bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of NUDT15 Genetic Variants and Incidence of Thiopurine-induced Leukopenia in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis
Authors: Yu Natalie , Sriranganathan Danujan , Walker Gareth J , Sazonovs Aleksejs , Wilding Helen , Roberts Christopher , Kennedy Nicholas A , Ahmad Tariq , Boyapati Ray K , Ding Nik S , Segal Jonathan P 
Published: June 2023

Abstract

Background and Aims
Nudix hydrolase 15 [NUDT15] genetic variants confer an increased risk of thiopurine-induced leukopenia [TIL]; however, their global prevalence in inflammatory bowel disease [IBD] patients is unknown. We aimed to evaluate the global prevalence of NUDT15 variants in IBD patients and incidence of TIL in these patients.

Methods
Six databases were searched from inception until July 2022. Studies reporting the frequency of any NUDT15 variant and/or frequency of leukopenia in adult IBD patients with these variants were included. A random effects model was performed to estimate the pooled prevalence of variants, incidence of early [≤8 weeks] and late [&gt;8 weeks] leukopenia, and relative risk of developing leukopenia.

Results
Twenty studies comprising 5232 patients were included. The pooled prevalence of the *1/*3 c.415C &gt; T C/T diplotype was 13% (95% confidence interval [CI]: 10–18%), *3/*3 c.415C &gt; T T/T diplotype was 2% [95% CI: 1–2%], *1/*5 c.52G &gt; A G/A diplotype was 2% [95% CI: 1–3%], and *1/*6 c.36_37insGGAGTC ins/- diplotype was 7% [95% CI: 4–12%]. The pooled prevalence of *1/*3 was high in Japanese [20%, 95% CI: 16–24%] and Chinese patients [18%, 95% CI: 12–27%]. The incidence of early leukopenia was 20% [95% CI: 16–26%] in *1/*3 patients, 99% [95% CI: 7–100%] in *3/*3 patients, and 49% [95% CI: 29–69%] in *1/*6 patients. The incidence of late leukopenia was 36% [95% CI: 26–49%] in *1/*3 patients.

Conclusions
NUDT15 variants are common and strongly predict TIL in IBD patients. Pre-treatment NUDT15 genotyping should be considered particularly in Asian populations, to guide thiopurine dosing and prevent myelotoxicity.
Safety and efficacy of colchicine for the prevention of post-operative atrial fibrillation in patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials
Authors: Agarwal Siddharth , Beard Christopher W , Khosla Jagjit , Clifton Shari , Anwaar Muhammad Faraz , Ghani Asad , Farhat Kassem , Pyrpyris Nikolaos , Momani Joud , Munir Muhammad Bilal , DeSimone Christopher V , Deshmukh Abhishek , Stavrakis Stavros , Jackman Warren M , Po Sunny , Asad Zain Ul Abideen 
Published: June 2023

Abstract

Background and Aims
Colchicine is an anti-inflammatory drug that may prevent post-operative atrial fibrillation (POAF). The effect of this drug has been inconsistently shown in previous clinical trials. We aimed to compare the efficacy and safety of colchicine vs. placebo to prevent POAF in patients undergoing cardiac surgery.

Methods and results
A systematic search of EMBASE, MEDLINE, SCOPUS, ClinicalTrials.gov, and the Cochrane Library for randomized controlled trials (RCTs) was conducted from inception till April 2023. The primary outcome was the incidence of POAF after any cardiac surgery. The secondary outcome was the rate of drug discontinuation due to adverse events and adverse gastrointestinal events. Risk ratios (RR) were reported using the Mantel Haenszel method. A total of eight RCTs comprising 1885 patients were included. There was a statistically significant lower risk of developing POAF with colchicine vs. placebo (RR: 0.70; 95% CI: 0.59–0.82; P &lt; 0.01, I2 = 0%), and this effect persisted across different subgroups. There was a significantly higher risk of adverse gastrointestinal events (RR: 2.20; 95% CI: 1.38–3.51; P &lt; 0.01, I2 = 55%) with no difference in the risk of drug discontinuation in patients receiving colchicine vs. placebo (RR: 1.33; 95% CI: 0.93–1.89; P = 0.11, I2 = 0%).

