Pub Date : 2026-03-23eCollection Date: 2026-01-01DOI: 10.1371/journal.pone.0345567
Faver Álvarez, Paula Andrea Ríos-Parra, Fernando Casanoves, Armando Sterling, Isabel Cristina Molina-Botero
This study aimed to evaluate the nutritional quality and in vitro total gas production of Piptocoma discolor (Kunth) Pruski forage collected from two contrasting landscapes (alluvial plain and hill) in the Colombian Amazon piedmont. To achieve this, leaf and non-lignified stem samples were collected from scattered trees in each landscape and analyzed for their nutritional composition, degradability, and gas production. Crude protein (CP) levels differed significantly between landscapes (p < 0.05), with higher concentrations in the alluvial plain compared to the hill (14.6% vs. 9.5%, respectively). A similar trend was observed for ash, phosphorus, and nitrogen content (p < 0.05). However, neutral detergent fiber (NDF) content was higher in the hill landscape. The concentrations of magnesium, potassium, calcium, sodium, zinc, manganese, copper, and iron did not differ significantly between landscapes (p < 0.05). Regardless of the landscape, P. discolor exhibited moderately acceptable degradability (72%). Cumulative gas production (CGP) at 96 h was significantly higher (p < 0.05) for forage collected in the hill landscape compared to the alluvial plain (66 vs. 53 ml CGP/g dry matter incubated, respectively). These results confirm the potential of P. discolor to improve ruminant nutrition and support sustainable silvopastoral practices in the region.
{"title":"Nutritional quality and in vitro gas production of Piptocoma discolor (Kunth) Pruski forage across contrasting landscapes in the Colombian Amazon Piedmont.","authors":"Faver Álvarez, Paula Andrea Ríos-Parra, Fernando Casanoves, Armando Sterling, Isabel Cristina Molina-Botero","doi":"10.1371/journal.pone.0345567","DOIUrl":"https://doi.org/10.1371/journal.pone.0345567","url":null,"abstract":"<p><p>This study aimed to evaluate the nutritional quality and in vitro total gas production of Piptocoma discolor (Kunth) Pruski forage collected from two contrasting landscapes (alluvial plain and hill) in the Colombian Amazon piedmont. To achieve this, leaf and non-lignified stem samples were collected from scattered trees in each landscape and analyzed for their nutritional composition, degradability, and gas production. Crude protein (CP) levels differed significantly between landscapes (p < 0.05), with higher concentrations in the alluvial plain compared to the hill (14.6% vs. 9.5%, respectively). A similar trend was observed for ash, phosphorus, and nitrogen content (p < 0.05). However, neutral detergent fiber (NDF) content was higher in the hill landscape. The concentrations of magnesium, potassium, calcium, sodium, zinc, manganese, copper, and iron did not differ significantly between landscapes (p < 0.05). Regardless of the landscape, P. discolor exhibited moderately acceptable degradability (72%). Cumulative gas production (CGP) at 96 h was significantly higher (p < 0.05) for forage collected in the hill landscape compared to the alluvial plain (66 vs. 53 ml CGP/g dry matter incubated, respectively). These results confirm the potential of P. discolor to improve ruminant nutrition and support sustainable silvopastoral practices in the region.</p>","PeriodicalId":20189,"journal":{"name":"PLoS ONE","volume":"21 3","pages":"e0345567"},"PeriodicalIF":2.6,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-23eCollection Date: 2026-01-01DOI: 10.1371/journal.pone.0345656
Alex Thabane, Diane Heels-Ansdell, Nicole Zytaruk, Deborah Cook
Introduction: The enrollment of a patient into more than one study (i.e., coenrollment) has risks which warrant exploration, particularly with respect to possible effects on trial outcomes. This pre-planned secondary analysis will examine the sensitivity of treatment effects to coenrollment in an international critical care trial (Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT).
Objective(s): The primary objective is to evaluate the sensitivity of the effect of probiotics on the primary endpoint of VAP to patient coenrollment in at least one other study. The secondary objectives are to describe the characteristics of coenrolled patients and the studies they were coenrolled into; examine any differences in baseline traits; understand differences in center-level characteristics between coenrolling and non-coenrolling centers; identify factors associated with coenrollment; and explore the relationship between coenrollment status and the incidence of adverse events.
