bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case report: Heterozygous mutation in HTRA1 causing typical cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy
Authors: Li Yu-Ming , Jia Wei , Xin Tao , Fang Yu-Qing 
Published: September 2023

Background: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an autosomal recessive disorder characterized by baldness, recurrent ischemic stroke, lumbago, headache, and dementia which is closely related to homozygous mutations of the high-temperature requirement serine peptidase A1 (HTRA1) gene. Heterozygous mutations of HTRA1 are usually considered to be non-pathogenic. Although it has been revealed that only a few patients with heterozygous mutations could present some manifestations, their clinical symptoms were atypical, milder, and always with a lower frequency of extra-neurological features. Here, a rare patient with heterozygous mutation of HTRA1 who had all typical features of CARASIL as well as severe clinical symptoms and rapid progression was initially reported in our study.Case presentation: A 43-year-old female patient presented with a gradual onset of headache and cognitive decline. As time progressed, her headache intensified and symptoms of dementia began to manifest gradually. During her early years, she had thinning hair and subsequently experienced two occurrences of ischemic strokes in her thirties. Furthermore, she also had a history of lumbago and urinary retention before visiting our hospital. The patient’s magnetic resonance imaging revealed the presence of widespread white matter lesions, infarctions, and microbleeds, in addition to lumbar disc herniation and degenerative lesions. The observed clinical characteristics had a strong correlation with CARASIL, and the patient was diagnosed with a heterozygous missense mutation of 905G&gt;A (Arg302Gln) in the HTRA1 gene. The patient has been under continuous follow-up for a duration exceeding 3 years subsequent to her release from the hospital. She underwent cystostomy, and symptoms of bulbar paralysis developed in a progressive way. Currently, there has been a notable decrease in motor function and activities of daily living, resulting in the individual being confined to bed for a duration exceeding 1 year.Conclusion: This case suggests that patients carrying a heterozygous mutation in G905A may also have typical clinical features of CARASIL, which allows us to have a more comprehensive understanding of CARASIL.
Multi-gene panel testing and association analysis in Cypriot breast cancer cases and controls
Authors: Zanti Maria , Loizidou Maria A. , O’Mahony Denise G. , Dorling Leila , Dennis Joe , Devilee Peter , Easton Douglas F. , Panayiotidis Mihalis I. , Hadjisavvas Andreas , Michailidou Kyriaki 
Published: September 2023

Introduction: It is estimated that around 5% of breast cancer cases carry pathogenic variants in established breast cancer susceptibility genes. However, the underlying prevalence and gene-specific population risk estimates in Cyprus are currently unknown.Methods: We performed sequencing on a population-based case-control study of 990 breast cancer cases and 1094 controls from Cyprus using the BRIDGES sequencing panel. Analyses were conducted separately for protein-truncating and rare missense variants.Results: Protein-truncating variants in established breast cancer susceptibility genes were detected in 3.54% of cases and 0.37% of controls. Protein-truncating variants in BRCA2 and ATM were associated with a high risk of breast cancer, whereas PTVs in BRCA1 and PALB2 were associated with a high risk of estrogen receptor (ER)-negative disease. Among participants with a family history of breast cancer, PTVs in ATM, BRCA2, BRCA1, PALB2 and RAD50 were associated with an increased risk of breast cancer. Furthermore, an additional 19.70% of cases and 17.18% of controls had at least one rare missense variant in established breast cancer susceptibility genes. For BRCA1 and PALB2, rare missense variants were associated with an increased risk of overall and triple-negative breast cancer, respectively. Rare missense variants in BRCA1, ATM, CHEK2 and PALB2 domains, were associated with increased risk of disease subtypes.Conclusion: This study provides population-based prevalence and gene-specific risk estimates for protein-truncating and rare missense variants. These results may have important clinical implications for women who undergo genetic testing and be pivotal for a substantial proportion of breast cancer patients in Cyprus.
KD_ConvNeXt: knowledge distillation-based image classification of lung tumor surgical specimen sections
Authors: Zheng Zhaoliang , Yao Henian , Lin Chengchuang , Huang Kaixin , Chen Luoxuan , Shao Ziling , Zhou Haiyu , Zhao Gansen 
Published: September 2023

