bluuebunny/crossref_metadata_2025_split huggingface dataset:
Residual burden of liver disease after HCV clearance in hemophilia: a word of caution in the era of gene therapy
Authors: La Mura Vincenzo , Bitto Niccolò , Capelli Cecilia , Caputo Camilla , Siboni Simona , Arcudi Sara , Ciavarella Alessandro , Gualtierotti Roberta , Fracanzani Anna Ludovica , Sangiovanni Angelo , Peyvandi Flora 
Published: July 2023

Abstract
Ruling out advanced fibrosis/cirrhosis is mandatory for persons with hemophilia (PWH) who are candidates for gene therapy. However, clinical evaluation and noninvasive tests (NITs) may be inaccurate after hepatitis C virus (HCV) clearance. We conducted a prospective hepatological screening to detect advanced fibrosis/cirrhosis in PWH after HCV clearance. Any risk factor of chronic liver damage was registered by using biochemical data, liver stiffness measurement (LSM), and ultrasound (US). A pre/post-HCV clearance analysis was conducted prospectively in a subgroup of patients who underwent LSM, US, and NITs for fibrosis. We evaluated 119 patients (median age, 53 years; range, 36-87 years) with a previous HCV infection (hemophilia A, n = 108; hemophilia B, n = 11). Ninety-six (81%) presented at least 1 potential risk factor of chronic liver damage. Metabolic risk factors were the most prevalent, with 51 patients (44%) having US steatosis. In 21 patients (18%), clinical, biochemical, liver morphology, and/or LSM were suggestive of advanced fibrosis/cirrhosis. Furthermore, 10 patients (8%) had esophageal varices and 3 (3%) had hepatocellular carcinoma. In 57 patients included in the prospective analysis, LSM and NITs were reduced after HCV clearance (P &lt; .05), but US signs specific of cirrhosis remained unchanged. Overall, 23 of 80 patients (29%) with LSM &lt;10 KPa had at least 1 US sign suggestive of advanced fibrosis/cirrhosis. A similar proportion (18%) was observed for LSM &lt;8 KPa. Overall, risk factors of chronic liver damage are frequent after HCV clearance, but changes in LSM and NITs after clearance may be inaccurate to rule out advanced fibrosis/cirrhosis. A specific diagnostic workup is warranted to evaluate liver health in PWH in the era of gene therapy.
The prevalence of colistin resistance in clinical Stenotrophomonas maltophilia isolates worldwide: a systematic review and meta-analysis
Authors: Delgarm Shams-Abadi Ali , Mohammadian-Hafshejani Abdollah , Paterson David L. , Arash Rezvan , Asadi Farsani Elham , Taji Asieh , Heidari Hamid , Shahini Shams Abadi Milad 
Published: July 2023

AbstractWhile trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line therapy of Stenotrophomonas maltophilia infections, colistin is one of the therapeutic options in cases of allergy or resistance to TMP-SMX. However, understanding the global status of resistance to colistin amongst S. maltophilia isolates could be helpful for appropriate antibiotic prescription. This study aimed to conduct a systematic review and meta-analysis to examine the prevalence of colistin resistance in clinical S. maltophilia isolates worldwide. According to eligibility criteria, a total of 61 studies were included in the analysis. The pooled prevalence for colistin resistance was 42% (95% CI: 35-49%), ranging from 0.1 to 97%. Subgroups analysis indicated that, the pooled prevalence of colistin resistance was 44% (95% CI: 29-60%) in 15 studies during 2000–2010, and it was estimated to be 41% (95% CI: 33-50%) in 46 articles from 2011 to 2021. It was 46% (95% CI: 35-58%) in the studies that used broth microdilution method, and 39% (95% CI: 30-49%) in the studies with other used methods. The resistance rate in Asian countries was 45% (95% CI: 31-60%), in European countries was 45% (95% CI: 34-56%) and in the countries of North and South America was 33% (95% CI: 20-46%). Our review showed notable resistance to colistin in clinical S. maltophilia isolates. Given the estimated resistance rates, alternative antibiotics could be preferred to treat serious infections due to S. maltophilia.
Metabolic-GWAS provides insights into genetic architecture of seed metabolome in buckwheat
Authors: Zargar Sajad Majeed , Manzoor Madhiya , Bhat Basharat , Wani Amir Bashir , Sofi Parvaze Ahmad , Sudan Jebi , Ebinezer Leonard Barnabas , Dall’Acqua Stefano , Peron Gregorio , Masi Antonio 
Published: July 2023

