bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shared graft-versus-leukemia minor histocompatibility antigens in DISCOVeRY-BMT
Authors: Olsen Kelly S. , Jadi Othmane , Dexheimer Sarah , Bortone Dante S. , Vensko Steven P. , Bennett Sarah , Tang Hancong , Diiorio Marisa , Saran Tanvi , Dingfelder David , Zhu Qianqian , Wang Yiwen , Haiman Christopher A. , Pooler Loreall , Sheng Xin , Webb Amy , Pasquini Marcelo C. , McCarthy Philip L. , Spellman Stephen R. , Weimer Eric , Hahn Theresa , Sucheston-Campbell Lara , Armistead Paul M. , Vincent Benjamin G. 
Published: December 2022

Abstract
T-cell responses to minor histocompatibility antigens (mHAs) mediate graft-versus-leukemia (GVL) effects and graft-versus-host disease (GVHD) in allogeneic hematopoietic cell transplantation. Therapies that boost T-cell responses improve allogeneic hematopoietic cell transplant (alloHCT) efficacy but are limited by concurrent increases in the incidence and severity of GVHD. mHAs with expression restricted to hematopoietic tissue (GVL mHAs) are attractive targets for driving GVL without causing GVHD. Prior work to identify mHAs has focused on a small set of mHAs or population-level single-nucleotide polymorphism–association studies. We report the discovery of a large set of novel GVL mHAs based on predicted immunogenicity, tissue expression, and degree of sharing among donor-recipient pairs (DRPs) in the DISCOVeRY-BMT data set of 3231 alloHCT DRPs. The total number of predicted mHAs varied by HLA allele, and the total number and number of each class of mHA significantly differed by recipient genomic ancestry group. From the pool of predicted mHAs, we identified the smallest sets of GVL mHAs needed to cover 100% of DRPs with a given HLA allele. We used mass spectrometry to search for high-population frequency mHAs for 3 common HLA alleles. We validated 24 predicted novel GVL mHAs that are found cumulatively within 98.8%, 60.7%, and 78.9% of DRPs within DISCOVeRY-BMT that express HLA-A∗02:01, HLA-B∗35:01, and HLA-C∗07:02, respectively. We confirmed the immunogenicity of an example novel mHA via T-cell coculture with peptide-pulsed dendritic cells. This work demonstrates that the identification of shared mHAs is a feasible and promising technique for expanding mHA-targeting immunotherapeutics.
Clinical application of RUBCN/SESN2 mediated inhibition of autophagy as biomarkers of diabetic kidney disease
Authors: Watany Mona M. , El-Horany Hemat E. , Elhosary Marwa M. , Elhadidy Ahmed A. 
Published: December 2022

Abstract
Background
Deregulated autophagy in diabetes has been a field of many experimental studies recently. Impaired autophagy in diabetic kidneys orchestrates every step of diabetic nephropathy (DN) pathogenesis. This study aimed to evaluate three autophagy regulators; RUBCN, mTOR, and SESN2 as clinically applicable indicators of DN progression and as early predictors of DN.

Methods
This retrospective study included 120 participants in 4 groups; G1: diabetic patients without albuminuria, G2: diabetic patients with microalbuminuria, G3: diabetic patients with macroalbuminuria and G4: healthy controls. RUBCN and SESN2 genes expression were tested by RT-qPCR. RUBCN, mTOR, and SESN2 serum proteins were quantitated by ELISA.

Results
RUBCN mRNA was over-expressed in diabetic patients relative to controls with the highest level found in G3 followed by G2 then G1; (9.04 ± 0.64, 5.18 ± 0.73, 1.94 ± 0.41 respectively. P < 0.001). SESN2 mRNA expression was at its lowest level in G3 followed by G2 then G1 (0.1 ± 0.06, 0.48 ± 0.11, 0.78 ± 0.13 respectively. P < 0.001). Similar parallel reduction in serum SENS2 was observed. Serum RUBCN and mTOR were significantly elevated in diabetic patients compared to controls, with the increase parallel to albuminuria degree. RUBCN expression, serum RUBCN and mTOR strongly correlated with albuminuria (r = 0.912, 0.925 and 0.867 respectively). SESN2 expression and serum level negatively correlated with albuminuria (r = − 0.897 and -0.828 respectively); (All p < 0.001). Regression analysis showed that serum RUBCN, mTOR, RUBCN and SESN2 mRNAs could successfully predict DN.

