bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of 1-(5-bromopyrazin-2-yl)-1-[3-(trifluoromethyl)benzyl]urea as a promising anticancer drug via synthesis, characterization, biological screening, and computational studies
Authors: Mohammed Yasser Hussein Issa , Shamkh Israa M. , Alharthi Nahed S. , Shanawaz Mohammed A. , Alzahrani Hind A. , Jabbar Basit , Beigh Saba , Alghamdi Saad , Alsakhen Nada , Khidir Elshiekh B. , Alhuthali Hayaa M. , Karamalla Taqwa Hafiz Elamin , Rabie Amgad M. 
Published: December 2023

AbstractCancer and different types of tumors are still the most resistant diseases to available therapeutic agents. Finding a highly effective anticancer drug is the first target and concern of thousands of drug designers. In our attempts to address this concern, a new pyrazine derivative, 1-(5-bromopyrazin-2-yl)-1-[3-(trifluoromethyl)benzyl]urea (BPU), was designed via structural optimization and synthesized to investigate its anticancer/antitumor potential. The in-vitro anticancer properties of BPU were evaluated by MTT assay using selected cell lines, including the Jurkat, HeLa, and MCF-7 cells. The Jurkat cells were chosen to study the effect of BPU on cell cycle analysis using flow cytometry technique. BPU exhibited an effective cytotoxic ability in all the three cell lines assessed. It was found to be more prominent with the Jurkat cell line (IC50 = 4.64 ± 0.08 µM). When it was subjected to cell cycle analysis, this compound effectively arrested cell cycle progression in the sub-G1 phase. Upon evaluating the antiangiogenic potential of BPU via the in-vivo/ex-vivo shell-less chick chorioallantoic membrane (CAM) assays, the compound demonstrated very significant findings, revealing a complementary supportive action for the compound to act as a potent anticancer agent through inhibiting blood vessel formation in tumor tissues. Moreover, the docking energy of BPU computationally scored − 9.0 kcal/mol with the human matrix metalloproteinase 2 (MMP-2) and − 7.8 kcal/mol with the human matrix metalloproteinase 9 (MMP-9), denoting promising binding results as compared to the existing drugs for cancer therapy. The molecular dynamics (MD) simulation outcomes showed that BPU could effectively bind to the previously-proposed catalytic sites of both MMP-2 and MMP-9 enzymes with relatively stable statuses and good inhibitory binding abilities and parameters. Our findings suggest that the compound BPU could be a promising anticancer agent since it effectively inhibited cell proliferation and can be selected for further in-vitro and in-vivo investigations. In addition, the current results can be extensively validated by conducting wet-lab analysis so as to develop novel and better derivatives of BPU for cancer therapy with much less side effects and higher activities.
Prognostic utility and characterization of left ventricular hypertrophy using global thickness
Authors: Lundin Magnus , Heiberg Einar , Nordlund David , Gyllenhammar Tom , Steding-Ehrenborg Katarina , Engblom Henrik , Carlsson Marcus , Atar Dan , van der Pals Jesper , Erlinge David , Borgquist Rasmus , Khoshnood Ardavan , Ekelund Ulf , Nickander Jannike , Themudo Raquel , Nordin Sabrina , Kozor Rebecca , Bhuva Anish N. , Moon James C. , Maret Eva , Caidahl Kenneth , Sigfridsson Andreas , Sörensson Peder , Schelbert Erik B. , Arheden Håkan , Ugander Martin 
Published: December 2023

AbstractCardiovascular magnetic resonance (CMR) can accurately measure left ventricular (LV) mass, and several measures related to LV wall thickness exist. We hypothesized that prognosis can be used to select an optimal measure of wall thickness for characterizing LV hypertrophy. Subjects having undergone CMR were studied (cardiac patients, n = 2543; healthy volunteers, n = 100). A new measure, global wall thickness (GT, GTI if indexed to body surface area) was accurately calculated from LV mass and end-diastolic volume. Among patients with follow-up (n = 1575, median follow-up 5.4 years), the most predictive measure of death or hospitalization for heart failure was LV mass index (LVMI) (hazard ratio (HR)[95% confidence interval] 1.16[1.12–1.20], p < 0.001), followed by GTI (HR 1.14[1.09–1.19], p < 0.001). Among patients with normal findings (n = 326, median follow-up 5.8 years), the most predictive measure was GT (HR 1.62[1.35–1.94], p < 0.001). GT and LVMI could characterize patients as having a normal LV mass and wall thickness, concentric remodeling, concentric hypertrophy, or eccentric hypertrophy, and the three abnormal groups had worse prognosis than the normal group (p < 0.05 for all). LV mass is highly prognostic when mass is elevated, but GT is easily and accurately calculated, and adds value and discrimination amongst those with normal LV mass (early disease).
BOO-ST and CBCEC: two novel hybrid machine learning methods aim to reduce the mortality of heart failure patients
Authors: Sutradhar Ananda , Al Rafi Mustahsin , Shamrat F M Javed Mehedi , Ghosh Pronab , Das Subrata , Islam Md Anaytul , Ahmed Kawsar , Zhou Xujuan , Azad A. K. M. , Alyami Salem A. , Moni Mohammad Ali 
Published: December 2023

