bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of fremanezumab in patients with migraine and inadequate response to prior preventive treatment: subgroup analyses by country of a randomized, placebo-controlled trial
Authors: Spierings Egilius L. H. , Kärppä Mikko , Ning Xiaoping , Cohen Joshua M. , Campos Verena Ramirez , Yang Ronghua , Reuter Uwe 
Published: April 2021

Abstract
Background
The FOCUS study evaluated the efficacy of migraine preventive medications across different countries within the same patient population, particularly for patients with difficult-to-treat migraine. These prespecified subgroup analyses evaluated efficacy by country in the FOCUS study of fremanezumab in adults with episodic migraine or chronic migraine and documented inadequate response to 2 to 4 migraine preventive medication classes.

Methods
Overall, 838 participants were enrolled in the FOCUS study, a randomized, double-blind, placebo-controlled, parallel-group, phase 3b study performed at 104 sites. For 12 weeks of double-blind treatment, patients were randomized (1:1:1) to quarterly fremanezumab, monthly fremanezumab, or matched placebo. The primary efficacy endpoint was the mean change from baseline in monthly average migraine days over 12 weeks of double-blind treatment, evaluated by country in these subgroup analyses.

Results
Of 14 countries contributing data, the Czech Republic (n = 188/838; 22%), the United States (n = 120/838; 14%), and Finland (n = 85/838; 10%) enrolled the most patients. Changes from baseline in monthly average migraine days over 12 weeks were significantly greater with fremanezumab versus placebo for patients in these countries: Czech Republic (least-squares mean difference versus placebo [95% confidence interval]: quarterly fremanezumab, − 1.9 [− 3.25, − 0.47]; P = 0.009; monthly fremanezumab, − 3.0 [− 4.39, − 1.59]; P < 0.001), the United States (quarterly fremanezumab, − 3.7 [− 5.77, − 1.58]; P < 0.001; monthly fremanezumab, − 4.2 [− 6.23, − 2.13]; P < 0.001), and Finland (quarterly fremanezumab, − 3.0 [− 5.32, − 0.63]; P = 0.014; monthly fremanezumab, − 3.9 [− 6.27, − 1.44]; P = 0.002). Results were comparable for the remaining 9 countries, with the least-squares mean difference versus placebo ranging from – 5.6 to – 2.4 with quarterly fremanezumab and from − 5.3 to − 1.5 with monthly fremanezumab. Incidences of serious adverse events and adverse events leading to discontinuation were low and comparable across countries and treatment groups.

Conclusions
Monthly and quarterly fremanezumab significantly reduced the monthly average number of migraine days versus placebo regardless of country and continent (North America versus Europe) in migraine patients with documented inadequate response to 2 to 4 migraine preventive medication classes.

Trial registration
ClinicalTrials.gov Identifier: NCT03308968.
Genome sequencing and comparative genomic analysis of highly and weakly aggressive strains of Sclerotium rolfsii, the causal agent of peanut stem rot
Authors: Yan Liying , Wang Zhihui , Song Wanduo , Fan Pengmin , Kang Yanping , Lei Yong , Wan Liyun , Huai Dongxin , Chen Yuning , Wang Xin , Sudini Hari , Liao Boshou 
Published: April 2021

Abstract
Background
Stem rot caused by Sclerotium rolfsii is a very important soil-borne disease of peanut. S. rolfsii is a necrotrophic plant pathogenic fungus with an extensive host range and worldwide distribution. It can infect peanut stems, roots, pegs and pods, leading to varied yield losses. S. rolfsii strains GP3 and ZY collected from peanut in different provinces of China exhibited a significant difference in aggressiveness on peanut plants by artificial inoculation test. In this study, de-novo genome sequencing of these two distinct strains was performed aiming to reveal the genomic basis of difference in aggressiveness.

