bluuebunny/crossref_metadata_2025 huggingface dataset:
Can vitamin B6 alleviate the adverse reactions of quadruple anti-Helicobacter pylori regimen? : randomized controlled trial
Authors: Cui Meng-Yan , Zhang Meng-Jie , Jiang Qiao-Li , Pei Zhong-Mei , Cui Zhen-Yu , Kang Mei , Lu Lun-Gen , Lu Ying-Ying
Published: September 2023

Background

Vitamin B6 is an essential water-soluble vitamin for humans. It is often used to prevent a variety of neuropathies, relieve vomiting, and relieve symptoms such as hand and foot neuritis.

Aim

To evaluate whether vitamin B6 can alleviate the adverse reactions caused by the quadruple anti-Helicobacter pylori treatment regimen containing minocycline and metronidazole.

Methods

In this randomized controlled trial, 280 patients with H. pylori infection were randomly placed into one of two treatment groups—the conventional treatment group and the vitamin B6 supplement treatment group—for 2 weeks. The primary endpoint was the total incidence of adverse reactions up to 2 weeks after treatment initiation. The study was designed according to CONSORT Medicinal Interventions. And it was registered with Chinese Clinical Trial Registry under the number ChiCTR2100053833.

Results

In terms of efficacy, vitamin B6 does not affect the efficacy of conventional regimen. In the vitamin B6 supplement treatment group, the incidence of adverse reactions was 56.92%, which was significantly lower than the 74.62% observed in the conventional treatment group. In addition, the severity of adverse reactions was also significantly reduced. The proportion of moderate to severe central nervous system symptoms decreased from 58.7 to 14.63%. And, the proportion of moderate to severe gastrointestinal reactions decreased from 33.33 to 0%. We speculate that the mechanism of vitamin B6 of reducing adverse reaction may be related to the production of GABA in the brain.

Conclusions

Vitamin B6 can alleviate adverse reactions of the quadruple anti-H. pylori regimen containing minocycline and metronidazole.
Analysis of risk factors of precocious puberty in children
Authors: Dong Yan , Dai Lili , Dong Yang , Wang Na , Zhang Jing , Liu Chao , Li Zhifang , Chu Limin , Chen Sisi
Published: September 2023

Background

The purpose of this study is to explore the related factors of precocious puberty in children.

Methods

1239 children who underwent physical examination in our hospital from January 2020 to December 2022 were analyzed, including 198 precocious children and 1041 normal children. According to the age of 198 precocious children and 1041 normal children, 205 normal children were selected, and the remaining 836 normal children were excluded. They were divided into precocious group and normal group. The general data of the two groups were recorded. Logistic regression was used to analyze the influencing factors of precocious puberty in children.

Results

There were statistically significant differences (P < 0.05) between the two groups in sex, bone age, daily exercise time, E2, FSH, LH, leptin, mother’s menarche time, living environment, consumption of nutritional supplements, consumption of foods containing pigments and preservatives, consumption of high-protein foods, and sleeping time. The multifactor logistic regression analysis shows that the risk factors of children’s precocious puberty included gender (female), bone age (> 10 years old), and daily exercise time (< 0.9 h), E2 (≥ 66.00pmol/L), FSH (≥ 6.00U/L), LH (≥ 3.50U/L), leptin (≥ 8.00 µ G/L), mother’s menarche time (< 12 years old), living environment (chemical industry zone), consumption of nutritional supplements (often), consumption of high-protein food (often), and sleep time (< 10 h).

Conclusion

In conclusion, children’s gender, bone age, exercise habits, E2, FSH, LH, leptin, mother’s menarche time, living environment, eating habits, sleep time and other factors are closely related to precocious puberty in children. Reminding parents to actively prevent related factors in clinical work is helpful to prevent the occurrence of precocious puberty in children.
Association between physicians’ characteristics and their knowledge, attitudes, and practices regarding advance care planning: a cross-sectional study
Authors: Sakamoto Ayaka , Inokuchi Ryota , Iwagami Masao , Hanari Kyoko , Tamiya Nanako
Published: September 2023

Background

Despite physicians’ vital role in advance care planning, a limited number of physicians practice it. This study assessed factors associated with physicians’ knowledge, attitudes, and practices regarding advance care planning.

Methods

This cross-sectional study used data from an anonymous survey conducted by the Japanese Ministry of Health, Labour and Welfare.

Questionnaires were mailed to 4500 physicians in November and December 2022. Data from 1260 respondents were analyzed.

Results

Of the respondents, 46.4%, 77.0%, and 82.0% reported good knowledge of advance care planning, agreed with promoting it, and with its provision by medical/care staff, respectively. Male physicians were significantly less likely to support advance care planning (odds ratio: 0.54, 95% confidence interval: 0.35–0.84) or agree to its provision by medical/care staff (odds ratio: 0.47, 95% confidence interval: 0.29–0.78) but significantly more likely to practice it (odds ratio: 1.58, 95% confidence interval: 1.05–2.36). Physicians specialized in surgery or internal/general/palliative medicine were more knowledgeable about advance care planning and more likely to practice it. Physicians working in clinics were significantly less knowledgeable (odds ratio: 0.33, 95% confidence interval: 0.25–0.44) about advance care planning and less likely to support it (odds ratio: 0.37, 95% confidence interval: 0.27–0.50), agree with its provision by medical/care staff (odds ratio: 0.54, 95% confidence interval: 0.39–0.75), or to practice it (odds ratio: 0.16, 95% confidence interval: 0.12–0.22).

