bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recommendations for the collection and annotation of biosamples for analysis of biomarkers in neurofibromatosis and schwannomatosis clinical trials
Authors: Sundby R Taylor , Rhodes Steven D , Komlodi-Pasztor Edina , Sarnoff Herb , Grasso Vito , Upadhyaya Meena , Kim AeRang , Evans D Gareth , Blakeley Jaishri O , Hanemann C Oliver , Bettegowda Chetan 
Published: October 2023

Introduction Neurofibromatosis 1 and schwannomatosis are characterized by potential lifelong morbidity and life-threatening complications. To date, however, diagnostic and predictive biomarkers are an unmet need in this patient population. The inclusion of biomarker discovery correlatives in neurofibromatosis 1/schwannomatosis clinical trials enables study of low-incidence disease. The implementation of a common data model would further enhance biomarker discovery by enabling effective concatenation of data from multiple studies. Methods The Response Evaluation in Neurofibromatosis and Schwannomatosis biomarker working group reviewed published data on emerging trends in neurofibromatosis 1 and schwannomatosis biomarker research and developed recommendations in a series of consensus meetings. Results Liquid biopsy has emerged as a promising assay for neurofibromatosis 1/schwannomatosis biomarker discovery and validation. In addition, we review recommendations for a range of biomarkers in clinical trials, neurofibromatosis 1/schwannomatosis–specific data annotations, and common data models for data integration. Conclusion These Response Evaluation in Neurofibromatosis and Schwannomatosis consensus guidelines are intended to provide best practices for the inclusion of biomarker studies in neurofibromatosis 1/schwannomatosis clinical trials, data, and sample annotation and to lay a framework for data harmonization and concatenation between trials.
Mapping healthy planning frameworks
Authors: De La Haye A , Jones A , van Herk S , Rofin-Serra M , Lake AA , Moore HJ 
Published: October 2023

Aims: The aim of this research was to map available healthy planning frameworks to discover the range, composition, design, and implementation of healthy planning frameworks. Methods: A systematic scoping review with date, location, and usability limitations was augmented by a grey literature search. Data were extracted on key details, design, outcomes considered, and implementation features of the final 61 frameworks. Results: Data extracted indicated that most frameworks tend to focus on one element of the built environment, with active mobility, active environments, and transport being the most prevalent ones (34%). Most frameworks (40) stated their intended outcomes on health in general terms, rather than targeting specific health outcomes. Very few frameworks (12%) were aimed at the public, and only 11% of frameworks included an evaluation. Conclusions: While there are a wide variety and number of frameworks available in the field of healthy urban planning, they are generally siloed, focusing on highly specific individual urban determinants, and rarely consider health outcomes in detail. There is significantly less provision available for citizen and community use. Frameworks tend to offer limited updating mechanisms and very rarely include ongoing evaluation processes, making their success difficult to assess.
Cost-effectiveness of endovascular treatment versus best medical management in basilar artery occlusion stroke: A U.S. healthcare perspective
Authors: Mehrens Dirk , Fabritius Matthias P , Reidler Paul , Liebig Thomas , Afat Saif , Ospel Johanna M , Fröhlich Matthias F , Schwarting Julian , Ricke Jens , Dimitriadis Konstantinos , Goyal Mayank , Kunz Wolfgang G 
Published: October 2023

