bluuebunny/crossref_metadata_2025 huggingface dataset:
Long Short Term Memory model for accurate predictions of Single Nucleotide Polymorphisms in Mycobacterium tuberculosis from timeseries genome analysis
Authors: Uttarkar Akshay , Farhan Syed , Kumar Jitendra , Niranjan Vidya
Published: April 2022

Drug resistance in tuberculosis is on the serious threat list of world health organization with a critical focus on addressing the genomic variations in Mycobacterium tuberculosis. This provides an opportunity for better understanding of evolutionary progression leading to anti-microbial resistance. This impacts on the economic stability of the global healthcare sector. A timeline genomic analysis from 2003 to 2021 of 578 mycobacterium genomes have been performed to understand the pattern underlying the genomic variations. A total of 4,76,053 mutations with Ts/Tv ratio of 0.448 was observed. In this regard, a recurrent neural network approach of Long short term memory model was optimized to predict the genome-wide mutations in the ratio of 80:20 test to training set respectively. The genomic sequences were split into batches and the error rate is averaged to 5.14% in 4 out of 5 batches and 38.99% in last batch with accurate position specific predictions. This has an impact on countering the anti-microbial resistance by identifying regions with high and low genomic variability providing insights on novel drug prospective targets. The further scope lies in improvising the model by enriching the datasets.
Subclinical infection occurs frequently following low dose exposure to prions by blood transfusion
Authors: Salamat M Khalid F , Stewart Paula , Brown Helen , Tan Kyle BC , Smith Allister , de Wolf Christopher , Blanco A Richard Alejo , Turner Marc , Manson Jean C , McCutcheon Sandra , Houston E Fiona
Published: April 2022

Infectious prion diseases have very long incubation periods, and the role that subclinical infections play in transmission, persistence and re-emergence of these diseases is unclear. In this study, we used a well-established model of vCJD (sheep experimentally infected with bovine spongiform encephalopathy, BSE) to determine the prevalence of subclinical infection following exposure by blood transfusion from infected donors. Many recipient sheep survived for years post-transfusion with no clinical signs and no disease-associated PrP (PrPSc) found in post mortem tissue samples by conventional tests. Using a sensitive protein misfolding cyclic amplification assay (PMCA), we found that the majority of these sheep had detectable PrPSc in lymph node samples, at levels approximately 105-106 times lower than in equivalent samples from clinically positive sheep. Further testing revealed the presence of PrPSc in other tissues, including brain, but not in blood samples. The results demonstrate that subclinical infection is a frequent outcome of low dose prion infection by a clinically relevant route for humans (blood transfusion). The long term persistence of low levels of infection has important implications for prion disease control and the risks of re-emergent infections in both humans and animals.
Ggraphene oxide loaded with nano-ZnO alters gut microbiota community to promote secondary bile acid synthesis and immunity response in fattening cattle
Authors: Zhang Haibo , Guan Weikun , Li Lizhi , Guo Dongsheng , Xing Qingfeng , Huang Chaoyong , Xiong Chuanshuai , Li Baofeng , Chen Ketian , Peng Cong
Published: April 2022

Background
To our knowledge, graphene oxide loaded with nano-ZnO (NZnOGO) represent a new nutritional additive for the food and animal husbandry industry. However, the mechanism by which NZnOGO mediates cattle growth and intestinal health are not fully understood. This study was conducted to evaluate the effects of NZnOGO on gut microbiota, bile acid (BA) concentration and intestinal immunity in fattening cattle.
Results
Twenty Simmental × Chinese Yellow Cattle were assigned to 2 dietary groups: control diet (CON) without Zn supplement and CON diet supplemented with NZnOGO. The trial lasted 60 d. The gut microbiota composition and BA concentration in the colon chyme samples were determined by microbiota metagenomics and gas chromatography methods, respectively. Colon mucosa immune factors and gene expression analysis were determined by ELISA and RT-PCR, respectively. The results showed that dietary NZnOGO supplementation significantly increased average daily gain (P < 0.05), and significantly decreased feed conversion ratio (P < 0.05). The relative abundance of the secondary BA synthesis microbiota genera Clostridium, Ruminococcus, Eubacterium, Enterococcus, Collinsella, Fusobacterium, Eggerthella, Brevibacillus and Peptostreptococcus in the NZnOGO group had significantly higher than the CON group (P < 0.05). At the secondary BA synthesis pathway, NZnOGO group had significantly higher 7α-hydroxysteroid dehydrogenase (EC:1.1.1.159) and bile acid-CoA ligase BaiB (EC:6.2.1.7) than the CON group (P < 0.05). Dietary NZnOGO supplementation significantly decreased primary BA (taurocholic acid, taurochenodeoxycholic acid and taurodeoxycholate acid) (P < 0.05), and significantly increased secondary BA (deoxycholic acid, beta-Muricholic acid, 12-ketolithocholic acid, hyodeoxycholic acid, lithocholic acid, isolithocholic acid, ursodeoxycholic acid and apocholic acid) (P < 0.05). The NZnOGO group significantly increased the abundance of gene expression at metabolism and higher defense mechanisms (P < 0.05). The expression of Takeda G-protein-coupled receptor 5, protein kinase A, cyclic-AMP response element binding protein, toll-like receptor 4 and interleukin-10 (IL-10) genes were increased by dietary NZnOGO supplementation (P < 0.05), while the expression of nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α) and IL-1β genes were significantly decreased (P < 0.05). IL-10 concentration was increased by dietary NZnOGO supplementation (P < 0.05), whereas TNF-α and IL-1β contents were significantly decreased (P < 0.05).
Conclusions
Taken together, dietary NZnOGO supplementation improved the growth performance and intestinal immune function of the fattening cattle, compared to the diet free of Zn supplement, which was associated with enhancing secondary BA synthesis microbiota growth and promoting secondary BA synthesis.
Metabolomic changes in crown of alfalfa (Medicago sativa L.) during de-acclimation
Authors: Li Zhensong , He Feng , Tong Zongyong , Li Xianglin , Yang Qingchuan , Hannaway David B.
Published: April 2022

