bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interventions to prevent or reduce the incidence and severity of ovarian hyperstimulation syndrome: a systematic umbrella review of the best clinical evidence
Authors: Palomba Stefano , Costanzi Flavia , Nelson Scott M. , Caserta Donatella , Humaidan Peter 
Published: July 2023

AbstractOvarian hyperstimulation syndrome (OHSS) is a potentially life-threating iatrogenic complication of the early luteal phase and/or early pregnancy after in vitro fertilization (IVF) treatment. The aim of the current study was to identify the most effective methods for preventing of and reducing the incidence and severity of OHSS in IVF patients. A systematic review of systematic reviews of randomized controlled trials (RCTs) with meta-analysis was used to assess each potential intervention (PROSPERO website, CRD 268626) and only studies with the highest quality were included in the qualitative analysis. Primary outcomes included prevention and reduction of OHSS incidence and severity. Secondary outcomes were maternal death, incidence of hospital admission, days of hospitalization, and reproductive outcomes, such as incidence of live-births, clinical pregnancies, pregnancy rate, ongoing pregnancy, miscarriages, and oocytes retrieved. A total of specific interventions related to OHSS were analyzed in 28 systematic reviews of RCTs with meta-analyses. The quality assessment of the included studies was high, moderate, and low for 23, 2, and 3 studies, respectively. The certainty of evidence (CoE) for interventions was reported for 37 specific situations/populations and resulted high, moderate, and low-to-very low for one, 5, and 26 cases, respectively, while it was not reported in 5 cases. Considering the effective interventions without deleterious reproductive effects, GnRH-ant co-treatment (36 RCTs; OR 0.61, 95% C 0.51 to 0.72, n = 7,944; I2 = 31%) and GnRH agonist triggering (8 RCTs; OR 0.15, 95% CI 0.05 to 0.47, n = 989; I2 = 42%) emerged as the most effective interventions for preventing OHSS with a moderate CoE, even though elective embryo cryopreservation exhibited a low CoE. Furthermore, the use of mild ovarian stimulation (9 RCTs; RR 0.26, CI 0.14 to 0.49, n = 1,925; I2 = 0%), and dopaminergic agonists (10 RCTs; OR 0.32, 95% CI 0.23 to 0.44, n = 1,202; I2 = 13%) coadministration proved effective and safe with a moderate CoE. In conclusion, the current study demonstrates that only a few interventions currently can be considered effective to reduce the incidence of OHSS and its severity with high/moderate CoE despite the numerous published studies on the topic. Further well-designed RCTs are needed, particularly for GnRH-a down-regulated IVF cycles.
Alzheimer’s disease-associated complement gene variants influence plasma complement protein levels
Authors: Veteleanu Aurora , Stevenson-Hoare Joshua , Keat Samuel , Daskoulidou Nikoleta , Zetterberg Henrik , Heslegrave Amanda , Escott-Price Valentina , Williams Julie , Sims Rebecca , Zelek Wioleta M. , Carpanini Sarah M. , Morgan Bryan Paul 
Published: July 2023

Abstract
Background
Alzheimer’s disease (AD) has been associated with immune dysregulation in biomarker and genome-wide association studies (GWAS). GWAS hits include the genes encoding complement regulators clusterin (CLU) and complement receptor 1 (CR1), recognised as key players in AD pathology, and complement proteins have been proposed as biomarkers.

Main body
To address whether changes in plasma complement protein levels in AD relate to AD-associated complement gene variants we first measured relevant plasma complement proteins (clusterin, C1q, C1s, CR1, factor H) in a large cohort comprising early onset AD (EOAD; n = 912), late onset AD (LOAD; n = 492) and control (n = 504) donors. Clusterin and C1q were significantly increased (p < 0.001) and sCR1 and factor H reduced (p < 0.01) in AD plasma versus controls. ROC analyses were performed to assess utility of the measured complement biomarkers, alone or in combination with amyloid beta, in predicting AD. C1q was the most predictive single complement biomarker (AUC 0.655 LOAD, 0.601 EOAD); combining C1q with other complement or neurodegeneration makers through stepAIC-informed models improved predictive values slightly. Effects of GWS SNPs (rs6656401, rs6691117 in CR1; rs11136000, rs9331888 in CLU; rs3919533 in C1S) on protein concentrations were assessed by comparing protein levels in carriers of the minor vs major allele. To identify new associations between SNPs and changes in plasma protein levels, we performed a GWAS combining genotyping data in the cohort with complement protein levels as endophenotype. SNPs in CR1 (rs6656401), C1S (rs3919533) and CFH (rs6664877) reached significance and influenced plasma levels of the corresponding protein, whereas SNPs in CLU did not influence clusterin levels.

