bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morpho‐Tectonic Evolution of the Southern Apennines and Calabrian Arc: Insights From Pollino Range and Surrounding Extensional Intermontane Basins
Authors: Clementucci R. , Lanari R. , Faccenna C. , Crosetto S. , Reitano R. , Zoppis G. , Ballato P. 
Published: May 2024

AbstractThe evolution of topography in forearc regions results from the complex interplay of crustal and mantle processes. The Southern Apennines represent a well‐studied forearc region that experienced several tectonic phases, initially marked by compressional deformation followed by extension and large‐scale uplift. We present a new structural, geomorphic and fluvial analysis of the Pollino Massif and surrounding intermontane basins (Mercure, Campotenese and Castrovillari) to unravel their evolution since the Pliocene. We constrain multiple tectonic transport directions, evolution of the drainage, and magnitude and timing of long‐term incision following base level falls. Two sets of knickpoints suggest two phases of base level lowering and allow to estimate ∼500 m of long‐term uplift (late Pleistocene), as observed in the Sila Massif. On a smaller spatial scale, the evolution and formation of topographic relief, sedimentation, and opening of intermontane basins is strongly controlled by the recent increase in rock uplift rate and fault activity. At the regional scale, an along‐strike, long‐wavelength uplift pattern from north to south can be explained by progressive lateral slab tearing and inflow of asthenospheric mantle beneath Pollino and Sila, which in turn may have promoted extensional tectonics. The lower uplift of Le Serre Massif may be explained as result of weak plate coupling due to narrowing of the Calabrian slab. The onset of uplift in the Pollino Massif, ranging from 400 to 800 ka, is consistent with that one proposed in the southern Calabrian forearc, suggesting a possible synchronism of uplift, and lateral tearing of the Calabrian slab.
Pre- and postsynaptic signatures in the prelimbic cortex associated with “alcohol use disorder” in the rat
Authors: Domi Ana , Cadeddu Davide , Lucente Erika , Gobbo Francesco , Edvardsson Christian , Petrella Michele , Jerlhag Elisabet , Ericson Mia , Söderpalm Bo , Adermark Louise 
Published: May 2024

AbstractThe transition to alcohol use disorder (AUD) involves persistent neuroadaptations in executive control functions primarily regulated by the medial prefrontal cortex. However, the neurophysiological correlates to behavioral manifestations of AUD are not fully defined. The association between cortical neuroadaptations and behavioral manifestations of addiction was studied using a multi-symptomatic operant model based on the DSM-5 diagnostic criteria for AUD. This model aimed to characterize an AUD-vulnerable and AUD-resistant subpopulation of outbred male Wistar rats and was combined with electrophysiological measurements in the prelimbic cortex (PL). Mirroring clinical observations, rats exhibited individual variability in their vulnerability to develop AUD-like behavior, including motivation to seek for alcohol (crit 1), increased effort to obtain the substance (crit 2), and continued drinking despite negative consequences (crit 3). Only a small subset of rats met all the aforementioned AUD criteria (3 crit, AUD-vulnerable), while a larger fraction was considered AUD-resilient (0 crit). The development of AUD-like behavior was characterized by disruptions in glutamatergic synaptic activity, involving decreased frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and heightened intrinsic excitability in layers 2/3 PL pyramidal neurons. These alterations were concomitant with a significant impairment in the ability of mGlu2/3 receptors to negatively regulate glutamate release in the PL but not in downstream regions like the basolateral amygdala or nucleus accumbens core. In conclusion alterations in PL synaptic activity were strongly associated with individual addiction scores, indicating their role as potential markers of the behavioral manifestations linked to AUD psychopathology.
NF1 with 47,XYY mosaicism diagnosed by mandibular neurofibromas
Authors: Tonouchi Erina , Morita Kei-ichi , Harazono Yosuke , Hoshino Kyoko , Yoda Tetsuya 
Published: May 2024

