bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of maize genotypes and harvest stages on in-silo fermentation quality and nutritional value of corn silage during hot summer condition of the tropics
Authors: Khan Nadar , Shah Tawaf Ali , Akhtar Hafiz Muhammad Saleem , Salamatullah Ahmad Mohammad , Bourhia Mohammed , Mekonnen Amare Bitew , Khan Muhammad Zahoor , Nazar Mudasir , Khan Nazir Ahmad
Published: June 2024

The aim of the experiment was to evaluate the potential of promising summer maize genotypes and optimal stage of harvesting these genotypes for ensiling in terms of dry matter (DM), starch, and crude protein (CP) yields, silage fermentation quality, nutrients profile, total digestible nutrients, metabolizable energy (ME) content, Cornell Net Carbohydrate and Protein System (CNCPS) carbohydrate (CHO) subfractions composition, in vitro DM digestibility (DMD) and in situ starch degradation characteristics. Six maize genotypes were chosen for the study: DK9108 from Monsanto, P30Y87, P3939 from Pioneer, QPM-300 (quality protein maize) and W94 from the International Maize and Wheat Improvement Center (CIMMYT), and a local cultivar, Afgoii, from the Cereal Research Institute (Persabaq, KP). A total of 72 plots (8 m × 10 m) were blocked in three replicate fields, and within each field, each genotype was sown in four replicate plots according to a randomized complete block design. For the data analysis, the Proc-Mixed procedure of Statistical Analysis System with repeated measure analysis of variance was used. The DM yield was strongly influenced (P < 0.001) by maize genotypes, varying from 12.6 to 17.0 tons/ha. Except for total CHO and ammonia nitrogen (NH3-N), the contents of all measured chemical components varied (P < 0.001) among the genotypes. Further comparison revealed that, genotype P3939 had a higher (P < 0.05) content of CP (7.27 vs. 6.92%), starch (36.7 vs. 27.9%), DMD (65.4 vs. 60.0%), ME (2.51 vs. 2.30 Mcal/kg) and lactic acid (5.32 vs. 4.83%) and lowest content of NDF (37.3 vs. 43.1%), pH (3.7 vs. 4.10) compared to the local cultivar (Afgoii). Advancement of post-flowering maturity from 25 to 35% DM (23 to 41 days after flowering (DAF)) increased (P < 0.05) the DM yield (10.4 to 17.8 tons/ha), starch content (29.1 to 35.0%), DMD (65.3 to 67.3%) and ME (2.34 to 2.47 Mcal/kg), and decreased (P < 0.001) the contents of CP (7.42–6.73%), NDF (48.8–38.5%), pH (4.10 to 3.60), NH3-N (8.93–7.80%N) and effective degradability of starch (95.4 to 89.4). Results showed that for higher yields and silage nutritional and fermentation quality, maize crops should be harvested at whole crop DM content of 30–35% (34 to 41 DAF). It was further concluded that genotype P3939 is the most suitable summer maize genotype for silage production in terms of yields and silage nutritional and fermentation quality under the hot environmental conditions of the tropics.
Use of systems thinking and adapted group model building methods to understand patterns of technology use among older adults with type 1 diabetes: a preliminary process evaluation
Authors: Kahkoska Anna R. , Smith Cambray , Young Laura A. , Hassmiller Lich Kristen
Published: June 2024

Background

A growing number of older adults (ages 65+) live with Type 1 diabetes. Simultaneously, technologies such as continuous glucose monitoring (CGM) have become standard of care. There is thus a need to understand better the complex dynamics that promote use of CGM (and other care innovations) over time in this age group. Our aim was to adapt methods from systems thinking, specifically a participatory approach to system dynamics modeling called group model building (GMB), to model the complex experiences that may underlie different trajectories of CGM use among this population. Herein, we report on the feasibility, strengths, and limitations of this methodology.

Methods

We conducted a series of GMB workshops and validation interviews to collect data in the form of questionnaires, diagrams, and recordings of group discussion. Data were integrated into a conceptual diagram of the “system” of factors associated with uptake and use of CGM over time. We evaluate the feasibility of each aspect of the study, including the teaching of systems thinking to older adult participants. We collected participant feedback on positive aspects of their experiences and areas for improvement.

Results

We completed nine GMB workshops with older adults and their caregivers (N = 33). Each three-hour in-person workshop comprised: (1) questionnaires; (2) the GMB session, including both didactic components and structured activities; and (3) a brief focus group discussion. Within the GMB session, individual drawing activities proved to be the most challenging for participants, while group activities and discussion of relevant dynamics over time for illustrative (i.e., realistic but not real) patients yielded rich engagement and sufficient information for system diagramming. Study participants liked the opportunity to share experiences with peers, learning and enhancing their knowledge, peer support, age-specific discussions, the workshop pace and structure, and the systems thinking framework. Participants gave mixed feedback on the workshop duration.

Conclusions

The study demonstrates preliminary feasibility, acceptability, and the value of GMB for engaging older adults about key determinants of complex health behaviors over time. To our knowledge, few studies have extended participatory systems science methods to older adult stakeholders. Future studies may utilize this methodology to inform novel approaches for supporting health across the lifespan.
Temporal composition of the cervicovaginal microbiome associates with hrHPV infection outcomes in a longitudinal study
Authors: Molina Mariano A. , Leenders William P. J. , Huynen Martijn A. , Melchers Willem J. G. , Andralojc Karolina M.
Published: June 2024

Background

Persistent infections with high-risk human papillomavirus (hrHPV) can cause cervical squamous intraepithelial lesions (SIL) that may progress to cancer. The cervicovaginal microbiome (CVM) correlates with SIL, but the temporal composition of the CVM after hrHPV infections has not been fully clarified.

