bluuebunny/crossref_metadata_2025 huggingface dataset:
Intestinal barrier damage contributes to a higher prevalence of frailty in aging people living with HIV: a retrospective case control study in a Chinese cohort
Authors: Xu Xiaolei , Ouyang Jing , Yan Jiangyu , Lu Yanqiu , Harypursat Vijay , Wu Hao , Chen Yaokai
Published: October 2024

Background

It has been previously demonstrated that intestinal barrier damage is one of the underlying mechanisms leading to frailty in non-HIV-infected aging populations. However, there is a paucity of direct evidence which demonstrates the association between intestinal barrier damage and frailty in people living with HIV (PLWH).

Methods

The present study is a retrospective case control study. Participants older than 50 years old were stratified into a frail/pre-frail group (case group) and non-frail group (control group) according to the Fried frailty phenotype. We collected and curated data concerning socio-demographic variables, psychological states and social functioning, and clinical information associated with the identification of biomarkers of intestinal barrier damage, microbial translocation, and levels of inflammatory cytokines of participants.

Results

The case group had significantly higher levels of Reg-3α (p=0.042) and I-FABP (p=0.045) compared to the control group. We further observed, after adjusting for confounding factors by logistic regression analysis, that I-FABP levels remained significantly higher in the case group compared to the control group (p=0.033). Also, Fried Phenotype scores positively correlated with I-FABP levels (rs=0.21, p=0.01), LPS levels (rs=0.20, p=0.02), and sCD14 levels (rs=0.18, p=0.04). Moreover, the study confirmed both the positive correlation between inflammatory cytokines (IL-6 and IP-10) with frailty in aging PLWH, and between inflammatory cytokines (IL-6, IL-8 and IP-10) with biomarkers of intestinal barrier dysfunction in older PLWH.

Conclusion

The present study indicates that the inflammation induced by intestinal barrier damage/dysfunction is likely to contribute to frailty in aging PLWH.
Autophagy and proteasomes in thymic epithelial cells: essential bulk protein degradation systems for immune homeostasis maintenance
Authors: Yamaguchi Noritaka , Takakura Yuki , Akiyama Taishin
Published: October 2024

The thymus is a central organ that controls T cell development. Thymic epithelial cells (TECs) create a unique microenvironment essential for the differentiation of major histocompatibility complex (MHC)-restricted and self-tolerant T cells. TECs present a complex of self-peptides and MHC molecules (self-pMHCs) to immature T cells and regulate their survival and differentiation based on their affinity for self-pMHCs. The processing of self-peptides in TECs depends on bulk protein degradation systems, specifically autophagy and proteasomes. Studies using autophagy- and proteasome-deficient mouse models have demonstrated that these degradation systems in TECs are indispensable for maintaining immune homeostasis. Although autophagy and proteasomes are ubiquitous in nearly all eukaryotic cells, TECs exhibit unique characteristics in their autophagy and proteasome functions. Autophagy in TECs is constitutively active and independent of stress responses, while TEC proteasomes contain specialized catalytic subunits. This review summarizes the distinctive characteristics of autophagy and proteasomes in TECs and their roles in immune system regulation.
Assessing the impact of a potential canine vaccine for the control of Chagas disease: a mathematical modeling study
Authors: Fiatsonu Edem , Deka Aniruddha , Ndeffo-Mbah Martial L.
Published: October 2024

Introduction

Chagas disease, a zoonotic infection transmitted by triatomine bugs, poses serious public health risks in endemic areas. As dogs are important reservoirs in the disease’s spread, developing a canine vaccine could be transformative for controlling disease transmission to dogs and humans.

Methods

We developed a compartmental Susceptible-Infected model to simulate the transmission dynamics of Trypanosoma cruzi, considering interactions among dogs, humans, cats, rodents, and triatomine vectors. We used the model to assess the direct and indirect impacts of two vaccine mechanisms—all-or-nothing and leaky—on disease incidence across different host populations. The sensitivity of the model’s outcomes to changes in input parameters was analyzed using univariate sensitivity analysis.

Results

Our model showed that with a 90% vaccine efficacy, an all-or-nothing vaccine could reduce the cumulative incidence of T. cruzi in dogs by 91.3% over five years. The 60% and 30% vaccine efficacies would result in reductions of 63.47% and 33%, respectively, over 5 years. Similarly, the leaky vaccine achieved a 92.62% reduction in dog infections over 5 years with 90% efficacy. The indirect effects on human T. cruzi infection were notable; the all-or-nothing vaccine reduced human disease incidence by 14.37% at 90% efficacy, while the leaky vaccine achieved a 32.15% reduction over 5 years. Both vaccine mechanisms may substantially reduce T. cruzi incidence among dogs, and generate indirect benefit to other hosts, such as humans, by reducing their infection risk. The indirect benefits of vaccination were heavily influenced by the proportion of triatomine bugs blood meals taken from dogs.

