Tag: pubmed

PLoS Genet. 2025 Jan 10;21(1):e1011563. doi: 10.1371/journal.pgen.1011563. Online ahead of print.

ABSTRACT

Understanding the genetic regulatory mechanisms of gene expression is an ongoing challenge. Genetic variants that are associated with expression levels are readily identified when they are proximal to the gene (i.e., cis-eQTLs), but SNPs distant from the gene whose expression levels they are associated with (i.e., trans-eQTLs) have been much more difficult to discover, even though they account for a majority of the heritability in gene expression levels. A major impediment to the identification of more trans-eQTLs is the lack of statistical methods that are powerful enough to overcome the obstacles of small effect sizes and large multiple testing burden of trans-eQTL mapping. Here, we propose ADELLE, a powerful statistical testing framework that requires only summary statistics and is designed to be most sensitive to SNPs that are associated with multiple gene expression levels, a characteristic of many trans-eQTLs. In simulations, we show that for detecting SNPs that are associated with 0.1%-2% of 10,000 traits, among the 8 methods we consider ADELLE is clearly the most powerful overall, with either the highest power or power not significantly different from the highest for all settings in that range. We apply ADELLE to a mouse advanced intercross line data set and show its ability to find trans-eQTLs that were not significant under a standard analysis. We also apply ADELLE to trans-eQTL mapping in the eQTLGen data, and for 1,451 previously identified trans-eQTLs, we discover trans association with additional expression traits beyond those previously identified. This demonstrates that ADELLE is a powerful tool at uncovering trans regulators of genetic expression.

PMID:39792937 | DOI:10.1371/journal.pgen.1011563

PLoS Negl Trop Dis. 2025 Jan 10;19(1):e0012786. doi: 10.1371/journal.pntd.0012786. Online ahead of print.

ABSTRACT

BACKGROUND: Severe respiratory distress and acute kidney injury (AKI) are key factors leading to poor outcomes in patients with dengue shock syndrome (DSS). There is still limited data on how much resuscitated fluid and the specific ratios of intravenous fluid types contribute to the development of severe respiratory distress necessitating mechanical ventilation (MV) and AKI in children with DSS.

METHODOLOGY/PRINCIPAL FINDINGS: This retrospective study was conducted at a tertiary pediatric hospital in Vietnam between 2013 and 2022. The primary outcomes were the need for MV and renal function within 48 h post-admission. A predictive model for MV was developed based on covariates from the first 24 h of PICU admission. Changes in renal function within 48 h were analyzed using a linear mixed-effects model. A total of 1,278 DSS children with complete clinical and fluid data were included. The predictive performance of MV based on the total intravenous fluid volume administered yielded an AUC of 0.871 (95% CI, 0.836-0.905), while the colloid-to-crystalloid ratio showed an AUC of 0.781 (95% CI, 0.743-0.819) (both P < 0.001). The optimal cut-off point of the cumulative fluid infusion was 181 mL/kg, whereas that of the colloid-to-crystalloid ratio was 1.6. Multivariable analysis identified female patients, severe bleeding, severe transaminitis, excessive fluid resuscitation, and a higher proportion of colloid solutions in the first 24 h as significant predictors of MV in DSS patients. The predictive model for MV demonstrated high accuracy, with a C-statistic of 89%, strong calibration, and low Brier score (0.04). Importantly, a more pronounced decline in glomerular filtration rate was observed in DSS patients who required MV than in those who did not.

CONCLUSIONS/SIGNIFICANCE: This study provides insights into optimizing fluid management protocols, highlighting the importance of monitoring fluid volume and the colloid-to-crystalloid ratio during early resuscitation to improve the clinical outcomes of DSS patients.

PMID:39792932 | DOI:10.1371/journal.pntd.0012786

PLoS Genet. 2025 Jan 10;21(1):e1011553. doi: 10.1371/journal.pgen.1011553. Online ahead of print.