Abstract
Neurofibromatosis type 1 (NF1) is an autosomal dominant nevus disease characterized by multiple manifestations, primarily café-au-lait macules and neurofibromas. Here, we present the case of an NF1 patient with 47,XYY mosaicism whose diagnosis was prompted by café-au-lait macules on the skin and mandibular neurofibromas. Targeted next-generation sequencing of the patient’s blood sample revealed a novel frameshift mutation in NF1 (NM_000267.3:c.6832dupA:p.Thr2278Asnfs*8) that is considered a pathogenic variant.
1q amplification and PHF19 expressing high-risk cells are associated with relapsed/refractory multiple myeloma
Authors: Johnson Travis S. , Sudha Parvathi , Liu Enze , Becker Nathan , Robertson Sylvia , Blaney Patrick , Morgan Gareth , Chopra Vivek S. , Dos Santos Cedric , Nixon Michael , Huang Kun , Suvannasankha Attaya , Zaid Mohammad Abu , Abonour Rafat , Walker Brian A. 
Published: May 2024

AbstractMultiple Myeloma is an incurable plasma cell malignancy with a poor survival rate that is usually treated with immunomodulatory drugs (iMiDs) and proteosome inhibitors (PIs). The malignant plasma cells quickly become resistant to these agents causing relapse and uncontrolled growth of resistant clones. From whole genome sequencing (WGS) and RNA sequencing (RNA-seq) studies, different high-risk translocation, copy number, mutational, and transcriptional markers can be identified. One of these markers, PHF19, epigenetically regulates cell cycle and other processes and is already studied using RNA-seq. In this study, we generate a large (325,025 cells and 49 patients) single cell multi-omic dataset and jointly quantify ATAC- and RNA-seq for each cell and matched genomic profiles for each patient. We identify an association between one plasma cell subtype with myeloma progression that we call relapsed/refractory plasma cells (RRPCs). These cells are associated with chromosome 1q alterations, TP53 mutations, and higher expression of PHF19. We also identify downstream regulation of cell cycle inhibitors in these cells, possible regulation by the transcription factor (TF) PBX1 on chromosome 1q, and determine that PHF19 may be acting primarily through this subset of cells.
Importance of social inequalities to contact patterns, vaccine uptake, and epidemic dynamics
Authors: Manna Adriana , Koltai Júlia , Karsai Márton 
Published: May 2024

AbstractIndividuals’ socio-demographic and economic characteristics crucially shape the spread of an epidemic by largely determining the exposure level to the virus and the severity of the disease for those who got infected. While the complex interplay between individual characteristics and epidemic dynamics is widely recognised, traditional mathematical models often overlook these factors. In this study, we examine two important aspects of human behaviour relevant to epidemics: contact patterns and vaccination uptake. Using data collected during the COVID-19 pandemic in Hungary, we first identify the dimensions along which individuals exhibit the greatest variation in their contact patterns and vaccination uptake. We find that generally higher socio-economic groups of the population have a higher number of contacts and a higher vaccination uptake with respect to disadvantaged groups. Subsequently, we propose a data-driven epidemiological model that incorporates these behavioural differences. Finally, we apply our model to analyse the fourth wave of COVID-19 in Hungary, providing valuable insights into real-world scenarios. By bridging the gap between individual characteristics and epidemic spread, our research contributes to a more comprehensive understanding of disease dynamics and informs effective public health strategies.
E-cardiac patch to sense and repair infarcted myocardium
Authors: Qiu Renjie , Zhang Xingying , Song Chen , Xu Kaige , Nong Huijia , Li Yi , Xing Xianglong , Mequanint Kibret , Liu Qian , Yuan Quan , Sun Xiaomin , Xing Malcolm , Wang Leyu 
Published: May 2024

