bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment benefit among migraine patients taking fremanezumab: results from a post hoc responder analysis of two placebo-controlled trials
Authors: Silberstein Stephen D. , Cohen Joshua M. , Yang Ronghua , Gandhi Sanjay K. , Du Evelyn , Jann Adelene E. , Marmura Michael J. 
Published: January 2021

AbstractBackgroundMonoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, including the fully humanized monoclonal antibody (IgG2Δa) fremanezumab, have demonstrated safety and efficacy for migraine prevention. Clinical trials include responders and nonresponders; efficacy outcomes describe mean values across both groups and thus provide little insight into the clinical benefit in responders. Clinicians and their patients want to understand the extent of clinical improvement in patients who respond. This post hoc analysis of fremanezumab treatment attempts to answer this question: what is the benefit in subjects who responded to treatment during the two, phase 3 HALO clinical trials?MethodsWe included subjects with episodic migraine (EM) or chronic migraine (CM) who received fremanezumab quarterly (675 mg/placebo/placebo) or monthly (EM: 225 mg/225 mg/225 mg; CM: 675 mg/225 mg/225 mg) during the 12-week randomized, double-blind, placebo-controlled HALO EM and HALO CM clinical trials. EM and CM responders were defined as participants with a reduction of ≥ 2 or ≥ 4 monthly migraine days, respectively. Treatment benefits evaluated included reductions in monthly migraine days, acute headache medication use, and headache-related disability, and changes in health-related quality of life (HRQoL).ResultsOverall, 857 participants from the HALO trials were identified as responders (EM: 429 [73.8%]; CM: 428 [56.7%]). Reductions in the monthly average number of migraine days were greater among EM (quarterly: 5.4 days; monthly: 5.5 days) and CM (quarterly: 8.7 days; monthly: 9.1 days) responders compared with the overall population. The proportion of participants achieving ≥ 50% reduction in the average monthly number of migraine days was also greater in responders (EM: quarterly, 59.8%; monthly, 63.7%; CM: quarterly, 52.8%; monthly, 59.0%) than in the overall population. Greater reductions in the average number of days of acute headache medication use, greater reductions in headache-related disability scores, and larger improvements in HRQoL were observed among EM and CM responders compared with the overall populations.ConclusionsFremanezumab responders achieved clinically meaningful improvements in all outcomes. The magnitude of improvements with fremanezumab across efficacy outcomes was far greater in responders than in the overall trial population, providing insight into expected treatment benefits in participants who respond to fremanezumab in clinical practice.Trial registrationClinicalTrials.govidentifiers: NCT02629861 (HALO EM) and NCT02621931 (HALO CM).
New genotypes of Helicobacter Pylori VacA d-region identified from global strains
Authors: Soyfoo Djaleel Muhammad , Doomah Yussriya Hanaa , Xu Dong , Zhang Chao , Sang Huai-Ming , Liu Yan-Yan , Zhang Guo-Xin , Jiang Jian-Xia , Xu Shun-Fu 
Published: January 2021

Abstract
Background
Pathogenesis of Helicobacter Pylori (HP) vacuolating toxin A (vacA) depends on polymorphic diversity within the signal (s), middle (m), intermediate (i), deletion (d) and c-regions. These regions show distinct allelic diversity. The s-region, m-region and the c-region (a 15 bp deletion at the 3′-end region of the p55 domain of the vacA gene) exist as 2 types (s1, s2, m1, m2, c1 and c2), while the i–region has 3 allelic types (i1, i2 and i3). The locus of d-region of the vacA gene has also been classified into 2 genotypes, namely d1 and d2. We investigated the “d-region”/“loop region” through bioinformatics, to predict its properties and relation to disease. One thousand two hundred fifty-nine strains from the NCBI nucleotide database and the dryad database with complete vacA sequences were included in the study. The sequences were aligned using BioEdit and analyzed using Lasergene and BLAST. The secondary structure and physicochemical properties of the region were predicted using PredictProtein.

Results
We identified 31 highly polymorphic genotypes in the “d-region”, with a mean length of 34 amino acids (9 ~ 55 amino acids). We further classified the 31 genotypes into 3 main types, namely K-type (strains starting with the KDKP motif in the “d-region”), Q-type (strains starting with the KNQT motif), and E-type (strains starting with the ESKT motif) respectively. The most common type, K-type, is more prevalent in cancer patients (80.87%) and is associated with the s1i1m1c1 genotypes (P < .01). Incidentally, a new region expressing sequence diversity (2 aa deletion) at the C-terminus of the p55 domain of vacA was identified during bioinformatics analysis.

