bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective removal of misfolded SOD1 delays disease onset in a mouse model of amyotrophic lateral sclerosis
Authors: Guan Teng , Zhou Ting , Zhang Xiaosha , Guo Ying , Yang Chaoxian , Lin Justin , Zhang Jiasi Vicky , Cheng Yongquan , Marzban Hassan , Wang Yu-Tian , Kong Jiming 
Published: February 2023

Abstract
Background
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. There is no cure currently. The discovery that mutations in the gene SOD1 are a cause of ALS marks a breakthrough for the search of effective treatments for ALS. SOD1 is an antioxidant that is highly expressed in motor neurons. Human SOD1 is prone to aberrant modifications. Familial ALS-linked SOD1 variants are particularly susceptible to aberrant modifications. Once modified, SOD1 undergoes conformational changes and becomes misfolded. This study aims to determine the effect of selective removal of misfolded SOD1 on the pathogenesis of ALS.
Methods
Based on chaperone-mediated protein degradation pathway, we designed a fusion peptide named CT4, and tested its efficiency in knocking down intracellularly misfolded SOD1 and its efficacy in modifying pathogenesis of ALS.
Results
Expression of plasmid carrying the CT4 sequence in human HEK cells resulted in robust removal of misfolded SOD1 induced by serum deprivation. Co-transfection of the CT4 and the human SOD1 G93A plasmids at various ratios in rat PC12 cells demonstrated a dose-dependent knockdown efficiency on G93A, which could be further increased when misfolding of SOD1 was enhanced by serum deprivation. Application of the full length CT4 peptide to primary cultures of neurons expressing the G93A variant of human SOD1 revealed a time-course of the degradation of misfolded SOD1; misfolded SOD1 started to decrease by 2 h after the application of CT4 and disappeared by 7 h. Intravenous administration of the CT4 peptide at 10 mg/kg to the G93A mice at the age of 4 months old induced reduction of human SOD1 in spinal cord tissue by 68% in 24 h and 54% in 48 h. Intraperitoneal administration of the CT4 peptide starting from 60 days of age significantly delayed the onset of ALS and prolonged the lifespan of the G93A mice.
Conclusions
The CT4 peptide directs degradation of misfolded SOD1 in high efficiency and specificity. Selective removal of misfolded SOD1 significantly delays the onset of ALS, demonstrating that misfolded SOD1 is the toxic form of SOD1 that causes motor neuron death. The study provides a proof of concept that selective removal of misfolded SOD1 is a promising treatment for ALS.
Anti-cgrp Monoclonal Antibodies in Chronic Migraine Prophilaxys: Efficacy and Safety in Patients Treated With Botulinum Toxin a
Authors: Butera Calogera , Cetta Ilaria , Messina Roberta , Zanandrea Laura , Santangelo Roberto , Colombo Bruno , Filippi Massimo , Carro Ubaldo Del 
Published: February 2023

Abstract
Since the high burden of chronic migraine (CM), it is challenging to identify the best prevention treatment. Based on the preclinical evidences about the different therapeutic targets of OnabotulinumtoxinA (BT-A), acting on C-fibers and anti-CGRP monoclonal antibodies (mAbs) acting on Aδ-fibers, the rationale of using as alternative or combining therapies has been hypothesized.
Until now, the association of BT-A and mAbs has been poorly investigated.
This study aimed to evaluate whether mAbs is effective and safe in CM patients previously treated with BT-A, either as alternative or add-on treatment. We enrolled 47 patients: according to the response to BT-A treatment, patients were defined Non-responder (NR) and Partial-responder (PR). NR were shifted to mAbs. PR were randomly divided into those who added mAbs therapy (PR-P) and those who shifted treatment (PR-S), interrupting BT-A. Clinical variables were collected at baseline, after three and six months.
Study results evidenced the efficacy of mAbs in improving clinical outcomes in CM patients, with a better response in PR group. No statistically significant differences of clinical changes were observed between PR-P and PR-S groups. No safety concerns were raised in combined treatments. Preventive prophylaxis with mAbs is effective, even in difficult to treat CM patients. Further studies, with a larger sample size, are needed to highlight a potential additive effect of combined therapies.
Effects of plant extracts on in-vitro gas production kinetics and ruminal fermentation of four fibrous feeds: Thought sustainable animal diets
Authors: Gonzalez-Ronquillo Manuel , Ghavipanje Navid , Sainz-Ramírez Aurora , Celis-Alvarez Maria Danaee , Plata-Reyes Dalia Andrea , Jimenez Lizbeth E. Robles , VARGAS-BELLO-PEREZ EINAR 
Published: February 2023

