bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of autologous, adipose-derived mesenchymal stem cells in patients with rheumatoid arthritis: a phase I/IIa, open-label, non-randomized pilot trial
Authors: Vij Ridhima , Stebbings Kevin A. , Kim Hosu , Park Hyeonggeun , Chang Donna 
Published: March 2022

Abstract
Objective
The present study is a phase I/IIa non-randomized, open-label study to evaluate safety and efficacy of a single, intravenous infusion of autologous, adipose-derived mesenchymal stem cells (adMSCs) over a period of 52 weeks, in patients with active rheumatoid arthritis (RA).

Methods
15 eligible RA patients aged 18–65 years were enrolled and followed up at weeks 4, 12, 26 and 52 after receiving a single intravenous dose of 2 × 108 adMSCs. Efficacy was examined using American College of Rheumatology (ACR66/68 score) criteria for swollen and tender joint counts (S/TJC), and serum TNF-α, IL-6, CRP, and ESR levels. Safety endpoints included measures of hematologic, hepatic, and renal function.

Results
ACR66/68 scores for both S/TJC showed significant improvements with large effect sizes (ES) at week 52 vs baseline (p < 0.01, ES = 0.83 and p < 0.001, ES = 0.93 respectively). Medium to large ES were also obvious for ACR66/68 scores measured at other timepoints. Levels of inflammatory markers, TNF-α, IL-6 and ESR remained unchanged compared to baseline. However, a difference in CRP levels with a small effect size was observed at week 4 (p = 0.229, ES = 0.33) with further improvement at week 52 (p = 0.183, ES = 0.37). Post-intervention, levels of hematologic, hepatic, and renal function remained largely unchanged (p > 0.05). No acute or long-term serious adverse events (AEs) occurred.

Conclusions
The results indicated that a single, intravenous administration of autologous adMSCs is safe and efficacious for improvement in joint function in patients with active RA. Data from the current study supports the exploration of ad-MSCs as a therapeutic intervention for RA.
Trial Registration Clinical trial registration number: NCT03691909. Registered September 27, 2018- Retrospectively registered (https://clinicaltrials.gov/show/NCT03691909).
Regulatory effects of Trichinella spiralis and a serine protease inhibitor on the endoplasmic reticulum stress response of intestinal epithelial cells
Authors: Xu Jingyun , Pang Zixuan , Zhang Jinpeng , Xia Shuang , Wang Ruibiao , Zhang Yuheng , Zhen Jingbo , Song Xuewei , Lin Lihao , Sun Feng , Xuan Xinxin , Lu Yixin 
Published: March 2022

AbstractThe accumulation of unfolded or misfolded proteins in the endoplasmic reticulum can cause an endoplasmic reticulum stress (ERS) response. If ERS continues or cannot be alleviated, it will cause the production of proapoptotic factors and eventually lead to apoptosis. Therefore, this study mainly explored whether Trichinella spiralis Kazal-type serine protease inhibitor (TsKaSPI) contributed to the invasion of intestinal epithelial cells during the infectious stage of T. spiralis by regulating ERS. First, in the T. spiralis infection model, H&E staining was used to analyse the damage to jejunum tissue, a TUNEL assay was used to examine cell apoptosis, and the expression of ERS-related and apoptosis-related molecules was also measured. The results showed that ERS occurred during the intestinal phase of T. spiralis infection, while remission began during the cyclic phase. Then, we selected TsKaSPI, one of the important components of T. spiralis ES antigens, for in vitro experiments. The results showed that TsKaSPI could induce apoptosis in a porcine small intestinal epithelial cell line (IPEC cells) by activating ERS and promote activation of the NF-κB signalling pathway. Inhibition experiments confirmed that the occurrence of ERS was accompanied by the activation of NF-κB, and the two processes regulated each other. Finally, we conducted in vivo experiments and administered TsKaSPI to mice. The results confirmed that TsKaSPI could activate ERS and lead to apoptosis in intestinal epithelial cells. In conclusion, T. spiralis infection and TsKaSPI can promote cell apoptosis by activating the ERS response in intestinal epithelial cells and activate the NF-κB signalling pathway to promote the occurrence and development of inflammation.
Characterization, antioxidant and anticoagulant properties of exopolysaccharide from marine microalgae
Authors: Mousavian Zahra , Safavi Maliheh , Azizmohseni Farzaneh , Hadizadeh Mahnaz , Mirdamadi Saeed 
Published: March 2022