Conclusions

Physicians working in clinics had less knowledge of advance care planning, less supportive attitudes, and less likely to practice it. Knowledge, attitudes and practice also varied by gender and specialty. Interventions should target physicians working in clinics.
Hesperetin attenuates the expression of markers of adipose tissue fibrosis in pre-adipocytes
Authors: Taheri Alemeh , Mobaser Samira Ezzati , Golpour Pegah , Nourbakhsh Mona , Tavakoli-Yaraki Masoumeh , Yarahmadi Sahar , Nourbakhsh Mitra
Published: September 2023

Background

Excessive extracellular matrix (ECM) deposition in adipose tissue is a hallmark of fibrosis, leading to disrupted adipose tissue homeostasis and metabolic dysfunction. Hesperetin, a flavonoid compound, has shown promising anti-inflammatory, anti-obesity and anti-diabetic properties. Therefore, we investigated the anti-fibrotic effects of hesperetin, through targeting ECM components and matrix metalloproteinase enzymes.

Methods

3T3-L1 cells were cultured in DMEM, containing 10% FBS and 1% penicillin/streptomycin. Cells were treated with a range of hesperetin concentrations, and the cell viability was determined using MTT assay. Subsequently, the expression of genes encoding collagen VI, osteopontin, matrix metalloproteinase-2 (Mmp-2) and Mmp-9 was analyzed using specific primers and real-time PCR technique. To evaluate protein levels of collagen VI and osteopontin, Western blotting was performed.

Results

Hesperetin affected the viability of 3T3-L1 adipocytes with IC50 of 447.4 µM, 339.2 µM and 258.8 µM (24 h, 48 and 72 h, respectively). Hesperetin significantly reduced the gene and protein expression of both collagen VI and osteopontin in 3T3-L1 pre-adipocytes, in a time- and dose-dependent manner. Hesperetin was also able to cause a remarkable decline in gene expression of Mmp2 and Mmp9.

Conclusion

Hesperetin could potently reduce the production of markers of adipose tissue fibrosis and might be considered a potential anti-fibrotic compound in obesity. Thus, hesperetin has the potency to be used for the treatment of obesity-associated fibrosis.
Block-based teaching method based on cybernetics: a trial with 115 Chinese undergraduate medical students
Authors: Liu Zhi-Ping , Liu Si-Han , Dai Xin , Chen Jie , Guo Qing-Feng , Zhang Da-Xin
Published: September 2023

Background

Class attendance is important for academic performance. Personal interactions between teachers and students are difficult in large classes; the number of medical undergraduate students in China ranges from dozens to over 100. It is important for teachers to control the teaching process to improve student attendance and participation.

Methods

Two classes of fourth-year undergraduate medical students, with each class comprising 115 students, participated in the study. One class, the trial group, was taught by the block-based teaching method based on cybernetics. This study was conducted with three of the courses in the Introduction to Oncology subject, and the trial group’s courses included several blocks. Each block had a test paper that the students responded to immediately in class using the Internet. The teacher obtained feedback from the students when the rate of correct responses to block-test questions was less than 90%. The teacher adjusted the teaching in the following blocks according to the feedback information. The other class, the control group, was taught using the traditional lecture-based teaching method.

Results

The average attendance in the trial group was 104/115 (90.43%), and that in the control group was 83/115 (72.17%) (p = 0.0003). The teacher adjusted the teaching three times in the radiotherapy course owing to the complex ideas. After feedback, information on chemotherapy for the upper body was adjusted once, as was that on chemotherapy for the lower body, owing to students’ attitudes. The average total score of the trial group was 86.06 ± 17.46 and that of the control group was 80.38 ± 6.97 (p = 0.041). Questionnaire I showed that the trial group students’ attendance and participation were better than in the control group. Questionnaire II showed that the block-based teaching method based on cybernetics was approved by the students.

Conclusions

The block-based teaching method based on cybernetics used in medical classes with large numbers of Chinese undergraduate students had positive effects.
Body landmarks and genetic algorithm-based approach for non-contact detection of head forward posture among Chinese adolescents: revitalizing machine learning in medicine
Authors: Yang Guang , He Shichun , Meng Deyu , Wei Meiqi , Cao Jianwei , Guo Hongzhi , Ren He , Wang Ziheng
Published: September 2023

Addressing the current complexities, costs, and adherence issues in the detection of forward head posture (FHP), our study conducted an exhaustive epidemiologic investigation, incorporating a comprehensive posture screening process for each participant in China. This research introduces an avant-garde, machine learning-based non-contact method for the accurate discernment of FHP. Our approach elevates detection accuracy by leveraging body landmarks identified from human images, followed by the application of a genetic algorithm for precise feature identification and posture estimation. Observational data corroborates the superior efficacy of the Extra Tree Classifier technique in FHP detection, attaining an accuracy of 82.4%, a specificity of 85.5%, and a positive predictive value of 90.2%. Our model affords a rapid, effective solution for FHP identification, spotlighting the transformative potential of the convergence of feature point recognition and genetic algorithms in non-contact posture detection. The expansive potential and paramount importance of these applications in this niche field are therefore underscored.
Barriers and facilitators to the participation and engagement of primary care in shared-care arrangements with community mental health services for preventive care of people with serious mental illness: a scoping review
Authors: Parker Sharon M. , Paine Katrina , Spooner Catherine , Harris Mark
Published: September 2023

Background

People with serious mental illness die about 20 years earlier than the general population from preventable diseases. Shared-care arrangements between general practitioners and mental health services can improve consumers’ access to preventive care, but implementing shared care is challenging. This scoping review sought to describe current evidence on the barriers and facilitators to the participation and engagement of primary care (specifically general practitioners) in shared-care arrangements with community mental health services for preventive health care of this population.