ABSTRACT

Elucidating the genetic components of plant genotype-by-environment interactions is of key importance in the context of increasing climatic instability, diversification of agricultural practices and pest pressure due to phytosanitary treatment limitations. The genotypic response to environmental stresses can be investigated through multi-environment trials (METs). However, genome-wide association studies (GWAS) of MET data are significantly more complex than that of single environments. In this context, we introduce metaGE, a flexible and computationally efficient meta-analysis approach for jointly analyzing single-environment GWAS of any MET experiment. The metaGE procedure accounts for the heterogeneity of quantitative trait loci (QTL) effects across the environmental conditions and allows the detection of QTL whose allelic effect variations are strongly correlated to environmental cofactors. We evaluated the performance of the proposed methodology and compared it to two competing procedures through simulations. We also applied metaGE to two emblematic examples: the detection of flowering QTLs whose effects are modulated by competition in Arabidopsis and the detection of yield QTLs impacted by drought stresses in maize. The procedure identified known and new QTLs, providing valuable insights into the genetic architecture of complex traits and QTL effects dependent on environmental stress conditions. The whole statistical approach is available as an R package.

PMID:39792927 | DOI:10.1371/journal.pgen.1011553

Hum Reprod. 2025 Jan 10:deae300. doi: 10.1093/humrep/deae300. Online ahead of print.

ABSTRACT

In recent years, the transfer of more than one embryo has become less frequent to diminish multiple pregnancies. Even so, there is still a risk of one embryo splitting into two or even three. This report presents the case of a triamniotic monochorionic gestation in a 35-year-old woman, obtained after the transfer of a single day 5 embryo that had been previously hatched with a laser and subsequently transferred in a fresh IVF cycle. The morphokinetics of this embryo as well as another eight that produced monozygotic twins were compared with nine embryos that achieved singleton gestations. An artificial intelligence (AI) system was used to perform this analysis objectively. Embryo divisions leading to multiple gestations were slower across all analysed parameters. This was most evident in the time taken to reach the 5-cell stage (t5) (48.74 ± 3.21 versus 44.69 ± 5.61 h) and the morula stage (tM) (85.08 ± 10.00 versus 78.13 ± 5.35 h). Moreover, blastocyst diameter (161.80 ± 26.50 versus 179.10 ± 25.88 μm) and area (21 684 ± 7267.4 versus 26 516 ± 7254.8 μm2) were smaller in these embryos, but the differences did not reach statistical significance. This is the first report, to our knowledge, to use AI to analyse and compare morphokinetic parameters between singleton pregnancies and a group of embryos that produced twin and triplet pregnancies.

PMID:39792920 | DOI:10.1093/humrep/deae300

J Med Internet Res. 2025 Jan 10;27:e52591. doi: 10.2196/52591.

ABSTRACT

BACKGROUND: The COVID-19 pandemic demonstrated the global need for accessible content to rapidly train health care workers during health emergencies. The massive open access online course (MOOC) format is a broadly embraced strategy for widespread dissemination of trainings. Yet, barriers associated with technology access, language, and cultural context limit the use of MOOCs, particularly in lower-resource communities. There is tremendous potential for MOOC developers to increase the global scale and contextualization of learning; however, at present, few studies examine the adaptation and sharing of health MOOCs to address these challenges.

OBJECTIVE: The World Health Organization’s Health Emergencies Programme Learning and Capacity Development Unit and the Stanford Center for Health Education collaborated to survey learners from 4 emergency health MOOCs on the OpenWHO platform to examine differences in course use by World Bank country income classification across three dimensions: (1) how health education MOOCs are used and shared, (2) how health workers adapt MOOC content to meet local training and information needs, and (3) how content adaptations help frontline health workers overcome barriers to using MOOCs.

METHODS: This study draws upon two sources of data: (1) course enrollment data collected from the 4 emergency health MOOCs (N=96,395) and (2) survey data collected from learners who participated in at least 1 of the 4 MOOCs (N=926). Descriptive statistics are used to summarize learner characteristics. Differences in enrollment, sharing, and adaptation by country income classification are examined using Pearson chi-square test.

RESULTS: Of the enrollees who indicated their country of residence, half were from lower-middle-income countries (LMICs; 43,168/85,882, 50%) and another 9% (7146/85,882) from low-income countries. The majority of all respondents shared content (819/926, 88%) and used content in official trainings (563/926, 61%). Respondents were more likely to share and use content for trainings in LMICs than in high-income countries (91% vs 81%; P=.001). Learners in LMICs also shared content with more people on average compared with high-income country learners although the difference is not statistically significant (9.48 vs 6.73 people; P=.084). Compared with learners in high-income countries, learners in LMICs were more likely to adapt materials to distribute via offline formats or technologies, such as WhatsApp or text message (31% vs 8%; P<.001); to address cultural, linguistic, or other contextual needs (20% vs 12%; P=.076); and to meet local guidelines (20% vs 9%; P=.010). Learners in LMICs indicated greater accessibility challenges due to technological and linguistic barriers.