Alfalfa is a high-quality forage legume species that is widely cultivated at high latitudes worldwide. However, a decrease in cold tolerance in early spring seriously affects regrowth and persistence of alfalfa. There has been limited research on the metabolomic changes that occur during de-acclimation. In this study, a liquid chromatography–mass spectrometry system was used to compare the metabolites in two alfalfa cultivars during a simulated overwintering treatment. In four pairwise comparisons, 367 differential metabolites were identified, of which 31 were annotated according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Many of these metabolites were peptides, carbohydrates, and lipids. At the subclass level, 17 major pathways were revealed to be significantly enriched (P < 0.05). The main differential metabolites included amino acids, peptides and analogs, carbohydrates, and glycerol phosphocholines. A metabolomic analysis showed that the up-regulation of unsaturated fatty acids and amino acids as well as the enhancement of the related metabolic pathways might be an effective strategy for increasing alfalfa cold tolerance. Furthermore, glycerophospholipid metabolism affects alfalfa cold tolerance in early spring. Study results provide new insights about the changes in alfalfa metabolites that occur during de-acclimation, with potential implications for the selection and breeding of cold-tolerant cultivars.
Rapid epidemic expansion of the SARS-CoV-2 Omicron BA.2 subvariant during China’s largest outbreaks
Authors: Dai Yeyu
Published: April 2022

A complete and accurate statistical panorama and analysis of cases contracted with theSARS-CoV-2 Omicron BA.2 subvariant are given under the conditions of strict mandatoryquarantine and isolation and of a high rate of full vaccination. Sars-Cov-2 is still new, and little isknown about either its direction of variation or its propagation laws. No country other than Chinahas been able to disclose every infected case and to have the data of heavily intervening largeoutbreaks. Here, my study reveals that the BA.2 subvariant can still spread very fast and wide inareas with strict “dynamic zero-COVID strategy”i in China, that there exist in different cities asmany as twenty-time large differences in morbidity rate unrelated to any of the influence factorsknown and that the Omicron BA.2 subvariant is unpredictable of its virulence, although its severerate of confirmed cases is low. This analysis provides first-hand solitary and valuable informationfor further research on similar epidemics in the future. It may bring new thoughts for correctionof present epidemiological theory and mathematical models. It may also give other countriestime to be better prepared for the coming 6th wave driven by Omicron BA.2.
Rapid epidemic expansion of the SARS-CoV-2 Omicron BA.2 subvariant during China’s largest outbreaks
Authors: Dai Yeyu
Published: April 2022

A complete and accurate statistical panorama and analysis of cases contracted with the SARS-CoV-2 Omicron BA.2 subvariant are given under the conditions of strict mandatory quarantine and isolation and of a high rate of full vaccination. Sars-Cov-2 is still new, and little is known about either its direction of variation or its propagation laws. No country other than China has been able to disclose every infected case and to have the data of heavily intervening large outbreaks. Here, my study reveals that the BA.2 subvariant can still spread very fast and wide in areas with strict “dynamic zero-COVID strategy”i in China, that there exist in different cities as many as twenty-time large differences in morbidity rate unrelated to any of the influence factors known and that the Omicron BA.2 subvariant is unpredictable of its virulence, although its severe rate of confirmed cases is low. This analysis provides first-hand solitary and valuable information for further research on similar epidemics in the future. It may bring new thoughts for correction of present epidemiological theory and mathematical models. It may also give other countries time to be better prepared for the coming 6th wave driven by Omicron BA.2.
Accurate prediction of microvascular invasion occurrence and effective prognostic estimation for patients with hepatocellular carcinoma after radical surgical treatment
Authors: Xiong Yuling , Cao Peng , Lei Xiaohua , Tang Weiping , Ding Chengming , Qi Shuo , Chen Guodong
Published: April 2022