Conclusion
This meta-analysis of eight RCTs shows that colchicine is effective at preventing POAF, with a significantly higher risk of adverse gastrointestinal events but no difference in the rate of drug discontinuation. Future studies are required to define the optimal duration and dose of colchicine for the prevention of POAF.
Ribosomal Intergenic Spacers Are Filled with Transposon Remnants
Authors: Bendich Arnold J , Rogers Scott O 
Published: June 2023

Abstract
Eukaryotic ribosomal DNA (rDNA) comprises tandem units of highly conserved coding genes separated by rapidly evolving spacer DNA. The spacers of all 12 species examined were filled with short direct repeats (DRs) and multiple long tandem repeats (TRs), completing the rDNA maps that previously contained unannotated and inadequately studied sequences. The external transcribed spacers also were filled with DRs and some contained TRs. We infer that the spacers arose from transposon insertion, followed by their imprecise excision, leaving short DRs characteristic of transposon visitation. The spacers provided a favored location for transposon insertion because they occupy loci containing hundreds to thousands of gene repeats. The spacers’ primary cellular function may be to link one ribosomal RNA transcription unit to the next, whereas transposons flourish here because they have colonized the most frequently used part of the genome.
RNA-Sequencing Analysis Identification of Potential Biomarkers for Diagnosis of Sarcopenia
Authors: Furutani Motoki , Suganuma Mutsumi , Akiyama Shintaro , Mitsumori Risa , Takemura Marie , Matsui Yasumoto , Satake Shosuke , Nakano Yukiko , Niida Shumpei , Ozaki Kouichi , Hosoyama Tohru , Shigemizu Daichi 
Published: June 2023

Abstract
Sarcopenia is a geriatric disease associated with increased mortality and disability. Early diagnosis and intervention are required to prevent it. This study investigated biomarkers for sarcopenia by using a combination of comprehensive clinical data and messenger RNA-sequencing (RNA-seq) analysis obtained from peripheral blood mononuclear cells. We enrolled a total of 114 older adults aged 66–94 years (52 sarcopenia diagnosed according to the Asian Working Group for Sarcopenia 2019 consensus and 62 normal older people). We used clinical data which were not included diagnosis criteria of sarcopenia, and stride length showed significance by logistic regression analysis (Bonferroni corrected p = .012, odds ratio = 0.14, 95% confidence interval [CI]: 0.05–0.40). RNA-seq analysis detected 6 differential expressed genes (FAR1, GNL2, HERC5, MRPL47, NUBP2, and S100A11). We also performed gene-set enrichment analysis and detected 2 functional modules (ie, hub genes, MYH9, and FLNA). By using any combination of the 9 candidates and basic information (age and sex), risk-prediction models were constructed. The best model by using a combination of stride length, HERC5, S100A11, and FLNA, achieved a high area under the curve (AUC) of 0.91 in a validation cohort (95% CI: 0.78–0.95). The quantitative PCR results of the 3 genes were consistent with the trend observed in the RNA-seq results. When BMI was added, the model achieved a high AUC of 0.95 (95% CI: 0.84–0.99). We have discovered potential biomarkers for the diagnosis of sarcopenia. Further refinement may lead to their future practical use in clinical use.
P-699 A clinical predictive model for live birth in women of advanced age undergoing PGT cycles
Authors: Bercovich O , Klar G , Shaulov T , Almog B , Kalma Y , Rahav R , Azem F , Malcov M , Cohen Y 
Published: June 2023

Abstract

Study question
In 37–45-year-old women undergoing preimplantation genetic testing, who will benefit from repeated cycles until birth?

Summary answer
The chance of delivering after repeated cycles is higher in those with at least one top-quality unaffected embryo in their first preimplantation genetic testing cycle.

