bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mercaptopurine induced myelosuppression in a child with a NUDT15 rs116855232 homozygous variant
Authors: Gupta Navya , Magatha Latha Sneha , Jayaraman Dhaarani , Scott Julius Xavier , Antony Sharon Benita , Koshy Teena 
Published: November 2022

Introduction Mercaptopurine (6-MP) is the backbone of the consolidation and maintenance therapy for paediatric acute lymphoblastic leukaemia (ALL). Nevertheless, it can cause critical myelosuppression. Predicting adverse reactions to 6-MP often involves the investigation of pharmacogenetic variants; in particular thiopurine S-methyltransferase ( TPMT) and nudix hydrolase 15 ( NUDT15). Lately, NUDT15 variants have been shown to play a significant pharmacogenetic role in predicting 6-MP intolerance in children of Asian descent. Case Report We present a six-year-old male child of Indian origin with persistent cytopenia after treatment. This prompted targeted sequencing of the genes TPMT and NUD15. The results revealed two copies of the variant of NUD15 rs116855232, that is, NUDT15*2 genotype. Management and Outcome Since the NUDT15*2 allele classified the patient as a poor metabolizer, he was restarted on a low dose of 6-MP, which he tolerated. Discussion Individuals with the NUDT15*2allele (*2/*2 genotype) are poor metabolizers of thiopurines which results in an adverse reaction to 6-MP. About 3.5% of Indians show variations in the TPMT gene as compared to 19.4% variations observed in NUDT15, which makes the latter a more reliable disease marker.
A Current Review of the Uses of Bioelectrical Impedance Analysis and Bioelectrical Impedance Vector Analysis in Acute and Chronic Heart Failure Patients: An Under-valued Resource?
Authors: Thanapholsart Jenjiratchaya , Khan Ehsan , Lee Geraldine A. 
Published: November 2022

Background There is a need to detect and prevent fluid overload and malnutrition in heart failure. Bioelectrical impedance analysis and bioelectrical impedance vector analysis are medical instruments that can advance heart failure management by generating values of body composition and body water, assisting clinicians to detect fluid and nutritional status. However, there is a lack of evidence to summarise how they have been used among heart failure patients. Method A systematic search was conducted. Result Two hundred and four papers were screened. Forty-eight papers were reviewed, and 46 papers were included in this review. The literature shows that bioelectrical impedance analysis and bioelectrical impedance vector analysis were mostly used to assess fluid and nutritional status, together with diagnostic and prognostic values. Contraindication of using BIA and implications for practice are also demonstrated. Conclusion The findings suggest that bioelectrical impedance vector analysis is superior to bioelectrical impedance analysis when assessing hydration/nutritional status in heart failure. Assessing a patient using bioelectrical impedance analysis /bioelectrical impedance vector analysis, together with natriuretic peptide -heart failure biomarkers, increases the diagnostic accuracy of heart failure. Further studies are required to examine the cost effectiveness of using these instruments in clinical practice.
Initial Single-Center Experience With the Knickerbocker Technique During Thoracic Endovascular Aortic Repair to Block Retrograde False Lumen Flow in Patients With Type B Aortic Dissection
Authors: de Beaufort Hector Willem Livius , Vos Jan Albert , Heijmen Robin H. 
Published: November 2022