Conclusions
The study proves the overexpression of RUBCN and mTOR in DN and the down-expression of SESN2. The three markers can be clinically used to predict DN and to monitor disease progression.
Critical role of Rho proteins in myosin light chain di-phosphorylation during early phase of endothelial barrier disruption
Authors: Hirano Mayumi , Hirano Katsuya 
Published: December 2022

AbstractWe previously reported the Rho-associated coiled-coil containing protein kinase (ROCK)-mediated di-phosphorylation of myosin light chain (MLC) and actin bundle formation at the cell periphery as early events of the endothelial barrier disruption. We herein examined the role of RhoA during early events of barrier disruption. Treatment of cultured porcine aortic endothelial cells with simvastatin prevented the decrease in trans-endothelial electrical resistance, MLC di-phosphorylation and peripheral actin bundle formation seen 3 min after thrombin stimulation. Co-treatment with geranylgeranyl pyrophosphate rescued the thrombin-induced events. Thrombin increased a GTP-bound form of RhoA and phosphorylation of myosin phosphatase target subunit 1 (MYPT1) at the ROCK site. The intracellular introduction of the inhibitory protein of RhoA inhibited the thrombin-induced di-phosphorylation of MLC. However, knockdown of either one of RhoA, RhoB or RhoC failed to inhibit thrombin-induced MLC di-phosphorylation. The findings suggest that Rho proteins play a critical role during early events of thrombin-induced barrier disruption.
Predicting drug characteristics using biomedical text embedding
Authors: Shtar Guy , Greenstein-Messica Asnat , Mazuz Eyal , Rokach Lior , Shapira Bracha 
Published: December 2022

AbstractBackgroundDrug–drug interactions (DDIs) are preventable causes of medical injuries and often result in doctor and emergency room visits. Previous research demonstrates the effectiveness of using matrix completion approaches based on known drug interactions to predict unknown Drug–drug interactions. However, in the case of a new drug, where there is limited or no knowledge regarding the drug’s existing interactions, such an approach is unsuitable, and other drug’s preferences can be used to accurately predict new Drug–drug interactions.MethodsWe propose adjacency biomedical text embedding (ABTE) to address this limitation by using a hybrid approach which combines known drugs’ interactions and the drug’s biomedical text embeddings to predict the DDIs of both new and well known drugs.ResultsOur evaluation demonstrates the superiority of this approach compared to recently published DDI prediction models and matrix factorization-based approaches. Furthermore, we compared the use of different text embedding methods in ABTE, and found that the concept embedding approach, which involves biomedical information in the embedding process, provides the highest performance for this task. Additionally, we demonstrate the effectiveness of leveraging biomedical text embedding for additional drugs’ biomedical prediction task by presenting text embedding’s contribution to a multi-modal pregnancy drug safety classification.ConclusionText and concept embeddings created by analyzing a domain-specific large-scale biomedical corpora can be used for predicting drug-related properties such as Drug–drug interactions and drug safety prediction. Prediction models based on the embeddings resulted in comparable results to hand-crafted features, however text embeddings do not require manual categorization or data collection and rely solely on the published literature.
Combined application of dinitrofluorobenzene and ovalbumin induced AD-like dermatitis with an increase in helper T-cell cytokines and a prolonged Th2 response
Authors: Jiang Pengju , Wu Yaguang , Liu Lu , Zhang Lian , Song Zhiqiang 
Published: December 2022

Abstract
Background
The progression of acute-to-chronic atopic dermatitis is accompanied by multiple helper T-cell cytokine responses, but the mechanisms and relative importance of these changes remain unclear. There is no animal model for atopic dermatitis that recapitulates these cytokine responses.

Objective
We sought to build a novel mouse model for atopic dermatitis (AD) that recapitulates these helper T-cell responses and some dynamic changes in cytokine responses in the progression of AD.

Methods
Female BALB/c mice were subjected to the application of dinitrofluorobenzene (DNFB) and ovalbumin (OVA) to induce AD-like dermatitis. Skin lesions and serum were collected from mice in the acute and chronic phases to detect changes in cytokine responses and other features of AD.

Results
Combined application of DNFB and OVA successfully induced AD-like dermatitis and histological changes as well as epidermal barrier dysfunction. In the acute phase of AD-like dermatitis, Th2-associated cytokines were mainly increased in serum and skin lesions. In the chronic phase of AD-like dermatitis, Th2-associated cytokines were still highly expressed, while Th1- and Th17-associated cytokines were also gradually increased. Compared with the acute phase, the JAK-STAT signaling pathway was highly expressed in the chronic phase of AD-like dermatitis.