Abstract
Background
Buckwheat (Fagopyrum spp.), belonging to the Polygonaceae family, is an ancient pseudo-cereal with high nutritional and nutraceutical properties. Buckwheat proteins are gluten-free and show balanced amino acid and micronutrient profiles, with higher content of health-promoting bioactive flavonoids that make it a golden crop of the future. Plant metabolome is increasingly gaining importance as a crucial component to understand the connection between plant physiology and environment and as a potential link between the genome and phenome. However, the genetic architecture governing the metabolome and thus, the phenome is not well understood. Here, we aim to obtain a deeper insight into the genetic architecture of seed metabolome in buckwheat by integrating high throughput metabolomics and genotyping-by-sequencing applying an array of bioinformatics tools for data analysis.

Results
High throughput metabolomic analysis identified 24 metabolites in seed endosperm of 130 diverse buckwheat genotypes. The genotyping-by-sequencing (GBS) of these genotypes revealed 3,728,028 SNPs. The Genome Association and Prediction Integrated Tool (GAPIT) assisted in the identification of 27 SNPs/QTLs linked to 18 metabolites. Candidate genes were identified near 100 Kb of QTLs, providing insights into several metabolic and biosynthetic pathways.

Conclusions
We established the metabolome inventory of 130 germplasm lines of buckwheat, identified QTLs through marker trait association and positions of potential candidate genes. This will pave the way for future dissection of complex economic traits in buckwheat.
Use of neuromuscular blockade for neck dissection and association with iatrogenic nerve injury
Authors: Smith Joshua D. , Mentz Graciela , Leis Aleda M. , Yuan Yuan , Stucken Chaz L. , Chinn Steven B. , Casper Keith A. , Malloy Kelly M. , Shuman Andrew G. , McLean Scott A. , Rosko Andrew J. , Prince Mark E. P. , Tremper Kevin K. , Spector Matthew E. , Schechtman Samuel A. 
Published: July 2023

Abstract
Background
Cranial nerve injury is an uncommon but significant complication of neck dissection. We examined the association between the use of intraoperative neuromuscular blockade and iatrogenic cranial nerve injury during neck dissection.

Methods
This was a single-center, retrospective, electronic health record review. Study inclusion criteria stipulated patients > 18 years who had ≥ 2 neck lymphatic levels dissected for malignancy under general anesthesia with a surgery date between 2008 – 2018. Use of neuromuscular blockade during neck dissection was the primary independent variable. This was defined as any use of rocuronium, cisatracurium, or vecuronium upon anesthesia induction without reversal with sugammadex prior to surgical incision. Univariate tests were used to compare variables between those patients with, and those without, iatrogenic cranial nerve injury. Multivariable logistic regression determined predictors of cranial nerve injury and was performed incorporating Firth’s estimation given low prevalence of the primary outcome.

Results
Our cohort consisted of 925 distinct neck dissections performed in 897 patients. Neuromuscular blockade was used during 285 (30.8%) neck dissections. Fourteen instances (1.5% of surgical cases) of nerve injury were identified. On univariate logistic regression, use of neuromuscular blockade was not associated with iatrogenic cranial nerve injury (OR: 1.73, 95% CI: 0.62 – 4.86, p = 0.30). There remained no significant association on multivariable logistic regression controlling for patient age, sex, weight, ASA class, paralytic dose, history of diabetes, stroke, coronary artery disease, carotid atherosclerosis, myocardial infarction, and cardiac arrythmia (OR: 1.87, 95% CI: 0.63 – 5.51, p = 0.26).

Conclusions
In this study, use of neuromuscular blockade intraoperatively during neck dissection was not associated with increased rates of iatrogenic cranial nerve injury. While this investigation provides early support for safe use of neuromuscular blockade during neck dissection, future investigation with greater power remains necessary.
Comprehensive analysis of m6A regulators associated with immune infiltration in Hepatitis B virus-related hepatocellular carcinoma
Authors: Zhang Zhen , Gao Wenhui , Liu Zhuo , Yu Shuxian , Jian Huiying , Hou Zongwei , Zeng Puhua 
Published: July 2023

Abstract
Background
N6A methylation (m6A) is a significant epigenetic modification that critically impacts post-transcriptional regulation and tumor occurrence and development. While previous studies have identified a role for epigenetic regulation in hepatocellular carcinoma (HCC), the potential function of the m6A cluster in Hepatitis B virus (HBV)-related HCC remains unclear.

