was 30%. The incidence of success in reducing fistula recurrence was statistically significant (P=0.04).

CONCLUSION: Adjustment of vitamin D level may be a successful tool in predicting the success of the alveolar cleft grafting procedure, especially regarding the elimination of fistula recurrence.

PMID:39919215 | DOI:10.1097/SCS.0000000000011127

Prehosp Emerg Care. 2025 Feb 7:1-16. doi: 10.1080/10903127.2025.2462774. Online ahead of print.

ABSTRACT

OBJECTIVES: Personal attitudes amongst emergency medical services (EMS) clinicians could influence successful implementation of prehospital buprenorphine administration programs (PBAPs), yet few studies have investigated EMS clinician perceptions concerning these innovative programs. This mixed-methods study assessed EMS clinician perceptions and concerns about PBAPs.

METHODS: Emergency Medical Technicians (EMTs), advanced EMTs and paramedics were recruited for focus groups from Upstate South Carolina. Researchers moderated groups of 12 or fewer and field personnel were interviewed separately from EMS training officers and leadership. Participants took a survey assessing demographic, employment, and contextual information on EMS-led interventions addressing the opioid epidemic. Moderators asked participants to provide confidential responses to four open-ended questions. Thematic analysis was applied to all responses using the framework method. A codebook was modeled using deductive themes from previous literature, while inductive themes and subthemes were added through researcher consensus. Final coding of themes and subthemes was constructed independently by two researchers with disagreements resolved by a third. Descriptive statistics summarized demographic, employment, and contextual information collected from the survey.

RESULTS: The 107 participants were predominantly male (69.2%) and White (96.3%) with an average age of 38.4 years (SD = 11.4). Half were paramedics and 35.5% were EMTs with EMS experience ranging from 3 months to 39 years, median of 10 years. Most (70.2%) heard of buprenorphine and 28.9% received education on medication for opioid use disorder (MOUD). Describing initial reactions to an overdose, themes included overdoses as a routine part of EMS and naloxone distribution changing overdose dynamics. Themes included opioid withdrawal is not a medical emergency, buprenorphine negatively affecting EMS operations, and PBAPs requiring culture shift. Themes surrounding concerns included EMS clinician perceptions of individuals with opioid use disorder (OUD), PBAPs increasing substance misuse, and buprenorphine increasing EMS clinician liability. At the end of the session 45.8% stated they would want their EMS agency to participate in a PBAP, 44.9% would not want their agency to participate, and 8 (7.5%) did not answer.

CONCLUSIONS: Emergency medical services clinicians’ perceptions towards prehospital buprenorphine administration could influence adoption of PBAP protocols. Findings may inform PBAP educational initiatives which mitigate these concerns and knowledge gaps.

PMID:39919214 | DOI:10.1080/10903127.2025.2462774

Prehosp Emerg Care. 2025 Feb 7:1-9. doi: 10.1080/10903127.2025.2462211. Online ahead of print.

ABSTRACT

OBJECTIVES: Emergency medical services (EMS) post-overdose outreach programs expand beyond traditional 9-1-1 response to offer overdose survivors linkage to substance use treatment and other related harm-reducing interventions. Although intuitive and increasingly popular, evidence to define expected outcomes is exceedingly limited. We evaluated process and patient outcomes of one large Midwestern post-overdose outreach program to describe outreach characteristics and linkage to substance use treatment.

METHODS: This retrospective cohort study used clinical program records of individuals referred to a multidisciplinary post-overdose outreach program following a non-fatal presumed opioid overdose with emergency response. Measures included (i) number of outreach attempts, (ii) modalities of outreach attempts (in-person visit, text message, letter, phone call, or electronic mail), (iii) outcome of outreach (i.e., if the individual was contacted), (iv) interventions provided including linkage to substance use treatment with coordinated admission and transportation. We used descriptive statistics to report patient characteristics, outreach frequency, outreach modality, successful contact, and treatment linkage through the program.

RESULTS: From 2020-2022, the program attempted outreach to 3,437 individuals. The median age was 37 years (interquartile range, IQR, 30-47). Most individuals were white/non-Hispanic (n = 2,077, 63.1%) and male (n = 2,084, 61.2%). Few were unhoused at the time of outreach (n = 246, 7.2%). The program made a total of 7,935 outreach attempts with a median of 2 outreach attempts (IQR 1-3) per individual. The most common outreach modalities were in-person visit (n = 3,300, 41.6%) and text message (n = 2,776, 35.0%), though phone calls and in-person visits most often resulted in successful contact (52.6% and 23.7%, respectively). Outreach attempts resulted in 743 (21.6%) successful contacts and the program linked 304 individuals (40.9% of all contacted individuals, 8.8% of all attempted outreach) to treatment. Notably, 160 (52.6%) of the 304 individuals linked to treatment required 3 or more outreach attempts before treatment linkage occurred.

CONCLUSIONS: Post-overdose outreach initiated by EMS can successfully find and link individuals to substance use treatment following a non-fatal opioid overdose. However, this intervention may be resource intensive, often requiring multiple attempts at outreach and several modalities of interaction to facilitate treatment linkage.

PMID:39919200 | DOI:10.1080/10903127.2025.2462211

Mol Pharmacol. 2025 Jan;107(1):100010. doi: 10.1016/j.molpha.2024.100010. Epub 2024 Dec 12.

ABSTRACT

Chemokine receptors CCR3, CCR4, and CCR5 are G protein-coupled receptors implicated in diseases like cancer, Alzheimer’s, asthma, human immunodeficiency virus (HIV), and macular degeneration. Recently, CCR3 and CCR4 have emerged as potential stroke targets. Although only the CCR5 antagonist maraviroc is US Food and Drug Administration-approved (for HIV), we curated data on CCR3, CCR4, and CCR5 antagonists from ChEMBL to develop and validate machine learning models. The top 5-fold cross-validation statistics for these models were high for both classification and regression models for CCR3 (receiver operating characteristic [ROC], 0.94; R² = 0.8), CCR4 (ROC, 0.98; R² = 0.57), and CCR5 (ROC, 0.96; R² = 0.78). The models for CCR3/4 were used to screen a small library of US Food and Drug Administration-approved drugs and 17 were initially tested in vitro against both CCR3/4 receptors. A promising compound lapatinib, a dual tyrosine kinase inhibitor, was identified as an antagonist for CCR3 (IC₅₀, 0.7 μM) and CCR4 (IC₅₀, 1.8 μM). Additional testing also identified it as an CCR5 antagonist (IC₅₀, 0.9 μM), and it showed moderate in vitro HIV I inhibition. We demonstrated how machine learning can be used to identify molecules for repurposing as antagonists for G protein-coupled receptors such as CCR3, CCR4, and CCR5. Lapatinib may represent a new orally available chemical probe for these 3 receptors, and it provides a starting point for further chemical optimization for multiple diseases impacting human health. SIGNIFICANCE STATEMENT: We describe the building of machine learning models for the chemokine receptors CCR3, CCR4, and CCR5 trained on data from the ChEMBL database. Using these models, we identified lapatinib as a potent inhibitor of CCR3, CCR4, and CCR5. Our study illustrates the potential of machine learning in identifying molecules for repurposing as antagonists for G protein-coupled receptors, including CCR3, CCR4, and CCR5, which have various therapeutic applications.

PMID:39919162 | DOI:10.1016/j.molpha.2024.100010