Introduction: Lung cancer is currently among the most prevalent and lethal cancers in the world in terms of incidence and fatality rates. In clinical practice, identifying the specific subtypes of lung cancer is essential in diagnosing and treating lung lesions.Methods: This paper aims to collect histopathological section images of lung tumor surgical specimens to construct a clinical dataset for researching and addressing the classification problem of specific subtypes of lung tumors. Our method proposes a teacher-student network architecture based on a knowledge distillation mechanism for the specific subtype classification of lung tumor histopathological section images to assist clinical applications, namely KD_ConvNeXt. The proposed approach enables the student network (ConvNeXt) to extract knowledge from the intermediate feature layers of the teacher network (Swin Transformer), improving the feature extraction and fitting capabilities of ConvNeXt. Meanwhile, Swin Transformer provides soft labels containing information about the distribution of images in various categories, making the model focused more on the information carried by types with smaller sample sizes while training.Results: This work has designed many experiments on a clinical lung tumor image dataset, and the KD_ConvNeXt achieved a superior classification accuracy of 85.64% and an F1-score of 0.7717 compared with other advanced image classification methods
Identification of a novel locus C2 controlling canary yellow flesh color in watermelons
Authors: Park Girim , Shahwar Durre , Jang Gaeun , Shin Jagyeong , Kwon Gibeom , Kim Younjae , Hong Chang Oh , Jin Bingkui , Kim Hoytaek , Lee Oakjin , Park Younghoon 
Published: September 2023

The flesh color of watermelon is an important trait that is determined by carotenoid composition and affects consumers’ fruit desirability. Although a complete dominant control by C locus (Cllcyb) for canary yellow flesh (CY) over red flesh has been reported, red and CY colors frequently appear as a mixed pattern in the same flesh (incomplete canary yellow, ICY) in F1 and inbred lines carrying dominant C alleles. Therefore, we examined the genetic control of the mixed color pattern in ICY using whole-genome resequencing of three ICY (ICY group) and three CY inbred lines (CY group), as well as genetic linkage mapping of an F2 population. The segregation pattern in 135 F2 plants indicated that CY is controlled by a single locus (named C2) dominant over ICY. The whole-genome resequencing of ICY and CY inbred lines revealed an ICY/CY-specific region of approximately 27.60–27.88 Mb on Chr. 2 that was polymorphic between the ICY and CY groups. Our genetic map, using nine cleaved amplified polymorphic sequence markers developed based on the single-nucleotide polymorphisms from the ICY/CY-specific region, confirmed that C2 is located on Chr. 2 and cosegregated with the marker (M7) derived from a non-synonymous single-nucleotide polymorphism of the pentatricopeptide repeat (PPR) gene (ClPPR, Cla97C02G039880). Additionally, 27 watermelon inbred lines of ICY, CY, and red flesh were evaluated using previously reported Cllcyb (C locus)-based markers and our C2 locus-linked ClPPR-based marker (M7). As a result, dominant alleles at the C2 locus were required to produce CY, in addition to dominant alleles at the C locus, while a recessive homozygous genotype at the C locus gave the red flesh irrespective of the genotype at the C2 locus. Using a ClPPR-based cleaved amplified polymorphic sequence developed in this study and Cllcyb-based markers, watermelon cultivars with CY, ICY, and red flesh could be successfully discerned, implying that the combined use of these markers will be efficient for marker-assisted selection of flesh color in watermelon breeding.
ITRPCA: a new model for computational drug repositioning based on improved tensor robust principal component analysis
Authors: Yang Mengyun , Yang Bin , Duan Guihua , Wang Jianxin 
Published: September 2023