What is known already
PGT for monogenic disease or structural chromosomal rearrangement (PGT-M and PGT-SR) is offered to couples when one or both carry a monogenic mutation or chromosomal rearrangement that put their future offspring at risk of having a genetic disorder so they can select an unaffected embryo for uterine transfer.
The tendency to delay childbirth has led to an increase in advanced-aged women seeking PGT treatments. This poses a major challenge to PGT treatments.

Study design, size, duration
A retrospective cohort study was conducted at a university hospital reproductive center. The computerized database of 158 women aged 37–45 undergoing 753 PGT-M/SR cycles between 2010 and 2021 was analyzed.

Participants/materials, setting, methods
The reproductive outcomes of women who were 37–45 years of age, starting a PGT-M/SR cycle, were analyzed until the first live birth or until the patient reached the age of 45.
Data were analyzed using univariate analysis, multivariable stepwise logistic regression, Kaplan–Meier method, and decision tree analysis. The cumulative live birth rate was calculated in a conservative manner because the assumption that patients who did not return for subsequent cycles had negative results was made.

Main results and the role of chance
The analysis included 158 women undergoing 753 preimplantation genetic testing cycles. The cumulative live birth rate was 37.342% (59/158). Decision tree analysis revealed that women aged ≤ 40.1 or women &gt; 40.1 with one or more top-quality embryos in their first cycle had the best chance for a live baby (41% and 56%, respectively). Those older than 40.1 without top-quality embryos and seven or fewer dominant follicles had no live births. A Kaplan–Meier curve showed that for autosomal dominant diseases, there was a negligible increase in live birth rate after three cycles, compared to six cycles in autosomal recessive inheritance.

Limitations, reasons for caution
This study is limited by its retrospective design and the low birth rate in this age group, which reduces its power to detect differences in birth rates between different modes of inheritance.

Wider implications of the findings
The predictive model for live births in women aged 37-45 developed in this study can be used for clinical decision making and patient consultation.
Additional PGT cycles after three in carriers of an autosomal dominant disorder and six in those with an autosomal recessive disorder should be considered prudently.

Trial registration number
Not applicable
P-754 Chronic poor healing wounds of post cesarean scar diverticulum: altered angiogenesis and immunobiology
Authors: Yang X , Liu Z 
Published: June 2023

Abstract

Study question
To detect the influences of cesarean section scar diverticula (CSD) on the pregnancy outcomes in ART and explore the mechanisms.

Summary answer
In the CSD group, the cumulative live birth rate （CLBR） was significantly reduced, accompanied by excessive proliferation of fibroblasts and expansion of vascular proliferation.

What is known already
Diverticulum can reduce the chances of embryo implantation and may lead to spontaneous miscarriages if the implantation is close to or in the CSD. The accumulation of bloody fluid can be detected in approximately 42% of women with large CSD. The trapped blood is slowly released and could affect cervical mucus, sperm transport, and implantation. The previously data have revealed that disrupted uterus microbiota is closely associated with local inflammatory cytokines which could also be a clue for impaired fecundity in CSD.

Study design, size, duration
This retrospective cohort study was conducted using data from a single, large university-affiliated fertility center. Data was retrospective analyzed among women underwent ART procedure from May 2010 to March 2021. Follow-up basic experiments to explore relevant mechanisms.

Participants/materials, setting, methods
Data was retrospective analyzed among 31375 women underwent ART procedure in the Sixth affiliated Hospital of Sun Yat-sen University. To optimize the precision of the study, patients in the CSD group and the NCS group were matched using propensity score matching method. Perform hysteroscopy and obtain cervical swab and endometrial tissue of lower segment. To explore the difference of uterine cavity environment between CSD group and vaginal birth (VB) group by histopathological and immunological analysis.

Main results and the role of chance
The CS group had significantly lower CLBR compared to NCS group. Histopathological analysis showed that the higher prevalent of chronic endometritis is accompanied by excessive fibroblast proliferation at the lower segment of uterus and significantly exaggerated vascular proliferation in situ. Intrauterine inflammatory cytokines including IL-1α, IL-1β, IL-6, IL-8, TNF-α and SDF-1α were also increased in CSD group.