AbstractThe sulfated exopolysaccharide extracted from marine microalgae attracted considerable attention from both the nutraceutical and pharmaceutical industries. In the present study biomass of five marine microalgae were screened to find strains with high capacity for the production of sulfated exopolysaccharides. The anticoagulant and antioxidant activities of extracted sulfated polysaccharides were evaluated using activated partial thromboplastin time (aPTT), prothrombin time (PT), DPPH and ABTS assays, respectively. The sulfated polysaccharides extracted from Picochlorum sp. showed a strong DPPH scavenging effect with 85% antioxidant activity. The sulfated polysaccharides of Chlorella sorokiniana, Chlorella sp. (L2) and Chlorella sp. (D1) scavenged more than 90% of the ABTS radicals. However, the sulfated polysaccharide extracted from Chlorella sorokiniana, and Chlorella sp. (N4) showed anticoagulant properties. The dual anticoagulant-antioxidant activities in Chlorella sorokiniana could be explained by the combination of various factors including sulfate content and their binding site, monosaccharide residue and glycoside bond which are involved in the polysaccharide’s bioactivity.
A systematic study of the production of Monacolin K by solid state fermentation of Monascus ruber
Authors: Liu Xiuhe , Sun Aonan , Li Qing , Du Yamin , Zhao Tao 
Published: March 2022

AbstractMonacolin K is one of the bioactive substances produced by Monascus ruber during fermentation. The multi-factors and their interactions on the effect of solid-state fermentation of Monascus for high yield of monacolin K were attractive to industrial production. A detailed study of 7 single-factor experiments and a series of experiments with Plackette-Burman and Box-Benhnken design, data fitting and modeling, and analyzing the visual 3D response surface plots for investigation of the key factors for Monacolin K production. The results showed that initial moisture (50 ~ 55%) and bran content (4.5 ~ 5.5%) as the key factors of transport for nutrients and oxygen during the solid-state fermentation (SSF) process of Monascus. Under the optimal conditions, a temperature shifting of the SSF with a higher Monacolin K yield of 14.53 ± 0.16 mg·g− 1 compared with the content of monacolin K in the commercially available functional red yeast rice of 8 mg g− 1.
Incidence and outcomes of in-hospital cardiac arrest in Japan 2011–2017: a nationwide inpatient database study
Authors: Ohbe Hiroyuki , Tagami Takashi , Uda Kazuaki , Matsui Hiroki , Yasunaga Hideo 
Published: March 2022

Abstract
Background
Although numerous studies have investigated out-of-hospital cardiac arrest, few studies have been conducted on in-hospital cardiac arrest (IHCA). Knowledge of the nationwide epidemiology of IHCA in Japan, with its super-aging society, is important to understand the current situation of IHCA and to establish evidenced-based medicine in the future. The present study aimed to determine the incidence and outcomes of IHCA and their trends in Japan.

Methods
This observational cohort study was performed using a national administrative inpatient database for more than 1600 acute-care hospitals covering about 50% of all acute-care hospital beds in Japan from April 2011 to March 2018. We defined cardiac arrest patients who received cardiopulmonary resuscitation (chest compression) during hospitalization as IHCA. We excluded out-of-hospital cardiac arrest patients from the source population. The incidence of IHCA per 1000 hospital admissions and survival to discharge rate was reported with trend analyses by calendar year 2011–2017.

Results
Among 53,871,101 hospitalized patients without out-of-hospital cardiac arrest patients in 1626 hospitals, 2,136,038 (4.0%) had cardiac arrest. Of them, 274,664 (12.9%) received cardiopulmonary resuscitation at least once during hospitalization and were identified as IHCA, and 1,861,374 (87.1%) did not receive cardiopulmonary resuscitation. The incidence of IHCA per 1000 hospital admissions was 5.1, with a significant decreasing trend from 6.1 in 2011 to 4.6 in 2017 (P for trend = 0.033). Our estimated incidence can be translated to approximately 87,000 IHCA cases in Japan each year. The percentage of IHCA patients among cardiac arrest patients was 12.9%, with a significant decreasing trend from 14.0% in 2011 to 12.2% in 2017 (P for trend = 0.006). The overall rate of survival to discharge was 12.7%, with a significant increasing trend from 10.5% in 2011 to 14.0% in 2017 (P for trend < 0.001).