Results
Scleotium rolfsii strains GP3 and ZY, with weak and high aggressiveness on peanut plants, exhibited similar growth rate and oxalic acid production in laboratory. The genomes of S. rolfsii strains GP3 and ZY were sequenced by Pacbio long read technology and exhibited 70.51 Mb and 70.61 Mb, with contigs of 27 and 23, and encoded 17,097 and 16,743 gene models, respectively. Comparative genomic analysis revealed that the pathogenicity-related gene repertoires, which might be associated with aggressiveness, differed between GP3 and ZY. There were 58 and 45 unique pathogen-host interaction (PHI) genes in GP3 and ZY, respectively. The ZY strain had more carbohydrate-active enzymes (CAZymes) in its secretome than GP3, especially in the glycoside hydrolase family (GH), the carbohydrate esterase family (CBM), and the polysaccharide lyase family (PL). GP3 and ZY also had different effector candidates and putative secondary metabolite synthetic gene clusters. These results indicated that differences in PHI, secreted CAZymes, effectors and secondary metabolites may play important roles in aggressive difference between these two strains.

Conclusions
The data provided a further understanding of the S. rolfsii genome. Genomic comparison provided clues to the difference in aggressiveness of S. rolfsii strains.
Long non-coding RNA pairs to assist in diagnosing sepsis
Authors: Zheng Xubin , Leung Kwong-Sak , Wong Man-Hon , Cheng Lixin 
Published: April 2021

Abstract
Background
Sepsis is the major cause of death in Intensive Care Unit (ICU) globally. Molecular detection enables rapid diagnosis that allows early intervention to minimize the death rate. Recent studies showed that long non-coding RNAs (lncRNAs) regulate proinflammatory genes and are related to the dysfunction of organs in sepsis. Identifying lncRNA signature with absolute abundance is challenging because of the technical variation and the systematic experimental bias.

Results
Cohorts (n = 768) containing whole blood lncRNA profiling of sepsis patients in the Gene Expression Omnibus (GEO) database were included. We proposed a novel diagnostic strategy that made use of the relative expressions of lncRNA pairs, which are reversed between sepsis patients and normal controls (eg. lncRNAi > lncRNAj in sepsis patients and lncRNAi < lncRNAj in normal controls), to identify 14 lncRNA pairs as a sepsis diagnostic signature. The signature was then applied to independent cohorts (n = 644) to evaluate its predictive performance across different ages and normalization methods. Comparing to common machine learning models and existing signatures, SepSigLnc consistently attains better performance on the validation cohorts from the same age group (AUC = 0.990 & 0.995 in two cohorts) and across different groups (AUC = 0.878 on average), as well as cohorts processed by an alternative normalization method (AUC = 0.953 on average). Functional analysis demonstrates that the lncRNA pairs in SepsigLnc are functionally similar and tend to implicate in the same biological processes including cell fate commitment and cellular response to steroid hormone stimulus.

Conclusion
Our study identified 14 lncRNA pairs as signature that can facilitate the diagnosis of septic patients at an intervenable point when clinical manifestations are not dramatic. Also, the computational procedure can be generalized to a standard procedure for discovering diagnostic molecule signatures.
Appetite, oral health and weight loss in community-dwelling older men: an observational study from the Concord Health and Ageing in Men Project (CHAMP)
Authors: Takehara Sachiko , Hirani Vasant , Wright F. A. Clive , Naganathan Vasi , Blyth Fiona M. , Le Couteur David G. , Waite Louise M. , Seibel Markus J. , Handelsman David J. , Cumming Robert G. 
Published: April 2021

Abstract
Background
Unintended weight loss and the reduction in appetite are common phenomenon among older people. Reduced appetite has been linked to medication related reductions in saliva production, reduced taste ability and poor oral health. Poor appetite can result in reduced nutrient intake ensuing weight loss. It is possible that poor appetite is a mediating step on the causal pathway between oral health and weight loss. This study investigates whether poor oral health and loss of appetite are related to weight loss.

Methods
This is an observational study where data were obtained from the Concord Health and Ageing in Men Project (CHAMP). Information on socio-demographics, appetite and health related behavior was collected by self-completed questionnaire. Intraoral assessment was conducted by calibrated oral health therapists. Height and weight were measured by trained staff. Regression analysis investigated associations between oral health and appetite as risk factors for weight loss.