AbstractConductive cardiac patches can rebuild the electroactive microenvironment for the infarcted myocardium but their repair effects benefit by carried seed cells or drugs. The key to success is the effective integration of electrical stimulation with the microenvironment created by conductive cardiac patches. Besides, due to the concerns in a high re-admission ratio of heart patients, a remote medicine device will underpin the successful repair. Herein, we report a miniature self-powered biomimetic trinity triboelectric nanogenerator with a unique double-spacer structure that unifies energy harvesting, therapeutics, and diagnosis in one cardiac patch. Trinity triboelectric nanogenerator conductive cardiac patches improve the electroactivity of the infarcted heart and can also wirelessly monitor electrocardiosignal to a mobile device for diagnosis. RNA sequencing analysis from rat hearts reveals that this trinity cardiac patches mainly regulates cardiac muscle contraction-, energy metabolism-, and vascular regulation-related mRNA expressions in vivo. The research is spawning a device that truly integrates an electrical stimulation of a functional heart patch and self-powered e-care remote diagnostic sensor.
Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity
Authors: Wang Shengjun , Ran Wei , Sun Lingyu , Fan Qingchi , Zhao Yuanqi , Wang Bowen , Yang Jinghong , He Yuqi , Wu Ying , Wang Yuanyuan , Chen Luoyi , Chuchuay Arpaporn , You Yuyu , Zhu Xinhai , Wang Xiaojuan , Chen Ye , Wang Yanqun , Chen Yao-Qing , Yuan Yanqiu , Zhao Jincun , Mao Yang 
Published: May 2024

AbstractThe multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus.
Magnetic voluntary head-fixation in transgenic rats enables lifespan imaging of hippocampal neurons
Authors: Rich P. Dylan , Thiberge Stephan Yves , Scott Benjamin B. , Guo Caiying , Tervo D. Gowanlock R. , Brody Carlos D. , Karpova Alla Y. , Daw Nathaniel D. , Tank David W. 
Published: May 2024

AbstractThe precise neural mechanisms within the brain that contribute to the remarkable lifetime persistence of memory are not fully understood. Two-photon calcium imaging allows the activity of individual cells to be followed across long periods, but conventional approaches require head-fixation, which limits the type of behavior that can be studied. We present a magnetic voluntary head-fixation system that provides stable optical access to the brain during complex behavior. Compared to previous systems that used mechanical restraint, there are no moving parts and animals can engage and disengage entirely at will. This system is failsafe, easy for animals to use and reliable enough to allow long-term experiments to be routinely performed. Animals completed hundreds of trials per session of an odor discrimination task that required 2–4 s fixations. Together with a reflectance fluorescence collection scheme that increases two-photon signal and a transgenic Thy1-GCaMP6f rat line, we are able to reliably image the cellular activity in the hippocampus during behavior over long periods (median 6 months), allowing us track the same neurons over a large fraction of animals’ lives (up to 19 months).
Machine learning designs new GCGR/GLP-1R dual agonists with enhanced biological potency
Authors: Puszkarska Anna M. , Taddese Bruck , Revell Jefferson , Davies Graeme , Field Joss , Hornigold David C. , Buchanan Andrew , Vaughan Tristan J. , Colwell Lucy J. 
Published: May 2024

AbstractSeveral peptide dual agonists of the human glucagon receptor (GCGR) and the glucagon-like peptide-1 receptor (GLP-1R) are in development for the treatment of type 2 diabetes, obesity and their associated complications. Candidates must have high potency at both receptors, but it is unclear whether the limited experimental data available can be used to train models that accurately predict the activity at both receptors of new peptide variants. Here we use peptide sequence data labelled with in vitro potency at human GCGR and GLP-1R to train several models, including a deep multi-task neural-network model using multiple loss optimization. Model-guided sequence optimization was used to design three groups of peptide variants, with distinct ranges of predicted dual activity. We found that three of the model-designed sequences are potent dual agonists with superior biological activity. With our designs we were able to achieve up to sevenfold potency improvement at both receptors simultaneously compared to the best dual-agonist in the training set.
Exploring SureChEMBL from a drug discovery perspective
Authors: Gadiya Yojana , Shetty Simran , Hofmann-Apitius Martin , Gribbon Philip , Zaliani Andrea 
Published: May 2024