AbstractHeart failure (HF) is a leading cause of mortality worldwide. Machine learning (ML) approaches have shown potential as an early detection tool for improving patient outcomes. Enhancing the effectiveness and clinical applicability of the ML model necessitates training an efficient classifier with a diverse set of high-quality datasets. Hence, we proposed two novel hybrid ML methods ((a) consisting of Boosting, SMOTE, and Tomek links (BOO-ST); (b) combining the best-performing conventional classifier with ensemble classifiers (CBCEC)) to serve as an efficient early warning system for HF mortality. The BOO-ST was introduced to tackle the challenge of class imbalance, while CBCEC was responsible for training the processed and selected features derived from the Feature Importance (FI) and Information Gain (IG) feature selection techniques. We also conducted an explicit and intuitive comprehension to explore the impact of potential characteristics correlating with the fatality cases of HF. The experimental results demonstrated the proposed classifier CBCEC showcases a significant accuracy of 93.67% in terms of providing the early forecasting of HF mortality. Therefore, we can reveal that our proposed aspects (BOO-ST and CBCEC) can be able to play a crucial role in preventing the death rate of HF and reducing stress in the healthcare sector.
Clinical characterisation of women with persistent genital arousal disorder: the iPGAD-study
Authors: Kümpers Franziska M. L. M. , Sinke Christopher , Schippert Cordula , Kollewe Katja , Körner Sonja , Raab Peter , Meyer Bernhard , Maschke Sabine , Karst Matthias , Sperling Christian , Dalkeranidis Eleni , Krüger Tillmann H. C. 
Published: December 2023

AbstractPersistent Genital Arousal Disorder (PGAD) is a rare condition—mostly in women—where patients perceive prolonged genital arousal without any sexual desire or stimulation. Etiopathological considerations reach from peripheral to central issues over local disturbance of the pudendal nerve to neuropathy, psychosocial, and pharmacological theories. Since well controlled clinical studies about PGAD in conjunction with a mental and somatic health status are missing, this study is a detailed clinical investigation of PGAD patients compared to healthy controls. 26 women who fulfilled diagnostic criteria for PGAD were compared to 26 age matched healthy controls. Investigations included comparison of vegetative, gynaecological and sexual history, psychiatric features as well as a (neuro-)radiological, neurophysiological and gynaecological examination. Moreover, a detailed clinical characterisation of PGAD symptoms was performed. PGAD symptoms were mostly characterised as tingling or prickling and were permanently present. In over 80%, PGAD symptoms were located in the clitoris. Almost 70% reported radiations to other regions of the body. Most frequent trigger factors were tight clothes, mental stress, driving a car/bus/bicycle and sexual intercourse. Relieving factors were mainly distraction, relaxation, physical exercise, masturbation and swimming. In group comparisons, PGAD presented with significant higher rates of sexual dysfunctions, spontaneous orgasms, swelling of the genitals, extraordinary lubrication as well as higher rates in depression, agoraphobia, generalized anxiety disorder and lifetime panic disorder. Significantly more PGAD patients were diagnosed with restless legs symptoms. In contrast childhood traumatization, somatization disorder, suicidality, gynaecological as well as neurophysiological examination of the pudendal nerve were not different between the groups. MRI of the brain, pelvis and spinal cord was unsuspicious and incidental findings - including Tarlov cysts or pelvic venous congestion - were equally distributed among the groups. In summary, our study provides a careful characterization of women with PGAD highlighting a serious mental burden, most probably as a consequence of PGAD. With the current set of clinical investigations there was no evidence of a clear causal relationship to a specific clinical finding as it has been previously discussed. Future studies and additional techniques will have to further explore where and how in the peripheral or central nervous systems PGAD develops.
Cervical vestibular evoked myogenic potential (cVEMP) findings in adults with sensorineural hearing loss (SNHL): comparisons between 500 Hz tone burst and narrowband CE-Chirp stimuli
Authors: Zakaria Mohd Normani , Salim Rosdan , Abdul Wahat Nor Haniza , Md Daud Mohd Khairi , Wan Mohamad Wan Najibah 
Published: December 2023