Conclusions
Prediction of secondary structures shows that the “d-region” adopts a loop conformation and is a disordered region.
Diversity and composition of the Panax ginseng rhizosphere microbiome in various cultivation modesand ages
Authors: Tong Ai-Zi , Liu Wei , Liu Qiang , Xia Guang-Qing , Zhu Jun-Yi 
Published: January 2021

Abstract
Background
Continuous cropping of ginseng (Panax ginseng Meyer) cultivated in farmland for an extended period gives rise to soil-borne disease. The change in soil microbial composition is a major cause of soil-borne diseases and an obstacle to continuous cropping. The impact of cultivation modes and ages on the diversity and composition of the P. ginseng rhizosphere microbial community and technology suitable for cropping P. ginseng in farmland are still being explored.

Methods
Amplicon sequencing of bacterial 16S rRNA genes and fungal ITS regions were analyzed for microbial community composition and diversity.

Results
The obtained sequencing data were reasonable for estimating soil microbial diversity. We observed significant variations in richness, diversity, and relative abundances of microbial taxa between farmland, deforestation field, and different cultivation years. The bacterial communities of LCK (forest soil where P. ginseng was not grown) had a much higher richness and diversity than those in NCK (farmland soil where P. ginseng was not grown). The increase in cultivation years of P. ginseng in farmland and deforestation field significantly changed the diversity of soil microbial communities. In addition, the accumulation of P. ginseng soil-borne pathogens (Monographella cucumerina, Ilyonectria mors-panacis, I. robusta, Fusarium solani, and Nectria ramulariae) varied with the cropping age of P. ginseng.

Conclusion
Soil microbial diversity and function were significantly poorer in farmland than in the deforestation field and were affected by P. ginseng planting years. The abundance of common soil-borne pathogens of P. ginseng increased with the cultivation age and led to an imbalance in the microbial community.
Hemolytic uremic syndrome caused by sea anemone sting: a case report
Authors: Kim A Young , Cho Kyu Hyang , Kang Seok Hui , Park Jong Won , Do Jun Young , Kim Min Kyoung 
Published: January 2021

Abstract
Background
Some sea anemone toxins cause renal injuries resembling hemolytic uremic syndrome (HUS). To date, only a few cases of HUS caused by sea anemone stings have been reported. In this case report, we have described an HUS case caused by a sea anemone sting.

Case presentation
In November 2019, a 37-year-old man with no underlying disease was admitted to our hospital. He presented with intense pain, a rash on, and swelling in his right thigh. Two days prior, he had been stung by a sea anemone while scuba diving in Cebu, Philippines. His blood tests revealed renal dysfunction, and his platelet count was normal. However, on day three, the platelet count decreased rapidly. His blood haptoglobin level decreased, and schistocytes were identified on the peripheral blood smear. We suspected thrombotic microangiopathy and started the conventional treatment, comprising hemodialysis, blood transfusion, and antibiotic administration. ADAMTS-13 and genetic test results associated with atypical HUS were normal. Therefore, the patient was diagnosed with HUS caused by a sea anemone toxin.

Conclusions
HUS caused by a sea anemone toxin is rare, but it is a serious medical disease. Clinicians should consider HUS in patients with such clinical presentations, and they should make prompt treatment-related decisions.
Doctors’ smoking control knowledge, attitudes and practices: a cross-sectional study conducted in Shandong Province, China
Authors: Wang Qiang , Zhang Xueli , Wang Zengwu , Feng Shangang , Li Yang , Zhang Chuanfeng , Wang Chunping 
Published: January 2021

Abstract
Background
Doctors play an important role in smoking control. This study aimed to assess doctors’ smoking control knowledge, attitudes and practices to help doctors raise awareness of smoking control assistance.

Methods
This cross-sectional study recruited 1046 doctors from Shandong Province, China, by using multistage sampling. Participants’ information was collected by questionnaire. Pearson’s χ2 test and Fisher’s exact probability method were used to compare the distributions of categorical variables between/among groups.

Results
Among the participants, 14.7% were current smokers. Approximately 50.3% of participants had heard of smoking cessation drugs and 59.2% of participants thought that low-tar and low-nicotine cigarettes were as harmful to health as common cigarettes. Approximately 98.2 and 60.9% of participants agreed that smoking was related to lung cancer and male sexual dysfunction, respectively. Although 72.0% of participants believed that doctors should actively provide smoking cessation assistance, only 58.1% of participants considered that doctors should be responsible for providing smoking cessation assistance. Similarly, 85.2% of participants often asked about the smoking history of patients or their family members, while only 4.9% of participants had prescribed smoking cessation drugs for patients. Pediatricians had a higher proportion of “Agree” responses to the assessment items than doctors in other departments.

