bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation spectra of the BRCA1/2 genes in human breast and ovarian cancer and germline
Authors: Koi Yumiko , Watanabe Arisa , Kawasaki Akari , Ideo Satomi , Matsutani Nao , Miyashita Kaname , Shioi Seijiro , Tokunaga Eriko , Shimokawa Mototsugu , Nakatsu Yoshimichi , Kuraoka Isao , Oda Shinya 
Published: June 2024

AbstractAnnotating genomic sequence alterations is sometimes a difficult decision, particularly in missense variants with uncertain pathogenic significance and also in those presumed as germline pathogenic variants. We here suggest that mutation spectrum may also be useful for judging them. From the public databases, 982 BRCA1/1861 BRCA2 germline missense variants and 294 BRCA1/420 BRCA2 somatic missense variants were obtained. We then compared their mutation spectra, i.e., the frequencies of two transition‐ and four transversion‐type mutations, in each category. Intriguingly, in BRCA1 variants, A:T to C:G transversion, which was relatively frequent in the germline, was extremely rare in somatic, particularly breast cancer, cells (p = .03). Conversely, A:T to T:A transversion was most infrequent in the germline, but not rare in somatic cells. Thus, BRCA1 variants with A:T to T:A transversion may be suspected as somatic, and those with A:T to C:G as being in the germline. These tendencies of mutation spectrum may also suggest the biological and chemical origins of the base alterations. On the other hand, unfortunately, variants of uncertain significance (VUS) were not distinguishable by mutation spectrum. Our findings warrant further and more detailed studies.
Characterizing Freshwater Ecotoxicity of More Than 9000 Chemicals by Combining Different Levels of Available Measured Test Data with In Silico Predictions
Authors: Douziech Mélanie , Oginah Susan Anyango , Golsteijn Laura , Hauschild Michael Zwicky , Jolliet Olivier , Owsianiak Mikołaj , Posthuma Leo , Fantke Peter 
Published: June 2024

Abstract
Ecotoxicological impacts of chemicals released into the environment are characterized by combining fate, exposure, and effects. For characterizing effects, species sensitivity distributions (SSDs) estimate toxic pressures of chemicals as the potentially affected fraction of species. Life cycle assessment (LCA) uses SSDs to identify products with lowest ecotoxicological impacts. To reflect ambient concentrations, the Global Life Cycle Impact Assessment Method (GLAM) ecotoxicity task force recently recommended deriving SSDs for LCA based on chronic EC10s (10% effect concentration, for a life-history trait) and using the 20th percentile of an EC10-based SSD as a working point. However, because we lacked measured effect concentrations, impacts of only few chemicals were assessed, underlining data limitations for decision support. The aims of this paper were therefore to derive and validate freshwater SSDs by combining measured effect concentrations with in silico methods. Freshwater effect factors (EFs) and uncertainty estimates for use in GLAM-consistent life cycle impact assessment were then derived by combining three elements: (1) using intraspecies extrapolating effect data to estimate EC10s, (2) using interspecies quantitative structure–activity relationships, or (3) assuming a constant slope of 0.7 to derive SSDs. Species sensitivity distributions, associated EFs, and EF confidence intervals for 9862 chemicals, including data-poor ones, were estimated based on these elements. Intraspecies extrapolations and the fixed slope approach were most often applied. The resulting EFs were consistent with EFs derived from SSD-EC50 models, implying a similar chemical ecotoxicity rank order and method robustness. Our approach is an important step toward considering the potential ecotoxic impacts of chemicals currently neglected in assessment frameworks due to limited test data. Environ Toxicol Chem 2024;43:1914–1927. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Numerical modeling of optimum spacing of TBM disk cutters, using a finite element method simulation
Authors: Tilehnoei Mohammadreza Faraji , Shahriar Kourosh , Madani Hassan 
Published: June 2024