AbstractThere has been a growing interest in studying the usefulness of chirp stimuli in recording cervical vestibular evoked myogenic potential (cVEMP) waveforms. Nevertheless, the study outcomes are debatable and require verification. In view of this, the aim of the present study was to compare cVEMP results when elicited by 500 Hz tone burst and narrowband (NB) CE-Chirp stimuli in adults with sensorineural hearing loss (SNHL). Fifty adults with bilateral SNHL (aged 20–65 years) underwent the cVEMP testing based on the established protocol. The 500 Hz tone burst and NB CE-Chirp (centred at 500 Hz) stimuli were presented to each ear at an intensity level of 120.5 dB peSPL. P1 latency, N1 latency, and P1–N1 amplitude values were analysed accordingly. The NB CE-Chirp stimulus produced significantly shorter P1 and N1 latencies (p < 0.001) with large effect sizes (d > 0.80). In contrast, both stimuli elicited cVEMP responses with P1–N1 amplitude values that were not statistically different from one another (p = 0.157, d = 0.15). Additionally, age and hearing level were found to be significantly correlated (r = 0.56, p < 0.001), as were age and cVEMP amplitude for each stimulus (p < 0.001). To conclude, since both stimuli were presented at an equivalent intensity level (in dB peSPL), the shorter P1 and N1 latencies of cVEMP produced by the NB CE-Chirp stimulus (centred at 500 Hz) were unlikely due to enhanced saccular stimulation. Another more sensible reason is the temporal adjustment of the chirp stimulus.
Significance of LHCGR polymorphisms in polycystic ovary syndrome: an association study
Authors: Singh Sukhjashanpreet , Kaur Mandeep , Beri Archana , Kaur Anupam 
Published: December 2023

AbstractThis study was conducted to analyze the association of Luteinizing Hormone/Choriogonadotropin Receptor (LHCGR) gene rs4953616 and rs7371084 polymorphisms with the risk of polycystic ovary syndrome (PCOS) in Punjab, India. A total of 823 women (443 PCOS cases and 380 healthy controls) were enrolled in the present study. The polymerase chain reaction-restriction fragment length polymorphism technique (PCR–RFLP) was used for genotyping. Anthropometric parameters, lipid and hormonal profiles, were compared between the two groups. Demographic features were compared using Mann Whitney U test while the Chi-square test and odds ratios (ORs) were used to assess the genetic association and risk towards PCOS, respectively. A one-way analysis of variance (ANOVA) test was employed to analyze the correlation of genotypes with baseline parameters in PCOS cases. A statistically significant difference was revealed in the genotypic and allelic frequencies of rs4953616 polymorphism between PCOS cases and controls (p = 0.01 and p = 0.004, respectively). The mutant genotype (TT), mutant allele (T), and recessive model of rs4953616 polymorphism conferred 1.77, 1.3, and 1.5 times risk towards PCOS, respectively. No significant distribution for genotypes and alleles was found for rs7371084 in both groups (p = 0.25 and p = 0.26, respectively). In addition to dyslipidemia, PCOS women also had significantly higher body mass index (BMI) and waist-to-hip ratio (WHR), testosterone (T), and luteinizing hormone (LH). Upon haplotype analysis, the TT haplotype was found to be significantly associated with the increased risk of PCOS. Our results demonstrated a significant role of LHCGR rs4953616 polymorphism in the development of PCOS.
Intestinal dysbiosis as an intraoperative predictor of septic complications: evidence from human surgical cohorts and preclinical models of peritoneal sepsis
Authors: Spari Daniel , Zwicky Simone N. , Yilmaz Bahtiyar , Salm Lilian , Candinas Daniel , Beldi Guido 
Published: December 2023