Conclusions
The results showed that doctors in Shandong Province did not have sufficient knowledge of smoking control. Slightly more than half of doctors thought that providing smoking cessation assistance was their responsibility. Only a few participants had prescribed smoking cessation drugs.
Physical and psychosocial quality of life in children with overweight and obesity from Sri Lanka
Authors: Gunawardana S. , Gunasinghe C. B. , Harshani M. S. , Seneviratne S. N. 
Published: January 2021

Abstract
Background
While childhood obesity is rising rapidly in South Asia, there is limited research on quality of life (QoL) of children with overweight and obesity from the region. This study assessed physical and psychosocial QoL in Sri Lankan children attending a specialized obesity clinic, from both children’s and parents’ perspective, and modifiable social factors affecting QoL.

Methods
We performed cross-cultural translation of the Pediatric Quality of Life Inventory (PedsQL™) 4.0 (Child-Self Report and Parent-Proxy forms), and assessed self-reported and parental-perception of physical and psychosocial QoL in 8–12 year-olds with overweight and obesity (n=110), referred for obesity management at a tertiary-care children’s hospital in Sri-Lanka. Body mass index (BMI) and pre-selected social factors affecting QoL were also assessed. Data were analyzed by non-parametric tests (Mann-Whitney U test, Wilcoxon test and Spearman correlation).

Results
The median physical QoL was lower than psychosocial QoL (78.1vs81.7, p=0.032) and physical QoL was inversely correlated with BMI. Parental-perception of children’s physical and psychosocial QoL correlated with child-reported QoL, but was lower. Being bullied (p=0.001) and not getting regular exercise (p=0.031) were associated with lower psychosocial QoL. Both physical and psychosocial QoL were lower in children having difficulties in finding suitable clothes (p< 0.001).

Conclusions
Children with overweight and obesity from Sri Lanka appeared to have greater impairment of physical QoL than psychosocial QoL. Higher BMI, bullying, lack of regular exercise and lack of suitable clothing, negatively affected QoL. Potential strategies to improve QoL include promoting regular exercise, addressing bullying and promoting availability of children’s clothes in larger sizes to fit children with overweight and obesity.
Effectiveness of recombinant Escherichia coli on the production of (R)-(+)-perillyl alcohol
Authors: Sun Chao , Dong Xianjuan , Zhang Rubing , Xie Congxia 
Published: January 2021

Abstract
Background
(R)-(+)-perillyl alcohol is a naturally oxygenated monoterpene widely used as the natural flavor additives, insecticides, jet fuels and anti-cancer therapies. It was also readily available monoterpene precursors. However, this natural product is present at low concentrations from plant sources which are not economically viable. Therefore, alternative microbial production methods are rapidly emerging as an attractive alternative to make (R)-(+)-perillyl alcohol production more sustainable and environmentally friendly.

Results
We engineered Escherichia coli to possess a heterologous mevalonate (MVA) pathway, including limonene synthase, P-cymene monoxygenase hydroxylase and P-cymene monoxygenase reductase for the production of (R)-(+)-perillyl alcohol. The concentration of (R)-(+)-limonene (the monoterpene precursor to (R)-(+)-perillyl alcohol) reached 45 mg/L from glucose. Enhanced (R)-(+)-perillyl alcohol production was therefore achieved. The strain produced (R)-(+)-perillyl alcohol at a titer of 87 mg/L and a yield of 1.5 mg/g glucose in a 5 L bioreactor fed batch system.

Conclusions
These datas highlight the efficient production of (R)-(+)-perillyl alcohol through the mevalonate pathway from glucose. This method serves as a platform for the future production of other monoterpenes.
Wrist-ankle acupuncture has a positive effect on cancer pain: a meta-analysis
Authors: Dong Bei , Lin Lu , Chen Qiuyun , Qi Yishu , Wang Fen , Qian Keyan , Tian Li 
Published: January 2021

