bluuebunny/crossref_metadata_2025_split huggingface dataset:
The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors: a nationwide cohort study
Authors: Chan Yi-Hsin , Chao Tze-Fan , Chen Shao-Wei , Lee Hsin-Fu , Li Pei-Ru , Chen Wei-Min , Yeh Yung-Hsin , Kuo Chi-Tai , See Lai-Chu , Lip Gregory Y. H. 
Published: June 2022

Abstract
Background
Although a few meta-analyses were conducted to compare the risk of incident atrial fibrillation (AF) between sodium-glucose cotransporter-2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and other anti-hyperglycemic agents using indirect or direct comparison, the above analyses showed conflicting results with each other. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i, GLP-1RA, and dipeptidyl peptidase-4 inhibitor (DPP4i) among a large longitudinal cohort of diabetic patients.

Methods
In this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, a total of 344,893, 44,370, and 393,100 consecutive patients with type 2 diabetes without preexisting AF receiving GLP-1RA, SGLT2i, and DPP4i, respectively, were enrolled from May 1, 2016, to December 31, 2019. We used 1:1 propensity score matching (PSM) to balance covariates across paired study groups. Patients were followed from the drug index date until the occurrence of AF, death, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first.

Results
After PSM, there were 245,442, 43,682, and 39,190 paired cohorts of SGLT2i-DPP4i, SGLT2i-GLP-1RA, and GLP-1RA-DPP4i, respectively. SGLT2i treatment was associated with lower risk of new-onset AF in participants with type 2 diabetes compared with either DPP4i [hazard ratio (HR):0.90; 95% confidential interval (CI) 0.84–0.96; P = 0.0028] or GLP-1RA [HR 0.74; 95% CI 0.63–0.88; P = 0.0007] treatment after PSM. There was no difference in the risk of incident AF between GLP-1RA and DPP4i users [HR 1.01; 95% CI 0.86–1.19; P = 0.8980]. The above findings persisted among several important subgroups. Dapagliflozin was specifically associated with a lower risk of new-onset AF compared with DPP4i (P interaction = 0.02).

Conclusions
Compared with DPP4i, SGLT2i but not GLP-1RA was associated with a lower risk of incident AF in patients with type 2 diabetes.
Improve individual treatment by comparing treatment benefits: cancer artificial intelligence survival analysis system for cervical carcinoma
Authors: Liang Jieyi , He Tingshan , Li Hong , Guo Xueqing , Zhang Zhiqiao 
Published: June 2022

AbstractPurposeThe current study aimed to construct a novel cancer artificial intelligence survival analysis system for predicting the individual mortality risk curves for cervical carcinoma patients receiving different treatments.MethodsStudy dataset (n = 14,946) was downloaded from Surveillance Epidemiology and End Results database. Accelerated failure time algorithm, multi-task logistic regression algorithm, and Cox proportional hazard regression algorithm were used to develop prognostic models for cancer specific survival of cervical carcinoma patients.ResultsMultivariate Cox regression identified stage, PM, chemotherapy, Age, PT, and radiation_surgery as independent influence factors for cervical carcinoma patients. The concordance indexes of Cox model were 0.860, 0.849, and 0.848 for 12-month, 36-month, and 60-month in model dataset, whereas it were 0.881, 0.845, and 0.841 in validation dataset. The concordance indexes of accelerated failure time model were 0.861, 0.852, and 0.851 for 12-month, 36-month, and 60-month in model dataset, whereas it were 0.882, 0.847, and 0.846 in validation dataset. The concordance indexes of multi-task logistic regression model were 0.860, 0.863, and 0.861 for 12-month, 36-month, and 60-month in model dataset, whereas it were 0.880, 0.860, and 0.861 in validation dataset. Brier score indicated that these three prognostic models have good diagnostic accuracy for cervical carcinoma patients. The current research lacked independent external validation study.ConclusionThe current study developed a novel cancer artificial intelligence survival analysis system to provide individual mortality risk predictive curves for cervical carcinoma patients based on three different artificial intelligence algorithms. Cancer artificial intelligence survival analysis system could provide mortality percentage at specific time points and explore the actual treatment benefits under different treatments in four stages, which could help patient determine the best individualized treatment. Cancer artificial intelligence survival analysis system was available at:https://zhangzhiqiao15.shinyapps.io/Tumor_Artificial_Intelligence_Survival_Analysis_System/.
Dual block HER2 assessment increased HER2 immunohistochemistry positive rate in resected specimens of gastric cancer: a prospective multicenter clinical trial from China
Authors: Xu Chen , Sun Miaomiao , Jin Mei , Li Zengshan , Qin Rong , Ren Guoping , Sun Wenyong , Chen Lirong , Luan Lijuan , Liu Yalan , Jiang Dongxian , Chen Lingli , Luo Rongkui , Hou Yingyong 
Published: June 2022