Methods: We developed a protocol and statistical analysis plan (SAP) for this secondary analysis involving the conduct of a Cox regression model, including treatment allocation, coenrollment status, and the interaction between the two as independent variables. We also describe our planned statistical analyses for the secondary objectives, involving descriptive statistics, univariable analyses, and multivariable analyses.
Ethics and dissemination: The results of this study will be published in a peer-reviewed journal focused on critical care research or trial methodology, and presented at local, national, and international conferences. As a secondary analysis, this study will not undergo secondary research ethics board approval. Data will be presented in aggregate and without patient identifiers.
{"title":"Coenrollment of critically ill patients in PROSPECT: A protocol and statistical analysis plan.","authors":"Alex Thabane, Diane Heels-Ansdell, Nicole Zytaruk, Deborah Cook","doi":"10.1371/journal.pone.0345656","DOIUrl":"https://doi.org/10.1371/journal.pone.0345656","url":null,"abstract":"<p><strong>Introduction: </strong>The enrollment of a patient into more than one study (i.e., coenrollment) has risks which warrant exploration, particularly with respect to possible effects on trial outcomes. This pre-planned secondary analysis will examine the sensitivity of treatment effects to coenrollment in an international critical care trial (Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT).</p><p><strong>Objective(s): </strong>The primary objective is to evaluate the sensitivity of the effect of probiotics on the primary endpoint of VAP to patient coenrollment in at least one other study. The secondary objectives are to describe the characteristics of coenrolled patients and the studies they were coenrolled into; examine any differences in baseline traits; understand differences in center-level characteristics between coenrolling and non-coenrolling centers; identify factors associated with coenrollment; and explore the relationship between coenrollment status and the incidence of adverse events.</p><p><strong>Methods: </strong>We developed a protocol and statistical analysis plan (SAP) for this secondary analysis involving the conduct of a Cox regression model, including treatment allocation, coenrollment status, and the interaction between the two as independent variables. We also describe our planned statistical analyses for the secondary objectives, involving descriptive statistics, univariable analyses, and multivariable analyses.</p><p><strong>Ethics and dissemination: </strong>The results of this study will be published in a peer-reviewed journal focused on critical care research or trial methodology, and presented at local, national, and international conferences. As a secondary analysis, this study will not undergo secondary research ethics board approval. Data will be presented in aggregate and without patient identifiers.</p>","PeriodicalId":20189,"journal":{"name":"PLoS ONE","volume":"21 3","pages":"e0345656"},"PeriodicalIF":2.6,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Postoperative lower limb lymphedema is a common complication following pelvic or para-aortic lymphadenectomy for gynecologic cancers. Early detection of lymphatic dysfunction is crucial, but the temporal relationship between functional and structural changes remains unclear. This prospective observational study aimed to compare indocyanine green (ICG) lymphography and lymphatic ultrasound findings at multiple time points in the early postoperative phase. We enrolled 23 patients (46 lower limbs) who underwent pelvic and/or para-aortic lymphadenectomy for gynecologic malignancies. Each patient underwent ICG lymphography and lymphatic ultrasound preoperatively and at 1, 3, and 9 months postoperatively. ICG patterns were categorized as linear, splash, or stardust, while lymphatic vessel dilation ≥0.3 mm was defined as abnormal on ultrasound. At least one abnormal ICG finding was observed in 52.2% of limbs, and abnormal ultrasound findings were present in 65.2%. Among limb-timepoints with abnormal ICG findings, lymphatic dilation on ultrasound was observed in 32.6% overall, increasing to 52.6% at 9 months postoperatively, indicating increasing concordance between functional and structural abnormalities over time. Splash patterns on ICG were often not accompanied by lymphatic dilation, whereas stardust patterns were more likely to coincide with structural changes, especially at 9 months. Skin thickness increased significantly in the medial and lateral lower leg regions in limbs with stardust patterns. Our findings demonstrate a temporal dissociation between functional abnormalities detected by ICG and structural changes detected by ultrasound, suggesting that ICG lymphography may be more sensitive in the early phase. The combined use of both modalities may help capture the continuum from early functional disturbance to later structural remodeling and inform the optimal timing of intervention.