CONCLUSIONS: Learners commonly share content from MOOCs about public health emergencies; this is especially true in low-income countries and LMICs. However, content is often adapted and shared via alternative formats. Our findings identify a critical opportunity to improve MOOC design and dramatically scale the impact of MOOCs to better meet diverse global needs.

PMID:39792445 | DOI:10.2196/52591

J Cancer Res Ther. 2024 Dec 1;20(7):2061-2065. doi: 10.4103/jcrt.jcrt_1281_24. Epub 2025 Jan 10.

ABSTRACT

PURPOSE: To investigate and compare the feasibility, safety, and clinical outcomes of antegrade and retrograde laparoscopic bilateral inguinal lymphadenectomy for penile cancer.

METHODS: We retrospectively analyzed the clinical data of 32 patients with penile cancer admitted between 2018 and 2022. Among them, 17 patients underwent antegrade laparoscopic inguinal lymphadenectomy (ALIL group) and 15 underwent retrograde laparoscopic inguinal lymphadenectomy (RLIL group). The key surgical procedures and techniques are described. Operative time, intraoperative blood loss, hospital stay, drainage duration, postoperative complications, and follow-up data in both groups were statistically analyzed.

RESULTS: Surgery in both groups was successfully completed without the need for intraoperative conversion to open surgery. The operative time was significantly shorter for ALIL than for RLIL (P < 0.001). Significantly less intraoperative blood loss was reported with ALIL than with RLIL (P < 0.001). The ALIL group had a significantly shorter hospital stay than the RLIL group (P = 0.027). The number of removed lymph nodes in the ALIL group differed insignificantly from that in the RLIL group (P = 0.360). Postoperative drainage duration, recurrence, short-term survival, and postoperative complications were similar between both groups.

CONCLUSION: In the patients with penile cancer, ALIL and RLIL yielded similar perioperative outcomes. However, ALIL was associated with shorter operative time, less blood loss, and shorter hospital stays. ALIL did not require repositioning of the laparoscopic instruments, thereby simplifying the procedure and minimizing patient trauma. Additionally, if needed, pelvic lymphadenectomy could be performed simultaneously from the same trocar position used in ALIL.

PMID:39792416 | DOI:10.4103/jcrt.jcrt_1281_24

J Cancer Res Ther. 2024 Dec 1;20(7):2013-2020. doi: 10.4103/jcrt.jcrt_338_24. Epub 2025 Jan 10.

ABSTRACT

OBJECTIVE: Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) serve as pivotal tumor markers in colorectal cancer (CRC). However, uncertainty persists regarding the prognostic significance of the two tumor markers when falling within the normal range. We attempt to compare the prognostic differences of tumor markers at different levels within the reference range.

METHODS: This retrospective study scrutinized 2,167 cases of stage II CRC verified by pathology after surgery at the Fudan University Shanghai Cancer Center. Using R software to calculate the optimal critical value to compare the clinical and pathological characteristics and prognosis of different levels of tumor markers. The survival and regression modeling strategies packages of R software drew the nomograms.

RESULTS: Utilizing R software, the optimal critical value of CA19-9 was determined as 12.12 U/mL and that of CEA as 1.89 U/mL. Kaplan-Meier survival analysis unveiled that, within the normal range, higher levels of CEA were linked to poorer overall survival (OS) [HR = 1.829 (1.280, 2.989), P = 0.0033] and disease-free survival (DFS) [HR = 1.472 (1.114, 1.944), P = 0.0444]. Similarly, heightened levels of CA19-9 also indicated inferior OS [HR = 1.750 (1.203, 2.455), P = 0.0076] and DFS [HR = 1.361 (1.098, 1.686), P = 0.0049]. Furthermore, multivariate analysis identified CA19-9 as an independent risk factor for OS (HR = 1.49,95% CI: 1.086-2.045, P = 0.014) and DFS (HR = 1.327,95% CI: 1.070-1.647, P = 0.01), while the impact of CEA on OS and DFS was not statistically significant. A nomogram constructed based on the Cox regression model can effectively evaluate the prognosis of CRC patients.

CONCLUSION: Although within the normal range, elevated CA19-9 was associated with an inferior prognosis, chemotherapy decisions of different intensities can be adjusted based on nomograms. This work will contribute to standardizing the diagnosis and treatment of stage II CRC and provide clinicians with essential insights for chemotherapy decisions.