Discussion

The study highlights the potential of targeted canine vaccination in controlling Chagas disease transmission and burden in endemic countries. It provides additional evidence for pursuing the development of a canine vaccine as a valuable tool for Chagas disease elimination.
Evaluation and fusion of multi-source sea ice thickness products with limited in-situ observations
Authors: Li Tongtong , Wang Yangjun , Wang Bin , Liu Kefeng , Chen Xi , Sun Rui
Published: October 2024

Sea ice thickness (SIT) is a critical and sensitive parameter in the climate system, with its dynamic changes profoundly influencing global climate models, navigational routes, and the potential for Arctic resource development. Given the widespread application of current satellite remote sensing technology in monitoring SIT, significant uncertainties remain. This study first underscores the importance of in-situ observations as a direct measurement method for SIT. However, the limitations of in-situ data in terms of acquisition cost, spatiotemporal coverage continuity, and distribution uniformity significantly hinder the effective evaluation of multi-source SIT products. To address this, the study innovatively introduces the Triple Collocation (TC) method, which effectively mitigates the impact of errors from individual data sources on the overall evaluation results through a mutual validation mechanism among multiple satellite data sources. This allows for a scientific assessment of multi-source SIT products even in the context of scarce in-situ observations. The findings indicate that the TC method not only successfully resolves the challenges of multi-source data evaluation but also facilitates data integration among these products, significantly enhancing the overall accuracy and spatiotemporal consistency of SIT data.
Proteome-wide Mendelian randomization provides novel insights into the pathogenesis and druggable targets of osteoporosis
Authors: Yan Jingchuan , Huai Ying , Liang Qi , Lin Li , Liao Bo
Published: October 2024

Background

With the aging population, the prevalence and impact of osteoporosis are expected to rise, and existing anti-osteoporosis agents have limitations due to adverse events. This study aims to discover novel drug targets for osteoporosis.

Methods

The protein data were obtained from the latest proteome-wide association studies (PWAS) including 54, 219 participants. The osteoporosis data were extracted from a GWAS meta-analysis, characterized by heel bone mineral density (HBMD) comprising 426,824 individuals. Mendelian randomization (MR) was the primary approach used to establish genetic causality between specific traits. Summary-data-based MR (SMR), colocalization analysis, heterogeneity test, and external validation were applied to ensure the findings were reliable. The underlying mechanisms behind these causal associations were investigated by additional analyses. Finally, the druggability of the identified proteins was assessed.

Results

After Bonferroni correction, a total of 84 proteins were found to have a genetic association with osteoporosis. With strong colocalization evidence, proteins such as ACHE, HS6ST1, LRIG1, and LRRC37A2 were found to negatively influence HBMD, whereas CELSR2, CPE, FN1, FOXO1, and FSHB exhibited a positive association with HBMD. No significant heterogeneity was found. Additionally, CELSR2, FN1, FSHB, HS6ST1, LRIG1, and LRRC37A2 were replicated in the external validation. The effect of FSHB on HBMD was more pronounced in females compared to males. Interestingly, ACHE, LRIG1, FN1, and FOXO1 were observed to partially act on HBMD through BMI. Phewas analysis indicated that CPE and FOXO1 did not have genetic associations with any phenotypes other than osteoporosis. FN1 was highlighted as the most significant protein by protein-protein interaction network analysis.

Conclusion

In conclusion, this study offers valuable insights into the role of specific proteins in the development of osteoporosis, and underscores potential therapeutic targets. Future studies should emphasize exploring these causal relationships and elucidating their underlying mechanisms.
Predicting risk for nocturnal hypoglycemia after physical activity in children with type 1 diabetes
Authors: Leutheuser Heike , Bartholet Marc , Marx Alexander , Pfister Marc , Burckhardt Marie-Anne , Bachmann Sara , Vogt Julia E.
Published: October 2024

Children with type 1 diabetes (T1D) frequently have nocturnal hypoglycemia, daytime physical activity being the most important risk factor. The risk for late post-exercise hypoglycemia depends on various factors and is difficult to anticipate. The availability of continuous glucose monitoring (CGM) enabled the development of various machine learning approaches for nocturnal hypoglycemia prediction for different prediction horizons. Studies focusing on nocturnal hypoglycemia prediction in children are scarce, and none, to the best knowledge of the authors, investigate the effect of previous physical activity. The primary objective of this work was to assess the risk of hypoglycemia throughout the night (prediction horizon 9 h) associated with physical activity in children with T1D using data from a structured setting. Continuous glucose and physiological data from a sports day camp for children with T1D were input for logistic regression, random forest, and deep neural network models. Results were evaluated using the F2 score, adding more weight to misclassifications as false negatives. Data of 13 children (4 female, mean age 11.3 years) were analyzed. Nocturnal hypoglycemia occurred in 18 of a total included 66 nights. Random forest using only glucose data achieved a sensitivity of 71.1% and a specificity of 75.8% for nocturnal hypoglycemia prediction. Predicting the risk of nocturnal hypoglycemia for the upcoming night at bedtime is clinically highly relevant, as it allows appropriate actions to be taken—to lighten the burden for children with T1D and their families.
Analysis of lactic acid bacteria species in Miang, a post-fermented tea in Thailand, and their potential use as probiotics
Authors: Horie Masanori , Ruengsomwong Supatjaree , Ohmiya Yoshihiro
Published: October 2024

Introduction

Miang is one of the post-fermented teas made in Northern Thailand. Although lactic acid bacteria are involved in fermentation of Miang, details are still not clear. This study investigated the diversity of Lactobacillaceae bacteria, related to fermentation of Miang. Probiotic potential of isolated Lactobacillaceae bacteria was examined.

Methods

Lactobacillaceae bacteria were isolated from 52 Miang samples collected from three provinces in northern Thailand and identified by MALDI-TOF MS. Hemolytic activity, antibiotic susceptibility, antimicrobial activity and tolerance to gastrointestinal juice were examined for probiotic potential of isolates.