Abstract
Background
Former single center studies indicated that HER2 assessment with two primary tumor blocks (dual block HER2 assessment) could be an efficient and practical approach to overcome the adverse impact of heterogeneity and acquire a HER2 positive rate in gastric cancer (GC). This multicenter prospective clinical trial (NCT 02843412) was launched to verify its value and generality.

Methods
A total of 3806 participants with primary GCs have been enrolled from 8 hospitals in China. Two primary tumor blocks were selected and recorded as block 1 and block 2 after histological evaluation. An HER2 (4B5) rabbit monoclonal antibody was used for the immunohistochemistry (IHC) analysis.

Results
In total patients, HER2 IHC positive (3+) rate with dual block assessment (9.4%) was higher than that with single block assessment (block 1: 7.8%, block 2: 7.8%) (P < 0.001). Compared with single-block assessment, dual-block assessment increased the positive rate by approximate 20%. Similarly, HER2 equivocal (2+) rate was increased in dual block assessment (25.8%), which was higher than that in single block assessment (block 1: 20.3%, block 2: 20.9%) (P < 0.001). Conversely, dual block assessment demonstrated a lower HER2 negative (0/1+) rate (64.8%) than single block assessment (block1: 71.9%, block 2: 71.3%) (P < 0.001). These findings were also confirmed in individual hospitals.

Conclusions
Dual block HER2 assessment effectively increased HER2 IHC positive rate in resected specimens of GC. We recommended dual block HER2 assessment be promoted in routine clinical practice in GC.

Trial registration
ClinicalTrials.gov, NCT 02843412. Registered 1 July 2016 - Retrospectively registered.
Ex vivo fluorescence confocal microscopy: chances and changes in the analysis of breast tissue
Authors: Nackenhorst Maja Carina , Kasiri Mohammad , Gollackner Bernd , Regele Heinz 
Published: June 2022

Abstract
Background
Rapid histologic diagnosis of frozen sections is essential for a variety of surgical procedures. Frozen sections however, require specialized lab equipment, are prone to freezing artifacts and are not applicable to all types of tissue. Adipose tissue is especially difficult to process in frozen sections. Although these limitations are well known, no alternative method for microscopic tissue analysis that might replace frozen sections could be established. Our objective was to evaluate whether tissue imaging based on ex vivo fluorescent confocal microscopy (FCM) is applicable for rapid microscopic assessment of breast tumors specimens with abundant adipose tissue.

Methods
We evaluated 17 tissue samples from mastectomy specimens, rich in adipose tissue, submitted to the department of pathology at the Medical University of Vienna. We conducted our study on the FCM VivaScope® 2500M-G4 (Mavig GmbH, Munich, Germany; Caliber I.D.; Rochester NY, USA).

Results
When comparing FCM to frozen sections, we found a very similar overall processing time for FCM images and frozen sections respectively. Image quality was mostly superior to frozen sections (especially for adipose tissue and nuclear detail) but inferior to H&E stained FFPE sections. Limitations of the technology were uneven coloring, invisibility of ink applied for marking tissue margins and distortion artifacts if too much pressure is applied to the tissue.

