bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cathepsin H deficiency decreases hypoxia-ischemia-induced hippocampal atrophy in neonatal mice through attenuated TLR3/IFN-β signaling
Authors: Ni Junjun , Zhao Juan , Zhang Xinwen , Reinheckel Thomas , Turk Vito , Nakanishi Hiroshi 
Published: August 2021

Abstract
Background
Cathepsin H (CatH) is a lysosomal cysteine protease with a unique aminopeptidase activity. Its expression level is increased in activated immune cells including dendritic cells, macrophages, and microglia. We have previously reported that CatH deficiency impairs toll-like receptor 3 (TLR3)-mediated activation of interferon regulatory factor 3 (IRF3), and the subsequent secretion of interferon (IFN)-β from dendritic cells. Furthermore, there is increasing evidence that IFN-β secreted from microglia/macrophages has neuroprotective effects. These observations prompted further investigation into the effects of CatH deficiency on neuropathological changes.

Methods
In this study, neuropathological changes were examined using histochemical staining (both hematoxylin-eosin (H&E) and Nissl) of the hippocampus of wild-type (WT) and CatH-deficient (CatH−/−) mice after hypoxia-ischemia (HI). The density and the localization of CatH and TLR3 were examined by immunofluorescent staining. CatH processing in microglia was assayed by pulse-chase experiments, while immunoblotting was used to examine TLR3 expression and IRF3 activation in microglia/macrophages in the presence of poly(I:C). Microglial cell death was examined by fluorescence-activated cell sorting (FACS), and primary astrocyte proliferation in the presence of IFN-β was examined using scratch wound assay.

Results
WT mice displayed severe atrophy in association with neuronal death and moderate astrogliosis in the hippocampus following neonatal HI. Somewhat surprisingly, CatH−/− mice showed marked neuronal death without severe atrophy in the hippocampus following HI. Furthermore, there was notable microglia/macrophages cell death and strong astrogliosis in the hippocampus. The TLR3 and phosphorylated IRF3 expression level in the hippocampus or splenocytes (mainly splenic macrophages); from CatH−/− mice was lower than in WT mice. In vitro experiments demonstrated that recombinant IFN-β suppressed HI-induced microglial cell death and astrocyte proliferation.

Conclusion
These observations suggest that CatH plays a critical role in the proteolytic maturation and stabilization of TLR3, which is necessary for IFN-β production. Therefore, impaired TLR3/IFN-β signaling resulting from CatH deficiency may induce microglial cell death after activation and astrogliosis/glial scar formation in the hippocampus following HI injury, leading to suppression of hippocampal atrophy.
A robot goes to rehab: a novel gamified system for long-term stroke rehabilitation using a socially assistive robot—methodology and usability testing
Authors: Feingold-Polak Ronit , Barzel Oren , Levy-Tzedek Shelly 
Published: August 2021

AbstractBackgroundSocially assistive robots (SARs) have been proposed as a tool to help individuals who have had a stroke to perform their exercise during their rehabilitation process. Yet, to date, there are no data on the motivating benefit of SARs in a long-term interaction with post-stroke patients.MethodsHere, we describe a robot-based gamified exercise platform, which we developed for long-term post-stroke rehabilitation. The platform uses the humanoid robot Pepper, and also has a computer-based configuration (with no robot). It includes seven gamified sets of exercises, which are based on functional tasks from the everyday life of the patients. The platform gives the patients instructions, as well as feedback on their performance, and can track their performance over time. We performed a long-term patient-usability study, where 24 post-stroke patients were randomly allocated to exercise with this platform—either with the robot or the computer configuration—over a 5–7 week period, 3 times per week, for a total of 306 sessions.ResultsThe participants in both groups reported that this rehabilitation platform addressed their arm rehabilitation needs, and they expressed their desire to continue training with it even after the study ended. We found a trend for higher acceptance of the system by the participants in the robot group on all parameters; however, this difference was not significant. We found that system failures did not affect the long-term trust that users felt towards the system.ConclusionsWe demonstrated the usability of using this platform for a long-term rehabilitation with post-stroke patients in a clinical setting. We found high levels of acceptance of both platform configurations by patients following this interaction, with higher ratings given to the SAR configuration. We show that it is not the mere use of technology that increases the motivation of the person to practice, but rather it is the appreciation of the technology’s effectiveness and its perceived contribution to the rehabilitation process. In addition, we provide a list of guidelines that can be used when designing and implementing other technological tools for rehabilitation.Trial registration: This trial is registered in the NIH ClinicalTrials.gov database. Registration number NCT03651063, registration date 21.08.2018.https://clinicaltrials.gov/ct2/show/NCT03651063.
Remote estimation of leaf area index (LAI) with unmanned aerial vehicle (UAV) imaging for different rice cultivars throughout the entire growing season
Authors: Gong Yan , Yang Kaili , Lin Zhiheng , Fang Shenghui , Wu Xianting , Zhu Renshan , Peng Yi 
Published: August 2021

