bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug reintroduction testing and beta-lactam hypersensitivity in children: Protocols and results, a 12-year experience
Authors: Daghfous Hafaoua , Moussa Chirine , Ben Mansour Amani , Slim Azza , Ben Saad Soumaya , Tritar Fatma 
Published: October 2023

Introduction: Oral provocation test (OPT) to beta-lactam antibiotics (BL) is a gold standard in allergology investigation. We aimed to demonstrate the contribution of OPT in BL hypersensitivity (HS) indicated as a first step in diagnosis. Methods: We conducted a retrospective study from 2007 to 2019, in a single Tunisian tertiary care academic center. It concerned children with presumed non-severe allergic manifestations to BL, with a reaction that has occurred at least 6 months before the OPT. Results: We identified 35 children for inclusion. After the first OPT, a second OPT with a different BL was performed in case of a positive result of the first one. In 12 cases (34.2%), the OPT elicited a reaction. In eight cases the allergy was to penicillin and in two cases to cephalosporins (cefixim). Cross-reactivity was noted in two cases. Conclusion: An OPT to BL indicated in the first instance in non-severe reaction in children will allow a rapid diagnosis in case of suspicion of HS to BL.
The Preoperative Lymphocyte-To-Monocyte Ratio Predicts Mortality Among Patients Undergoing Endovascular Aortic Repair for Abdominal Aortic Aneurysm
Authors: Nishibe Toshiya , Kano Masaki , Akiyama Shinobu , Koizumi Jun , Dardik Alan 
Published: October 2023

Purpose The purpose of this study was to investigate the preoperative lymphocyte-to-monocyte ratio (LMR) as a potential surrogate biomarker predictive of overall mortality in patients undergoing endovascular aortic repair (EVAR) for abdominal aortic aneurysm (AAA). Methods Data on patients with AAA treated by EVAR between March 2012 and December 2016 were obtained from a prospectively maintained EVAR database at Tokyo Medical University Hospital, Tokyo, Japan. The LMR was calculated by dividing the absolute lymphocyte count by the absolute monocyte count. Results One hundred seventy-six patients were included in this study after selection based on the exclusion criteria. The subjects consisted of 148 males and 28 females with a mean age of 78.5 years (range, 51-89 years). The median follow-up period was 4.98 years (range, .03-9.28). A receiver operating characteristic curve analysis determined the optimal cut-off value of the preoperative LMR for predicting overall mortality with 3.21 (area under the curve, .71; 95% confidence interval [CI], .62-.79; sensitivity, 57.4%; specificity, 77.0%; P < .001). On univariable and multivariable analyses, octogenarian (hazard ratio [HR], 1.89; 95%CI, 1.10-3.22; P = .020), poor nutritional status (HR, 2.95; 95%CI, 1.73-5.03; P < .001), chronic obstructive pulmonary disease (HR, 1.79; 95%CI, 1.06-3.03; P = .031), active cancer (HR, 2.60; 95%CI, 1.53-4.41; P < .001), and low preoperative LMR (HR, 2.56; 95%CI, 1.53-4.30; P < .001) were identified as independent predictors for overall mortality. Conclusion This study showed that a low preoperative LMR (<3.21) is an independent predictor of overall mortality after EVAR for AAA. The LMR may help in decision-making regarding the prediction of poor prognosis after EVAR.
Baseline measures for women with mesh complications accessing a pain service (as part of the London Complex Mesh Centre)
Authors: Thillainathan Anish , Cambitizi Julia , Tidman Victoria , Petersen Katrine , Tavakkoli Moein , Baranowski Andrew Paul 
Published: October 2023