Methods

To determine the association between the CVM composition and infection outcome, we applied high-resolution microbiome profiling using the circular probe-based RNA sequencing technology on a longitudinal cohort of cervical smears obtained from 141 hrHPV DNA-positive women with normal cytology at first visit, of whom 51 were diagnosed by cytology with SIL six months later.

Results

Here we show that women with a microbial community characterized by low diversity and high Lactobacillus crispatus abundance at both visits exhibit low risk to SIL development, while women with a microbial community characterized by high diversity and Lactobacillus depletion at first visit have a higher risk of developing SIL. At the level of individual species, we observed that a high abundance for Gardnerella vaginalis and Atopobium vaginae at both visits associate with SIL outcomes. These species together with Dialister micraerophilus showed a moderate discriminatory power for hrHPV infection progression.

Conclusions

Our results suggest that the CVM can potentially be used as a biomarker for cervical disease and SIL development after hrHPV infection diagnosis with implications on cervical cancer prevention strategies and treatment of SIL.
Association between oxidative balance score and kidney stones: data from the national health and nutrition examination survey (NHANES)
Authors: Song Rundong , Wu Ke , Ma Minghai , Wang Lu , Jiang Yunzhong , Li Jianpeng , Fan Jinhai
Published: June 2024

Purpose

Some studies have found that the pathological formation of kidney stones is closely related to injury and inflammatory response. Behaviors such as dietary composition, physical activity, obesity and smoking can all affect the body’s oxidative stress levels. In order to evaluate the effects of various diets and lifestyles on the body’s oxidative and antioxidant systems, an oxidative balance score was developed. To investigate whether the OBS is associated with the development of kidney stones.

Methods

Data were taken from the National Health and Nutrition Examination Survey (NHANES) from 2007–2018, followed by retrospective observational studies. The association between kidney stones and OBS was analyzed using survey-weighted logistic regression by adjusting for demographics, laboratory tests, and medical comorbidity covariates. The oxidative balance score is calculated by screening 16 nutrients and 4 lifestyle factors, including 5 prooxidants and 15 antioxidants, based on prior information about the relationship between oxidation levels in the body and nutrients or lifestyle factors.

Results

A total of 26,786 adult participants were included in the study, of which 2,578, or 9.62%, had a history of nephrolithiasis. Weighted logistic regression analysis found an association between OBS and kidney stones. In the fully tuned model, i.e., model 3, the highest quartile array of OBS was associated with the lowest quartile array of OBS (OR = 0.73 (0.57, 0.92)) with the risk of kidney stone (p = 0.01), and was statistically significant and remained relatively stable in each model. At the same time, the trend test in the model is also statistically significant. With the increase of OBS, the OR value of kidney stones generally tends to decrease.

Conclusions

There is an inverse correlation between OBS and kidney stone disease. At the same time, higher OBS suggests that antioxidant exposure is greater than pro-oxidative exposure in diet and lifestyle, and is associated with a lower risk of kidney stones
Trifluridine–tipiracil plus bevacizumab versus trifluridine–tipiracil monotherapy for chemorefractory metastatic colorectal cancer: a systematic review and meta-analysis
Authors: Aquino de Moraes Francisco Cezar , Dantas Leite Pessôa Felipe Dircêu , Duarte de Castro Ribeiro Caio Henrique , Rodrigues Fernandes Marianne , Rodríguez Burbano Rommel Mario , Carneiro dos Santos Ney Pereira
Published: June 2024

Colorectal cancer is the leading cause of cancer death worldwide. The first and second lines of treatment for metastatic colorectal cancer (mCRC) include chemotherapy based on 5-fluorouracil. However, treatment following progression on the first and second line is still unclear. We searched PubMed, Scopus, Cochrane, and Web of Science databases for studies investigating the use of trifluridine-tipiracil with bevacizumab versus trifluridine-tipiracil alone for mCRC. We used RStudio version 4.2.3; and we considered p < 0.05 significant. Seven studies and 1,182 patients were included − 602 (51%) received trifluridine-tipiracil plus bevacizumab. Compared with control, the progression-free survival (PFS) (HR 0.52; 95% CI 0.42–0.63; p < 0.001) and overall survival (OS) (HR 0.61; 95% CI 0.52–0.70; p < 0.001) were significantly higher with bevacizumab. The objective response rate (ORR) (RR 3.14; 95% CI 1.51–6.51; p = 0.002) and disease control rate (DCR) (RR 1.66; 95% CI 1.28–2.16; p = 0.0001) favored the intervention. Regarding adverse events, the intervention had a higher rate of neutropenia (RR 1.38; 95% CI 1.19–1.59; p = 0.00001), whereas the monotherapy group had a higher risk of anemia (RR 0.60; 95% CI 0.44–0.82; p = 0.001). Our results support that the addition of bevacizumab is associated with a significant benefit in PFS, OS, ORR and DCR.