Abstract
Background
Rice is one of the most important grain crops worldwide. The accurate and dynamic monitoring of Leaf Area Index (LAI) provides important information to evaluate rice growth and production.

Methods
This study explores a simple method to remotely estimate LAI with Unmanned Aerial Vehicle (UAV) imaging for a variety of rice cultivars throughout the entire growing season. Forty eight different rice cultivars were planted in the study site and field campaigns were conducted once a week. For each campaign, several widely used vegetation indices (VI) were calculated from canopy reflectance obtained by 12-band UAV images, canopy height was derived from UAV RGB images and LAI was destructively measured by plant sampling.

Results
The results showed the correlation of VI and LAI in rice throughout the entire growing season was weak, and for all tested indices there existed significant hysteresis of VI vs. LAI relationship between rice pre-heading and post-heading stages. The model based on the product of VI and canopy height could reduce such hysteresis and estimate rice LAI of the whole season with estimation errors under 24%, not requiring algorithm re-parameterization for different phenology stages.

Conclusions
The progressing phenology can affect VI vs. LAI relationship in crops, especially for rice having quite different canopy spectra and structure after its panicle exsertion. Thus the models solely using VI to estimate rice LAI are phenology-specific and have high uncertainties for post-heading stages. The model developed in this study combines both remotely sensed canopy height and VI information, considerably improving rice LAI estimation at both pre- and post-heading stages. This method can be easily and efficiently implemented in UAV platforms for various rice cultivars during the entire growing season with no rice phenology and cultivar pre-knowledge, which has great potential for assisting rice breeding and field management studies at a large scale.
Decoding distinctive features of plasma extracellular vesicles in amyotrophic lateral sclerosis
Authors: Pasetto Laura , Callegaro Stefano , Corbelli Alessandro , Fiordaliso Fabio , Ferrara Deborah , Brunelli Laura , Sestito Giovanna , Pastorelli Roberta , Bianchi Elisa , Cretich Marina , Chiari Marcella , Potrich Cristina , Moglia Cristina , Corbo Massimo , Sorarù Gianni , Lunetta Christian , Calvo Andrea , Chiò Adriano , Mora Gabriele , Pennuto Maria , Quattrone Alessandro , Rinaldi Francesco , D’Agostino Vito Giuseppe , Basso Manuela , Bonetto Valentina 
Published: August 2021

AbstractBackgroundAmyotrophic lateral sclerosis (ALS) is a multifactorial, multisystem motor neuron disease for which currently there is no effective treatment. There is an urgent need to identify biomarkers to tackle the disease’s complexity and help in early diagnosis, prognosis, and therapy. Extracellular vesicles (EVs) are nanostructures released by any cell type into body fluids. Their biophysical and biochemical characteristics vary with the parent cell’s physiological and pathological state and make them an attractive source of multidimensional data for patient classification and stratification.MethodsWe analyzed plasma-derived EVs of ALS patients (n = 106) and controls (n = 96), and SOD1G93Aand TDP-43Q331Kmouse models of ALS. We purified plasma EVs by nickel-based isolation, characterized their EV size distribution and morphology respectively by nanotracking analysis and transmission electron microscopy, and analyzed EV markers and protein cargos by Western blot and proteomics. We used machine learning techniques to predict diagnosis and prognosis.ResultsOur procedure resulted in high-yield isolation of intact and polydisperse plasma EVs, with minimal lipoprotein contamination. EVs in the plasma of ALS patients and the two mouse models of ALS had a distinctive size distribution and lower HSP90 levels compared to the controls. In terms of disease progression, the levels of cyclophilin A with the EV size distribution distinguished fast and slow disease progressors, a possibly new means for patient stratification. Immuno-electron microscopy also suggested that phosphorylated TDP-43 is not an intravesicular cargo of plasma-derived EVs.ConclusionsOur analysis unmasked features in plasma EVs of ALS patients with potential straightforward clinical application. We conceived an innovative mathematical model based on machine learning which, by integrating EV size distribution data with protein cargoes, gave very high prediction rates for disease diagnosis and prognosis.
SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis
Authors: Castelli Lydia M. , Cutillo Luisa , Souza Cleide Dos Santos , Sanchez-Martinez Alvaro , Granata Ilaria , Lin Ya-Hui , Myszczynska Monika A. , Heath Paul R. , Livesey Matthew R. , Ning Ke , Azzouz Mimoun , Shaw Pamela J. , Guarracino Mario R. , Whitworth Alexander J. , Ferraiuolo Laura , Milo Marta , Hautbergue Guillaume M. 
Published: August 2021