Conclusion
The combined application of DNFB and OVA could be used to build a new mouse model for atopic dermatitis. This mouse model recapitulates the helper T-cell responses and some dynamic changes in cytokine responses in the progression of acute-to-chronic in human AD. The JAK-STAT signaling pathway plays a pivotal role in the chronicity of AD.
Comparison of the red blood cell indices based on accuracy, sensitivity, and specificity to predict one-year mortality in heart failure patients
Authors: Hosseinpour Morteza , Hatamnejad Mohammad Reza , Montazeri Mohammad Nima , Bazrafshan drissi Hamed , Akbari Khezrabadi Ali , Shojaeefard Ehsan , Khanzadeh Shokoufeh 
Published: December 2022

Abstract
Background
Various investigations have specified the role of each RBC indices separately [including hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red blood cell distribution width (RDW)] to predict the prognosis of acute heart failure (AHF) patients. However, in the current study, these variables were compared based on accuracy, sensitivity, and specificity to determine the best prognostic factor.

Methods
Of 734 heart failure patients referred to the emergency department, 400 cases were enrolled based on the inclusion and exclusion criteria. Data of them were documented, and patients were followed for one year. Eventually, the association of clinical variables and RBC indices with one-year mortality was explored.

Results
The study included 226 (56%) men and 174 (44%) women with a median age of 66 years. Body Mass Index (HR 1.098, p = 0.016), Hb (HR 0.728, p = 0.024), HTC (HR 0.875, p = 0.066), MCHC (HR 0.795, p = 0.037), and RDW-CV (HR 1.174, p = 0.006) were confirmed as predictors of long-term mortality. Despite confirming the predictive role of these variables by ROC curves, their sensitivity and specificity were reported as follows: [72% and 50% for Hb], [75% and 52% for HCT], [88% and 27% for MCHC], and [49% and 81% for RDW]. In addition, stratified groups of patients, based on normal cut-off values obtained from scientific literature, had significantly different survival in Kaplan–Meier analyses.

Conclusion
Whilst proving the predictive role of Hb, HCT, MCHC, and RDW in AHF patients, the most sensitive measurement was MCHC and the most specific one was RDW; therefore, these variables should be considered for risk stratification purposes of AHF patients in daily clinical practice.
Factors affecting prescription of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes mellitus with established cardiovascular disease/ chronic kidney disease in Hong Kong: a qualitative study
Authors: Ng Ngai Mui , Ng Yeung Shing , Chu Tsun Kit , Lau Phyllis 
Published: December 2022

Abstract
Background
Sodium-glucose co-transporter 2 inhibitors (SGLT2 I) has cardiorenal protective properties and are recommended for patients with diabetes and established atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). Although cardiorenal complications are high in diabetes and pose a significant financial burden on the Hong Kong health care system, the use of SGLT2 I in these populations remains low. And yet this issue has not been explored in Hong Kong primary care. This study aimed to explore factors affecting primary care doctors’ prescribing of SGLT2 I in patients with diabetes and established ASCVD/CKD in Hong Kong.

Methods
A phenomenological qualitative research using semi-structured interviews was conducted between January and May 2021 in one Hospital Authority cluster in Hong Kong. Purposive sampling was employed to recruit primary care doctors in the cluster. The Theoretical Domains Framework (TDF) underpinned the study and guided the development of the interview questions. Data was analysed using both inductive and deductive approaches. The Consolidated criteria for reporting qualitative research (COREQ) checklist was used to guide the reporting.

Results
Interviews were conducted with 17 primary care doctors. Four overarching themes were inductively identified: knowledge and previous practice patterns influence prescription, balancing risks and benefits, doctors’ professional responsibilities, and system barriers. The four themes were then deductively mapped to the nine specific domains of the TDF: knowledge; intention; memory; beliefs about capabilities; beliefs about consequences; goals; role and identity; emotion; and environmental constraints. Most interviewees, to varying extent, were aware of the cardio-renal advantages and safety profile of SGLT2 I but are reluctant to prescribe or change their patients to SGLT2 I because of their knowledge gap that the cardio-renal benefits of SGLT2 I was independent of glyacemic efficacy. Other barriers included their considerations of patients’ age and renal impairment, and patients’ perceptions and preferences.