Introduction: Two recent studies showed clinical benefit for endovascular treatment (EVT) in basilar artery occlusion (BAO) stroke up to 12 h (ATTENTION) and between 6 and 24 h from onset (BAOCHE). Our aim was to investigate the cost-effectiveness of EVT from a U.S. healthcare perspective. Materials and Methods: Clinical input data were available for both trials, which were analyzed separately. A decision model was built consisting of a short-run model to analyze costs and functional outcomes within 90 days after the index stroke and a long-run Markov state transition model (cycle length of 12 months) to estimate expected lifetime costs and outcomes from a healthcare and a societal perspective. Incremental cost-effectiveness ratios (ICER) were calculated, deterministic (DSA) and probabilistic (PSA) sensitivity analyses were performed. Results: EVT in addition to best medical management (BMM) resulted in additional lifetime costs of $32,063 in the ATTENTION trial and lifetime cost savings of $7690 in the BAOCHE trial (societal perspective). From a healthcare perspective, EVT led to incremental costs and effectiveness of $37,389 and 2.0 QALYs (ATTENTION) as well as $3516 and 1.9 QALYs (BAOCHE), compared to BMM alone. The ICER values were $−4052/QALY (BAOCHE) and $15,867/QALY (ATTENTION) from a societal perspective. In each trial, PSA showed EVT to be cost-effective in most calculations (99.9%) for a willingness-to-pay threshold of $100,000/QALY. Cost of EVT and age at stroke represented the greatest impact on the ICER. Discussion: From an economic standpoint with a lifetime horizon, EVT in addition to BMM is estimated to be highly effective and cost-effective in BAO stroke.
Patterns of CMV infection after letermovir withdrawal in recipients of posttransplant cyclophosphamide–based transplant
Authors: Lin Andrew , Brown Samantha , Chinapen Stephanie , Lee Yeon Joo , Seo Susan K. , Ponce Doris M. , Shahid Zainab , Giralt Sergio , Papanicolaou Genovefa A. , Perales Miguel-Angel , Shaffer Brian C. 
Published: October 2023

Abstract
Reactivation of latent cytomegalovirus (CMV) is increased in recipients of allogeneic hematopoietic cell transplantation (allo-HCT) with seropositive CMV using posttransplant cyclophosphamide (PT-Cy)–based graft-versus-host disease (GVHD) prophylaxis. Letermovir, a novel DNA terminase complex inhibitor, reduces the incidence of clinically significant CMV infection (csCMVi) in this population; however, parameters that predict csCMVi after letermovir withdrawal are not well described. Here, we examined clinical and immunological parameters in 294 recipients of PT-Cy–based allo-HCT, including 157 patients with CMV, of whom 80 completed letermovir prophylaxis without csCMVi and subsequently stopped letermovir. In this population, the median duration of letermovir exposure was 203 days (interquartile range [IQR], 160-250 days). After letermovir withdrawal, the 90-day cumulative incidence of csCMVi was 23.0% (95% confidence interval, 14.3-32.8). There were no episodes of CMV end-organ disease. Hypogammaglobulinemia before letermovir discontinuation was predictive of csCMVi (hazard ratio, 0.33; 95% confidence interval, 0.12-0.93; P = .03), whereas T-cell and B-cell reconstitution before letermovir withdrawal were not predictive of csCMVi. Higher numbers of natural killer cells were found before letermovir withdrawal in patients who experienced csCMVi (median, 202 vs 160; P = .03). In recipients with seropositive CMV, CD3+CD4–CD8+ T-cell reconstitution was faster in patients with CMV regardless of letermovir exposure. Taken together, these data suggest that csCMVi after letermovir withdrawal was frequent in patients treated with PT-Cy, despite prolonged exposure. Strategies to boost CMV-specific adaptive immunity in patients with persistent hypogammaglobulinemia is a logical pathway to reduce csCMVi after letermovir withdrawal.
Genomic architecture of resistance to latania scale (H. lataniae) in kiwifruit (A. chinensis var. chinensis)
Authors: Flay Casey , Tahir Jibran , Hilario Elena , Fraser Lena , Stannard Kate , Symonds Vaughan , Datson Paul 
Published: October 2023

Abstract
Background
Latania scale (Hemiberlesia lataniae Signoret) is an armoured scale insect known to cause damage to kiwifruit plants and fruit, which ultimately reduces crop values and creates post-harvest export and quarantine issues. Resistance to H. lataniae does exist in some commercial cultivars of kiwifruit. However, some of the commercial cultivars bred in New Zealand have not inherited alleles for resistance to H. lataniae carried by their parents. To elucidate the architecture of resistance in the parents and develop molecular markers to assist breeding, these experiments analysed the inheritance of resistance to H. lataniae from families related to commercial cultivars.

Results
The first experiment identified a 15.97 Mb genomic region of interest for resistance to H. lataniae in rtGBS data of 3.23 to 19.20 Mb on chromosome 10. A larger population was then QTL mapped, which confirmed the region of interest as the sole locus contributing to H. lataniae resistance. inDel markers mapping the region of low recombination under the QTL peak further narrowed the region associated with H. lataniae resistance to a 5.73 Mb region.