Results

A total of 1,181 Lactobacillaceae bacteria strains were isolated from Miang. The most abundant isolates were Lactiplantibacillus pentosus. Besides Lactiplantibacillus plantarum, Levilactobacillus brevis, Paucilactobacillus suebicus, Lacticaseibacillus pantheris, and Secundilactobacillus collinoides were also found with frequency. Of these isolates, 450 with a high score for MALDI-TOF identification were then screened for probiotic ability. Most isolates were resistant to aminoglycosides and clindamycin. Then, 35 isolates were tested for their antimicrobial activity against pathogens using the well diffusion method, and 31 isolates exhibited inhibition zones against Staphylococcus aureus, Staphylococcus epidermidis, Salmonella enterica serovar Typhimurium, S. enterica serovar Enteritidis, Listeria monocytogenes, Propionibacterium acnes, and Streptococcus mutans. All 31 isolates were non-hemolytic and readily tolerated simulated gastric juice at pH 3 and simulated intestinal juice at pH 8.

Discussion

Miang contains lactic acid bacteria that could potentially be used as probiotics.
Chlorine dioxide is a broad-spectrum disinfectant against Shiga toxin-producing Escherichia coli and Listeria monocytogenes in agricultural water
Authors: Van Blair Jared , Lacombe Alison , Harvey Beatrice L. , Wu Vivian C. H.
Published: October 2024

Agricultural water is commonly treated with chlorine-based disinfectants, which are impacted by water quality. Understanding how water quality influences disinfectants such as chlorine dioxide (ClO2) against pathogenic bacteria is important for creating efficacious sanitation regimens. In this study, the minimum inhibitory concentration (MIC) of ClO2 needed to achieve a 3-Log reduction against Shiga toxin-producing Escherichia coli (STEC) and Listeria monocytogenes was compared across agricultural water samples. Sterile ddH2O served as a control to compare with environmental samples from Salinas Valley, CA, and laboratory standards. To test different dosages and water qualities, stock ClO2 was diluted in 24-well plates with target concentrations of 10, 5, 2.5, and 1.25 mg/L. Well plates were inoculated with pathogens and treated with sanitizer for 5 min. Following treatment, surviving pathogens were enumerated using viable cell counts. The results demonstrate that groundwater samples had the highest water quality of the environmental samples and required the lowest concentration of disinfectant to achieve 3-Log reduction against both bacteria, with MIC between 1.4 and 2.0 mg/L. Open-source samples had lower water quality and required a higher concentration of ClO2 for 3-Log reduction, with MIC between 2.8 and 5.8 mg/L for both pathogens. There was no correlation between pH, turbidity, or conductivity/TDS and reduction for either STEC or L. monocytogenes, suggesting no individual water metric was driving reduction. A lower dosage was required to achieve 3-Log reduction against STEC, while L. monocytogenes required greater concentrations to achieve the same level of reduction. Overall, these results help guide growers in using ClO2 as a broad-spectrum disinfectant and demonstrate its efficacy in reaching 3-Log reduction across agricultural water samples.
The HALP (hemoglobin, albumin, lymphocyte, and platelet) score is associated with hemorrhagic transformation after intravenous thrombolysis in patients with acute ischemic stroke
Authors: Chen Jiahao , Hu Rui , Shang Lejia , Li Xiaoqin , Lin Yisi , Yao Yu , Hu Chuanchen
Published: October 2024

Background

Hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) with rt-PA can precipitate rapid neurological deterioration, poor prognosis, and even death. The HALP score (hemoglobin, albumin, lymphocyte, and platelet) is a novel indicator developed to reflect both systemic inflammation and the nutritional status of patients. The goal of this study was to reveal the relationship between the HALP score and the risk of HT after IVT in people with acute ischemic stroke (AIS).

Methods

A total of 753 patients with AIS were included in this study. Patients were divided into quartiles according to baseline HALP score. The HALP score was calculated as follows: hemoglobin (g/L) × albumin (g/L) × lymphocytes (/L)/platelets (/L). Binary logistic regression was used to reveal the connection between HALP score and HT.

Results

The baseline HALP score were significantly lower in the HT than non-HT patients (p < 0.001). The HALP score were divided into four quartiles: Q1 (<27.4), Q2 (27.4–37.6), Q3 (37.7–49.6), Q4 (>49.6), respectively. Moreover, the severity of HT increased with decreasing HALP level (p < 0.001). In multivariable logistic regression, taking the Q4 as the reference, the association between Q1 and HT remained, after adjusting for confounding variables [odds ratio (OR) = 3.197, 95% confidence interval (CI) = 1.634–6.635, p = 0.003].

Conclusion

The HALP value can predict the HT risk after IVT in patients with AIS. A lower HALP level was associated with an increased severity of HT post-IVT.
Global burden of multiple sclerosis and its attributable risk factors, 1990–2019
Authors: Safiri Saeid , Ghaffari Jolfayi Amir , Mousavi Seyed Ehsan , Nejadghaderi Seyed Aria , Sullman Mark J. M. , Kolahi Ali-Asghar
Published: October 2024

Background

Multiple sclerosis (MS) is a progressively debilitating disorder that has seen a notable rise in prevalence in recent years. This study examines the burden of MS from 1990 to 2019, providing a detailed analysis by age, sex, and sociodemographic index (SDI) across 204 countries and territories.

Methods

Data on the prevalence, death and disability-adjusted life years (DALYs) attributable to MS were obtained from the publically available Global Burden of Disease 2019 project. The estimates are reported as numbers, percentages, and age-standardized rates per 100,000, accompanied by 95% uncertainty intervals.

Results

In 2019, MS accounted for 1.8 million prevalent cases, 22.4 thousand deaths and 1.2 million DALYs worldwide. There were significant declines in the global age-standardized prevalence, mortality and DALY rates of MS over the period 1990–2019. In 2019, females exhibited a higher global point prevalence and a greater total number of prevalent MS cases than males across all age groups. At the regional level, a non-linear relationship was observed between the age-standardized DALY rate of MS and SDI.