Objective: Effectiveness of thoracic endovascular aortic repair in type B aortic dissection is impaired by persistent retrograde false lumen flow via distal re-entry tears. Controlled, stentgraft-assisted balloon dilatation of the true lumen at its lower end, or Knickerbocker technique, may block retrograde false lumen flow and consequently improve effectiveness by inducing immediate thrombosis along the entire descending thoracic aorta. Materials and Methods: A single-center retrospective analysis was performed for all consecutive patients with aortic dissection treated with the Knickerbocker technique to block retrograde false lumen flow. Results: Eleven patients were included for analysis. Intraoperative control angiography showed successful occlusion of the false lumen at the level of balloon dilatation in 9 out of 11 patients (82%). There was one perioperative mortality (9%), due to stroke. There were 2 early reinterventions, due to retroperitoneal bleeding and due to chyle leakage in the neck after left subclavian artery bypass. Median clinical follow-up duration was 6 (interquartile range [IQR] 2–11] months. There were 2 deaths during follow-up, one at 2 months after TEVAR from unknown cause of death, and one after 11 months due to rupture of an ascending aortic pseudoaneurysm. The Knickerbocker technique led to positive aortic remodeling. At 3 months follow-up, 100% of patients showed complete false lumen thrombosis in the thoracic aorta proximal to the level of balloon dilatation, with decreasing false lumen diameters (100%) and stable (44%) or decreasing (56%) total aortic diameters. In most patients, the false lumen distal to the stentgraft (i.e. at visceral level) remained patent (11% false lumen thrombosis rate), leading to ≥2 mm dilatation at this level (78% of patients) and in the infrarenal abdominal aorta (56% of patients) at 3 months postoperatively. No distal stent-graft-induced new entry tears were noticed during follow-up. Conclusion: The Knickerbocker technique is feasible and effective, leading to positive aortic remodeling of the aorta covered by stentgraft in all of a small cohort of patients. Clinical Impact Persistent, retrograde false lumen perfusion from distal re-entries following thoracic endovascular aortic repair (TEVAR) for Stanford type B aortic dissection, may lead to progressive, aneurysmal dilatation. Controlled, stent graft-assisted balloon dilatation of the true lumen in the distal descending aorta (i.e. Knickerbocker technique) during TEVAR effectively excludes the false lumen from persistent flow resulting in positive aortic remodeling in our small cohort of patients, and hence potentially eliminates the risk of late post-dissection aneurysm formation in the descending thoracic aorta.
Outcomes of Endoscopic Treatment for Plantar Fasciitis: A Systematic Review
Authors: Ward Leona , Mercer Nathaniel P. , Azam Mohammad T. , Hoberman Alexander , Hurley Eoghan T. , Butler James J. , Ubillus Hugo , Cronin Joseph , Kennedy John G. 
Published: November 2022

Background Endoscopic plantar fascia release (EPFR) is an established operative treatment for recalcitrant plantar fasciitis. The purpose of this systematic review is to provide a comprehensive review on the outcomes of EPFR in the treatment of plantar fasciitis at mid-term and long-term follow-up. Methods A systematic review was performed using, MEDLINE, EMBASE, and Cochrane library databases in May 2020 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies included were evaluated regarding level of evidence (LOE) and quality of evidence (QOE) using the modified Coleman methodological score. Clinical outcomes and complications were also evaluated. Results Twenty-six studies including 978 feet were included in this systematic review with a weighted mean follow-up of 25.6 ± 21.0 months. Eighteen papers used the American Orthopaedic Foot and Ankle Society (AOFAS) score. The weighted mean preoperative AOFAS score was 55.66 ± 10.3, and the postoperative score was 89.6 ± 5.2 out of 100. The total number of patients who had complications was 88 of 994 (8.9%). The most common complication was recurrence of pain experienced by 41 patients (4.2%). Conclusion Endoscopic plantar fascia release provides good clinical and functional outcomes in patients with refractory plantar fasciitis. However, this procedure is associated with a moderately high complication rate (8.9%) and should only be considered following failure of conservative management. Future prospective studies comparing the various endoscopic and open techniques with nonoperative treatment are required to elucidate the most effective management for recalcitrant plantar fasciitis. Levels of Evidence: Level I: Systematic review of level IV studies
Analysis of CRSsNP Proteome Using a Highly Multiplexed Approach in Nasal Mucus
Authors: Pesold Vanessa-Vivien , Wendler Olaf , Morgenthaler Lisa , Gröhn Franziska , Mueller Sarina K. 
Published: November 2022