Methods

We searched Medline, Embase, CINAHL, Scopus, APA PsychINFO and EBM Reviews from 2010 to 2022. Data was extracted against a Microsoft Excel template developed for the review. Data was synthesised through tabulation and narrative methods.

Results

We identified 295 records. After eligibility screening and full-text review, seven studies were included. Facilitators of engagement included a good fit with organisation and practice and opportunities to increase collaboration, specific roles to promote communication and coordination and help patients to navigate appointments, multidisciplinary teams and teamwork, and access to shared medical/health records. Barriers included a lack of willingness and motivation on the part of providers and low levels of confidence with tasks, lack of physical structures to produce capacity, poor alignment of funding/incentives, inability to share patient information and challenges engaging people with severe mental illness in the service and with their care.

Conclusion

Our results were consistent with other research on shared care and suggests that the broader literature is likely to be applicable to the context of general practitioner/mental health services shared care. Specific challenges relating to this cohort present difficulties for recruitment and retention in shared care programs. Sharing “goals and knowledge, mutual respect” and engaging in “frequent, timely, accurate, problem-solving communication”, supported by structures such as shared information systems are likely to engage primary care in shared care arrangements more than the traditional focus on incentives, education, and guidelines.
Unlocking the potential of microRNAs: machine learning identifies key biomarkers for myocardial infarction diagnosis
Authors: Samadishadlou Mehrdad , Rahbarghazi Reza , Piryaei Zeynab , Esmaeili Mahdad , Avcı Çığır Biray , Bani Farhad , Kavousi Kaveh
Published: September 2023

Background

MicroRNAs (miRNAs) play a crucial role in regulating adaptive and maladaptive responses in cardiovascular diseases, making them attractive targets for potential biomarkers. However, their potential as novel biomarkers for diagnosing cardiovascular diseases requires systematic evaluation.

Methods

In this study, we aimed to identify a key set of miRNA biomarkers using integrated bioinformatics and machine learning analysis. We combined and analyzed three gene expression datasets from the Gene Expression Omnibus (GEO) database, which contains peripheral blood mononuclear cell (PBMC) samples from individuals with myocardial infarction (MI), stable coronary artery disease (CAD), and healthy individuals. Additionally, we selected a set of miRNAs based on their area under the receiver operating characteristic curve (AUC-ROC) for separating the CAD and MI samples. We designed a two-layer architecture for sample classification, in which the first layer isolates healthy samples from unhealthy samples, and the second layer classifies stable CAD and MI samples. We trained different machine learning models using both biomarker sets and evaluated their performance on a test set.

Results

We identified hsa-miR-21-3p, hsa-miR-186-5p, and hsa-miR-32-3p as the differentially expressed miRNAs, and a set including hsa-miR-186-5p, hsa-miR-21-3p, hsa-miR-197-5p, hsa-miR-29a-5p, and hsa-miR-296-5p as the optimum set of miRNAs selected by their AUC-ROC. Both biomarker sets could distinguish healthy from not-healthy samples with complete accuracy. The best performance for the classification of CAD and MI was achieved with an SVM model trained using the biomarker set selected by AUC-ROC, with an AUC-ROC of 0.96 and an accuracy of 0.94 on the test data.

Conclusions

Our study demonstrated that miRNA signatures derived from PBMCs could serve as valuable novel biomarkers for cardiovascular diseases.
Effect of dietary intervention on the prevalence of asymptomatic malaria among 6–18-month-old children in rural Malawi
Authors: Sady Hany , Chaima David , Hallamaa Lotta , Kortekangas Emma , Ashorn Ulla , Banda Jomo , Mangani Charles , Maleta Kenneth , Ashorn Per , Fan Yue-Mei
Published: September 2023

Background

The complex interaction between malaria and undernutrition leads to increased mortality and morbidity rate among young children in malaria-endemic regions. Results from previous interventions suggest that improving nutritional status of young children may reduce the burden of malaria. This study tested a hypothesis that provision of lipid-based nutrient supplements (LNS) or corn-soy blend (CSB) supplementation to 6–18-month-old children in Malawi would reduce the prevalence of asymptomatic malaria among them.

Methods

A total of 840 6-month-old children were enrolled in a randomized trial. The participants received 12-month supplementation with three different daily dietary supplementations: CSB, soy-LNS, or milk-LNS, and one control group without supplementation. The prevalence rate of asymptomatic Plasmodium falciparum was determined by real-time PCR from the participant’s dried blood spots (DBS) collected at the baseline and every 3 months. The global null hypothesis was tested using modified Poisson regression to estimate the prevalence ratio (PR) between the control group and three intervention groups at all ages combined. All the models were adjusted for malaria at baseline, season of DBS sample collection, site of enrolment, and household asset Z-score.