AbstractIn the pharmaceutical industry, the patent protection of drugs and medicines is accorded importance because of the high costs involved in the development of novel drugs. Over the years, researchers have analyzed patent documents to identify freedom-to-operate spaces for novel drug candidates. To assist this, several well-established public patent document data repositories have enabled automated methodologies for extracting information on therapeutic agents. In this study, we delve into one such publicly available patent database, SureChEMBL, which catalogues patent documents related to life sciences. Our exploration begins by identifying patent compounds across public chemical data resources, followed by pinpointing sections in patent documents where the chemical annotations were found. Next, we exhibit the potential of compounds to serve as drug candidates by evaluating their conformity to drug-likeness criteria. Lastly, we examine the drug development stage reported for these compounds to understand their clinical success. In summary, our investigation aims at providing a comprehensive overview of the patent compounds catalogued in SureChEMBL, assessing their relevance to pharmaceutical drug discovery.
Homocysteine thiolactone and other sulfur-containing amino acid metabolites are associated with fibrin clot properties and the risk of ischemic stroke
Authors: Sikora Marta , Bretes Ewa , Perła-Kaján Joanna , Utyro Olga , Borowczyk Kamila , Piechocka Justyna , Głowacki Rafał , Wojtasz Izabela , Kaźmierski Radosław , Jakubowski Hieronim 
Published: May 2024

AbstractHomocysteine (Hcy) and Hcy-thiolactone (HTL) affect fibrin clot properties and are linked to cardiovascular disease. Factors that influence fibrin clot properties and stroke are not fully understood. To study sulfur-containing amino acid metabolites, fibrin clot lysis time (CLT) and maximum absorbance (Absmax) in relation to stroke, we analyzed plasma and urine from 191 stroke patients (45.0% women, age 68 ± 12 years) and 291 healthy individuals (59.7% women, age 50 ± 17 years). Plasma and urinary levels of sulfur-containing amino acid metabolites and fibrin clot properties were significantly different in stroke patients compared to healthy individuals. Fibrin CLT correlated with fibrin Absmax in healthy males (R2 = 0.439, P = 0.000), females (R2 = 0.245, P = 0.000), female stroke patients (R2 = 0.187, P = 0.000), but not in male stroke patients (R2 = 0.008, P = ns). Fibrin CLT correlated with age in healthy females but not males while fibrin Absmax correlated with age in both sexes; these correlations were absent in stroke patients. In multiple regression analysis in stroke patients, plasma (p)CysGly, pMet, and MTHFR A1298C polymorphism were associated with fibrin Absmax, while urinary (u)HTL, uCysGly, and pCysGly were significantly associated with fibrin CLT. In healthy individuals, uHTL and uGSH were significantly associated with fibrin Absmax, while pGSH, and CBS T833C 844ins68 polymorphism were associated with fibrin CLT. In logistic regression, uHTL, uHcy, pCysGly, pGSH, MTHFR C677T polymorphism, and Absmax were independently associated with stroke. Our findings suggest that HTL and other sulfur-containing amino acid metabolites influence fibrin clot properties and the risk of stroke.
d-arabinose induces cell cycle arrest by promoting autophagy via p38 MAPK signaling pathway in breast cancer
Authors: Tang Zhenning , Song Hanying , Qin Shaojie , Tian Zengjian , Zhang Chaolin , Zhou Yang , Cai Ruizhi , Zhu Yongzhao 
Published: May 2024

AbstractBreast cancer patients often have a poor prognosis largely due to lack of effective targeted therapy. It is now well established that monosaccharide enhances growth retardation and chemotherapy sensitivity in tumor cells. We investigated whether d-arabinose has capability to restrict the proliferation of tumor cells and its mechanism. Here, we report that d-arabinose induced cytotoxicity is modulated by autophagy and p38 MAPK signaling pathway in breast cancer cell lines. The proliferation of cells was evaluated by CCK-8 and Colony formation assay. The distribution of cells in cell cycle phases was analyzed by flow cytometry. Cell cycle, autophagy and MAPK signaling related proteins were detected by western blotting. Mouse xenograft model was used to evaluate the efficacy of d-arabinose in vivo. The proliferation of cells was dramatically inhibited by d-arabinose exposure in a dose-dependent manner, which was relevant to cell cycle arrest, as demonstrated by G2/M cell cycle restriction and ectopic expression of cell cycle related proteins. Mechanistically, we further identified that d-arabinose is positively associated with autophagy and the activation of the p38 MAPK signaling in breast cancer. In contrast, 3-Ma or SB203580, the inhibitor of autophagy or p38 MAPK, reversed the efficacy of d-arabinose. Additionally, d-arabinose in vivo treatment could significantly inhibit xenograft growth of breast cancer cells. Our findings were the first to reveal that d-arabinose triggered cell cycle arrest by inducing autophagy through the activation of p38 MAPK signaling pathway in breast cancer cells.
Self-reported depression and its risk factors among hypertensive patients, Morocco: a cross-sectional study
Authors: Boukhari Fatima Zahra , Belayachi Safae , Essayagh Firdaous , Terkiba Othmane , Naji Ahmed Anouar , Amine Mohammed , Lambaki Abdellah , Essayagh Meriem , Essayagh Sanah , Essayagh Touria 
Published: May 2024