Conclusion
Complement dysregulation is evident in AD and may contribute to pathology. AD-associated SNPs in CR1, C1S and CFH impact plasma levels of the encoded proteins, suggesting a mechanism for impact on disease risk.
Mapping intron retention events contributing to complex traits using splice quantitative trait locus
Authors: Wang Siyuan , Wu Hongyu , Zhao Yongyan , Wang Luyao , Guan Xueying , Zhao Ting 
Published: July 2023

Abstract
Background
Alternative splicing (AS) of mRNA plays an important roles in transcriptome diversity, involving regulation of plant growth and stress response. Understanding the variation of AS events underlying GWAS loci in a crop population can provide insight into the molecular mechanisms of complex agronomic traits. To date, genome-wide association studies relating AS events to agronomic traits have rarely been conducted at the population level in crops.

Results
Here, a pipeline was constructed to identify candidate AS events related to complex traits. Firstly, ovule transcriptome data were used to characterize intron retention (IR), the predominant type of AS in plants, on a genome-wide scale. This was done in a natural population consisting of 279 upland cotton lines. Secondly, splice quantitative trait locus (sQTL) analysis was carried out, which yielded a total of 2295 sQTLs involving 1607 genes. Of these, 14.25% (n = 427) were cis-regulatory loci. Integration with expression quantitative trait loci (eQTL) revealed that 53 (21.4%) cis-sGenes were regulated by both cis-sQTLs and cis-eQTLs. Finally, co-localization analysis integrated with GWAS loci in this population showed 32 cis-QTLs to be co-located with genetic regulatory loci related to fiber yield and quality traits, indicating that sQTLs are likely to participate in regulating cotton fiber yield and quality. An in-depth evaluation confirmed that differences in the IR rates of sQTL-regulated candidate genes such as GhLRRK1 and GhGC1 are associated with lint percentage (LP), which has potential in breeding applications.

Conclusion
This study provides a clue that AS of mRNA has an impact on crop yield, along with functional sQTLs are new genetic resources for cotton precision breeding.
The relative value of Pre-Implementation stages for successful implementation of evidence-informed programs
Authors: Alley Zoe M. , Chapman Jason E. , Schaper Holle , Saldana Lisa 
Published: July 2023

Abstract
Background
Most implementations fail before the corresponding services are ever delivered. Measuring implementation process fidelity may reveal when and why these attempts fail. This knowledge is necessary to support the achievement of positive implementation milestones, such as delivering services to clients (program start-up) and competency in treatment delivery. The present study evaluates the extent to which implementation process fidelity at different implementation stages predicts achievement of those milestones.

Methods
Implementation process fidelity data—as measured by the Stages of Implementation Completion (SIC)—from 1287 implementing sites across 27 evidence-informed programs were examined in mixed effects regression models with sites nested within programs. Implementation process fidelity, as measured by the proportion of implementation activities completed during the three stages of the SIC Pre-Implementation phase and overall Pre-Implementation (Phase 1) and Implementation (Phase 2) proportion scores, was assessed as a predictor of sites achieving program start-up (i.e., delivering services) and competency in program delivery.

Results
The predicted probability of start-up across all sites was low at 35% (95% CI [33%, 38%]). When considering the evidence-informed program being implemented, that probability was nearly twice as high (64%; 95% CI [42%, 82%]), and 57% of the total variance in program start-up was attributable to the program. Implementation process fidelity was positively and significantly associated with achievement of program start-up and competency. The magnitude of this relationship varied significantly across programs for Pre-Implementation Stage 1 (i.e., Engagement) only. Compared to other stages, completing more Pre-Implementation Stage 3 (Readiness Planning) activities resulted in the most rapid gains in probability of achieving program start-up. The predicted probability of achieving competency was very low unless sites had high scores in both Pre-Implementation and Implementation phases.

