bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Precision Medicine Competency Framework for the Therapeutics Industry
Authors: Conway Nicholette , Chisholm Orin 
Published: September 2023

Abstract
INTRODUCTION: The successful adoption of precision medicine relies on the development of effective treatments and judicious utilization within a supportive healthcare system. Embracing a learning healthcare capability will be crucial to navigating the disruptions arising from rapid scientific and technological innovation.
AIM: to build a Precision Medicine (PM) competency framework that can be used across the Medical Technology and Pharmaceutical (MTP) industries to build a confident and capable workforce, support cross-disciplinary work and collaboration, and instil a continuous learning mindset.
METHODOLOGY: A desktop research review of current literature, curriculum, and healthcare trends identified a core set of domains and subdomains related to precision medicine competencies. A survey was distributed to the Industry Genomics Network Alliance (InGENA) members in 2021 to confirm the relevance and applicability of the domains and subdomains to their current work practice and their expected work practice in 5 years’ time.
RESULTS: Four domains were identified: medical science and technology; translational and clinical application; governance and regulation and professional practice. Each domain has a series of subdomains and patient needs were integrated across all four of the domains. Survey results confirmed the applicability of these domains to the MTP industry.
CONCLUSION: The Framework was well accepted by industry, with a strong interest from related disciplines including allied health professionals. Given the pace of change this framework will need regular review and updating. The principles can be used to define frameworks for other technologies such as Cell and Gene Technologies (CGT) and Regenerative Medicines (RM).
Investigation on micro milling of cemented carbide with ball nose and corner radius diamond coated end mills
Authors: Figueiredo Daniel Amaral , Silva Joana , Silva Tiago , Jesus Abílio , Fernandes Cristina , Davim Paulo 
Published: September 2023

Abstract
Micro milling of cemented carbides is a challenging task due to their high hardness, low toughness and high wear resistance. Ensuring good surface quality and dimensional accuracy is crucial for extending parts service life, which in turn enhances economical and environmental sustainability. This paper is mainly focused on evaluating surface formation mechanisms, scale effects, fracture behaviour and chip formation using distinct cemented carbide micro milling tools with multi layer diamond HF-CVD. In order to achieve higher precision and more efficient micro milling operations on WC-15Co and WC-10Co, a systematic experimental approach has been carried out. The influence of cutting parameters, achievable surface quality and defects occurrence were thoroughly examined. Experimental results evidence the influence of operational conditions on the chip formation of cemented carbides as well as an important impact of the utilized cutting tool. Micro pits, cracks, thin ploughing layer and fractured workpiece edges are amongst the observed surface damage mechanisms. A ductile cutting regime of the high-hardness composite material is confirmed, exhibited by the plastic deformation even when small depths of cut are considered.
NOL3 induced feedback loop between RCC cells and TAMs promotes TKI resistance and unfavorable prognosis in renal cancer
Authors: Cui Xingang , Wang Hongru , Tian Yijun , Lv Jianmin , Shi Xiaokai , Sun Ye , Qian Cheng , Song Xu , Gan Sishun 
Published: September 2023