AbstractDue to the growing demand for underground communication methods, water transfer, and utility tunnels, employing mechanized tunneling methods is unavoidable. Diverse disk cutters are built and operated. A proper cutterhead design will have a direct impact on the net advance rate and therefore significantly contribute to the project success. The research effort presented in this contribution is dealing with the spacing effect on the forces on disk cutters, and their specific energy (SE) has been investigated. It uses finite element numerical modeling with ABAQUS software to simulate the rock‐cutting process to find an optimal spacing in barre granite. The results show that theratio of the disk spacing to the penetration rate, the normal and rotational forces on the disk cutters, and the SE values increase to the optimal level and then decrease. The optimal spacing for the examined rock type is discussed in further detail, and a recommendation for the optimum cutterhead layout is presented.
Local restrictions, population movement, and spillovers during the pandemic: Evidence from Japan's restaurant restriction
Authors: Xu Zihan , Shimokawa Satoru 
Published: June 2024

AbstractWe investigate how a local restaurant restriction aimed at containing the COVID‐19 pandemic influenced population movement and COVID‐19 prevalence within and outside the restricted districts. Using data on restaurant location and hourly population at the 500‐m‐mesh level and on COVID‐19 prevalence at both prefecture and municipality level in Japan, we employ a triple‐difference approach and a difference‐in‐differences approach with fixed effects. While the policy decreased population movement to restaurant areas in the restricted districts, it caused spillovers of increasing population movement to restaurant areas in the neighboring nonrestricted districts. Consequently, COVID‐19 prevalence worsened in the neighboring nonrestricted districts but improved in the restricted districts. Our findings suggest that imposing such local restrictions in the context of the pandemic may contain the pandemic only in the restricted districts while sacrificing economic activities within these districts and public health in neighboring nonrestricted districts.
Detection of oral cancer and oral potentially malignant disorders using artificial intelligence‐based image analysis
Authors: Kouketsu Atsumu , Doi Chiaki , Tanaka Hiroaki , Araki Takashi , Nakayama Rina , Toyooka Tsuguyoshi , Hiyama Satoshi , Iikubo Masahiro , Osaka Ken , Sasaki Keiichi , Nagai Hirokazu , Sugiura Tsuyoshi , Yamauchi Kensuke , Kuroda Kanako , Yanagisawa Yuta , Miyashita Hitoshi , Kajita Tomonari , Iwama Ryosuke , Kurobane Tsuyoshi , Takahashi Tetsu 
Published: June 2024

AbstractBackgroundWe aimed to construct an artificial intelligence‐based model for detecting oral cancer and dysplastic leukoplakia using oral cavity images captured with a single‐lens reflex camera.Subjects and methodsWe used 1043 images of lesions from 424 patients with oral squamous cell carcinoma (OSCC), leukoplakia, and other oral mucosal diseases. An object detection model was constructed using a Single Shot Multibox Detector to detect oral diseases and their locations using images. The model was trained using 523 images of oral cancer, and its performance was evaluated using images of oral cancer (n = 66), leukoplakia (n = 49), and other oral diseases (n = 405).ResultsFor the detection of only OSCC versus OSCC and leukoplakia, the model demonstrated a sensitivity of 93.9% versus 83.7%, a negative predictive value of 98.8% versus 94.5%, and a specificity of 81.2% versus 81.2%.ConclusionsOur proposed model is a potential diagnostic tool for oral diseases.
The relationship between borderline personality disorder and self‐injurious/suicidal behaviors in adolescents and young adults: A protocol for systematic review and meta‐analysis
Authors: Thakur Bhaskar , Pathak Mona , Strenth Chance , Wilmoth Kristin , Arnold Elizabeth Mayfield 
Published: June 2024

AbstractBackground & AimsBorderline personality disorder (BPD) is a common psychiatric disorder associated with a high risk of suicide attempts, death by suicide, and non‐suicidal self‐injury (NSSI). A systematic and comprehensive understanding of the link between BPD and suicide and self‐injury in adolescents and young adults is crucial for effective public health prevention strategies. This protocol outlines our approach to summarize the evidence on the association between BPD diagnosis and self‐injurious/suicidal behaviors including death by suicide, nonfatal suicide attempts, NSSI, and self‐harm behavior through a systematic review and meta‐analysis.MethodsThe protocol is registered (PROSPERO: CRD42022363329) and developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses Protocols (PRISMA‐P)‐2015 statement. We will conduct a comprehensive literature search using electronic databases including MEDLINE, EMBASE, SCOPUS, Web of Science, CINHAL, and PsycINFO. The review will include studies that meet the specific inclusion criteria and will be searched using multiple databases A meta‐analysis will be conducted using a fixed‐effects or random‐effects approach based on the level of heterogeneity. Subgroup analysis and meta‐regression will be performed if necessary.ConclusionThis study is unique, as it is the first of its kind to systematically review and analyze the existing literature on this topic. The results of this study will provide important evidence on the magnitude of this relationship overall and in different subgroups, which can be used to inform the development of effective prevention and treatment strategies.
The Nrf2/HO‐1 pathway participates in the antiapoptotic and anti‐inflammatory effects of platelet‐rich plasma in the treatment of osteoarthritis
Authors: Du Guangyu , Sun Xuegang , He Shengwei , Mi Lidong 
Published: June 2024