Conclusion

Although the global age-standardized DALY rate of MS decreased between 1990 and 2019, MS continues to account for a considerable number of DALYs and prevalent cases. Integrating MS and its associated risk factors into healthcare planning is vital, especially in areas with high levels of socioeconomic development.
Overlapping conditions in Long COVID at a multisite academic center
Authors: Grach Stephanie L. , Dudenkov Daniel V. , Pollack Beth , Fairweather DeLisa , Aakre Chris A. , Munipalli Bala , Croghan Ivana T. , Mueller Michael R. , Overgaard Joshua D. , Bruno Katelyn A. , Collins Nerissa M. , Li Zhuo , Hurt Ryan T. , Tal Michal C. , Ganesh Ravindra , Knight Dacre T. R.
Published: October 2024

Background

Many patients experience persistent symptoms after COVID-19, a syndrome referred to as Long COVID (LC). The goal of this study was to identify novel new or worsening comorbidities self-reported in patients with LC.

Methods

Patients diagnosed with LC (n = 732) at the Mayo Long COVID Care Clinic in Rochester, Minnesota and Jacksonville, Florida were sent questionnaires to assess the development of new or worsening comorbidities following COVID-19 compared to patients with SARS-CoV-2 that did not develop LC (controls). Both groups were also asked questions screening for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), generalized joint hypermobility (GJH) and orthostatic intolerance. 247 people with LC (33.7%) and 40 controls (50%) responded to the surveys.

Results

In this study LC patients averaged 53 years of age and were predominantly White (95%) women (75%). The greatest prevalence of new or worsening comorbidities following SARS-CoV-2 infection in patients with LC vs. controls reported in this study were pain (94.4% vs. 0%, p < 0.001), neurological (92.4% vs. 15.4%, p < 0.001), sleep (82.8% vs. 5.3%, p < 0.001), skin (69.8% vs. 0%, p < 0.001), and genitourinary (60.6% vs. 25.0%, p = 0.029) issues. 58% of LC patients screened positive for ME/CFS vs. 0% of controls (p < 0.001), 27% positive for GJH compared to 10% of controls (p = 0.026), and a positive average score of 4.0 on orthostatic intolerance vs. 0 (p < 0.001). The majority of LC patients with ME/CFS were women (77%).

Conclusion

We found that comorbidities across 12 surveyed categories were increased in patients following SARS-CoV-2 infection. Our data also support the overlap of LC with ME/CFS, GJH, and orthostatic intolerance. We discuss the pathophysiologic, research, and clinical implications of identifying these conditions with LC.
Interactions between the human milk oligosaccharide 2′-fucosyllactose and Bifidobacterium longum subspecies infantis in influencing systemic immune development and function in piglets
Authors: Daniels Victoria C. , Monaco Marcia H. , Hirvonen Johanna , Ouwehand Arthur C. , Jensen Henrik Max , Mukerjea Ratna , Christensen Niels , Lehtinen Markus J. , Dilger Ryan N. , Donovan Sharon M.
Published: October 2024

Introduction

The oligosaccharide 2′-fucosyllactose (2′-FL) is a predominant component of human milk, serving as a prebiotic for gut microbiota and influencing immune development in infants. Bifidobacterium longum subspecies infantis (B. infantis) is a commensal bacterium found in breastfed infants. Both 2′-FL and a specific strain of B. infantis, Bi-26™, are commercially available. This study investigates the potential synbiotic relationship between 2′-FL and Bi-26™ on immune development.

Methods

Two-day-old piglets (n = 53) were randomized in a 2 × 2 design, receiving either a commercial milk replacer ad libitum without (CON) or with 1.0 g/L 2′-FL (FL). Piglets in each diet were further randomized to receive either glycerol stock alone or Bi-26™ (109 CFU) (BI and FLBI) orally once daily. On postnatal day (PND) 34/35, animals were euthanized, and blood was collected for serum cytokine analysis. Additionally, peripheral blood mononuclear cells (PBMCs) were isolated for ex vivo stimulation and flow cytometry analysis. Serum and ex vivo cytokines were analyzed using a multivariate model. All other outcomes were analyzed using a two-way ANOVA, considering prebiotic and probiotic fixed effects. The significance level was set at a p value <0.05, with trends reported for 0.05 < p < 0.1.

Results

Immune cell populations in PBMCs were unaffected by the experimental treatment. However, serum interleukin (IL)-1RA, IL-1β, IL-12, and IL-18 were all higher (p < 0.05) in the FL group than in the CON group. In isolated PBMCs, lipopolysaccharide (LPS) stimulation resulted in higher IL-1RA and a trend for higher IFN-γ secretion in the FL group vs. the CON group.

Conclusion

2′-FL stimulates a balanced cytokine profile in healthy piglets without changing immune cell populations. When immune cells are stimulated ex vivo with LPS, 2′-FL primes T-cells for a proinflammatory response, which is moderated by co-administration of Bi-26™.
The prevention and improvement effects of vitamin D on type 2 diabetes mellitus: evidence from an umbrella review on Meta-analyses of cohort studies and randomized controlled trials
Authors: Cheng Le , Lv Chenhui , Xue Lushan , Zhang Cheng , Wang Lili , Wang Xi , Chen Shuangzhi , Li Xuemin , Feng Wenjuan , Xie Haoran , Zhao Haifeng
Published: October 2024

Background

To clarify whether Vitamin D prevent the occurrence of type 2 diabetes mellitus (T2DM) and improve glucose control in T2DM patients, we conducted this umbrella review, taking into account the inconsistent results of existing Meta-analyses. We aim to reveal the causal relationship between Vitamin D and T2DM through summarizing Meta-analyses of observational studies, and clarify the improvement on glucose control in T2DM patients through summarizing Meta-analyses of RCT studies between Vitamin D supplementation and T2DM patients, especially in T2DM patients with Vitamin D deficiency.