Results
Participants included 542 community dwelling older males. 99 older men (18.3%) experienced 5% or more weight loss over 3 years. Men who lost weight from baseline had lower BMI and lower body weight, had higher prevalence of frailty and depression, reported poorer appetite, and had fewer teeth (13.8 ± 9.5) than those who did not lose weight (16.3 ± 9.3). Before adjustment, the prevalence ratio (PR) for weight loss was 1.76 (95% Confidence Interval (CI), 1.19–2.59) for participants with 0–19 natural teeth present compared to those with 20 or more teeth. When adding appetite and other variables to the model, the PR for number of teeth and weight loss was unchanged: 1.78 (95% CI, 1.06–3.00). The mediation analysis showed that the indirect effect of appetite on the association between number of natural teeth on weight loss was not found to be significant.

Conclusion
This study found that number of natural teeth present and appetite are independently related to weight change among elderly men in Australia. Tooth loss can increase the risk of swallowing difficulty leading to change in food preference, avoidance of foods and a decrease in energy intake. Our study showed the importance of oral health interventions to encourage maintenance of 20 or more natural teeth in older people.
RETRACTED ARTICLE: Methylene blue photochemical treatment as a reliable SARS-CoV-2 plasma virus inactivation method for blood safety and convalescent plasma therapy for COVID-19
Authors: Jin Changzhong , Yu Bin , Zhang Jie , Wu Hao , Zhou Xipeng , Yao Hangping , Liu Fumin , Lu Xiangyun , Cheng Linfang , Jiang Miao , Wu Nanping 
Published: April 2021

AbstractBackgroundIn 2020, a new coronavirus, SARS-CoV-2, quickly spread worldwide within a few months. Although coronaviruses typically infect the upper or lower respiratory tract, the virus RNA can be detected in plasma. The risk of transmitting coronavirus via transfusion of blood products remains. As more asymptomatic infections are identified in COVID-19 cases, blood safety has become particularly important. Methylene blue (MB) photochemical technology has been proven to inactivate lipid-enveloped viruses with high efficiency and safety. The present study aimed to investigate the SARS-CoV-2 inactivation effects of MB in plasma.MethodsThe SARS-CoV-2 virus strain was isolated from Zhejiang University. The live virus was harvested from cultured VERO-E6 cells, and mixed with MB in plasma. The MB final concentrations were 0, 1, 2, and 4 μM. The “BX-1 AIDS treatment instrument” was used at room temperature, the illumination adjusted to 55,000 ± 0.5 million Lux, and the plasma was irradiated for 0, 2, 5, 10, 20, and 40 mins using light at a single wavelength of 630 nm. Virus load changes were measured using quantitative reverse transcription- PCR.ResultsBX-1 could effectively eliminate SARS-CoV-2 within 2 mins in plasma, and the virus titer declined to 4.5 log10 TCID50 (median tissue culture infectious dose)/mL.ConclusionBX-1 is based on MB photochemical technology, which was designed to inactivate HIV-1 virus in plasma. It was proven to be safe and reliable in clinical trials of HIV treatment. In this study, we showed that BX-1 could also be applied to inactivate SARS-CoV-2. During the current outbreak, this technique it has great potential for ensuring the safety of blood transfusions, for plasma transfusion therapy in recovering patients, and for preparing inactivated vaccines.
Development of a patient-reported outcome measure for patients who have recovered from a subarachnoid hemorrhage: the “questionnaire for the screening of symptoms in aneurysmal subarachnoid hemorrhage” (SOS-SAH)
Authors: Nobels-Janssen Edith , Abma Inger L. , Verhagen Wim I. M. , Bartels Ronald H. M. A. , van der Wees Philip J. , Boogaarts Jeroen D. 
Published: April 2021

Abstract
Background
Patients who have been successfully treated for an aneurysmal subarachnoid hemorrhage (aSAH) often retain multiple health complaints, including mood disorders, cognitive complaints, fatigue, and problems with social participation. These problems are not always fully addressed during hospital visits or in current outcome measures, such as the modified Rankin score and the Glasgow Outcome Scale. Here, we present the development of the “Questionnaire for the Screening of Symptoms in aneurysmal Subarachnoid Hemorrhage” (SOS-SAH), which screens for the self-reported symptoms of patients with mild disabilities.