{"title":"Time lag between functional and structural lymphatic changes after lymphadenectomy: Insights from ICG lymphography and lymphatic ultrasound.","authors":"Hisako Hara, Mitsuko Hirai, Makoto Mihara, Takashi Hirayama, Yasuhisa Terao","doi":"10.1371/journal.pone.0345408","DOIUrl":"https://doi.org/10.1371/journal.pone.0345408","url":null,"abstract":"<p><p>Postoperative lower limb lymphedema is a common complication following pelvic or para-aortic lymphadenectomy for gynecologic cancers. Early detection of lymphatic dysfunction is crucial, but the temporal relationship between functional and structural changes remains unclear. This prospective observational study aimed to compare indocyanine green (ICG) lymphography and lymphatic ultrasound findings at multiple time points in the early postoperative phase. We enrolled 23 patients (46 lower limbs) who underwent pelvic and/or para-aortic lymphadenectomy for gynecologic malignancies. Each patient underwent ICG lymphography and lymphatic ultrasound preoperatively and at 1, 3, and 9 months postoperatively. ICG patterns were categorized as linear, splash, or stardust, while lymphatic vessel dilation ≥0.3 mm was defined as abnormal on ultrasound. At least one abnormal ICG finding was observed in 52.2% of limbs, and abnormal ultrasound findings were present in 65.2%. Among limb-timepoints with abnormal ICG findings, lymphatic dilation on ultrasound was observed in 32.6% overall, increasing to 52.6% at 9 months postoperatively, indicating increasing concordance between functional and structural abnormalities over time. Splash patterns on ICG were often not accompanied by lymphatic dilation, whereas stardust patterns were more likely to coincide with structural changes, especially at 9 months. Skin thickness increased significantly in the medial and lateral lower leg regions in limbs with stardust patterns. Our findings demonstrate a temporal dissociation between functional abnormalities detected by ICG and structural changes detected by ultrasound, suggesting that ICG lymphography may be more sensitive in the early phase. The combined use of both modalities may help capture the continuum from early functional disturbance to later structural remodeling and inform the optimal timing of intervention.</p>","PeriodicalId":20189,"journal":{"name":"PLoS ONE","volume":"21 3","pages":"e0345408"},"PeriodicalIF":2.6,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Back ground: Trophic feeding generally refers to providing small quantities of enteral feeding soon after birth. A study in Ethiopia highlighted substantial delays in starting therapeutic feeding (TF) for newborns. While guidelines recommend initiating TF within 24 hours of birth, an alarming 80-90% of infants did not begin feeding within 48 hours. Only 20% started TF within the advised timeframe. Furthermore, 29% of these infants did not survive until discharge, and 86.2% experienced extrauterine growth restriction. As a result, this study aims to assess the time to initiation of TF and its predictors among preterm neonates in the Tigray region.
Method: A prospective, institutional-based follow-up study was conducted on 193 preterm neonates admitted to the Neonatal Intensive Care Unit, with participants selected using systematic random sampling from a group of public hospitals.:The data collection period was from December 20, 2024, to February 30, 2025. Data was entered into Epi-Data version 4.7 and then exported to STATA version 14 for cleaning and analysis. To compare survival curves, Kaplan-Meier analysis and the log-rank test were used, bivariate and multivariate Cox regression analysis were used, all statistical tests were considered significant at a p-value of <0.05.
Result: A total of 193 neonates were followed for 8382 person-hours of risk time and 173 (89.6%) of neonates were initiated trophic feeding. The incidence rate of initiating trophic feeding was 2 per 100 person hours' observations with a median time of 45 hours (95% CI: 42-56). Birth weight <1500 gram (AHR: 0.16,95% CI:0.075-0.35), APGAR score at first minute < 7 (AHR: 0.46,95% CI:0.26-0.76),APGAR score at fifth minute < 7 (AHR: 0.38,95%CI:0.21-0.68, having respiratory distress syndrome (AHR: 0.41,95% CI:0.25-0.66, and absence of Kangaroo mother care (AHR: 0.41,95% CI:0.21-0.77), were statistically Significant associated factors for the delay of initiation of trophic feeding.
Conclusion: In this study, a significant delay in the initiation time of trophic feeding. Therefore, health institutions should work on very low birth weight, APGAR scores below seven at one and five minutes, the presence of RDS, and the absence of KMC to shorten the initiation time and reduce complications associated with the delay.