Abstract
This study was conducted to investigate the effects of increasing doses: 0 (control), 6 (low), 12 (medium), and 18 (high) ml/g DM of plant extracts (Moringa, Thyme, and Rosemary) on in-vitro gas production (IVGP) of four fibrous feeds (Penisetum clandestium, Alfalfa hay, Oat hay, and corn stover). IVGP were assessed using three fistulated goats and incubation of samples at specified times. At the end of incubation, the dry matter degradability (DMd), gas yield (GY24), metabolizable energy (ME), short chain fatty acids (SCFA), and microbial crude protein production (MCP) were determined. The results showed that the increasing extract dose had neither linear nor quadratic effect (P > 0.05) on gas production (GP) of all fibrous feeds. Addition of plant extract also increased (P ≤ 0.05) GP at all incubation times being higher for Thyme. Addition of Moringa, Thyme, and Rosemary extracts altered ruminal fermentation parameters including ME, MCP, SCFA, the partitioning factor at 72 h of incubation (PF72), and DMd being higher for Thyme followed by Rosemary and Moringa. As a conclusion, the inclusion of Thyme increases GP, ME, MCP, SCFA, PF72, and DMd compared with Rosemary and Moringa plant extracts. However, additional in-vivo studies should be conducted to confirm these effects.
Molecular evolution in different subtypes of multifocal hepatocellular carcinoma
Authors: Ding Keyue , Tang Xia , Xiang Lei , Li Qingshu , Shao Yue , Wan Li , Zhao Dachun , Li Xiaoyuan , Wu Songfeng , Wang Haijian , Li Dewei 
Published: February 2023

Abstract
Background: Multifocal hepatocellular carcinoma (MF-HCC) accounts for >40% of HCCs, demonstrating a poor prognosis than single primary HCCs. Characterizing the dynamic changes of mutation signature along with clonal evolution, quantifying intrahepatic metastatic timing, and investigating the genetic structure in the preneoplastic stage underlying different subtypes of MF-HCC are important for understanding their molecular evolution and developing a precision management strategy.
Methods: We conducted whole-exome sequencing in 74 tumor samples from spatially distinct regions in 35 resected tumor lesions and adjacent non-cancerous tissues in 11 patients with synchronous MF-HCCs, 15 histologically confirmed preneoplastic lesions and six samples from peripheral blood mononuclear cell. We also used the previously published MF-HCC cohorts (n=9) as an independent validation dataset.
Results: We classified MF-HCCs into three subtypes, including intrahepatic metastasis, multicentric occurrence, and mixed intrahepatic metastasis and multicentric occurrence. The dynamic changes in mutation signatures between tumor subclonal expansions demonstrated varied etiologies underlying the clonal progression in different MF-HCC subtypes, especially the contribution of aristolochic acid exposure decreased along with subclonal expansions. The clonal evolution in intrahepatic metastasis exhibited an early metastatic seeding that occurred at 10-4–0.01 cm3 in primary tumor volume, below the limitation in clinical detection. These findings were validated in another independent cohort. In addition, for multicentric occurrence MF-HCC, mutational footprints in the preneoplastic lesions revealed common preneoplastic arising clones, evidently being ancestors of different tumor sites.
Conclusion: Our study comprehensively characterized the dynamic mutational signature, early metastatic timing, and common preneoplastic clones in multicentric occurrence that characterized the varied tumor clonal evolutionary history underlying different subtypes of MF-HCC, and provided important implications for optimizing personalized clinical management for MF-HCC.
Almajiri Health; A Scoping Review on Disease, Health Literacy and Space for Participatory Research
Authors: Muhammad Muzzammil Imran , Abdulsalam Amna Hassana , Petit-Clair Fadhina , Acquaye Amber , Nobles Autumn , Fleischer Brian , Konkwo Chigoziri , Ransome Yusuf , Paintsil Elijah 
Published: February 2023