Background Chronic rhinosinusitis without nasal polyps (CRSsNP) represents a phenotype of CRS, whose immunological mechanisms are still unclear. So far there are neither suitable biomarkers to determine the course of the disease nor an individual therapy. Objective The purpose of this study was to characterize the CRSsNP endotype by identifying and validating non-invasive proteomic biomarkers. Methods A highly-multiplexed proteomic array consisting of antibodies against 2000 proteins was used to identify proteins that are differentially expressed in the nasal mucus of the CRSsNP and control groups (n = 7 per group). The proteins identified to be most differentially expressed were validated in matched nasal mucus samples using western blots and enzyme-linked immunosorbent assay (ELISA). Validation was also done in a second cohort using western blots (CRSsNP n = 25, control n = 23) and ELISA (n = 30 per group). Additionally, immunohistochemistry in CRSsNP and control tissue samples was performed to characterize the selected proteins further. Results Out of the 2000 proteins examined, 7 from the most differentially expressed proteins were chosen to be validated. The validation results showed that 4 proteins were significantly upregulated in CRSsNP mucus, including macrophage inflammatory protein-1beta (MIP-1β), resistin, high mobility group box 1 (HMGB1), and forkhead box protein 3 (FOXP3). Cartilage acidic protein 1 (CRTAC1) was not significantly upregulated. Two proteins were significantly downregulated including scavenger receptor class F member 2 (SCARF2) and P-selectin. All proteins selected are mainly associated with inflammation, cell proliferation/differentiation, apoptosis and cell–cell or cell–matrix interaction. Conclusion Proteomic analysis of CRSsNP and control mucus has confirmed known and revealed novel disease-associated proteins that could potentially serve as a new biosignature for CRSsNP. Analysis of the associated pathways will specify endotypes of CRSsNP and will lead to an improved understanding of the pathophysiology of CRSsNP. Furthermore, our data contribute to the development of a reproducible, non-invasive, and quantitative “liquid biopsy” for rhinosinusitis.
The Incidence, Characteristics and Outcomes of Vertebral Artery Injury Associated with Cervical Spine Trauma: A Systematic Review
Authors: Temperley Hugo C. , McDonnell Jake M. , O’Sullivan Niall J. , Waters Caitlin , Cunniffe Gráinne , Darwish Stacey , Butler Joseph S. 
Published: November 2022

Study design Systematic Review Objectives Vertebral Artery Injury (VAI) is a potentially serious complication of cervical spine fractures. As many patients can be asymptomatic at the time of injury, the identification and diagnosis of VAI can often prove difficult. Due to the high rates of morbidity and mortality associated with VAI, high clinical suspicion is paramount. The purpose of this review is to elucidate incidence, diagnosis, treatment and outcomes of VAI associated with cervical spine injuries. Methods A systematic search of electronic databases was performed using ‘PUBMED’, ‘EMBASE’,‘Medline (OVID)’, and ‘Web of Science, for articles pertaining to traumatic cervical fractures with associated VAI. Results 24 studies were included in this systematic review. Data was included from 48 744 patients. In regards to the demographics of the focus groups that highlighted information on VAI, the mean average age was 46.6 (32.1-62.6). 75.1% (169/225) were male and 24.9% (56/225) were female. Overall incidence of VAI was 596/11 479 (5.19%). 190/420 (45.2%) of patients with VAI had fractures involving the transverse foramina. The right vertebral artery was the most commonly injured 114/234 (48.7%). V3 was the most common section injured (16/36 (44.4%)). Grade I was the most common (103/218 (47.2%)) injury noted. Collective acute hospital mortality rate was 32/226 (14.2%), ranging from 0-26.2% across studies. Conclusion VAI secondary to cervical spine trauma has a notable incidence and high associated mortality rates. The current available literature is limited by a low quality of evidence. In order to optimise diagnostic protocols and treatment strategies, in addition to reducing mortality rates associated with VAI, robust quantitative and qualitative studies are needed.
The long-term effects of insulin use in incident cystic fibrosis-related diabetes: a target trial emulated using longitudinal national registry data
Authors: Granger Emily , Keogh Ruth H. , Frost Freddy 
Published: November 2022

IntroductionCystic fibrosis-related diabetes (CFRD) is a common complication of cystic fibrosis and is associated with deleterious clinical outcomes. Insulin is recommended as a treatment by international guidelines. However, there are scarce clinical trial data to support the use of insulin, and little is known about the long-term outcomes of treatment. The aim of this study was to compare the long-term impacts of insulin useversusnon-use in CFRD.MethodsWe used data from the national UK Cystic Fibrosis Registry and adopted a target trial framework. Eligible individuals included those 12 years and older with a new diagnosis of CFRD. Outcomes were change in % predicted forced expiratory volume in 1 s (FEV1%) and body mass index z-scores (BMI) over a 5-year follow-up period. Treatment strategies were to receive insulin or not for the duration of follow-up. Treatment effect estimates were obtained using two methods to control for confounding: inverse-probability-of-treatment weighted estimation of marginal structural models and the G-formula.ResultsWe identified 1613 individuals diagnosed with CFRD between 2008 and 2016 and included 1196 and 1192 in the FEV1% and BMI outcome analyses respectively. We found no evidence of an effect of insulin on FEV1% over the 5-year study period. Similarly, we found no overall effect of insulin on BMI; however, there was some evidence for a positive treatment effect in patients with lower baseline BMI.ConclusionUsing well-established national registry data, we found no evidence of long-term treatment effects for insulin on FEV1% or BMI in people with incident CFRD.
Proposal for a tiered approach to evaluate the risk of transformation products formed from pesticide residues during drinking water treatment
Authors: Michel Amandine , Armbruster Dominic , Benz-Birck Angelika , Deppermann Nina , Doetzer Reinhard , Flörs Markus , Frericks Markus , Li Shanghua , Gebler Sebastian , Schröder Tom , Seitz Wolfram 
Published: November 2022