Graphical Abstract
Hotspots and trends in health-oriented physical literacy research: a visual analysis based on the WOS database
Authors: Fang Xinyuan , Zhang Zhen
Published: June 2024

Background

The World Health Organization has proposed that physical activity is a meaningful way to improve the quality of human life and reduce the probability of chronic non-communicable diseases and that humans should change their mindset from the actual effectiveness of physical activity in promoting health to the new view that “physical activity makes life more meaningful.” The introduction and development of physical literacy reveal the critical role of physical activity in improving human health and the importance of human initiative in physical activity for healthy development. Therefore, the objectives of this paper are (1) to conduct a bibliometric analysis of the literature on physical literacy, assessing the scope, frequency, and geographical distribution of research publications from various countries and institutions from 2015 to 2023; (2) to visualize keywords in articles on the topic of Physical literacy to analyze whether there is a link between physical literacy and health, and (3) based on the results of the visual analysis, we propose that proper health is built on the sense of physical literacy and further construct the circular path of physical literacy, physical activity, and physical health improvement.

Methods

Using VOSviewer software v.1.6.18, this study searched the core collection of the Web of Science database from 2015 to April 15, 2023, using “physical literacy” as a keyword to explore the current international research on physical literacy.

Results

A total of 3,446 articles were included, and a correlation map was derived based on the co-occurrence frequency of keywords, which showed that physical literacy was highly correlated with six concepts: health literacy, physical activity, health, children, adolescents, and prevention.

Conclusion

Based on the analysis of literature visualization techniques, there is a high correlation between physical literacy and health, and international physical literacy research is in a trend of multi-point amplification, with research hotspots gradually shifting from the field of sports to the field of health and closely related to the field of health, indicating that physical literacy aims to promote the achievement of individual health by driving humans to increase physical activity.
Condom use increased after a peer group intervention implemented by community volunteers in Malawi
Authors: Norr Kathleen F. , Banda Chimwemwe K. , Chang Cecilia , Krishna Shruthi , Kumbani Lily C. , Liu Li , McCreary Linda L. , Patil Crystal L.
Published: June 2024

Background

HIV prevention remains a global priority, especially in sub-Saharan Africa. Our research team previously developed an evidence-based peer group program for HIV prevention called Mzake ndi Mzake (Friend to Friend). A community-engaged collaboration adapted the program for community ownership and implementation. Here we report whether this HIV prevention program, implemented by community volunteers, increased condom use among sexually active individuals in rural Malawi.

Methods

Three communities sequentially rolled out the program. Effectiveness was evaluated using a stepped wedge design. Repeated surveys 11–13 months apart were conducted between 2016 and 2019. At Time 1, no community had offered the intervention. At Time 2, the first community had offered the intervention and two had not (control group). At Time 3, two communities had offered the intervention and one had not (control group). We used two condom use indicators; condom use frequency in the last 2 months (N = 771) and condom use at last sex (N = 880). The analytical sample included all sexually active persons answering that question at one or more time points. Mixed-effects cumulative logit and Generalized Estimating Equation (GEE) models were used to model the two condom indicators over time, controlling for demographic factors, UNAIDS HIV knowledge, safer sex self-efficacy and partner communication.

Results

This peer group intervention implemented by trained community volunteers increased both condom use indicators at Times 2 and 3. In the final adjusted models with non-significant factors removed, condom use in the last two months increased for the intervention group vs. control group [Time 2: Adjusted Odds Ratio (AOR) = 1.59 (1.15, 2.21); Time 3: AOR 2.01 (1.23, 3.30)]. Similarly, condom use at last sex increased for the intervention group vs. control group [Time 2: AOR = 1.48 (1.08, 2.03); Time 3: AOR 1.81 (1.13, 2.90)]. Other significant predictors of greater condom use were also described. Although the intervention increased UNAIDS HIV knowledge, knowledge did not predict condom use.

Conclusions

In this community-engaged implementation study, an evidence-based peer group program for HIV prevention increased condom use when delivered by trained community volunteers. Community ownership and program delivery by trained volunteers offer an innovative and cost-effective strategy to address ongoing HIV prevention needs without overburdening healthcare systems in sub-Saharan Africa.

Trial registration

Clinical Trials.gov NCT02765659 Registered May 6, 2016.
The management pattern and outcomes of chronic thromboembolic pulmonary hypertension: rationale and design for a Chinese real-world study
Authors: Zhang Shuai , Li Yishan , Yang Yuanhua , Gong Sugang , Yang Zhenwen , Hong Cheng , Cui Xiaopei , Wan Jun , Ji Yingqun , Chen Hong , Zhu Ling , Li Chenghong , Cheng Zhaozhong , Zhang Yunhui , Wang Qiguang , Luo Qin , Guo Lu , Ma Guofeng , Han Baoshi , Liu Zhihong , Xiong Changming , Wang Lan , Ji Qiushang , Li Fajiu , Wang Shengfeng , Zhang Zhu , Zhang Yunxia , Wang Dingyi , Gao Qian , Huang Qiang , Xie Wanmu , Zhai Zhenguo , Wang Chen
Published: June 2024

Background

Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disorder with substantial morbidity and mortality, also a disease underdiagnosed and undertreated. It is potentially curable by pulmonary endarterectomy (PEA) in patients with surgically accessible thrombi. Balloon pulmonary angioplasty (BPA) and targeted medical therapy are options for patients with distal lesions or persistent/recurrent pulmonary hypertension after PEA. There is an urgent need to increase the awareness of CTEPH. Qualified CTEPH centers are still quite limited. Baseline characteristics, management pattern and clinical outcome of CTEPH in China needs to be reported.