Abstract
TKI resistance of advanced ccRCC patients usually leads to poor prognosis. Interaction between tumor cells and tumor-associated macrophages (TAMs) has been reported to facilitate tumor progression. However, the underlying mechanism remains unclear. This study employed cell functional experiments, IHC, ELISA, and subcutaneous tumor formation models to explore the interaction between ccRCC and TAMs. We found that the expression of NOL3 was upregulated in ccRCC using the online database. The NOL3 over-expressing ccRCC cell lines ACHN and 786-O showed enhanced proliferation and anti-apoptosis ability. In addition, THP1-derived macrophages co-cultured with ccRCC cells exhibited an increased trend towards M2-like polarization. TAMs could stimulate ccRCC to secret more VEGF, which promotes TKI resistance. ccRCC patients from two independent cohorts were screened to investigate the prediction accuracy of NOL3 and the relationship between NOL3 expression and TAMs infiltration. IHC staining quantified by H-score revealed a negative correlation between NOL3 expression and disease progression and a positive correlation with TAMs infiltration. Moreover, NOL3, CD163, and TNM Stage were also found to be the independent risk factors for predicting the outcome of ccRCC patients. Integrating NOL3, TAMs and TNM Stage could predict the prognosis of ccRCC with better accuracy. Overexpressing NOL3 enhanced the infiltration of TAMs and VEGF secretion in mouse tumors, while depletion of macrophages enhanced TKI efficacy. In summary, a positive feedback loop between ccRCC cells and TAMs induced by NOL3 promotes TKI resistance, and targeting NOL3/TAMs might be a potential strategy to alleviate TKI resistance.
Pathogenic variants in SMARCA1 cause an X-linked neurodevelopmental disorder modulated by NURF complex composition
Authors: Picketts David , Mirzaa Ghayda , Yan Keqin , Relator Raissa , Timpano Sara , Yalcin Binnaz , Collins Stephan , Ziegler Alban , Pao Emily , Oyama Nora , Brischoux-Boucher Elise , PIARD Juliette , Monaghan Kristin , Sacoto Maria Guillen , Dobyns William , Park Kristen , Fernández-Mayoralas Daniel , Fernández-Jaén Alberto , Jayakar Parul , Brusco Alfredo , Antona Vincenzo , Giorgio Elisa , Kvarnung Malin , Isidor Bertrand , Conrad Solène , Cogné Benjamin , Deb Wallid , Stuurman K.E. , Sterbova Katalin , Smal Noor , Weckhuysen Sarah , Oegema Renske , Innes Micheil , Latsko Maeson , Ben-Omran Tawfeg , Yeh Rebecca , Kruer Michael , Bakhtiari Somayeh , Papavasiliou Antigone , Moutton Sébastien , Nambot Sophie , Chanprasert Sirisak , Paolucci Sarah , Miller Kait , Burton Barbara , Kim Katherine , O'Heir Emily , Bruwer Zandre , Donald Kirsten , Kleefstra Tjitske , Goldstein Amy , Angle Brad , Bontempo Kelly , Miny Peter , Joset Pascal , Demurger Florence , Hobson Emma , Pang Lewis , Carpenter Lori , Li Dong , Bonneau Dominique , Sadikovic Bekim 
Published: September 2023

Abstract
Pathogenic variants in ATP-dependent chromatin remodeling proteins are a recurrent cause of neurodevelopmental disorders (NDDs). The NURF complex consists of BPTF and either the SNF2H (SMARCA5) or SNF2L (SMARCA1) ISWI-chromatin remodeling enzyme. Pathogenic variants in BPTF and SMARCA5 were previously implicated in NDDs. Here, we describe 40 individuals from 30 families with de novo or maternally inherited pathogenic variants in SMARCA1. This novel NDD was associated with mild to severe ID/DD, delayed or regressive speech development, and some recurrent facial dysmorphisms. Individuals carrying SMARCA1 loss-of-function variants exhibited a mild genome-wide DNA methylation profile and a high penetrance of macrocephaly. Genetic dissection of the NURF complex using Smarca1, Smarca5, and Bptfsingle and double mouse knockouts revealed the importance of NURF composition and dosage for proper forebrain development. Finally, we propose that genetic alterations affecting different NURF components result in a NDD with a broad clinical spectrum.
Debonding Stresses of Metal Orthodontic Brackets Retained to Tooth Enamel with Co-Cured Self-Etch Primer
Authors: Abdelaziz Khalid M. , Alshahrani Abdulaziz M. , Algarni Youssef A. , Alayyash Afnan 
Published: September 2023

Abstract
Background: Applying the recently suggested resin primer co-curing technique could save some of patients’ and orthodontists’ time. This study evaluated the efficiency of self-etch primer co-curing protocol in retaining orthodontic brackets.
Methods: A self-etch orthodontic resin primer was pre-cured or co-cured together with the resin adhesive (Groups 1 and 2) to retain either non-coated or pre-coated orthodontic brackets (Subgroups 1 and 2) on the buccal surfaces of extracted premolars. The debonding stress values were evaluated immediately after bonding (category 1) and after exposure to cyclic intraoral hydraulic, thermal, and mechanical stress simulations (Category 2). The adhesive remanent index (ARI) was also assessed for each test category.
Results: The co-cured primer provided higher immediate debonding stress values of both non- and pre-coated brackets (Tukey’s, P<0.05) than did the pre-cured primer. The delayed debonding stress values were lower than the immediately assessed values (Tukey’s, P<0.05) for both types of brackets. No difference (Mann Whitney’s, P>0.05) was noticed in the ARIs of all test categories.
Conclusions: Although the intraoral stress simulations reduce the brackets’ debonding stress values, co-curing the self-etch orthodontic primer can offer clinically efficient bonding of both non- and pre-coated metal brackets with no harm to the tooth enamel on debonding.
Chromosome abnormalities and copy number variations in fetuses with ultrasound soft markers: a retrospective study
Authors: Zhang Hao , Chen Quan , Li Xue , Chen Huijuan , Liu Lin , Zhou Shijie , Xu Zhihong 
Published: September 2023

