bluuebunny/crossref_metadata_2025_split huggingface dataset:
Borderline Personality Disorder and Outcome of Electroconvulsive Therapy in Patients With Depression
Authors: Nicolini Alain P. , Sienaert Pascal 
Published: February 2023

AbstractMajor depressive disorder (MDD) commonly coincides with borderline personality disorder (BPD), aggravating depressive symptom severity and reducing the odds of responding to antidepressant treatments. In this systematic review, we summarize the available evidence assessing the question whether the presence of BPD reduces the response to electroconvulsive therapy (ECT) in individuals with MDD.We conducted a systematic literature search (up to December 2021) without language restriction, using the PubMed/MEDLINE, Web of Science (Core Collection), Embase, and Cochrane Library databases, for prospective and retrospective studies, which assessed the efficacy of ECT in patients with MDD and comorbid BPD.Of the 2548 records screened, 6 articles were selected, 2 of which were based on the same population, leading to 5 included articles. The included studies are reporting on 3465 patients with MDD, of which 1206 had a comorbid BPD. Five of the 6 studies found a less robust response to ECT in patients with MDD and BPD compared with those without BPD.Our results suggest that, in patients with MDD, the presence of BPD is associated with a less robust acute response to ECT. Patients with BPD, however, showed a significant response to ECT in all of the included studies. More longitudinal studies with higher accuracy in BPD diagnosis are needed. Although a comorbid BPD seems to decrease the efficacy of ECT for MDD, ECT remains an effective treatment option in this severely ill patient group.
RevGel-seq: instrument-free single-cell RNA sequencing using a reversible hydrogel for cell-specific barcoding
Authors: Komatsu Jun , Cico Alba , Poncin Raya , Le Bohec Maël , Morf Jörg , Lipin Stanislav , Graindorge Antoine , Eckert Hélène , Saffarian Azadeh , Cathaly Léa , Guérin Frédéric , Majello Sara , Ulveling Damien , Vayaboury Anaïs , Fernandez Nicolas , Dimitrova Dilyana , Bussell Xavier , Fourne Yannick , Chaumat Pierre , André Barbara , Baldivia Elodie , Godet Ulysse , Guinin Mathieu , Moretto Vivien , Ismail Joy , Caille Olivier , Roblot Natacha , Beaupère Carine , Liboz Alexandrine , Guillemain Ghislaine , Blondeau Bertrand , Walrafen Pierre , Edelstein Stuart 
Published: February 2023

ABSTRACTProgress in sample preparation for scRNA-seq is reported based on RevGel™-seq, a reversible-hydrogel technology optimized for samples of fresh cells. Complexes of one cell paired with one barcoded bead are stabilized by a chemical linker and dispersed in a hydrogel in the liquid state. Upon gelation on ice the complexes are immobilized and physically separated without requiring nanowells or droplets. Cell lysis is triggered by detergent diffusion, and RNA molecules are captured on the adjacent barcoded beads for further processing with reverse transcription and preparation for cDNA sequencing. As a proof of concept, analysis of PBMC using RevGel-seq achieves results similar to microfluidic-based technologies when using the same original sample and the same data analysis software. In addition, a clinically relevant application of RevGel-seq is presented for pancreatic islet cells. Furthermore, characterizations carried out on cardiomyocytes demonstrate that the hydrogel technology readily accommodates very large cells. Standard analyses are in the 10,000-input cell range with the current gelation device, in order to satisfy common requirements for single-cell research. A convenient stopping point after two hours has been established by freezing at the cell lysis step, with full preservation of gene expression profiles. Overall, our results show that RevGel-seq represents an accessible and efficient instrument-free alternative, enabling flexibility in terms of experimental design and timing of sample processing, while providing broad coverage of cell types.
Durable reprogramming of neutralising antibody responses following breakthrough Omicron infection
Authors: Lee Wen Shi , Tan Hyon-Xhi , Reynaldi Arnold , Esterbauer Robyn , Koutsakos Marios , Nguyen Julie , Amarasena Thakshila , Kent Helen E , Aggarwal Anupriya , Turville Stuart G , Taiaroa George , Kinsella Paul , Liew Kwee Chin , Tran Thomas , Williamson Deborah A , Cromer Deborah , Davenport Miles P , Kent Stephen J , Juno Jennifer A , Khoury David S , Wheatley Adam K 
Published: February 2023

