bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 vaccine effectiveness and variants in Nepal: study protocol for a test-negative case–control study with SARS-CoV-2 genetic sequencing
Authors: Bijukchhe Sanjeev M , O'Reilly Peter J , Theiss-Nyland Katherine , Gurung Meeru , Pokhrel Bhishma , Kelly Sarah , Acharya Samita , Maharjan Shreekrishna , Shrestha Ashis , Pandey Bimal , Lama Mipsang , Shrestha Ira , Voysey Merryn , Eordogh Agnes , Shrestha Sonu , Feng Elaine Shuo , Li Grace , Shah Ganesh , Pollard Andrew J , Shrestha Shrijana 
Published: April 2023

IntroductionInactivated, viral vector and mRNA vaccines have been used in the Nepali COVID-19 vaccination programme but there is little evidence on the effectiveness of these vaccines in this setting. The aim of this study is to describe COVID-19 vaccine effectiveness in Nepal and provide information on infections with SARS-CoV-2 variants.Methods and analysisThis is a hospital-based, prospective test-negative case–control study conducted at Patan Hospital, Kathmandu. All patients >18 years of age presenting to Patan Hospital with COVID-19-like symptoms who have received a COVID-19 antigen/PCR test are eligible for inclusion. The primary outcome is vaccine effectiveness of licensed COVID-19 vaccines against laboratory-confirmed COVID-19 disease.After enrolment, information will be collected on vaccine status, date of vaccination, type of vaccine, demographics and other medical comorbidities. The primary outcome of interest is laboratory-confirmed SARS-CoV-2 infection. Cases (positive for SARS-CoV-2) and controls (negative for SARS-CoV-2) will be enrolled in a 1:4 ratio. Vaccine effectiveness against COVID-19 disease will be analysed by comparing vaccination status with SARS-CoV-2 test results.Positive SARS-CoV-2 samples will be sequenced to identify circulating variants and estimate vaccine effectiveness against common variants.Measuring vaccine effectiveness and identifying SARS-CoV-2 variants in Nepal will help to inform public health efforts. Describing disease severity in relation to specific SARS-CoV-2 variants and vaccine status will also inform future prevention and care efforts.Ethics and disseminationEthical approval was obtained from the University of Oxford Tropical Ethics Committee (OxTREC) (ref: 561-21) and the Patan Academy of Health Sciences Institutional Review Board (ref: drs2111121578). The protocol and supporting study documents were approved for use by the Nepal Health Research Council (NHRC 550-2021). Results will be disseminated in peer-reviewed journals and to the public health authorities in Nepal.
What is complexity of hospital-based physiotherapy from the perspective of physiotherapists themselves? A grounded theory study
Authors: de Zwart Lieven , Koenders Niek , Steenbruggen Rudi , Nijhuis-van der Sanden Ria , Hoogeboom Thomas J 
Published: April 2023

BackgroundThe concept of ‘complexity’ is widely used by healthcare professionals in patient care. However, it is not completely understood. The inappropriate use and incorrect understanding of complexity lead to ambiguity for hospital-based physiotherapists in dealing with complex patients and work situations.ObjectivesTo develop an understanding of complexity for hospital-based physiotherapy from the perspective of physiotherapists themselves.DesignA grounded theory study was conducted using data from face-to-face, semi-structured interviews with purposive sampled hospital-based physiotherapists. The sampling was used to incorporate variety in hospital work experience, field of expertise and gender. The interviews were conducted in three different types of Dutch hospitals. A conceptual model and grounded theory were constructed after open, axial and selective coding.ResultsTwenty-four hospital-based physiotherapists were interviewed. Two core themes emerged from the data: ‘puzzle-solving’ and ‘reflecting on decisions’. The third theme—‘relationship between learning, adapting and complexity’—describes how hospital-based physiotherapists’ perceptions of complexity change over time. Complexity as a construct was interpreted as the balance between context and patient-related factors on the one hand and therapist-related factors on the other.ConclusionsHospital-based physiotherapists encounter complexity during performing job-related activities and decision-making. Complexity depends on balancing context and patient-related factors and therapist-related factors. In hospital-based physiotherapy, it was perceived as challenging yet meaningful. Complexity contributes to becoming more competent and, as such, a balance between complex and non-complex activities should be sought for hospital-based physiotherapists.
Direct active rehabilitation after reverse total shoulder arthroplasty: an international multicentre prospective cohort safety study with 1-year follow up
Authors: Kornuijt Anke , de Vries Lieke , van der Weegen Walter , Hillen Robert Jan , Bogie Rob , Stokman Remco , van Kampen Derk 
Published: April 2023