{"title":"Time to initiate trophic feeding and predictors among preterm neonates admitted at General Hospitals in Tigray, 2025.","authors":"Teklebrhan Welderufael Kidane, Zeray Baraki, Asefa Iyasu, Tekle Gebremeskel Ygzaw, Binyam Gebrehiwet Tesfay, Ngsti Gebremichael Beyene, Teklewoini Mariye Zemicheal, Nebiat Desale Gidey, Geberziher Gebreslassie Welearegay","doi":"10.1371/journal.pone.0335385","DOIUrl":"https://doi.org/10.1371/journal.pone.0335385","url":null,"abstract":"<p><strong>Back ground: </strong>Trophic feeding generally refers to providing small quantities of enteral feeding soon after birth. A study in Ethiopia highlighted substantial delays in starting therapeutic feeding (TF) for newborns. While guidelines recommend initiating TF within 24 hours of birth, an alarming 80-90% of infants did not begin feeding within 48 hours. Only 20% started TF within the advised timeframe. Furthermore, 29% of these infants did not survive until discharge, and 86.2% experienced extrauterine growth restriction. As a result, this study aims to assess the time to initiation of TF and its predictors among preterm neonates in the Tigray region.</p><p><strong>Method: </strong>A prospective, institutional-based follow-up study was conducted on 193 preterm neonates admitted to the Neonatal Intensive Care Unit, with participants selected using systematic random sampling from a group of public hospitals.:The data collection period was from December 20, 2024, to February 30, 2025. Data was entered into Epi-Data version 4.7 and then exported to STATA version 14 for cleaning and analysis. To compare survival curves, Kaplan-Meier analysis and the log-rank test were used, bivariate and multivariate Cox regression analysis were used, all statistical tests were considered significant at a p-value of <0.05.</p><p><strong>Result: </strong>A total of 193 neonates were followed for 8382 person-hours of risk time and 173 (89.6%) of neonates were initiated trophic feeding. The incidence rate of initiating trophic feeding was 2 per 100 person hours' observations with a median time of 45 hours (95% CI: 42-56). Birth weight <1500 gram (AHR: 0.16,95% CI:0.075-0.35), APGAR score at first minute < 7 (AHR: 0.46,95% CI:0.26-0.76),APGAR score at fifth minute < 7 (AHR: 0.38,95%CI:0.21-0.68, having respiratory distress syndrome (AHR: 0.41,95% CI:0.25-0.66, and absence of Kangaroo mother care (AHR: 0.41,95% CI:0.21-0.77), were statistically Significant associated factors for the delay of initiation of trophic feeding.</p><p><strong>Conclusion: </strong>In this study, a significant delay in the initiation time of trophic feeding. Therefore, health institutions should work on very low birth weight, APGAR scores below seven at one and five minutes, the presence of RDS, and the absence of KMC to shorten the initiation time and reduce complications associated with the delay.</p>","PeriodicalId":20189,"journal":{"name":"PLoS ONE","volume":"21 3","pages":"e0335385"},"PeriodicalIF":2.6,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-23eCollection Date: 2026-01-01DOI: 10.1371/journal.pone.0345517
Deniz Bozkurt, Maria Duaso, Iliatha Papachristou Nadal, Rosie Walker, Jackie Sturt
Objective: The Women's Wellness with Type 2 Diabetes Programme (WWDP) is a complex intervention, encouraging positive lifestyle behaviours to enhance wellness outcomes. A previous feasibility study found the original WWDP had a good effect signal and was acceptable to women but had challenges with national scalability. In response, the programme was revised (WWDP+). This study evaluated the feasibility of delivering the WWDP+ and its evaluation procedures and assessed physical and psychosocial outcomes in midlife women to inform the design of a future randomised controlled trial.
Methods: A single arm, pre- and post-intervention design were conducted. Women living with type 2 diabetes and aged between 45-65 years were recruited via a social media campaign using purposive sampling targeting individuals who had previously expressed interest in type 2 diabetes research. Alongside recruitment and completion rates, clinical and behavioural study outcomes were assessed at baseline, 3 months and 6 months post baseline. Individualised goals were set at week 3 and assessed at 12-week. Analysis comprised descriptive statistics, Wilcoxon's signed-rank and paired t tests.
Results: Thirty-four women (mean age = 55.4) from diverse backgrounds participated. Feasibility targets were met: 77% recruitment of eligible women, 88% 12-week completion, and data completeness of 82% at 3 months and 79% at 6 months. Post-intervention diabetes distress decreased by 1.52 points (p < 0.001), self-reported HbA1c decreased by 13 mmol/mol (p < 0.02) and BMI by 0.6 kg/m2 (p < 0.049). Menopausal symptoms declined by 13 points on the Greene scale (p < 0.001). Improvements were observed in diabetes self-efficacy (+7.4 points, p < 0.001), general health (+27.5 points, p < 0.01), sleep disturbance (-6.2 points, p < 0.002), and confidence in making dietary choices (+1.1 points, p < 0.02). Goal attainment scores indicated that 68% of participants achieved or exceeded their expectations.