Conclusion
FCM has the potential to expand the application and usefulness of rapid tissue analysis as speed is comparable and quality exceeds that of frozen sections especially in tissues rich in adipose cells such as breast specimen.
Economic evaluation of a multi-strategy intervention that improves school-based physical activity policy implementation
Authors: Lane Cassandra , Nathan Nicole , Reeves Penny , Sutherland Rachel , Wolfenden Luke , Shoesmith Adam , Hall Alix 
Published: June 2022

AbstractBackgroundInternationally, government policies mandating schools to provide students with opportunities to participate in physical activity are poorly implemented. The multi-componentPhysically Active Children in Education(PACE) intervention effectively assists schools to implement one such policy. We evaluated the value of investment by health service providers tasked with intervention delivery, and explored where adaptations might be targeted to reduce program costs for scale-up.MethodsA prospective trial-based economic evaluation of an implementation intervention in 61 primary schools in New South Wales (NSW), Australia. Schools were randomised to the PACE intervention or a wait-list control. PACE strategies included centralised technical assistance, ongoing consultation, principal's mandated change, identifying and preparing in-school champions, educational outreach visits, and provision of educational materials and equipment. Effectiveness was measured as the mean weekly minutes of physical activity implemented by classroom teachers, recorded in a daily log book at baseline and 12-month follow-up. Delivery costs (reported in $AUD, 2018) were evaluated from a public finance perspective. Cost data were used to calculate: total intervention cost, cost per strategy and incremental cost (overall across all schools and as an average per school). Incremental cost-effectiveness ratios (ICERs) were calculated as the incremental cost of delivering PACE divided by the estimated intervention effect.ResultsPACE cost the health service provider a total of $35,692 (95% uncertainty interval [UI] $32,411, $38,331) to deliver; an average cost per school of $1151 (95%UI $1046, $1236). Training in-school champions was the largest contributor: $19,437 total; $627 ($0 to $648) average per school. Educational outreach was the second largest contributor: $4992 total; $161 ($0 to $528) average per school. The ICER was $29 (95%UI $17, $64) for every additional minute of weekly physical activity implemented per school.ConclusionPACE is a potentially cost-effective intervention for increasing schools implementation of a policy mandate. The investment required by the health service provider makes use of existing funding and infrastructure; the additional cost to assist schools to implement the policy is likely not that much. PACE strategies may be adapted to substantially improve delivery costs.Trial registrationAustralia New Zealand Clinical Trials Registry ACTRN12617001265369; Prospectively registered 1st September 2017https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373520
COVID-19 in Fabry disease: a reference center prospective study
Authors: Bothou Christina , Saleh Lanja , von Eckardstein Arnold , Beuschlein Felix , Nowak Albina 
Published: June 2022

Abstract
Background
During the coronavirus disease-19 (COVID-19) pandemic, vulnerable populations must be identified to prevent increased mortality. Fabry disease (FD) is a rare X-linked lysosomal storage disorder leading to chronic kidney disease (CKD), cardiomyopathy, pneumonopathy and premature strokes. Little is known whether SARS-CoV-2 infection bears a particular risk for FD patients.

Methods
During pandemic (02.2020–03.2021) we have regularly followed 104 unvaccinated FD patients. In 61/104, titre of serum antibodies against SARS-CoV-2 were measured and SARS-CoV-2 PCR test was performed in symptomatic patients or in case of positivity of other family members. The symptoms and duration of COVID-19 were reported by the patients or the treating physician.

Results
No deaths or intensive care unit hospitalizations occurred. 13/104 (12.5%) were diagnosed with SARS-CoV-2 infection (16.7% (4/24) men 12.2% (6/49) women of classic phenotype, 25% (3/12) of the men and 0% (0/8) of the women of later- onset phenotype). Of those, 2/13 (15.4%) patients—both kidney transplant recipients—developed severe COVID-19, were hospitalized, and required a high-flow oxygen mask. The rest either developed mild COVID-19 manifestations (8/13, 61.5%) or were asymptomatic (3/13, 23.1%). 2/13 (15.4%) of the patients experienced Fabry pain crisis and 3/13 (23.1%) long COVID-19 like symptoms.