Abstract
Purpose
Although previous results revealed that genetic aberrations were associated with ultrasound soft markers, the detection rates of chromosomal aberrations and P/LP CNVs varied among different studies. Thus, the detection of chromosome abnormalities and copy number variations (CNVs) in fetuses with ultrasound soft markers were investigated in our study.
Methods
A total of 2422 fetuses, including 1005 fetuses with ultrasound soft markers and 1417 fetuses without ultrasound soft markers, were included in our study. CNV-seq, combined with karyotyping or QF-PCR, was performed to detect chromosome abnormalities and CNVs. Statistical analysis was performed using SPSS 19.0.
Results
Our study detected 28 and 22 chromosome abnormalities in fetuses with and without ultrasound soft markers, respectively. Meanwhile, 24 and 10 P/LP CNVs were detected in fetuses with and without ultrasound soft markers, respectively. These results revealed that the detection rates of chromosome abnormalities and P/LP CNVs were significantly increased in fetuses with ultrasound soft markers. Subsequent analysis unveiled that the detection rates of chromosome abnormalities and P/LP CNVs varied in fetuses with different ultrasound soft markers. The detection rates of chromosome abnormalities in fetuses with thickened NT elevated significantly, while P/LP CNVs were more likely detected in fetuses with renal abnormalities. Additionally, our results showed that the detection rates of chromosome abnormalities were positively correlated with NT thickness in fetuses with thickened NT.
Conclusion
Our results revealed that fetuses with ultrasound soft markers had a higher risk of chromosome abnormalities and P/LP CNVs.
Establishment and Validation of a Predictive Model for the Risk of Invasive Mechanical Ventilation in Elderly Patients with Sepsis
Authors: Zhu Simeng 
Published: September 2023

Abstract
Background
The aim of the research was to discover risk elements and create a useful nomogram for predicting the occurrence of invasive mechanical ventilation (IMV) in elderly patients with sepsis.
Methods
Sepsis patients who were elderly, aged 65 years or older, were selected from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Demographic and laboratory test information were collected on the first day of Intensive Care Unit (ICU) admission. Participants were 7:3 randomly assigned divisions into training and validation sets. The features of training set were used to determine risk factors for predicting invasive mechanical ventilation. The least absolute shrinkage and selection operator (LASSO) regression was employed to recognize predictors. Subsequently, the training set was utilized to create a nomogram. The validity of the nomogram was evaluated using receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and calibration curve analysis.
Results
We enrolled 7,868 patients, with 5,259 (66.8%) receiving invasive mechanical ventilation. In the IMV group, hospital mortality was higher than in the non-IMV group (23% vs. 13%, p < 0.001). Logistic regression analysis identified SpO2, hemoglobin, anion gap, chloride, vasopressor drugs, and ICU length of stay (LOS) as predictors, which were integrated into a nomogram. The AUC of the nomogram was 0.84 in both training set and validation set. The calibration plot demonstrated that the nomogram effectively predicted the requirement for IMV in both datasets. DCA proved the clinical values of the nomogram.
Conclusion
The nomogram provides a predictive tool for identifying the demand for invasive mechanical ventilation in sepsis patients who aged 65 or older. This model can aid healthcare professionals in identifying high-risk patients earlier and implementing timely interventions to improve their prognosis.
Rise of oligodendroglioma hypermutator phenotype from a subclone harboring TP53 mutation after TMZ treatment
Authors: Higuchi Fumi , Uzuka Takeo , Matsuda Hadzki , Sumi Takuma , Iwata Kayoko , Namatame Takashi , Shin Masahiro , Akutsu Hiroyoshi , Ueki Keisuke 
Published: September 2023

