bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteoarthritis Disease Severity in the Temporomandibular Joint and the Knee Joint: A Comparative Cadaveric Study
Authors: Immonen Jessica A. , Ciccotelli Jason , Nguyen Linh M. , Gilmer Lesley , Broadhead Landen , Kitchen Mackenzie , Paul Conner , James Jeremy 
Published: August 2023

Objective The objective of this study was to determine the level of disease severity in a pilot cohort of temporomandibular joints (TMJs) and compare them to the pathology findings previously characterized in cadaveric knee joints. Design Thirty-one intact TMJs from 17 cadaveric donors were harvested and arthritic lesioning seen in the knee joint was investigated on the condyle and the fossa of the TMJ. Prevalence of gross alterations was equated and disease severity was determined for sex- and age-based donor pools using a validated, osteoarthritis (OA) disease severity scale (DSS). Knee joint DSS scores were also compared to the TMJ condyle and fossa DSS scores and a case study was carried out on a male donor that demonstrated severe OA in the both joints. Results The mandibular fossa demonstrated an increase in disease severity compared to the mandibular condyle in a mixed sex donor pool ( P = 0.035). It was discovered that the younger females demonstrated statistically more pathological condyles compared to the older half of the female subgroup ( P = 0.02). TMJ fossa and knee joints demonstrated comparable OA severity and similar signs of cartilage disease in a single donor highlighting the systemic nature of OA. Conclusions This study demonstrates that gross signs of OA in the TMJs of cadavers are comparable to pathology found in the knee. The mandibular fossa appears to be the site of more profound disease, implying translational movements may be more likely to induce biomechanically abnormal movement, loading, and OA.
Murine erythroid differentiation kinetics in vivo under normal and anemic stress conditions
Authors: Myers Greggory , Wang Yu , Wang Qing , Friedman Ann , Sanchez-Martinez Alejandra , Liu Xiaofang , Sharon Singh A. , Lim Kim-Chew , Khoriaty Rami , Engel James Douglas , Yu Lei 
Published: August 2023

Abstract
Our current understanding of the kinetics and dynamics of erythroid differentiation is based almost entirely on the ex vivo expansion of cultured hematopoietic progenitor cells. In this study, we used an erythroid-specific, inducible transgenic mouse line to investigate for the first time, the in vivo erythroid differentiation kinetics under steady-state conditions. We demonstrated that bipotent premegakaroycyte/erythroid (PreMegE) progenitor cells differentiate into erythroid–committed proerythroblast/basophilic erythroblasts (ProBasoE) after 6.6 days under steady-state conditions. During this process, each differentiation phase (from PreMegE to precolony forming unit-erythroid [PreCFU-E], PreCFU-E to CFU-E, and CFU-E to ProBasoE) took ∼2 days in vivo. Upon challenge with 5-flurouracil (5-FU), which leads to the induction of stress erythropoiesis, erythroid maturation time was reduced from 6.6 to 4.7 days. Furthermore, anemia induced in 5-FU-treated mice was shown to be due not only to depleted bone marrow erythroid progenitor stores but also to a block in reticulocyte exit from the bone marrow into the circulation, which differed from the mechanism induced by acute blood loss.
Pacritinib is a potent ACVR1 inhibitor with significant anemia benefit in patients with myelofibrosis
Authors: Oh Stephen T. , Mesa Ruben A. , Harrison Claire N. , Bose Prithviraj , Gerds Aaron T. , Gupta Vikas , Scott Bart L. , Kiladjian Jean-Jacques , Lucchesi Alessandro , Kong Tim , Buckley Sarah A. , Tyavanagimatt Shanthakumar , Harder Bryan G. , Roman-Torres Karisse , Smith Jennifer , Craig Adam R. , Mascarenhas John , Verstovsek Srdan 
Published: August 2023