Methods

We collected the Meta-analyses of observational studies and RCTs in PubMed, Scopus, Embase, Web of Science, and Cochrane.

Results

16 Meta-analyses (6 effect sizes for cohort studies and 10 effect sizes for RCTs) were included in the umbrella Meta-analyses. Random-effects model was carried out to calculate the pooled point estimates and their respective 95% confidence intervals (CI). The results revealed that lower 25(OH)D levels increased the risk of T2DM (Pooled ESRR = 1.34; 95%CI: 1.16, 1.53), Vitamin D supplementation ameliorated FBG (ES = −0.56; 95%CI: −1.00, −0.11), HbA1c (ES = −0.11; 95%CI: −0.20, −0.02), insulin (ES = −0.38; 95%CI: −0.59, −0.18) and HOMA-IR (ES = −0.37; 95%CI: −0.57, −0.16) in T2DM patients, especially in those with Vitamin D deficiency (FBG = −0.98; HbA1c = −0.27; HOMA-IR = −0.52).

Conclusion

The present umbrella Meta-analyses demonstrates the potential benefits of higher serum Vitamin D levels and Vitamin D supplementation in reducing the development and symptoms of T2DM.
Plant-based diet and risk of all-cause mortality: a systematic review and meta-analysis
Authors: Tan Junwen , Zhang Shipeng , Jiang Yanjie , Li Jie , Yang Chuan
Published: October 2024

Objective

A systematic analysis was conducted to determine the relationship between a plant-based diet and all-cause mortality.

Methods

The PubMed, Embase and Web of Science databases were searched. Two authors selected English documents from the database. Then the other two authors extracted the data and evaluated the Newcastle–Ottawa Scale (NOS). This study adhered to the guidelines of the Preferred Reporting Project (PRISMA) and the PROSPERO Registry protocols. A mixed-effects model combined maximum adjusted estimates, with heterogeneity measured using the I2 statistic. The sensitivity analysis validated the analysis’s robustness, while publication bias was assessed.

Results

The results of the meta-analysis of 14 articles revealed that a plant-based diet (PDI) can reduce cancer mortality (RR = 0.88, [95% CI 0.79–0.98], τ2: 0.02, I2: 84.71%), cardiovascular disease (CVD) mortality (RR = 0.81, [95% CI 0.76–0.86], τ2: 0.00, I2: 49.25%) and mortality (RR = 0.84, [95% CI 0.79–0.89], τ2: 0.01, I2: 81.99%) risk. Adherence to a healthy plant-based diet (hPDI) was negatively correlated with cancer mortality (RR = 0.91, [95% CI 0.83–0.99], τ2:0.01, I2:85.61%), CVD mortality (RR = 0.85, [95% CI 0.77–0.94], τ2: 0.02, I2: 85.13%) and mortality (RR = 0.85, [95% CI 0.80–0.90], τ2: 0.01, I2: 89.83%). An unhealthy plant-based diet (uPDI) was positively correlated with CVD mortality (RR = 1.19, [95% CI 1.07–1.32], τ2: 0.02, I2: 80.03%) and mortality (RR = 1.18, [95% CI 1.09–1.27], τ2: 0.01, I2: 89.97%) and had a certain correlation with cancer mortality (RR = 1.10, [95% CI 0.97–1.26], τ2: 0.03, I2: 93.11%). Sensitivity analysis showed no contradictory results.

Conclusion

The hPDI was negatively associated with all-cause mortality, and the uPDI was positively associated with all-cause mortality.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/#loginpage.
Obesity and lack of breastfeeding: a perfect storm to augment risk of breast cancer?
Authors: Ormiston Kate , Kulkarni Anagh , Sarathy Gautam , Alsammerai Sara , Shankar Eswar , Majumder Sarmila , Stanford Kristin I. , Ganju Ramesh K. , Ramaswamy Bhuvaneswari
Published: October 2024

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer with higher rates of recurrence and distant metastasis, as well as decreased 5-year survival rates. Racial disparities are evident in the incidence and mortality rates of triple negative breast cancer particularly increased in young African American women. Concurrently, young African American women have multiple risk factors for TNBC including higher rates of premenopausal abdominal obesity (higher waist-hip ratio) and lower rates of breastfeeding with higher parity, implicating these factors as potentially contributors to poor outcomes. By understanding the mechanisms of how premenopausal obesity and lack of breastfeeding may be associated with increased risk of triple negative breast cancer, we can determine the best strategies for intervention and awareness to improve outcomes in TNBC.
Endoscopic far-lateral supracerebellar infratentorial approach for resection of clival chordoma: case report
Authors: Han Song , Bai Yang , Sun Xiaoyu , Chen Ligang , Gao Yang , Liu Hongzhe , Li Huanhuan , Lai Jieyu , Feng Sizhe
Published: October 2024

Introduction

The surgery of clival chordoma remains one of the most formidable challenges for neurosurgeons because of its location at great depth in the cranium and proximity to critical neurovascular structures. Here, we describe the technique and feasibility of the purely endoscopic far-lateral supracerebellar infratentorial approach (EF-SCITA) for resection of an intradural clival chordoma.

