bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

AbstractNecessity 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

Abstract
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

AbstractResolving 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

Abstract
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

AbstractThis 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

AbstractObjectiveThe 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.ResultsThe 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

Abstract
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

Abstract
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

AbstractDysregulation 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

Abstract
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.