Methods and design

The CHinese reAl-world study to iNvestigate the manaGEment pattern and outcomes of chronic thromboembolic pulmonary hypertension (CHANGE) study is designed to provide the multimodality treatment pattern and clinical outcomes of CTEPH in China. Consecutive patients who are ≥ 14 year-old and diagnosed with CTEPH are enrolled. The diagnosis of CTEPH is confirmed in right heart catheterization and imaging examinations. The multimodality therapeutic strategy, which consists of PEA, BPA and targeted medical therapy, is made by a multidisciplinary team. The blood sample and tissue from PEA are stored in the central biobank for further research. The patients receive regular follow-up every 3 or 6 months for at least 3 years. The primary outcomes include all-cause mortality and changes in functional and hemodynamic parameters from baseline. The secondary outcomes include the proportion of patients experiencing lung transplantation, the proportion of patients experiencing heart and lung transplantation, and changes in health-related quality of life. Up to 31 December 2023, the study has enrolled 1500 eligible patients from 18 expert centers.

Conclusions

As a real-world study, the CHANGE study is expected to increase our understanding of CTEPH, and to fill the gap between guidelines and the clinical practice in the diagnosis, assessment and treatment of patients with CTEPH.

Registration Number in ClinicalTrials.gov

NCT05311072.
Causal impact of DNA methylation on refracture in elderly individuals with osteoporosis – a prospective cohort study
Authors: Wen Bingtao , Zhang Yaning , He Jianhua , Tan Lei , Xiao Guanggui , Wang Zunliang , Cui Wei , Wu Bingxuan , Wang Xianhai , He Lei , Li Ming , Zhu Zhongjiao , Sang Dacheng , Zeng Changqing , Jia Peilin , Liu Fan , Liu Tianzi
Published: June 2024

Background

Osteoporotic vertebral compression fractures (OVCF) in the elderly increase refracture risk post-surgery, leading to higher mortality rates. Genome-wide association studies (GWAS) have identified susceptibility genes for osteoporosis, but the phenotypic variance explained by these genes has been limited, indicating the need to explore additional causal factors. Epigenetic modifications, such as DNA methylation, may influence osteoporosis and refracture risk. However, prospective cohorts for assessing epigenetic alterations in Chinese elderly patients are lacking. Here, we propose to conduct a prospective cohort study to investigate the causal network of DNA polymorphisms, DNA methylation, and environmental factors on the development of osteoporosis and the risk of refracture.

Methods

We will collect vertebral and peripheral blood from 500 elderly OVCF patients undergoing surgery, extract DNA, and generate whole genome genotype data and DNA methylation data. Observation indicators will be collected and combined with one-year follow-up data. A healthy control group will be selected from a natural population cohort. Epigenome-wide association studies (EWAS) of osteoporosis and bone mineral density will be conducted. Differential methylation analysis will compare candidate gene methylation patterns in patients with and without refracture. Multi-omics prediction models using genetic variants and DNA methylation sites will be built to predict OVCF risk.

Discussion

This study will be the first large-scale population-based study of osteoporosis and bone mineral density phenotypes based on genome-wide data, multi-time point methylation data, and phenotype data. By analyzing methylation changes related to osteoporosis and bone mineral density in OVCF patients, the study will explore the feasibility of DNA methylation in evaluating postoperative osteoporosis intervention effects. The findings may identify new molecular markers for effective anti-osteoporosis treatment and inform individualized prevention and treatment strategies.

Trial registration

chictr.org.cn ChiCTR2200065316, 02/11/2022.
Factors associated with glycemic control in patients with T2DM: evidence from a cross-sectional study in China
Authors: Luo Wenting , Zhang Jiayu , Luo Yanxing , Wu Qiuwan , Chen Longfei , Liu Changqin , Lin Minqiang
Published: June 2024

Objective

This study aimed to analyze the factors influencing glycemic control in patients with type 2 diabetes mellitus (T2DM).

Methods

Baseline data, encompassing basic information, lifestyle habits, and treatment of 305 T2DM patients from March 2021 to January 2023, were collected and analyzed using SPSS 26.0 software.

Results

Univariate and multivariate logistic regression analyses identified insulin therapy (OR = 2.233; 95%Cl = 1.013–4.520; P = 0.026) and regular clinic visits (OR = 0.567; 95%Cl = 0.330–0.973; P = 0.040) as independent factors influencing glycemic control. No observed interactions between the two variables were noted.

Conclusion

History of insulin therapy and regular clinic visits were significantly and independently associated with glycated hemoglobin control in T2DM patients. Tailored interventions based on individual circumstances are recommended to optimize glycemic control.
Continue nursing education: an action research study on the implementation of a nursing training program using the Holton Learning Transfer System Inventory
Authors: Shen MingYan , Feng ZhiXian
Published: June 2024

Objective

To address the gap in effective nursing training for quality management, this study aims to implement and assess a nursing training program based on the Holton Learning Transfer System Inventory, utilizing action research to enhance the practicality and effectiveness of training outcomes.

Methods

The study involved the formation of a dedicated training team, with program development informed by an extensive situation analysis and literature review. Key focus areas included motivation to transfer, learning environment, and transfer design. The program was implemented in a structured four-step process: plan, action, observation, reflection.