Abstract
Background
Loss of motor neurons in amyotrophic lateral sclerosis (ALS) leads to progressive paralysis and death. Dysregulation of thousands of RNA molecules with roles in multiple cellular pathways hinders the identification of ALS-causing alterations over downstream changes secondary to the neurodegenerative process. How many and which of these pathological gene expression changes require therapeutic normalisation remains a fundamental question.

Methods
Here, we investigated genome-wide RNA changes in C9ORF72-ALS patient-derived neurons and Drosophila, as well as upon neuroprotection taking advantage of our gene therapy approach which specifically inhibits the SRSF1-dependent nuclear export of pathological C9ORF72-repeat transcripts. This is a critical study to evaluate (i) the overall safety and efficacy of the partial depletion of SRSF1, a member of a protein family involved itself in gene expression, and (ii) a unique opportunity to identify neuroprotective RNA changes.

Results
Our study shows that manipulation of 362 transcripts out of 2257 pathological changes, in addition to inhibiting the nuclear export of repeat transcripts, is sufficient to confer neuroprotection in C9ORF72-ALS patient-derived neurons. In particular, expression of 90 disease-altered transcripts is fully reverted upon neuroprotection leading to the characterisation of a human C9ORF72-ALS disease-modifying gene expression signature. These findings were further investigated in vivo in diseased and neuroprotected Drosophila transcriptomes, highlighting a list of 21 neuroprotective changes conserved with 16 human orthologues in patient-derived neurons. We also functionally validated the high neuroprotective potential of one of these disease-modifying transcripts, demonstrating that inhibition of ALS-upregulated human KCNN1–3 (Drosophila SK) voltage-gated potassium channel orthologs mitigates degeneration of human motor neurons and Drosophila motor deficits.

Conclusions
Strikingly, the partial depletion of SRSF1 leads to expression changes in only a small proportion of disease-altered transcripts, indicating that not all RNA alterations need normalization and that the gene therapeutic approach is safe in the above preclinical models as it does not disrupt globally gene expression. The efficacy of this intervention is also validated at genome-wide level with transcripts modulated in the vast majority of biological processes affected in C9ORF72-ALS. Finally, the identification of a characteristic signature with key RNA changes modified in both the disease state and upon neuroprotection also provides potential new therapeutic targets and biomarkers.
Impact of baseline beta-blocker use on inotrope response and clinical outcomes in cardiogenic shock: a subgroup analysis of the DOREMI trial
Authors: Di Santo Pietro , Mathew Rebecca , Jung Richard G. , Simard Trevor , Skanes Stephanie , Mao Brennan , Ramirez F. Daniel , Marbach Jeffrey A. , Abdel-Razek Omar , Motazedian Pouya , Parlow Simon , Boczar Kevin E. , D’Egidio Gianni , Hawken Steven , Bernick Jordan , Wells George A. , Dick Alexander , So Derek Y. , Glover Christopher , Russo Juan J. , McGuinty Caroline , Hibbert Benjamin ,   the CAPITAL DOREMI investigators
Published: August 2021