Methods
The related information was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Based on the expression of 20 m6A regulators, we comprehensively evaluated the m6A clusters and systematically explored the correlation between these clusters and immune cell infiltration characteristics of the tumor microenvironment (TME). The patients were divided into low- and high-m6A score groups. Then, the immune cell infiltration, chemokines, and cytokines levels, and drug sensitivity were further explored between the two groups.

Results
The m6A cluster predicted a better prognosis that was accompanied by increased immune cell infiltration. Using these results, an m6A score was established that could predict overall survival, immune checkpoints, and clinical treatments for patients with HBV-related HCC. This study demonstrated that m6A modifications affected tumorigenesis, TME, and the prognosis of patients with HBV-related HCC.

Conclusion
A comprehensive assessment of m6A patterns could improve the current understanding of immune cell infiltration patterns and inform the development of individualized cancer treatments.
Influence of COVID-19 on the notification of drug-resistant pulmonary tuberculosis cases
Authors: Orfão Nathalia Halax , Andrade Rubia Laine de Paula , Ruffino-Netto Antônio , da Silva Leila Wiedmann Florentino , Villa Tereza Cristina Scatena , Seifert Marva Lynn , Zilly Adriana , Arcoverde Marcos Augusto Moraes , Hoare Ismael , Izurieta Ricardo , da Silva-Sobrinho Reinaldo Antônio 
Published: July 2023

Abstract
Background
To analyze the influence of the COVID-19 pandemic on the process of diagnosis and monitoring of drug-resistant pulmonary tuberculosis (TB) cases reported in the state of Paraná, Brazil, from 2015 to 2020.

Methods
Ecological study with quantitative approach. This study was based on diagnosed cases of pulmonary TB reported in the Notifiable Disease Information System in residents of Paraná; as well as through the number of confirmed cases of COVID-19 in the state epidemiological bulletin for the year 2020. The study data were analyzed using descriptive statistics.

Results
It was found that, although the number of reported pulmonary TB cases (drug-resistant and general) increased between 2015 and 2019, there was a drop in notification in 2020, the first year of the COVID-19 pandemic. The notification of TB cases was also influenced monthly during the year according to the increase in the number of COVID-19 cases. For cases of drug-resistant pulmonary TB, the provision of diagnostic tests and Directly Observed Treatment decreased by more than half in 2020, especially when compared to 2019.

Conclusions
In view of these findings, the influence of COVID-19 on the diagnosis and monitoring of drug-resistant and general pulmonary TB cases is evident, showing that the pandemic has compromised the advances of recent decades in achieving the goals established for its eradication by 2035.
Non-contrast CT-based radiomics nomogram of pericoronary adipose tissue for predicting haemodynamically significant coronary stenosis in patients with type 2 diabetes
Authors: Chen Can , Chen Meng , Tao Qing , Hu Su , Hu Chunhong 
Published: July 2023

Abstract
Background
Type 2 diabetes mellitus (T2DM) patients have a higher incidence of coronary artery disease than the general population. The aim of this study was to develop a radiomics nomogram of pericoronary adipose tissue (PCAT) based on non-contrast CT to predict haemodynamically significant coronary stenosis in T2DM patients.

Methods
The study enrolled 215 T2DM patients who underwent non-contrast CT and coronary computed tomography angiography (CCTA). CCTA derived fractional flow reserve (FFRCT) ≤ 0.80 was defined as hemodynamically significant stenosis.1691 radiomics features were extracted from PCAT on non-contrast CT. Minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) were used to select useful radiomics features to construct Radscore. Logistic regression was applied to select significant factors among Radscore, fat attenuation index (FAI) and coronary artery calcium score (CACS) to construct radiomics nomogram.

Results
Radscore [odds ratio (OR) = 2.84; P < 0.001] and CACS (OR = 1.00; P = 0.023) were identified as independent predictors to construct the radiomics nomogram. The radiomics nomogram showed excellent performance [training cohort: area under the curve (AUC) = 0.81; 95% CI: 0.76–0.86; validation cohort: AUC = 0.83; 95%CI: 0.76–0.90] to predict haemodynamically significant coronary stenosis in patients with T2DM. Decision curve analysis demonstrated high clinical value of the radiomics nomogram.