Results

Over a 11-month period, 22 nurses completed 14 h of theoretical training and 18 h of practical training with a 100% attendance rate and 97.75% satisfaction rate. The nursing team successfully led and completed 22 quality improvement projects, attaining a practical level of application. Quality management implementation difficulties, literature review, current situation analysis, cause analysis, formulation of plans, implementation plans, and report writing showed significant improvement and statistical significance after training.

Conclusion

The study confirms the efficacy of action research guided by Holton’s model in significantly enhancing the capabilities of nursing staff in executing quality improvement projects, thereby improving the overall quality of nursing training. Future research should focus on refining the training program through long-term observation, developing a multidimensional evaluation index system, exploring training experiences qualitatively, and investigating the personality characteristics of nurses to enhance training transfer effects.
Trichuris Globulosa Von Linstow, 1901 from one-humped camel (Camelus dromedarius) in Egypt: prevalence, morphological and molecular study
Authors: Ismail Badawy I. B. , El-Seify Mahmoud A. , Khalafalla Reda E. , Sorour Shimaa S. , Sultan Khaled , Elhawary Nagwa M.
Published: June 2024

Background

Trichuris spp. (whipworms) are soil-transmitted helminths distributed worldwide, parasitizing several mammalian hosts such as ruminants, primates, and rodents. Trichuris spp. is one of the most common intestinal parasites affecting both humans and animals, and it can spread directly through the fecal-oral route, resulting in severe illness and financial loss. So, this work aims to detect the frequency of Trichuris spp. in camels in Beheira Governorate, Egypt, and to identify Trichuris spp. through morphometrical studies, molecular analysis, and phylogenetic analysis.

Results

A total of 35 dromedaries out of 127 investigated had Trichuris spp. infection, meaning that the overall prevalence was 27.56%. The age of the camel affected the infection rate, older animals (> 5 years) having a higher prevalence of infection (24%) than animals of ages (< 3 years) (20%) than animals of ages (3–5 years) (19.14%). According to season: Trichuris spp. showed a unique pattern in camels in different seasons: summer (31.25%) > autumn (28.13%) > spring (25.8%) > winter (25%) indicating year-round infection. T. globulosa was identified morphometrically from camels in Beheira Governorate, Egypt. The BLAST analysis revealed the presence of T. globulosa isolate from camels using the Genbank database depending on nuclear small subunit ribosomal RNA (18s) and cytochrome b (Cytb) genes.

Conclusion

A high prevalence of T. globulosa was found in camels in Beheira Governorate, Egypt. This is the first report to confirm the identification of T. globulosa from camel based on morphometrical studies and molecular and phylogenetic analysis in Egypt. More thorough studies on the incidence, molecular, and genetic analysis of Trichuris spp. in Egypt are required in addition to camel control programs.
Delayed diagnosis of mild mucopolysaccharidosis type IVA
Authors: Yi Mengni , Shen Pinquan , Zhang Huiwen
Published: June 2024

Background

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease caused by biallelic variants in the N-acetylgalactosamine-6-sulfatase (GALNS) gene and is characterized by progressive and multi-system involvements, dominantly with skeletal deformities. A mild form of MPS IVA often presents with atypical symptoms and can go unrecognized for years.

Methods

The diagnosis of MPS IVA was confirmed via GALNS enzyme activity testing in leukocytes. Clinical features were collected. Molecular analysis was performed by next generation sequence and Sanger sequencing of the GALNS gene. The pathogenicity of the deep intron variant was verified by mRNA analyses.

Results

Thirteen patients with mild MPS IVA from six families were included. All probands first visit pediatric orthopedists and it took 5.6 years to be diagnosed after the disease onset. The most common symptoms in our series were waddling gait (85%), short neck (69%) and flat feet (62%). Radiologic findings indicated skeletal abnormalities in all patients, especially modification of the vertebral bodies (100%) and acetabular and femoral head dysplasia (100%). Five novel GALNS variants, including c.121-2_121-1insTTTGCTGGCATATGCA, E2 deletion, c.569 A > G, c.898 + 2 T > A, and c.1139 + 2 T > C, were identified. The most common variant, a deep intron variant NM_000512.5: c.121–210 C > T (NM_001323544.2: c.129 C > T, p.G43G), was revealed to result in an 11 bp deletion (c.128_138delGCGATGCTGAG, p.Gly43Aspfs*5) on GALNS mRNA in the GALNS transcript of NM_001323544.2.

Conclusions

This study provides significant insights into the clinical features and molecular characteristics that contribute to the early diagnosis of mild MPS IVA. On the basis of our cohort, orthopedists need to be able to recognize signs and symptoms of mild MPS IVA as well as the molecular and biochemical diagnosis so that an early diagnosis and treatment can be instituted.
Arsenic modifies the effect of folic acid in spina bifida prevention, a large hospital-based case-control study in Bangladesh
Authors: Wei Chih-Fu , Mukherjee Sudipta Kumer , Ekramullah Sheikh Muhammad , Arman D. M. , Islam Md Joynul , Azim Mubinul , Rahman Asifur , Rahman Md Nafaur , Ziauddin Md , Tindula Gwen , Suchanda Hafiza Sultana , Gomberg Diana F. , Weisskopf Marc G. , Liang Liming , Warf Benjamin C. , Christiani David C. , Mazumdar Maitreyi
Published: June 2024

Background

Spina bifida, a developmental malformation of the spinal cord, is associated with high rates of mortality and disability. Although folic acid-based preventive strategies have been successful in reducing rates of spina bifida, some areas continue to be at higher risk because of chemical exposures. Bangladesh has high arsenic exposures through contaminated drinking water and high rates of spina bifida. This study examines the relationships between mother’s arsenic exposure, folic acid, and spina bifida risk in Bangladesh.