Introduction Pelvic mesh was first used for stress urinary incontinence in 1998 following which its usage rapidly expanded to include treatment of pelvic organ prolapse. Numerous complications relating to mesh insertion soon became apparent, culminating in the Independent Medicines and Medical Devices Safety: First Do No Harm Report published by Baroness Cumberlege in 2020. Following this report, the UCLH London Complex Mesh Centre funded by NHS England, was one of a small number of specialist centres set up for mesh-injured women. The Pelvic Pain service of the Pain Management Centre at UCLH provides a service for patients attending the London Complex Mesh Centre. The aim of our study was to distinguish the differing needs of mesh-injured women from those with chronic pelvic pain by comparing patient-reported outcome measures between these two cohorts. Methods Distribution of data was calculated using the D’Agostino–Pearson normality test. Mann–Whitney tests were used to ascertain statistical difference between the two cohorts. Ethnicity was compared between groups using Fisher’s exact test. Quantile regression models were used to assess whether differences in medians between groups remained after adjustment for age and ethnicity. Statistical significance was set at p < .05. Results Patients with mesh were significantly older than those with chronic pelvic pain and were more likely to be of white ethnicity. After adjustment for age and ethnicity, analysis revealed that bladder interference, sex interference and DAPOS A were significantly higher amongst mesh-injured women, whereas GP and hospital admissions were significantly lower. Discussion Our data shows the importance of mesh-injured women having access to pain management services with pathways of care integrated within women’s and mental health services. It is essential that these programmes include support to discuss ways of returning to sexual relationships and have models to address anxiety such as graded exposure and psychological input.
Trends Over Time in the Use, Carbon Footprint and Costs of Facet Joint Injections and Medial Branch Blocks to Manage Lumbar Pain in England: Retrospective Analysis of an Administrative Dataset
Authors: Ojelade Elizabeth , Koris Jacob , Van-Hove Maria , Gray William K. , Briggs Tim W. R. , Hutton Mike 
Published: October 2023

Study Design Retrospective analysis of an administrative dataset. Objective This study aims to investigate changing practice over a six-year period in the use of repeated lumbar facet joint injections/medial branch blocks in England. Methods Patient data were extracted from the Hospital Episodes Statistics database for the period 1st April 2015 to 31st March 2021 for the index lumbar injection and for repeat lumbar injections performed within one year of the first. The exposure of interest was two injections within 180 days or three within one year. Patients aged <17 years and where the body site was listed as cervical, thoracic or sacral were excluded. Results Data were available for 134,249 patients of which, 8,922 (6.6%) had either two injections within 180 days or three injections within one year. First injections fell from 42,511 in 2015/16 to 13,368 in 2019/20 as did the number of repeat injections: 4,018 to 424 for the same period. If all years had the same carbon footprint as 2019/20, 2.8 kilotons of CO2e would have been saved over the five years, enough to power 2,575 average UK homes for 1 year. The financial cost of injections decreased from £27.6 million in 2015/16 to £7.9 million in 2019/20. Conclusions The number of patients having repeated lumbar injections has decreased over time but has not been eliminated. More work is needed to educate patients and clinicians regarding alternative and more effective treatments.
Association of Systemic Hormonal Contraceptives With Reconstruction Procedures for Patellar Instability
Authors: Martinazzi Brandon J. , Bertha Nicholas , Nam Hannah H. , Lorenz F. Jeffrey , Bonaddio Vincenzo , Ptasinski Anna , Gallo Robert A. 
Published: October 2023

Background: Previous research suggests that estrogen plays a role in increased ligamentous laxity observed within the female population. Whereas many studies have sought to evaluate the impact of exogenous estrogen on anterior cruciate ligament injuries, research has not yet explored its impact on the medial patellofemoral ligament. Furthermore, less is known about the role of exogenous progesterone on ligamentous structures. Purpose: To determine whether women prescribed systemic estrogen (ethinyl estradiol) or progesterone (norgestimate or etonogestrel) hormonal contraceptives had an increased risk of undergoing reconstruction surgery for patellar instability compared with women without a prescription for systemic hormonal contraceptives. Study Design: Cross-sectional study; Level of evidence, 3. Methods: The TriNetX Research Network database was queried using International Classification of Disease and Common Procedural Terminology codes for women aged 15 to 26 years who underwent reconstruction procedures for patellar instability between 2012 and 2022. Women were grouped according to whether they had a coded prescription for a systemic hormonal contraceptive containing either ethinyl estradiol or etonogestrel; controls were matched by age, sex, race, and ethnicity. The relative risk (RR) of undergoing reconstruction for patellar instability was determined for each contraceptive. Results: After 1-to-1 propensity score matching, 0.054% (525/980,878) of women prescribed a systemic contraceptive containing ethinyl estradiol underwent reconstruction procedures for patellar instability compared with 0.043% (417/980,878) of controls (RR, 1.3; 95% CI, 1.1-1.4; P = .0004). Likewise, 0.058% (67/116,260) of women prescribed a form of systemic contraceptive containing only etonogestrel underwent reconstruction procedures for patellar instability compared with 0.026% (30/116,260) of controls (RR, 2.2; 95% CI, 1.5-3.4; P = .0002). Conclusion: Female patients prescribed systemic contraceptives containing estrogen or progesterone had an increased rate of reconstruction procedures for patellar instability.
Incidence of Craniofacial Trauma Changes With the Seasons
Authors: Wilkins Sarah G. , Shah Hemali P. , Bourdillon Alexandra T. , Salehi Parsa P. , Steren Benjamin , Sawan Tareq , Torabi Sina J. , Lee Yan Ho 
Published: October 2023

