bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclic workflow to improve implementation of learning points from morbidity and mortality meetings
Authors: Myren B.J. , de Hullu J.A. , Koksma J.J. , Gelderblom M.E. , Hermens R.P.M.G. , Zusterzeel P.L.M. 
Published: October 2022

AbstractBackgroundMorbidity and mortality meetings (M&MMs) are organized in most hospital departments with an educational purpose to learn from adverse events (AEs) to improve patient care. M&MMs often lack effectiveness due to unsuccessful systematic follow-up of areas of improvement. This can have an effect on improving patient safety and care. Therefore, a new strategy that focuses on implementing areas of improvement into daily practice is necessary. The study aim is to see if we could improve the implementation of meeting outcomes from the M&MM by using a cyclic workflow, and which factors are important to achieve its implementation.MethodsThis prospective study took place at the department of gynecologic oncology of a university hospital. Research was conducted with a participatory action research (PAR) approach using 10 consecutive M&MMs in 2019 and 2020. The cyclical workflow consisted of an action list based on the PDCA-cycle, a check of the implementation of areas for improvement at the next M&MM and regular monitoring of tasks. Each M&MM was observed and each professional with an assigned task was interviewed and gave their informed consent. Thematic content analysis was performed with the program Atlas.ti 8.4.20.ResultsOut of the 39 tasks that resulted from 10 M&MMs, 37 (94.8%) followed all the steps in the PDCA-cycle and were implemented. In total, 16 interviews were conducted with consultants, nurses, registrars and residents. Five main factors were important to achieve follow-up of areas for improvement: organizational culture, motivation, commitment, communication to mobilize employees and skills. Repetition of the cyclic workflow at the M&MM and an external person who reminded professionals of their assigned task(s) was important to change habits and motivate professionals.ConclusionCyclical tools can support the implementation of areas for improvement to optimize the M&MM. A M&MM with an organizational culture where attendees can discuss openly and freely may motivate attendees to take on tasks successfully. A positive stimulant to reach commitment of professionals is team participation. Integrating new habits of reflection may lead to a deeper level of learning from the PDCA-cycle and of the M&MM. Creating a learning environment outside of the M&MM may support professionals to take on actions and engage in improvement practices. Future research may focus on including a comparative analysis to show a success rate of the implementation of learning points from the M&MM more clearly.
Clinical implications of circulating tumor DNA in predicting the outcome of diffuse large B cell lymphoma patients receiving first-line therapy
Authors: Li Miaomiao , Mi Lan , Wang Chunyang , Wang Xiaojuan , Zhu Jianhua , Qi Fei , Yu Hui , Ye Yingying , Wang Dedao , Cao Jiaowu , Hu Dingyao , Yang Quanyu , Zhao Dandan , Ma Tonghui , Song Yuqin , Zhu Jun 
Published: October 2022

Abstract

Background
Circulating tumor DNA (ctDNA) has been proven to be a promising tumor-specific biomarker in solid tumors, but its clinical utility in risk stratification and early prediction of relapse for diffuse large B cell lymphoma (DLBCL) has not been well explored.

Methods
Here, using a lymphoma-specific sequencing panel, we assessed the prognostic and predictive utilities of ctDNA measurements before, during, and after first-line therapy in 73 Chinese DLBCL patients.

Results
The pretreatment ctDNA level serving as an independent prognostic factor for both progression-free survival (PFS, adjusted HR 2.47; p = 0.004) and overall survival (OS, adjusted HR 2.49; p = 0.011) was confirmed in our cohort. Furthermore, the patients classified as molecular responders who presented a larger decrease in ctDNA levels after the initial two treatment cycles had more favorable PFS (unreached vs. 6.25 months; HR 5.348; p = 0.0015) and OS (unreached vs. 25.87; HR 4.0; p = 0.028) than non-responders. In addition, interim ctDNA clearance may be an alternative noninvasive method of positron emission tomography and computed tomography (PET-CT) for predicting better PFS (HR 3.65; p = 0.0033) and OS (HR 3.536; p = 0.016). We also demonstrated that posttreatment ctDNA was a sensitive indicator for detecting minimal residual disease (MRD) in patients with a high risk of recurrence (HR 6.471; p = 0.014), who were otherwise claimed to achieve radiographic CR (complete remission).