Conclusions
The kiwifruit populations and genomic methods used in this study identify the same non-recombinant region of chromosome 10 which confers resistance of A. chinensis var. chinensis to H. lataniae. The markers developed to target the H. lataniae resistance loci will reduce the amount of costly and time-consuming phenotyping required for breeding H. lataniae scale resistance into new kiwifruit cultivars.
Transcriptional and protein structural characterization of homogentisate phytyltransferase genes in barley, wheat, and oat
Authors: Zeng Zhanghui , Jia Yong , Huang Xiaoping , Chen Zhehao , Xiang Taihe , Han Ning , Bian Hongwu , Li Chengdao 
Published: October 2023

Abstract
Background
Homogentisate phytyltransferase (HPT) is the critical enzyme for the biosynthesis of tocopherols (vitamin E), which are the major lipid-soluble antioxidants and help plants adapt to various stress conditions. HPT is generally strictly conserved in various plant genomes; however, a divergent lineage HPT2 was identified recently in some Triticeae species. The molecular function and transcriptional profiles of HPT2 remain to be characterized.

Results
In this study, we performed comprehensive transcriptome data mining of HPT1 and HPT2 in different tissues and stages of barley (Hordeum vulgare), wheat (Triticum aestivum), and oat (Avena sativa), followed by qRT-PCR experiments on HPT1 and HPT2 in different tissues of barley and wheat. We found that the common HPT1 genes (HvHPT1, TaHPT1s, and AsHPT1s) displayed a conserved transcriptional pattern in the three target species and were universally transcribed in various tissues, with a notable preference in leaf. In contrast, HPT2 genes (HvHPT2, TaHPT2, and AsHPT2) were specifically transcribed in spike (developmentally up-regulated) and shoot apex tissues, displaying a divergent tissue-specific pattern. Cis-regulatory elements prediction in the promoter region identified common factors related to light-, plant hormone-, low temperature-, drought- and defense- responses in both HPT1s and HPT2s. We observed the transcriptional up-regulation of HvHPT1 and HvHPT2 under various stress conditions, supporting their conserved function in environmental adaption. We detected a clear, relaxed selection pressure in the HPT2 lineage, consistent with the predicted evolution pattern following gene duplication. Protein structural modelling and substrate docking analyses identified putative catalytic amino acid residues for HvHPT1 and HvHPT2, which are strictly conserved and consistent with their function in vitamin E biosynthesis.

Conclusions
We confirmed the presence of two lineages of HPT in Triticeae and Aveninae, including hexaploid oat, and characterized their transcriptional profiles based on transcriptome and qRT-PCR data. HPT1s were ubiquitously transcribed in various tissues, whilst HPT2s were highly expressed in specific stages and tissue. The active transcription of HPT2s, together with its conserved cis-elements and protein structural features, support HPT2s’ role in tocopherol production in Triticeae. This study is the first protein structural analysis on the membrane-bound plant HPTs and provides valuable insights into its catalytic mechanism.
Metabolic disorders and risk of cardiovascular diseases: a two-sample mendelian randomization study
Authors: Wang Zhe , Chen Jiawei , Zhu Longyang , Jiao Siqi , Chen Yinong , Sun Yihong 
Published: October 2023

Abstract
Background
Metabolic disorders are increasing worldwide and are characterized by various risk factors such as abdominal obesity, insulin resistance, impaired glucose metabolism, and dyslipidemia. Observational studies suggested a bidirectional association between cardiovascular diseases and metabolic disorders and its components. However, the causal associations between them remained unclear. This study aims to investigate the causal relationship between metabolic disorders and cardiovascular disease through Mendelian randomization (MR) analysis.

Methods
A two-sample MR analysis based on publicly available genome-wide association studies were used to infer the causality. The single-nucleotide polymorphisms with potential pleiotropy were excluded by MR-PRESSO. The effect estimates were constructed using the random-effects inverse-variance-weighted method as the primary estimate. Furthermore, MR-Egger and weighted median were also performed to detect heterogeneity and pleiotropy.

Results
Genetically predicted metabolic disorders increased the risk for coronary heart disease (OR = 1.77, 95% CI: 1.55–2.03, p < 0.001), myocardial infarction (OR = 1.75, 95% CI: 1.52–2.03, p < 0.001), heart failure (OR = 1.26, 95% CI: 1.14–1.39, p < 0.001), hypertension (OR = 1.01, 95% CI: 1.00-1.02, p = 0.002), and stroke (OR = 1.19, 95% CI: 1.08–1.32, p < 0.001). The concordance of the results of various complementary sensitivity MR methods reinforces the causal relationship further.