AbstractMajor surgery exposes the intestinal microbiota to inflammatory and antibiotic stressors, which alter the microbiota composition of the intestinal lumen and fecal contents. However, it is not sufficiently understood, if such dysbiosis develops already during surgery and if alterations in microbiota may be the cause of surgical complications. End-of-surgery composition of the microbiota in the rectum was assessed in 41 patients undergoing either rectal or duodenopancreatic resection and was compared to baseline before surgery using 16S-rRNA sequencing. A subset of patients developed severe dysbiosis at the end of surgery, which was characterized by an overgrowth of the Proteobacteria phylum that includes the facultative pathogen E. coli. To test if dysbiosis impacts on surgical outcomes, dysbiosis was modeled in mice by a single oral administration of vancomycin prior to cecal ligation and puncture. Dysbiosis was associated with impaired post-surgical survival, dysregulation of the host’s immune response, elevated bacterial virulence and reduced bacterial metabolism of carbon sources. In conclusion, dysbiosis can be detected already at the end of surgery in a fraction of patients undergoing major surgery. Modelling surgery-associated dysbiosis in mice using single-shot administration of vancomycin induced dysbiosis and resulted in elevated mortality.
Investigation of SARS-CoV-2 individual proteins reveals the in vitro and in vivo immunogenicity of membrane protein
Authors: Haystead Timothy , Lee Eric , Cho Kirstin , Gullickson Gail , Hughes Philip , Krafsur Greta , Freeze Robert , Scarneo Scott 
Published: December 2023

AbstractEvidence in SARS-CoV-2 patients have identified that viral infection is accompanied by the expression of inflammatory mediators by both immune and stromal cells within the pulmonary system. However, the immunogenicity of individual SARS-CoV-2 proteins has yet to be evaluated. The SARS-CoV-2 virus consists of 29 proteins, categorized either as nonstructural proteins (NSP’s), structural proteins (SP’s) or accessory proteins. Here we sought to evaluate the immunogenicity of NSP 1, 7, 8, 9, 10, 12, 14, 16 and the SP’s spike protein (full length, S1, S2 and receptor binding domain subunits), nucleocapsid and membrane SARS-CoV-2 proteins against THP-1 and human peripheral blood mononuclear cells (PBMCs). Our results indicate that various SARS-CoV-2 proteins elicit a proinflammatory immune response indicated by increases in cytokines TNF, IL-6 and IL-1β. Our results support that SARS-CoV-2 membrane protein induced a robust increase of TNF, IL-6, IL-1β and IL-10 expression in both THP-1 and human PBMC’s. Further evaluation of intranasal membrane protein challenge in male and female BALB/c mice show increases in BALF (bronchalveolar lavage fluid) proinflammatory cytokine expression, elevated cellularity, predominantly neutrophilic, and concomitant peribronchiolar and perivascular lymphomononuclear and neutrophilic inflammation. Our results suggest that individual membrane associated SARS-CoV-2 proteins induce a robust immune response that may contribute to viral induced cytokine release syndrome (CRS) in the lungs of moderate to severe COVID-19 patients. We posit that SARS-CoV-2 membrane challenges in immune-competent mice can serve as an adequate surrogate for the development of novel treatments for SARS-CoV-2 induced pulmonary inflammation, thereby avoiding expensive live virus studies under BSL-3 conditions.
A reliable benchmark of the last 640,000 years millennial climate variability
Authors: Rousseau Denis-Didier , Bagniewski Witold , Cheng Hai 
Published: December 2023

AbstractHow often have past climates undergone abrupt transitions? While our understanding of millennial variability during the past 130,000 years is well established, with precise dates available, such information on previous climate cycles is limited. To address this question, we identified 196 abrupt transitions in the δ18O record of the well-dated Chinese composite speleothem for the last 640,000 years. These results correspond to abrupt changes in the strength of the East Asian Monsoon, which align with the Greenland stadials and interstadials observed in the North Atlantic region during the last 130,000 years before present. These precise dates of past abrupt climate changes constitute a reliable and necessary benchmark for Earth System models used to study future climate scenarios.
Number agreement processing in adolescents with and without developmental language disorder (DLD): evidence from event-related brain potentials
Authors: Courteau Émilie , Royle Phaedra , Steinhauer Karsten 
Published: December 2023

