bluuebunny/crossref_metadata_2025_split huggingface dataset:
Program Evaluation Activities in Competence by Design: A Survey of Specialty/Subspecialty Program Directors
Authors: Milosek Jenna , Eady Kaylee , Moreau Katherine A. 
Published: October 2023

Abstract

Background The evaluation of Competence by Design (CBD) residency programs is essential for improving program effectiveness. There is limited literature on the evaluation of CBD programs. We investigated the extent to which program evaluation activities are occurring in CBD residency programs in Canada and the reasons why these programs are engaging or not engaging in them. Methods We surveyed program directors whose programs transitioned to CBD. We calculated descriptive statistics for the 22 closed-ended survey items. Results We obtained 149 responses (response rate 33.5%). Of the 149 respondents, 127 (85.2%) indicated that their programs do engage in evaluation while 22 (14.8%) indicated that their programs do not. Of the 127 whose programs do engage in evaluation, 29 (22.8%) reported that their programs frequently or always develop evaluation questions and 23 (18.1%) noted that their programs design evaluation proposals/plans. Reasons for engaging in evaluation included: to make decisions about the program, and to stimulate changes in educational practices. Reasons for not engaging in evaluation comprised: no knowledge on how to do it, no personnel to do evaluation, and no funding to do it. Conclusions While most CBD programs are doing program evaluation the quality of it is questionable.
NMN supplementation promotes liver growth-The result of the regulated transcription and metabolism
Authors: Su Mengzhu , Wang Jingtai , Yuan Yang , Wang Chuanzhi , Shao Yingchun , Sun Wenshe , Hao Minglu , Xiu Haoren , Zhou Sha , Sun Li , Xu Jiazhen , Zhang Shuangshuang , Xing Dongming 
Published: October 2023

Abstract
Immunodeficient individuals are not only prone to infections, endangering the health, but also encounter restricted growth and development. In the present study, we confirmed the role of NMN and found the preferred supplementation dosage in promoting liver growth of immunodeficient mice in vivio, and explored the underlying mechanism. Fifty 8-week-old inbred BALB/c immunodeficient mice were randomly divided into placebo Control group (C), Low-dosage NMN supplementation group (N50), Medium-dosage NMN supplementation group (N100), High-dosage supplementation NMN group (N200) and NMN + 78c supplementation group (N100 + 78c), with 10 mice in each group. In the low, medium and high NMN supplementation groups, mice were supplemented with 50 mg/kg/d, 100 mg/kg/d and 200 mg/kg/d NMN by gavage respectively for 21 days. During the period of supplementation with 100 mg/kg/d, 78c was supplemented to the mice by intraperitoneal injection on the first, eighth and 15th day of the 21 days. On the next day after supplementation treatment, the mice were anesthetized and the livers were excised and weighted. The expression of GHR, IGF-1, SIRT1, YAP1, p-YAP1, JAK1 and STAT3 was detected by Western Blot, the co-localisation level of SIRT1-JAK1, SIRT1-STAT3, JAK1-STAT3, YAP1-JAK1 and YAP1-STAT3 were detected by the immunofluorescence double labeling technique. Untargeted metabolomics was detected for analysing the effects of NMN on liver metabolism. It was found that the weight of the liver of mice in N100 group increased compared with C group, and the expression of SIRT1, JAK1, STAT3, YAP1, GHR and IGF-1 was increased. The co-localisation level of SIRT1-JAK1, JAK1-STAT3, YAP1-JAK1 and YAP1-STAT3 was increased after the supplementation of 100 mg/kg/d NMN. These changes were not significant in N50 and N200 groups. Upon the injection of 78c, the effect of NMN on transcription was inhibited, suggesting that the effect was CD38 dependent. We also found that, the improved amino acid metabolism after NMN supplementation was supposed to be one of the important mechanisms underlying liver growth.
Surgical Therapy and Outcome of Descending Necrotizing Mediastinitis in a Single- Center Series
Authors: Zhao Zhewei , Ma Dongjie , Xu Yuan , Guo Chao , Li Shanqing , Wang Jian , Wang Mu , Qin Yingzhi , Hongsheng Liu 
Published: October 2023