Abstract
In patients with cytopenic myelofibrosis, treatment with the JAK2/IRAK1 inhibitor pacritinib was associated with anemia benefit in the phase 3 PERSIST-2 study. The impact of pacritinib on transfusion independence (TI) has not been previously described, nor has the mechanism by which pacritinib improves anemia been elucidated. Because it has been previously postulated that inhibition of activin A receptor, type 1 (ACVR1)/activin receptor-like kinase-2 improves anemia in patients with myelofibrosis via suppression of hepcidin production, we assessed the relative inhibitory potency of pacritinib compared with other JAK2 inhibitors against ACVR1. Pacritinib inhibited ACVR1 with greater potency (half-maximal inhibitory concentration [IC50] = 16.7 nM; Cmax:IC50 = 12.7) than momelotinib (IC50 = 52.5 nM; Cmax:IC50 = 3.2), fedratinib (IC50 = 273 nM; Cmax:IC50 = 1.0), or ruxolitinib (IC50 &gt; 1000; Cmax:IC50 &lt; 0.01). Pacritinib’s inhibitory activity against ACVR1 was corroborated via inhibition of downstream SMAD signaling in conjunction with marked suppression of hepcidin production. Among patients on PERSIST-2 who were not transfusion independent at baseline based on Gale criteria, a significantly greater proportion achieved TI on pacritinib compared with those treated on best available therapy (37% vs 7%, P = .001), and significantly more had a ≥50% reduction in transfusion burden (49% vs 9%, P &lt; .0001). These data indicate that the anemia benefit of the JAK2/IRAK1 inhibitor pacritinib may be a function of potent ACVR1 inhibition.
A computational peptide model induces cancer cells’ apoptosis by docking Kringle 5 to GRP78
Authors: Khater Ibrahim , Nassar Aaya 
Published: August 2023

Abstract
Background
Cells can die through a process called apoptosis in both pathological and healthy conditions. Cancer development and progression may result from abnormal apoptosis. The 78-kDa glucose-regulated protein (GRP78) is increased on the surface of cancer cells. Kringle 5, a cell apoptosis agent, is bound to GRP78 to induce cancer cell apoptosis. Kringle 5 was docked to GRP78 using ClusPro 2.0. The interaction between Kringle 5 and GRP78 was investigated.

Results
The interacting amino acids were found to be localized in three areas of Kringle 5. The proposed peptide is made up of secondary structure amino acids that contain Kringle 5 interaction residues. The 3D structure of the peptide model amino acids was created using the PEP-FOLD3 web tool.

Conclusions
The proposed peptide completely binds to the GRP78 binding site on the Kringle 5, signaling that it might be effective in the apoptosis of cancer cells.
A protocol for randomized controlled trial on multidisciplinary interventions for mobility limitation in the older adults (M-MobiLE)
Authors: Wang Guanzhen , Zhang Li , Ji Tong , Zhang Wanshu , Peng Linlin , Shen Shanshan , Liu Xiaolei , Shi Yanqing , Chen Xujiao , Chen Qiong , Li Yun , Ma Lina ,   the M-MobiLE Study Working Group
Published: August 2023

Abstract
Background
Mobility limitation—the loss of exercise capacity or independent living ability—is a common geriatric syndrome in older adults. As a potentially reversible precursor to disability, mobility limitation is influenced by various factors. Moreover, its complex physiological mechanism hinders good therapeutic outcomes with a single-factor intervention. Most hospitals have not incorporated the diagnosis and evaluation of mobility limitation into medical routines nor developed a multidisciplinary team (MDT) treatment plan. We aim to conduct a clinical trial titled “A Multidisciplinary-team approach for management of Mobility Limitation in Elderly (M-MobiLE)” to explore the effect of the MDT decision-making intervention for mobility limitation.

Methods
The M-MobiLE study will be a multicenter, randomized, and controlled trial. We will recruit a minimum of 66 older inpatients with mobility limitation from at least five hospitals. Older patients with mobility limitation admitted to the geriatrics department will be included. Short-Physical Performance Battery (SPPB), Activities of Daily Living (ADL), Function Impairment Screening Tool (FIST), Geriatric Depression Scale (GDS-15), Short Form − 12 (SF-12), Fried frailty phenotype, social frailty, Morse Fall Risk Scale, SARC-CalF, Mini-Mental State Examination (MMSE), Mini-Nutritional Assessment Short-Form (MNA-SF), and intrinsic capacity will be assessed. The intervention group will receive an exercise-centered individualized MDT treatment, including exercise, educational, nutritional, medical, and comorbidity interventions; the control group will receive standard medical treatment. The primary outcome is the change in the SPPB score, and the secondary outcomes include increased SF-12, ADL, FIST, MMSE, MNA-SF, and intrinsic capacity scores and decreased GDS-15 and SARC-CalF scores.