Limitations, reasons for caution
The main limitation of our study is its retrospective nature and single center, which might have underestimated the total number of women with CSD and could lead to a bias.

Wider implications of the findings
Lay emphasis on anti-infective therapy, modulate the imbalance of reproductive tract flora and enhance early lesion healing post-operation are of great necessity. Future studies exploring the preventive and therapeutic strategies of CSD should focus on immune inflammatory response and angiogenesis.

Trial registration number
Not applicable
P-758 Impact of serum estradiol levels prior to progesterone administration in artificial frozen embryo transfer cycles:a retrospective study over 26,000 cycles
Authors: Chen Q 
Published: June 2023

Abstract

Study question
To investigate whether serum estradiol (E2) levels prior to progesterone administration in the FET-cycle affect the Clinical pregnancy rate (CPR) and live birth rate (LBR).

Summary answer
High serum E2 levels prior to progesterone administration in Artificial endometrial preparation are associated with a decreased live birth rate and clinical pregnancy rate .

What is known already
Although the use of FET has progressively increased, it is still unknown whether a specific endometrial preparation protocol should be favored over another. Owing to their minimal need for clinic visits and a larger scheduling flexibility, artificial cycles for FET are widely used. Additional to the ultrasonographic endometrial thickness check prior to FET, the need for endocrine monitoring in artificial cycles remains unclear. Specifically, the value of proliferative phase serum hormone measurements remains a point of discussion.

Study design, size, duration
A total of 26,194 artificial FETs performed in a Tertiary-care academic medical centre between 2016 and 2021 were subdivided into 3 groups according to the following late-proliferative serum E2 level percentiles: ≤p33.3 (E2 ≤118 pg/ml; n = 8784), p33.4–p66.6 (E2 from 118.1 to 231.9 pg/ml; n = 8662) and ≥p66.7 (E2 ≥232 pg/ml; n = 8748).

Participants/materials, setting, methods
A retrospective study over 26,194 cycles,from 2016 to 2021 were included.Univariable and multivariable logistic regression analysis was performed.

Main results and the role of chance
In 26,194 cycles, there were significant differences in CPR and LBR among the tri-sectional quantiles groups with E2 levels. After stratifying the analysis by age, BMI, infertility diagnosis, type of embryo transferred, number of transferred embryos, infertility factors, method of fertilization, and endometrial thickness on transfer day, there were still significant differences in CPR and LBR among the tri-sectional quantiles group with E2 levels. Multivariate regression analysis showed that female age, thin endometrium, high serum E2 level, tubal factor infertility were risk factors for CPR and LBR, ICSI fertilization, blastocyst transfer, the number of transferred embryos, ovulation disorder infertility and male factor infertility were protective factors for CPR and LBR, BMI was only a risk factor for LBR.

Limitations, reasons for caution
•Different routes of administration affect serum estrogen levels,and the relationship of serum estrogen levels and endometrial estrogen concentrations is unclear

Wider implications of the findings
High miscarriage rate following FET has been a point of debate in literature.Future research should definitely focus on the the usefulness of serum E2 evaluation to optimize the success rate.

Trial registration number
Not applicable
O-095 Different phenotypes of PCOS: Implications to clinical practice
Authors: Franks S 
Published: June 2023