Case description

A 68-year-old women presented with sudden ptosis on the left side for two weeks. Imaging examinations revealed an upper-middle clival lesion that transgressed dural confines towards the posterior fossa, which was separated from the sphenoid cavity by an intact thin layer of membrane structure in front. For surgery, the EF-SCITA approach via suboccipital craniotomy was attempted for protecting surrounding neurovascular tissue and the membrane barrier under direct vision. The patients were placed in a “head-up” lateral park-bench position. With the endoscopic holder, endoscopic procedures were performed using standard two-hand microsurgical techniques by one surgeon. Tentorium incision allowed a working corridor toward the clival bulge through the crural cistern, without brain traction seen in traditional retrosigmoid approach. Efficient tumor debulking facilitated the exposure of surrounding critical structures, including ipsilateral CN III and superior cerebellar artery above, the brainstem and basilar artery posteriorly, as well as ipsilateral CN VI displaced laterally, and subsequent tumor separation from them. Step-wise tumor resection was performed within dural and bone confines. After significant tumor removal, the pituitary stalk could be visualized anteriorly, together with contralateral internal carotid artery and CN III. Postoperative MRI depicted gross total excision of the lesion. The patient on follow-up at one year had complete recovery of cranial nerve functions, without signs of cerebrospinal fluid rhinorrhea.

Discussion

This technique combines advantages of the posterolateral approach and endoscopy, allowing access to the upper-middle clivus with seemingly low risks of postoperative morbidity. It would be a safe and effective alternative for resection of this rare entity.
Telehealth based parental support over 6 months improves physical activity and sleep quality in children with autism: a randomized controlled trial
Authors: Shen Xin , Huang Peiying , Liu Qian , Guo Yin , Zheng Lan
Published: October 2024

Purpose

Sleep disturbances are prevalent in autistic children. The emergence of telehealth offers new possibilities for remote professional intervention. By combining telehealth with parental support, this study aims to explore a novel family-based model to enhance moderate-to-vigorous physical activity (MVPA) and improve sleep quality in children with autism.

Methods

Thirty-four autistic children (mean age = 15.7 years) were randomly assigned to either a 6-month intervention group or a control group. Both groups received standard physical education classes at school. The intervention group received additional after-school telehealth support. MVPA and sleep quality were assessed 1 week before the intervention and at the 6-month follow-up.

Results

After 6 months, children in the intervention group nearly doubled their daily MVPA compared to the control group (Cohen's d = 8.34, CI95% = 6.17–10.52). Actigraphy-assessed sleep efficiency was notably higher (d = 2.35, CI95% = 1.44–3.26), and there were reductions in wake time (d = 1.65, CI95% = 0.84–2.46), sleep fragmentation (d = 0.80, CI95% = 0.07–1.52), and sleep latency (d = 0.82, CI95% = 0.09–1.54) were all reduced. These improvements in objective sleep metrics were corroborated by subjective assessments using the Sleep Disturbance Scale for Children (d = 0.86, CI95% = 0.13–1.59).

Conclusions

Telehealth combined with parental support addresses barriers to enhancing health behaviors at home. This innovative model not only improves after-school MVPA and sleep quality in autistic children but also holds significant potential for benefiting other populations requiring remote support.

Clinical Trial Registration

https://clinicaltrials.gov/study/NCT06444659?id=NCT06444659&rank=1 (NCT06444659).
Dopamine internalization via Uptake2 and stimulation of intracellular D5-receptor-dependent calcium mobilization and CDP-diacylglycerol signaling
Authors: Kang Wenfei , Siewe Arlette Deukam , Oluigbo Chizurum C. , Arijesudade Mercy O. , Brailoiu Eugen , Undieh Ashiwel S.
Published: October 2024

Dopamine stimulates CDP-diacylglycerol biosynthesis through D1-like receptors, particularly the D5 subtype most of which is intracellularly localized. CDP-diacylglycerol regulates phosphatidylinositol-4,5-bisphosphate-dependent signaling cascades by serving as obligatory substrate for phosphatidylinositol biosynthesis. Here, we used acute and organotypic brain tissues and cultured cells to explore the mechanism by which extracellular dopamine acts to modulate intracellular CDP-diacylglycerol. Dopamine stimulated CDP-diacylglycerol in organotypic and neural cells lacking the presynaptic dopamine transporter, and this action was selectively mimicked by D1-like receptor agonists SKF38393 and SKF83959. Dopaminergic CDP-diacylglycerol stimulation was blocked by decynium-22 which blocks Uptake2-like transporters and by anti-microtubule disrupters of cytoskeletal transport, suggesting transmembrane uptake and guided transport of the ligands to intracellular sites of CDP-diacylglycerol regulation. Fluorescent or radiolabeled dopamine was saturably transported into primary neurons or B35 neuroblastoma cells expressing the plasmamembrane monoamine transporter, PMAT. Microinjection of 10-nM final concentration of dopamine into human D5-receptor-transfected U2-OS cells rapidly and transiently increased cytosolic calcium concentrations by 316%, whereas non-D5-receptor-expressing U2-OS cells showed no response. Given that U2-OS cells natively express PMAT, bath application of 10 μM dopamine slowly increased cytosolic calcium in D5-expressing cells. These observations indicate that dopamine is actively transported by a PMAT-implicated Uptake2-like mechanism into postsynaptic-type dopaminoceptive cells where the monoamine stimulates its intracellular D5-type receptors to mobilize cytosolic calcium and promote CDP-diacylglycerol biosynthesis. This is probably the first demonstration of functional intracellular dopamine receptor coupling in neural tissue, thus challenging the conventional paradigm that postsynaptic dopamine uptake serves merely as a mechanism for deactivating spent or excessive synaptic transmitter.
Efficacy and safety of Shenmai injection in the treatment of viral myocarditis: a systematic review and meta-analysis
Authors: Yang Qianhe , Qin Jie , Li Ziyue , He Yue , Zhou Yabin
Published: October 2024

Purpose

To evaluate the efficacy and safety of Shenmai injection for the treatment of viral myocarditis (VMS) through systematic evaluation and meta-analysis.