Background: Drug repositioning is considered a promising drug development strategy with the goal of discovering new uses for existing drugs. Compared with the experimental screening for drug discovery, computational drug repositioning offers lower cost and higher efficiency and, hence, has become a hot issue in bioinformatics. However, there are sparse samples, multi-source information, and even some noises, which makes it difficult to accurately identify potential drug-associated indications.Methods: In this article, we propose a new scheme with improved tensor robust principal component analysis (ITRPCA) in multi-source data to predict promising drug–disease associations. First, we use a weighted k-nearest neighbor (WKNN) approach to increase the overall density of the drug–disease association matrix that will assist in prediction. Second, a drug tensor with five frontal slices and a disease tensor with two frontal slices are constructed using multi-similarity matrices and an updated association matrix. The two target tensors naturally integrate multiple sources of data from the drug-side aspect and the disease-side aspect, respectively. Third, ITRPCA is employed to isolate the low-rank tensor and noise information in the tensor. In this step, an additional range constraint is incorporated to ensure that all the predicted entry values of a low-rank tensor are within the specific interval. Finally, we focus on identifying promising drug indications by analyzing drug–disease association pairs derived from the low-rank drug and low-rank disease tensors.Results: We evaluate the effectiveness of the ITRPCA method by comparing it with five prominent existing drug repositioning methods. This evaluation is carried out using 10-fold cross-validation and independent testing experiments. Our numerical results show that ITRPCA not only yields higher prediction accuracy but also exhibits remarkable computational efficiency. Furthermore, case studies demonstrate the practical effectiveness of our method.
GPX8 regulates pan-apoptosis in gliomas to promote microglial migration and mediate immunotherapy responses
Authors: Chen Zigui , Zheng Dandan , Lin Ziren , Zhang Chunyuan , Wei Cheng , Deng Xiandong , Yan Peng , Zheng Chuanhua , Lan Chuanliu , Qin Chengjian , Wei Xuanlei , Qin Deling , Wu Yongfang , Peng Jun , Miao Changfeng , Lu Liuxue , Xia Ying , Luo Qisheng 
Published: September 2023

IntroductionGliomas have emerged as the predominant brain tumor type in recent decades, yet the exploration of non-apoptotic cell death regulated by the pan-optosome complex, known as pan-apoptosis, remains largely unexplored in this context. This study aims to illuminate the molecular properties of pan-apoptosis-related genes in glioma patients, classifying them and developing a signature using machine learning techniques.MethodsThe prognostic significance, mutation features, immunological characteristics, and pharmaceutical prediction performance of this signature were comprehensively investigated. Furthermore, GPX8, a gene of interest, was extensively examined for its prognostic value, immunological characteristics, medication prediction performance, and immunotherapy prediction potential. ResultsExperimental techniques such as CCK-8, Transwell, and EdU investigations revealed that GPX8 acts as a tumor accelerator in gliomas. At the single-cell RNA sequencing level, GPX8 appeared to facilitate cell contact between tumor cells and macrophages, potentially enhancing microglial migration. ConclusionsThe incorporation of pan-apoptosis-related features shows promising potential for clinical applications in predicting tumor progression and advancing immunotherapeutic strategies. However, further in vitro and in vivo investigations are necessary to validate the tumorigenic and immunogenic processes associated with GPX8 in gliomas.
Differential molecular programs of cutaneous anaplastic large cell lymphoma and CD30-positive transformed mycosis fungoides
Authors: Lai Pan , Liu Fengjie , Liu Xiangjun , Sun Jingru , Wang Yang 
Published: September 2023

BackgroundDiscriminating between cutaneous anaplastic large cell lymphoma (cALCL) and CD30-positive transformed mycosis fungoides (CD30+ TMF) is challenging, particularly when they arise in the context of pre-existing mycosis fungoides. The development of molecular diagnostic tools was hampered by the rarity of both diseases and the limited understanding of their pathogenesis.MethodsIn this study, we established a cohort comprising 25 cALCL cases and 25 CD30+ TMF cases, with transcriptomic data obtained from 31 samples. We compared the clinicopathological information and investigated the gene expression profiling between these two entities. Furthermore, we developed an immunohistochemistry (IHC) algorithm to differentiate these two entities clinically.ResultsOur investigation revealed distinct clinicopathological features and unique gene expression programs associated with cALCL and CD30+ TMF. cALCL and CD30+ TMF displayed marked differences in gene expression patterns. Notably, CD30+ TMF demonstrated enrichment of T cell receptor signaling pathways and an exhausted T cell phenotype, accompanied by infiltration of B cells, dendritic cells, and neurons. In contrast, cALCL cells expressed high levels of HLA class II genes, polarized towards a Th17 phenotype, and exhibited neutrophil infiltration. An IHC algorithm with BATF3 and TCF7 staining emerged as potential diagnostic markers for identifying these two entities.ConclusionsOur findings provide valuable insights into the differential molecular signatures associated with cALCL and CD30+ TMF, which contribute to their distinct clinicopathological behaviors. An appropriate IHC algorithm could be used as a potential diagnostic tool.
Large-scale seabird community structure along oceanographic gradients in the Scotia Sea and northern Antarctic Peninsula
Authors: Ollus Victoria Marja Sofia , Biuw Martin , Lowther Andrew , Fauchald Per , Deehr Johannessen John Elling , Martín López Lucía Martina , Gkikopoulou Kalliopi C. , Oosthuizen W. Chris , Lindstrøm Ulf 
Published: September 2023