Conclusions
We found substantial associations between mortality and loss of health and IHCA in Japan. The incidence of IHCA showed a decreasing trend over time, the percentage of treated cardiac arrest patients also had a decreasing trend, and the overall survival to discharge rate improved over time.
Educational data mining: prediction of students' academic performance using machine learning algorithms
Authors: Yağcı Mustafa 
Published: March 2022

AbstractEducational data mining has become an effective tool for exploring the hidden relationships in educational data and predicting students' academic achievements. This study proposes a new model based on machine learning algorithms to predict the final exam grades of undergraduate students, taking their midterm exam grades as the source data. The performances of the random forests, nearest neighbour, support vector machines, logistic regression, Naïve Bayes, and k-nearest neighbour algorithms, which are among the machine learning algorithms, were calculated and compared to predict the final exam grades of the students. The dataset consisted of the academic achievement grades of 1854 students who took the Turkish Language-I course in a state University in Turkey during the fall semester of 2019–2020. The results show that the proposed model achieved a classification accuracy of 70–75%. The predictions were made using only three types of parameters; midterm exam grades, Department data and Faculty data. Such data-driven studies are very important in terms of establishing a learning analysis framework in higher education and contributing to the decision-making processes. Finally, this study presents a contribution to the early prediction of students at high risk of failure and determines the most effective machine learning methods.
Differentiating Black and Hispanic: outcome differences of segregated communities and police shootings in the USA, 2015–2020
Authors: Leslie Timothy F. , Frankenfeld Cara L. , Hattery Angela J. 
Published: March 2022

AbstractBackgroundPolice shootings are unevenly spatially distributed, with substantive spikes throughout the USA. While minorities are disproportionately the victims of police force, social or structural factors associated with this distribution are not well understood. The objective of this work was to evaluate police shootings in relation to victim race or ethnicity and residential segregation and racial diversity.MethodsValidated crowdsourced data from the Washington Post’s Fatal Force (2015–2020) were linked with census tract-level data from the American Community Survey. Residential minority dissimilarity, interaction, and a racial and ethnic diversity metric were calculated in order to assess the potentially variant importance of evenness in distribution, exposure likelihood, and general representation. Logistic and multinomial regression was used to model associations between segregation and diversity, adjusted for other ecological characteristics. Analyses were stratified by victim race or ethnicity (Black, Asian, or Hispanic).ResultsAcross all races combined, the odds of a police shooting in a particular census tract were associated with non-Hispanic Black dissimilarity (OR = 0.98, 95% CI 0.97, 0.99) and racial and ethnic diversity (1.046, 95% CI 1.044, 1.060). Areas with higher racial diversity had a higher likelihood of having a police shooting event with Black victims (OR = 1.092, 95% CI 1.064, 1.120) or Asian victims (OR = 1.188, 1.051, 1.343) than less diverse areas. Higher non-Hispanic Black interaction was associated with a lower likelihood of having a police shooting event with Black victims (OR = 0.914, 95% CI 0.833, 0.946) than lower interaction areas. Higher Hispanic dissimilarity was associated with a lower likelihood of having a police shooting event with a Hispanic victim (OR = 0.398, 95% CI 0.324, 0.489) than lower dissimilarity areas.ConclusionsThe variant effects of residential segregation are only seen when victims are analyzed separately by race. There appears to be a protective effect for Hispanic populations in Hispanic communities, while the reverse is true of Black individuals. We urge law enforcement responsible for locations with segregated communities to monitor individual interactions that police have with residents as well as the patterns of frequency and context of those interactions.
The Use of Fitness-Fatigue Models for Sport Performance Modelling: Conceptual Issues and Contributions from Machine-Learning
Authors: Imbach Frank , Sutton-Charani Nicolas , Montmain Jacky , Candau Robin , Perrey Stéphane 
Published: March 2022