Conclusions
CtDNA is a promising noninvasive tool for prognosis prediction, response assessment, and early relapse prediction of first-line treatment in DLBCL patients.
Immunogenicity, efficacy, and safety of SARS-CoV-2 vaccine dose fractionation: a systematic review and meta-analysis
Authors: Yang Bingyi , Huang Xiaotong , Gao Huizhi , Leung Nancy H. , Tsang Tim K. , Cowling Benjamin J. 
Published: October 2022

Abstract
Background
Dose fractionation of a coronavirus disease 2019 (COVID-19) vaccine could effectively accelerate global vaccine coverage, while supporting evidence of efficacy, immunogenicity, and safety are unavailable, especially with emerging variants.

Methods
We systematically reviewed clinical trials that reported dose-finding results and estimated the dose-response relationship of neutralizing antibodies (nAbs) of COVID-19 vaccines using a generalized additive model. We predicted the vaccine efficacy against both ancestral and variants, using previously reported correlates of protection and cross-reactivity. We also reviewed and compared seroconversion to nAbs, T cell responses, and safety profiles between fractional and standard dose groups.

Results
We found that dose fractionation of mRNA and protein subunit vaccines could induce SARS-CoV-2-specific nAbs and T cells that confer a reasonable level of protection (i.e., vaccine efficacy > 50%) against ancestral strains and variants up to Omicron. Safety profiles of fractional doses were non-inferior to the standard dose.

Conclusions
Dose fractionation of mRNA and protein subunit vaccines may be safe and effective, which would also vary depending on the characteristics of emerging variants and updated vaccine formulations.
Promoting equity in health emergencies through health systems strengthening: lessons learned from disability inclusion in the COVID-19 pandemic
Authors: Pearce Emma , Kamenov Kaloyan , Barrett Darryl , Cieza Alarcos 
Published: October 2022

AbstractDiscriminatory health systems and inequalities in service provision inevitably create barriers for certain populations in a health emergency. Persons with disabilities have been disproportionately affected by the COVID-19 pandemic. They commonly experience three increased risks - of contracting the disease, of severe disease or death, and of new or worsening health conditions. These added risks occur due to a range of barriers in the health sector, including physical barriers that prevent access to health facilities and specific interventions; informational barriers that prevent access to health information and/or reduce health literacy; and attitudinal barriers which give rise to stigma and exclusion, all of which add to discrimination and inequality. Furthermore, national health emergency preparedness and planning may fail to consider the needs and priorities of persons with disabilities, in all their diversity, thus leaving them behind in responses. This commentary discusses the importance of inclusive health systems strengthening as a prerequisite for accessible and comprehensive health emergency preparedness and response plans that reach everyone. Lessons learned relating to disability inclusion in the COVID-19 pandemic can inform health systems strengthening in recovery efforts, addressing underlying barriers to access and inclusion, and in turn improving preparedness for future health emergencies.
Efficacy and safety of carbon ion radiotherapy for bone sarcomas: a systematic review and meta-analysis
Authors: Dong Meng , Liu Ruifeng , Zhang Qiuning , Luo Hongtao , Wang Dandan , Wang Yuhang , Chen Junru , Ou Yuhong , Wang Xiaohu 
Published: October 2022

Abstract
Objective
This study aimed to systematically evaluate and conduct a meta-analysis of the efficacy and safety of carbon ion radiotherapy for bone sarcomas.

Methods
We searched for articles using the PubMed, Embase, Cochrane Library, and the Web of Science databases from their inception to January 12, 2022. Two researchers independently screened the literature and extracted data based on the inclusion and exclusion criteria. Statistical analyses were performed using STATA version 14.0.

Results
We searched for 4378 candidate articles, of which 12 studies were included in our study according to the inclusion and exclusion criteria. Of the 897 BSs patients who received carbon ion radiotherapy in the studies, 526 patients had chordoma, 255 patients had chondrosarcoma, 112 patients had osteosarcoma, and 4 patients had other sarcomas. The local control rate at 1, 2, 3, 4, 5, and 10 years in these studies were 98.5% (95% confidence interval [CI] = 0.961–1.009, I2 = 0%), 85.8% (95% CI = 0.687–1.030, I2 = 91%), 86% (95% CI = 0.763–0.957, I2 = 85.3%), 91.1% (95% CI = 0.849–0.974), 74.3% (95% CI = 0.666–0.820, I2 = 85.2%), and 64.7% (95% CI = 0.451–0.843, I2 = 95.3%), respectively. The overall survival rate at 1, 2, 3, 4, 5, and 10 years in these studies were 99.9% (95% CI = 0.995–1.004, I2 = 0%), 89.6% (95% CI = 0.811–0.980, I2 = 96.6%), 85% (95% CI = 0.750–0.950, I2 = 89.4%), 92.4% (95% CI = 0.866–0.982), 72.7% (95% CI = 0.609–0.844, I2 = 95.3%), and 72.1% (95% CI = 0.661–0.781, I2 = 46.5%), respectively. Across all studies, the incidence of acute and late toxicities was mainly grade 1 to grade 2, and grade 1 to grade 3, respectively.