Conclusion
Our results will help develop a multidisciplinary decision-making clinical pathway for inpatients with mobility limitation, which can be used to identify patients with mobility limitation more effectively, improve mobility, and reduce the risk of falls, frailty, and death in older inpatients. The implementation of this MDT strategy may standardize the treatment of mobility limitation, reduce adverse prognosis, and improve quality of life.

Trial registration
ChiCTR, ChiCTR2200056756, Registered 19 February 2022.
Burden of care and coping strategies among informal caregivers of people with behavioral and psychological symptoms of dementia in rural south-western Uganda
Authors: Owokuhaisa Judith , Kamoga Ronald , Musinguzi Pius , Muwanguzi Moses , Natukunda Sylivia , Mubangizi Vincent , Asiime Keith , Rukundo Godfrey Zari 
Published: August 2023

Abstract
Background
Caregiving is a draining role that inflicts a significant level of burden upon caregivers for older people with Behavioral and Psychological Symptoms of Dementia (BPSD). Caregiver burden is associated with poor health outcomes for both the people with BPSD and their caregivers. This study explored the burden of care and coping strategies used by informal caregivers of older people with BPSD in rural Southwestern Uganda.

Methods
This was a qualitative study among informal caregivers of older people with BPSD in Rubanda and Rukiga districts. We conducted in-depth interviews with a purposive sample of 27 caregivers using an interview guide. The interviews were conducted in the local language, audio recorded, transcribed, translated into English, and thematically analyzed.

Results
There were two major themes: caregiver burden and coping strategies. Caregiver burden was described as financial, physical, psychological and social. Caregivers mainly used emotion-focused coping strategies (religious coping, acceptance and emotional support seeking). Problem-focused coping strategies (planning) and dysfunctional coping strategies (self-distraction) were used to a lesser extent.

Conclusion
Informal caregivers of people with BPSD adopted both emotional and problem-focused coping strategies to cope with the burden of care for people with BPSD. Such coping strategies seemed to lighten the burden of caring, in the long motivating the caregivers to continue with the caring role.
Handling polypharmacy –a qualitative study using focus group interviews with older patients, their relatives, and healthcare professionals
Authors: Mikkelsen Thorbjørn Hougaard , Søndergaard Jens , Kjaer Niels Kristian , Nielsen Jesper Bo , Ryg Jesper , Kjeldsen Lene Juel , Mogensen Christian Backer 
Published: August 2023

Abstract
Background
On average, older patients use five or more medications daily. A consequence is an increased risk of adverse drug reactions, interactions, or medication errors. Therefore, it is important to understand the challenges experienced by the patients, relatives, and healthcare professionals pertinent to the concomitant use of many drugs.

Methods
We conducted a qualitative study using focus group interviews to collect information from patients, relatives, and healthcare professionals regarding older patients’ management of prescribed medicine. We interviewed seven patients using five or more medications daily, three relatives, three general practitioners, nine nurses from different healthcare sectors, one home care assistant, two hospital physicians, and four pharmacists.

Results
The following themes were identified: (1) Unintentional non-adherence, (2) Intentional non-adherence, (3) Generic substitution, (4) Medication lists, (5) Timing and medication schedule, (6) Medication reviews and (7) Dose dispensing/pill organizers.

Conclusion
Medication is the subject of concern among patients and relatives. They become confused and insecure about information from different actors and the package leaflets. Therefore, patients often request a thorough medication review to provide an overview, knowledge of possible side effects and interactions, and a clarification of the medication’s timing. In addition, patients, relatives and nurses all request an indication of when medicine should be taken, including allowable deviations from this timing. Therefore, prescribing physicians should prioritize communicating information regarding these matters when prescribing.
Disseminated non-tuberculous mycobacterial infection caused by Mycobacterium obuense in an immunocompromised patient: a case report
Authors: Naito Maiko , Fukushima Kentaro , Kusakabe Shinsuke , Endo Takaya , Shiroyama Takayuki , Ohira Kika , Azuma Koji , Tanizaki Satoshi , Yamamoto Yumiko , Hosono Yuki , Naito Yujiro , Futami Shinji , Miyake Kotaro , Hirata Haruhiko , Takeda Yoshito , Kumanogoh Atsushi 
Published: August 2023

Abstract
Background
Mycobacterium obuense (M. obuense) is a rapidly growing mycobacterium (RGM) which has been considered nonpathogenic. Here, we report a case of disseminated non-tuberculous mycobacterial (NTM) infection caused by M. obuense in an immunocompromised patient.