AbstractThe emergence of the first Fitness-Fatigue impulse responses models (FFMs) have allowed the sport science community to investigate relationships between the effects of training and performance. In the models, athletic performance is described by first order transfer functions which represent Fitness and Fatigue antagonistic responses to training. On this basis, the mathematical structure allows for a precise determination of optimal sequence of training doses that would enhance the greatest athletic performance, at a given time point. Despite several improvement of FFMs and still being widely used nowadays, their efficiency for describing as well as for predicting a sport performance remains mitigated. The main causes may be attributed to a simplification of physiological processes involved by exercise which the model relies on, as well as a univariate consideration of factors responsible for an athletic performance. In this context, machine-learning perspectives appear to be valuable for sport performance modelling purposes. Weaknesses of FFMs may be surpassed by embedding physiological representation of training effects into non-linear and multivariate learning algorithms. Thus, ensemble learning methods may benefit from a combination of individual responses based on physiological knowledge within supervised machine-learning algorithms for a better prediction of athletic performance.In conclusion, the machine-learning approach is not an alternative to FFMs, but rather a way to take advantage of models based on physiological assumptions within powerful machine-learning models.
AMP5A modulates Toll-like receptors 7 and 8 single-stranded RNA immune responses in PMA-differentiated THP-1 and PBMC
Authors: Thomas Gregory , Hirter Kristen , Frederick Elizabeth , Hausburg Melissa , Bar-Or Raphael , Mulugeta Yetti , Roshon Michael , Mains Charles , Bar-Or David 
Published: March 2022

Abstract
Background
Dysregulation of antiviral immunity has been implicated in the progression of acute respiratory syndrome coronavirus 2 infection into severe cases of coronavirus disease of 2019 (COVID-19). Imbalances in the inflammatory response drive the overabundant production of pro-inflammatory cytokines and chemokines. The low molecular weight fraction of 5% human serum albumin commercial preparation (AMP5A) is a novel biologic drug currently under clinical investigation for the treatment of osteoarthritis and the hyperinflammatory response associated with COVID-19. This study aims to elucidate AMP5A effects following the activation of immune cells with agonists of Toll-like receptor (TLR) 7 and/or 8, which detect ssRNA viral sequences.

Methods
CXCL10 ELISAs were used to evaluate the dynamics of myeloid cells activated with CL075 and CL307, agonists of TLR7/8 and TLR7, respectively. In addition, enrichment analysis of gene sets generated by ELISA arrays was utilized to gain insight into the biologic processes underlying the identified differentially expressed cytokine profiles. Finally, relative potency (REP) was employed to confirm the involvement of mechanisms of action paramount to AMP5A activity.

Results
AMP5A inhibits the release of CXCL10 from both CL075- and CL307-activated PMA-differentiated THP-1 and peripheral blood mononuclear cells. Furthermore, AMP5A suppresses a distinct set of pro-inflammatory cytokines (including IL-1β, IL-6, IL-12, and CXCL10) associated with COVID-19 and pro-inflammatory NF-κB activation. REP experiments using antagonists specific for the immunomodulatory transcription factors, peroxisome proliferator-activated receptor γ, and aryl hydrocarbon receptor, also indicate that these pathways are involved in the ability of AMP5A to inhibit CXCL10 release.

Conclusion
Due to the biphasic course of COVID-19, therapeutic approaches that augment antiviral immunity may be more beneficial early in infection, whereas later interventions should focus on inflammation suppression. In this study, we show that AMP5A inhibits TLR 7/8 signaling in myeloid cells, resulting in a decrease in inflammatory mediators associated with hyperinflammation and autoimmunity. Furthermore, data demonstrating that AMP5A activates immunomodulatory transcription factors found to be protective in lung disease is provided. These findings suggest that the modes and mechanisms of action of AMP5A are well suited to treat conditions involving dysregulated TLR 7/8 activation.

Graphical Abstract
Toxicity and lethal effects of herbaceous plant crude extracts against Spodoptera litura
Authors: Singh Divyansh , Bapatla Kiran Gandhi 
Published: March 2022

Abstract
Background
Tobacco caterpillar, Spodoptera litura, attacks various cultivated plants and causes significant yield losses. In this study, an eco-friendly approach like using botanical insecticides was adopted to examine the toxicological effect of six herbaceous plants (Phyllanthus niruri, Cyperus rotundus, Euphorbia hirta, Boerhavia diffusa, Parthenium hysterophorus and Cynodon dactylon) against S. litura.

Results
Six herbaceous plants crude extract showed a definite level of toxicity against S. litura larvae (3rd instar) using the surface diet contamination method. Among tested herbaceous plants crude extract at 5 μg/ml concentration, C. dactylon showed significant high larval mortality (75%) against S. litura larvae compared to P. niruri (39%), C. rotundus (36%), P. hysterophorus (26%), B. diffusa (22%) and E. hirta (22%) treatments. A cent percent S. litura larval mortality was achieved at lower concentration from crude extract of C. dactylon (11.2 μg/ml) compared to E. hirta (18.6 μg/ml), B. diffusa (24.39 μg/ml), P. hysterophorus (31.4 μg/ml) crude extracts. The lethal concentration (LC50) of C. dactylon, P. hysterophorus, C. rotundus, P. niruri, B. diffusa and E. hirta crude extracts was estimated to be 1.45, 4.09, 5.74, 6.75, 10.92 and 13.62 μg/ml, respectively.