Conclusion
This study provides evidence of a causal relationship between metabolic disorders and increased risk of coronary heart disease, myocardial infarction, heart failure, hypertension, and stroke. Special attention should be paid to improving metabolic disorders to reduce the development of cardiovascular diseases.
Symmetry of computerised tomography of the brain in traumatic brain injury: a quality improvement audit
Authors: George Ajish Sam , Chitteti Pragnitha , Nair Shalini , Karuppasami Reka , Joseph Mathew 
Published: October 2023

Abstract
Background
Non-contrast Computerised Tomography (NCCT) of brain is the gold standard investigation for diagnosis and management of Traumatic brain injury (TBI). Asymmetrical CT brain images as a result of improper head positioning in the CT gantry will compromise the diagnostic value. Therefore, this audit aimed to assess the degree of asymmetry in CT brain studies carried out in TBI patients.

Methods
This audit was carried out at a level one trauma centre and included CT scans of TBI patients with a Glasgow come scale (GCS) score ≤ 13, admitted to the Neurological intensive care unit (NICU). The first cycle involved a period of three months. The data collected included demographic data and variables such as GCS at the time of the scan and whether the patient was intubated or not. The visualisation of bilateral internal auditory meatuses was used as landmark to determine scan symmetry. If the internal auditory meatus on both sides were visible on the same slice of CT scan, it was considered symmetric. The degree of asymmetry was gauged based on the axial slice difference between bilateral meatuses. The data collected was tabulated and presented to Neurosurgery residents and a checklist was formulated which had to be followed while positioning the patient on CT table prior to imaging.

Results
The first cycle of the audit showed that 83.8% of scans were asymmetric and among them 44.1% revealed gross asymmetry affecting interpretation of the scan. Following, implementation of the checklist the percentage of gross asymmetry dropped to 21.86% in the second and to 22.22% in the third audit.

Conclusion
The use of checklist prior to CT brain studies showed sustainable improvement in reducing gross asymmetry and in acquisition of symmetrical CT brain images.
Epidemiological trends and risk factors related to lower urinary tract symptoms around childbirth: a one-year prospective study
Authors: Wang Xiaojuan , Wang Hongyan , Xu Ping , Mao Minna , Feng Suwen 
Published: October 2023

Abstract
Background
Lower urinary tract symptoms (LUTS) are prevalent and distressing concerns for women worldwide. The prevalence of LUTS reaches the first peak during pregnancy and postnatal period. However, less attention has been paid to LUTS around childbirth and little progress has been made in the prevention of LUTS. Understanding the epidemiological characteristics of LUTS around childbirth would inform decision making for health care providers and perinatal women in the prevention of LUTS. The study aims to investigate the epidemiological trends and associated risk factors related to LUTS around childbirth.

Methods
Pregnant women were consecutively enrolled during pregnancy in the obstetrical wards of a tertiary hospital and followed up at 6–8 weeks and one year postpartum through a prospective design. Urinary incontinence was assessed with the International Consultation on Incontinence Modular Questionnaire-Urinary Incontinence Short Form. Other symptoms were measured with questions based on definitions of the International Incontinence Society. Multiple logistic regression was used to examine the risk factors for LUTS including urinary incontinence, increased daytime frequency, nocturia and urgency. The report followed the STROBE statement.

Results
A total of 1243 pregnant women participated in this study. The prevalence of at least one type of storage symptoms was 94%, 55% and 35% in late pregnancy, at 6–8 weeks and one year postpartum, respectively. The prevalence of urinary incontinence remained at 21% within one year postpartum. The majority of the participants suffered from mild to moderate urinary incontinence. Age, job, BMI before pregnancy, gestational diabetes mellitus, urinary tract infection history, previous history of LUTS, age at first birth and birth mode were predictors of LUTS one year postpartum.