Results

All children combined, the prevalence of P. falciparum was 14.1% at enrollment, 8.7% at 9 months, 11.2% at 12 months, 13.0% at 15 months and 22.4% at 18 months of age. Among all samples that were taken after enrolment, the prevalence was 12.1% in control group, 12.2% in milk-LNS, 14.0% in soy-LNS, and 17.2% in CSB group. Compared to children in the control group the prevalence ratio of positive malaria tests was 1.19 (95% CI 0.81–1.74; P = 0.372) in the milk-LNS group, 1.32 (95% CI 0.88–1.96; P = 0.177) in the soy-LNS group and 1.72 (95% CI 1.19–2.49; P = 0.004) in the CSB group.

Conclusion

The study findings do not support a hypothesis that LNS or CSB supplementation would reduce the prevalence of asymptomatic malaria among Malawian children. In contrast, there was a signal of a possible increase in malaria prevalence among children supplemented with CSB.
Current evidence for designing self-management support for underserved populations: an integrative review using the example of diabetes
Authors: Litchfield Ian , Barrett Tim , Hamilton-Shield Julian , Moore Theresa , Narendran Parth , Redwood Sabi , Searle Aidan , Uday Suma , Wheeler Jess , Greenfield Sheila
Published: September 2023

Aims

With numerous and continuing attempts at adapting diabetes self-management support programmes to better account for underserved populations, its important that the lessons being learned are understood and shared. The work we present here reviews the latest evidence and best practice in designing and embedding culturally and socially sensitive, self-management support programmes.

Methods

We explored the literature with regard to four key design considerations of diabetes self-management support programmes: Composition - the design and content of written materials and digital tools and interfaces; Structure - the combination of individual and group sessions, their frequency, and the overall duration of programmes; Facilitators - the combination of individuals used to deliver the programme; and Context – the influence and mitigation of a range of individual, socio-cultural, and environmental factors.

Results

We found useful and recent examples of design innovation within a variety of countries and models of health care delivery including Brazil, Mexico, Netherlands, Spain, United Kingdom, and United States of America. Within Composition we confirmed the importance of retaining best practice in creating readily understood written information and intuitive digital interfaces; Structure the need to offer group, individual, and remote learning options in programmes of flexible duration and frequency; Facilitators where the benefits of using culturally concordant peers and community-based providers were described; and finally in Context the need to integrate self-management support programmes within existing health systems, and tailor their various constituent elements according to the language, resources, and beliefs of individuals and their communities.

Conclusions

A number of design principles across the four design considerations were identified that together offer a promising means of creating the next generation of self-management support programme more readily accessible for underserved communities. Ultimately, we recommend that the precise configuration should be co-produced by all relevant service and patient stakeholders and its delivery embedded in local health systems.
Tetracyclines resistance in Mycoplasma and Ureaplasma urogenital isolates derived from human: a systematic review and meta-analysis
Authors: Wen Xiaoyan , Nobakht Mojgan Sarabi , Yang Yue , Kouhsari Ebrahim , Hajilari Sara , Shakourzadeh Matin Zafar , Azizian Khalil
Published: September 2023

Background

Urogenital Mycoplasma infections are considered an important public health problem, owing to the presence of antibiotic resistance or decreased susceptibility, the treatment options are limited.

Objective

Therefore, this meta-analysis aimed to estimate resistance rates of genital Mycoplasmas to tetracyclines (tetracycline, doxycycline, and minocycline).

Methods

We searched the relevant published studies in PubMed, Scopus, and Embase until 3, March 2022. All statistical analyses were carried out using the statistical package R.

Results

The 26 studies included in the analysis were performed in 15 countries. In the metadata, the proportions of tetracycline, doxycycline, and minocycline resistance in Mycoplasma and Ureaplasma urogenital isolates were reported 14.2% (95% CI 8.2–23.2%), 5% (95% CI 3–8.1%), and 11.9% (95% CI 6.3–21.5%), respectively. According to the meta-regression, the tetracycline and minocycline resistance rate decreased over time. Although, the doxycycline resistance rate increased over time. There was a statistically significant difference in the tetracyclines resistance rates between different continents/countries (P < 0.05).

Conclusion

The prevalence rate and antibiotic susceptibility profiles vary geographically. Therefore, rigorous or improved antimicrobial stewardship, contact tracing, and enhanced intensive surveillance systems are necessitated for preventing the emergence and further spreading of tetracyclines resistance in genital Mycoplasmas.
Bivalirudin for cardiopulmonary bypass in a patient with heparin allergy
Authors: Boysan Emre , Circi Renda , Beyazal Osman Fehmi , Şener Erol
Published: September 2023

Background

Hypersensitivity reactions to heparin are uncommon conditions but pose a serious clinical problem for patients requiring cardiopulmonary bypass. Bivalirudin is a reversible direct thrombin inhibitor that can be used instead of heparin.

Case Report

A 49-year-old male patient was admitted to our hospital for coronary artery bypass graft operation with mitral insufficiency and tricuspid valve insufficiency. Heparin allergy was confirmed by skin biopsy and skin tests. Due to this allergy, we used bivalirudin (Bivacard VEM drug, Turkey) during the surgery. A loading dose of 1.0 mg/kg (100 mg) bivalirudin was administered through the central line and a continuous infusion of 2.5 mg/kg/h of the anticoagulant was initiated following the approved protocol. Serial ACTs were obtained at 15-minute intervals during the procedure and the measurements were 330s, 320s, 350s, 360s, and 340s consecutively. Additional boluses of 0.5 mg/kg (50 mg) were administered for each measurement. Left anterior descending, obtuse marginal arteries and the right coronary artery were grafted with the left internal mammary and saphenous veins. Also, mitral valve replacement with St Jude mechanical heart valve and tricuspid ring annuloplasty was performed with Medtronic Duran ring. After the surgery, the patient had an uneventful period in the postoperative intensive care unit with a total of 600ml and 300ml chest tube drainage for two days and was discharged on the 7th day.