Abstract
Introduction Almajirai are male children in Northern Nigeria and Southern Niger who study Islam in the almajiranci system. Almajiranci has been associated with non-participation in formal education, abuse, poverty, and underdevelopment. However, the peer-reviewed literature around health among almajirai remains limited. We conduct a scoping review around almajiri health to synthesize evidence for health problems, draw links between findings, identify research gaps, indicate areas for intervention, and assess participatory approaches in this literature. Methods We searched the academic literature for articles concerning almajiri heath using a framework integrating the biopsychosocial and socio-ecological models of health. We included articles in English and French published between 2000 and 2022. For each study we collected information regarding authorship, study year and location(s), study design and aims, sample characteristics, findings, and almajiri participation in research design, execution, interpretation and dissemination. Results Of 1,944 studies, 17 were found relevant for data extraction. These included 14 cross-sectional studies, 2 descriptive articles, and one case-control study. All were conducted in Nigeria, though one included Nigerien almajirai. No study engaged almajirai in participatory roles. Domains evaluated included infectious disease (10 studies), oral health (2 studies), workplace injury, nutrition, health status, health determinants, and mental health (1 study each). Almajirai represented ranged from 3 to 28 years old. Included studies find high rates of malaria, intestinal parasitosis, urinary tract infection, N. meningitidis, and occupational injury among almajirai. Studies comparing almajirai to controls find significantly higher rates of cholera, urinary schistosomiasis, and psychiatric disorders, lower levels of rabies awareness and poorer oral hygiene among almajirai (p < 0.05). One study, concerning nutrition, describes an intervention to improve almajiri health, though does not provide health outcomes for that intervention. Conclusion We observe that the literature around almajiri health has concerned many domains, though the number of studies within these remains limited. We further note limitations in the geographic scope of this literature, interventions to improve almajiri health, and the consideration of demographic features, like age, that may influence almajiri health. We stress the need for further study in these areas, and for participatory approaches, which may be more likely to effectively improve almajiri health.
A Deep Insight into the Selectivity Difference Between Y(III) and La(III) Ions Toward D2EHPA Ligand: Experimental and DFT Study
Authors: Alizadeh Shahab , Abdollahy Mahmoud , Darban Ahmad Khodadadi , Mohseni Mehdi 
Published: February 2023

Abstract
The twofold extraction behavior of light and heavy rare earth elements transforms into a more selective extraction of heavy rare earth elements when Di-(2-ethylhexyl) phosphoric acid (D2EHPA), one of the commonest cation exchange extractants, is employed. However, why this phenomenon has not been fully investigated from the quantum perspective yet. To confirm and interpret the laboratory-observed selectivity results in the extraction of Y(III) over than La(III), this study utilized the Density Functional theory (DFT) connected with Born Haber thermodynamic besides importing the solvent effect through the Conductor-Like Screening Model (COSMO). The hydration reaction energies of La(III) and Y(III) were estimated at -383.7 kcal/mol and -171.83 kcal/mol according to the cluster solvation model. It was observed that, among other influential factors, hydration energy is a critical one in the rate of the extraction free energy of every rare earth element and its tendency to be transferred to the organic phase in reacting to the extractant ligand. It was shown that the experimental ∆∆Gext results (2.1 kcal/mol) enjoyed a proper consonance with the ∆∆Gext results of DFT calculations (1.3 kcal/mol). In the pursuit of discovering the reasons for this phenomenon, the orbital structure of every aqueous and organic complex was studied, and the significant differences in energy magnitudes were discussed. The current comprehensive design of experimental studies and calculations can give birth to a deeper understanding of the interactions of the D2EHPA extractant with La(III) and Y(III).
Development of the entropy theory for wind speed monitoring by using copula-based approach
Authors: Tahroudi Mohammad Nazeri , Ramezani Yousef , De Michele Carlo , Mirabbasi Rasoul 
Published: February 2023