Conclusions: This feasibility study suggests that the WWDP+ is acceptable and feasible for midlife women with type 2 diabetes. The findings will directly inform the design, sample size, and recruitment strategies of a fully powered randomised controlled trial to evaluate WWDP+ effectiveness.
{"title":"The Women's Wellness with Type 2 Diabetes Programme: Feasibility of an online peer support and goal-setting intervention for midlife women.","authors":"Deniz Bozkurt, Maria Duaso, Iliatha Papachristou Nadal, Rosie Walker, Jackie Sturt","doi":"10.1371/journal.pone.0345517","DOIUrl":"https://doi.org/10.1371/journal.pone.0345517","url":null,"abstract":"<p><strong>Objective: </strong>The Women's Wellness with Type 2 Diabetes Programme (WWDP) is a complex intervention, encouraging positive lifestyle behaviours to enhance wellness outcomes. A previous feasibility study found the original WWDP had a good effect signal and was acceptable to women but had challenges with national scalability. In response, the programme was revised (WWDP+). This study evaluated the feasibility of delivering the WWDP+ and its evaluation procedures and assessed physical and psychosocial outcomes in midlife women to inform the design of a future randomised controlled trial.</p><p><strong>Methods: </strong>A single arm, pre- and post-intervention design were conducted. Women living with type 2 diabetes and aged between 45-65 years were recruited via a social media campaign using purposive sampling targeting individuals who had previously expressed interest in type 2 diabetes research. Alongside recruitment and completion rates, clinical and behavioural study outcomes were assessed at baseline, 3 months and 6 months post baseline. Individualised goals were set at week 3 and assessed at 12-week. Analysis comprised descriptive statistics, Wilcoxon's signed-rank and paired t tests.</p><p><strong>Results: </strong>Thirty-four women (mean age = 55.4) from diverse backgrounds participated. Feasibility targets were met: 77% recruitment of eligible women, 88% 12-week completion, and data completeness of 82% at 3 months and 79% at 6 months. Post-intervention diabetes distress decreased by 1.52 points (p < 0.001), self-reported HbA1c decreased by 13 mmol/mol (p < 0.02) and BMI by 0.6 kg/m2 (p < 0.049). Menopausal symptoms declined by 13 points on the Greene scale (p < 0.001). Improvements were observed in diabetes self-efficacy (+7.4 points, p < 0.001), general health (+27.5 points, p < 0.01), sleep disturbance (-6.2 points, p < 0.002), and confidence in making dietary choices (+1.1 points, p < 0.02). Goal attainment scores indicated that 68% of participants achieved or exceeded their expectations.</p><p><strong>Conclusions: </strong>This feasibility study suggests that the WWDP+ is acceptable and feasible for midlife women with type 2 diabetes. The findings will directly inform the design, sample size, and recruitment strategies of a fully powered randomised controlled trial to evaluate WWDP+ effectiveness.</p><p><strong>Trial registration: </strong>ISRCTN: ISRCTN93338547. https://doi.org/10.1186/ISRCTN93338547.</p>","PeriodicalId":20189,"journal":{"name":"PLoS ONE","volume":"21 3","pages":"e0345517"},"PeriodicalIF":2.6,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Intracerebral hemorrhage (ICH) is a devastating condition characterized by rapid onset, high rates of disability and mortality, and prolonged recovery. Dysregulated γ-aminobutyric acid type A receptor (GABAAR) signaling contributes to ICH-induced neurotoxicity, presenting a promising therapeutic target.
Objective: To assess the neurorestorative effects of the GABAAR α1-selective partial positive allosteric modulator (PAM) CL218872 and the α5-selective negative allosteric modulator (NAM) MRK-016 on synaptic plasticity and neural repair following ICH.
Methods: An ICH mouse model was constructed using collagenase IV, and ICH mice were administered the GABAAR modulators CL218872 or MRK-016. Differences in inflammation and neurological deficit score were compared between different groups of mice. Morphologic and functional changes in mouse neuronal cells were next determined by Nissl and Golgi-Cox staining. Synaptic structural changes in ICH mice were visualized by transmission electron microscopy, and changes in synaptic plasticity-related molecules were quantified to assess the effects of GABAAR modulators on synapses in ICH mice.