Case presentation
A 16-year-old boy was referred to our hospital due to acute myeloid leukemia. During the treatment of leukemia, the patient exhibited continuous fever, and diffuse miliary nodules with random distribution were found on chest computed tomography. Repeated examinations of bacterial culture tests revealed sputum and urine samples to be smear-positive for acid-fast bacillus, and blood culture from a peripherally inserted central catheter line showed the growth of NTM. The NTM species was identified as M. obuense by mass spectrometry and confirmed by genome sequencing. Combination therapy with amikacin, rifampicin, azithromycin, and moxifloxacin significantly improved the patient’s symptoms and radiological findings.

Conclusion
We report a case of disseminated NTM infection caused by M. obuense for which combination anti-microbial therapy was effective. An immunocompromised host indwelling catheter is at risk of RGM bloodstream infections. Although relatively rare, M. obuense may be considered as a potential pathogen causing infectious diseases, especially in high-risk patients.
Genomic insights into biased allele loss and increased gene numbers after genome duplication in autotetraploid Cyclocarya paliurus
Authors: Yu Rui-Min , Zhang Ning , Zhang Bo-Wen , Liang Yu , Pang Xiao-Xu , Cao Lei , Chen Yi-Dan , Zhang Wei-Ping , Yang Yang , Zhang Da-Yong , Pang Er-Li , Bai Wei-Ning 
Published: August 2023

Abstract
Background
Autopolyploidy is a valuable model for studying whole-genome duplication (WGD) without hybridization, yet little is known about the genomic structural and functional changes that occur in autopolyploids after WGD. Cyclocarya paliurus (Juglandaceae) is a natural diploid–autotetraploid species. We generated an allele-aware autotetraploid genome, a chimeric chromosome-level diploid genome, and whole-genome resequencing data for 106 autotetraploid individuals at an average depth of 60 × per individual, along with 12 diploid individuals at an average depth of 90 × per individual.

Results
Autotetraploid C. paliurus had 64 chromosomes clustered into 16 homologous groups, and the majority of homologous chromosomes demonstrated similar chromosome length, gene numbers, and expression. The regions of synteny, structural variation and nonalignment to the diploid genome accounted for 81.3%, 8.8% and 9.9% of the autotetraploid genome, respectively. Our analyses identified 20,626 genes (69.18%) with four alleles and 9191 genes (30.82%) with one, two, or three alleles, suggesting post-polyploid allelic loss. Genes with allelic loss were found to occur more often in proximity to or within structural variations and exhibited a marked overlap with transposable elements. Additionally, such genes showed a reduced tendency to interact with other genes. We also found 102 genes with more than four copies in the autotetraploid genome, and their expression levels were significantly higher than their diploid counterparts. These genes were enriched in enzymes involved in stress response and plant defense, potentially contributing to the evolutionary success of autotetraploids. Our population genomic analyses suggested a single origin of autotetraploids and recent divergence (~ 0.57 Mya) from diploids, with minimal interploidy admixture.

Conclusions
Our results indicate the potential for genomic and functional reorganization, which may contribute to evolutionary success in autotetraploid C. paliurus.
Overview of the main methods used for estimating catastrophic health expenditure
Authors: Nguyen Huyen Anh , Ahmed Sayem , Turner Hugo C. 
Published: August 2023

AbstractOut-of-pocket payments are expenditures borne directly by an individual/household for health services that are not reimbursed by any third-party. Households can experience financial hardship when the burden of such out-of-pocket payments is significant. This financial hardship is commonly measured using the “catastrophic health expenditure” (CHE) metric. CHE has been applied as an indicator in several health sectors and health policies. However, despite its importance, the methods used to measure the incidence of CHE vary across different studies and the terminology used can be inconsistent. In this paper, we introduce and raise awareness of the main approaches used to calculate CHE and discuss critical areas of methodological variation in a global health context. We outline the key features, foundation and differences between the two main methods used for estimating CHE: the budget share and the capacity-to-pay approach. We discuss key sources of variation within CHE calculation and using data from Ethiopia as a case study, illustrate how different approaches can lead to notably different CHE estimates. This variation could lead to challenges when decisionmakers and policymakers need to compare different studies' CHE estimates. This overview is intended to better understand how to interpret and compare CHE estimates and the potential variation across different studies.
COVPRIG robustly predicts the overall survival of IDH wild-type glioblastoma and highlights METTL1+ neural-progenitor-like tumor cell in driving unfavorable outcome
Authors: Ji Hang , Wang Fang , Liu Zhihui , Li Yue , Sun Haogeng , Xiao Anqi , Zhang Huanxin , You Chao , Hu Shaoshan , Liu Yi 
Published: August 2023

Abstract
Background
Accurately predicting the outcome of isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) remains hitherto challenging. This study aims to Construct and Validate a Robust Prognostic Model for IDH wild-type GBM (COVPRIG) for the prediction of overall survival using a novel metric, gene–gene (G × G) interaction, and explore molecular and cellular underpinnings.