AbstractIntroductionWe aimed to explore the molecular mechanisms through which platelet‐rich plasma (PRP) attenuates osteoarthritis (OA)‐induced pain, apoptosis, and inflammation.MethodsAn in vivo model of OA was established by injuring rats using the anterior cruciate ligament transection method, whereas an in vitro model was generated by exposing chondrocytes to interleukin (IL)‐1β. Both models were then treated with PRP.ResultsIn both the in vivo and in vitro models, OA led to the suppression of the nuclear factor erythroid 2‐related factor 2 (Nrf2)/heme oxygenase‐1 (HO‐1) pathway, whereas treatment with PRP reactivated this molecular axis. Inhibition of the Nrf2/HO‐1 pathway using the Nrf2 inhibitor brusatol or through Nrf2 gene silencing counteracted the effects of PRP in reducing the tenderness and thermal pain thresholds of OA rats. Additionally, PRP reduced the mRNA expression of IL‐1β, IL‐6, tumor necrosis factor‐alpha (TNF‐α), and matrix metallopeptidase 13 (MMP‐13) and the protein expression of B‐cell lymphoma 2 (Bcl‐2), Bcl‐2 associated X‐protein (Bax), and caspase‐3. Furthermore, inflammation and apoptosis were induced by brusatol treatment or Nrf2 silencing. Additionally, in the in vitro model, PRP treatment increased the proliferation of chondrocytes and attenuated their inflammatory response and apoptosis, effects that were abrogated by Nrf2 depletion.ConclusionsThe Nrf2/HO‐1 pathway participates in the PRP‐mediated attenuation of OA development by suppressing inflammation and apoptosis.
Prevalence of depression and anxiety in women with pelvic floor dysfunctions: A systematic review and meta‐analysis
Authors: Peinado Molina Rocio Adriana , Martínez Vázquez Sergio , Martínez Galiano Juan Miguel , Rivera Izquierdo Mario , Khan Khalid Saeed , Cano‐Ibáñez Naomi 
Published: June 2024

AbstractBackgroundFemale pelvic floor dysfunction (PFD) is a common condition affecting the emotional well‐being of women.ObjectiveTo estimate the prevalence of depressive and anxiety symptoms in women with PFD.Search Strategy, Selection Criteria, Data Collection and AnalysisFollowing prospective registration (PROSPERO CRD42022362095) we conducted a search of three electronic databases (PubMed, Web of Science and Scopus) from inception to April 2023 without language restriction to capture studies reporting the prevalence of depression/anxiety among women with PFD (chronic pelvic pain [CPP], urinary incontinence [UI], pelvic organ prolapse [POP], and/or fecal incontinence [FI]). Only studies with validated tools were included. Data extraction and study quality assessment were performed by two independent reviewers. Stratifying by type of PFD, rates of depression and anxiety were pooled using random effects model computing 95% confidence interval (CI) and assessing heterogeneity using the I2 statistic. Funnel plots were used to detect potential reporting biases and small‐study effects.Main ResultsThe search yielded 767 articles, from which 54 studies containing 632 605 women were included. All the studies were high quality. The prevalence of depression was: CPP 26.8% (95% CI: 19.2–34.4, I2 = 98.7%; 12 studies, 4798 participants with 491 cases; Egger's P value = 0.009); UI 26.3% (95% CI: 19.4–33.2, I2 = 99.9%; 26 studies, a total of 346 114 participants with 25 050 cases; Egger's P value = 0.944); POP 34.9% (95% CI: 24.3–45.6, I2 = 68%; three studies, 297 participants with 104 cases; Egger's P value = 0.973); and FI 25.3% (95% CI: 0.68–49.9, I2 = 99.7%; six studies, 14 663 participants with 1773 cases; Egger's P value = 0.780). The prevalence of anxiety was: CPP 29.5% (95% CI: 16.3–42.7, I2 = 97.7%; nine studies, 2483 participants with 349 cases; Egger's P value = 0.001); UI 46.91% (95% CI: 39.1–54.6, I2 = 99.6%; 11 studies, 198 491 participants with 40 058 cases; Egger's P value = 0.337); and POP 28% (95% CI: 13.6–42.4, I2 = 89%; three studies with 355 participants with 90 cases; Egger's P value = 0.306).ConclusionThe prevalence of mental health illness was variable in the different types of PFDs. This meta‐analysis helps quantify the burden of depression and anxiety in PFD and will help inform the policies regarding screening of emotional well‐being by healthcare professionals engaged in care of women with PFD.
Oral subchronic toxicity study and genetic toxicity evaluation of mitoquinone mesylate
Authors: Mitchell E. Siobhan , Lemke Shawna , Woodhead Brendon , Coleman David 
Published: June 2024