AbstractSARS-CoV-2 breakthrough infection of vaccinated individuals is increasingly common with the circulation of highly immune evasive and transmissible Omicron variants. Here, we report the dynamics and durability of recalled spike-specific humoral immunity following BA.1 or BA.2 breakthrough infection, with longitudinal sampling up to 8 months post-infection. Both BA.1 and BA.2 infection robustly boosted neutralisation activity against the infecting strain while expanding breadth against other Omicron strains. Cross-reactive memory B cells against both ancestral and Omicron spike were predominantly expanded by infection, with limited recruitment ofde novoOmicron-specific B cells or antibodies. Modelling of neutralisation titres predicts that protection from symptomatic reinfection against antigenically similar strains will be remarkably durable, but is undermined by novel emerging strains with further neutralisation escape.One sentence summaryOmicron breakthrough infection elicits durable neutralising activity by recalling cross-reactive vaccine-elicited memory B cells.
Training parameters and longitudinal adaptations that most strongly mediate walking capacity gains from high-intensity interval training post-stroke
Authors: Boyne Pierce , Miller Allison , Schwab Sarah M. , Sucharew Heidi , Carl Daniel , Billinger Sandra A. , Reisman Darcy S. 
Published: February 2023

ABSTRACTBackgroundLocomotor high-intensity interval training (HIIT) has been shown to improve walking capacity more than moderate-intensity aerobic training (MAT) after stroke, but it is unclear which training parameter(s) should be prioritized (e.g. speed, heart rate, blood lactate, step count) and to what extent walking capacity gains are the result of neuromotor versus cardiorespiratory adaptations.ObjectiveAssess which training parameters and longitudinal adaptations most strongly mediate 6-minute walk distance (6MWD) gains from post-stroke HIIT.MethodsThe HIT-Stroke Trial randomized 55 persons with chronic stroke and persistent walking limitations to HIIT or MAT and collected detailed training data. Blinded outcomes included 6MWD, plus measures of neuromotor gait function (e.g. fastest 10-meter gait speed) and aerobic capacity (e.g. ventilatory threshold). This ancillary analysis used structural equation models to compare mediating effects of different training parameters and longitudinal adaptations on 6MWD.ResultsNet gains in 6MWD from HIIT versus MAT were primarily mediated by faster training speeds and longitudinal adaptations in neuromotor gait function. Training step count was also positively associated with 6MWD gains, but was lower with HIIT versus MAT, which decreased the net 6MWD gain. HIIT generated higher training heart rate and lactate than MAT, but aerobic capacity gains were similar between groups, and 6MWD changes were not associated with training heart rate, training lactate, or aerobic adaptations.ConclusionsTo increase walking capacity with post-stroke HIIT, training speed and step count appear to be the most important parameters to prioritize.
Repurposing chlorpromazine as add-on in the adjuvant phase of first-line glioblastoma therapeutic protocol in patients carrying hypo-/un-methylatedMGMTgene promoter: RACTAC, a Phase II multicenter single-arm clinical trial
Authors: Pace Andrea , Lombardi Giuseppe , Villani Veronica , Benincasa Dario , Abbruzzese Claudia , Cestonaro Ilaria , Corrà Martina , Cerretti Giulia , Caccese Mario , Silvani Antonio , Gaviani Paola , Giannarelli Diana , Paggi Marco G. 
Published: February 2023

AbstractBackgroundGlioblastoma (GBM) is a devastating brain tumor with poor prognosis, characterized by rapid growth and invasion into surrounding brain tissue. It is a hard-to-treat cancer and represents an unmet medical need. In recent years, there has been a growing interest in developing novel approaches to improve the outcomes of GBM patients; among these, drug repurposing. Our preclinical studies identified the antipsychotic chlorpromazine (CPZ) as an important modulator of signal transduction and energy metabolism in GBM cells, so we embarked on a Phase II clinical trial in which CPZ has been added to the standard disease treatment.MethodsWith these assumptions, we started a multicenter phase II clinical trial on newly diagnosed GBM patients carrying hypo-/un-methylatedMGMTgene promoter by adding CPZ to temozolomide (TMZ) in the adjuvant phase of the standard first-line therapeutic protocol RACTAC schedule). Primary endpoints: Progression-Free Survival (PFS) and Combination treatment toxicity. Secondary endpoints: Overall Survival (OS) and Quality of Life (QoL)ResultsThe RACTAC schedule showed an overall clinical benefit in GBM patients carrying hypo-/un-methylatedMGMTgene promoter. When compared with historical cohorts, these patients displayed longer PFS, with toxicity described as a dose-dependent sedation and liver toxicity, both expected. One case of severe liver toxicity has been reported. OS and QoL are still under evaluation.ConclusionsThis clinical trial confirms the anticancer properties of CPZ, as described in several preclinical studies. In addition, the RACTAC study can be considered at least as a proof-of-concept in demonstrating the effectiveness of interfering with the well-described oncogenic monoamine signaling between neurons and GBM.
Nano Sensing for Early Diagnosis of Pancreatic Cancer
Authors: Krishna Sidarth , McClelland Arthur , Zeng Tingying Helen 
Published: February 2023