Results: Treatment with CL218872 resulted in a reduction in hemorrhage and improved neurobehavioral outcomes in ICH mice. Additionally, CL218872 mitigated inflammation by downregulating phospho-p65, IL-6 and TNF-α expression. Histological analysis revealed an increase in neuronal density, preservation of cell morphology, and enhanced synaptic connectivity following CL218872 treatment. Furthermore, synaptic structure was restored, and there was an upregulation of brain-derived neurotrophic factor (BDNF), growth-associated protein-43 (GAP-43), postsynaptic density protein 95 (PSD-95), and synaptophysin in ICH mice. However, treatment with MRK-016 yielded the opposite result.
Conclusion: The GABAAR α1-selective PAM CL218872 exerts neuroprotective and neurorestorative effects in ICH, suggesting its therapeutic potential for ICH management.
{"title":"Effects of GABAAR modulators CL218872 and MRK-016 on neural repair and synaptic plasticity in mice with Intracerebral hemorrhage.","authors":"Tingting Chen, Hongxia He, Fei Huang, Junwu Liu, Hongli Zhou, Lei Xu","doi":"10.1371/journal.pone.0345025","DOIUrl":"https://doi.org/10.1371/journal.pone.0345025","url":null,"abstract":"<p><strong>Background: </strong>Intracerebral hemorrhage (ICH) is a devastating condition characterized by rapid onset, high rates of disability and mortality, and prolonged recovery. Dysregulated γ-aminobutyric acid type A receptor (GABAAR) signaling contributes to ICH-induced neurotoxicity, presenting a promising therapeutic target.</p><p><strong>Objective: </strong>To assess the neurorestorative effects of the GABAAR α1-selective partial positive allosteric modulator (PAM) CL218872 and the α5-selective negative allosteric modulator (NAM) MRK-016 on synaptic plasticity and neural repair following ICH.</p><p><strong>Methods: </strong>An ICH mouse model was constructed using collagenase IV, and ICH mice were administered the GABAAR modulators CL218872 or MRK-016. Differences in inflammation and neurological deficit score were compared between different groups of mice. Morphologic and functional changes in mouse neuronal cells were next determined by Nissl and Golgi-Cox staining. Synaptic structural changes in ICH mice were visualized by transmission electron microscopy, and changes in synaptic plasticity-related molecules were quantified to assess the effects of GABAAR modulators on synapses in ICH mice.</p><p><strong>Results: </strong>Treatment with CL218872 resulted in a reduction in hemorrhage and improved neurobehavioral outcomes in ICH mice. Additionally, CL218872 mitigated inflammation by downregulating phospho-p65, IL-6 and TNF-α expression. Histological analysis revealed an increase in neuronal density, preservation of cell morphology, and enhanced synaptic connectivity following CL218872 treatment. Furthermore, synaptic structure was restored, and there was an upregulation of brain-derived neurotrophic factor (BDNF), growth-associated protein-43 (GAP-43), postsynaptic density protein 95 (PSD-95), and synaptophysin in ICH mice. However, treatment with MRK-016 yielded the opposite result.</p><p><strong>Conclusion: </strong>The GABAAR α1-selective PAM CL218872 exerts neuroprotective and neurorestorative effects in ICH, suggesting its therapeutic potential for ICH management.</p>","PeriodicalId":20189,"journal":{"name":"PLoS ONE","volume":"21 3","pages":"e0345025"},"PeriodicalIF":2.6,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-23eCollection Date: 2026-01-01DOI: 10.1371/journal.pone.0345286
Kai Yan, Guang Yang, Lixuan Yan, Li Wu, Yang Wang, Peifeng He, Qi Yu
Background: Cervical cancer (CCA) remains a major cause of morbidity and mortality among women globally, particularly in low- and middle-income countries. Although human papillomavirus (HPV) vaccination is central to prevention, safety concerns may affect vaccine acceptance. We integrated global disease-burden trends with real-world post-marketing safety data to provide complementary public health evidence for CCA prevention.