IntroductionThe Scotia Sea and Antarctic Peninsula are warming rapidly and changes in species distribution are expected. In predicting habitat shifts and considering appropriate management strategies for marine predators, a community-level understanding of how these predators are distributed is desirable. Acquiring such data, particularly in remote areas, is often problematic given the cost associated with the operation of research vessels. Here we use cruise vessels as sampling platforms to explore seabird distribution relative to habitat characteristics.MethodsData on seabird at-sea distribution were collected using strip-transect counts throughout the Antarctic Peninsula and Scotia Sea in the austral summer of 2019-2020. Constrained correspondence analysis (CCA) and generalized additive models (GAM) were used to relate seabird community composition, density, and species richness to environmental covariates.ResultsSpecies assemblages differed between oceanographic areas, with sea surface temperature and distance to coast being the most important predictors of seabird distribution. Our results further revealed a geographic separation of distinct communities rather than hotspot regions in the study area in summer.DiscussionThese findings highlight the importance of large-scale environmental characteristics in shaping seabird community structure, presumably through underlying prey distribution and interspecific interactions. The present study contributes to the knowledge of seabird distribution and habitat use as well as the baseline for assessing the response of Antarctic seabird communities to climate warming. We argue that cruise vessels, when combined with structured research surveys, can provide a cost-effective additional tool for the monitoring of community and ecosystem level changes.
Hydrogel assistant synthesis of new Ti-MOF cross-linked oxidized pectin and chitosan with anti-breast cancer properties
Authors: Alkhathami Ali G. , Khaled Younis Albahadly Waleed , Jawad Mohammed Abed , Ramadan Montather F. , Alsaraf Khulood Majid , Riyad Muedii Zainab Al-Hawraa , Alsaikhan Fahad , Suliman Muath 
Published: September 2023

Breast cancer is one of the most common diseases of the modern age. Although many methods for its treatment have been reported so far, the report and synthesis of new compounds based on new technologies, especially nanotechnology, is important. One of the laboratory methods for evaluating the anticancer properties of compounds is the in vitro MTT method (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide). In this study, the in vitro anti-breast cancer activity of the newly synthesized (Titanium Metal-Organic Framework) Ti-MOF cross-linked oxidized pectin and chitosan hydrogel, which uses biopolymers in its synthesis and structure, was investigated. The anticancer activity results showed that the synthetic nanopolymer had cell proliferation and viability of 27% more than the control and (the half maximal inhibitory concentration) IC50 of 111 μg/mL against breast cancer cells. Before the anticancer evaluation, the structure of the synthesized Ti-MOF cross-linked oxidized pectin, and chitosan hydrogel was confirmed by (X-Ray Diffraction) XRD pattern (Fourier Transform Infrared) FT-IR spectrum (Energy-dispersive X-ray) EDAX spectroscopy, N2 adsorption/desorption isotherm and (Scanning Electron Microscope) Scanning Electron Microscope images. The results of identification and characterization showed that the synthetic nanopolymer was in the range of nanoparticles. The peaks of the expected functional groups and reactant elements were observed in the FT-IR spectrum and energy-dispersive X-ray spectroscopy of the final product. High physicochemical capabilities such as the uniform morphology, crystallization of particles, and high specific surface area from synthesized Ti-MOF cross-linked oxidized pectin, and chitosan hydrogel were observed. The unique properties of the synthesized Ti-MOF cross-linked oxidized pectin and chitosan hydrogel can be attributed to the appropriate method of its synthesis that was carried out in this study.
Increasing incidence and prevalence of metabolic syndrome in people living with HIV during the COVID-19 pandemic
Authors: Papaioannu Borjesson Rebecka , Galli Laura , Muccini Camilla , Poli Andrea , Clemente Tommaso , Bottanelli Martina , Gianotti Nicola , Nozza Silvia , Castagna Antonella , Spagnuolo Vincenzo 
Published: September 2023

