bluuebunny/crossref_metadata_2025 huggingface dataset:
Basket weaving as an Aboriginal methodology and theoretical framework
Authors: Humphrey Kelly , Barlo Stuart , Lasczik Alexandra
Published: August 2023

This article explores the development of an Aboriginal basket-weaving theoretical-methodological framework developed as part of a doctoral study that explores Aboriginal and Torres Strait Islander teachers’ aspirations towards school leadership in Australia. Aboriginal basket weaving framed as theory-methodology is positioned through the cultural lens of Indigenous and post-structural theoretical frameworks. Connected and relational ontology is woven through the methodologies of storying and yarning that are held by the basket-weaving theoretical framing yet to be enacted in the fieldwork and analysis. This article is a first look at the framework developed by the lead author in concert with her doctoral supervisors.
Reliability-based assessment of reasonable mid-tower lateral stiffness for a three-tower suspension bridge
Authors: Chen Yu-peng , Zhang Wen-ming , Liu Tian-cheng
Published: August 2023

A reasonable lateral stiffness of the bridge mid-tower should ensure that the deflection-to-span ratio and sliding resistance coefficient satisfy the design requirements. However, if this stiffness is determined by the deterministic parametric analysis, the above two verification indices may exceed the threshold due to the randomness of the high-dimensional structure and load parameters. To satisfy the structural safety requirements of a three-tower suspension bridge during its design life, this study proposes a method to quickly and accurately evaluate the reliability indices of the deflection-to-span ratio and sliding resistance coefficient of the three-tower suspension bridge. Based on advanced first-order second-moment, the proposed method transforms the reliability problem into an optimization problem with constraint functions, uses the single-cable theory to establish the limit state function, and combines the manta ray foraging optimization algorithm and penalty function to derive the reliability index. The effectiveness of the proposed method is verified by performing Latin hypercube sampling for an examplary three-tower suspension bridge. These results prove that the new technique avoids tedious finite element simulation and surrogate model fitting, ensuring the accuracy of the reliability index while improving the calculation efficiency. The study further identifies critical structural parameters by parametric analysis. Based on the inverse reliability, the dimensionless stiffness range for the mid-tower with the randomness of the parameters is derived, and the preliminary design method of the lateral stiffness of the mid-tower based on the reliability is established.
Optical phase mode analysis method for pipeline bolt looseness identification using distributed optical fiber acoustic sensing
Authors: Ma Tianjiao , Feng Qian , Tan Zhisen , Ou Jinping
Published: August 2023

Distributed optical fiber acoustic sensing (DAS) technique has been applied in pipeline health monitoring, and the commonly used sensor is phase-sensitive optical time domain reflectometry. Most DAS monitoring systems can localize leakages of a pipeline but fail to identify potential non-destructive damages like bolt looseness on joints before the leakage occurs. An early damage identification is indispensable to averting severe leakages and secondary disasters. In this study, an optical phase mode analysis method is proposed for identifying pipeline bolt looseness. This method combines structure mode analysis and distributed optical phase demodulation to extract damage-related phase mode parameters. Two algorithms are specially designed for denoising and selecting signals essential for mode analysis. Phase time histories are retrieved from the original optical phase, which are decomposed to acquire phase mode shapes that can localize bolt looseness through Hilbert-Huang transform enhanced with bandwidth restricted empirical mode decomposition. Phase damping ratio is proposed to further quantify the looseness degree. Polarization diversity technique is employed to avoid polarization fading. An experiment was conducted upon a 3.2 m steel pipeline with flange joints. Bolt looseness on three joints are respectively localized even if only one bolt is loosened, obtaining a localization error of 0.07 m and 85.7% recognition ratio. The phase damping ratio shows apparent positive correlation with the number of loose bolts. The error of quantified loose bolt number is 0.79. The present study demonstrates how to localize and quantify pipeline bolt looseness through dynamical mode analysis for distributed optical phase. The developed method can identify potential damages that change the mechanical properties of a pipeline before they get severe, and holds promise in the long-distance health monitoring of other structures.
Endotension as a Rare Complication to Endovascular Abdominal Aortic Aneurysm Repair
Authors: Papadoulas Spyros , Pitros Christos , Papageorgopoulou Chrysanthi , Mulita Francesk
Published: August 2023

Endotension remains an enigmatic rare cause of endovascular abdominal aortic aneurysm repair failure leading to aneurysm growth and/or rupture. We present a patient with a long-standing endotension treated with open reconstruction and graft explantation. We also provide a unique clinical video, which gives a key view of the intrasac operative findings.
Presence of risk factors associated with colectomy among patients with ulcerative colitis: a post hoc analysis of data from the tofacitinib OCTAVE ulcerative colitis clinical program
Authors: Rubin David T. , Salese Leonardo , Cohen Mitchell , Kotze Paulo G. , Woolcott John C. , Su Chinyu , Mundayat Rajiv , Paulissen Jerome , Torres Joana , Long Millie D.
Published: August 2023

Background:

Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC).