AbstractOxidative treatment methods are valuable tools for the microbial safety of drinking water. However, the reaction of oxidants with natural substances or anthropogenic contaminants present in the raw water can potentially lead to the formation of harmful transformation products (TPs). The present paper proposes a tiered approach for the risk evaluation of TPs formed from pesticide residues during drinking water treatment. First, the concentrations of pesticide residues in raw water used for drinking water production are evaluated (step 1). Substances with a predicted concentration in raw water above 0.1 µg/L proceed further to a reactivity assessment, examining the behavior in water treatment plants (step 2). Using information available in the scientific literature, prediction of structural elements in the TPs can be made and allow a worst-case assessment based on the Threshold of Toxicological Concern (TTC) (step 3). If concerns remain, experiments may be conducted to simulate water treatment (step 4). Because of their complexity and variability, experiments for the simulation of water treatment should focus on prioritized substances of potential concern. The test conditions should be realistic (i.e., close to EU-representative conditions in waterworks) and ozonation and chlorination should be combined with pre- and post-treatment steps, as is normally the case in European waterworks. As a first screening option, we propose to test the toxicity of the reaction mixture. If the treated water shows an enhanced toxicity, further experiments can be conducted to identify and quantify the major TPs (step 5). We propose to define major TPs as substances present at more than 10% of the initially applied test substance. For major TPs, a tiered dietary risk assessment is conducted, starting with the TTC concept, and continuing with toxicity testing of the TP, according to EFSA and ECHA and internationally agreed guidance.
Patient Clinical Outcomes in Standalone Versus a Combined Ophthalmology-rheumatology Uveitis Clinic
Authors: Ross Bing X. , Habhab Samantha , Syeda Sarah , Baiyasi Ahmad , Benchaala Ilyes , Okeagu Chinwenwa , Barbosa Joshua , Im Jacob , Le Kim , Lin Xihui 
Published: November 2022

Abstract
Background
To evaluate uveitis care outcomes in standalone versus a combined ophthalmology-rheumatology clinic.

Methods
Participants were patients aged 18 years and older with a minimum 12-month history of chronic uveitis prior to being referred to the combined uveitis clinic at Kresge Eye Institute and who were treated in the combined clinic for at least 6 months. Best corrected visual acuity (BCVA), objective markers of inflammation, and achieving targeted dose of immunomodulatory therapy (IMT) were compared in the cohort of uveitis patients 6 months prior to and after the initial evaluation in the combined clinic.

Results
Sixty-six percent of study participants were female with a mean age of 51.5 years. BCVA improved from 0.58 logMAR (Snellen: ~20/74) at the initial combined clinic visit to 0.50 logMAR (Snellen: ~20/63) 6 months after the first combined visit (p = 0.0137). The establishment of the combined uveitis clinic led to higher frequency of patients at target dose of IMT: an increase from 49.0% at 6 months prior to the combined visit to 70.1.4% and 79.8% at the initial combined visit and 6 months after the combined visit, respectively.

Conclusion
A combined model of management for chronic uveitis patients wherein rheumatological services are coupled with ophthalmic care leads to improvement in patient clinical outcomes and achieving target therapy.
Unveiling a hotspot of genetic diversity in southern Italy for the endangered Hermann’s tortoise Testudo hermanni
Authors: Chiocchio Andrea , Zampiglia Mauro , Biaggini Marta , Biello Roberto , Di Tizio Luciano , Leonetti Francesco Luigi , Olivieri Oliviero , Sperone Emilio , Trabalza-Marinucci Massimo , Corti Claudia , Canestrelli Daniele 
Published: November 2022

Abstract
Background
Hotspots of intraspecific genetic diversity represent invaluable resources for species to cope with environmental changes, and their identification is increasingly recognized as a major goal of conservation ecology research. However, even for iconic and endangered species, conservation strategies are often planned without thorough information on the geographic patterns of genetic variation. Here, we investigated the spatial patterns of genetic variation of the endangered Hermann’s tortoise Testudo hermanni in the Italian Peninsula by genotyping 174 individuals at 7 microsatellite loci, with the aim to contribute to planning effective conservation strategies.

