bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rituximab with high-dose methotrexate is effective and cost-effective in newly diagnosed primary central nervous system lymphoma
Authors: Yuan Xianggui , Yu Teng , Huang Yurong , Jiang Huawei , Xu Xiaohua , Liang Yun , Qian Wenbin 
Published: December 2022

AbstractInduction chemotherapy based on high-dose methotrexate is considered as the standard approach for newly diagnosed primary central nervous system lymphomas (PCNSLs). However, the best combination chemotherapeutic regimen remains unclear. This study aimed to determine the efficacy and toxicities of rituximab with methotrexate (R-M regimen). Consecutive 37 Chinese patients receiving R-M regimen as induction chemotherapy were retrospectively identified from January 2015 to June 2020 from our center in eastern China. Fourteen patients receiving rituximab plus methotrexate with cytarabine (R-MA regimen) at the same period were identified as the positive control group. The response rates, survival, toxicities, length of hospital stay (LOS), and cost were compared. Compared with the R-MA regimen, the R-M regimen showed comparable response rate and survival outcomes, but had fewer grade 3–4 hematological toxicities, shorter LOS, lower mean total hospitalization cost and lower mean total antibiotic cost. Complete remission at the end of induction chemotherapy and ECOG > 3 were independent prognostic factors for overall survival. In conclusion, R-M regimen is an effective and cost-effective combination treatment for PCNSLs, which warrants further evaluation in randomized trials.
New fossil assemblages from the Early Ordovician Fezouata Biota
Authors: Saleh Farid , Vaucher Romain , Vidal Muriel , Hariri Khadija El , Laibl Lukáš , Daley Allison C. , Gutiérrez-Marco Juan Carlos , Candela Yves , Harper David A. T. , Ortega-Hernández Javier , Ma Xiaoya , Rida Ariba , Vizcaïno Daniel , Lefebvre Bertrand 
Published: December 2022

AbstractThe Fezouata Biota (Morocco) is a unique Early Ordovician fossil assemblage. The discovery of this biota revolutionized our understanding of Earth’s early animal diversifications—the Cambrian Explosion and the Ordovician Radiation—by suggesting an evolutionary continuum between both events. Herein, we describe Taichoute, a new fossil locality from the Fezouata Shale. This locality extends the temporal distribution of fossil preservation from this formation into the upper Floian, while also expanding the range of depositional environments to more distal parts of the shelf. In Taichoute, most animals were transported by density flows, unlike the in-situ preservation of animals recovered in previously investigated Fezouata sites. Taichoute is dominated by three-dimensionally preserved, and heavily sclerotized fragments of large euarthropods—possibly representing nektobenthic/nektic bivalved taxa and/or hurdiid radiodonts. Resolving whether this dominance reflects a legitimate aspect of the original ecosystem or a preservational bias requires an in-depth assessment of the environmental conditions at this site. Nevertheless, Taichoute provides novel preservational and palaeontological insights during a key evolutionary transition in the history of life on Earth.
A soft supernumerary hand for rehabilitation in sub-acute stroke: a pilot study
Authors: Trompetto Carlo , Catalano Manuel G. , Farina Alessandro , Grioli Giorgio , Mori Laura , Ciullo Andrea , Pittaluga Matteo , Rossero Martina , Puce Luca , Bicchi Antonio 
Published: December 2022

AbstractIn patients with subacute stroke, task specific training (TST) has been shown to accelerate functional recovery of the upper limb. However, many patients do not have sufficient active extension of the fingers to perform this treatment. In these patients, here we propose a new rehabilitation technique in which TST is performed through a soft robotic hand (SoftHand-X). In short, the extension of the robotic fingers is controlled by the patient through his residual, albeit minimal, active extension of the fingers or wrist, while the patient was required to relax the muscles to achieve full flexion of the robotic fingers. TST with SoftHand-X was attempted in 27 subacute stroke patients unable to perform TST due to insufficient active extension of the fingers. Four patients (14.8%) were able to perform the proposed treatment (10 daily sessions of 60 min each). They reported an excellent level of participation. After the treatment, both clinical score of spasticity and its electromyographic correlate (stretch reflex) decreased. In subacute stroke patients, TST using SoftHand-X is a well-accepted treatment, resulting in a decrease of spasticity. At present, it can be applied only in a small proportion of the patients who cannot perform conventional TST, though extensions are possible.
Quantitative environmental DNA metabarcoding shows high potential as a novel approach to quantitatively assess fish community
Authors: Tsuji Satsuki , Inui Ryutei , Nakao Ryohei , Miyazono Seiji , Saito Minoru , Kono Takanori , Akamatsu Yoshihisa 
Published: December 2022