Objective: Craniofacial fractures are commonly attributed to exposures that may vary with seasons. While it is commonly thought that summer months tend to have more craniofacial trauma, exact seasonality of such traumas across anatomic sites have not yet been elucidated. We aimed to characterize trends of craniofacial trauma across seasons. Study Design: Retrospective medical record review. Setting: Single-institution study at Level 1 trauma center. Methods: Patient and admission data for craniofacial trauma from June 2013 to June 2019 were systematically extracted by the hospital analyst team using International Classification of Diseases, 10th edition (ICD-10) diagnosis codes. For each ICD-10 diagnosis, anatomic sites affected by trauma were categorized. Trends across seasons and injury site were investigated using Student’s t-test and analysis of variance (ANOVA). Results: Across 925 admissions that met inclusion criteria, the volume of admissions did not significantly differ by season (ANOVA: P = .33). Frequency of admissions for jaw and maxilla fractures was significantly lower in the winter compared to summer (jaw: P = .024; maxilla: P = .018). Number of admissions involving zygoma fractures was lower in the winter compared to summer ( P = .044) and compared to fall ( P = .028). When examining number of fracture sites (eg, 1, 2, or ≥3) for each admission, there was a significantly greater number of admissions with ≥3 fracture sites during summer compared to winter ( P = .017) and fall compared to winter ( P = .011). Conclusion: Rates of craniofacial trauma admissions appear to follow seasonal trends, with significantly fewer craniofacial trauma presentations during winter when compared to summer, especially among non-occipital injuries. These findings, along with future efforts to elucidate seasonal trends nationally, may enable forecasting patterns of fractures to better guide resource allocation and inform prevention strategies.
Genome editing of patient-derived iPSCs identifies a deep intronic variant causing aberrant splicing in hemophilia A
Authors: Hiramoto Takafumi , Inaba Hiroshi , Baatartsogt Nemekhbayar , Kashiwakura Yuji , Hayakawa Morisada , Kamoshita Nobuhiko , Nishimasu Hiroshi , Nureki Osamu , Kinai Ei , Ohmori Tsukasa 
Published: October 2023

Abstract
The importance of genetic diagnosis for patients with hemophilia has been recently demonstrated. However, the pathological variant cannot be identified in some patients. Here, we aimed to identify the pathogenic intronic variant causing hemophilia A using induced pluripotent stem cells (iPSCs) from patients and genome editing. We analyzed siblings with moderate hemophilia A and without abnormalities in the F8 exon. Next-generation sequencing of the entire F8 revealed 23 common intron variants. Variant effect predictor software indicated that the deep intronic variant at c.5220-8563A&gt;G (intron 14) might act as a splicing acceptor. We developed iPSCs from patients and used genome editing to insert the elongation factor 1α promoter to express F8 messenger RNA (mRNA). Then, we confirmed the existence of abnormal F8 mRNA derived from aberrant splicing, resulting in a premature terminal codon as well as a significant reduction in F8 mRNA in iPSCs due to nonsense-mediated RNA decay. Gene repair by genome editing recovered whole F8 mRNA expression. Introduction of the intron variant into human B-domain–deleted F8 complementary DNA suppressed factor VIII (FVIII) activity and produced abnormal FVIII lacking the light chain in HEK293 cells. Furthermore, genome editing of the intron variant restored FVIII production. In summary, we have directly proven that the deep intronic variant in F8 results in aberrant splicing, leading to abnormal mRNA and nonsense-mediated RNA decay. Additionally, genome editing targeting the variant restored F8 mRNA and FVIII production. Our approach could be useful not only for identifying causal variants but also for verifying the therapeutic effect of personalized genome editing.
Evaluating the prevalence of inborn errors of immunity in adults with chronic immune thrombocytopenia or Evans syndrome
Authors: Jiang Debbie , Rosenlind Kira , Baxter Sarah , Gernsheimer Terry , Gulsuner Suleyman , Allenspach Eric J. , Keel Siobán B. 
Published: October 2023