Conclusion
LUTS were highly prevalent during pregnancy and postnatal period. The prevalence of urinary incontinence was more stable than that of other LUTS within one year postpartum. Women aged more than 35 years, engaging in manual work, with gestational diabetes mellitus, with a history of urinary tract infection and LUTS, with advanced age at first birth and vaginal delivery were more likely to suffer from LUTS postpartum. The findings provided a novel and deep insight into the epidemiological trends and related risk factors of LUTS around childbirth.
Pharmacotechnical aspects of a stable probiotic formulation toward multidrug-resistance antibacterial activity: design and quality control
Authors: Karimi Farkhonde , Azadi Amir , Omidifar Navid , Najafabady Nima Montazeri , Mohammadi Fatemeh , Kazemi Radmehr , Gholami Ahmad 
Published: October 2023

AbstractAs a well-known group of the probiotic family, the Lactobacillus has increasingly contributed to hindering the growth of pathogens, particularly resistant species, in the last decades. Since antibiotic resistance has become a severe problem in global healthcare systems and considerably increased the mortality and morbidity rate in infectious diseases, we aimed to obtain a new stable formulation of Lactobacillus to overcome resistant infections. For this purpose, we designed various gel formulations containingLactobacillus rhamnosus(L. rhamnosus) as an active pharmaceutical ingredient (API) in a water base and oil base gel, evaluated the probiotic stability in formulation to obtain an optimum formulation, and finally, investigated the antibacterial activities of that against two common hospital-associated multidrug-resistant pathogens, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Furthermore, the pharmaceutical aspects of the optimum formulation, including stability, homogeneity, spreadability, pH value, conductivity, and rheological behavior, were assessed.The results indicated that the optimum formulation based on glycerol exhibited desirable pharmaceutical properties, including long-term stability, a perfect level of homogeneity, an acceptable range of spreadability with pseudo-plastic thixotropic behavior, and a promising antibacterial potential against MRSA and VRE. Our findings indicate that this novel probiotic formulation could be an excellent candidate to cope with antibiotic-resistant species, representing a hopeful treatment potential for topical applications, particularly in incurable infections. However, further in vivo studies seem warranted to evaluate their bactericidal activity against multi-drug resistant microorganisms.
Two zinc finger proteins, VdZFP1 and VdZFP2, interact with VdCmr1 to promote melanized microsclerotia development and stress tolerance in Verticillium dahliae
Authors: Li Huan , Sheng Ruo-Cheng , Zhang Chen-Ning , Wang Li-Chao , Li Min , Wang Ya-Hong , Qiao Yu-Hang , Klosterman Steven J. , Chen Jie-Yin , Kong Zhi-Qiang , Subbarao Krishna V. , Chen Feng-Mao , Zhang Dan-Dan 
Published: October 2023

Abstract
Background
Melanin plays important roles in morphological development, survival, host–pathogen interactions and in the virulence of phytopathogenic fungi. In Verticillum dahliae, increases in melanin are recognized as markers of maturation of microsclerotia which ensures the long-term survival and stress tolerance, while decreases in melanin are correlated with increased hyphal growth in the host. The conserved upstream components of the VdCmr1-regulated pathway controlling melanin production in V. dahliae have been extensively identified, but the direct activators of this pathway are still unclear.

Results
We identified two genes encoding conserved C2H2-type zinc finger proteins VdZFP1 and VdZFP2 adjacent to VdPKS9, a gene encoding a negative regulator of both melanin biosynthesis and microsclerotia formation in V. dahliae. Both VdZFP1 and VdZFP2 were induced during microsclerotia development and were involved in melanin deposition. Their localization changed from cytoplasmic to nuclear in response to osmotic pressure. VdZFP1 and VdZFP2 act as modulators of microsclerotia melanization in V. dahliae, as confirmed by melanin biosynthesis inhibition and supplementation with the melanin pathway intermediate scytalone in albino strains. The results indicate that VdZFP1 and VdZFP2 participate in melanin biosynthesis by positively regulating VdCmr1. Based on the results obtained with yeast one- and two-hybrid (Y1H and Y2H) and bimolecular fluorescence complementation (BiFC) systems, we determined the melanin biosynthesis relies on the direct interactions among VdZFP1, VdZFP2 and VdCmr1, and these interactions occur on the cell walls of microsclerotia. Additionally, VdZFP1 and/or VdZFP2 mutants displayed increased sensitivity to stress factors rather than alterations in pathogenicity, reflecting the importance of melanin in stress tolerance of V. dahliae.

Conclusions
Our results revealed that VdZFP1 and VdZFP2 positively regulate VdCmr1 to promote melanin deposition during microsclerotia development, providing novel insight into the regulation of melanin biosynthesis in V. dahliae.