AbstractPancreatic Cancer is becoming the second leading cause of cancer deaths, mainly attributed to late diagnosis. Surgical resection remains the only plausible treatment for curing patients of this cancer, but this is only possible when the cancer is localized making early detection vital. Currently, the most common early diagnostic method is the tri-phasic pancreatic-protocol CT scan. This method however has a low accuracy and specificity making it an ineffective early diagnostic. This purpose of this research was to develop a non-invasive, fast, and highly sensitive early diagnostic method for pancreatic cancer through the applications of nanotechnology. Surface Enhanced Raman Spectroscopy (SERS) is an innovative nano sensing method which results from plasmonic effect through molecules interacting with the surface of metal nanoparticles. This is a new method for trace biomarker detections and shows great potential to be an early nano-diagnostic method for Pancreatic cancer. This project uses Leucine as a biomarker for the demonstration of SERS for early pancreatic cancer detection. This is because recent studies show that Leucine has linked its overexpression with pancreatic cancer; studies have found a specificity of 100% with the use of Leucine and early diagnosis 2 to 5 years earlier than current diagnostic methods for pancreatic cancer. The parameters for SERS enhancement were optimized for the detection of Leucine using 20 nm Ag NPs. Predictive curves with linear fits were generated from an analysis of feature peaks giving the highest sensitivity for trace concentrations. This new finding shows the promising development of an early diagnostic method that is non-invasive, efficient and highly accurate for pancreatic cancer through SERS nano sensing.
Treatment of Slow-flow After Primary Percutaneous Coronary Intervention With Flow-mediated Hyperemia. The Randomized RAIN-FLOW Study
Authors: Gomez-Lara Josep , Gracida Montserrat , Rivero Fernando , Gutiérrez Alejandro , Muntané-Carol Guillem , Romaguera Rafael , Fuentes Lara , Marcano Ana , Roura Gerard , Ferreiro José Luis , Teruel Luis , Brugaletta Salvatore , Alfonso Fernando , Comín-Colet Josep , Gomez-Hospital Joan-Antoni 
Published: February 2023

AbstractBackgroundST-segment Elevation Myocardial Infarction (STEMI) complicated with no reflow after primary percutaneous coronary intervention is associated with adverse outcomes. Although several hyperemic drugs have shown to improve the Thrombolysis In Myocardial Infarction (TIMI) flow, optimal treatment of no reflow remains unsettled. Saline infusion at 20 ml/min via a dedicated microcatheter causes (flow-mediated) hyperemia. The objective is to compare the efficacy of pharmacologicvs. flow-mediated hyperemia in STEMI patients complicated with no reflow.MethodsSTEMI patients with no reflow were randomized to receive either adenosine or nitroprussidevs. flow-mediated hyperemia. The angiographic corrected TIMI Frame Count (cTFC) and the Minimal Microcirculatory Resistance (MMR), as assessed with intracoronary pressure-thermistor wire, dedicated microcatheter and thermodilution techniques, were compared after study interventions.ResultsSixty-seven were included (30 allocated to pharmacologic and 37 to flow-mediated hyperemia). After study interventions, cTFC (40.2±23.1vs. 39.2±20.7; p=0.858) and MMR (753.6±661.5vs. 993.3±740.8 Wood units; p=0.174) were similar between groups. TIMI 3 flow was observed in 26.7%vs. 27.0% (p=0.899). Flow-mediated hyperemia showed two different thermodilution patterns during saline infusion indicative of the severity of the no reflow phenomenon. In-hospital death and non-fatal heart failure were observed in 10.4% and 26.9%, respectively.ConclusionsBoth treatments showed similar (and limited) efficacy restoring coronary flow. Flow-mediated hyperemia with thermodilution pattern assessment allowed the simultaneous characterization of the no reflow degree and response to hyperemia. No reflow was associated with a high rate of adverse outcomes. Further research is warranted to prevent and to treat no reflow in STEMI patients (NCT04685941).
Predicting elevated natriuretic peptide in chest radiography: Emerging utilization gap for artificial intelligence
Authors: Kagawa Eisuke , Kato Masaya , Oda Noboru , Kunita Eiji , Nagai Michiaki , Yamane Aya , Matsui Shogo , Yoshitomi Yuki , Shimajiri Hiroto , Hirokawa Tatsuya , Ishida Shunsuke , Kurimoto Genki , Dote Keigo 
Published: February 2023