Conclusion
The study results suggested that C. dactylon crude extract possesses the potential to reduce the S. litura damage on crops as a natural alternative to the chemical insecticides with no toxicity to beneficial species.
Prevalence and sero-epidemiology of bluetongue with special reference to eastern and north-eastern states of India
Authors: Joardar Siddhartha Narayan 
Published: March 2022

AbstractBackgroundBluetongue (BT), an infectious, non-contagious arthropod borne viral disease of domestic and wild ruminants is caused by bluetongue virus (BTV), a type species ofOrbivirusgenus andReoviridaefamily. Albeit bluetongue in India is endemic to southern and western parts, eastern and north-eastern parts of the country didn’t experience any outbreak or reported active disease.Main body of abstractInternational, national and regional disease statuses including some un-published data were narrated to give a clear picture. Until 1940s, BT was mainly restricted to African countries, however started spearheading to Asian and European countries subsequently. Extensive epidemiological surveys were conducted in central parts of America and Caribbean countries during late 80’s. Massive ingression of BT was observed in northern Europe 2006 onward. In India, although first reported in 1964, BT became endemic in southern states during 1980s and became alarming in late 1990s. A thorough sero-epidemiological study was conducted in different agro-climatic zones of eastern and north-eastern states of India during 2001 to 2017. Sero-epidemiological information of different states had been tabulated. This was the first comprehensive document of BT sero-epidemiology of eastern and north-eastern parts of India. Although BT was not reported officially, sero-epidemiology showed BTV was in circulation in animals and vectors of eastern and north-eastern states of India. Published as also un-published data clearly showed animals and vectors harbor BTV in this part of the country.Short conclusionAll the epidemiological components of BT are present in eastern and north-eastern parts of India that warrants presence of the disease in these parts also. Hence, further surveillance and preparedness are recommended to avoid future BT outbreak, if any.
Impact of different diets' nutrition on the fitness and hemocytic responses of the greater wax moth larvae, Galleria mellonella (Linnaeus) (Lepidoptera: Pyralidae)
Authors: Mohamed Hend O. , Amro Abdulraouf 
Published: March 2022

Abstract
Background
The greater wax moth, Galleria mellonella (L.) (Lepidoptera: Pyralidae), is the major devastating insect pest of beekeeping industry all over the world; however their larvae were valuable to be the most favorable alternative invertebrate model. For this purpose, new-hatched larvae were reared on five different nutritional diets based on: old wax-comb (natural food); wheat flour diet (Triticum aestivum L.); soybean diet (Glycine max); wheat germ diet; and date syrup diet (Phoenix dactylifera L.) till reaching the fully grown 6th instars to evaluate their fitness and hemocytic responses.

Results
Fully grown larvae from soybean diet had the highest rates of fresh (280 mg) and dry weights (104 mg), water contents (175.6 mg), carbohydrates (1.97%), total hemocyte count (THC) (4746/mm3), total soluble solid (TSS) (21.7%), hemolymph protein concentration (HPC) (1662.5 mg/100 ml), and hemolymph content (density 3.82 mg/µl and volume 70.35 µl/larva), followed by wheat germ diet in comparable to the natural food. All suggested diets considered as rich protein-materials; recording high protein rates on their larvae (39.51–41.87%), with only the exception of old wax-comb had the lowest one (36.63%). Moreover, five types of hemocytes were classified in the larval hemolymph as (prohemocytes (PR), plasmatocytes (PL), granulocytes (GR), oenocytoids (OE) and spherulocytes (SP)), but with different rates related to different diets. Regardless the rearing diets, PR type was the most frequently recorded cell type (73.31%) in hemolymph, followed by PL (8.37%), and the lowest one was OE cells (5.82%).

Conclusions
The suggested diets of soybean and wheat germ recorded the best results than the other diets used almost, and could be recommended as standard diets to mass-produce healthy and high-quality G. mellonella for in vivo experimentation and/or microbiological studies.