ObjectivesTo gain insight in the safety of direct active rehabilitation without immobilisation in patients undergoing reverse total shoulder arthroplasty without subscapularis reattachment, measured by the occurrence of complications until 1-year follow up. Next, to explore improvement in shoulder function and in patient-reported outcome measures.DesignAn international multicentre prospective cohort safety study.SettingPatients indicated for reverse total shoulder arthroplasty, visiting the orthopaedics outpatient clinic at two hospitals in the Netherlands and one hospital in Curaçao between January 2019 and July 2021, were selected.Participants100 patients (68% female, mean age 74±7.0 years) undergoing unilateral primary shoulder replacement were included if: ≥50 years, diagnosed with shoulder osteoarthritis, rotator cuff arthropathy or avascular necrosis, and selected for reverse total shoulder arthroplasty. A sling was used for only 1 day, followed by a progressive active rehabilitation for ≥12 weeks with no precautions.Main outcome measuresComplications, range of motion and patient-reported outcome measures (Oxford Shoulder Score, Pain Numeric Rating Scale and EuroQol-5D for quality of life). Patients were evaluated preoperatively and 6 weeks, 3 months and 1 year postoperatively.ResultsIn total, 17 complications were registered (17.0%) including five (5.0%) categorised as potentially related to the rehabilitation strategy: one dislocation, one acromion fracture and three cases with persistent pain. Anteflexion, abduction and external rotation, pain scores and the Oxford Shoulder Score all improved significantly (p<0.05) at all time points compared with preoperative. Quality of life improved significantly from 3 months onwards. These secondary outcomes improved further until 1 year postoperatively.ConclusionDirect active rehabilitation after reverse total shoulder arthroplasty seems to be safe and effective. Potentially, this approach will lead to less dependent patients and faster recovery. Larger studies, preferably including a control group, should corroborate our results.Trial registration numberNL7656.
Dominant neoantigen verification in hepatocellular carcinoma by a single-plasmid system coexpressing patient HLA and antigen
Authors: Chen Pu , Chen Dongbo , Bu Dechao , Gao Jie , Qin Wanying , Deng Kangjian , Ren Liying , She Shaoping , Xu Wentao , Yang Yao , Xie Xingwang , Liao Weijia , Chen Hongsong 
Published: April 2023