AbstractBackgroundCardiogenic shock (CS) is associated with significant morbidity and mortality. The impact of beta-blocker (BB) use on patients who develop CS remains unknown. We sought to evaluate the clinical outcomes and hemodynamic response profiles in patients treated with BB in the 24 h prior to the development of CS.MethodsPatients with CS enrolled in the DObutamine compaREd to MIlrinone trial were analyzed. The primary outcome was a composite of all-cause mortality, resuscitated cardiac arrest, need for cardiac transplant or mechanical circulatory support, non-fatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite and hemodynamic response profiles derived from pulmonary artery catheters.ResultsAmong 192 participants, 93 patients (48%) had received BB therapy. The primary outcome occurred in 47 patients (51%) in the BB group and in 52 (53%) in the no BB group (RR 0.96; 95% CI 0.73–1.27;P = 0.78) throughout the in-hospital period. There were fewer early deaths in the BB group (RR 0.41; 95% CI 0.18–0.95;P = 0.03). There were no differences in other individual components of the primary outcome or in hemodynamic response between the two groups throughout the remainder of the hospitalization.ConclusionsBB therapy in the 24 h preceding the development of CS did not negatively influence clinical outcomes or hemodynamic parameters. On the contrary, BB use was associated with fewer deaths in the early resuscitation period, suggesting a paradoxically protective effect in patients with CS.Trial registrationClinicalTrials.gov Identifier: NCT03207165
MAAPER: model-based analysis of alternative polyadenylation using 3′ end-linked reads
Authors: Li Wei Vivian , Zheng Dinghai , Wang Ruijia , Tian Bin 
Published: August 2021

AbstractMost eukaryotic genes express alternative polyadenylation (APA) isoforms. A growing number of RNA sequencing methods, especially those used for single-cell transcriptome analysis, generate reads close to the polyadenylation site (PAS), termednearSitereads, hence inherently containing information about APA isoform abundance. Here, we present a probabilistic model-based method named MAAPER to utilize nearSite reads for APA analysis. MAAPER predicts PASs with high accuracy and sensitivity and examines different types of APA events with robust statistics. We show MAAPER’s performance with both bulk and single-cell data and its applicability in unpaired or paired experimental designs.
Intervention with inulin prior to and during sanative therapy to further support periodontal health: study protocol for a randomized controlled trial
Authors: Zanatta Carly A. R. , Fritz Peter C. , Comelli Elena M. , Ward Wendy E. 
Published: August 2021

Abstract
Background
Periodontal disease is a chronic state of inflammation that can destroy the supporting tissues around the teeth, leading to the resorption of alveolar bone. The initial strategy for treating periodontal disease is non-surgical sanative therapy (ST). Periodontal disease can also induce dysbiosis in the gut microbiota and contribute to low-grade systemic inflammation. Prebiotic fibers such as inulin can selectively alter the intestinal microbiota and support homeostasis by improving gut barrier functions and preventing inflammation. Providing an inulin supplement prior to and post-ST may influence periodontal health while providing insight into the complex relationship between periodontal disease and the gut microbiota. The primary objective is to determine if inulin is more effective than the placebo at improving clinical periodontal outcomes including probing depth (PD) and bleeding on probing (BOP). Secondary objectives include determining the effects of inulin supplementation pre- and post-ST on salivary markers of inflammation and periodontal-associated pathogens, as these outcomes reflect more rapid changes that can occur.

Methods
We will employ a single-center, randomized, double-blind, placebo-controlled study design and recruit and randomize 170 participants who are receiving ST to manage the periodontal disease to the intervention (inulin) or placebo (maltodextrin) group. A pilot study will be embedded within the randomized controlled trial using the first 48 participants to test the feasibility for the larger, powered trial. The intervention period will begin 4 weeks before ST through to their follow-up appointment at 10 weeks post-ST. Clinical outcomes of periodontal disease including the number of sites with PD ≥ 4 mm and the presence of BOP will be measured at baseline and post-ST. Salivary markers of inflammation, periodontal-associated pathogens, body mass index, and diet will be measured at baseline, pre-ST (after 4 weeks of intervention), and post-ST (after 14 weeks of intervention).

Discussion
We expect that inulin will enhance the positive effect of ST on the management of periodontal disease. The results of the study will provide guidance regarding the use of prebiotics prior to and as a supportive adjunct to ST for periodontal health.