Results
Ordination-based and Bayesian clustering analyses consistently identified three main genetic clusters, one spread in the central and northern part of the peninsula, and two restricted to southern Italy and Sicily, respectively. The highest levels of genetic diversity were found in populations of the southern cluster and, in particular, at the northern edges of its distribution (He > 0.6, Ar > 2.8 ), that correspond to areas of putative secondary contact and admixture between distinct lineages. Our results clearly identify a hotspot of genetic diversity for the Hermann’s tortoise in southern Italy.

Conclusion
We inferred the evolutionary history and the spatial patterns of genetic variation of the Hermann’s tortoise in the Italian Peninsula. We identified three main genetic clusters along the peninsula and a hotspot of intraspecific diversity in southern Italy. Our results underline the urgent need for conservation actions to warrant the long-term persistence of viable tortoise populations in this area. Furthrmore, these data add further evidence to the role of southern Italy as a biodiversity hotspot for temperate fauna, claiming for higher consideration of this area in large scale conservation programs.
Prevalence of Hepatitis B Virus infection in the Gulf Cooperation Council: a systematic review and meta-analysis
Authors: Alali Ali A. , Abo-Shehada Mahmoud N. 
Published: November 2022

AbstractBackgroundHepatitis B virus (HBV) infection is a global public-health problem. Since the introduction of an effective vaccine, the epidemiology of HBV infection is changing. We aimed to estimate the prevalence of HBV infection in the Gulf Cooperation Council (GCC) region and delineate any variation in member-countries, special sub-groups, and over time.MethodsThis is a systematic review and meta-analysis to review studies of HBV prevalence in the GCC region. Databases were searched and all studies from inception to July 31st, 2021, were considered for inclusion. The pooled HBV prevalence was analyzed using the random-effect model after assessment for heterogeneity. True prevalence was adjusted using the Rogan-Gladen estimator. Pre-defined subgroup analysis was performed, and publication bias was assessed.ResultsOverall, 99 studies (n = 1,944,200 participants) met the inclusion criteria. The overall HBV apparent prevalence was 3.05% (95% CI 2.60, 3.52) and the true prevalence was 1.67% (95% CI 1.66, 1.68). The apparent prevalence varied between subgroups. Over time, the apparent prevalence of HBV infection has declined from 9.38% (95% CI 7.26, 11.74) before 1990 to 1.56% (95% CI 1.07, 2.12) during the period 2010 to 2020.ConclusionOver the last four decades the overall prevalence of HBV infection in the GCC region has decreased from high- to low-endemicity level. However, due to poor methodology of the included studies, further high-quality community-based studies are needed to obtain more precise estimate of HBV infection in this region.
Visual outcomes of epiretinal membrane removal after diffractive-type multifocal intraocular lens implantation
Authors: Kim Hyungil , Jeon Sohee 
Published: November 2022

Abstract
Background
To assess visual outcomes of epiretinal membrane (ERM) removal in multifocal intraocular lens (MIOL)-implanted eyes, according to ERM stage.

Methods
Retrospective chart reviews were undertaken in patients with diffractive-type MIOL implants, each undergoing pars plana vitrectomy and ERM removal between February 2018 and November 2020 at Gyeongju St. Mary's Eye Clinic and KEYE Eye Center. Assessments focused on monocular uncorrected and corrected values of distant visual acuity (UDVA and CDVA) and uncorrected near visual acuity (UNVA) at postoperative 12 months according to the stage of ERM.

Results
The present study included a total of 49 MIOL-implanted eyes from 49 enrollees, 25 undergoing pars plana vitrectomy for ERM removal (11 eyes with Stage 2 and 14 eyes with Stage 3), and 24 acting as age-matched controls. There was a significant difference in UDVA and UNVA between control and Stage 3 ERM (UDVA; 0.01 ± 0.04 for control, and 0.07 ± 0.08 for stage 3 ERM, p = 0.035, UNVA; 0.03 ± 0.05 for control, and 0.13 ± 0.16 for Stage 3 ERM, p = 0.029). There were no significant differences in CDVA between groups (p = 0.121, ANOVA test).

Conclusions
Eyes with Stage 3 ERM did not achieve visual acuity comparable to control eyes, suggesting the necessity of an early intervention for ERM in eyes with diffractive type MIOL. A meticulous preoperative retinal evaluation for ERM development is mandatory when planning diffractive-type MIOL implantation.