Conclusions
Strong implementation process fidelity—as measured by SIC Pre-Implementation and Implementation phase proportion scores—was associated with sites’ achievement of program start-up and competency in program delivery, with early implementation process fidelity being especially potent. These findings highlight the importance of a rigorous Pre-Implementation process.
Validation of clinical exome sequencing in the diagnostic procedure of patients with intellectual disability in clinical practice
Authors: Ballesta-Martínez María Juliana , Pérez-Fernández Virginia , López-González Vanesa , Sánchez-Soler María José , Serrano-Antón Ana Teresa , Rodríguez-Peña Lidia Isolina , Barreda-Sánchez Maria , Armengol-Dulcet Lluís , Guillén-Navarro Encarna 
Published: July 2023

AbstractIntellectual disability (ID) has a prevalence of 1–3% and aproximately 30–50% of ID cases have a genetic cause. Development of next-generation sequencing has shown a high diagnostic potential. The aim of this work was to evaluate the diagnostic yield of clinical exome sequencing in 188 ID patients and the economic impact of its introduction in clinical practice. An analysis of diagnostic yield according to the different clinical variables was performed in order to establish an efficient diagnostic protocol for ID patients. Diagnostic yield of clinical exome sequencing was significant (34%) supporting its utility in diagnosis of ID patients. Wide genetic heterogeneity and predominance of autosomal dominant de novo variants in ID patients were observed. Time to diagnosis was shortened and diagnostic study costs decreased by 62% after implementation of clinical exome sequencing. No association was found between any of the variables analyzed and a higher diagnostic yield; added to the fact that many of the diagnoses weren’t clinically detectable, the reduction of time to diagnosis and the economic savings with respect to classical diagnostic studies, strengthen the clinical and economical convenience of early implementation of clinical exome sequencing in the diagnostic workup of ID patients in clinical practice.
New retinal findings in NLRP3-associated autoinflammatory disease
Authors: Wei Zhangwanyu , Yang Zhikun , Li Donghui , Zhang Xiao , Li Bing , Zhao Xufeng , Yan Wenyu , Wu Bingxuan , Wu Na , Wang Xuqian , Yu Weihong , Shen Min 
Published: July 2023

Abstract
Purpose
To determine whether the rare NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) is associated with retinal changes and to assess the ocular involvement.

Methods
A retrospective cohort study of 20 patients(40 eyes) diagnosed with rare NLRP3-AID at Peking Union Medical College Hospital, from April 2015 to August 2022. Patients underwent a comprehensive ophthalmological examination, including visual acuity, intraocular pressure examination, slit-lamp examination, fundus photography, optical coherence tomography(OCT), and fluorescence angiography (FA). Some patients also underwent optical coherence tomography angiography (OCTA).

Results
This study analyzed 40 eyes of 20 patients (11 [55.0%] male; median age, 25.0 years [range, 12–52 years]) and 13 patients (26 eyes, 65%) demonstrated ocular involvement. The most common ophthalmologic manifestation was conjunctivitis (22 eyes, 84.6%), followed by papilledema (14 eyes, 53.8%), retinopathy (10 eyes, 38.5%), optic atrophy (6 eyes, 23.1%), uveitis (4 eyes, 15.4%), reduced pupil light reflex (3 eyes, 11.5%) and cataracts (2 eyes, 7.7%). Ocular involvement was bilateral in 11 patients (55.0%). Five kinds of retinal lesions were seen in 5 patients (10 eyes, 25%) with NLRP3-AID, including peripheral retinal vascular leakage, microaneurysms, macular ischemia, macular epiretinal membrane formation and drusen.

Conclusions
Peripheral retinal vascular leakage, macular ischemia, microaneurysms and drusen are newly identified retinal findings in patients with NLRP3-AID, which suggests the importance of detailed retinal examination in these patients.
Optimising DTwP-containing vaccine infant immunisation schedules (OptImms) — a protocol for two parallel, open-label, randomised controlled trials
Authors: Kelly Sarah , Liu Xinxue , Theiss-Nyland Katherine , Voysey Merryn , Murphy Sarah , Li Grace , Nyantaro Mary , Gurung Meeru , Basnet Sudha , Pokhrel Bhishma , Bijukchhe Sanjeev M. , Eordogh Agnes , Gombe Ben , Kakande Ayoub , Kerridge Simon , Kimbugwe Geofrey , Kusemererwa Sylvia , Lubyayi Lawrence , Luzze Henry , Mazur Olga , Mujadidi Yama F. , Nabukenya Shamim , Nagumo Walter-Rodney , Nareeba Tryphena , Noristani Rabiullah , O’Reilly Peter , Roberts Andrew , Shah Ganesh , Shrestha Sonu , Shrestha Laxman P. , Thapa Surya B. , Kibengo Freddie M. , Sharma Arun K. , Elliott Alison , Shrestha Shrijana , Pollard Andrew J. 
Published: July 2023