AbstractBackgroundWrist-ankle acupuncture (WAA) as a kind of micro acupuncture therapy has been used to management cancer pain, however, the effects of WAA on cancer pain were controversial in the current studies. Therefore, the purpose of this meta-analysis was to critically evaluate the effect of wrist-ankle acupuncture (WAA) on cancer pain.MethodsSeven digital databases were searched from the inception of databases to July 2020, including CNKI, Wanfang, VIP, CBM, Cochrane Library, PubMed and Embase. Randomized controlled trials conforming to the inclusion and exclusion criteria were screened and extracted; the risk of bias was evaluated using the Cochrane Collaboration criteria. The primary outcome indicators included pain relief rate and pain score, and the secondary outcome was adverse reaction incidence. All analyses were performed with Review Manager 5.3.ResultsA total of 13 studies with 1005 cancer patients (intervention group: 568, control group: 437) were included in this meta-analysis. The results demonstrated that the pain relief rate of experimental group (WAA / WAA + drug intervention) was better than that of control group (analgesic drug intervention), and the difference was statistically significant [RR = 1.31, 95%CI: 1.15 ~ 1.49,P < 0.01].ConclusionsWAA has certain effect on cancer pain, and the effect of WAA combined with pharmacological intervention is better than that of drug therapy alone.
High dose rate intra-cavitary brachytherapy with cobalt 60 source for locally advanced cervical cancer: the Zimbabwean experience
Authors: Chibonda Shirley , Ndlovu Ntokozo , Tsikai Nomsa , Munangaidzwa Lameck , Ndarukwa Sandra , Nyamhunga Albert , Mazhindu Tinashe 
Published: January 2021

Abstract
Background and purpose
Cervical cancer is the fourth commonest cancer in women in the world with the highest regional incidence and mortality seen in Southern, Eastern and Western Africa. It is the commonest cause of cancer morbidity and mortality among Zimbabwean women. Most patients present with locally advanced disease that is no longer amenable to surgery. Definitive concurrent chemoradiation (CCRT), which is the use of external beam radiotherapy (EBRT) and weekly cisplatin, includes use of intracavitary brachytherapy, as the standard treatment. In the setting of this study, cobalt-60 (Co60)-based high dose rate brachytherapy (HDR-BT) has been in use since 2013. This study sought to review practices pertaining to use of brachytherapy in Zimbabwe, including timing with external beam radiotherapy, adverse effects and patient outcomes.

Methods
A retrospective analysis of data from records of patients with histologically confirmed cervical cancer treated with HDR-BT at the main radiotherapy centre in Zimbabwe from January 2013 to December 2014 was done. Outcome measures were local control, overall survival as well as gastro-intestinal and genito-urinary toxicity.

Results
A total of 226 patients were treated with HDR-BT during the study period, with a 97% treatment completion rate. All patients received between 45-50Gy of pelvic EBRT. Seventy-four percent received concurrent platinum-based chemotherapy. In 52% of the patients, HDR-BT was started when they were still receiving EBRT. The commonest fractionation schedule used was the 7Gy × 3 fractions, once a week (87%). Clinical complete tumour response was achieved in 75% at 6 weeks post treatment, 23% had partial response. Follow-up rates at 1 year and 2 years were 40 and 19% respectively. Disease free survival at 1 year and 2 years was 94 and 95% respectively. Vaginal stenosis was the commonest toxicity recorded, high incidence noted with increasing age. Four patients developed vesico-vaginal fistulae and two patients had rectovaginal fistulae.

Conclusion
One hundred and seventeen patients patients started HDR-BT during EBRT course, with a treatment completion rate of 97%. The overall treatment duration was within 56 days in the majority of patients. Early local tumour control was similar for all the HDR-BT fractionation regimes used in the study, with a high rate (75%) of complete clinical response at 6 weeks post-treatment. Prospective studies to evaluate early and long-term outcomes of HDR-BT in our setting are recommended.
Alcoholic fatty liver disease inhibited the co-expression of Fmo5 and PPARα to activate the NF-κB signaling pathway, thereby reducing liver injury via inducing gut microbiota disturbance
Authors: Kong Lingjian , Chen Jing , Ji Xiaoli , Qin Qian , Yang Huiyu , Liu Dan , Li Deliang , Sun Meiling 
Published: January 2021

Abstract
Background
Alcohol-induced intestinal dysbiosis disrupts and inflammatory responses are essential in the development of alcoholic fatty liver disease (AFLD). Here, we investigated the effects of Fmo5 on changes in enteric microbiome composition in a model of AFLD and dissected the pathogenic role of Fmo5 in AFLD-induced liver pathology.

Methods
The expression profile data of GSE8006 and GSE40334 datasets were downloaded from the GEO database. The WGCNA approach allowed us to investigate the AFLD-correlated module. DEGs were used to perform KEGG pathway enrichment analyses. Four PPI networks were constructed using the STRING database and visualized using Cytoscape software. The Cytohubba plug-in was used to identify the hub genes. Western blot and immunohistochemistry assays were used to detect protein expression. ELISA assay was used to detect the levels of serum inflammatory cytokines. Lipid droplets in the cytoplasm were observed using Oil Red O staining. Apoptosis was detected using a TUNEL assay and flow cytometry analysis. ROS levels were detected using flow cytometry analysis. Nuclear translocation of NF-κB p65 was observed using immunofluorescence staining. Co-immunoprecipitation was used to detect the co-expression of PPARα and Fmo5 in L02 cells. 16S rDNA sequencing defined the bacterial communities in mice with AFLD.