Conclusion

Alternative anticoagulation strategies are needed for cardiopulmonary bypass in patients unable to use heparin. Bivalirudin may be recommended as a viable alternative anticoagulant in patients with heparin allergy during cardiopulmonary bypass. However, each patient should be evaluated individually and it should not be forgotten that more than recommended doses may be needed.
Data saves lives: optimising routinely collected clinical data for rare disease research
Authors: Solebo Ameenat Lola , Hysi Pirro , Horvat-Gitsels Lisanne Andra , Rahi Jugnoo Sangeeta
Published: September 2023

Necessity driven organisational change in the post-pandemic landscape has seen health care providers adopting innovations to manage and process health data. These include the use of ‘real-world’ datasets of routinely collected clinical information, enabling data-driven delivery. Rare disease risks being ‘left-behind’ unless our clinical and research communities engage with the challenges and opportunities afforded by the burgeoning field of health data informatics. We address the challenges to the meaningful use and reuse of rare disease data, and, through a series of recommendations around workforce education, harmonisation of taxonomy, and ensuring an inclusive health data environment, we highlight the role that those who manage rare disease must play in addressing them.
Impact of chemotherapeutic agents on liver microenvironment: oxaliplatin create a pro-metastatic landscape
Authors: Ma Yuanyuan , Guo Chang , Wang Xijun , Wei Xundong , Ma Jie
Published: September 2023

Background

Chemotherapeutic agents are used to control tumor proliferation. However, their influence in the pre-metastatic niche of target organs has not been well studied. Oxaliplatin (OXA) is a drug applied in standard treatments of colorectal cancer (CRC), while the direct effect of which on the pre-metastatic microenvironment of the liver remains unclear.

Methods

Models of liver metastases were established with luciferase expressing CT26 cells in BALB/c and BALB/c-nude mice. Single-cell RNA Sequencing was performed to examine the immune microenvironment in the liver elicited by OXA. Immunofluorescence and flowcytometry were utilized to confirm the changes in the number of immune cells. LDH, CellTrace CFSE Cell Proliferation and apoptosis assays were conducted to explore the impact of OXA on T cells ex vivo. The correlation between chemotherapy-related lymphopenia and metastases was assessed by meta-analysis.

Results

Herein we discovered that administration of OXA prior to the occurrence of liver metastasis actually accelerated tumor development and colonization in the liver. Single-cell RNA sequencing revealed that the landscape of the liver immune microenvironment had been changed to immunosuppressive phenotype. Macrophages after the treatment of OXA exhibited a high ability to inhibit the activation of T cells. Further investigation revealed a significant decrease in the number of T cells in the liver, particularly CD8+ T cells with reduced capacity of proliferation, activation, and killing. When mice were treated with T cell supplementation, the OXA-induced metastasis was notably abolished, indicating that the OXA-primed liver microenvironment could be reversed by the infusion of T cells. Consistent with our findings in mice, a meta-analysis was performed to verify that chemotherapy-related lymphopenia was associated with an inferior prognosis related with high incidence of metastasis, suggesting the pivotal role of chemotherapy in pre-metastatic niche formation. Furthermore, a notable reduction in the count of both macrophages and T cells was observed in the liver of colorectal cancer (CRC) patient undergoing OXA-based chemotherapy.

Conclusions

Our findings proposed that immunosuppressive microenvironment in liver induced by OXA enhanced liver metastasis of colorectal cancer, which highlighted a new consideration to balance the pro metastases and anti-cancer possibility of OXA treatment.
PhaseDancer: a novel targeted assembler of segmental duplications unravels the complexity of the human chromosome 2 fusion going from 48 to 46 chromosomes in hominin evolution
Authors: Poszewiecka Barbara , Gogolewski Krzysztof , Karolak Justyna A. , Stankiewicz Paweł , Gambin Anna
Published: September 2023

Resolving complex genomic regions rich in segmental duplications (SDs) is challenging due to the high error rate of long-read sequencing. Here, we describe a targeted approach with a novel genome assembler PhaseDancer that extends SD-rich regions of interest iteratively. We validate its robustness and efficiency using a golden-standard set of human BAC clones and in silico-generated SDs with predefined evolutionary scenarios. PhaseDancer enables extension of the incomplete complex SD-rich subtelomeric regions of Great Ape chromosomes orthologous to the human chromosome 2 (HSA2) fusion site, informing a model of HSA2 formation and unravelling the evolution of human and Great Ape genomes.
Precise management system for chronic intractable pain patients implanted with spinal cord stimulation based on a remote programming platform: study protocol for a randomized controlled trial (PreMaSy study)
Authors: Cheng Yuanchen , Xie Duo , Han Yan , Guo Siying , Sun Zhenxing , Jing Linkai , Man Weitao , Liu Dongkang , Yang Kaiyuan , Lei Dan , Meng Zhe , Zhang Huifang , Wang Guoqin , Wu Weiwei , Wang Guihuai , Lu Yang
Published: September 2023

Background

Spinal cord stimulation (SCS) is a surgical technique used in patients with chronic intractable pain, and its effectiveness and safety have been validated by multiple studies. However, to maintain an optimal and steady long-term effect is still challenging. Here, we report a new management paradigm integrating smartphone application and remote programming. Chronic pain patients with SCS implants can monitor their pain status on the phone and change stimulation parameters accordingly. The PreMaSy study is a randomized controlled trial to evaluate the clinical effectiveness and safety of this precise management system.