Abstract
Background Descending Necrotizing Mediastinitis (DNM) is an acute and often fatal infection that affects the neck and mediastinum. DNM treatment consists of broad-spectrum antibiotics, early diagnosis, and surgical debridement with multidisciplinary cooperation. However, owing to the rarity and complexity of this disease, the mortality rate is high. This retrospective study analyzed a single-center experience of managing DNM over the last ten years.Methods A single-center, retrospective, observational, and descriptive study was conducted on 31 patients with DNM at Peking Union Medical College Hospital from 2012 to 2022. Case report forms were used to collect data which were then analyzed with a focus on surgical management and outcomes.Results This study examined the outcomes of 31 patients diagnosed with DNM at our hospital. The most common comorbidities on admission were hypertension (48%) and diabetes mellitus (42%). The degree of diffusion of DNM according to Endo’s classification was classified as follows: type I in 7 patients (22.6%), type IIA in 5 (16.1%), and type IIB in 19 patients (61.3%). Among these patients, 13 (41.9%) were found to have a single microbial infection, while 16 (51.6%) were found to have polymicrobial infections. In all cases, neck drainage was performed via cervicotomy, with multiple drains (64.5%) and vacuum sealing drainage (VSD) (35.5%). Mediastinal drainage was performed via a cervical mediastinotomy (51.6%), video-assisted thoracic surgery (VATS) (41.9%), or thoracotomy (6.5%). The 30-day mortality rate was 25.8% and 24.0 days of the average length of hospital stay.Conclusions Early accurate diagnosis and timely intervention have been shown to be correlated with a positive prognosis. Cervicothoracic CT (computed tomography) is essential for the diagnosis, staging, and evaluation of the optimal surgical treatment. Cervicotomy and video-assisted thoracoscopic surgery with percutaneous drainage is effective, even in advanced cases. Additionally, the application of VSD in cervical incision did not improve prognosis but may shorten the length of ICU (intensive care unit) and hospital stays.
Cancer driver genes and opportunities for precision oncology revealed by whole genome sequencing 10,478 cancers
Authors: Houlston Richard , Kinnersley Ben , Sud Amit , Everall Andrew , Cornish Alex , Chubb Daniel , Culliford Richard , Gruber Andreas , Lärkeryd Adrian , Mitsopoulos Costas , Consortium GEL Genomics England Research , Wedge David 
Published: October 2023

Abstract

Identifying cancer driver genes is key for delivering the vision of precision oncology. The falling cost of whole genome sequencing (WGS) potentially makes WGS an attractive single all-encompassing test to identify cancer drivers in a patient, which may not be captured by standard panel testing but are targetable by small molecules. We analysed WGS data on 10,478 patients spanning 35 cancer types recruited to the UK 100,000 Genomes Project. We identified 330 driver genes, including 74 which are novel to any cancer. Across all cancer types 16% of the patients would be eligible for a currently approved therapy. Computational chemogenomic analysis of cancer mutations identified 96 additional targets of compounds that are potentially active and represent candidates for future clinical trials, expanding opportunities for improved patient care.
Exhaustive Variant Interaction Analysis using Multifactor Dimensionality Reduction
Authors: Gómez-Sánchez Gonzalo , Alonso Lorena , Pérez Miguel Ángel , Morán Ignasi , Torrents David , Berral Josep Lluis 
Published: October 2023

Abstract

One of the main goals of human genetics is to understand the connections between genomic variation and the predisposition to develop a complex disorder. These disease-variant associations are usually studied in a single independent manner, disregarding the possible effect derived from the interaction between genomic variants. In particular, in a background of complex diseases, these interactions can be directly linked to the disorder and may play an important role in disease development. Although their study has been suggested to help to complete the understanding of the genetic bases of complex diseases, this still represents a big challenge due to large computing demands. Here, we have taken advantage of High-Performance Computing technologies to tackle this problem using a combination of machine learning methods and statistical approaches. As a result, we have created a containerized framework that uses Multifactor Dimensionality Reduction to detect pairs of variants associated with Type 2 Diabetes (T2D). This methodology has been tested in the Northwestern University NUgene project cohort using a dataset of 1,883,192 variant pairs with a certain degree of association with T2D.Out of the pairs studied, we have identified 104 significant pairs, two of which exhibit a potential functional relationship with T2D.
Personalised Learning in Vocational Higher Education: A Model for Diverse Learners
Authors: Fariani Rida , Junus Kasiyah , Santoso Harry 
Published: October 2023