AbstractHypertensive patients are at an elevated risk of developing mental diseases such as depression, which can impair their quality of life. The purpose of this study is to measure the prevalence of self-reported depression among hypertensive patients treated at primary health care facilities in Marrakech. Between May 2021 and December 2022, a cross-sectional study of 1053 hypertensive patients attending primary health care facilities in Marrakech was conducted. A face-to-face questionnaire was used to collect socio-demographic, behavioral, and clinical data, as well as hypertension treatment characteristics and the care-patient-physician triad. The Patient Health Questionnaire-9 was used to assess self-reported depression. To identify self-reported depression risk factors, multivariate logistic regression was used. Depressive symptoms were reported by 56.1% of hypertensive patients. The patients' average age was 63.2 ± 9.5 years, and 508 (85.9%) were female. Female sex, stress, a low-salt diet, pain and physical discomfort, an urban living environment, a lack of self-monitoring of hypertension, an unsatisfactory relationship with the healthcare system, a family history of hypertension, and the perception of adverse effects of the antihypertensive drug were all associated with self-reported depression. Self-reported depression is prevalent among hypertensive patients in Marrakech. The mental health component should be emphasized while addressing hypertensive patients in primary health care facilities.
Approach for determining micro-strength parameters of rock based on particle flow code
Authors: Miao Luli , Liu Xinrong , Fu Yan 
Published: May 2024

AbstractDiscrete Element Method (DEM) has been successfully utilized to model rock behavior based on particle flow code (PFC), which is extensively employed in solving various problems related to rock engineering and geomechanics. Therefore, a convenient method for selecting appropriate microparameters of PFC for model generation is necessary. The present study aims to develop a novel approach that calculates proper micro-strength parameters for the contact bond model (CBM). Firstly, based on Plackett–Burman (PB) design, qualitative research is conducted and it is found that the main factors that influence the Brazilian tensile strength is microscopic tensile strength. We analyzed the stress conditions of a Brazilian disc’s vertical diameter using both continuum models and DEM. From this analysis, we establish a theoretical relationship between rock tensile strength and micro-strength parameters. Subsequently, a large number of numerical Brazilian tests were conducted to obtain the statistical relationship between the geometric parameters of balls, micro-strength parameters and the Brazilian tension strength. The results of the numerical simulation were then used to refine the theoretical equation mentioned above, resulting in a modified equation for rock tensile strength and micro-strength parameters. Finally, after verification, we confirm the feasibility of the method in this paper.
Identification of Mycobacterium abscessus using the peaks of ribosomal protein L29, L30 and hemophore-related protein by MALDI-MS proteotyping
Authors: Takei Satomi , Teramoto Kanae , Sekiguchi Yuji , Ihara Hiroaki , Tohya Mari , Iwamoto Shinichi , Tanaka Koichi , Khasawneh Abdullah , Horiuchi Yuki , Misawa Shigeki , Naito Toshio , Kirikae Teruo , Tada Tatsuya , Tabe Yoko 
Published: May 2024

AbstractMycobacteroides (Mycobacterium) abscessus, which causes a variety of infectious diseases in humans, is becoming detected more frequently in clinical specimens as cases are spreading worldwide. Taxonomically, M. abscessus is composed of three subspecies of M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp. massiliense, with different susceptibilities to macrolides. In order to identify rapidly these three subspecies, we determined useful biomarker proteins, including ribosomal protein L29, L30, and hemophore-related protein, for distinguishing the subspecies of M. abscessus using the matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) profiles. Thirty-three clinical strains of M. abscessus were correctly identified at the subspecies-level by the three biomarker protein peaks. This study ultimately demonstrates the potential of routine MALDI-MS-based laboratory methods for early identification and treatment for M. abscessus infections.