Abstract

Background
Universal immunisation is the cornerstone of preventive medicine for children, The World Health Organisation (WHO) recommends diphtheria-tetanus-pertussis (DTP) vaccine administered at 6, 10 and 14 weeks of age as part of routine immunisation. However, globally, more than 17 unique DTP-containing vaccine schedules are in use. New vaccines for other diseases continue to be introduced into the infant immunisation schedule, resulting in an increasingly crowded schedule. The OptImms trial will assess whether antibody titres against pertussis and other antigens in childhood can be maintained whilst adjusting the current Expanded Programme on Immunisation (EPI) schedule to provide space for the introduction of new vaccines.

Methods
The OptImms studies are two randomised, five-arm, non-inferiority clinical trials in Nepal and Uganda. Infants aged 6 weeks will be randomised to one of five primary vaccination schedules based on age at first DTwP-vaccination (6 versus 8 weeks of age), number of doses in the DTwP priming series (two versus three), and spacing of priming series vaccinations (4 versus 8 weeks). Additionally, participants will be randomised to receive their DTwP booster at 9 or 12 months of age. A further sub-study will compare the co-administration of typhoid vaccine with other routine vaccines at one year of age. The primary outcome is anti-pertussis toxin IgG antibodies measured at the time of the booster dose. Secondary outcomes include antibodies against other vaccine antigens in the primary schedule and their safety.

Discussion
These data will provide key data to inform policy decisions on streamlining vaccination schedules in childhood.

Trial registrations
ISRCTN12240140 (Nepa1, 7th January 2021) and ISRCTN6036654 (Uganda, 17th February 2021).
Mmwave massive MIMO: one joint beam selection combining cuckoo search and ant colony optimization
Authors: Zhu Chunhua , Ji Qinwen , Guo Xinying , Zhang Jiankang 
Published: July 2023

AbstractIn order to degrade the inter-user interference caused by the same beam selected for different users in mmWave massive MIMO systems, this paper proposes a joint beam selection combining cuckoo search (CS) and ant colony optimization (ACO) (referred to as CSACO). Differently from the existing interference-aware beam selection, a candidate beam set (CBS) for all users is created according to the power distribution of the beamspace channel, thereby all users can be classified into non-interfering users (NIUs) and interfering users (IUs), and NIUs will be assigned the beams with large power directly, while for IUs, the beams are selected by the CSACO; in the proposed CSACO, all beams for IUs are regarded as an optimizable individual, which is continuously evolved towards the direction of sum-rate maximization. Simulation results verify that the proposed beam selection can obtain the higher sum-rate and energy efficiency compared with the existing ones.
Chagas disease is related to structural changes of the gut microbiota in adults with chronic infection (TRIPOBIOME Study)
Authors: Pérez-Molina José A. , Crespillo-Andújar Clara , Trigo Elena , Chamorro Sandra , Arsuaga Marta , Olavarrieta Leticia , Navia Beatriz , Martín Oihane , Monge-Maillo Begoña , Norman Francesca F. , Lanza Val F. , Serrano-Villar Sergio 
Published: July 2023

Background
The implications of the gut microbial communities in the immune response against parasites and gut motility could explain the differences in clinical manifestations and treatment responses found in patients with chronic Chagas disease.

Methodology/Principal findings
In this pilot prospective cross-sectional study, we included 80 participants: 29 with indeterminate CD (ICD), 16 with cardiac CD (CCD), 15 with digestive CD (DCD), and 20 controls without CD. Stool was collected at the baseline visit and faecal microbial community structure DNA was analyzed by whole genome sequencing. We also performed a comprehensive dietary analysis. Ninety per cent (72/80) of subjects were of Bolivian origin with a median age of 47 years (IQR 39–54) and 48.3% (29/60) had received benznidazole treatment. There were no substantial differences in dietary habits between patients with CD and controls. We identified that the presence or absence of CD explained 5% of the observed microbiota variability. Subjects with CD exhibited consistent enrichment of Parabacteroides spp, while for Enterococcus hirae, Lactobacillus buchneri and Megamonas spp, the effect was less clear once excluded the outliers values. Sex, type of visceral involvement and previous treatment with benznidazole did not appear to have a confounding effect on gut microbiota structure. We also found that patients with DCD showed consistent Prevotella spp enrichment.