Abstract
Inborn errors of immunity (IEIs) are monogenic disorders that predispose patients to immune dysregulation, autoimmunity, and infection. Autoimmune cytopenias, such as immune thrombocytopenia (ITP) and Evans syndrome (a combination of ITP and autoimmune hemolytic anemia), are increasingly recognized phenotypes of IEI. Although recent findings suggest that IEIs may commonly underlie pediatric ITP and Evans syndrome, its prevalence in adult patients with these disorders remains undefined. This study sought to estimate the prevalence of underlying IEIs among adults with persistent or chronic ITP or Evans syndrome using a next-generation sequencing panel encompassing &gt;370 genes implicated in IEIs. Forty-four subjects were enrolled from an outpatient adult hematology clinic at a tertiary referral center in the United States, with a median age of 49 years (range, 20-83). Fourteen subjects (31.8%) had secondary ITP, including 8 (18.2%) with Evans syndrome. No cases of IEI were identified despite a high representation of subjects with a personal history of autoimmunity (45.5%) and early onset of disease (median age at diagnosis of 40 years [range, 2-77]), including 20.5% who were initially diagnosed as children. Eight subjects (18.2%) were found to be carriers of pathogenic IEI variants, which, in their heterozygous state, are not disease-causing. One case of TUBB1-related congenital thrombocytopenia was identified. Although systematic screening for IEI has been proposed for pediatric patients with Evans syndrome, findings from this real-world study suggest that inclusion of genetic testing for IEI in the routine work-up of adults with ITP and Evans syndrome has a low diagnostic yield.
Laboratory scale evaluation of the feasibility of locally found bladderworts as biological agents to control dengue vector, Aedes aegypti in Sri Lanka
Authors: Gunathilaka Nayana , Perera Ravina , Amerasinghe Deepika , Udayanga Lahiru 
Published: October 2023

Abstract
Background
The carnivorous genus Utricularia also includes aquatic species that have the potential to trap a wide range of prey, leading its death due to anoxia. However, the effectiveness of such an approach with carnivorous plants for vector control has not been evaluated in Sri Lanka.

Methods
Early instar (i & ii) and late instar (iii & iv) larvae of Aedes aegypti were exposed to locally found bladderwort (U. aurea Lour and Utricularia sp.). The experimental design was set with 10 larvae (both early and late instars separately) in 250 mL of water with bladderworts containing approximately 100 bladders in plant segments of both species, separately. Each treatment and control were repeated 50 times. The survival status of larvae was recorded daily until death or adult emergence. The larvae found whole or partially inside the bladders were attributed to direct predation. The Cox-regression model and Mantel-Cox log rank test were carried out to assess the survival probabilities of larvae in the presence of two bladderworts separately.

Results
The highest predation was observed when using early instar larvae in both U. aurea (97.8%) and Utricularia sp. (83.8%). The mortality caused due to predation by U. aurea was observed to be significantly higher according to the Mantel-Cox log-rank test (HR = 60.71, CI; 5.69–999.25, P = 0.004). The mortality rates of late instar stages of Ae. aegypti were observed to be lower in both U. aurea (82.6%) and Utricularia sp. (74.8%). Overall, the highest predation efficacy was detected from U. aurea (HR = 45.02; CI: 5.96–850.51, P = 0.017) even in late instar stages. The results suggested the cumulative predation in both plants on Ae. aegypti larvae was > 72%.