Abstract
Oligodendrogliomas characterized and defined by 1p/19q co-deletion are slowly glowing tumors showing better prognosis than astrocytomas. TP53 mutation is rare in oligodendrogliomas while the vast majority of astrocytomas harbor the mutation, making TP53 mutation mutually exclusive with 1p/19q codeletion in lower grade gliomas virtually. We report a case of 51-year-old women with a left fronto-temporal oligodendroglioma that contained a small portion with a TP53 mutation, R248Q, at the initial surgery. On a first, slow-growing recurrence 29 months after radiation and nitrosoures-based chemotherapy, the patient underwent TMZ chemotherapy. The recurrent tumor responded well to TMZ, but developed a rapid progression after 6 cycles as a malignant hypermutator tumor with a MSH6 mutation. Most of the recurrent tumor lacked typical oligodendroglioma morphology that was observed in the primary tumor, while it retained the IDH1 mutation and 1p/19q co-deletion. The identical TP53 mutation observed in the small portion of the primary tumor was universal in the recurrence. This case embodied the theoretically understandable clonal expansion of the TP53 mutation with additional mismatch repair gene dysfunction leading to hypermutator phenotype, and thus indicated that TP53 mutation in oligodendroglioma, although not common, may play a critical role in the development of hypermutator after TMZ treatment.
MiR-146a-5p plays a therapeutic role in temporomandibular joint osteoarthritis in rats: an in vivo study
Authors: Jingfen Cun , Congchong Shi , Yong Chen , Li Zhang , Zhi Zhou , Yu Ding 
Published: September 2023

Abstract
Methods
TMJ-OA disease model was established by combined injection of IL-1β and TNF-α, and miR-146a-5p agomir was injected into the rat’s joint cavity, then, observe the changes of temporomandibular joint tissue structure and related proteins by HE, safranine O-fast green, immunohistochemical staining.
Results
The inflammatory secretions were significantly reduced in the experimental group (injection of miR-146a-5p agomir), the structure of cartilage layers was clearer than that of the control group, and the expression of MMP9 and COX2 decreased compared with the control group, while the expression of type II collagen increased.
Conclusion
MiR-146a-5p, as a "protective factor", it has the potential to treat osteoarthritis, attenuates the inflammatory response of osteoarthritis and moderates the progression of osteoarthritis through its apparent anti-inflammatory ability.
Joint Application of Multiple Inflammatory Cytokines in Development of Heart Failure
Authors: Yu Mingyan , Zhang Qingquan , Zhu Jiaoyan , Xu Louyuan , Chen Liang , Zheng Koulong 
Published: September 2023

Abstract
Background
Heart failure is a serious heart ailment that affects millions of people globally in terms of their quality of life and general health. In the development and pathophysiology of heart failure, cytokines play a pivotal role. In-depth comprehension of the role cytokines assume in heart failure holds the potential to offer more precise grounds for early diagnosis, therapeutic interventions, and prognostic assessments of this cardiac ailment.
Purpose
This article aimed to explore the correlation between inflammation-related cytokines and heart failure.
Methods
The study recruited a total of 116 participants who were subsequently divided into a heart failure group (n = 59) and a non-heart failure group (n = 57). Laboratory tests were conducted for various inflammatory markers, and the level of each marker was compared between the heart failure group and the healthy control group (n = 57) matched for age and gender to determine the correlation with heart failure. Compared with patients in the non-heart failure group, significantly higher levels of inflammatory response markers (hs-CRP, ESR) and cytokines (IL-6, IL-8, IL-10, IL-17, TNF-α), and decreased levels of albumin, complement C3, and phospholipase A2 were noted in heart failure patients.
Results
Through logistic regression analysis, it has been elucidated that the cytokines IL-6(OR = 1.269,95% CI:1.049–1.472,P = 0.002), IL-8(OR = 1.071,95% CI:1.012–1.134,P = 0.018), and IL-17(OR = 1.180,95% CI:1.010–1.378,P = 0.037) act as autonomous risk factors in the development of heart failure, while Lp-PLA2(OR = 0.986,95% CI:0.972–0.999,P = 0.036) and albumin(OR = 0.476,95% CI:0.267–0.848,P = 0.012) exhibit a protective role against this condition.According to the analysis of ROC curves: the combined use of multiple cytokines(AUC = 0.9277,95% CI:0.8788–0.9767, P < 0.0001,YI = 0.7779) demonstrates higher efficacy in diagnosing heart failure, yet NTpro-BNP(AUC = 0.9914,95% CI:0.9805-1.000, P < 0.0001,YI = 0.9914) remains the clinical preference. In the context of systemic inflammation, the combined diagnostic approach of multiple cytokines with hsCRP(AUC = 0.9358,95% CI:0.8919–0.9797, P < 0.0001,YI = 0.7942) exhibits greater sensitivity and specificity.
Body composition assessment by Artificial Intelligence can be a predictive tool for short-term postoperative complications in Hartmann’s reversals
Authors: Suthakaran Reshi , Cao Ke , Arafat Yasser , Yeung Josephine , Chan Steven , Master Mobin , Faragher Ian G. , Baird Paul N. , Yeung Justin M.C 
Published: September 2023