Abstract
Implementing blended learning in vocational higher education (VHE) is more effective considering the characteristics of the VHE curriculum, which is predominantly focused on practical learning and emphasises mastery of specific competencies. Due to the diversity of students in VHE, a 'one size fits all' blended learning design can be developed to be more adaptive and personalised. However, personalised blended learning (p-BL) design still needs to be improved, especially in VHE in Indonesia. Therefore, this paper offers a p-BL model that can be applied in VHE. Through an exploratory sequential mixed methods research design involving a literature review, seven interviews and a survey of 53 VHE lecturers and instructors, we identified the student model, knowledge model and personalisation model as the components of the p-BL model. The student model categorises students based on their knowledge levels and learning styles. The knowledge model annotates learning objects based on the level of difficulty and learning style dimensions. The personalisation model comprises learning objects and assessment recommendations; it also has a suggestion system that provides recommendations for assessment items for students who have failed, and it is recursive until the student passes the assessment. This suggestion system ensures that students master the competencies according to the characteristics of VHE learning in Indonesia. The personalisation process is integrated into blended learning using a station rotation and flexible model. The proposed p-BL model can be a reference for VHE institutions implementing personalised learning in their teaching and learning practices.
The effects of postoperative Trimetazidine treatment on ishaemia-reperfusion injury after isolated surgical myocardial revascularisation
Authors: Stanev Kamen , Rahman Hristo , Darbokliev Svetoslav , Gonovski Todor , Dobreva-Yatseva Bistra , Nachev Gencho 
Published: October 2023

Abstract
Background: The gold standard in managing patients with multi-vessel coronary artery disease (CAD) remains the surgical myocardial revascularization or coronary artery bypass grafting (CABG). Well-known, and described in details, is the pathophysiological process of free radical release in circulation, as a result of increased oxidative stress during the ischemia-reperfusion time and post surgical revascularization procedures. This process could reversibly or irreversibly cause marked myocardial damage.
The focus of the present trial, which is prospective single-blinded, controlled and randomised, is on detecting and analysing the trimetazidine drug effect on decreasing postoperative ischaemia-reperfusion myocardial damage. The aim is the evaluation of trimetazidine effects on reactive oxygen species (ROS), which may appear after myocardial ischemia-reperfusion period or systemic inflammatory response after on-pump surgical revascularization.
Methods: The present study included 90 elective surgery patients, operated through a time frame from March 2018 till October 2018. The studied population was further divided into two subgroups of comparison. The patients of the first subgroup received regular therapy of trimetazidine 35 mg b.d., immediately after tracheal extuba+tion. The rest of the prescribed medical therapy was standard and identical to all the participants of the studied patient population. Pre-and postoperative levels of specific blood biomarkers such as: high-sensitivity troponin T (hs-TnT), creatinine kinase-MB fraction (CK-MB) and malondialdehyde (MDA) were evaluated. The data was analysed and classified at the time of sample collection.
Results: The retrieved data information analysis concluded that regular drug therapy with trimetazidine leads to less malondialdehyde (MDA) release, consequently reduction in oxidative stress and improved cardiomyocyte protection by augmentation of the antioxidant status. The follow-up period was extended and conducted up to 6 months after the surgical revascularization. Excellent results were documented by conducting the Quality of life assessment by Minnesota Living with Heart Failure Questionnaire.
Conclusions: Improvement of myocardial cell metabolism and decreasing the level of postoperative ischemia-reperfusion damage is alleviated by postoperative regular trimetazidine drug therapy.
NKG2D ligand MICA regulates macrophage phenotype through PPAR/EHHADH pathway altering fatty acid oxidation (FAO) in hepatocellular carcinoma (HCC)
Authors: Huang Jingquan , Wu Qiulin , Yang Yan , Du Qiang , Yan Peng , Li Xicai , Yao Ming , Li Jianjun , Huang Yubin , Cai Xiaoyong , Geller David A , Yan Yihe 
Published: October 2023