Objective:

To assess colectomy incidence rates (IRs) and baseline characteristics for the presence of identified colectomy risk factors among patients in the tofacitinib OCTAVE UC clinical program.

Design:

This post hoc analysis evaluated patients in the 8-week OCTAVE Induction 1 and 2, 52-week OCTAVE Sustain, and OCTAVE Open (open-label, long-term extension) studies.

Methods:

IRs [95% confidence interval (CI)] for colectomy were analyzed. Baseline risk factors based on clinical guidelines: aged <40 years at diagnosis, extensive colitis, severe endoscopic disease [Mayo endoscopic subscore (MES) = 3], hospitalization for UC within 12 months, C-reactive protein (CRP) >3 mg/L, and serum albumin <3.5 g/dL. Baseline risk factors were evaluated in patients who underwent colectomy by study and summarized descriptively.

Results:

Over a maximum of 7.8 years of tofacitinib exposure, 14 patients underwent colectomy: 3/1139 (0.3%) in OCTAVE Induction 1 and 2 [tofacitinib 10 mg twice daily (BID): n = 2; placebo: n = 1], 3/593 (0.5%) in OCTAVE Sustain (placebo: n = 3), and 8/944 (0.8%) in OCTAVE Open (tofacitinib 10 mg BID: n = 8). Colectomy IR per 100 patient-years for all patients who received ⩾1 tofacitinib dose was 0.34 (95% CI: 0.16–0.63). All patients who underwent colectomy had ⩾1 risk factor and prior tumor necrosis factor inhibitor (TNFi) failure, among which the most common risk factors were a MES of 3 ( n = 13), CRP >3 mg/L ( n = 11), and aged <40 years at diagnosis ( n = 9).

Conclusions:

Among patients with moderate to severe UC receiving tofacitinib, colectomies were infrequent; all patients undergoing colectomy had prior TNFi failure, and most had multiple additional risk factors. This provides important information to discuss with patients and inform management decisions.

Registration:

NCT01465763; NCT01458951; NCT01458574; and NCT01470612.
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

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

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 > 1000; Cmax:IC50 < 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 < .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

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

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

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

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

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

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

Out-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

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

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.
Risk factors and nomogram predictive model of surgical site infection in closed pilon fractures
Authors: Ke Chenrong , Dong Xiaoyu , Xiang Guangheng , Zhu Juanjuan
Published: August 2023

Objectives

In this study, we try to investigate the risk factors of postoperative surgical site infection (SSI) in closed pilon fractures and establish a nomogram prediction model.

Methods

From January 2012 to June 2021, 516 closed pilon fracture patients were included in this study. Of these, 387 patients were randomly assigned to the training group and 129 patients were assigned to the validation group (3:1). By univariate and multivariate Cox analysis, we identified independent risk factors for postoperative SSI after Pilon fracture. We established a nomogram model and used receiver operating characteristic (ROC) and calibration chart to evaluate its discriminant and calibration.

Results

SSI occurred in 71 patients in the training group and 23 patients in the validation group. Ultimately, age, preoperative blood sugar, operative time, Tscherne classification and fracture classification were identified as independent risk factors for SSI. The AUC values for SSI of the training and validation group were 0.898 and 0.880, and the P value of the Hosmer–Lemeshow test was 0.125. We established a nomogram prediction model based on age, preoperative blood sugar, operative time, Tscherne classification and fracture classification.