Methods

Seven databases were searched to identify randomized controlled trials that examined the use of Shenmai injection for the treatment of VMS. The databases were searched from inception to 20 January 2024. The quality of the included studies was evaluated via the Cochrane risk of bias tool (RoB 2) version 2. Data analysis was performed using Review Manager 5.4 and Stata 16.

Results

In total, 18 randomized controlled trials were included. The trials were conducted in 2006–2024 and included 1,661 patients with VMS. The results reveal that Shenmai injection combined with conventional treatment was superior to conventional treatment alone in terms of the following outcomes: total effective rate [RR = 1.22, 95% CI (1.16, 1.28)], CKMB [SMD = −3.33, 95% CI (−4.85, −1.81)], electrocardiogram (ECG) efficacy [RR = 1.30, 95% CI (1.20, 1.40)], AST [SMD = -0.70, 95% CI (−1.28, −0.11)], LDH [SMD = −1.17, 95% CI (−1.37, −0.97], p < 0.00001], CK [SMD = −1.74, 95% CI (−2.34, −1.13)], TNF-α [SMD = −1.35, 95% CI (−1.85, −0.84)], and IL-6 [SMD = −1.40, 95% CI (−1.76, −1.05)]. There were no significant differences in the incidence of adverse reactions [RR = 1.56, 95% CI (0.73, 3.33), p = 0.25] or cTnI levels [SMD = −3.35, 95% CI (−6.81, 0.11)] between the groups.

Conclusion

Shenmai injection with conventional treatment can reduce the degree of myocardial injury in patients with VMS, weaken the inflammatory response and improve the clinical efficacy of the conventional treatment. This approach was found to be safe. However, additional high-quality studies are necessary to confirm the reliability of this treatment method.

Systematic Review Registration:

https://www.crd.york.ac.uk/PROSPERO/logout.php, identifier PROSPERO (CRD42024518665).
Lefamulin dosing optimization using population pharmacokinetic and pharmacokinetic/pharmacodynamic assessment in Chinese patients with community-acquired bacterial pneumonia
Authors: Bian Xingchen , Li Nanyang , Li Yi , Zhu Xu , Yu Jicheng , Hu Yingying , Yang Haijing , Wei Qiong , Wu Xiaojie , Wang Jingjing , Cao Guoying , Wu Jufang , Wang Yang , Zhang Jing
Published: October 2024

Purpose

Lefamulin is the first pleuromutilin antibiotic approved for the treatment of community-acquired bacterial pneumonia (CABP). However, the pharmacokinetic/pharmacodynamic (PK/PD) characteristics in Chinese CABP patients are not fully understood. This study aimed to evaluate its microbiological efficacy against Streptococcus pneumoniae and Staphylococcus aureus via PK/PD analysis.

Methods

The population PK (PopPK) model, established with foreign data was validated using data from Chinese CABP patients. PK/PD analysis was conducted for the intravenous administration of 150 mg q12 h for 1-h, 1.5-h and extended 2-h infusion. Oral administrations of 600 mg q12 h were assessed, considering original and higher plasma protein binding.

Results

Lefamulin displayed similar PK characteristics in both Chinese and Western populations. The PopPK model effectively predicted lefamulin concentrations in Chinese CABP patients. Under the dosage regimen of 150 mg q12 h via intravenous infusion for 1/1.5/2 h, the probability of target attainments reached 98% at the minimum inhibitory concentration for both 90% S. pneumoniae and S. aureus, considering both original and higher protein binding rates. It is advisable to extend the infusion duration from 1/1.5 h–2 h to minimize the risk of adverse effects at the infusion site. Regardless of fasted or fed conditions, the PTAs for 600 mg q12 h lefamulin via oral administration proved comparable to those for intravenous administration.

Conclusion

This study proved that intravenous and oral administrations of lefamulin can reach preclinical PK/PD targets of S. pneumoniae and S. aureus. These findings support the optimal use of lefamulin for the safe and effective treatment of Chinese CABP patients.
Safety assessment of sapropterin dihydrochloride: real-world adverse event analysis based on the FDA adverse event reporting system (FAERS)
Authors: Zhong Jiahong , Yu Xihui , Lin Zhuomiao
Published: October 2024

Objective

Sapropterin dihydrochloride is the first drug for the therapy of phenylketonuria, which is a rare disease that occurs one of 10,000–15,000 newborns. As a result, detailed and comprehensive reports on the safety of sapropterin in large, real-world populations are required. The purpose of this study is to undertake a complete analysis of sapropterin’s adverse events (AEs) using the FDA Adverse Event Reporting System (FAERS) database.

Methods

We retrieved reports of adverse events with sapropterin as the principal suspect from FAERS between the first quarter of 2008 and the first quarter of 2024. The Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN) were utilized to detect AE signals.

Results

The study collected 4,953 suspected AE cases from the FAERS database, with sapropterin as the major suspect. A total of 130 positive signals were obtained utilizing the ROR, PRP, and BCPNN. The FAERS database revealed that common clinical AEs of sapropterin included vomiting, upper respiratory infection, rhinorrhea, and a reduction in amino acid concentrations. Furthermore, we detected probable unexpected adverse events (AEs) using disproportionality analysis, including gastroesophageal reflux disease, flatulence, influenza, ear infection, viral infection, pharyngitis streptococcal, spontaneous abortion, and nephrolithiasis.