Conclusions
Despite evidence-based recommendations of the utilisation of SGLT2 I in patients with established ASCVD/CKD, the prescription behaviour among primary care doctors was affected by various factors, most of which were amendable. Our findings will inform the development of structured interventions to address these factors to improve patients’ cardio-renal outcomes.
Psychiatric consultation in general practitioners’ daily practice: a qualitative study on the experience of consultation-liaison psychiatry interventions in primary care settings in French-speaking Switzerland
Authors: Tzartzas Konstantinos , Oberhauser Pierre-Nicolas , Marion-Veyron Régis , Saillant Stéphane 
Published: December 2022

AbstractBackgroundMental disorders are frequent in primary care settings, which is challenging for primary care physicians. In Neuchâtel (Switzerland), a Consultation-Liaison psychiatrist integrated three primary care group practices, proposing both clinical interventions and supervisions/psychiatric training. Primary care physicians’ experience regarding this collaboration was investigated.MethodsA qualitative study was conducted. Three focus groups were organized in each primary care group practice involved in the project (10 primary care physicians participated in focus groups). Data were analysed with thematic content analysis.ResultsSix major themes emerged from our analysis, describing primary care physicians’ collaboration with psychiatrists: 1) Impact on a difficult to reach and “reluctant to consult” population; 2) Fluidity of the intraprofessional collaboration; 3) Influence on the doctor-patient relationship; 4) Positive emotional experiences; 5) Psychiatric counselling and training; 6) Long-term prospects for the project.ConclusionsConsultation-Liaison psychiatrist’s presence came as a relief for participating primary care physicians, facilitating accessibility to mental healthcare, introducing a common culture of care, and offering “in-situ” psychiatric training. Primary care physicians felt that their relationships with patients benefited from such interventions, being better able to deal with complex emotional experiences and found patients more confident regarding proposed care. Models of psychiatric intervention provided in primary care must establish settings of collaboration that reinforce relationships between primary care physicians, psychiatrists, and patients.
Case report of Salmonella derby septicemia complicated with co-occurrence of disseminated intravascular coagulation and thrombotic microangiopathy
Authors: Lin Yingxin , Huang Lei , Tu Yunliang , Huang Bin , Zhang Sheng , Chen Yingqun , Li Weijia 
Published: December 2022

Abstract
Background
Both disseminated intravascular coagulation and thrombotic microangiopathy are complications of sepsis as Salmonella septicemia, respectively. They are related and have similar clinical characteristics as thrombopenia and organ dysfunctions. They rarely co-occur in some specific cases, which requires a clear distinction.

Case presentation
A 22-year-old woman had just undergone intracranial surgery and suffered from Salmonella derby septicemia with multiorgan involvement in the hospital. Laboratory workup demonstrated coagulation disorder, hemolytic anemia, thrombocytopenia, and acute kidney injury, leading to the co-occurrence of disseminated intravascular coagulation and secondary thrombotic microangiopathy. She received antibiotics, plasma exchange therapy, dialysis, mechanical ventilation, fluids, and vasopressors and gained full recovery without complications.

Conclusion
Disseminated intravascular coagulation and secondary thrombotic microangiopathy can co-occur in Salmonella derby septicemia. They should be treated cautiously in diagnosis and differential diagnosis. Thrombotic microangiopathy should not be missed just because of the diagnosis of disseminated intravascular coagulation. Proper and timely identification of thrombotic microangiopathy with a diagnostic algorithm is essential for appropriate treatment and better outcomes.
Spirulina as a daily nutritional supplement of young pre-school Cambodian children of deprived settings: a single-blinded, placebo-controlled, cross-over trial
Authors: Barennes Hubert , Houdart Laetitia , de Courville Caroline , Barennes Florent 
Published: December 2022

Abstract
Background
Spirulina (SP) is widely used as a nutritional supplement to enhance child nutrition in low-income countries. We assessed Spirulina’s efficacy of the current dose supplied by institutions in Cambodia on improving growth and anemia in a cross-over randomized controlled trial in preschool underprivileged children from similar settings.

Methods
Preschool children cared by a not-for-profit institution were randomly and blindly allocated (2 to 1) to spirulina or placebo: 100 g in total, given in 2 g per day. After 5 weeks of wash-out, participants were crossed-over to the other group. Anthropometric gain and selected hematological data (blood cell count, ferritin, and C-reactive protein) were assessed at each phase.