Methods: Using Global Burden of Disease (GBD) 2021 data, we assessed global prevalence, incidence, death, and disability-adjusted life years (DALYs) for women with CCA from 1990-2021, and applied age-period-cohort (APC) models to characterize temporal patterns. Bayesian APC models were used to project future incidence and death, with retrospective validation. For vaccine safety, adverse event (AE) reports following HPV vaccination in females (Cervarix, Gardasil, Gardasil 9; 2006-2025) were extracted from the Vaccine Adverse Event Reporting System (VAERS). We performed disproportionality analyses using four algorithms to identify reporting signals, with designated medical event (DME) screening and subgroup analyses by age and vaccine type.
Results: Globally, the age-standardized incidence rate of CCA decreased from 18.1 to 15.3 cases per 100,000 women from 1990 to 2021, while new cases increased from 0.41 million to 0.67 million. The highest incidence and death rates were observed in sub-Saharan Africa and selected Pacific Island countries. Projections suggest continued declines in age-standardized incidence and death through 2050, although the absolute burden will likely remain substantial. In VAERS, 41,731 HPV vaccine-related reports were identified; most were non-serious (80.9%). Syncope (ROR = 5.81, 95%CI:5.64-5.99), loss of consciousness (ROR = 5.26, 95%CI: 5.06-5.47) and pallor (ROR = 6.39, 95%CI: 6.10-6.70) were the most frequently reported events, and six potential DME-related signals were detected.
Conclusions: Despite declining age-standardized rates, CCA continues to impose a substantial global burden with marked regional disparities. Sustained HPV vaccine prevention efforts should be supported by epidemiological evidence and transparent, evidence-based safety communication.
{"title":"Global trends and forecasts of cervical cancer and a real-world safety assessment of human papillomavirus vaccines in women: A systematic analysis of the Global Burden of Disease study 2021 and the Vaccine Adverse Event Reporting System database.","authors":"Kai Yan, Guang Yang, Lixuan Yan, Li Wu, Yang Wang, Peifeng He, Qi Yu","doi":"10.1371/journal.pone.0345286","DOIUrl":"https://doi.org/10.1371/journal.pone.0345286","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer (CCA) remains a major cause of morbidity and mortality among women globally, particularly in low- and middle-income countries. Although human papillomavirus (HPV) vaccination is central to prevention, safety concerns may affect vaccine acceptance. We integrated global disease-burden trends with real-world post-marketing safety data to provide complementary public health evidence for CCA prevention.</p><p><strong>Methods: </strong>Using Global Burden of Disease (GBD) 2021 data, we assessed global prevalence, incidence, death, and disability-adjusted life years (DALYs) for women with CCA from 1990-2021, and applied age-period-cohort (APC) models to characterize temporal patterns. Bayesian APC models were used to project future incidence and death, with retrospective validation. For vaccine safety, adverse event (AE) reports following HPV vaccination in females (Cervarix, Gardasil, Gardasil 9; 2006-2025) were extracted from the Vaccine Adverse Event Reporting System (VAERS). We performed disproportionality analyses using four algorithms to identify reporting signals, with designated medical event (DME) screening and subgroup analyses by age and vaccine type.</p><p><strong>Results: </strong>Globally, the age-standardized incidence rate of CCA decreased from 18.1 to 15.3 cases per 100,000 women from 1990 to 2021, while new cases increased from 0.41 million to 0.67 million. The highest incidence and death rates were observed in sub-Saharan Africa and selected Pacific Island countries. Projections suggest continued declines in age-standardized incidence and death through 2050, although the absolute burden will likely remain substantial. In VAERS, 41,731 HPV vaccine-related reports were identified; most were non-serious (80.9%). Syncope (ROR = 5.81, 95%CI:5.64-5.99), loss of consciousness (ROR = 5.26, 95%CI: 5.06-5.47) and pallor (ROR = 6.39, 95%CI: 6.10-6.70) were the most frequently reported events, and six potential DME-related signals were detected.</p><p><strong>Conclusions: </strong>Despite declining age-standardized rates, CCA continues to impose a substantial global burden with marked regional disparities. Sustained HPV vaccine prevention efforts should be supported by epidemiological evidence and transparent, evidence-based safety communication.</p>","PeriodicalId":20189,"journal":{"name":"PLoS ONE","volume":"21 3","pages":"e0345286"},"PeriodicalIF":2.6,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-23eCollection Date: 2026-01-01DOI: 10.1371/journal.pone.0345463
Xiaofang Ma
The effectiveness of online teaching has emerged as a critical concern during the COVID-19 pandemic, with a particular emphasis on fostering a sustained interest in online instruction among educators. This study employs fuzzy-set qualitative comparative analysis (fsQCA) to investigate the complex causal relationships that underpin the online teaching efficacy of elementary school teachers. A comprehensive questionnaire was administered to 171 elementary school teachers, capturing their perspectives across six key dimensions: the acceptability of online teaching, teachers' Technological Pedagogical Content Knowledge (TPACK), students' autonomous learning, teacher-student interaction, course design and implementation, and technological support for teaching. The findings reveal a multiplicity of configurations that contribute to enhanced online teaching effectiveness, with teachers' acceptance of online teaching and their TPACK being identified as central conditions, pivotal for the improvement of online teaching effectiveness.