Background
Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide with an overall 5-year survival rate was less than 18%, which may be related to the tumor microvascular invasion (MVI). This study aims to compare the clinical prognosis of HCC patients with or without MVI after radical surgical treatment, and further analyze the preoperative risk factors related to MVI to detect a new treatment strategy for HCC.
Methods
According to postoperative pathological diagnostic of MVI occurrence, 160 study patients undergoing radical hepatectomy were divided into MVI negative group (n = 68) and MVI positive group (n = 92). The clinical outcomes and prognosis of HCC patients was compared between the two groups, and then the clinical characteristic parameters were analyzed by multivariate Logistic regression to construct a MVI prediction model. Then, the practicability and validity of the model were evaluated, and the clinical prognosis of different MVI risk groups were subsequently compared.
Result
There were no significant differences between the MVI negative and MVI positive group in clinical baseline, haematological and imageological data. Also, the clinical outcome comparison between the two groups presented no significant differences excepted the pathological grading (P = 0.002) and survival and recurrence rate after surgery (P < 0.001). The MVI prediction model, based on preoperative AFP, tumor diameter and TNM stage, presented superior predictive efficacy (AUC = 0.7997) and good practicability (high H-L goodness of fit, P = 0.231). Compared the MVI high-risk group, the patients in the MVI low-risk group shown higher survival rate (P = 0.002) and lower recurrence rate (P = 0.004).
Conclusion
MVI is an independent risk factor of HCC for poor prognosis after radical resection. The MVI prediction model, consist of AFP, tumor diameter and TNM stage, exhibits a superior predictive efficacy and strong clinical practicability for MVI prediction and prognosis estimation, which provides a new therapeutic strategy for clinical standardized treatment of HCC patients.
ARLE GPS: A computational tool to aid solve the creative design of a house. Case study.
Authors: Martins Daniel das Neves
Published: April 2022

The computational tool ARLE GPS "geometric planning solver of floor plan layout", converts the spatial planning of a house, conceptualized as a "wicked" problem, into a "well-defined" problem; and thus, helps the architect to solve it in a rational, innovative, and creative way, using a physical-biological meta-model. The physical model simulates solutions of the candidate FPL repetitively, in real time, and evaluates the geometric qualification of the FPL, representative of the quality of the solution, in an analogy with the physical functional performance of the house. The biological model makes it possible to build and explore design spaces, with the goal of retrieving information about inheritance and genetic transmission of high-performance solutions, to transcribe them into the development of innovative and creative designs. Thus, ARLE GPS evaluates creative design against the social value of the house, represented by its utility/functionality, and the quantitative innovation established by the fulfillment of the home purpose, by the user. Through geometric qualification (QQL) and optimization, in relation to the defining qualification of the house's required performance. (QQA). Associated with the evaluation of the house's performance over its useful life, represented by its usability. Computed by the ARLE GPS robust design model, through the geometric cost of losses (AN) variable, induced by the FPL design solution, as in the case of confined rooms, which persist during the house's lifetime.
Isolated non-immune hydrops fetalis: an observational study on complete spontaneous resolution, perinatal outcome, and long-term follow-up
Authors: Neveling Sophie , Knippel Alexander Johannes , Kozlowski Peter
Published: April 2022

Purpose The aim of our study was to investigate spontaneous resolution and postnatal outcome in non-immune hydrops fetalis (NIHF). We specifically studied NIHF cases that occurred without any other anomalies in the prenatal diagnostic workup, defined as isolated NIHF (iNIHF).MethodsTo identify iNIHF we retrospectively classified prenatal findings of 703 NIHF singletons, diagnosed in our prenatal referral center between 1997 and 2016. We studied the occurrence of prenatal resolution in iNIHF and linked it to the perinatal outcome. We obtained long-term outcome by contacting the parents, children, and the pediatricians and listed all functional and structural anomalies and temporary logopedic, psychosocial and motoric impairments.ResultsAmong 73 iNIHF cases, 57 (78.1%) resolved completely prenatally. The baby-take-home rate was 98.2% in these cases. In contrast, the baby-take-home rate in the subgroup without complete resolution was 25.0%. We achieved pediatric long-term outcome in 28 of 60 survivors (46.6%) of iNIHF with a mean follow-up period of 10.4 years. Among these 28 children, fetal hydrops had completely resolved prenatally in 27 cases and had regressed to a mild effusion in one case. In the pediatric development, two children had significant functional impairment and three children showed recurrent skin edema.ConclusionComplete spontaneous resolution was the most common intrauterine course of iNIHF in our collective. Completely resolved iNIHF had a favorable perinatal outcome in our study. Our data on the long-term outcomes are consistent with the assumption of an increased rate of functional impairments. TRIAL REGSTRATION NUMBERInternal study number of Heinrich-Heine-University, Duesseldorf: 6177RDate of registration: December 2017
Weighted gene coexpression network analysis reveals negative regulation of maximum left ventricular wall thickness by carboxylesterase 1 and cathepsin C in hypertrophic cardiomyopathy
Authors: Kuang Ye , Wang Jia , Dong Yulin , Wang Yang , Ji Yong , Gao Hui , Peng Chuanmei
Published: April 2022