Results
Fmo5 is a key DEG and is closely associated with the gut microbiota and PPAR signaling pathway. Gut microbiome function in AFLD was significantly related to the PPAR signaling pathway. AFLD induced shifts in various bacterial phyla in the cecum, including a reduction in Bacteroidetes and increased Firmicutes. Fmo5 and PPARα co-expression in cell and animal models with AFLD, which decreased significantly. Silencing of Fmo5 and PPARα aggravated the functions of AFLD inducing apoptosis and inflammatory response, promoting liver injury, and activating the NF-κB signaling pathway in vivo and in vitro. The NF-κB inhibitor abolished the functions of silencing of Fmo5 and PPARα promoting AFLD-induced apoptosis, inflammatory response, and liver injury.

Conclusion
Our data indicated that the co-expression of Fmo5 and PPARα was involved in AFLD-related gut microbiota composition and alleviated AFLD-induced liver injury, apoptosis, and inflammatory response by inhibiting the nuclear translocation of NF-κB p65 to inhibit the NF-κB signaling pathway.
Clinical warning of hemophagocytic syndrome caused by Epstein-Barr virus
Authors: Shi Jinjin , Chu Chu , Yu Min , Zhang Dandan , Li Yuqin , Fan Yujie , Yu Yixue , Luo Yali , Zhou Weifang 
Published: January 2021

Abstract
Objectives
This study aimed to compare the clinical features and laboratory tests of infectious mononucleosis (IM) and hemophagocytic syndrome (HLH) caused by Epstein-Barr virus (EBV) in 1–3-year-old children and to explore the risk factor of HLH caused by EBV (EBV-HLH).

Methods
The clinical data of 92 children with EBV infection admitted in our hospital from 2011 to 2019 were collected; 61 cases were diagnosed as EBV-IM, and 31 cases were diagnosed as EBV-HLH. The subjects’ clinical manifestations and laboratory tests were analyzed retrospectively.

Results
Compared with EBV-IM patients, EBV-HLH patients had longer durations of fever, both before hospitalization and overall, and a higher probability of hepatomegaly. The levels of ALT, AST, LDH, TG, SF, D-Dimer and the plasma EBV DNA load of EBV-HLH patients were significantly higher than those of EBV-IM patients. The absolute values of CD3+, CD4+, CD8+, NK, and CD3-CD19+ cells and IgA and IgM levels of EBV-HLH patients were significantly lower than those of EBV-IM patients. The plasma EBV DNA load was positively correlated with the PT, TT, α-HBDH, AST, LDH, CK, Scr, BUN, UA, TG, and CRP levels in EBV-HLH patients, and the plasma EBV DNA load was positively correlated with the D-Dimer level in the EBV-IM patients. Among the 10 different potential markers, at the cut-off point of 1721.500 μg/L, the sensitivity and specificity of D-Dimer was 88.90 and 90.20%, respectively.

Conclusion
The D-Dimer level may be a good prognostic indicator of EBV-HLH caused by EBV.
Retrospective study of frequency of ABO and Rhesus blood group among population of Safdarabad and Faisalabad cities of Pakistan
Authors: Sabir Ali , Iftikhar Arslan , Ijaz Muhammad Umar , Hussain Ghulam , Rasul Azhar , Iqbal Rana Khalid , Sajid Faiqa , Anwar Haseeb 
Published: January 2021

Abstract
Objective
The current study aimed to investigate the ABO and rhesus (Rh) blood group frequency in the people of District Faisalabad and Sheikhupura, Punjab Province, Pakistan. The retrospective study was conducted on more than thirty thousand people including both male and female patients admitted to the Tehsil Headquarter Hospital, Safdarabad and The Best Hospital, Faisalabad. Blood samples were taken from each subject and subsequently ABO and Rh blood groups were evaluated separately. The antigen antibody agglutination slide test for blood grouping (ABO) and Rh were used to assess the blood group frequencies.

Results
The frequencies of ABO blood group distribution indicated that blood group B was predominant in the people of Safdarabad followed by O, A and AB respectively. While, among people of Faisalabad, blood group O was predominant followed B, A and AB respectively. Rh negative phenotype was found lesser distributed as compared to the positive Rh phenotype.