Conclusion

Our nomogram model had good discrimination and calibration power, so it could be used to predict SSI risk in patients with pilon fracture.
GATA2 co-opts TGFβ1/SMAD4 oncogenic signaling and inherited variants at 6q22 to modulate prostate cancer progression
Authors: Yang Xiayun , Zhang Qin , Li Shuxuan , Devarajan Raman , Luo Binjie , Tan Zenglai , Wang Zixian , Giannareas Nikolaos , Wenta Tomasz , Ma Wenlong , Li Yuqing , Yang Yuehong , Manninen Aki , Wu Song , Wei Gong-Hong
Published: August 2023

Background

Aberrant somatic genomic alteration including copy number amplification is a hallmark of cancer genomes. We previously profiled genomic landscapes of prostate cancer (PCa), yet the underlying causal genes with prognostic potential has not been defined. It remains unclear how a somatic genomic event cooperates with inherited germline variants contribute to cancer predisposition and progression.

Methods

We applied integrated genomic and clinical data, experimental models and bioinformatic analysis to identify GATA2 as a highly prevalent metastasis-associated genomic amplification in PCa. Biological roles of GATA2 in PCa metastasis was determined in vitro and in vivo. Global chromatin co-occupancy and co-regulation of GATA2 and SMAD4 was investigated by coimmunoprecipitation, ChIP-seq and RNA-seq assays. Tumor cellular assays, qRT-PCR, western blot, ChIP, luciferase assays and CRISPR-Cas9 editing methods were performed to mechanistically understand the cooperation of GATA2 with SMAD4 in promoting TGFβ1 and AR signaling and mediating inherited PCa risk and progression.

Results

In this study, by integrated genomics and experimental analysis, we identified GATA2 as a prevalent metastasis-associated genomic amplification to transcriptionally augment its own expression in PCa. Functional experiments demonstrated that GATA2 physically interacted and cooperated with SMAD4 for genome-wide chromatin co-occupancy and co-regulation of PCa genes and metastasis pathways like TGFβ signaling. Mechanistically, GATA2 was cooperative with SMAD4 to enhance TGFβ and AR signaling pathways, and activated the expression of TGFβ1 via directly binding to a distal enhancer of TGFβ1. Strinkingly, GATA2 and SMAD4 globally mediated inherited PCa risk and formed a transcriptional complex with HOXB13 at the PCa risk-associated rs339331/6q22 enhancer, leading to increased expression of the PCa susceptibility gene RFX6.

Conclusions

Our study prioritizes causal genomic amplification genes with prognostic values in PCa and reveals the pivotal roles of GATA2 in transcriptionally activating the expression of its own and TGFβ1, thereby co-opting to TGFβ1/SMAD4 signaling and RFX6 at 6q22 to modulate PCa predisposition and progression.
“What’s measured gets done”: a call for a European semester for cancer to improve cancer outcomes in Central and Southeastern Europe
Authors: Zielinski Christoph , Thallinger Christiane , Rödiger Alexander
Published: August 2023

Cancer mortality varies widely across Europe, and survival depends on where you live. In particular, the inequality between countries in Central and South-Eastern Europe (CEE) and Western Europe (WE) is striking. The COVID-19 pandemic has brought existing inequalities into sharp focus, and the economic disruption it has caused threatens to deepen them. The Central European Cooperative Oncology Group (CECOG) has created a platform with the aim to reduce health inequalities and to improve patient access to cancer care. The subject of discussion is the value of new treatments to create willingness to invest in improving cancer outcomes while managing the budget. The platform includes various stakeholders as scientific leaders, policy makers, payers, patients and industry.
Randomized controlled trial of liberal vs. standard fasting instructions in percutaneous cardiac procedures
Authors: Atkinson Derek J. , Romeiser Jamie L. , Almasry Ibrahim O. , Tannous Henry J. , Parikh Puja B. , Bennett-Guerrero Elliott
Published: August 2023

Background

Pre-procedural fasting to reduce aspiration risk is usual care prior to surgery requiring anesthesia. Prolonged fasting, however, can result in dehydration and may adversely affect patient experience and outcomes. Previous studies suggest that providing a supplemental beverage to patients undergoing cardiac and a variety of other surgical procedures improves patients’ subjective assessment of thirst and hunger and potentially decreases the need for inotrope and vasopressor therapy. Less is known, however, about the effects of ad libitum clear liquids up to 2 h prior to surgery.

Methods

Adult patients undergoing transcatheter aortic valve replacement (TAVR) or arrhythmia ablation were randomized (1:1) to ad libitum clear liquids up to 2 h prior to their procedure vs. nil per os (NPO) after midnight (control group, usual care). The primary endpoint was a composite satisfaction score that included patient-reported thirst, hunger, headache, nausea, lightheadedness, and anxiousness prior to surgery. The incidence of case-delay was recorded. Intraoperative vasopressor administration, changes in creatinine, anti-emetic use, and hospital length of stay (LOS) were recorded. Safety endpoints including aspiration were assessed.