Methods

We conducted a hospital-based case-control study at the National Institute of Neurosciences & Hospital (NINS&H) in Dhaka, Bangladesh, between December 2016 and December 2022. Cases were infants under age one year with spina bifida and further classified by a neurosurgeon and imaging. Controls were drawn from children seen at NINS&H and nearby Dhaka Shishu Hospital. Mothers reported folic acid use during pregnancy, and we assessed folate status with serum assays. Arsenic exposure was estimated in drinking water using graphite furnace atomic absorption spectrophotometry (GF-AAS) and in toenails using inductively coupled plasma mass spectrometry (ICP-MS). We used logistic regression to examine the associations between arsenic and spina bifida. We used stratified models to examine the associations between folic acid and spina bifida at different levels of arsenic exposure.

Results

We evaluated data from 294 cases of spina bifida and 163 controls. We did not find a main effect of mother’s arsenic exposure on spina bifida risk. However, in stratified analyses, folic acid use was associated with lower odds of spina bifida (adjusted odds ratio [OR]: 0.50, 95% confidence interval [CI]: 0.25-1.00, p = 0.05) among women with toenail arsenic concentrations below the median value of 0.46 µg/g, and no association was seen among mothers with toenail arsenic concentrations higher than 0.46 µg/g (adjusted OR: 1.09, 95% CI: 0.52–2.29, p = 0.82).

Conclusions

Mother’s arsenic exposure modified the protective association of folic acid with spina bifida. Increased surveillance and additional preventive strategies, such as folic acid fortification and reduction of arsenic, are needed in areas of high arsenic exposure.
Fertility-sparing uterine displacement for pelvic malignancies: surgical options and radiotherapy dosimetry on a human cadaver
Authors: Pavone Matteo , Waeldin Laure , Seeliger Barbara , Bizzarri Nicolò , Mutter Didier , Jarnet Delphine , Forgione Antonello , Georges Noel , Akladios Cherif , Scambia Giovanni , Marescaux Jacques , Lecointre Lise , Querleu Denis
Published: June 2024

Background

Radio(chemo)therapy is often required in pelvic malignancies (cancer of the anus, rectum, cervix). Direct irradiation adversely affects ovarian and endometrial function, compromising the fertility of women. While ovarian transposition is an established method to move the ovaries away from the radiation field, surgical procedures to displace the uterus are investigational. This study demonstrates the surgical options for uterine displacement in relation to the radiation dose received. 

Methods

The uterine displacement techniques were carried out sequentially in a human female cadaver to demonstrate each procedure step by step and assess the uterine positions with dosimetric CT scans in a hybrid operating room. Two treatment plans (anal and rectal cancer) were simulated on each of the four dosimetric scans (1. anatomical position, 2. uterine suspension of the round ligaments to the abdominal wall 3. ventrofixation of the uterine fundus at the umbilical level, 4. uterine transposition). Treatments were planned on Eclipse® System (Varian Medical Systems®,USA) using Volumetric Modulated Arc Therapy. Data about maximum (Dmax) and mean (Dmean) radiation dose received and the volume receiving 14 Gy (V14Gy) were collected.

Results

All procedures were completed without technical complications. In the rectal cancer simulation with delivery of 50 Gy to the tumor, Dmax, Dmean and V14Gy to the uterus were respectively 52,8 Gy, 34,3 Gy and 30,5cc (1), 31,8 Gy, 20,2 Gy and 22.0cc (2), 24,4 Gy, 6,8 Gy and 5,5cc (3), 1,8 Gy, 0,6 Gy and 0,0cc (4). For anal cancer, delivering 64 Gy to the tumor respectively 46,7 Gy, 34,8 Gy and 31,3cc (1), 34,3 Gy, 20,0 Gy and 21,5cc (2), 21,8 Gy, 5,9 Gy and 2,6cc (3), 1,4 Gy, 0,7 Gy and 0,0cc (4).

Conclusions

The feasibility of several uterine displacement procedures was safely demonstrated. Increasing distance to the radiation field requires more complex surgical interventions to minimize radiation exposure. Surgical strategy needs to be tailored to the multidisciplinary treatment plan, and uterine transposition is the most technically complex with the least dose received.
Gasdermin D deficiency aborts myeloid calcium influx to drive granulopoiesis in lupus nephritis
Authors: Shen Jiani , Li Feng , Han Xu , Fu Dongying , Xu Yiping , Zhu Changjian , Liang Zhou , Tang Ziwen , Zheng Ruilin , Hu Xinrong , Lin Ruoni , Pei Qiaoqiao , Nie Jing , Luo Ning , Li Xiaoyan , Chen Wei , Mao Haiping , Zhou Yi , Yu Xueqing
Published: June 2024