Abstract
The purpose of this study is to development of the entropy theory by using copula-based approach for temporal and spatial monitoring of wind speeds in the Lut Desert, Iran at Bam, Tabas and Birjand stations in the period of 1973–2020. The conventional entropy method was improved by the two methods. In the first method, vine copulas were used to evaluate the interaction between the stations. At the second method, in addition to the first method, a 2-D copula function was used to analyze the joint frequency and conditional occurrence probability. In the first method, A D-vine copula was selected to simulate the wind speed at each station according to the wind speed at the other stations. In the second method, Frank copula function was used to joint probability analysis. The results of comparing the information transfer index in the two methods and the conventional entropy method showed that the percentage increase of this index in the first method at the Bam, Birjand and Tabas stations compared to the conventional entropy method is 25, 0 and 23%, respectively. This increase in the second method compared to the conventional entropy method at the mentioned stations is 24, 10 and 33%, respectively.
Radial deformation and stress distribution of grinding wheel on surface grinding
Authors: Zhang Chengxiang , Li Yanguo , Zou Qin , Luo Wenqi , Dai Lifeng , Lv Junyi , Li Kenan 
Published: February 2023

Abstract
High machining accuracy is the unremitting pursuit of grinding technology. The radial deformation of grinding wheel is an important factor affecting the machining accuracy of workpiece. In this study, a force model of grinding wheel during grinding was established, considering centrifugal force and distribution grinding force. The radial displacement and Mises stress distribution of grinding wheel under different grinding parameters (peripheral velocity, grinding depth and feed speed) were obtained by finite element simulation based on the established force model. The simulation results showed that the radial deformation of lowest point of the grinding wheel was most affected by peripheral speed, which increased with the increase of peripheral speed, and decreased with the increase of grinding depth and feed speed. The actual grinding depth had deviation caused by the radial deformation of grinding wheel, especially in grinding with large grinding depth and feed speed. The deviation value of grinding depth was also calculated. This work can provide reference for compensating the deviation and has certain engineering significance for improving the machining accuracy of workpieces.
Exploring the Link Between Mtor Inhibitors and Interstitial Lung Diseases: A Disproportionality Analysis Using Fda Adverse Event Reporting System Database
Authors: Shaji Anakha , Sony Aliena , Mytheen Shefin , Tom Antriya Annie 
Published: February 2023

Abstract
Background: The mammalian target of rapamycin (mTOR) inhibitors are immunosuppressive agents used to prevent organ transplant rejection. This class of drugs has shown significant high incidence of interstitial lung disease (ILD).
Objective: This study aims to find out the potential safety signal associated between mTOR inhibitors and ILD by Food and Drug Administration Adverse Event Reporting System (FAERS) databases.
Methods: Publicly available FAERS database was used to perform a case/non-case retrospective disproportionality analysis (2009Q1 to 2022Q3). OpenVigil 2.1MedDRA v24 was used to extract and filter data from FAERS database. The preferred term used for the study was “interstitial lung disease” and the drugs included ere everolimus, sirolimus and temsirolimus. Reporting odds ratio (ROR), proportional reporting ratio (PRR) and information component (IC) were used to detect signal.
Results: Overall, 62,117 AE reports related to mTOR inhibitors were recorded during the period. Of these 1,027 AE reports on ILD were submitted to the FAERS database. Everolimus accounted for 723, sirolimus for 191 and temsirolimus for 113 cases of ILD reports associated with mTOR inhibitors. On performing age and gender stratification, it was found that the age group of 19-64yrs and female sex had the highest signal strength.
Conclusion: This study has shown positive signals for ILD with everolimus, sirolimus, and temsirolimus which were not yet established in clinical trials. Further study with well-designed epidemiological data is required to validate these results.
A collection of control time varying delayed systems: Lyapunov Razumikhin-Approach
Authors: Rzig Ines Ben , Kharrat Thouraya 
Published: February 2023

Abstract
Time delay is frequently a source of instability in several modern systems. Therefore, stability and control is of practical and theoretical importance. Based on a common control Lyapunov Razumikhin approach, we study the problem of stabilization for a collection of time varying delay systems. We prove that if a collection of systems with varying delay satisfies some conditions then a delay feedback law, which renders the collection of closed loop systems asymptotically stable, is explicitly constructed.
AMS classification: 93C10,93D15, 93D20.
Quality Indicators in Paediatric and Perinatal Care in Japan: Development and Feasibility Testing
Authors: Shinjo Daisuke , Ozawa Nobuaki , Nakadate Naoya , Kanamori Yutaka , Matsumoto Kimikazu , Noguchi Takashi , Ohtera Shosuke , Kato Hitoshi 
Published: February 2023