Abstract
Background Tumor-associated macrophages (TAMs) play a crucial role in the tumor microenvironment (TME), and the metabolic activities of both tumor cells and TAMs have an impact on the TME. Moreover, the expression of MICA in tumor cells is closely associated with immune cells in hepatocellular carcinoma (HCC). However, it remains unclear whether MICA expression correlates with TAMs and influences the switch in macrophage phenotype by mediating metabolic alterations.
Methods Various biostatistical tools, qPCR, and IHC staining experiments were utilized to analyze data from The Cancer Genome Atlas (TCGA) and collected HCC tumor tissues. Single-cell RNA sequencing (scRNA-seq) analyses and a co-culture model of HCC cells with macrophages were performed to validate the findings from the biostatistical analyses.
Results Through the intersection of differentially expressed genes (DEGs), metabolism-related genes (MRGs), and co-expression genes (CEGs) with MICA in HCC, the EHHADH gene was identified. Gene set enrichment analyses were conducted to further confirm the role of EHHADH. EHHADH expression is decreased in HCC tumors and can serve as a prognostic biomarker for HCC. Expressions of MICA and EHHADH exhibited significant correlations with various phenotypic macrophages and exerted opposing effects on M1-like and M2-like macrophages infiltrating HCC. The underlying metabolic and molecular mechanisms revealed that MICA in tumor cells induced M2-like polarization through the PPAR/EHHADH pathway, which regulates fatty acid oxidation (FAO) in both tumor cells and macrophages.
Conclusions The metabolic gene EHHADH, which is associated with MICA, led to alterations in M2-like macrophages by promoting heightened fatty acid uptake and augmenting levels of FAO within macrophages.
Characterization of the interactions between Xanthan Gum and Trypsin with Spectroscopic and Molecular Docking technology
Authors: sun jisheng , wang xiaoxia , nie zhihua , ma litong , sai huazheng , cheng jianguo , liu yunying , duan jianguo 
Published: October 2023

Abstract
The interaction between xanthan gum and trypsin was studied using fluorescence spectroscopy, UV-vis absorption spectroscopy, circular dichroism chromatography, synchronous fluorescence spectroscopy, and molecular docking simulation. The quenching constant (KSV) and dynamic fluorescence quenching rate constant (Kq) were calculated in the study of fluorescence spectra, confirming that trypsin on xanthan gum exhibits static quenching. The interaction distance between xanthan gum and trypsin (r = 2.350 nm) is calculated using Förster theory, indicating non-radiative energy transfer occurs between them. Based on the formula, ΔH, ΔS, ΔG (298K, 303K, 308K) are all negative. Therefore, it can be concluded that the interaction force between xanthan gum and trypsin mainly consists of hydrogen bonds and van der Waals forces. The UV-vis absorption spectra were used to investigate the interaction between the two compounds. It was observed that the absorption peak of trypsin shifted towards longer wavelengths, indicating a change in its conformation. The addition of xanthan gum altered the environment and conformation of tryptophan residues in trypsin molecules, as shown by synchronous fluorescence spectra. The molecular docking simulation method shows that the main forces of xanthan gum and TRY are hydrogen bond and van der Waals force. The findings align with the thermodynamic parameters, suggesting that xanthan gum alters the secondary structure of trypsin. In the three-dimensional fluorescence spectrum, a redshift is observed in the maximum emission wavelengths of PEAK 1 and PEAK 2, indicating structural changes in trypsin upon binding with xanthan gum. Circular dichroic chromatography results demonstrate a significant decrease in β-fold content, implying an effect of xanthan gum on trypsin's structure.
CDH1 methylation analysis in invasive lobular breast carcinomas with and without gene mutation
Authors: González-Martínez Silvia , Kajabova Viera Horvathova , Pérez-Mies Belén , Carretero-Barrio Irene , Sarrió David , Moreno-Bueno Gema , Gión María , Perez-García José , Cortés Javier , Smolkova Bozena , Palacios José 
Published: October 2023