PMID:39792411 | DOI:10.4103/jcrt.jcrt_338_24

JAMA Netw Open. 2025 Jan 2;8(1):e2453807. doi: 10.1001/jamanetworkopen.2024.53807.

ABSTRACT

IMPORTANCE: An unhealthy lifestyle is believed to increase the development and persistence of low back pain, but there is uncertainty about whether integrating support for lifestyle risks in low back pain management improves patients’ outcomes.

OBJECTIVE: To assess the effectiveness of the Healthy Lifestyle Program (HeLP) compared with guideline-based care for low back pain disability.

DESIGN, SETTING, AND PARTICIPANTS: This superiority, assessor-blinded randomized clinical trial was conducted in Australia from September 8, 2017, to December 30, 2020, among 346 participants who had activity-limiting chronic low back pain and at least 1 lifestyle risk (overweight, poor diet, physical inactivity, and/or smoking), referred from hospital, general practice, and community settings. Statistical analysis was performed from January to December 2021.

INTERVENTIONS: Participants were block randomized to the HeLP intervention (n = 174; 2 postrandomization exclusions) or guideline-based physiotherapy care (n = 172), stratified by body mass index, using a concealed function in REDCap. HeLP integrated healthy lifestyle support with guideline-based care using physiotherapy and dietetic consultations, educational resources, and telephone-based health coaching over 6 months.

MAIN OUTCOMES AND MEASURES: The primary outcome was low back pain disability (Roland Morris Disability Questionnaire [RMDQ] score; 0-24 scale, where higher scores indicate greater disability) at 26 weeks. Secondary outcomes were weight, pain intensity, quality of life, and smoking. Analyses were performed by intention to treat. We estimated the complier average causal effect (CACE) as sensitivity analyses.

RESULTS: The sample of 346 individuals (mean [SD] age, 50.2 [14.4] years; 190 female participants [55%]) had a baseline mean (SD) RMDQ score of 14.7 (5.4) in the intervention group and 14.0 (5.5) in the control group. At 26 weeks, the between-group difference in disability was -1.3 points (95% CI, -2.5 to -0.2 points; P = .03) favoring HeLP. CACE analysis revealed clinically meaningful benefits in disability among compliers, favoring HeLP (-5.4 points; 95% CI, -9.7 to -1.2 points; P = .01). HeLP participants lost more weight (-1.6 kg; 95% CI, -3.2 to -0.0 kg; P = .049) and had greater improvement in quality of life (physical functioning score; 1.8, 95% CI, 0.1-3.4; P = .04) than control participants.

CONCLUSIONS AND RELEVANCE: Combining healthy lifestyle management with guideline-based care for chronic low back pain led to small improvements in disability, weight, and quality of life compared with guideline-based care alone, without additional harm. Targeting lifestyle risks in the management of chronic low back pain may be considered safe and may offer small additional health benefits beyond current guideline-based care.

TRIAL REGISTRATION: http://anzctr.org.au Identifier: ACTRN12617001288314.

PMID:39792385 | DOI:10.1001/jamanetworkopen.2024.53807

JAMA Netw Open. 2025 Jan 2;8(1):e2454319. doi: 10.1001/jamanetworkopen.2024.54319.

ABSTRACT

IMPORTANCE: Understanding environmental risk factors for gestational diabetes (GD) is crucial for developing preventive strategies and improving pregnancy outcomes.

OBJECTIVE: To examine the association of county-level radon exposure with GD risk in pregnant individuals.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, population-based cohort study used data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) cohort, which recruited nulliparous pregnant participants from 8 US clinical centers between October 2010 and September 2013. Participants who had pregestational diabetes or were missing data on GD or county-level radon measurements were excluded from the current study. Data were analyzed from September 2023 to January 2024.

EXPOSURES: County-level radon data were created by the Lawrence Berkeley National Laboratory based on the Environmental Protection Agency’s short- and long-term indoor home radon assessments. Radon exposure was categorized into 3 groups: less than 1, 1 to less than 2, and 2 or more picocuries (pCi)/L (to convert to becquerels per cubic meter, multiply by 37). Because radon, smoking, and fine particulate matter air pollutants (PM2.5) may share similar biological pathways, participants were categorized by joint classifications of radon level (<2 and ≥2 pCi/L) with smoking status (never smokers and ever smokers) and radon level with PM2.5 level (above or below the median).