BackgroundPrevious studies confirmed that most neoantigens predicted by algorithms do not work in clinical practice, and experimental validations remain indispensable for confirming immunogenic neoantigens. In this study, we identified the potential neoantigens with tetramer staining, and established the Co-HA system, a single-plasmid system coexpressing patient human leukocyte antigen (HLA) and antigen, to detect the immunogenicity of neoantigens and verify new dominant hepatocellular carcinoma (HCC) neoantigens.MethodsFirst, we enrolled 14 patients with HCC for next-generation sequencing for variation calling and predicting potential neoantigens. Then, the Co-HA system was established. To test the feasibility of the system, we constructed target cells coexpressing HLA-A*11:01 and the reportedKRASG12D neoantigen as well as specific T-cell receptor (TCR)-T cells. The specific cytotoxicity generated by this neoantigen was shown using the Co-HA system. Moreover, potential HCC-dominant neoantigens were screened out by tetramer staining and validated by the Co-HA system using methods including flow cytometry, enzyme-linked immunospot assay and ELISA. Finally, antitumor test in mouse mode and TCR sequencing were performed to further evaluate the dominant neoantigen.ResultsFirst, 2875 somatic mutations in 14 patients with HCC were identified. The main base substitutions were C>T/G>A transitions, and the main mutational signatures were 4, 1 and 16. The high-frequency mutated genes includedHMCN1,TTNandTP53. Then, 541 potential neoantigens were predicted. Importantly, 19 of the 23 potential neoantigens in tumor tissues also existed in portal vein tumor thrombi. Moreover, 37 predicted neoantigens restricted by HLA-A*11:01, HLA-A*24:02 or HLA-A*02:01 were performed by tetramer staining to screen out potential HCC-dominant neoantigens. HLA-A*24:02-restricted epitope 5'-FYAFSCYYDL-3' and HLA-A*02:01-restricted epitope 5'-WVWCMSPTI-3' demonstrated strong immunogenicity in HCC, as verified by the Co-HA system. Finally, the antitumor efficacy of 5'-FYAFSCYYDL-3'-specific T cells was verified in the B-NDG-B2mtm1Fcrntm1(mB2m)mouse and their specific TCRs were successfully identified.ConclusionWe found the dominant neoantigens with high immunogenicity in HCC, which were verified with the Co-HA system.
A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a bupivacaine hydrochloride implant in patients undergoing abdominoplasty
Authors: Beaton Alina C , Solanki Daneshvari , Salazar Hernan , Folkerth Steve , Singla Neil , Minkowitz Harold S , Leiman David , Vaughn Ben , Skuban Nina , Niebler Gwendolyn 
Published: April 2023

IntroductionSurgical site infiltration with bupivacaine hydrochloride (HCl) is a standard element of postoperative analgesia for soft tissue surgeries, but results in short-lived analgesia. A novel bupivacaine implant, XARACOLL (bupivacaine HCl), is Food and Drug Administration approved for treatment of acute postsurgical pain following adult inguinal herniorrhaphy. This study examined the efficacy and safety of the bupivacaine implant (300 mg) compared with placebo for postsurgical pain after abdominoplasty.MethodsIn this double-blind, placebo-controlled study, patients undergoing abdominoplasty were randomized to three 100 mg bupivacaine implants or three placebo collagen implants, in a 1:1 ratio, implanted intraoperatively. No other analgesics were administered into the surgical site. Patients were allowed opioids and acetaminophen for postoperative pain. Patients were followed for up to 30 days after treatment. Primary outcome: the analgesic effect of the bupivacaine implants through 24 hours postsurgery, measured by the sum of time-weighted pain intensity (SPI24). Prespecified key secondary outcomes included SPI48 and SPI72, percentage of opioid-free patients through 24, 48, and 72 hours, and adverse events, which were tested sequentially to control for multiplicity (ie, if the first variable failed to reach significance, no subsequent variables were declared statistically significant).ResultsThe bupivacaine implant patients (n=181) reported statistically significant lower SPI24 (mean (SD) SPI24=102 (43), 95% CI 95 to 109) compared with placebo patients (n=184; SPI24=117 (45), 95% CI 111 to 123, p=0.002). SPI48 was 190 (88, 95% CI 177 to 204) for INL-001 and 206 (96, 95% CI 192 to 219) for placebo, and not significantly different between groups. The subsequent secondary variables were therefore declared not statistically significant. SPI72 was 265 (131, 95% CI 244 to 285) for INL-001 and 281 (146, 95% CI 261 to 301) for placebo. The opioid-free percentage of patients at 24, 48, and 72 hours was 19%, 17%, and 17% for INL-001 and 6.5% for placebo patients (at all timepoints). The only adverse event occurring in ≥5% of patients and for which proportion INL-001 >placebo was back pain (7.7% vs 7.6%).ConclusionThe study design was limited by not containing an active comparator. Compared with placebo, INL-001 provides postoperative analgesia that is temporally aligned with the period of maximal postsurgical pain in abdominoplasty and offers a favorable safety profile.Trial registration numberNCT04785625.
Heart failure symptom burden in outpatient cardiology: observational cohort study
Authors: Walsh Maria , Bowen Elizabeth , Vaughan Carl , Kiely Fiona 
Published: April 2023