AbstractIn morphologically richer languages, including French, one must learn the specific properties of number agreement in order to understand the language, and this learning process continues into adolescence. This study examined similarities and differences between French-speaking adolescents with and without developmental language disorder (DLD) when processing number agreement, and investigated how morpho-syntactic regularity affected language processing. Using event-related potentials (ERP) and only grammatical sentences with audio-visual mismatches, we studied ERP correlates to three types of number agreement: (1) regular determiner agreement in noun phrases, (2) regular subject-verb plural liaison, and (3) irregular subject-verb agreement. We also included a lexico-semantic mismatch condition to investigate lexico-semantic processing in our participants. 17 adolescents with DLD (M = 14.1 years) and 20 (pre)teens with typical language (TL, M = 12.2 years) participated in the study. Our results suggest three patterns. First, French-speaking teenagers without DLD are still consolidating their neurocognitive processing of morpho-syntactic number agreement and generally display ERP profiles typical of lower language proficiency than adult native speakers. Second, differences in morphosyntactic processing between teenagers with and without DLD seem to be limited to rule-based (regular) number agreement. Third, there is little evidence for corresponding differences in lexico-semantic processing.
Identification of differences in CD4+ T-cell gene expression between people with asthma and healthy controls
Authors: Tutino Mauro , Hankinson Jenny , Murray Clare , Lowe Lesley , Kerry Gina , Rattray Magnus , Custovic Adnan , Johnston Sebastian L. , Shi Chenfu , Orozco Gisela , Eyre Stephen , Martin Paul , Simpson Angela , Curtin John A. 
Published: December 2023

AbstractFunctional enrichment analysis of genome-wide association study (GWAS)-summary statistics has suggested that CD4+ T-cells play an important role in asthma pathogenesis. Despite this, CD4+ T-cells are under-represented in asthma transcriptome studies. To fill the gap, 3'-RNA-Seq was used to generate gene expression data on CD4+ T-cells (isolated within 2 h from collection) from peripheral blood from participants with well-controlled asthma (n = 32) and healthy controls (n = 11). Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify sets of co-expressed genes (modules) associated with the asthma phenotype. We identified three modules associated with asthma, which are strongly enriched for GWAS-identified asthma genes, antigen processing/presentation and immune response to viral infections. Through integration of publicly available eQTL and GWAS summary statistics (colocalisation), and protein–protein interaction (PPI) data, we identified PTPRC, a potential druggable target, as a putative master regulator of the asthma gene-expression profiles. Using a co-expression network approach, with integration of external genetic and PPI data, we showed that CD4+ T-cells from peripheral blood from asthmatics have different expression profiles, albeit small in magnitude, compared to healthy controls, for sets of genes involved in immune response to viral infections (upregulated) and antigen processing/presentation (downregulated).
Early diagnosis and meta-agnostic model visualization of tuberculosis based on radiography images
Authors: Natarajan Sasikaladevi , Sampath Pradeepa , Arunachalam Revathi , Shanmuganathan Vimal , Dhiman Gaurav , Chakrabarti Prasun , Chakrabarti Tulika , Margala Martin 
Published: December 2023

AbstractDespite being treatable and preventable, tuberculosis (TB) affected one-fourth of the world population in 2019, and it took the lives of 1.4 million people in 2019. It affected 1.2 million children around the world in the same year. As it is an infectious bacterial disease, the early diagnosis of TB prevents further transmission and increases the survival rate of the affected person. One of the standard diagnosis methods is the sputum culture test. Diagnosing and rapid sputum test results usually take one to eight weeks in 24 h. Using posterior-anterior chest radiographs (CXR) facilitates a rapid and more cost-effective early diagnosis of tuberculosis. Due to intraclass variations and interclass similarities in the images, TB prognosis from CXR is difficult. We proposed an early TB diagnosis system (tbXpert) based on deep learning methods. Deep Fused Linear Triangulation (FLT) is considered for CXR images to reconcile intraclass variation and interclass similarities. To improve the robustness of the prognosis approach, deep information must be obtained from the minimal radiation and uneven quality CXR images. The advanced FLT method accurately visualizes the infected region in the CXR without segmentation. Deep fused images are trained by the Deep learning network (DLN) with residual connections. The largest standard database, comprised of 3500 TB CXR images and 3500 normal CXR images, is utilized for training and validating the recommended model. Specificity, sensitivity, Accuracy, and AUC are estimated to determine the performance of the proposed systems. The proposed system demonstrates a maximum testing accuracy of 99.2%, a sensitivity of 98.9%, a specificity of 99.6%, a precision of 99.6%, and an AUC of 99.4%, all of which are pretty high when compared to current state-of-the-art deep learning approaches for the prognosis of tuberculosis. To lessen the radiologist’s time, effort, and reliance on the level of competence of the specialist, the suggested system named tbXpert can be deployed as a computer-aided diagnosis technique for tuberculosis.