Gasdermin D (GSDMD) is emerging as an important player in autoimmune diseases, but its exact role in lupus nephritis (LN) remains controversial. Here, we identified markedly elevated GSDMD in human and mouse LN kidneys, predominantly in CD11b+ myeloid cells. Global or myeloid-conditional deletion of GSDMD was shown to exacerbate systemic autoimmunity and renal injury in lupus mice with both chronic graft-versus-host (cGVH) disease and nephrotoxic serum (NTS) nephritis. Interestingly, RNA sequencing and flow cytometry revealed that myeloid GSDMD deficiency enhanced granulopoiesis at the hematopoietic sites in LN mice, exhibiting remarkable enrichment of neutrophil-related genes, significant increases in total and immature neutrophils as well as granulocyte/macrophage progenitors (GMPs). GSDMD-deficient GMPs and all-trans-retinoic acid (ATRA)-stimulated human promyelocytes NB4 were further demonstrated to possess enhanced clonogenic and differentiation abilities compared with controls. Mechanistically, GSDMD knockdown promoted self-renewal and granulocyte differentiation by restricting calcium influx, contributing to granulopoiesis. Functionally, GSDMD deficiency led to increased pathogenic neutrophil extracellular traps (NETs) in lupus peripheral blood and bone marrow-derived neutrophils. Taken together, our data establish that GSDMD deletion accelerates LN development by promoting granulopoiesis in a calcium influx-regulated manner, unraveling its unrecognized critical role in LN pathogenesis.
The transcriptional landscape of cancer stem-like cell functionality in breast cancer
Authors: Baldasici Oana , Soritau Olga , Roman Andrei , Lisencu Carmen , Visan Simona , Maja Laura , Pop Bogdan , Fetica Bogdan , Cismaru Andrei , Vlase Laurian , Balacescu Loredana , Balacescu Ovidiu , Russom Aman , Tudoran Oana
Published: June 2024

Background

Cancer stem-like cells (CSCs) have been extensively researched as the primary drivers of therapy resistance and tumor relapse in patients with breast cancer. However, due to lack of specific molecular markers, increased phenotypic plasticity and no clear clinicopathological features, the assessment of CSCs presence and functionality in solid tumors is challenging. While several potential markers, such as CD24/CD44, have been proposed, the extent to which they truly represent the stem cell potential of tumors or merely provide static snapshots is still a subject of controversy. Recent studies have highlighted the crucial role of the tumor microenvironment (TME) in influencing the CSC phenotype in breast cancer. The interplay between the tumor and TME induces significant changes in the cancer cell phenotype, leading to the acquisition of CSC characteristics, therapeutic resistance, and metastatic spread. Simultaneously, CSCs actively shape their microenvironment by evading immune surveillance and attracting stromal cells that support tumor progression.

Methods

In this study, we associated in vitro mammosphere formation assays with bulk tumor microarray profiling and deconvolution algorithms to map CSC functionality and the microenvironmental landscape in a large cohort of 125 breast tumors.

Results

We found that the TME score was a significant factor associated with CSC functionality. CSC-rich tumors were characterized by an immune-suppressed TME, while tumors devoid of CSC potential exhibited high immune infiltration and activation of pathways involved in the immune response. Gene expression analysis revealed IFNG, CXCR5, CD40LG, TBX21 and IL2RG to be associated with the CSC phenotype and also displayed prognostic value for patients with breast cancer.

Conclusion

These results suggest that the characterization of CSCs content and functionality in tumors can be used as an attractive strategy to fine-tune treatments and guide clinical decisions to improve patients therapy response.
Next-generation sequencing of primary testicular lymphoma and relapse in the glans penis after prophylactic radiation therapy: a rare case report
Authors: Ishibashi Naoya , Nakanishi Yoko , Maebayashi Toshiya , Miura Katsuhiro , Ohni Sumie , Masuda Shinobu , Amano Yasuo , Okada Masahiro
Published: June 2024

Background

Primary testicular lymphoma (PTL) is relatively rare. The contralateral testis is a common site of PTL relapse; therefore, once complete remission is achieved, radiation therapy (RT) is administered to the contralateral testis to prevent relapse.

Case presentation

A 76-year-old man was diagnosed with PTL and received RT as described above. However, despite achieving and maintaining complete remission, a mass diagnosed as diffuse large B-cell lymphoma by tissue biopsy developed in the glans penis 6.5 years after prophylactic RT. We investigated whether the glans penile lymphoma was PTL relapse or a new malignancy by genomic analysis using next-generation sequencing of DNA extracted from two histopathological specimens.

Conclusions

We found the same variant allele fraction in four somatic genes (MYD88, IL7R, BLNK, and FLT3) at similar frequencies, indicating that the glans penile lymphoma had the same origin as the PTL. To the best of our knowledge, this is the first case report of PTL relapse in the glans penis.
Chrysanthemum morifolium Ramat extract and probiotics combination ameliorates metabolic disorders through regulating gut microbiota and PPARα subcellular localization
Authors: Gao Xinxin , Zhu Zhigang , Bao Yiyang , Li Yifan , Zhu Weize , He Xiaofang , Ge Xinyu , Huang Wenjin , Wang Hao , Wei Wenjing , Du Jun , Chen Liang , Li Houkai , Sheng Lili
Published: June 2024

Background

Chrysanthemum morifolium Ramat, a traditional Chinese medicine, has the effects on liver clearing, vision improving, and anti-inflammation. C. morifolium and probiotics have been individually studied for their beneficial effects on metabolic diseases. However, the underlying molecular mechanisms were not completely elucidated. This study aims to elucidate the potential molecular mechanisms of C. morifolium and probiotics combination (CP) on alleviating nonalcoholic fatty liver disease (NAFLD) and the dysregulation of glucose metabolism in high-fat diet (HFD)-fed mice.