AbstractMitochondrial dysfunction and excessive reactive oxygen species production contributes to the pathophysiology of aging. Coenzyme Q10 is thought to protect mitochondria from oxidative damage; thus, mitoquinone was developed as mitochondria‐targeted analogue with similar antioxidant activity. Mitoquinone is the oxidized form of mitoquinol. Mitoquinone/mitoquinol mesylate has been proposed as a food ingredient. As part of the safety analysis, we performed genotoxicity assays and a 39‐week toxicity study to determine overall toxicity potential. Mitoquinone mesylate showed no evidence of genotoxic potential in two in vitro assays, bacterial reverse mutation and human lymphocyte chromosome aberration, nor in the in vivo micronucleus test in rats. In the 39‐week study in dogs, there were no findings observed, which were considered to represent adverse systemic toxicity; therefore, the high dose level (40 mg/kg/day) was considered the NOAEL. The principal findings in this study were fecal disturbances and vomiting. These findings were considered to be due to a local, possibly irritant effect of the test substance on the gastrointestinal tract and were not considered adverse as there were no impacts on clinical or histopathology. This highest dose exceeds the expected daily human intake more than 100‐fold. Data from well‐designed clinical trials actively collecting safety endpoints corroborate that 20 mg/day can be safely consumed and is not likely to result in significant gastrointestinal complaints. These results support the conclusion that the use of mitoquinone/mitoquinol mesylate as a food ingredient is safe.
BMP1 Promotes Keloid by Inducing Fibroblast Inflammation and Fibrogenesis
Authors: Wang Yi , Chen Yahui , Wu Jinfeng , Shi Xiangguang 
Published: June 2024

ABSTRACTKeloid is a typical fibrotic and inflammatory skin disease with unclear mechanisms and few therapeutic targets. In this study, we found that BMP1 was significantly increased in a collagen high‐expressing subtype of fibroblast by reanalyzing a public single‐cell RNA‐sequence data set of keloid. The number of BMP1‐positive fibroblast cells was increased in keloid fibrotic loci. Increased levels of BMP1 were further validated in the skin tissues and fibroblasts from keloid patients. Additionally, a positive correlation between BMP1 and the Keloid Area and Severity Index was found in keloid patients. In vitro analysis revealed collagen production, the phosphorylation levels of p65, and the IL‐1β secretion decreased in BMP1 interfered keloid fibroblasts. Besides, the knockdown of BMP1 inhibited the growth and migration of keloid fibroblast cells. Mechanistically, BMP1 inhibition downregulated the noncanonical TGF‐β pathways, including p‐p38 and p‐ERK1/2 signaling. Furthermore, we found the delivery of BMP1 siRNAs could significantly alleviate keloid in human keloid‐bearing nude mice. Collectively, our results indicated that BMP1 exhibited various pathogenic effects on keloids as promoting cell proliferation, migration, inflammation, and ECM deposition of fibroblast cells by regulating the noncanonical TGF‐β/p38 MAPK, and TGF‐β/ERK pathways. BMP1‐lowing strategies may appear as a potential new therapeutic target for keloid.
Association between three‐dimensional gait kinematics and joint‐line inclination in osteoarthritic knees compared with normal knees: An epidemiological study
Authors: Chi Fangzhou , Mochizuki Tomoharu , Koga Hiroshi , Omori Go , Nishino Katsutoshi , Takagi Shigeru , Koga Yoshio , Kawashima Hiroyuki 
Published: June 2024