Results

A total of 200 patients were randomized and 181 patients were included in the final analysis. Overall, 92% of patients were ASA class III or IV and 23% of patients had NYHA class III or IV symptoms. Groups were well balanced with no significant differences in age, sex or baseline cardiac or renal disease. The composite satisfaction score (primary endpoint) was not significantly different between groups (Ad libitum median = 12, IQR = [6, 17], vs Standard NPO median = 10, IQR = [5, 15], [95% CI = [-1, 4]). No significant differences between the two groups were observed in any of the individual survey questions (thirst, hunger, headache, nausea, lightheadedness, anxiousness). No significant differences between groups were observed for intra-operative vasopressor use, changes in creatinine, rescue anti-emetic use or hospital LOS. There were no case delays attributed to the intervention. There were no cases of suspected aspiration.

Conclusion

No adverse events or case delays were observed in the ad libitum clears group. No significant benefit, however, was observed in patient satisfaction or any of the pre-specified secondary endpoints in patients randomized to ad libitum clear liquids up to 2 h prior to their procedure.

Trial registration

NCT04079543.
Incoming plate structure at the Japan Trench subduction zone revealed in densely spaced reflection seismic profiles
Authors: Nakamura Yasuyuki , Kodaira Shuichi , Fujie Gou , Yamashita Mikiya , Obana Koichiro , Miura Seiichi
Published: August 2023

The structure of the incoming plate is an important element that is often considered to be related to the occurrence of great earthquakes in subduction zones. In the Japan Trench, where the 2011 Tohoku earthquake occurred, we collected seismic profiles along survey lines separated by 2–8 km to examine the structural characteristics of the incoming Pacific plate in detail. The average thickness of the incoming sediments was < 500 m along most of the Japan Trench, and it was < 300 m at ~ 38° N, where the large shallow megathrust slip occurred during the 2011 Tohoku earthquake. We mapped bending-related normal faults, including their dip direction and amount of throw. The numbers of eastward (oceanward) and westward (trenchward) dipping normal faults were generally comparable in the Japan Trench. Eastward dipping normal faults were dominant in the northern and southern parts of the Japan Trench, whereas westward dipping normal faults were more numerous in the central part. Graben-fill sediments deposited at the landward edge of the graben were bounded by eastward dipping normal faults. Trench-fill sediments were also observed along the trench axis. The sediment fills locally increased the thickness of the input sediments where they were deposited. The along-axis variation in input sediment and sediment fill distribution, and the variations in normal fault dip direction between the central and other parts of the Japan Trench may correspond to different slip styles along the plate boundary.
Digital learning and the ESL online classroom in higher education: teachers’ perspectives
Authors: Lo Noble Po-kan
Published: August 2023

This study explores teachers’ perspectives with regards to teaching English in virtual classrooms, specifically with regards to teaching English as a second language within the context of emergency remote learning in Hong Kong during COVID-19. Through undertaking thematic analysis of six interviews with English language teachers at a university in Hong Kong, this study explores how teachers view the benefits, challenges and personal and professional consequences of the shift to emergency remote teaching during the pandemic. Taking a social constructivist approach to the topic, the study also seeks to uncover how teachers view such provisions as being improved under future emergencies and with respect to online English language teaching moving forwards generally. This research topic contributes both to a longstanding debate on the ways in which digital technologies can enhance education and language learning, as well as the emerging body of literature examining how teachers and students have responded to the implementation of digital learning in online classrooms during the COVID-19 pandemic.
Emergence of National Nutrition Policy in the Lao People’s Democratic Republic: an analysis of collaborations between governmental and external actors
Authors: Sengchaleun Viengsamay , Kounnavong Sengchanh , Reinharz Daniel
Published: August 2023

Background

In most developing countries, addressing malnutrition involves a coalition of stakeholders that includes the government and international development partners. This study explores the evolution of the malnutrition actor coalition landscape before and after the emergence of the National Nutrition Policy in the Lao People’s Democratic Republic (Lao PDR) in 2008.