AbstractThe simultaneous conservation of species richness and evenness is important to effectively reduce biodiversity loss and keep ecosystem health. Environmental DNA (eDNA) metabarcoding has been used as a powerful tool for identifying community composition, but it does not necessarily provide quantitative information due to several methodological limitations. Thus, the quantification of eDNA through metabarcoding is an important frontier of eDNA-based biomonitoring. Particularly, the qMiSeq approach has recently been developed as a quantitative metabarcoding method and has attracted much attention due to its usefulness. The aim here was to evaluate the performance of the qMiSeq approach as a quantitative monitoring tool for fish communities by comparing the quantified eDNA concentrations with the results of fish capture surveys. The eDNA water sampling and the capture surveys using the electrical shocker were conducted at a total of 21 sites in four rivers in Japan. As a result, we found significant positive relationships between the eDNA concentrations of each species quantified by qMiSeq and both the abundance and biomass of each captured taxon at each site. Furthermore, for seven out of eleven taxa, a significant positive relationship was observed between quantified DNA concentrations by sample and the abundance and/or biomass. In total, our results demonstrated that eDNA metabarcoding with the qMiSeq approach is a suitable and useful tool for quantitative monitoring of fish communities. Due to the simplicity of the eDNA analysis, the eDNA metabarcoding with qMiSeq approach would promote further growth of quantitative monitoring of biodiversity.
Deep kernel learning of dynamical models from high-dimensional noisy data
Authors: Botteghi Nicolò , Guo Mengwu , Brune Christoph 
Published: December 2022

AbstractThis work proposes a stochastic variational deep kernel learning method for the data-driven discovery of low-dimensional dynamical models from high-dimensional noisy data. The framework is composed of an encoder that compresses high-dimensional measurements into low-dimensional state variables, and a latent dynamical model for the state variables that predicts the system evolution over time. The training of the proposed model is carried out in an unsupervised manner, i.e., not relying on labeled data. Our learning method is evaluated on the motion of a pendulum—a well studied baseline for nonlinear model identification and control with continuous states and control inputs—measured via high-dimensional noisy RGB images. Results show that the method can effectively denoise measurements, learn compact state representations and latent dynamical models, as well as identify and quantify modeling uncertainties.
Role of poly(ADP-ribose) polymerase-1 in regulating human islet cell differentiation
Authors: Dadheech Nidheesh , Srivastava Abhay , Shah Rashmi G. , Shah Girish M. , Gupta Sarita 
Published: December 2022

AbstractPoly(ADP-ribose) polymerase-1 (PARP1), a fundamental DNA repair enzyme, is known to regulate β cell death, replication, and insulin secretion. PARP1 knockout (KO) mice are resistant to diabetes, while PARP1 overactivation contributes to β cell death. Additionally, PARP1 inhibition (PARPi) improves diabetes complications in patients with type-2 diabetes. Despite these beneficial effects, the use of PARP1 modulating agents in diabetes treatment is largely neglected, primarily due to the poorly studied mechanistic action of PARP1 catalytic function in human β cell development. In the present study, we evaluated PARP1 regulatory action in human β cell differentiation using the human pancreatic progenitor cell line, PANC-1. We surveyed islet census and histology from PARP1 wild-type versus KO mice pancreas in a head-to-head comparison with PARP1 regulatory action for in-vitro β cell differentiation following either PARP1 depletion or its pharmacological inhibition in PANC-1-differentiated islet cells. shRNA mediated PARP1 depleted (SiP) and shRNA control (U6) PANC-1 cells were differentiated into islet-like clusters using established protocols. We observed complete abrogation of new β cell formation with absolute PARP1 depletion while its inhibition using the potent inhibitor, PJ34, promoted the endocrine β cell differentiation and maturation. Immunohistochemistry and immunoblotting for key endocrine differentiation players along with β cell maturation markers highlighted the potential regulatory action of PARP1 and augmented β cell differentiation due to direct interaction of unmodified PARP1 protein elicited p38 MAPK phosphorylation and Neurogenin-3 (Ngn3) re-activation. In summary, our study suggests that PARP1 is required for the proper development and differentiation of human islets. Selective inhibition with PARPi can be an advantage in pushing more insulin-producing cells under pathological conditions and delivers a potential for pilot clinical testing for β cell replacement cell therapies for diabetes.
A novel small molecule inhibitor of human Drp1
Authors: Rosdah Ayeshah A. , Abbott Belinda M. , Langendorf Christopher G. , Deng Yali , Truong Jia Q. , Waddell Helen M. M. , Ling Naomi X. Y. , Smiles William J. , Delbridge Lea M. D. , Liu Guei-Sheung , Oakhill Jonathan S. , Lim Shiang Y. , Holien Jessica K. 
Published: December 2022