ABSTRACTAimsThis study assessed an artificial intelligence (AI) model’s performance in predicting elevated brain natriuretic peptide (BNP) levels from chest radiograms and its effect on human diagnostic performance.Methods and resultsPatients who underwent chest radiography and BNP testing on the same day were included. Data were sourced from two hospitals: one for model development, and the other for external testing. Two final ensemble models were developed to predict elevated BNP levels of >= 200 pg/mL and >= 100 pg/mL, respectively. Humans were evaluated to predict elevated BNP levels, followed by the same test, referring to the AI model’s predictions. The 8390 images from 1334 patients were collected for model creation, and 1713 images from 273 patients for tests. The AI model achieved an accuracy of 0.855, precision of 0.873, sensitivity of 0.827, specificity of 0.882, f1 score of 0.850, and receiver-operating-characteristics area-under-curve of 0.929. The accuracy of the testing with the 100 images by 35 participants significantly improved from 0.708±0.049 to 0.829±0.069 (P < 0.001) with the AI assistance (an accuracy of 0.920). Without the AI assistance, the accuracy of the experts was higher than that of non-experts (0.728±0.051 vs. 0.692±0.042, P = 0.030); however, with the AI assistance, the accuracy of the non-experts was rather higher than that of the experts (0.851±0.074 vs. 0.803±0.054, P = 0.033).ConclusionThe AI model can predict elevated BNP levels from chest radiograms and has the potential to improve human performance. The gap in utilizing new tools represents one of the emerging issues.Graphical AbstractWe developed AI models using an ensemble method to predict elevated BNP levels. The AI model achieved a higher accuracy rate than any individual participant. While the accuracy of experts was higher in the non-assisted test, with the AI assistance, the accuracy of non-experts surpassed that of the experts. AI, artificial intelligence; AUC, area-under-curve; BNP, brain natriuretic peptide; GPU, graphic processing unit; PR, precision-recall; ROC, receiver-operating-characteristics.
Towards the Genome-scale Discovery of Bivariate Monotonic Classifiers
Authors: Fourquet Océane , Krejca Martin S. , Doerr Carola , Schwikowski Benno 
Published: February 2023

AbstractMotivationBivariate monotonic classifiers (BMCs) are based on pairs of input features. Like many other models used for machine learning, they can capture non-linear patterns in high-dimensional data. At the same time, they are simple and easy to interpret. Until now, the use of BMCs on a genome scale was hampered by the high computational complexity of the search for pairs of features with a high leave-one-out performance estimate.ResultsWe introduce thefastBMCalgorithm, which drastically speeds up the identification of BMCs. The algorithm is based on a mathematical bound for the BMC performance estimate while maintaining optimality. We show empirically that fastBMC speeds up the computation by a factor of at least 15 already for a small number of features, compared to the traditional approach. For two of the three clinical datasets that we consider here, the resulting possibility of considering much larger sets of features translates into significantly improved classification performance. As an example for the high degree of interpretability of BMCs, we discuss a straightforward interpretation of a BMC glioblastoma survival predictor, an immediate novel biomedical hypothesis, options for biomedical validation, and treatment implications.ConclusionsfastBMC enables the rapid construction of robust and interpretable ensemble models using BMC, facilitating the discovery of interesting gene pairs and their contributions to the underlying biology.AvailabilityWe provide the first open-source implementation for learning BMCs, and an implementation of fastBMC in particular, all in Python, athttps://github.com/oceanefrqt/fastBMC.
Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer
Authors: García-Martínez José Manuel , Chocarro-Calvo Ana , Martínez-Useros Javier , Fernández-Aceñero María Jesús , Fiuza M. Carmen , Cáceres-Rentero Jose , De la Vieja Antonio , Barbáchano Antonio , Muñoz Alberto , Larriba María Jesús , García-Jiménez Custodia 
Published: February 2023