Conclusion

By analyzing huge amounts of real-world data from the FAERS database, we found potential novel AEs of sapropterin using disproportionate analysis. It is advantageous for healthcare professionals and pharmacists to focus on efficiently managing sapropterin’s high-risk adverse events, improving drug levels in clinical settings, and ensuring patient medication safety.
Ecotypic differentiation of leaf silicon concentration in the grass Brachypodium hybridum along a rainfall gradient
Authors: Kurze Susanne , Ouyang Jinyu , Gade Florian , Katz Ofir , Schaller Jörg , Metz Johannes
Published: October 2024

Ecotypic differentiation, reflected in substantial trait differences across populations, has been observed in various plant species distributed across aridity gradients. Nevertheless, ecotypic differentiation in leaf silicon concentration, known to alleviate drought stress in plants, remained hardly explored. Here, we provide a systematic test for ecotypic differentiation in leaf silicon concentration along two aridity gradients in the grass Brachypodium hybridum in Israel. Seed material was sampled in 15 sites along a macroclimatic aridity gradient (89 – 926 mm mean annual rainfall) and from corresponding north (moister) and south (more arid) exposed slopes (microclimatic gradient) at similar altitudes (mean north: 381 m a.s.l., mean south: 385 m a.s.l.). Plants were subsequently grown under common conditions and their leaf silicon concentration was analysed. Leaf silicon concentration increased with increasing aridity across the macroclimatic gradient, but did not differ between north and south slopes. The higher leaf silicon concentrations under more arid conditions can enhance the ability of plants to cope with more arid conditions by two mutually not exclusive mechanisms: (i) withstanding drought by reducing water loss and increasing water uptake or (ii) escaping drought by facilitating fast growth. Our study highlights that leaf silicon concentration contributes to ecotypic differentiation in annual grasses along macroclimatic aridity gradients.
Mapping and cloning of pepper fruit color-related genes based on BSA-seq technology
Authors: Feng Shuo , Zhou Ling , Sharif Rahat , Diao Weiping , Liu Jiali , Liu Xinxin , Chen Kunhao , Chen Guoju , Cao Bihao , Zhu Zhangsheng , Liao Yi , Lei Jianjun , Chen Changming
Published: October 2024

Fruit color is an important qualitative trait that greatly influences the marketability of peppers. Fruit color can be divided into two categories. Green fruit color denotes commercial maturity, whereas ripe fruit indicates physiological maturity. Herein, segregation populations were created using the ‘D24’ with pale green in the green fruit stage, orange in the mature fruit stage, and ‘D47’ with green in the green fruit stage and red in the mature fruit stage. BSA-seq and genetic linkage map analysis revealed green fruit color was linked to (gyqtl1.1) on Chr1 and (gyqtl10.1) on Chr10, while mature fruit color was linked to Chr6. Using functional annotation, sequence, and expression analysis, we speculate that an SNP mutation in the CapGLK2 gene at the gyqtl10.1 interval could initiate premature termination of translation, thus yielding green to pale green fruits in D47. Conversely, the orange color in mature D24 fruits is due to the Indel-mediated premature termination of translation of the CapCCS gene. Our research offers a theoretical foundation for choosing different varieties of pepper fruit based on their color.
Beyond humanism: telling response-able stories about significant otherness in human–chatbot relations
Authors: Holohan Michael , Müller Ruth
Published: October 2024

AI-enabled chatbots intended to build social relations with humans are becoming increasingly common in the marketplace, with millions of registered users using these chatbots as virtual companions or therapists. These chatbots make use of what is often called the “Eliza effect”—the tendency of human users to attribute human-like knowledge and understanding to a computer program. A common interpretation of this phenomenon is to consider this form of relating in terms of delusion, error, or deception, where the user misunderstands or forgets they are talking to a computer. As an alternative, we draw on the work of feminist Science and Technology Studies scholars as providing a robust and capacious tradition of thinking and engaging with human–nonhuman relationships in non-reductive ways. We closely analyze two different stories about encounters with chatbots, taking up the feminist STS challenge to attend to the agency of significant otherness in the encounter. The first is Joseph Weizenbaum's story about rejecting the ELIZA chatbot technology he designed to mimic a therapist as a monstrosity, based on his experiences watching others engage with it. The second is a story about Julie, who experiences a mental health crisis, and her chatbot Navi, as told through her descriptions of her experiences with Navi in the recent podcast Radiotopia presents: Bot Love. We argue that a reactionary humanist narrative, as presented by Weizenbaum, is incapable of attending to the possibilities of pleasure, play, or even healing that might occur in human–chatbot relatings. Other forms of engaging with, understanding, and making sense of this new technology and its potentialities are needed both in research and mental health practice, particularly as more and more patients will begin to use these technologies alongside engaging in traditional human-led psychotherapy.
Mapping perceived sentiments in university campuses with varied landscape metrics and climatic conditions
Authors: Yan Qiyuan , Sun Yuxiang
Published: October 2024

A sustainable university campus should accommodate students to experience positive emotions, which can be evoked by sustainable landscape with green and blue spaces (GBS). This effect is location-dependent because local vegetative type is climate-determinative, but evidence is not sufficient for sentiments of people experiencing campus landscapes. Forty-seven university campuses were selected along a latitudinal gradient in mainland China, and 100 subjects were chosen per campus (50 indoor and 50 outdoor). Photos of the subjects’ faces on Sina Weibo were collected. Facial expressions were assigned happy, sad, and neutral scores (n = 4,334). The average temperature (AveT) and blue space area (BlueA) showed negative relationships with latitude, thereby generating neutral emotion scores for subjects at indoor and outdoor locations. The ratio of green space area to host campus was the only landscape metric that depressed the presentation of happiness and enhanced sadness levels. Large water bodies should be built on campuses to induce calmness, and a high ratio of green spaces should be avoided. Mapping results show that campuses in eastern regions (Beijing and Liaoning) tend to elicit positive sentiments more frequently.