ObjectivesTo assess the self-reported symptom burden in patients with a diagnosis of heart failure attending an outpatient cardiology clinic through the utilisation of validated patient-reported outcome measures.MethodsEligible patients were invited to partake in this observational cohort study. Participant demographics and comorbidities were recorded, followed by participants recording their symptoms using the Integrated Palliative care Outcome Scale (IPOS) and Brief Pain Inventory (BPI) outcome measure tools.ResultsA total of 22 patients were included in the study. The majority were male (n=15). The median age was 74.5 (range 55–94) years. Atrial fibrillation and hypertension were the most common comorbidities (n=10). Dyspnoea, weakness and poor mobility were the most prevalent symptoms, affecting 15 (68%) of the 22 patients. Dyspnoea was reported as being the most troublesome symptom. The BPI was completed by 68% (n=15) of the study participants. Median average pain score was 5/10; median worst pain score in the preceding 24 hours was 6/10 and median pain score at time of BPI completion was 3/10. The impact of pain on daily living during the preceding 24 hours ranged from impacting on all activities (n=7) to not impacting on activities (n=1).ConclusionsPatients with heart failure experience a range of symptoms that vary in severity. Introduction of a symptom assessment tool in the cardiology outpatient setting could help identify patients with a high symptom burden and prompt timely referral to specialist palliative care services.
Spherical Heisenberg flux of magnetic Heisenberg optical ferromagnetic model
Authors: Körpinar Talat , Körpinar Zeliha 
Published: April 2023

In this paper, we introduce optical normalized spherical Heisenberg total ferromagnetic recursional flux of Heisenberg spherical [Formula: see text]-particle with electromagnetic microscale in Heisenberg spherical space [Formula: see text]. Hence, we investigate the properties of spherical Heisenberg normalized electromagnetic microscale by ferromagnetic recursional model. Also, we study optical normalized spherical ferromagnetic Heisenberg recursional density with normalized ferromagnetic microscale for spherical Heisenberg [Formula: see text]-fiber in spherical Heisenberg space [Formula: see text]. Finally, we obtain spherical Heisenberg sonic crystal of spherical Heisenberg [Formula: see text]-fiber with spherical Heisenberg normalized microscale.
Exploring the Complex Relationship between Gut Microbiota and Risk of Colorectal Neoplasia Using Bidirectional Mendelian Randomization Analysis
Authors: Li Wanxin , Zhou Xuan , Yuan Shuai , Wang Lijuan , Yu Lili , Sun Jing , Chen Jie , Xiao Qian , Wan Zhongxiao , Zheng Ju-Sheng , Zhang Cai-Xia , Larsson Susanna C. , Farrington Susan M. , Law Philip , Houlston Richard S. , Tomlinson Ian , Ding Ke-Feng , Dunlop Malcolm G. , Theodoratou Evropi , Li Xue 
Published: April 2023

Abstract

Background:
Human gut microbiome has complex relationships with the host, contributing to metabolism, immunity, and carcinogenesis.