Conclusion
As an advanced radiotherapy, carbon ion radiotherapy is promising for patients with bone sarcomas that are unresectable or residual after incomplete surgery. The data indicated that carbon ion radiotherapy was safe and effective for bone sarcomas, showing promising results for local control, overall survival, and lower acute and late toxicity.

PROSPERO registration number

CRD42021258480.
Matrix Gla protein (MGP), GATA3, and TRPS1: a novel diagnostic panel to determine breast origin
Authors: Du Tian , Pan Lu , Zheng Chengyou , Chen Keming , Yang Yuanzhong , Chen Jiewei , Chao Xue , Li Mei , Lu Jiabin , Luo Rongzhen , Zhang Jinhui , Wu Yu , He Jiehua , Jiang Dongping , Sun Peng 
Published: October 2022

Abstract
Background
Metastatic breast carcinoma is commonly considered during differential diagnosis when metastatic disease is detected in females. In addition to the tumor morphology and documented clinical history, sensitive and specific immunohistochemical (IHC) markers such as GCDFP-15, mammaglobin, and GATA3 are helpful for determining breast origin. However, these markers are reported to show lower sensitivity in certain subtypes, such as triple-negative breast cancer (TNBC).

Materials and methods
Using bioinformatics analyses, we identified a potential diagnostic panel to determine breast origin: matrix Gla protein (MGP), transcriptional repressor GATA binding 1 (TRPS1), and GATA-binding protein 3 (GATA3). We compared MGP, TRPS1, and GATA3 expression in different subtypes of breast carcinoma of (n = 1201) using IHC. As a newly identified marker, MGP expression was also evaluated in solid tumors (n = 2384) and normal tissues (n = 1351) from different organs.

Results
MGP and TRPS1 had comparable positive expression in HER2-positive (91.2% vs. 92.0%, p = 0.79) and TNBC subtypes (87.3% vs. 91.2%, p = 0.18). GATA3 expression was lower than MGP (p < 0.001) or TRPS1 (p < 0.001), especially in HER2-positive (77.0%, p < 0.001) and TNBC (43.3%, p < 0.001) subtypes. TRPS1 had the highest positivity rate (97.9%) in metaplastic TNBCs, followed by MGP (88.6%), while only 47.1% of metaplastic TNBCs were positive for GATA3. When using MGP, GATA3, and TRPS1 as a novel IHC panel, 93.0% of breast carcinomas were positive for at least two markers, and only 9 cases were negative for all three markers. MGP was detected in 36 cases (3.0%) that were negative for both GATA3 and TRPS1. MGP showed mild-to-moderate positive expression in normal hepatocytes, renal tubules, as well as 31.1% (99/318) of hepatocellular carcinomas. Rare cases (0.6–5%) had focal MGP expression in renal, ovarian, lung, urothelial, and cholangiocarcinomas.

Conclusions
Our findings suggest that MGP is a newly identified sensitive IHC marker to support breast origin. MGP, TRPS1, and GATA3 could be applied as a reliable diagnostic panel to determine breast origin in clinical practice.
INSERT-seq enables high-resolution mapping of genomically integrated DNA using Nanopore sequencing
Authors: Ivančić Dimitrije , Mir-Pedrol Júlia , Jaraba-Wallace Jessica , Rafel Núria , Sanchez-Mejias Avencia , Güell Marc 
Published: October 2022