MAIN OUTCOMES AND MEASURES: The main outcome was GD, identified based on glucose tolerance testing and information from medical record abstraction. Multiple logistic regression models were used to assess the association between radon exposure and GD.

RESULTS: Among the 9107 participants, mean (SD) age was 27.0 (5.6) years; 3782 of 9101 (41.6%) had ever used tobacco. The mean (SD) county-level radon concentration was 1.6 (0.9) pCi/L, and 382 participants (4.2%) had GD recorded. After adjusting for potential confounders, individuals living in counties with the highest radon level (≥2 pCi/L) had higher odds of developing GD compared with those living in counties with the lowest radon level (<1 pCi/L) (odds ratio [OR], 1.37; 95% CI, 1.02-1.84); after additional adjustment for PM2.5, the OR was 1.36 (95% CI, 1.00-1.86). Elevated odds of GD were also observed in ever smokers living in counties with a higher (≥2 pCi/L) radon level (OR, 2.09; 95% CI, 1.41-3.11) and participants living in counties with higher radon and PM2.5 levels (OR, 1.93; 95% CI, 1.31-2.83), though no statistically significant interactions were observed.

CONCLUSIONS AND RELEVANCE: This cohort study suggests that higher radon exposure is associated with greater odds of GD in nulliparous pregnant individuals. Further studies are needed to confirm the results and elucidate the underlying mechanisms, especially with individual-level residential radon exposure assessment.

PMID:39792382 | DOI:10.1001/jamanetworkopen.2024.54319

JAMA Netw Open. 2025 Jan 2;8(1):e2454330. doi: 10.1001/jamanetworkopen.2024.54330.

ABSTRACT

IMPORTANCE: Preventive efforts in pregnancy-related alloimmunization have considerably decreased the prevalence of hemolytic disease of the fetus and newborn (HDFN). International studies are therefore essential to obtain a deeper understanding of the postnatal management and outcomes of HDFN. Taken together with numerous treatment options, large practice variations among centers may exist.

OBJECTIVES: To assess variations in postnatal management and outcomes of HDFN among international centers and to identify opportunities to improve care.

DESIGN, SETTING, AND PARTICIPANTS: In this international, retrospective, cohort study, 31 expert centers from 22 countries retrieved data on neonates with HDFN managed between January 1, 2006, and July 1, 2021. Statistical analysis was performed from July 19, 2023, to October 28, 2024.

MAIN OUTCOMES AND MEASURES: Main outcomes included the frequency of exchange transfusions, administration of intravenous immunoglobulin, administration of erythropoiesis-stimulating agents, and red blood cell transfusions, as well as the association of gestational age at birth with exchange transfusion frequency and risk factors for adverse neonatal outcomes.

RESULTS: The study included 1855 neonates (median gestational age at birth, 36.4 weeks [IQR, 35.0-37.3 weeks]; 1034 boys [55.7%]), of whom 1017 (54.8%) received any form of antenatal treatment. Most neonates (1447 [78.0%]) had anti-D antibodies. Exchange transfusions were performed in 436 neonates (23.5%), with proportions in exchange transfusion frequency varying from 0% to 78% among centers. Intravenous immunoglobulin was administered to 429 of 1743 neonates (24.6%), with proportions varying from 0% to 100% among centers. A higher gestational age at birth was associated with a reduction in exchange transfusion frequency in neonates with intrauterine transfusion, decreasing from approximately 38.2% (13 of 34) at 34 weeks to 16.8% (18 of 107) after 37 weeks and 0 days. A weekly increase in gestational age at birth was associated with a 43.3% decrease (95% CI, 36.1%-49.7%) in the likelihood of adverse neonatal outcomes, and neonates who received an exchange transfusion were 1.55 (95% CI, 1.10-2.18) times more likely to experience unfavorable outcomes.

CONCLUSIONS AND RELEVANCE: In this cohort study of neonates with HDFN managed at 31 centers in 22 countries, significant practice variations in the postnatal management of HDFN were identified, highlighting the lack of, and need for, consensus. The study suggests that there is a potential beneficial clinical association of waiting for delivery until after 37 weeks and 0 days with frequency of exchange transfusions among neonates with HDFN. The framework to implement international guidelines is provided.

PMID:39792381 | DOI:10.1001/jamanetworkopen.2024.54330