Methods
During the development of the SOS-SAH we adhered to the PROM-cycle framework for the selection and implementation of patient-reported outcome measures (PROMs). The SOS-SAH was developed in an iterative process informed by a literature study. Patients and healthcare professionals were involved in the development process through participating in a working group, interviews, and a cognitive validation study.

Results and conclusions
Relevant patient-reported outcomes (PROs) were identified for patients with aSAH. The SOS-SAH was developed primarily using domains and items from existing PROMs and, if necessary, by developing new items. The SOS-SAH consists of 40 items and covers 14 domains: cognitive abilities, hypersensitivity to stimuli, anxiety, depression, fatigue, social roles, personality change, language, vision, taste, smell, hearing, headache, and sexual function. It also includes a proxy measurement for use by family members to assess cognitive functioning and personality change.
The effect of sevoflurane anesthesia for dental procedure on neurocognition in children: a prospective, equivalence, controlled trial
Authors: Zhou Pinping , Zhang Chao , Huang Guijin , Hu Yuan , Ma Wenzhu , Yu Cong 
Published: April 2021

Abstract
Background
Dental procedures under general anesthesia (DGA) was found to improve the oral health-related quality of children’s life. However, some parents and pediatricians expressed concern about the neurotoxicity of general anesthesia. The purpose of this trial was to whether DGA in children has an adverse effect on neurocognition.

Methods
In this prospective, assessor-masked, controlled, equivalence trial, we recruited 340 children younger than 7 years who were undergoing caries treatment between Feb 1, 2019, and Aug 31, 2019, without factors affecting neurodevelopment. They received either sevoflurane-based general anesthesia or awake-local anesthesia. The Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition was used to evaluate the neurocognitive function of children at 6 months after surgery, and the Full-Scale IQ (FSIQ) was selected as the primary outcome. The predefined clinical equivalence margin was 5 (1/3 SD of FSIQ score). If the 95% CI of the difference between the average FSIQ score of the two groups is within − 5 to + 5, then the two groups are equivalent.

Results
The outcome data were obtained from 129 children in the general anesthesia group and 144 in the local anesthesia group. The median length of general anesthesia was 130 min (IQR 110–160). The mean FSIQ score in the general anesthesia group was 103·12 (SD 8.94), and the mean of the local anesthesia group was 103·58 (SD 8.40). There was equivalence in means of FSIQ score between the two groups (local minus general anesthesia 0.46, 95% CI − 2.35 to 1.61). There was no significant difference in FSIQ scores between different age groups and different anesthesia durations. Only the mother’s education could affect the primary outcome.

Conclusions
In this trial, prolonged DGA with a sevoflurane-only anesthetic in preschool children, does not adversely affect neurocognitive function at 6 months after surgery compared with awake-local anesthesia.

Trial registration
Chinese Clinical Trial Registry, ChiCTR1800015216. Registered Mar 15 2018.
Association of source country gender inequality with experiencing assault and poor mental health among young female immigrants to Ontario, Canada
Authors: Lebenbaum Michael , Stukel Therese A. , Saunders Natasha Ruth , Lu Hong , Urquia Marcelo , Kurdyak Paul , Guttmann Astrid 
Published: April 2021

Abstract
Background
Gender inequality varies across countries and is associated with poor outcomes including violence against women and depression. Little is known about the relationship of source county gender inequality and poor health outcomes in female immigrants.

Methods
We used administrative databases to conduct a cohort study of 299,228 female immigrants ages 6–29 years becoming permanent residence in Ontario, Canada between 2003 and 2017 and followed up to March 31, 2020 for severe presentations of suffering assault, and selected mental health disorders (mood or anxiety, self-harm) as measured by hospital visits or death. Poisson regression examined the influence of source-country Gender Inequality Index (GII) quartile (Q) accounting for individual and country level characteristics.