Methods:
Summary-level data for gut microbiota and metabolites were obtained from MiBioGen, FINRISK and human metabolome consortia. Summary-level data for colorectal cancer were derived from a genome-wide association study meta-analysis. In forward Mendelian randomization (MR), we employed genetic instrumental variables (IV) for 24 gut microbiota taxa and six bacterial metabolites to examine their causal relationship with colorectal cancer. We also used a lenient threshold for nine apriori gut microbiota taxa as secondary analyses. In reverse MR, we explored association between genetic liability to colorectal neoplasia and abundance of microbiota studied above using 95, 19, and 7 IVs for colorectal cancer, adenoma, and polyps, respectively.

Results:
Forward MR did not find evidence indicating causal relationship between any of the gut microbiota taxa or six bacterial metabolites tested and colorectal cancer risk. However, reverse MR supported genetic liability to colorectal adenomas was causally related with increased abundance of two taxa: Gammaproteobacteria (β = 0.027, which represents a 0.027 increase in log-transformed relative abundance values of Gammaproteobacteria for per one-unit increase in log OR of adenoma risk; P = 7.06×10−8), Enterobacteriaceae (β = 0.023, P = 1.29×10−5).

Conclusions:
We find genetic liability to colorectal neoplasia may be associated with abundance of certain microbiota taxa. It is more likely that subset of colorectal cancer genetic liability variants changes gut biology by influencing both gut microbiota and colorectal cancer risk.

Impact:
This study highlights the need of future complementary studies to explore causal mechanisms linking both host genetic variation with gut microbiome and colorectal cancer susceptibility.
EIF4A3 Acts on the PI3K–AKT–ERK1/2–P70S6K Pathway through FLOT1 to Influence the Development of Lung Adenocarcinoma
Authors: Yu Wenhao , Liang Jinghui , Fang Tao , Jiang Jin , Zhao Renchang , Li Rongyang , Han Jingyi , Tian Hui 
Published: April 2023

Abstract

Lung adenocarcinoma (LUAD) is a major lung cancer subtype. In this study, we discovered that the eukaryotic translation initiation factor EIF4A3 expression was significantly higher in LUAD tissues and that this higher expression was closely linked to a poor prognosis for LUAD. In addition, we demonstrated that the knockdown of EIF4A3 significantly inhibited the proliferation, invasion, and migration of LUAD cells in vitro and in vivo. The findings of mass spectrometry analysis revealed that EIF4A3 could interact with Flotillin-1 in LUAD cells and that EIF4A3 could positively regulate the expression of FLOT1 at the protein level. Meanwhile, transcriptome sequencing showed that EIF4A3 could influence the development of LUAD by affecting PI3K–AKT–ERK1/2–P70S6K and PI3K class III–mediated autophagy in the Apelin pathway. In addition, we confirmed that Flotillin-1 expression was upregulated in LUAD based on the existing literature, and knockdown of FLOT1 could inhibit the proliferation and migration of LUAD cells. In addition, the knockdown of Flotillin-1 reversed the increase of cell proliferation and migration caused by EIF4A3 overexpression. Furthermore, we found that the activation of PI3K–AKT–ERK1/2–P70S6K signaling pathway and PI3K class III–mediated autophagy caused by EIF4A3 overexpression was rescued by the knockdown of FLOT1. In a word, we proved that EIF4A3 positively regulates the expression of FLOT1 and plays a procancer role in LUAD.

Implications:
Our study revealed the role of EIF4A3 in prognosis and tumor progression in LUAD, indicating that EIF4A3 could be used as the molecular diagnostic and prognostic therapeutic target.
Sex Differences in Association Between Gut Microbiome and Essential Hypertension Based on Ambulatory Blood Pressure Monitoring
Authors: Virwani Preeti Dinesh , Qian Gordon , Hsu Matthew S.S. , Pijarnvanit Tommy K.K.T.S. , Cheung Carman Nga-Man , Chow Yick Hin , Tang Lok Kan , Tse Yiu-Hei , Xian Jia-Wen , Lam Shirley Sau-Wing , Lee Crystal P.I. , Lo Chelsea C.W. , Liu Roxanna K.C. , Ho Tsi Lok , Chow Bak Yue , Leung Kin Sum , Tsang Hing Wai , Lo Emily K.K. , Tung Keith T.S. , Chung Sookja Kim , Yuen Man-Fung , Leung Suet Yi , Ip Patrick , Hung Ivan Fan-Ngai , Louie Jimmy Chun Yu , El-Nezami Hani , Ho Joshua Wing Kei , Lau Kui Kai 
Published: April 2023