Conclusion
The non-contrast CT-based radiomics nomogram of PCAT could effectively predict haemodynamically significant coronary stenosis in patients with T2DM, which might be a potential noninvasive tool for screening of high-risk patients.
Association of age-related declined renal function and osteoporosis based on trabecular bone score in Bushehr Elderly Health (BEH) program
Authors: Mahmudpour Mehdi , Homayoun Narges , Nabipour Iraj , Kalantar Hormozi Mohammad Reza , boushehri Saeid Najafpour , Larijani Bagher , Ostovar Afshin , Amini Azam , Marzban Maryam 
Published: July 2023

Abstract
Purpose
Osteoporosis is a systemic disease characterized by decreased bone strength and an increased risk of fracture in old age. Age and pathologic renal failure are independent risk factors for osteoporosis. However, it is not determined whether age-related decreased renal function, in the context of senescence, can be considered as an independent risk factor for osteoporosis. Therefore, this study was conducted to evaluate the effect of senescence-induced renal failure on bone quality and trabecular bone score.

Methods
This study used a cross-sectional design and was carried out based on data collected during the Bushehr Elderly Health (BEH) program, Phase II. A total of 2,125 elderly participants aged over 60 years old entered the study after meeting the inclusion criteria and providing informed consent. They underwent examinations for weight, height, abdominal and hip circumference, as well as blood pressure measurement. All participants also underwent DXA to assess bone mass density (BMD). Trabecular bone score (TBS) was calculated using the DXA apparatus software output. Univariate and adjusted multivariate linear regression analyses were used to evaluate the associations.

Results
In the univariate linear regression analysis, there was a direct correlation between age-related renal failure and TBS (β = 0.038, p < 0.0001), neck of femur BMD (β = 0.047, p < 0.0001), and lumbar BMD (β = 0.055, p < 0.0001). However, after adjusting for BMI, age, sex, smoking, and physical activity, no significant association was observed for these variables.

Conclusion
It is hypothesized that age-related renal failure cannot be considered as an independent risk factor for osteoporosis in elderly individuals aged over 60 years old.
A phase Ib/II study of galunisertib in combination with nivolumab in solid tumors and non-small cell lung cancer
Authors: Nadal Ernest , Saleh Mansoor , Aix Santiago Ponce , Ochoa-de-Olza Maria , Patel Sandip Pravin , Antonia Scott , Zhao Yumin , Gueorguieva Ivelina , Man Michael , Estrem Shawn T. , Liu Jiangang , Avsar Emin , Lin Wen Hong , Benhadji Karim A. , Gandhi Leena , Guba Susan C. , Diaz Inmaculada Ales 
Published: July 2023

Abstract
Background
In this phase Ib/II open-label study, tumor immune suppression was targeted in patients with advanced refractory solid tumors and patients with recurrent/refractory non-small cell lung cancer (NSCLC) using galunisertib with nivolumab.

Methods
Eligible patients were ≥ 18 years old, had an Eastern Cooperative Oncology Group performance status ≤ 1, and were treatment-naive for anti-programmed cell death-1, its ligand, or transforming growth factor β receptor 1 kinase inhibitors. Phase Ib was an open-label, dose-escalation assessment of the safety and tolerability of galunisertib with nivolumab in patients with advanced refractory solid tumors. Phase II evaluated the safety of galunisertib with nivolumab in NSCLC patients who had received prior platinum-based treatment but were immuno-oncology agent-naive.

Results
This trial was conducted between October 2015 and August 2020. No dose-limiting toxicities were observed in phase I. In the phase II NSCLC cohort (n = 25), patients received 150 mg twice daily galunisertib (14 days on/14 days off dosing schedule for all phases) plus nivolumab at 3 mg/kg (intravenously every 2 weeks). In this phase, the most frequent treatment-related adverse events (AEs) were pruritus (n = 9, 36%), fatigue (n = 8, 32%), and decreased appetite (n = 7, 28%). No grade 4 or 5 treatment-related AEs were observed. Six (24%) patients had confirmed partial response (PR) and 4 (16%) had stable disease; 1 additional patient had confirmed PR after initial pseudo-progression. The median duration of response was 7.43 months (95% confidence interval [CI]: 3.75, NR). Among the 7 responders, including the delayed responder, 1 had high PD-L1 expression (≥ 50%). The median progression-free survival was 5.26 months (95% CI: 1.77, 9.20) and the median overall survival was 11.99 months (95% CI: 8.15, NR). Interferon gamma response genes were induced post-treatment and cell adhesion genes were repressed, although the association of these observations with tumor response and clinical outcomes was not statistically powered due to limited samples available.