AbstractComprehensive characterisation of genome engineering technologies is relevant for their development and safe use in human gene therapy. Short-read based methods can overlook insertion events in repetitive regions. We develop INSERT-seq, a method that combines targeted amplification of integrated DNA, UMI-based correction of PCR bias and Oxford Nanopore long-read sequencing for robust analysis of DNA integration. The experimental pipeline improves the number of mappable insertions at repetitive regions by 4.8–7.3% and larger repeats are processed with a computational peak calling pipeline. INSERT-seq is a simple, cheap and robust method to quantitatively characterise DNA integration in diverse ex vivo and in vivo samples.
Innate immunity changes in soccer players after whole-body cryotherapy
Authors: Selleri Valentina , Mattioli Marco , Lo Tartaro Domenico , Paolini Annamaria , Zanini Giada , De Gaetano Anna , D’Alisera Roberta , Roli Laura , Melegari Alessandra , Maietta Pasqualino , Tripi Ferdinando , Guerra Emanuele , Chester Johanna , Savino Gustavo , Trenti Tommaso , Cossarizza Andrea , Mattioli Anna Vittoria , Pinti Marcello , Nasi Milena 
Published: October 2022

AbstractWhole-body cryotherapy (WBC) consists of short exposure (up to 2–3 min) to dry air at cryogenic temperatures (up to -190 °C) and has recently been applied for muscle recovery after injury to reduce the inflammation process. We aimed to determine the impact of cryotherapy on immunological, hormonal, and metabolic responses in non-professional soccer players (NPSPs). Nine male NPSPs (age: 20 ± 2 years) who trained regularly over 5 consecutive days, immediately before and after each training session, were subjected to WBC treatment (WBC-t). Blood samples were collected for the evaluation of fifty analytes including hematologic parameters, serum chemistry, and hormone profiles. Monocytes phenotyping (Mo) was performed and plasmatic markers, usually increased during inflammation [CCL2, IL-18, free mitochondrial (mt)DNA] or with anti-inflammatory effects (IL2RA, IL1RN), were quantified. After WBC-t, we observed reduced levels of ferritin, mean corpuscular hemoglobin, mean platelet volume, testosterone, and estradiol, which however remain within the normal ranges. The percentage of the total, intermediates and non-classical Mo increased, while classical Mo decreased. CXCR4 expression decreased in each Mo subset. Plasma IL18 and IL2RA levels decreased, while IL1RN only exhibited a tendency to decrease and CCL2 showed a tendency to increase. Circulating mtDNA levels were not altered following WBC-t. The differences observed in monocyte subsets after WBC-t may be attributable to their redistribution into the surrounding tissue. Moreover, the decrease of CXCR4 in Mo subpopulations could be coherent with their differentiation process. Thus, WBC through yet unknown mechanisms could promote their differentiation having a role in tissue repair.
Machine learning algorithms to identify cluster randomized trials from MEDLINE and EMBASE
Authors: Al-Jaishi Ahmed A. , Taljaard Monica , Al-Jaishi Melissa D. , Abdullah Sheikh S. , Thabane Lehana , Devereaux P. J. , Dixon Stephanie N. , Garg Amit X. 
Published: October 2022

Abstract
Background
Cluster randomized trials (CRTs) are becoming an increasingly important design. However, authors of CRTs do not always adhere to requirements to explicitly identify the design as cluster randomized in titles and abstracts, making retrieval from bibliographic databases difficult. Machine learning algorithms may improve their identification and retrieval. Therefore, we aimed to develop machine learning algorithms that accurately determine whether a bibliographic citation is a CRT report.

Methods
We trained, internally validated, and externally validated two convolutional neural networks and one support vector machine (SVM) algorithm to predict whether a citation is a CRT report or not. We exclusively used the information in an article citation, including the title, abstract, keywords, and subject headings. The algorithms’ output was a probability from 0 to 1. We assessed algorithm performance using the area under the receiver operating characteristic (AUC) curves. Each algorithm’s performance was evaluated individually and together as an ensemble. We randomly selected 5000 from 87,633 citations to train and internally validate our algorithms. Of the 5000 selected citations, 589 (12%) were confirmed CRT reports. We then externally validated our algorithms on an independent set of 1916 randomized trial citations, with 665 (35%) confirmed CRT reports.

Results
In internal validation, the ensemble algorithm discriminated best for identifying CRT reports with an AUC of 98.6% (95% confidence interval: 97.8%, 99.4%), sensitivity of 97.7% (94.3%, 100%), and specificity of 85.0% (81.8%, 88.1%). In external validation, the ensemble algorithm had an AUC of 97.8% (97.0%, 98.5%), sensitivity of 97.6% (96.4%, 98.6%), and specificity of 78.2% (75.9%, 80.4%)). All three individual algorithms performed well, but less so than the ensemble.