AbstractMitochondrial dynamin-related protein 1 (Drp1) is a large GTPase regulator of mitochondrial dynamics and is known to play an important role in numerous pathophysiological processes. Despite being the most widely used Drp1 inhibitor, the specificity of Mdivi-1 towards human Drp1 has not been definitively proven and there have been numerous issues reported with its use including off-target effects. In our hands Mdivi-1 showed varying binding affinities toward human Drp1, potentially impacted by compound aggregation. Herein, we sought to identify a novel small molecule inhibitor of Drp1. From an initial virtual screening, we identified DRP1i27 as a compound which directly bound to the human isoform 3 of Drp1 via surface plasmon resonance and microscale thermophoresis. Importantly, DRP1i27 was found to have a dose-dependent increase in the cellular networks of fused mitochondria but had no effect in Drp1 knock-out cells. Further analogues of this compound were identified and screened, though none displayed greater affinity to human Drp1 isoform 3 than DRP1i27. To date, this is the first small molecule inhibitor shown to directly bind to human Drp1.
How, where and when to screen for porcine cytomegalovirus (PCMV) in donor pigs for xenotransplantation
Authors: Halecker S. , Hansen S. , Krabben L. , Ebner F. , Kaufer B. , Denner J. 
Published: December 2022

AbstractPorcine cytomegalovirus (PCMV), that is actually a porcine roseolovirus (PRV), is a common herpesvirus in domestic pigs and wild boars. In xenotransplantation, PCMV/PRV has been shown to significantly reduce the survival time of pig kidneys and hearts in preclinical trials with different non-human primates. Furthermore, PCMV/PRV has been transmitted in the first pig to human heart xenotransplantation and contributed to the death of the patient. Although transmitted to the recipient, there is no evidence that PCMV/PRV can infect primate cells including human cells. PCMV/PRV is closely related to the human herpesviruses 6 and 7, and only distantly related to the human CMV (HCMV). Antiviral drugs used for the treatment of HCMV are less effective against PCMV/PRV. However, there are well described strategies to eliminate the virus from pig facilities. In order to detect the virus and to eliminate it, highly sensitive detection methods and the knowledge of how, where and when to screen the donor pigs is required. Here, a comparative testing of organs from pigs of different ages using polymerase chain reaction (PCR)-based and immunological methods was performed. Testing young piglets, PCMV/PRV was detected effectively by PCR in blood, bronchoalveolar lavage fluid, tonsils and heart. In adult animals, detection by PCR was not successful in most cases, because the virus load was below the detection limit or the virus was in its latent stage. Therefore, detection of antibodies against selected recombinant proteins corresponding to epitopes detected by nearly all infected animals in a Western blot assay is advantageous. By contrast, immunological testing is not beneficial in young animals as piglets might have PCMV/PRV-specific antibodies obtained from their infected mother via the colostrum. Using a thoughtful combination of PCR-based and immunological methods, detection of PCMV/PRV in donor pigs for xenotransplantation is feasible and a controlled elimination of the virus by early weaning or other methods is possible.
Integrated analysis of Hashtgerd plain deformation, using Sentinel-1 SAR, geological and hydrological data
Authors: Khoshlahjeh Azar Mahdi , Shami Siavash , Nilfouroushan Faramarz , Salimi Maryam , Ghayoor Bolorfroshan Mahdieh , Reshadi Mir Amir Mohammad 
Published: December 2022