Methods

Patients with chronic intractable pain will be screened for eligibility, and 82 participants are anticipated to be enrolled in this trial. After the electrode implantation, the stimulation effectiveness will be tested. Participants with a reduction of more than 50% in the visual analog scale (VAS) will receive implantation of an implantable pulse generator and randomized (1:1) into the experimental group or control group. All participants will be asked to take online follow-ups and complete assessments using a smartphone application. Daily pain characteristic assessments and monthly quality of life questionnaires are integrated into the App, and participants will be required to complete these assessments. The daily VAS for pain intensity will be monitored and a threshold will be set based on baseline VAS score. The interventional appointment will be scheduled once the threshold is reached. The primary outcome is the health condition and quality of life assessed by the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L). Utility values of EQ-5D-5L will be assessed at baseline and 1, 3, and 6 months post-operative.

Discussion

The PreMaSy study aims to evaluate the effectiveness and safety of a novel App-based, patient-centered, self-assessment management system for chronic intractable pain. A randomized controlled trial is designed to test the non-inferiority of this precise management system compared to the monthly online follow-ups. It is also expected to yield valuable experiences regarding precision medicine.

Trial registration

ClinicalTrials.gov NCT05761392. Registered on March 07, 2023.
Dietary approach to stop hypertension and healthy eating index 2015, modify the association between FTO polymorphisms and obesity phenotypes
Authors: Hosseini-Esfahani Firoozeh , Rezaei Mahshid , Koochakpoor Glareh , Daneshpour Maryam S. , Mirmiran Parvin , Azizi Fereidoun
Published: September 2023

This study aimed to investigate the interaction of the healthy eating index (HEI) and the dietary approach to stop hypertension (DASH) diet scores with FTO polymorphisms in relation to change in obesity traits. A total of 4480 subjects aged ≥ 18 years were selected from participants of the Tehran lipid and glucose study and followed-up 3 years. Selected polymorphisms (rs1421085, rs1121980, rs8050136) were genotyped and genetic risk score (GRS) was computed. HEI and DASH scores were computed based on dietary data. Changes in body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and visceral adiposity index (VAI) were measured. Higher adherence to both DASH and HEI scores were increased with higher ages. Individuals with high GRS had a lower change in BMI when they had higher adherence to HEI, compared to subjects with lower HEI score (P trend = 0.01). Change in WC in participants in the fourth quartile of HEI score in minor allele carriers of FTO variants was lower compared to the first quartile; conversely, higher adherence to the DASH score by this genotypic group was related to increase in WC. No significant interaction was seen between FTO polymorphisms and both diet scores regarding changes in any of obesity traits. In conclusion, in individuals with high GRS higher adherence to HEI score was associated with lower change in BMI and WC, while higher adherence to DASH diet was associated with higher change in WC, compared to individuals with lower adherence to both scores.
Detection of virulence genes among Staphylococcus saprophyticus isolated from women with urinary tract infections: first report from Iran
Authors: Rafiee Maryam , Ghaemi Ezzat Allah
Published: September 2023

Objective

The purpose of the present study was to investigate the biofilm production, and the presence of virulence genes and biochemical characteristics among theS. saprophyticusclinical isolates. A total of 35 clinical isolates ofS. saprophyticuswere collected from patients referred to several hospitals. By the crystal violet staining method, the capability of biofilm formation was performed. The genes associated with surface ofS. saprophyticuswere investigated by the PCR-sequencing techniques. Hemagglutination and lipase activity assays were also performed.

Results

The results of crystal violet staining assay showed that 32 isolates (91%) form biofilm. Moreover, seven (20%), 13 (37%), and 12(34%) isolates were categorized as weak, moderate, and strong biofilm producers, respectively. virulence genes including UafA, Aas and Ssp had an overall prevalence of 88%, 91% and 80%, respectively. None of the isolates exhibited lipolytic activities. Regarding hemagglutination properties, only 11 (31%) isolates demonstrated hemagglutination of sheep erythrocytes. The results of this study indicate a high prevalence of UafA and Aas genes that can enhance the pathogenicity ofS. saprophyticus, and Identification and better understanding of the functions of these genes can be used for therapeutic purposes. Maybe in the future we will be switch to anti-adhesion therapy because of drug resistance.
Retrospective digital study of mandibular flexure in patients with long-span fixed restorations supported by natural teeth
Authors: El Charkawi Hussein , Nassar Hossam I. , Abdelaziz Medhat Sameh
Published: September 2023

Purpose

This retrospective study aims to evaluate the mandibular flexure on a long-span rigid fixed prosthesis supported by natural teeth.

Materials and methods

Nine patients (five males and four females) were included in this study who had long-span rigid mandibular fixed prostheses for long-term (10–15 years) that have led to radiographic changes around the supporting teeth. The mandibular flexure was measured digitally after adhering reference markers to the prostheses. Intraoral scans were obtained at the minimum and maximum mouth openings before and after splitting the preexisting prostheses. The distances between the markers were measured, and mandibular flexure was calculated.