Abstract
Background
Hartmann’s reversal is a complex elective procedure that requires careful planning and patient optimisation to help reduce postoperative complications. Preoperative evaluation of body composition has been useful in identifying patients at high risk of short-term postoperative outcomes following colorectal cancer surgery. We sought to explore the use of our in-house derived Artificial Intelligence (AI) algorithm to measure body composition within patients undergoing Hartmann’s reversal procedure in the prediction of short-term postoperative complications.
Methods
A retrospective study of all patients who underwent Hartmann's reversal within a single tertiary referral centre (Western) in Melbourne, Australia and who had a preoperative Computerised Tomography (CT) scan performed. Body composition was measured using our previously validated AI algorithm for body segmentation developed by the Department of Surgery, Western Precinct, University of Melbourne.
Results
Between 2010 and 2020, 47 patients (mean age 63.1 ± 12.3 years; male, n = 28 (59.6%)underwent body composition analysis. Twenty-one patients (44.7%) were sarcopenic, and 12 (25.5%) had evidence of sarcopenic obesity. The most common postoperative complication was surgical site infection (SSI) (n = 8, 17%). Sarcopenia (n = 7, 87.5%, p = 0.02) and sarcopenic obesity (n = 5, 62.5%, p = 0.02) were significantly associated with SSIs. The risks of developing an SSI were 8.7 times greater when sarcopenia was present.
Conclusion
Sarcopenia and sarcopenic obesity were related to postoperative complications following Hartmann’s reversal. Body composition measured by a validated AI algorithm may be a beneficial tool for predicting short-term surgical outcomes for these patients.
Use of body weight-adjusted FEV1/FVC as an index to predict the risk of sarcopenia among elderly people in the community
Authors: Wang Cai-xia , Zhu Gui-qi , Meng Qiong , Lyu Xiao-yu , lou Ling-zhi , Liu Jian-zhong , Xu Xue-fan , Jiang Hai-xian , Peng Lu-lu , Fu Li-li , Lyu Jie-wen , Bai Chun , Mo Bao-qing , Tao Hai-qi , Yu Yang 
Published: September 2023

Abstract

Background
The quality and function of skeletal muscle decrease with aging in humans. Meanwhile, sarcopenia leads to increased fat mass and decreased muscle mass in the elderly. Furthermore, sarcopenia results in decreased respiratory muscle mass and strength in the elderly, as well as reduced respiratory function. Sarcopenia is an important cause of death from aspiration pneumonia, chronic obstructive pulmonary disease, lung cancer, and other respiratory diseases in the elderly. Therefore, it is of great significance to develop an inexpensive and simple respiratory function test to identify elderly patients at risk of sarcopenia.
Methods
In this cross-sectional survey, subjects who participated in the physical examination project of the second Community Health Service Center of Pengpu Town, Jing’an District, Shanghai, China were eligible. From April to September 2021, 1257 elderly people underwent a health screening. Demographic data were collected via self-completed forms. Physical data such as height, weight, and disease history were collected via consultation and physical examination by clinicians. Medical examination data included the results of bioelectrical impedance analysis, respiratory function tests, chest X-ray, and electrocardiogram. Statistical analysis was performed using Student’s t-test, the chi-squared test, Spearman’s correlation analysis, and receiver operating characteristic (ROC) curve analysis.
Results
In total, 663 subjects were enrolled in this study, including 285 women (70.154 ± 3.931 years old) and 207 men (70.437 ± 3.891 years old) without sarcopenia and 101 women (71.237 ± 4.858 years old) and 70 men (72.12 ± 5.232 years old) with sarcopenia. Age and body mass index significantly differed between subjects with and without sarcopenia. In addition, combined forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, maximum inspiratory pressure (MIP), and peak inspiratory flow (PIF) adjusted for body weight significantly differed between subjects with and without sarcopenia for both men and women. The sensitivity and specificity of body weight-adjusted FEV1/FVC for predicting the risk of sarcopenia in elderly subjects were high. For body weight-adjusted FEV1/FVC in men, the area under the ROC curve, sensitivity, specificity, and cutoff were 0.816, 0.829, 0.676, and 0.012, respectively, whereas the values were 0.830, 0.782, 0.785, and 0.015, respectively, in women.
Conclusions
The results in our study clearly indicate that body weight-adjusted FEV1/FVC was positivity correlated with the risk of sarcopenia in elderly men and women.