AbstractDue to its proximity to Tehran, the Hashtgerd catchment in Iran is an important region that has experienced alarming subsidence rates in recent years. This study estimated the ground surface deformation in the Hashtgerd plain between 2015 and 2020 using Sentinel-1 SAR data and InSAR technique. The average LOS displacement of the ascending and descending tracks was − 23 cm/year and − 22 cm/year, respectively. The central area of the plain experienced the greatest vertical subsidence, with a more than − 100 cm cumulative displacement. The Karaj-Qazvin railway and highway that pass through this area have been damaged by subsidence, according to an analysis of profiles drawn along the transportation lines. The southern sections of Hashtgerd city have experienced a total displacement of − 30 cm/year over the course of about 6 years. The relationship between changes in groundwater level and subsidence rate in this region was examined using piezometer and precipitation data. Geoelectric sections and piezometric well logs were also utilized to investigate the geological characteristics of the Hashtgerd aquifer. According to the findings, the leading causes of subsidence were uncontrolled groundwater abstraction. This research highlights the need to comprehend the spatial distribution of confined aquifers and their effect on subsidence, which can aid in the development of a suitable management strategy to restore these aquifers.
A few-shot approach for COVID-19 screening in standard and portable chest X-ray images
Authors: Cores Daniel , Vila-Blanco Nicolás , Pérez-Alarcón María , Martínez-de-Alegría Anxo , Mucientes Manuel , Carreira María J. 
Published: December 2022

AbstractReliable and effective diagnostic systems are of vital importance for COVID-19, specifically for triage and screening procedures. In this work, a fully automatic diagnostic system based on chest X-ray images (CXR) has been proposed. It relies on the few-shot paradigm, which allows to work with small databases. Furthermore, three components have been added to improve the diagnosis performance: (1) a region proposal network which makes the system focus on the lungs; (2) a novel cost function which adds expert knowledge by giving specific penalties to each misdiagnosis; and (3) an ensembling procedure integrating multiple image comparisons to produce more reliable diagnoses. Moreover, the COVID-SC dataset has been introduced, comprising almost 1100 AnteroPosterior CXR images, namely 439 negative and 653 positive according to the RT-PCR test. Expert radiologists divided the negative images into three categories (normal lungs, COVID-related diseases, and other diseases) and the positive images into four severity levels. This entails the most complete COVID-19 dataset in terms of patient diversity. The proposed system has been compared with state-of-the-art methods in the COVIDGR-1.0 public database, achieving the highest accuracy (81.13% ± 2.76%) and the most robust results. An ablation study proved that each system component contributes to improve the overall performance. The procedure has also been validated on the COVID-SC dataset under different scenarios, with accuracies ranging from 70.81 to 87.40%. In conclusion, our proposal provides a good accuracy appropriate for the early detection of COVID-19.
Delivery of streptomycin to the rat colon by use of electrospun nanofibers
Authors: Guerra Priscila R. , Ajalloueian Fatemeh , Wei Shaodong , Kristensen Katja Ann , Bahl Martin Iain , Boisen Anja , Licht Tine Rask 
Published: December 2022

AbstractDrug-loaded electrospun nanofibers are potential drug carrier systems that may optimize disease treatment while reducing the impact on commensal microbes. The feasibility of streptomycin-loaded pullulan nanofibers fabricated from a green electrospinning procedure using water as the solvent was assessed. We conducted a rat study including a group treated with streptomycin-loaded nanofibers (STR-F, n = 5), a group treated with similar concentrations of streptomycin in the drinking water (STR-W, n = 5), and a non-treated control group (CTR, n = 5). Streptomycin was successfully loaded into nanofibers and delivered by this vehicle, which minimized the quantity of the drug released in the ileal compartment of the gut. Ingested streptomycin-resistant E. coli colonized of up to 106 CFU/g feces, revealing a selective effect of streptomycin even when given in the low amounts allowed by the nanofiber-based delivery. 16S amplicon sequencing of the indigenous microbiota revealed differential effects in the three groups. An increase of Peptostreptococcaceae in the cecum of STR-F animals may indicate that the fermentation of nanofibers directly or indirectly promoted growth of bacteria within this family. Our results elucidate relevant properties of electrospun nanofibers as a novel vehicle for delivery of antimicrobials to the large intestine.
Polytrauma patients with severe cervical spine injuries are different than with severe TBI despite similar AIS scores
Authors: van Wessem Karlijn J. P. , Niemeyer Menco J. S. , Leenen Luke P. H. 
Published: December 2022