Conclusions
We found a detectable effect of Chagas disease on overall microbiota structure with several potential disease biomarkers, which warrants further research in this field. The analysis of bacterial diversity could prove to be a viable target to improve the prognosis of this prevalent and neglected disease.
Neighborhood deprivation in relation to lung cancer in individuals with type 2 diabetes—A nationwide cohort study (2005–2018)
Authors: Li Xinjun , Jansåker Filip , Sundquist Jan , Crump Casey , Hamano Tsuyoshi , Sundquist Kristina 
Published: July 2023

Background
Neighborhood deprivation has been found associated with both type 2 diabetes and lung cancer. The aim of this study was to examine the potential association between neighborhood deprivation and lung cancer incidence or mortality in individuals diagnosed with type 2 diabetes. The results may identify a new risk or prognostic factor for lung cancer in this important subgroup and help develop a more contextual approach to prevention that includes neighborhood environment.

Methods and findings
The study population included adults (n = 613,650) aged ≥ 30 years with type 2 diabetes during 2005 to 2018 in Sweden. Cox regression was used to compute hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incidence or mortality of lung cancer associated with neighborhood deprivation. All models were conducted in both men and women and adjusted for individual-level characteristics (e.g. age, smoking- and alcohol-related comorbidities, sociodemographic factors). The cumulative incidence and mortality for lung cancer were 1.08% (95% CI, 1.06 to 1.11) and 0.93% (0.90 to 0.95), respectively, in the study population during the study period. Neighborhood deprivation was associated with both incidence and mortality of lung cancer in patients with type 2 diabetes independently of the individual-level characteristics. In the fully adjusted models, comparing high- with low-deprivation neighborhoods, the HRs for lung cancer incidence were 1.21 (1.10 to 1.33) in men and 1.08 (0.95 to 1.21) in women. The corresponding HRs for lung cancer mortality were 1.04 (1.00 to 1.07) in men and 0.97 (0.94 to 1.00) in women. Competing risk analyses including cardiovascular mortality attenuated the results.

Conclusion
In this large cohort of individuals with type 2 diabetes, we found higher lung cancer incidence and mortality in patients living in areas with high neighborhood deprivation, even after adjusting for individual-level characteristics. These findings may help develop a more contextual approach that includes the neighborhood environment when allocating resources for disease prevention and care in patients with type 2 diabetes. These findings could also help inform clinical care for patients with type 2 diabetes, particularly those living in deprived neighborhoods.
A scoping review protocol on diagnostic strategies to detect occult malignancies in individuals with ischemic stroke
Authors: Leentjens Jenneke , Chornenki Nicholas L. J. , Spiegelenberg Janneke , Ly Valentina , Dowlatshahi Dariush , Siegal Deborah M. 
Published: July 2023

Background
Emerging data show an increased risk of ischemic stroke in patients with a new diagnosis of cancer. As the risk of stroke begins to increase 150 days before cancer is diagnosed, stroke may be the first clinical manifestation of undiagnosed cancer. About 6% of patients with cryptogenic ischemic stroke (unknown etiology after diagnostic evaluations) are diagnosed with cancer within one year. However, the optimal cancer screening strategy in this population is not known. We aim to conduct a scoping review of screening strategies for occult cancer in individuals with ischemic stroke.

Methods
Electronic databases including MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCOhost) and Scopus will be systematically searched to identify articles that report on screening strategies for occult cancer in individuals with ischemic stroke. At least two investigators will independently perform two-stage study selection consisting of title/abstract screening and full-text review, followed by data extraction. Thereafter, a thematic analysis will be conducted to provide an overview of what diagnostic tests/strategies have been used, and their clinical utility in terms of positive and negative predictive value (when available).

Conclusion
We anticipate that the findings of this scoping review will identify strategies used to detect occult cancer in individuals with ischemic stroke and summarize their clinical utility (if reported). Addressing this knowledge gap will help guide the development of future clinical trials on occult cancer screening patients with ischemic stroke.