Results

This study showed a significant deviation (narrowing) of the mandible before and after splitting the rigid fixed prostheses (P value < 0.05).

Conclusion

Digital analysis of the data collected from the patients in this retrospective study indicated that deviations occur during mandibular flexure.

Clinical relevance

Splitting the full arch prosthesis could prevent the negative consequences of mandibular flexure on restorations.

Trial registration The study was registered on clinicaltrials.gov with registration number NCT05617274 (15/11/2022)
Low levels of circulating methylated IRX3 are related to worse outcome after transcatheter aortic valve implantation in patients with severe aortic stenosis
Authors: Kanwischer Leon , Xu Xingbo , Saifuddin Afifa Binta , Maamari Sabine , Tan Xiaoying , Alnour Fouzi , Tampe Björn , Meyer Thomas , Zeisberg Michael , Hasenfuss Gerd , Puls Miriam , Zeisberg Elisabeth M.
Published: September 2023

Background

Aortic stenosis (AS) is one of the most common cardiac diseases and major cause of morbidity and mortality in the elderly. Transcatheter aortic valve implantation (TAVI) is performed in such patients with symptomatic severe AS and reduces mortality for the majority of these patients. However, a significant percentage dies within the first two years after TAVI, such that there is an interest to identify parameters, which predict outcome and could guide pre-TAVI patient selection. High levels of cardiac fibrosis have been identified as such independent predictor of cardiovascular mortality after TAVI. Promoter hypermethylation commonly leads to gene downregulation, and the Iroquois homeobox 3 (IRX3) gene was identified in a genome-wide transcriptome and methylome to be hypermethylated and downregulated in AS patients. In a well-described cohort of 100 TAVI patients in which cardiac fibrosis levels were quantified histologically in cardiac biopsies, and which had a follow-up of up to two years, we investigated if circulating methylated DNA of IRX3 in the peripheral blood is associated with cardiac fibrosis and/or mortality in AS patients undergoing TAVI and thus could serve as a biomarker to add information on outcome after TAVI.

Results

Patients with high levels of methylation in circulating IRX3 show a significantly increased survival as compared to patients with low levels of IRX3 methylation indicating that high peripheral IRX3 methylation is associated with an improved outcome. In the multivariable setting, peripheral IRX3 methylation acts as an independent predictor of all-cause mortality. While there is no significant correlation of levels of IRX3 methylation with cardiac death, there is a significant but very weak inverse correlation between circulating IRX3 promoter methylation level and the amount of cardiac fibrosis. Higher levels of peripheral IRX3 methylation further correlated with decreased cardiac IRX3 expression and vice versa.

Conclusions

High levels of IRX3 methylation in the blood of AS patients at the time of TAVI are associated with better overall survival after TAVI and at least partially reflect myocardial IRX3 expression. Circulating methylated IRX3 might aid as a potential biomarker to help guide both pre-TAVI patient selection and post-TAVI monitoring.

Graphical abstract
Unlocking the potential of targeting histone-modifying enzymes for treating IBD and CRC
Authors: Liang Bing , Wang Yanhong , Xu Jiazhen , Shao Yingchun , Xing Dongming
Published: September 2023

Dysregulation of histone modifications has been implicated in the pathogenesis of both inflammatory bowel disease (IBD) and colorectal cancer (CRC). These diseases are characterized by chronic inflammation, and alterations in histone modifications have been linked to their development and progression. Furthermore, the gut microbiota plays a crucial role in regulating immune responses and maintaining gut homeostasis, and it has been shown to exert effects on histone modifications and gene expression in host cells. Recent advances in our understanding of the roles of histone-modifying enzymes and their associated chromatin modifications in IBD and CRC have provided new insights into potential therapeutic interventions. In particular, inhibitors of histone-modifying enzymes have been explored in clinical trials as a possible therapeutic approach for these diseases. This review aims to explore these potential therapeutic interventions and analyze previous and ongoing clinical trials that examined the use of histone-modifying enzyme inhibitors for the treatment of IBD and CRC. This paper will contribute to the current body of knowledge by exploring the latest advances in the field and discussing the limitations of existing approaches. By providing a comprehensive analysis of the potential benefits of targeting histone-modifying enzymes for the treatment of IBD and CRC, this review will help to inform future research in this area and highlight the significance of understanding the functions of histone-modifying enzymes and their associated chromatin modifications in gastrointestinal disorders for the development of potential therapeutic interventions.
Degradation of methylation signals in cryopreserved DNA
Authors: Lee Ning Yuan , Hum Melissa , Tan Guek Peng , Seah Ai Choo , Kin Patricia T. , Tan Ngiap Chuan , Law Hai-Yang , Lee Ann S. G.
Published: September 2023

Background

Blood-based DNA methylation has shown great promise as a biomarker in a wide variety of diseases. Studies of DNA methylation in blood often utilize samples which have been cryopreserved for years or even decades. Therefore, changes in DNA methylation associated with long-term cryopreservation can introduce biases or otherwise mislead methylation analyses of cryopreserved DNA. However, previous studies have presented conflicting results with studies reporting hypomethylation, no effect, or even hypermethylation of DNA following long-term cryopreservation. These studies may have been limited by insufficient sample sizes, or by their profiling of methylation only on an aggregate global scale, or profiling of only a few CpGs.