Methods

The therapeutic effect of CP on metabolism was evaluated by liver histology and serum biochemical analysis, as well as glucose tolerance test. The impact of CP on gut microbiota was analyzed by 16S rRNA sequencing and fecal microbiota transplantation. Hepatic transcriptomic analysis was performed with the key genes and proteins validated by RT-qPCR and western blotting. In addition, whole body Pparα knockout (Pparα−/−) mice were used to confirm the CP-mediated pathway.

Results

CP supplementation ameliorated metabolic disorders by reducing body weight and hepatic steatosis, and improving glucose intolerance and insulin resistance in HFD fed mice. CP intervention mitigated the HFD-induced gut microbiota dysbiosis, which contributed at least in part, to the beneficial effect of improving glucose metabolism. In addition, hepatic transcriptomic analysis showed that CP modulated the expression of genes associated with lipid metabolism. CP downregulated the mRNA level of lipid droplet-binding proteins, such as Cidea and Cidec in the liver, leading to more substrates for fatty acid oxidation (FAO). Meanwhile, the expression of CPT1α, the rate-limiting enzyme of FAO, was significantly increased upon CP treatment. Mechanistically, though CP didn’t affect the total PPARα level, it promoted the nuclear localization of PPARα, which contributed to the reduced expression of Cidea and Cidec, and increased expression of CPT1α, leading to activated FAO. Moreover, whole body PPARα deficiency abolished the anti-NAFLD effect of CP, suggesting the importance of PPARα in CP-mediated beneficial effect.

Conclusion

This study revealed the hypoglycemic and hepatoprotective effect of CP by regulating gut microbiota composition and PPARα subcellular localization, highlighting its potential for therapeutic candidate for metabolic disorders.
YY1 mediated DCUN1D5 transcriptional activation promotes triple-negative breast cancer progression by targeting FN1/PI3K/AKT pathway
Authors: Lin Yuxiang , Li Yan , Chen Xiaobin , Jin Xuan , Jiang Meichen , Xiao Han , Chen Lili , Chen Minyan , Zhang Wenzhe , Chen Hanxi , Nie Qian , Guo Rongrong , Guo Wenhui , Fu Fangmeng , Wang Chuan
Published: June 2024

Triple-negative breast cancer (TNBC) is more aggressive and has a higher metastasis rate compared with other subtypes of breast cancer. Due to the lack of drug-targetable receptors, chemotherapy is now the only available systemic treatment for TNBC. However, some patients might still develop drug resistance and have poor prognosis. Therefore, novel molecular biomarkers and new treatment targets are urgently needed for patients with TNBC. To provide molecular insights into TNBC progression, we investigated the function and the underlying mechanism of Defective in cullin neddylation 1 domain containing 5 (DCUN1D5) in the regulation of TNBC. By TCGA dataset and surgical specimens with immunohistochemical (IHC) staining method, DCUN1D5 was identified to be significantly upregulated in TNBC tumor tissues and negatively associated with prognosis. A series of in vitro and in vivo experiments were performed to confirm the oncogenic role of DCUN1D5 in TNBC. Overexpression of FN1 or PI3K/AKT activator IGF-1 could restore the proliferative and invasive ability induced by DCUN1D5 knockdown and DCUN1D5 could act as a novel transcriptional target of transcription factor Yin Yang 1 (YY1). In conclusion, YY1-enhanced DCUN1D5 expression could promote TNBC progression by FN1/PI3K/AKT pathway and DCUN1D5 might be a potential prognostic biomarker and therapeutic target for TNBC treatment.
Effect of 2-hydroxyethylammonium carboxylate protic ionic liquids on the solubility and cytotoxicity of indomethacin
Authors: Akbarzadeh Gondoghdi Parisa , Khorsandi Mohammad , Mokhtarpour Masumeh , Shekaari Hemayat , Hamishehkar Hamed
Published: June 2024

Recently, there is a particular interest to utilize protic ionic liquids (PILs) in drug solubility. This study is exploring the effect of three protic ionic liquids (PILs) based on 2-hydroxyethylammonium carboxylate [2-hydroxyethylammonium acetate (MEAA), 2-hydroxyethylammonium lactate (MEAL), and 2-hydroxyethylammonium propionate (MEAP)] on the solubility of the very poorly soluble drug in water, indomethacin (IMC). The shake flask method was used to measure the experimental solubility of IMC at the different temperatures range (298.15–313.15) K. The results demonstrate significantly enhancment the solubility of IMC in PILs compared to pure water, with an approximate increase of 200 times. The experimental solubility data have been correlated using the empirical models which showed the performance as the order: Modified Apelblat–Jouyban–Acree > Van’t Hoff–Jouyban–Acree > Modified Apelblat equations and also the performance for the Wilson model indicated as the order (absolute relative deviation): 2-hydroxyethylammonium acetate (3.030) > 2-hydroxyethylammonium propionate (3.239) > 2-hydroxyethylammonium lactate (7.665). Then the thermodynamic dissolution properties were obtained by usage of Gibbs and Van’t Hoff equations to investigate the thermodynamic behavior of the IMC in the aqueous solution PILs. Eventually, the cytotoxicity of the co-solvents (PILs) under study was evaluated using a standard MTT assay. The results showed that the cell viability percentage increased in the following order: MEAA < MEAP < MEAL. These findings indicated that these PILs had low to moderate toxicity. It is noteworthy that the functional groups of the anions were not the only determinant factor of the cytotoxicity. Other factors encompassing concentration, exposure time, and cell line characteristics also had significant effects.