Conclusions
Utricularia aurea is a competent predator of Ae. aegypti larvae. Further, it is recommended to evaluate the feasibility of this plant to be used in the field as a control intervention in integrated vector management programmes.
Structural and functional implications of SLC13A3 and SLC9A6 mutations: an in silico approach to understanding intellectual disability
Authors: Hussain Syeda Iqra , Muhammad Nazif , Shah Salah Ud Din , Fardous Fardous , Khan Sher Alam , Khan Niamatullah , Rehman Adil U , Siddique Mehwish , Wasan Shoukat Ali , Niaz Rooh , Ullah Hafiz , Khan Niamat , Muhammad Noor , Mirza Muhammad Usman , Wasif Naveed , Khan Saadullah 
Published: October 2023

Abstract
Background
Intellectual disability (ID) is a condition that varies widely in both its clinical presentation and its genetic underpinnings. It significantly impacts patients’ learning capacities and lowers their IQ below 70. The solute carrier (SLC) family is the most abundant class of transmembrane transporters and is responsible for the translocation of various substances across cell membranes, including nutrients, ions, metabolites, and medicines. The SLC13A3 gene encodes a plasma membrane-localized Na+/dicarboxylate cotransporter 3 (NaDC3) primarily expressed in the kidney, astrocytes, and the choroid plexus. In addition to three Na + ions, it brings four to six carbon dicarboxylates into the cytosol. Recently, it was discovered that patients with acute reversible leukoencephalopathy and a-ketoglutarate accumulation (ARLIAK) carry pathogenic mutations in the SLC13A3 gene, and the X-linked neurodevelopmental condition Christianson Syndrome is caused by mutations in the SLC9A6 gene, which encodes the recycling endosomal alkali cation/proton exchanger NHE6, also called sodium-hydrogen exchanger-6. As a result, there are severe impairments in the patient’s mental capacity, physical skills, and adaptive behavior.

Methods and results
Two Pakistani families (A and B) with autosomal recessive and X-linked intellectual disorders were clinically evaluated, and two novel disease-causing variants in the SLC13A3 gene (NM 022829.5) and the SLC9A6 gene (NM 001042537.2) were identified using whole exome sequencing. Family-A segregated a novel homozygous missense variant (c.1478 C > T; p. Pro493Leu) in the exon-11 of the SLC13A3 gene. At the same time, family-B segregated a novel missense variant (c.1342G > A; p.Gly448Arg) in the exon-10 of the SLC9A6 gene. By integrating computational approaches, our findings provided insights into the molecular mechanisms underlying the development of ID in individuals with SLC13A3 and SLC9A6 mutations.

Conclusion
We have utilized in-silico tools in the current study to examine the deleterious effects of the identified variants, which carry the potential to understand the genotype-phenotype relationships in neurodevelopmental disorders.
Investigating associations between maternal stress, smoking and adverse birth outcomes: evidence from the All Our Families cohort
Authors: Yamamoto Shelby S. , Premji Shahirose S. , Saini Vineet , McDonald Sheila W. , Jhangri Gian S. 
Published: October 2023

Abstract
Background
Independently, active maternal and environmental tobacco smoke exposure and maternal stress have been linked to an increased risk of preterm birth and low birth weight. An understudied relationship is the potential for interactive effects between these risk factors.

Methods
Data was obtained from the All Our Families cohort, a study of 3,388 pregnant women < 25 weeks gestation recruited from those receiving prenatal care in Calgary, Canada between May 2008 and December 2010. We investigated the joint effects of active maternal smoking, total smoke exposure (active maternal smoking plus environmental tobacco smoke) and prenatal stress (Perceived Stress Scale, Spielberger State-Trait Anxiety Inventory), measured at two time points (< 25 weeks and 34–36 weeks gestation), on preterm birth and low birth weight.

Results
A marginally significant association was observed with the interaction active maternal smoking and Spielberger State-Trait Anxiety Inventory scores in relation to low birth weight, after imputation (aOR = 1.02, 95%CI: 1.00-1.03, p = 0.06). No significant joint effects of maternal stress and either active maternal smoking or total smoke exposure with preterm birth were observed. Active maternal smoking, total smoke exposure, Perceived Stress Scores, and Spielberger State-Trait Anxiety Inventory scores were independently associated with preterm birth and/or low birth weight.

Conclusions
Findings indicate the role of independent effects of smoking and stress in terms of preterm birth and low birthweight. However, the etiology of preterm birth and low birth weight is complex and multifactorial. Further investigations of potential interactive effects may be useful in helping to identify women experiencing vulnerability and inform the development of targeted interventions.