Results

We analyzed two large prospective cohorts: a discovery (n = 126) and a validation (n = 136) cohort, where DNA was cryopreserved for up to four years. In both cohorts there was no detectable change in mean global methylation across increasing storage durations as DNA. However, when analysis was performed on the level of individual CpG methylation both cohorts exhibited a greater number of hypomethylated than hypermethylated CpGs at q-value < 0.05 (4049 hypomethylated but only 50 hypermethylated CpGs in discovery, and 63 hypomethylated but only 6 hypermethylated CpGs in validation). The results were the same even after controlling for age, storage duration as buffy coat prior to DNA extraction, and estimated cell type composition. Furthermore, we find that in both cohorts, CpGs have a greater likelihood to be hypomethylated the closer they are to a CpG island; except for CpGs at the CpG islands themselves which are less likely to be hypomethylated.

Conclusion

Cryopreservation of DNA after a few years results in a detectable bias toward hypomethylation at the level of individual CpG methylation, though when analyzed in aggregate there is no detectable change in mean global methylation. Studies profiling methylation in cryopreserved DNA should be mindful of this hypomethylation bias, and more attention should be directed at developing more stable methods of DNA cryopreservation for biomedical research or clinical use.
Fc-engineered monoclonal antibodies to reduce off-target liver uptake
Authors: Mangeat Tristan , Gracia Matthieu , Pichard Alexandre , Poty Sophie , Martineau Pierre , Robert Bruno , Deshayes Emmanuel
Published: September 2023

Background

Radiolabeled-antibodies usually display non-specific liver accumulation that may impair image analysis and antibody biodistribution. Here, we investigated whether Fc silencing influenced antibody biodistribution. We compared recombinant 89Zr-labeled antibodies (human IgG1 against different targets) with wild-type Fc and with mutated Fc (LALAPG triple mutation to prevent binding to Fc gamma receptors; FcγR). After antibody injection in mice harboring xenografts of different tumor cell lines or of immortalized human myoblasts, we analyzed antibody biodistribution by PET-CT and conventional biodistribution analysis.

Results

Accumulation in liver was strongly reduced and tumor-specific targeting was increased for the antibodies with mutated Fc compared with wild-type Fc.

Conclusion

Antibodies with reduced binding to FcγR display lower liver accumulation and better tumor-to-liver ratios. These findings need to be taken into account to improve antibody-based theragnostic approaches.
Exogenous nitrogen input skews estimates of microbial nitrogen use efficiency by ecoenzymatic stoichiometry
Authors: Sun Lifei , Moorhead Daryl L. , Cui Yongxing , Wanek Wolfgang , Li Shuailin , Wang Chao
Published: September 2023

Background

Ecoenzymatic stoichiometry models (EEST) are often used to evaluate microbial nutrient use efficiency, but the validity of these models under exogenous nitrogen (N) input has never been clarified. Here, we investigated the effects of long-term N addition (as urea) on microbial N use efficiency (NUE), compared EEST and 18O-labeling methods for determining NUE, and evaluated EEST’s theoretical assumption that the ratios of standard ecoenzymatic activities balance resource availability with microbial demand.

Results

We found that NUE estimated by EEST ranged from 0.94 to 0.98. In contrast, estimates of NUE by the 18O-labeling method ranged from 0.07 to 0.30. The large differences in NUE values estimated by the two methods may be because the sum of β-N-acetylglucosaminidase and leucine aminopeptidase activities in the EEST model was not limited to microbial N acquisition under exogenous N inputs, resulting in an overestimation of microbial NUE by EEST. In addition, the acquisition of carbon by N-acquiring enzymes also likely interferes with the evaluation of NUE by EEST.

Conclusions

Our results demonstrate that caution must be exercised when using EEST to evaluate NUE under exogenous N inputs that may skew standard enzyme assays.
Ferrostatin-1 facilitated neurological functional rehabilitation of spinal cord injury mice by inhibiting ferroptosis
Authors: Zhou Zhenhai , Luo Hao , Yu Honggui , Liu Zhiming , Zhong Junlong , Xiong Jiachao , Cao Kai
Published: September 2023

Background

To seek the potential therapy for spinal cord injury, Ferrostatin-1, the first ferroptosis inhibitor, was administrated in spinal cord injury mice to identify the therapeutic effect.

Methods

Spinal cord injury model was established by a modified Allen’s method. Then, ferrostatin-1 was administrated by intraspinal injection. Cortical evoked motor potential and BMS were indicated to assess the neurological function rehabilitation. H&E, Nissl’s staining, NeuN, and GFAP immunofluorescence were used to identify the histological manifestation on the mice with the injured spinal cord. Spinosin, a selective small molecule activator of the Nrf2/HO-1 signaling pathway, was administrated to verify the underlying mechanism of ferrostatin-1.

Results

Ferrostatin-1 promoted the rehabilitation of cortical evoked motor potential and BMS scores, synchronized with improvement in the histological manifestation of neuron survival and scar formation. Spinosin disturbed the benefits of ferrostatin-1 administration on histological and neurobehavioral manifestation by deranging the Nrf2/HO-1 signaling pathway.

Conclusions

Ferrostatin-1 improved the rehabilitation of spinal cord injury mice by regulating ferroptosis through the Nrf2/HO-1 signaling pathway.