Results
Immigrants from countries with the highest gender inequality (GII Q4) accounted for 40% of the sample, of whom 83% were from South Asia (SA) or Sub-Saharan Africa (SSA). The overall rate of assault was 10.9/10,000 person years (PY) while the rate of the poor mental health outcome was 77.5/10,000 PY. Both GII Q2 (Incident Rate Ratio (IRR): 1.48, 95% Confidence Interval (CI): 1.08, 2.01) and GII Q4 (IRR: 1.58, 95%CI: 1.08, 2.31) were significantly associated with experiencing assault but not with poor mental health. For females from countries with the highest gender inequality, there were significant regional differences in rates of assault, with SSA migrants experiencing high rates compared with those from SA. Relative to economic immigrants, refugees were at increased risk of sustaining assaults (IRR: 2.96, 95%CI: 2.32, 3.76) and poor mental health (IRR: 1.73, 95%CI: 1.50, 2.01). Higher educational attainment (bachelor’s degree or higher) at immigration was protective (assaults IRR: 0.64, 95%CI: 0.51, 0.80; poor mental health IRR: 0.69, 95% CI: 0.60, 0.80).

Conclusion
Source country gender inequality is not consistently associated with post-migration violence against women or severe depression, anxiety and self-harm in Ontario, Canada. Community-based research and intervention to address the documented socio-demographic disparities in outcomes of female immigrants is needed.
Effectiveness of a 23-valent pneumococcal polysaccharide vaccine for the prevention of pneumococcal pneumonia in the elderly with chronic respiratory diseases: a case–control study of a single center
Authors: Masuda Toshihiro , Nakatani Eiji , Shirai Toshihiro , Akamatsu Taisuke , Tamura Kanami , Takahashi Shingo , Tanaka Yuko , Watanabe Hirofumi , Endo Yoshinari , Suzuki Takahito , Saigusa Mika , Yamamoto Akito , Morita Satoru , Sato Yoko , Asada Kazuhiro 
Published: April 2021

Abstract
Background
The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in preventing pneumococcal pneumonia has been controversial.

Methods
To evaluate the effectiveness of the PPSV23 in elderly outpatients with chronic respiratory diseases, we carried out a case–control study, including 4128 outpatients aged ≥ 65 years, in the respiratory department.

Results
There were 320 vaccinated patients, of which 164 were diagnosed with pneumococcal pneumonia. The adjusted odds ratio was 0.39 (95% confidence interval (CI), 0.17 to 0.89). In the subsets consisting of age groups ≥ 70 and ≥ 75 years, the adjusted odds ratio (95% CI) was respectively 0.16 (0.04 to 0.67) and 0.15 (0.02 to 1.12).

Conclusion
This real-world study suggests that PPSV23 can be useful in preventing pneumococcal pneumonia in the elderly with chronic respiratory diseases.
Bilateral neck fracture in bimodular femoral stem after primary total hip arthroplasty: a case report
Authors: Fokter Samo K. , Gubeljak Nenad , Predan Jožef , Sevšek Jure , Zajc Jan , Krajnc Zmago 
Published: April 2021

Abstract
Background
Bi-modular stems were introduced in primary total hip arthroplasty (THA) to enable better control of the femoral offset, leg length, and hip stability. Despite numerous reports on modular femoral neck fractures, some designs are still marketed worldwide. While the risk factors for the sudden failure are multifactorial and mostly known, the timing of this new THA complication is not predictable by any means.

Case presentation
In this report, the literature regarding one of the most popular bi-modular stems with specific neck-stem coupling (oval Morse taper) is reviewed and illustrated with a case of bilateral modular neck fracture in a patient with idiopathic aseptic necrosis of femoral heads treated with primary bi-modular THA. Because of bilateral modular femoral neck fracture, which occurred 3 years on the left side and 20 years after implantation on the right side, the patient required a total of 6 revisions and 208 days of hospitalized care.

Conclusion
To our knowledge, this is the first report of bilateral modular neck fracture in a single patient. Even though the same surgeon performed both operations and used the same neck length and orientation, fractures occurred with a 17-year time difference after implantation. This shows that we cannot predict with certainty when a fracture might occur. Orthopaedic surgeons should use bi-modular stem designs for primary THA very cautiously.