Conclusions
Similar to the general population, in FD patients the risk for severe COVID-19 seems to be driven by the immune system rather than by FD itself. Immunosuppression in kidney transplant recipients represented the highest risk in this population.
Cloning, expression, and one-step purification/immobilization of two carbohydrate-binding module-tagged alcohol dehydrogenases
Authors: Benito Mario , Román Ramón , Ortiz Garazi , Casablancas Antoni , Álvaro Gregorio , Caminal Gloria , González Gloria , Guillén Marina 
Published: June 2022

AbstractBackgroundThe feasibility of biochemical transformation processes is usually greatly dependent on biocatalysts cost. Therefore, immobilizing and reusing biocatalysts is an approach to be considered to bring biotransformations closer to industrial feasibility, since it does not only allow to reuse enzymes but can also improve their stability towards several reaction conditions. Carbohydrate-Binding Modules (CBM) are well-described domains involved in substrate binding which have been already used as purification tags.ResultsIn this work, two different Carbohydrate-Binding Modules (CBM3 and CBM9) have been successfully fused to an alcohol dehydrogenase fromSaccharomyces cerevisiae, which has been produced in bench-scale reactor using an auxotrophic M15-derivedE. colistrain, following a fed-batch strategy with antibiotic-free medium. Around 40 mg·g− 1DCW of both fusion proteins were produced, with a specific activity of > 65 AU·mg− 1. Overexpressed proteins were bound to a low-cost and highly selective cellulosic support by one-step immobilization/purification process at > 98% yield, retaining about a 90% of initial activity. Finally, the same support was also used for protein purification, aiming to establish an alternative to metal affinity chromatography, by which CBM9 tag proved to be useful, with a recovery yield of > 97% and 5-fold increased purity grade.ConclusionCBM domains were proved to be suitable for one-step immobilization/purification process, retaining almost total activity offered. However, purification process was only successful with CBM9.
Prenatal diagnosis of Williams-Beuren syndrome by ultrasound and chromosomal microarray analysis
Authors: Huang Ruibin , Zhou Hang , Fu Fang , Li Ru , Lei Tingying , Li Yingsi , Cheng Ken , Wang You , Yang Xin , Li Lushan , Jing Xiangyi , Zhang Yongling , Li Fucheng , Li Dongzhi , Liao Can 
Published: June 2022

Abstract
Background
There are a few literature reports of prenatal ultrasound manifestations of Williams-Beuren syndrome. We aimed to explore the prenatal diagnosis of Williams-Beuren syndrome by ultrasound and chromosomal microarray analysis and describe the prenatal ultrasound performance of this syndrome.

Methods
In this retrospective study, we reported eight cases of Williams-Beuren syndrome diagnosed at our prenatal diagnostic center from 2016 to 2021. We systematically reviewed clinical data from these cases, including indications for invasive testing, sonographic findings, QF-PCR results, chromosomal microarray analysis results, and pregnancy outcomes.

Results
In this study, the common ultrasound features were ventricular septal defect (37.5%), intrauterine growth retardation (25%), and aortic coarctation (25%). Moreover, all patients were found to have a common deletion in the Williams-Beuren syndrome chromosome region at the 7q11.23 locus, which contained the elastin gene. Deletion sizes ranged from 1.42 to 2.07 Mb. Seven parents asked for termination of pregnancy, and one patient was lost to follow-up.