Abstract
Polycystic ovary syndrome (PCOS) is a very common, heterogeneous syndrome which presents with a spectrum of clinical and biochemical features. It is associated with both reproductive and metabolic dysfunction and has a negative impact on long term health, including mental health. Although there appears to be a common genetic background to PCOS, regardless of presentation, environmental factors, including diet, play an important part in determining the phenotype. The most commonly used diagnostic criteria, the Rotterdam criteria, takes account of the heterogenous nature of the syndrome but the spectrum of presentation can be categorised as four clinical and biochemical subtypes which comprise (A) ovulatory dysfunction, hyperandrogenism, polycystic ovaries (PCO), (B) ovulatory dysfunction, hyperandrogenism but without PCO, (C) hyperandrogenism without ovulatory dysfunction but with PCO and (D) ovulatory dysfunction with PCO but without hyperandrogenism. These are not rigid categories since some women may go from one to another, for example weight gain may lead to anovulation in a woman who previously had hirsutism but regular cycles. Nevertheless, the diagnostic sub-category has a significance influence on clinical management.
Women who have both hyperandrogenism and ovulatory dysfunction (A&B) are at higher risk of metabolic dysfunction which is exacerbated by obesity (and carries a high long-term risk of diabetes and cardiovascular disease) and so merit thorough investigation which includes assessment of glucose tolerance and lipids. Those who have predominantly ovulatory problems may require fertility treatment or regulation of menses but some who simply have irregular menses may need no specific treatment. Symptoms of hyperandrogenism (hirsutism, acne, alopecia) can be particularly distressing and may be best managed in collaboration with a dermatologist. The negative impact of PCOS on mental health is a very common problem, the high prevalence of which has only recently been appreciated. Not surprisingly, it is particularly relevant in those women who have moderate to severe symptoms of hyperandrogenism.
In summary, PCOS is a syndrome characterised by a variety of symptoms and endocrine abnormalities and it is important to tailor treatment individually, according to the need for symptom relief and with regard to concerns about long-term health.
O-140 studying the effect of mosaicism on the outcome of micro-TESE among Klinefelter syndrome patients
Authors: Al-Ahwani A , Dawood R , Fawzy A , Elrefaey F , AlAhwany H 
Published: June 2023

Abstract

Study question
Does mosaicism affect sperm retrieval rate in Klinefelter patients?

Summary answer
Patients with mosaic Klinefelter syndrome (KS) have a higher success rate of sperm retrieval than those with non-mosaic KS.

What is known already
Klinefelter syndrome is characterised by the presence of an extra X chromosome in male individuals leading to a 47XXY karyotype and rarely to 46XY/47XXY Mosaicism; it is the most common sex chromosomal aneuploidy and the most common genetic cause of Azoospermia (Kanakis GA et al., 2018 and Gravholt CH et al.,2018). It accounts for 3–4% of male infertility cases and 10–12% of men with Azoospermia (Winters SJ,2018).

Study design, size, duration
After approval of the ethical committee of the faculty of medicine at Cairo University, This prospective study was conducted where 70 men who complained of primary infertility and azoospermia and were diagnosed with Klinefelter Syndrome were recruited for this study between 1/11/2021 and 30/11/2022. Patients with previous testicular disease (torsion, trauma) or who had a history of undescended testes or received chemotherapy or radiotherapy were excluded.

Participants/materials, setting, methods
Seventy patients (n = 70) aged between 20 and 50 who fit the inclusion criteria were recruited and underwent micro_TESE. Semen analysis (Azoospermia), hormonal profile, scrotal colour doppler ultrasonography, Karyotyping and FISH for Y and X chromosomes were performed. Statistical analysis was conducted using SPSS 22nd edition.

Main results and the role of chance
Our study groups comprised 14 patients with mosaic KS and 56 with non-mosaic KS. The clinical characteristics were not significantly different statistically between the two groups. Micro_TESE was performed in all 70 patients; in 26 patients (37.1%), mature sperm were found in the wet preparation.
No statistically significant correlation was found between the presence of spermatozoa in the extraction specimen and age, serum follicle-stimulating hormone, serum testosterone, prolactin or oestradiol. The statistically significant predictor variable for sperm extraction was mosaicism, luteinising hormone, testicular volume and FISH. The sperm retrieval rate of the patients with mosaic and non-mosaic KS was 57.1% and 32.1%, respectively.

Limitations, reasons for caution
1) Larger (n) number of patients was needed.
2) Despite our valuable findings, further studies should be performed to illuminate the relation between FISH for X and Y chromosomes and sperm retrieval rate success.

Wider implications of the findings
Klinefelter patients with mosaicism should be offered high sperm retrieval rate during IVF counselling.

Trial registration number
n/a