Abstract
Purpose
Few paediatric and perinatal quality indicators (QIs) have been developed in the Japanese setting, and the quality of care is not assured or validated. The aim of this study was to develop QIs in paediatric and perinatal care in Japan using an administrative database and confirm the feasibility and applicability of the indicators using a single-site practice test.
Methods
We used a RAND-modified Delphi method that integrates evidence review with expert consensus development. QI candidates were generated from clinical practice guidelines (CPGs) available in English or Japanese and existing QIs in nine selected paediatric or perinatal conditions. Consensus building was based on independent panel ratings. The performance of each QI was retrospectively assessed using data from an administrative database at the National Children’s Hospital.
Results
From the literature review conducted between 2010 and 2020, 124 CPGs and 193 existing indicators were identified to generate QI candidates. Through the consensus-building process, 133 QI candidates were assessed, and 79 QIs were accepted. The practice test revealed wide variations in the process-level performance of QIs in four categories (patient safety: median 43.9% (interquartile range (IQR) 16.7–85.6%), general paediatrics: median 98.8% (IQR 84.2–100%), advanced paediatrics: median 94.4% (IQR 46.0–100%), and advanced obstetrics: median 80.3% (IQR 59.6–100%).
Conclusions
We established 79 QIs for paediatric and perinatal care in Japan using an administrative database that can be applied to hospitals nationwide. The practice test confirmed the measurability of the developed QIs. Benchmarking these QIs will be an attractive approach to improving the quality of paediatric and perinatal care.
Low-dose interleukin-2 for psoriasis therapy based on the regulation of Th17/Treg cell balance in peripheral blood
Authors: Qiao Zusha , Zhao Wenpeng , Liu Yan , Feng Wenli , Ma Yan , Jin Hongzhong 
Published: February 2023

AbstractThe imbalance between regulatory T (Treg) cells and efficient T cells plays an important role in psoriasis. Low-dose interleukin (IL)-2 can preferentially activate Treg cells and ameliorate the imbalance of Treg/efficient T cells. This study focused on the status of circulating CD4 + T subsets and the clinical efficacy of low-dose IL-2 therapies in psoriasis. This retrospective study included peripheral blood samples obtained from 45 psoriasis patients and 40 healthy controls. The 45 psoriasis patients received three cycles of subcutaneous low-dose IL-2 treatment (0.5 million IU/day for 2 weeks) combined with conventional therapies. Inflammatory indices, CD4+T lymphocyte subsets, and cytokines were measured in all patients before and after treatment. The percentage of Treg cells was dramatically decreased in the psoriasis group compared to the healthy group, and the percentage of Treg cells negatively correlated with the disease indices and the psoriasis area and severity index (PASI) (P < 0.001). The Th17/Treg ratio was significantly increased in the psoriasis group compared to the healthy group, and the Th17/Treg ratio positively correlated with disease indices and PASI (P < 0.001). Low-dose IL-2 treatment significantly amplified the percentage of Treg cells and restored the Th17 and Treg immune balance in psoriasis (P < 0.001). Low-dose IL-2 combination therapy effectively improved the clinical manifestations of psoriasis but decreased the inflammatory indicators of the disease activity, with no apparent side effects. Thus, low-dose IL-2 provides a new strategy for the treatment of psoriasis.
New existence result of positive solutions for a class of fractional Kirchhoff-type systems with multiple parameters
Authors: Guefaifia Rafik , Bouali Tahar , Rasouli S.H. 
Published: February 2023

Abstract
This paper is devoted to the existence of positive weak solutions for a class of fractional Kirchhoff-type systems with multiple parameters. By using the sub-supersolution method and some analysis techniques, we prove a new existence result. To the best of our knowledge, our results are new in the study of fractional Kirchhoff-type systems.
Mathematics Subject Classifications: Primary 35J60, 35B30, 35B40.