Conclusions
This study is the most extensive prenatal study using chromosomal microarray analysis technology for detailed molecular analysis of Williams-Beuren syndrome cases. We reported three cases combined with first-reported ultrasound manifestations. Case 1 was concomitant with multicystic dysplastic kidney and duodenal atresia combined with case 3. Notably, case 4 was combined with multiple cardiovascular malformations: Tetralogy of Fallot, right aortic arch, and supravalvar aortic stenosis. These manifestations expand the intrauterine ultrasound phenotype of Williams-Beuren syndrome in previous literature reports.
Emerging role of exosomes in cancer progression and tumor microenvironment remodeling
Authors: Paskeh Mahshid Deldar Abad , Entezari Maliheh , Mirzaei Sepideh , Zabolian Amirhossein , Saleki Hossein , Naghdi Mohamad Javad , Sabet Sina , Khoshbakht Mohammad Amin , Hashemi Mehrdad , Hushmandi Kiavash , Sethi Gautam , Zarrabi Ali , Kumar Alan Prem , Tan Shing Cheng , Papadakis Marios , Alexiou Athanasios , Islam Md Asiful , Mostafavi Ebrahim , Ashrafizadeh Milad 
Published: June 2022

AbstractCancer is one of the leading causes of death worldwide, and the factors responsible for its progression need to be elucidated. Exosomes are structures with an average size of 100 nm that can transport proteins, lipids, and nucleic acids. This review focuses on the role of exosomes in cancer progression and therapy. We discuss how exosomes are able to modulate components of the tumor microenvironment and influence proliferation and migration rates of cancer cells. We also highlight that, depending on their cargo, exosomes can suppress or promote tumor cell progression and can enhance or reduce cancer cell response to radio- and chemo-therapies. In addition, we describe how exosomes can trigger chronic inflammation and lead to immune evasion and tumor progression by focusing on their ability to transfer non-coding RNAs between cells and modulate other molecular signaling pathways such as PTEN and PI3K/Akt in cancer. Subsequently, we discuss the use of exosomes as carriers of anti-tumor agents and genetic tools to control cancer progression. We then discuss the role of tumor-derived exosomes in carcinogenesis. Finally, we devote a section to the study of exosomes as diagnostic and prognostic tools in clinical courses that is important for the treatment of cancer patients. This review provides a comprehensive understanding of the role of exosomes in cancer therapy, focusing on their therapeutic value in cancer progression and remodeling of the tumor microenvironment.Graphical Abstract
Effects of robot-assisted therapy on upper limb and cognitive function in patients with stroke: study protocol of a randomized controlled study
Authors: Wang Yana , Ye Mingzhu , Tong Yujie , Xiong Li , Wu Xuejiao , Geng Chao , Zhang Wen , Dai Ziqi , Tian Wei , Rong Jifeng 
Published: June 2022

AbstractBackgroundImpairments in upper limb motor function and cognitive ability are major health problems experienced by stroke patients, necessitating the development of novel and effective treatment options in stroke care. The aim of this study is to examine the effects of robot-assisted therapy on improving upper limb and cognitive functions in stroke patients.MethodsThis will be a single-blinded, 2-arm, parallel design, randomized controlled trial which will include a sample size of 86 acute and subacute stroke patients to be recruited from a single clinical hospital in Shanghai, China. Upon qualifying the study eligibility, participants will be randomly assigned to receive either robot-assisted therapy or conventional therapy with both interventions being conducted over a 6-week period in a clinical rehabilitation setting. In addition to comprehensive rehabilitation, the robot-assisted therapy group will receive a 30-min Armguider robot-assisted therapy intervention 5 days a week. Primary efficacy outcomes will include Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and Mini-Mental Status Examination (MMSE). Other secondary outcomes will include Trail Making Test (TMT), Auditory Verbal Learning Test (AVLT), Digit Symbol Substitution Test (DSST), and Rey–Osterrieth Complex Figure Test (ROCFT). All trial outcomes will be assessed at baseline and at 6-week follow-up. Intention-to-treat analyses will be performed to examine changes from baseline in the outcomes. Adverse events will be monitored throughout the trial period.DiscussionThis will be the first randomized controlled trial aimed at examining the effects of robot-assisted therapy on upper limb and cognitive functions in acute and subacute stroke patients. Findings from the study will contribute to our understanding of using a novel robotic rehabilitation approach to stroke care and rehabilitation.Trial registrationChinese Clinical Trial RegistryChiCTR2100050856. Registered on 5 September 2021.