Trial registration
ClinicalTrials.gov NCT04670133. Registered on 17 December 2020.
Recurrent Hurthle cell thyroid carcinoma does not preclude long-term survival: a case report and review of the literature
Authors: Blossey Richard David , Kleine-Döpke Dennis , Ringe Kristina Imeen , Pöhnert Daniel , Ringe Bastian , Klempnauer Jürgen , Beetz Oliver 
Published: August 2021

Abstract
Background
Follicular thyroid carcinoma is the second most common malignancy of the thyroid gland. In 2016, the so-called Hurthle cell thyroid carcinoma, formerly known as the oxyphilic variant of the follicular thyroid carcinoma, was reclassified by the World Health Organization as a separate pathological entity, which accounts for approximately 3% of all thyroid cancers. Although Hurthle cell thyroid carcinomas are known for their more aggressive tumor biology, metastases are observed in a minority of cases, and long-term survival can be expected. However, disseminated disease is often associated with poor outcome.

Case presentation
In the presented case, a 63-year-old Caucasian female was incidentally diagnosed with Hurthle cell thyroid carcinoma after undergoing hemithyroidectomy for a nodular goiter. Following completion thyroidectomy, two courses of radioactive iodine therapy were administered. After 4 years of uneventful follow-up, the patient gradually developed metastases in five different organs, with the majority representing unusual sites, such as heart, kidney, and pancreas over a course of 14 years. The lesions were either treated with radioactive iodine therapy or removed surgically, depending on iodine avidity.

Conclusion
Follicular and Hurthle cell thyroid carcinoma are known to potentially spread hematogenously to typical sites, such as lung or bones, however; unusual metastatic sites as presented in our case can also be observed. A search of the literature revealed only scattered reports on patients with multiple metastases in unusual locations. Furthermore, the observed long-term survival of our patient is contradictory to the existing data. As demonstrated, recurrent disease may appear years after the initial diagnosis, emphasizing the importance of consistent aftercare. Radioactive iodine therapy, extracorporeal radiation therapy, and surgical metastasectomy are central therapeutic components. In summary, our case exemplifies that thorough aftercare and aggressive treatment enables long-term survival even in recurrent Hurthle cell thyroid carcinoma displaying unusual multisite metastases.
A qualitative study on generalized Caputo fractional integro-differential equations
Authors: Kassim Mohammed D. , Abdeljawad Thabet , Shatanawi Wasfi , Ali Saeed M. , Abdo Mohammed S. 
Published: August 2021

AbstractThe aim of this article is to discuss the uniqueness and Ulam–Hyers stability of solutions for a nonlinear fractional integro-differential equation involving a generalized Caputo fractional operator. The used fractional operator is generated by iterating a local integral of the form$(I_{a}^{\rho }f)(t)=\int _{a}^{t}f(s)s^{\rho -1}\,ds$(Iaρf)(t)=∫atf(s)sρ−1ds. Our reported results are obtained in the Banach space of absolutely continuous functions that rely on Babenko’s technique and Banach’s fixed point theorem. Besides, our main findings are illustrated by some examples.
Are Latin American ecologists recognized at the world level? A global comparison
Authors: Rau Jaime R. , Jaksic Fabian M. 
Published: August 2021

Abstract
Background
Ioannidis et al. (2020) reported a standardized estimate of scientific productivity obtained from a worldwide database of 6,880,389 scientists who published at least 5 papers picked up by the Scopus database, and elaborated a ranking of ca. 120,000 scientists by both whole trajectory (career-long) impact and their current impact at year 2019. The goal of our paper is to contextualize Latin American ecologists’ contribution at the world level based on the four most scientifically productive countries in the region.

Methods and findings
Ioannidis et al. (2020) proposed a composite index that is the sum of six scientometric indicators: (1) The number of allocites, (2) the h index, (3) a per capita corrected version of h, (4) the allocites received as single author, (5) those received as single + first author, and (6) those as single + first + last author. We selected data for ecologists from Argentina, Brazil, Chile, and Mexico and comparatively analyzed their productivity according to the proposed index. We also compared these data with those obtained from a global sample of the top ecologists worldwide.

Conclusions
Based on Ioannidis et al.’s proposition to evaluate scientific productivity we extract three lessons: (1) It does not pay to publish many papers; what counts is the number of allocites (i.e., self-citations do not add up). (2) Either be single, first, or last author; it does not pay to be in the middle of an authorship line. (3) Even worse it is to be among many co-authors because the proposed index allocates credits on a per capita basis.