AbstractTraumatic cervical spine injuries (TCSI) are rare injuries. With increasing age the incidence of TCSI is on the rise. TCSI and traumatic brain injury (TBI) are often associated. Both TCSI and TBI are allocated to the Abbreviated Injury Scale (AIS) head region. However, the nature and outcome of these injuries are potentially different. Therefore, the aim of this study was to investigate the epidemiology, demographics and outcome of severely injured patients with severe TCSI, and compare them with polytrauma patients with severe TBI in the strict sense. Consecutive polytrauma patients aged ≥ 15 years with AIShead ≥ 3 who were admitted to a level-1 trauma center Intensive Care Unit (ICU) from 2013 to 2021 were included. Demographics, treatment, and outcome parameters were analyzed for patients who had AIShead ≥ 3 based on TCSI and compared to patients with AIShead ≥ 3 based on proper TBI. Data on follow-up were collected for TCSI patients. Two hundred eighty-four polytrauma patients (68% male, Injury Severity Score (ISS) 33) with AIShead ≥ 3 were included; Thirty-one patients (11%) had AIShead ≥ 3 based on TCSI whereas 253 (89%) had AIShead ≥ 3 based on TBI. TCSI patients had lower systolic blood pressure in the Emergency Department (ED) and stayed longer in ICU than TBI patients. There was no difference in morbidity and mortality rates. TCSI patients died due to high cervical spine injuries or respiratory insufficiency, whereas TBI patients died primarily due to TBI. TCSI was mainly located at C2, and 58% had associated spinal cord injury. Median follow-up time was 22 months. Twenty-two percent had improvement of the spinal cord injury, and 10% died during follow-up. In this study the incidence of severe TCSI in polytrauma was much lower than TBI. Cause of death in TCSI was different compared to TBI demonstrating that AIShead based on TCSI is a different entity than based on TBI. In order to avoid data misinterpretation injuries to the cervical spine should be distinguished from TBI in morbidity and mortality analysis.
DCZ19931, a novel multi-targeting kinase inhibitor, inhibits ocular neovascularization
Authors: Zhang Huiying , Li Bo , Ding Jingjuan , Ye Rong , Xu Zhijian , Zhang Qiuyang , Feng Siguo , Jiang Qin , Zhu Weiliang , Yan Biao 
Published: December 2022

AbstractNeovascularization is a prominent cause of irreversible blindness in a variety of ocular diseases. Current therapies for pathological neovascularization are concentrated on the suppression of vascular endothelial growth factors (VEGF). Despite the remarkable efficacy of anti-VEGF drugs, several problems still exist, including ocular complications and drug resistance. Thus, it is still required to design novel drugs for anti-angiogenic treatment. This study aimed to investigate the anti-angiogenic effects of a small molecule multi-target tyrosine kinase inhibitor, DCZ19931, on ocular neovascularization. The results showed that administration of DCZ19931 at the tested concentrations did not cause obvious cytotoxicity and tissue toxicity. DCZ19931 could reduce the size of choroidal neovascularization (CNV) lesions in laser-induced CNV model and suppress ocular neovascularization in oxygen-induced retinopathy (OIR) model. DCZ19931 could suppress VEGF-induced proliferation, migration, and tube formation ability of endothelial cells, exhibiting similar anti-angiogenic effects as Ranibizumab. DCZ19931 could reduce the levels of intercellular cell adhesion molecule-1 (ICAM-1) expression in vivo and in vitro. Network pharmacology prediction and western blots revealed that DCZ19931 exerted its anti-angiogenic effects through the inactivation of ERK1/2-MAPK signaling and p38-MAPK signaling. In conclusion, this study indicates that DCZ19931 is a promising drug for anti-angiogenic therapy for ocular diseases.