Background:
Sex differences in the pathogenesis of hypertension exist. While gut microbiota (GM) has been associated with hypertension, it is unclear whether there are sex-linked differences in the association between GM and hypertension.

Methods:
We conducted a cross-sectional study to investigate the sex differences in associations between GM characterized by shotgun sequencing, GM-derived short-chain fatty acids, and 24-hour ambulatory blood pressure in 241 Hong Kong Chinese (113 men and 128 women; mean age, 54±6 years).

Results:

The hypertensive group was associated with GM alterations; however, significant differences in β-diversity and GM composition in hypertensive versus normotensive groups were only observed in women and not in men under various statistical models adjusting for the following covariates: age, sex, body mass index, sodium intake estimated by spot urine analysis, blood glucose, triglycerides, low- and high-density lipoprotein cholesterol, smoking, menopause, and fatty liver status. Specifically,
Ruminococcus gnavus
,
Clostridium bolteae
, and
Bacteroides ovatus
were significantly more abundant in the hypertensive women, whereas
Dorea formicigenerans
was more abundant in the normotensive women. No bacterial species were found to be significantly associated with hypertension in men. Furthermore, total plasma short-chain fatty acids and propionic acid were independent predictors of systolic and diastolic blood pressure in women but not men.

Conclusions:
GM dysregulation was strongly associated with 24-hour ambulatory blood pressure in women but not men, which may be mediated through propionic acid. Our work suggests that sex differences may be an important consideration while assessing the role of GM in the development and treatment of hypertension.
Exercise and Artery Function in Twins: Sex Differences in a Cross-Over Trial
Authors: Green Daniel J. , Marsh Channa E. , Thomas Hannah J. , Lester Leanne , Scurrah Katrina J. , Haynes Andrew , Naylor Louise H. 
Published: April 2023

Background:
Physical activity reduces cardiovascular risk, partly via direct effects on the arterial wall. We hypothesized that vascular function responses would be modality-specific, sex-dependent, and express a high degree of heritability.

Methods:
We recruited 90 same-sex twins (31 monozygotic, 14 dizygotic dizygotic pairs; 25.8±6.0 years) and randomized 70 (25 monozygotic, 10 dizygotic) to complete, as pairs, 3 months each of resistance and endurance training, separated by a 3-month washout.

Results:

Brachial artery flow-mediated (FMD%) and glyceryl-trinitrate induced dilation (GTN%) both increased following endurance (FMD%: ∆1.46%,
P
<0.001; GTN%: ∆1.76%,
P
=0.004) and resistance (FMD%: ∆1.73%,
P
<0.001; GTN%: ∆1.68%,
P
=0.045). About one-third of participants failed to respond to one or other mode; 10% failed to respond to both for FMD% (17% for GTN%). FMD% and GTN% increased significantly in response to both resistance and endurance in females (
P
<0.05), but not males. Twin analysis revealed that responses to both FMD% and GTN% with exercise training for both modalities were dependent on factors shared by monozygotic pairs and that a large contribution from genetic effects is unlikely.

Conclusions:
Our findings indicate that both endurance and resistance can enhance vascular function and that responses in females were more marked. Most individuals respond to one or other form of training, with few unresponsive to both; a finding that has implications for optimizing exercise-based approaches for individualized benefit. Focusing on characteristics of exercise prescription may be more important than the impact of distinct candidate genes when considering exercise as a form of vascular medicine.

Registration:

URL:
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371222
; Unique identifier: ACTRN 12616001095459.