ABSTRACTPosttranslational modifications of epigenetic modifiers provide a flexible and timely mechanism for rapid adaptations to the dynamic environment of cancer cells. SIRT1 is an NAD+-dependent epigenetic modifier whose activity is classically associated with healthy aging and longevity, but its function in cancer is not well understood. Here, we reveal that 1α,25-dihydroxyvitamin D3(1,25(OH)2D3, calcitriol), the active metabolite of vitamin D (VD), promotes SIRT1 activation through auto-deacetylation in human colon carcinoma cells, and identify lysine 610 as an essential driver of SIRT1 activity. Remarkably, our data show that the post-translational control of SIRT1 activity mediates the antiproliferative action of 1,25(OH)2D3. This effect is reproduced by the SIRT1 activator SRT1720, suggesting that SIRT1 activators may offer new therapeutic possibilities for colon cancer patients who are VD deficient or unresponsive. Moreover, this might be extrapolated to inflammation and other VD deficiency-associated and highly prevalent diseases in which SIRT1 plays a prominent role.
Synthetic lipid rafts formed by cholesterol nano-patch induce early T cell activation
Authors: Jung Yunmin , Kim Young-Joo , Noh Kunwoo , Lee Sunmi , Kwak Minsuk 
Published: February 2023

AbstractLipid rafts cluster at the immunological synapse during activation and serve as signaling hubs in T cells. While cholesterol plays a crucial role in lipid raft formation, the impact of their spatial configuration remains less understood. Here, we introduce programmable DNA origami, cholesterol nano-patch, for nanoscale spatial control of cholesterols on live T cell membranes, enabling us to elucidate their roles in lipid raft formation, receptor activation, and intracellular signaling. We demonstrate that CNPs with high-density cholesterol arrangements efficiently bind to the T cell plasma membrane and form a large and polarized coalescence, leading to the stabilization of ordered lipid membrane domains by increasing the local concentration of cholesterols. These synthetic lipid rafts colocalize with flotillin-1, a raft-associated protein, and promote the membrane reorganization and physical segregation of key signaling molecules, such as T cell receptors, Lck and LAT kinases, and CD45. Consequently, this leads to early T cell activation in the absence of antigenic stimulation. Our DNA origami approach demonstrates the direct role of cholesterol in lipid raft formation, leading to membrane phase separation and protein reorganization, which are sufficient to induce early T cell activation.
Lupus RGMX: Social and Clinical Characteristics and their Contribution to Quality of Life in a Mexican Cohort with SLE
Authors: Ana Laura Hernández-Ledesma , Domingo Martínez , Elizabeth Fajardo-Brigido , Román-López Talía V. , Karen Nuñez-Reza , Sandra Valentina Vera del Valle , Donaji Domínguez-Zúñiga , Lizbet Tinajero-Nieto , Angélica Peña-Ayala , Estefania Torres-Valdez , Gabriel Frontana-Vázquez , Maria Gutierrez-Arcelus , Florencia Rosetti , Sarael Alcauter , Rentería Miguel E. , Ruiz-Contreras Alejandra E. , Deshiré Alpízar-Rodríguez , Alejandra Medina-Rivera 
Published: February 2023

ABSTRACTBACKGROUNDAlthough higher prevalence, disease activity, damage accumulation and mortality of systemic lupus erythematosus (SLE) are observed among Latin American, North American admixed population, African descendants and Native Americans, the information about SLE in Latin American countries, such as Mexico, is scarce.OBJECTIVESTo present Lupus RGMX, a multidisciplinary effort to generate a national digital patient registry to enrich the understanding of Mexican people with SLE.METHODSMexican patients with SLE registered between May 2021 and January 2023 in Lupus RGMX were included. Sociodemographic, socioeconomic, and clinical characteristics, along with quality-of-life perception (QoL) were assessed using self-reported data. We compared the QoL obtained from patients with SLE with two groups of non-SLE Mexican subjects. Descriptive statistics, comparisons analyses and a multivariate nonparametric regression model were performed.RESULTSA total of 1172 of lupus patients were included; of which 93.9% were women. The mean age±SD was 36.6±10.7 years, with 37.1% of the individuals between 41 and 50 years. The 24.9% reported a calculated monthly income of 430 USD (8,612 MXN). Lower QoL scores were observed in the SLE group, especially in subjects with lower socioeconomic level. Health perception, QoL perception and socioeconomic status were the variables with greater importance to predict total WHOQoL scores.CONCLUSIONThe design and implementation of Lupus RGMX imply a pioneering approach to unraveling SLE in Mexicans. Further studies from Lupus RGMX will be focused on enriching the representation of the Mexican population and include other aspects that may allow us to improve our understanding of the disease in our population.