Conclusions
We successfully developed high-performance algorithms that identified whether a citation was a CRT report with high sensitivity and moderately high specificity. We provide open-source software to facilitate the use of our algorithms in practice.
Development and validation of a short-term breast health measure as a supplement to screening mammography
Authors: Daily Anna , Ravishankar Prashanth , Wang Wanyi , Krone Ryan , Harms Steve , Klimberg V. Suzanne 
Published: October 2022

Abstract
Background
There is a growing body of evidence to support tears as a non-traditional biological fluid in clinical laboratory testing. In addition to the simplicity of tear fluid processing, the ability to access key cancer biomarkers in high concentrations quickly and inexpensively is significantly enhanced. Tear fluid is a dynamic environment rich in both proteomic and genomic information, making it an ideal medium for exploring the potential for biological testing modalities.

Methods
All protocols involving human subjects were reviewed and approved by the University of Arkansas IRB committee (13-11-289) prior to sample collection. Study enrollment was open to women ages 18 and over from October 30, 2017-June 19, 2019 at The Breast Center, Fayetteville, AR and Bentonville, AR. Convenience sampling was used and samples were age/sex matched, with enrollment open to individuals at any point of the breast health continuum of care. Tear samples were collected using the Schirmer strip method from 847 women. Concentration of selected tear proteins were evaluated using standard sandwich ELISA techniques and the resulting data, combined with demographic and clinical covariates, was analyzed using logistic regression analysis to build a model for classification of samples.

Results
Logistic regression analysis produced three models, which were then evaluated on cases and controls at two diagnostic thresholds and resulted in sensitivity ranging from 52 to 90% and specificity from 31 to 79%. Sensitivity and specificity variation is dependent on the model being evaluated as well as the selected diagnostic threshold providing avenues for assay optimization.

Conclusions and relevance
The work presented here builds on previous studies focused on biomarker identification in tear samples. Here we show successful early classification of samples using two proteins and minimal clinical covariates.
Bioactive compounds, nutritional profile and health benefits of colostrum: a review
Authors: Poonia Amrita , Shiva  
Published: October 2022

AbstractBovine colostrum is defined as first milk by milching animals responsible for providing the innate immunity to the neonatal and possess many immunoglobulins for preventing the calf from diseases. Colostrum consist of many bioactive compounds like proteins, enzymes, growth factors, immunoglobulins and nucleotides that provides several benefits to human health. Numerous clinical and pre-clinical studies have demonstrated the therapeutic benefits of the bovine colostrum. This review focusses on bioactive compounds, their health benefits, potential of colostrum for developing several health foods and prevention of respiratory and gastrointestinal tract disorders. Processing can also be done to extend shelf-life and extraction of bioactive constituents either as encapsulated or as extracts. The products derived from bovine colostrum are high-end supplements possessing high nutraceutical value.
Graphical Abstract
Processing of the BC to extend the shelf -life to obtain bioactive compounds for manufacturing functional foods.
β1-Integrin—A Key Player in Controlling Pancreatic Beta-Cell Insulin Secretion via Interplay With SNARE Proteins
Authors: Barillaro Malina , Schuurman Meg , Wang Rennian 
Published: October 2022

Abstract
Shortcomings in cell-based therapies for patients with diabetes have been revealed to be, in part, a result of an improper extracellular matrix (ECM) environment. In vivo, pancreatic islets are emersed in a diverse ECM that provides physical support and is crucial for healthy function. β1-Integrin receptors have been determined to be responsible for modulation of beneficial interactions with ECM proteins influencing beta-cell development, proliferation, maturation, and function. β1-Integrin signaling has been demonstrated to augment insulin secretion by impacting the actin cytoskeleton via activation of focal adhesion kinase and downstream signaling pathways. In other secretory cells, evidence of a bidirectional relationship between integrins and exocytotic machinery has been demonstrated, and, thus, this relationship could be present in pancreatic beta cells. In this review, we will discuss the role of ECM–β1-integrin interplay with exocytotic proteins in controlling pancreatic beta-cell insulin secretion through their dynamic and unique signaling pathway.