Results
A total of 179 children completed the trial, 149 (83.2%) completed all the anthropometrics, and 99 (55.3%) all hematological measures. Mean BMI was 14.18 (95%CI: 14.00–14.37) and 31(20.8%) children had thinness. Mean blood hemoglobin was 11.9 g/dL (95%CI: 11.8–12.1). The weight gain of the SP group showed a modest higher trend compared to placebo (0.63 kg; 95%CI: 0.54–0.72 and 0.46 kg; 95%CI: 0.33–0.58, respectively; p = 0.07). Height increased similarly in both groups. The number of anemic children decreased by 6 (6.06%) and 11 (11.11%) on Placebo or SP, respectively (p = 0.004). Tolerance was good.

Conclusion
SP may be recommended to improve childhood anemia. The analysis of the usual daily dose (2 g) provided by organizations in Cambodia shows a tendency to improve weight gain in the group supplemented with SP very close to significance, but no trend in height. Increased doses and longer supplementation should be evaluated further.

Trial registration
The study was retrospectively registered at ISRCTN under number 11696165 on 12/12/2018.
Education level has an effect on the recovery of total knee arthroplasty: a retrospective study
Authors: Zhou Yuan-yuan , Zhang Bo-kai , Ran Tian-fei , Ke Song , Ma Tian-ying , Qin Yin-yin , Zhang Yuan , Xu Yuan , Wang Min 
Published: December 2022

Abstract
Objective
This study aimed to observe the relationship between education level and outcomes after total knee arthroplasty (TKA).

Methods
One thousand two hundred sixty four patients after TKA in our hospital from April 2016 to April 2020 were reviewed. These patients were divided into 4 groups (A who were illiterate, B who had elementary school degree, C who had junior high school degree, D who had senior high school degree or higher) by the educational level, which was blinded to the observers. The postoperative outcomes of KSS score, pain, joint extension and flexion function were observed 1 year after discharged from hospital.

Results
Among 1253 patients met the inclusion criteria, the average age was 68.63 years, the average body mass was 57.73 kg. There are no distinctions among 4 groups one day after the surgery. However, the outcomes of the follow up were that, the KSS score was: 77.84 ± 10.635; 80.70 ± 8.956; 87.92 ± 8.123;91.27 ± 8.262, with significant differences (P < 0.05). The mean VAS scores were: 1.97 ± 1.60; 2.07 ± 1.66; 1.197 ± 1.5265, 1.044 ± 1.4662. Patients in Group C and D had significantly less pain than that in Group A and B (P < 0.05). The knee flexion range of motion (ROM) was: 91.21 ± 11.69°; 91.77 ± 11.95°; 102.12 ± 11.38°; 109.96 ± 10.64°, Group D performed best, with significant differences (P < 0.05). The knee extension ROM were: – 2.41 ± 4.49°; – 0.91 ± 2.82°; – 0.83 ± 2.87°; – 0.35 ± 1.60°, with significant difference between Group D and the others (P < 0.05).

Conclusion
Education level affects the outcomes such as VAS score, KSS score, the extension and flexion ROM of the knee after TKA. The patients with higher education level have better outcomes.
Elevated serum Meteorin-like levels in patients with hyperthyroidism
Authors: Wen Xiaohui , Ding Xiaoyu , Chang Xiaona , Wang Jiaxuan , Wang Qiu , Liu Jia , Wang Guang 
Published: December 2022

Abstract
Background
Meteorin-like (Metrnl) is a newly discovered adipomyokine that regulates systemic energy homeostasis. Both thyroid hormones and Metrnl increase energy expenditure and induce browning of adipose tissue. Thus, the aim of this study was to investigate serum Metrnl levels in hyperthyroid patients and the association of serum Metrnl levels with hyperthyroidism.

Methods
The study included 88 patients with newly diagnosed untreated overt hyperthyroidism and 100 age- and sex- matched healthy controls. Serum Metrnl levels were determined using the enzyme-linked immunosorbent assay (ELISA) method.

Results
Serum Metrnl levels were significantly elevated in patients with hyperthyroidism compared with controls. Linear regression analyses indicated that serum Metrnl levels were independently associated with FT3 (β = 0.324, P = 0.001), FT4 (β = 0.293, P = 0.001), and TSH (β = -0.234, P = 0.006) after full adjustment. Additionally, further logistic regression analyses revealed that the highest Metrnl tertile was significantly associated with hyperthyroidism compared with the lowest tertile (P for trend < 0.001). The relationship remained significant even after adjusting for potential confounders. Meanwhile, each one-unit increase in circulating Metrnl was independently associated with hyperthyroidism (OR 1.021, 95%CI 1.007–1.036, P < 0.01).

Conclusion
Serum Metrnl levels were elevated in patients with hyperthyroidism and were independently associated with hyperthyroidism.