Abstract

The proposed role of CDH1 (E-cadherin gene) methylation as a mechanism of gene inactivation in Invasive Lobular Carcinoma (ILC) remains inconclusive. Using pyrosequencing, we analyzed CDH1 hypermethylation in E-cadherin deficient ILC cases with varied CDH1mutation status and Invasive Breast Carcinomas Non-Special Type (IBC-NSTs), finding no hypermethylation in any group of ILCs. In addition, CDH1 methylation correlated with the presence of Tumor-Infiltrating Lymphocytes (TILs). These findings challenge CDH1 methylation as a CDH1 inactivation mechanism in ILC and highlight TILs as a potential confounding factor in the gene methylation.
A customizable multiplex protein microarray for antibody testing and its application for tick-borne and other infectious diseases.
Authors: Krishnamurthy Hari , Jayaraman Vasanth , Krishna Karthik , Wang Tianhao , Bei Kang , Suresh Chithra , Matilda Shiny , Rai Alex , Welc-Falęciak Renata , Pawełczyk Agnieszka , Blanton Lucas , Chrdle  Aleš , Fořtová Andrea , Růžek Daniel , Nasrallah Gheyath , Abu-Raddadi Laith , Al-Sadeq Duaa , Abdallah Marah , Lilleri Daniele , Fornara Chiara , D'Angelo Piera , Furione Milena , Söderlund-Venerm Maria , Hedman Klaus , Chochlakis Dimosthenis , Psaroulaki Anna , Makridaki Eirini , Ntoula Artemis , Rajasekaran John 
Published: October 2023

Abstract
Tick-borne infections are the most common vector-borne diseases in the USA. Ticks harbor and spread several infections with Lyme disease being the most common tickborne infection in the US and Europe. Lack of awareness about tick populations, specific diagnostic tests, and overlapping symptoms of tick-borne infections can often lead to misdiagnosis affecting treatment and the prevalence data reported especially for non-Lyme tick-borne infections. The diagnostic tests currently available for tick-borne diseases are severely limited in their ability to provide accurate results and cannot detect multiple pathogens in a single run. The multiplex protein microarray developed at Vibrant was designed to detect multiple serological antibodies thereby detecting exposure to multiple pathogens simultaneously. Our microarray in its present form can accommodate 400 antigens and can multiplex across antigen types, whole cell sonicates, recombinant proteins, and peptides. A designed array containing multiple antigens of several microbes including Borrelia burgdorferi, the Lyme disease spirochete, was manufactured and evaluated. The immunoglobulin M (IgM) and G (IgG) responses against several tick-borne microbes and other infectious agents were analyzed for analytical and clinical performance. The microarray improved IgM and IgG sensitivities and specificities of individual microbes when compared with the respective gold standards. The testing was also performed in a single run in comparison to multiple runs needed for comparable testing standards. In summary, our study presents a flexible multiplex microarray platform that can provide quick results with high sensitivity and specificity for evaluating exposure to varied infectious agents especially tick-borne infections.
SAPHO syndrome treated with iguratimod combined with NSAIDs, and bisphosphonates: a prospective cohort study
Authors: Duan Hongji , Gao Shuang , Zhang Lihua , Song Le , Zhai Jiayu , Deng Xiaoli 
Published: October 2023

Abstract
Background
To evaluate the effectiveness of iguratimod combined with NSAIDs, and bisphosphonates treatment for rapid symptom relief in patients with SAPHO syndrome.
Methods
We recruited all patients seen in our unit from 2018 to 2023 diagnosed with SAPHO syndrome, who were treated with iguratimod combined with NSAIDs, and bisphosphonates, and were followed up for 12 weeks.
Results
A total of 19 patients were included. There were 14(73.7%) women and 5(26.3%) men. The average age was 49.5 years old (ranging from 26 to 67 years). During the follow-up period, a total of 5 patients terminated the experiment. 13/14(92.9%) patients responded favourably to the treatment of iguratimod combined with NSAIDs, and bisphosphonates. Younger patients might be better treated by iguratimod combined with NSAIDs, and bisphosphonates (p = 0.038)
Conclusion
Iguratimod combined with NSAIDs, and bisphosphonates seem to be a very effective mode of therapy in quickly relieving the symptoms of patients with SAPHO syndrome. Iguratimod may be a new choice for the treatment of SAPHO syndrome patients.