Conclusions
The study met its primary endpoint as galunisertib combined with nivolumab was well tolerated. Preliminary efficacy was observed in a subset of patients in the Phase 2 NSCLC cohort.

Trial registration
Trial registered with ClinicalTrials.gov (NCT02423343; 22.04.2015).
Changes in health-related rehabilitation trajectories following a major Norwegian welfare reform
Authors: Wittlund Sina , Lorentzen Thomas 
Published: July 2023

Abstract
Background
In this study we investigated the health-related rehabilitation trajectories of young Norwegian adults between 2004–2019. The study period is interesting because it overlaps with an extensive welfare system reform that occurred in Norway between 2006–2011. In parallel with the reform there was a substantial increase in health-related welfare dependency among young people due to mental health conditions.
To better understand this group, we addressed three questions: 1) what were the most typical health-related rehabilitation trajectories for young Norwegians aged 23–27 between 2004–2019, 2) did the trajectories and composition of health-related benefit recipients change overtime and 3) in parallel with the welfare reform, do we see improved labour market outcomes in our study population?

Methods
Using high-quality Norwegian registry data, we established four cohorts of Norwegian health-related rehabilitation benefit recipients aged 23–27 in either 2004 (cohort 1), 2008 (cohort 2), 2011 (cohort 3) or 2014 (cohort 4). The follow-up period for each cohort was six years. We used sequence and cluster analyses to identify typical health-related rehabilitation trajectories. In addition, descriptive statistics and multinomial logistic regression were used to scrutinise the relationship between trajectory types, sociodemographic characteristics and cohort membership.

Results
The majority follow trajectories consisting of welfare dependency, unemployment and unstable, low-income work. Both the trajectories and composition of the study population changed across cohorts. Over the observation period there was a 1) three-fold increase in the proportion following a trajectory ending in permanent disability benefits, 2) nine-fold increase in the proportion following trajectories characterised by long periods of health-related rehabilitation, 3) five-fold decrease in the share following unemployment occupational handicap trajectories 4) 6.9% increase in the proportion of early school leavers and 5) 8.9% decrease in the share with disabled parents.

Conclusion
Our study population is a vulnerable group with suboptimal mental health, functioning and employment outcomes. In conjunction with the welfare reform, we witnessed a significant drop in use of work-related benefits, accompanied by a substantial increase in uptake of health-related rehabilitation- and disability benefits. Thus, it appears that rather than improving employment outcomes, welfare policy changes have created a new problem by steering a greater proportion into disability benefits.
Mental health impact of cuts to local government spending on cultural, environmental and planning services in England: a longitudinal ecological study
Authors: Fahy Katie , Alexiou Alexandros , Daras Konstantinos , Mason Kate , Bennett Davara , Taylor-Robinson David , Barr Ben 
Published: July 2023

Abstract
Background
Over the past decade, there have been significant and unequal cuts to local authority (LA) budgets, across England. Cultural, environmental and planning (CEP) budgets have been cut by 17% between 2011 and 2019. This funding supports services such as parks, leisure centres, community development and libraries, all of which have potential to influence population mental health. We therefore investigated whether cuts to CEP services have affected mental health outcomes and the extent to which they have contributed to mental health inequalities between areas.

Methods
Using fixed effects regression applied to longitudinal LA-level panel data in England, we assessed whether trends in CEP spend were associated with trends in mental health outcomes, between 2011 and 2019. The exposure was CEP spend and the primary outcome was the LA-average Small Area Mental Health Index (SAMHI). Additionally, we considered subcategories of CEP spend as secondary exposures, and antidepressant prescription rate and self-reported anxiety levels as secondary outcomes, both aggregated to LA-level. We adjusted all models for confounders and conducted subgroup analysis to examine differential mental health effects of spending cuts based on the level of area deprivation.

Results
The average decrease in CEP spend of 15% over the period was associated with a 0.036 (95% CI: 0.005, 0.067) increase in SAMHI score, indicating worsening mental health. Amongst subcategories of CEP spending, cuts to planning and development services impacted mental health trends the most, with a 15% reduction in spend associated with a 0.018 (95% CI: 0.005, 0.031) increase in the SAMHI score. The association between cuts in CEP and deteriorating mental health was greater in more affluent areas.

Conclusion
Cuts to spending on cultural, environmental, planning and development services were associated with worsening population mental health in England. Impacts were driven by cuts to planning and development services in particular. Reinvesting in these services may contribute to improved public mental health.