Methods

A qualitative study was conducted based on the theory of coalition structuring. Twenty semi-structured interviews were performed with representatives of national and international organisations involved in addressing malnutrition in Lao PDR. The information obtained from the interviews was complemented by an analysis of relevant documents dating back to 1990. Interviews were recorded and transcribed verbatim. A thematic analysis was performed using NVivo 11 software and the diagrams of collaboration drawn by the participants were turned into a visual collaboration map using SocNetV software. We relied on various types of triangulation to increase the analysis's credibility, reliability, and confirmability.

Results

The results showed that before the emergence of the National Nutrition Policy, three coalitions representing the health, agriculture, and education sectors coexisted. These colalitions worked largely in silos, although with some interactions when deemed necessary mainly by United Nations agencies. The emergence of the National Nutrition Policy provided the government with an effective political tool for coalescing the three coalitions into a unique coalition involving all major stakeholders in the nutrition field. All three forces that incite actors to collaborate inside a coalition according to the theory of coalition structuring (transactions, control, intangible factors) were mobilised in the creation of the single coalition.

Conclusions

Combating malnutrition is a government priority in the Lao PDR. The current study showed that the National Nutrition Policy in Lao PDR has led to a significant evolution in the malnutrition coalition landscape, resulting in improved collaboration among stakeholders. This finding highlights the effectiveness of public policies in facilitating intersectoral activities to tackle complex problems, such as malnutrition.
A Sox17 downstream gene Rasip1 is involved in the hematopoietic activity of intra-aortic hematopoietic clusters in the midgestation mouse embryo
Authors: Melig Gerel , Nobuhisa Ikuo , Saito Kiyoka , Tsukahara Ryota , Itabashi Ayumi , Kanai Yoshiakira , Kanai-Azuma Masami , Osawa Mitsujiro , Oshima Motohiko , Iwama Atsushi , Taga Tetsuya
Published: August 2023

Background

During mouse embryonic development, definitive hematopoiesis is first detected around embryonic day (E) 10.5 in the aorta-gonad-mesonephros (AGM) region. Hematopoietic stem cells (HSCs) arise in the dorsal aorta’s intra-aortic hematopoietic cell clusters (IAHCs). We have previously reported that a transcription factor Sox17 is expressed in IAHCs, and that, among them, CD45lowc-Kithigh cells have high hematopoietic activity. Furthermore, forced expression of Sox17 in this population of cells can maintain the formation of hematopoietic cell clusters. However, how Sox17 does so, particularly downstream signaling involved, remains poorly understood. The purpose of this study is to search for new Sox17 targets which contribute to cluster formation with hematopoietic activity.

Methods

RNA-sequencing (RNA-seq) analysis was done to identify genes that are upregulated in Sox17-expressing IAHCs as compared with Sox17-negative ones. Among the top 7 highly expressed genes, Rasip1 which had been reported to be a vascular-specific regulator was focused on in this study, and firstly, the whole-mount immunostaining was done. We conducted luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay to examine whether Sox17 regulates Rasip1 gene expression via binding to its enhancer element. We also analyzed the cluster formation and the multilineage colony-forming ability of Rasip1-transduced cells and Rasip1-knockdown Sox17-transduced cells.

Results

The increase of the Rasip1 expression level was observed in Sox17-positive CD45lowc-Kithigh cells as compared with the Sox17-nonexpressing control. Also, the expression level of the Rasip1 gene was increased by the Sox17-nuclear translocation. Rasip1 was expressed on the membrane of IAHCs, overlapping with the endothelial cell marker, CD31, and hematopoietic stem/progenitor marker (HSPC), c-Kit. Rasip1 expression was observed in most part of c-Kit+Sox17+ cells in IAHCs. Luciferase reporter assay and ChIP assay indicated that one of the five putative Sox17-binding sites in the Rasip1 enhancer region was important for Rasip1 expression via Sox17 binding. Rasip1 knockdown in Sox17-transduced cells decreased the cluster formation and diminished the colony-forming ability, while overexpression of Rasip1 in CD45lowc-Kithigh cells led to a significant but transient increase in hematopoietic activity.

Conclusions

Rasip1 knockdown in Sox17-transduced CD45lowc-Kithigh cells displayed a significant decrease in the multilineage colony-forming ability and the cluster size. Rasip1 overexpression in Sox17-untransduced CD45lowc-Kithigh cells led to a significant but transient increase in the multilineage colony-forming ability, suggesting the presence of a cooperating factor for sustained hematopoietic activity.