{"title":"Optimizing online teaching effectiveness in elementary education: Exploring multifaceted pathways based fsQCA analysis.","authors":"Xiaofang Ma","doi":"10.1371/journal.pone.0345463","DOIUrl":"https://doi.org/10.1371/journal.pone.0345463","url":null,"abstract":"<p><p>The effectiveness of online teaching has emerged as a critical concern during the COVID-19 pandemic, with a particular emphasis on fostering a sustained interest in online instruction among educators. This study employs fuzzy-set qualitative comparative analysis (fsQCA) to investigate the complex causal relationships that underpin the online teaching efficacy of elementary school teachers. A comprehensive questionnaire was administered to 171 elementary school teachers, capturing their perspectives across six key dimensions: the acceptability of online teaching, teachers' Technological Pedagogical Content Knowledge (TPACK), students' autonomous learning, teacher-student interaction, course design and implementation, and technological support for teaching. The findings reveal a multiplicity of configurations that contribute to enhanced online teaching effectiveness, with teachers' acceptance of online teaching and their TPACK being identified as central conditions, pivotal for the improvement of online teaching effectiveness.</p>","PeriodicalId":20189,"journal":{"name":"PLoS ONE","volume":"21 3","pages":"e0345463"},"PeriodicalIF":2.6,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Households play a crucial role in the propagation of infectious diseases due to the frequent and prolonged interactions that typically occur between their members. Recent studies have emphasized the need to include socioeconomic variables in epidemic models to account for the heterogeneity induced by human behavior. While sub-Saharan Africa suffers the highest burden of infectious disease diffusion, few studies have investigated the mixing patterns in the countries and their relation with social indicators. This work analyzes household contact matrices measured with wearable proximity sensors in a rural and an urban village in South Africa. Leveraging a rich data collection describing additional individual and household attributes, we investigate how the household contact matrix varies according to the household type (whether it is composed only of a familiar nucleus or by a larger group), the gender of its head (the primary decision-maker), the rural or urban context, and the season in which it was measured. We show the household type and the gender of its head induce differences in the interaction patterns between household members, particularly regarding child caregiving, suggesting they are relevant attributes to include in epidemic modeling.
{"title":"Relationship between household attributes and contact patterns in urban and rural South Africa.","authors":"Kausutua Tjikundi, Jackie Kleynhans, Stefano Tempia, Cheryl Cohen, Daniela Paolotti, Ciro Cattuto, Lorenzo Dall'Amico","doi":"10.1371/journal.pone.0344732","DOIUrl":"https://doi.org/10.1371/journal.pone.0344732","url":null,"abstract":"<p><p>Households play a crucial role in the propagation of infectious diseases due to the frequent and prolonged interactions that typically occur between their members. Recent studies have emphasized the need to include socioeconomic variables in epidemic models to account for the heterogeneity induced by human behavior. While sub-Saharan Africa suffers the highest burden of infectious disease diffusion, few studies have investigated the mixing patterns in the countries and their relation with social indicators. This work analyzes household contact matrices measured with wearable proximity sensors in a rural and an urban village in South Africa. Leveraging a rich data collection describing additional individual and household attributes, we investigate how the household contact matrix varies according to the household type (whether it is composed only of a familiar nucleus or by a larger group), the gender of its head (the primary decision-maker), the rural or urban context, and the season in which it was measured. We show the household type and the gender of its head induce differences in the interaction patterns between household members, particularly regarding child caregiving, suggesting they are relevant attributes to include in epidemic modeling.</p>","PeriodicalId":20189,"journal":{"name":"PLoS ONE","volume":"21 3","pages":"e0344732"},"PeriodicalIF":2.6,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}