IntroductionThe aim of this study was to analyze the impact of COVID-19 pandemic restrictions on the prevalence and incidence of metabolic syndrome (MS), and to identify predictors of new MS cases in people living with HIV (PLWH).MethodsThis cohort study included PLWH followed at the IRCCS San Raffaele, Milan, Italy, with at least one body mass index (BMI) determination during the pre-pandemic period (1 December 2018 to 29 February 2020) and the pandemic period (1 March 2020 to 31 May 2021). MS diagnosis was based on NCEP ATP III 2005 criteria. Univariable Poisson regression model was used to compare MS incidence rates. Univariable mixed linear models estimated the crude mean change in metabolic parameters during each time period. Multivariable Cox proportional hazards model was used to assess risk factors for MS.ResultsThis study included 1,564 PLWH, of whom 460 and 1,104 were with and without a diagnosis of MS, respectively, at the beginning of the pre-pandemic period, with an overall prevalence of MS of 29.4%. During the pre-pandemic period, 528/1,564 PLWH had MS, with a prevalence of 33.8% (95%CI = 31.5%–36.1%), while during the pandemic period, the number of PLWH with a diagnosis of MS increased to 628/1,564, with a prevalence of 40.2% (95%CI 37.8%–42.6%; McNemar’s test: p &lt; 0.0001). Similarly, the MS incidence rate increased from 13.7/100 person-years of follow-up (PYFU; 95%CI = 11.7–16.0) in the pre-pandemic period to 18.5/100 PYFU (95%CI = 16.2–21.1) in the pandemic period (p = 0.004), with 201 subjects developing MS during the pandemic period. In addition, we observed a significant increase in the crude mean change during the pandemic period compared with the pre-pandemic period for: total cholesterol, LDL cholesterol, plasma glucose, blood pressure, and atherosclerotic cardiovascular disease (ASCVD) risk score. Finally, after adjustment for HIV risk factors, HBV, HCV, ART duration, duration of virologic suppression and use of INSTIs, age [adjusted hazard ratio (AHR) per 3 years older = 1.12 (95%CI = 1.08–1.17)], sex [AHR female vs. male = 0.62 (95%CI = 0.44–0.87)] and CD4+ cell count [AHR per 100 cells/μL higher = 1.05 (95%CI = 1.01–1.09)] were associated with the risk of MS.ConclusionThe COVID-19 pandemic affected the metabolic profile of PLWH and increased the prevalence and incidence of MS.
Hierarchical machine learning model predicts antimicrobial peptide activity against Staphylococcus aureus
Authors: Khabaz Hosein , Rahimi-Nasrabadi Mehdi , Keihan Amir Homayoun 
Published: September 2023

Introduction:Staphylococcus aureus is a dangerous pathogen which causes a vast selection of infections. Antimicrobial peptides have been demonstrated as a new hope for developing antibiotic agents against multi-drug-resistant bacteria such as S. aureus. Yet, most studies on developing classification tools for antimicrobial peptide activities do not focus on any specific species, and therefore, their applications are limited.Methods: Here, by using an up-to-date dataset, we have developed a hierarchical machine learning model for classifying peptides with antimicrobial activity against S. aureus. The first-level model classifies peptides into AMPs and non-AMPs. The second-level model classifies AMPs into those active against S. aureus and those not active against this species.Results: Results from both classifiers demonstrate the effectiveness of the hierarchical approach. A comprehensive set of physicochemical and linguistic-based features has been used, and after feature selection steps, only some physicochemical properties were selected. The final model showed the F1-score of 0.80, recall of 0.86, balanced accuracy of 0.80, and specificity of 0.73 on the test set.Discussion: The susceptibility to a single AMP is highly varied among different target species. Therefore, it cannot be concluded that AMP candidates suggested by AMP/non-AMP classifiers are able to show suitable activity against a specific species. Here, we addressed this issue by creating a hierarchical machine learning model which can be used in practical applications for extracting potential antimicrobial peptides against S. aureus from peptide libraries.