AbstractPurposeNo report has proven how tibial and femoral joint‐line inclinations affect thigh and shank motion, respectively, according to Kellgren–Lawrence grade in motion analysis with a sufficient sample size. Therefore, this study aimed to evaluate the motion of the thigh and shank individually from the ground and the relative motion between bones in a large‐sample motion analysis to determine the differences between normal and osteoarthritic knees and examine the effects of tibial and femoral joint‐line inclination on motion according to osteoarthritis (OA) grade.MethodsOf 459 participants with healthy knees and varus knee OA undergoing three‐dimensional gait analysis, 383 (218 females and 165 males) with an average age of 68 ± 13 years were selected. Gait analysis was performed using a motion–capture system. The six degrees of freedom motion parameters of the knee in the Grood and world coordinate systems and the joint‐line inclination in the standing radiographs were measured.ResultsOsteoarthritic knees demonstrated a relative motion different from that of normal knees, with responsibility for the thigh in the sagittal and rotational planes and the thigh and shank in the coronal plane. The involvement of joint‐line inclination in motion was mainly on the tibial side, and the effect was minimal in normal knees.ConclusionsThe details of the relative motion of both the thigh and shank can be clarified by analysing individual motions to determine the responsible part. The tibial joint‐line affected knee motion: however, the effect was minimal in normal knees. This finding implies that if physical ability can be improved, the negative effects of deformity in osteoarthritic knees may be compensated for.Level of EvidenceLevel Ⅱ.
Parallel CNN‐Deep Learning Clinical‐Imaging Signature for Assessing Pathologic Grade and Prognosis of Soft Tissue Sarcoma Patients
Authors: Guo Jia , Li Yi‐ming , Guo Hongwei , Hao Da‐peng , Xu Jing‐xu , Huang Chen‐cui , Han Hua‐wei , Hou Feng , Yang Shi‐feng , Cui Jian‐ling , Wang He‐xiang 
Published: June 2024

BackgroundTraditional biopsies pose risks and may not accurately reflect soft tissue sarcoma (STS) heterogeneity. MRI provides a noninvasive, comprehensive alternative.PurposeTo assess the diagnostic accuracy of histological grading and prognosis in STS patients when integrating clinical‐imaging parameters with deep learning (DL) features from preoperative MR images.Study TypeRetrospective/prospective.Population354 pathologically confirmed STS patients (226 low‐grade, 128 high‐grade) from three hospitals and the Cancer Imaging Archive (TCIA), divided into training (n = 185), external test (n = 125), and TCIA cohorts (n = 44). 12 patients (6 low‐grade, 6 high‐grade) were enrolled into prospective validation cohort.Field Strength/Sequence1.5 T and 3.0 T/Unenhanced T1‐weighted and fat‐suppressed‐T2‐weighted.AssessmentDL features were extracted from MR images using a parallel ResNet‐18 model to construct DL signature. Clinical‐imaging characteristics included age, gender, tumor‐node‐metastasis stage and MRI semantic features (depth, number, heterogeneity at T1WI/FS‐T2WI, necrosis, and peritumoral edema). Logistic regression analysis identified significant risk factors for the clinical model. A DL clinical‐imaging signature (DLCS) was constructed by incorporating DL signature with risk factors, evaluated for risk stratification, and assessed for progression‐free survival (PFS) in retrospective cohorts, with an average follow‐up of 23 ± 22 months.Statistical TestsLogistic regression, Cox regression, Kaplan–Meier curves, log‐rank test, area under the receiver operating characteristic curve (AUC)，and decision curve analysis. A P‐value <0.05 was considered significant.ResultsThe AUC values for DLCS in the external test, TCIA, and prospective test cohorts (0.834, 0.838, 0.819) were superior to clinical model (0.662, 0.685, 0.694). Decision curve analysis showed that the DLCS model provided greater clinical net benefit over the DL and clinical models. Also, the DLCS model was able to risk‐stratify patients and assess PFS.Data ConclusionThe DLCS exhibited strong capabilities in histological grading and prognosis assessment for STS patients, and may have potential to aid in the formulation of personalized treatment plans.Level of Evidence4.Technical EfficacyStage 2.