Methods
Univariate and multivariate Cox regression of four independent trans-ethnic cohorts containing a total of 800 samples. Prediction efficacy was comprehensively evaluated and compared with previous models by a systematic literature review. The molecular underpinnings of COVPRIG were elucidated by integrated analysis of bulk-tumor and single-cell based datasets.

Results
Using a Cox-ph model-based method, six of the 93,961 G × G interactions were screened to form an optimal combination which, together with age, comprised the COVPRIG model. COVPRIG was designed for RNA-seq and microarray, respectively, and effectively identified patients at high risk of mortality. The predictive performance of COVPRIG was satisfactory, with area under the curve (AUC) ranging from 0.56 (CGGA693, RNA-seq, 6-month survival) to 0.79 (TCGA RNAseq, 18-month survival), which can be further validated by decision curves. Nomograms were constructed for individual risk prediction for RNA-seq and microarray-based cohorts, respectively. Besides, the prognostic significance of COVPRIG was also validated in GBM including the IDH mutant samples. Notably, COVPRIG was comprehensively evaluated and externally validated, and a systemic review disclosed that COVPRIG outperformed current validated models with an integrated discrimination improvement (IDI) of 6–16%. Moreover, integrative bioinformatics analysis predicted an essential role of METTL1+ neural-progenitor-like (NPC-like) malignant cell in driving unfavorable outcome.

Conclusion
This study provided a powerful tool for the outcome prediction for IDH wild-type GBM, and preliminary molecular underpinnings for future research.
Perioperative blood loss reduction using a sterile exsanguination tourniquet for orthopedic femoral-related surgeries in children: a randomized controlled study
Authors: Rattanathanya Terapat , Adulkasem Nath , Wongcharoenwatana Jidapa , Ariyawatkul Thanase , Chotigavanichaya Chatupon , Eamsobhana Perajit 
Published: August 2023

Abstract
Objectives
The sterile exsanguination tourniquet (SET) could be an alternative for providing bloodless surgeries in orthopedic femoral-related surgeries in pediatric patients where the standard pneumatic tourniquet would not be feasible. This randomized-controlled study aimed to evaluate the efficacy of SET in decreasing total perioperative blood loss and blood transfusion.

Methods
We conducted an unplanned interim analysis of data from a randomized-controlled trial. At the time of the analysis, 31 pediatric patients had been randomly assigned to undergo surgery with the SET application (the SET group, 15 patients) and without the SET application (the control group, 16 patients). An intention-to-treat analysis was performed to evaluate the total perioperative blood loss, postoperative blood transfusion, estimated intraoperative blood loss, total drainage volume, postoperative hemoglobin level, and operative time according to the significance level adjusted for multiplicity (p < 0.029).

Results
There was a borderline statistically significant lower body weight-adjusted TBL in the SET group (SET = 14.1 (7.7, 16.9) ml/kg vs. control 18.3 (14.8, 37.2) ml/kg, p-value = 0.027). The body weight-adjusted transfusion volume was statistically significantly greater in the control group (SET = 0.0 (0.0, 0.0) ml/kg vs. control = 2.1 (0.0, 9.7) ml/kg, p = 0.017). Body weight-adjusted estimated intraoperative blood loss was significantly lower in the SET group (SET = 0.8 (0.2, 3.5) ml/kg vs. control = 5.6 (3.4, 21.5) ml/kg, p < 0.001). In addition, the operative time was lower in the SET group with borderline statistical significance (SET = 105 (85.0, 125.0) vs. control = 130 (101.3, 167.5), p =  0.039).

Conclusion
Utilization of a sterile exsanguination tourniquet (SET) significantly reduced an estimated intraoperative blood loss while preventing the need for blood transfusion after pediatric orthopedic femoral-related surgeries.
Trial registration TCTR20220412003.