Hypertrophic cardiomyopathy (HCM) is a primary cardiomyopathy characterized by hypertrophic cardiomyocytes. It is one of the leading causes of sudden death in adolescents. However, the molecular mechanism of HCM is not clear. In our study, ribonucleic acid (RNA) sequence data of myocardial tissue in HCM patients was extracted from the Gene Expression Omnibus (GEO) database and analyzed by weighted gene co-expression network analysis (WGCNA). A total of 31 co-expression modules were identified. The co-expression black module significantly correlated with maximum left ventricular wall thickness (Maxi LVWT). We screened the differentially expressed mRNAs between normal tissues and HCM tissues using the dplyr and tidyr packet in R3.6.2. The genes in the black module and differentially expressed genes were further intersected. We found that the expression of carboxylesterase 1 (CES1) and cathepsin C (CTSC) was down regulated in HCM tissues, and negatively correlated with Maxi LVWT. We further verified the above conclusion in clinical samples from HCM patients. We found the expression of CES1 and CTSC was down regulated in HCM tissues, and negatively correlated with Maxi LVWT. The above conclusion was further verified in clinical samples from HCM patients. In summary, the study suggests that CES1 and CTSC negatively regulate development of HCM and have potential as a therapeutic and diagnostic target for HCM.
Hyperphosphatemia and its Relationship with Blood Pressure, Vasoconstriction, and Endothelial Cell Dysfunction in Hypertensive Hemodialysis Patients
Authors: Jung Jinwoo , Jeon-Slaughter Haekyung , Nguyen Hang , Patel Jiten , Sambandam Kamalanathan K. , Shastri Shani , Buren Peter Noel
Published: April 2022

BackgroundHyperphosphatemia occurs frequently in end-stage renal disease patients on hemodialysis and is associated with increased mortality. Hyperphosphatemia contributes to vascular calcification in these patients, but there is emerging evidence that it is also associated with endothelial cell dysfunction. MethodsWe conducted a cross-sectional study in hypertensive hemodialysis patients. We obtained pre-hemodialysis measurements of total peripheral resistance index (TPRI, non-invasive cardiac output monitor) and plasma levels of endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA). We ascertained the routine peridialytic blood pressure (BP) measurements from that treatment and the most recent pre-hemodialysis serum phosphate levels. We used generalized linear regression analyses to determine independent associations between serum phosphate with BP, TPRI, ET-1, and ADMA while controlling for demographic variables, parathyroid hormone (PTH), and interdialytic weight gain. ResultsThere were 54 patients analyzed. Mean pre-HD supine and seated systolic and diastolic BP were 164 (27), 158 (21), 91.5 (17), and 86.1 (16) mmHg. Mean serum phosphate was 5.89 (1.8) mg/dL. There were significant correlations between phosphate with all pre-hemodialysis BP measurements (r=0.3, p=.04; r=0.4, p=.002; r=0.5, p<.0001; and r=0.5, p=.0003.) The correlations with phosphate and TPRI, ET-1, and ADMA were 0.3 (p=.01), 0.4 (p=.007), and 0.3 (p=.04). In our final linear regression analyses controlling for baseline characteristics, PTH, and interdialytic weight gain, independent associations between phosphate with pre-hemodialysis diastolic BP, TPRI, and ET-1 were retained (β=4.33, p=.0002; log transformed β=0.05, p=.005; reciprocal transformed β= -0.03, p=.047). ConclusionsSerum phosphate concentration is independently associated with higher pre-HD BP, vasoconstriction, and markers of endothelial cell dysfunction. These findings demonstrate an additional negative impact of hyperphosphatemia on cardiovascular health beyond vascular calcification. The study was part of a registered clinical trial, NCT01862497 (May 24, 2013).
Exploring Effects of the HEP® (Homeostasis-Enrichment-Plasticity) Approach as a Comprehensive Therapy Intervention for an Infant with Cerebral Palsy: A Case Report
Authors: Balıkçı Aymen
Published: April 2022

Background: Cerebral palsy (CP) is a common non-progressive neurodevelopmental disorder which causes developmental disabilities in children. Varied interventions for CP exist to address medical and physical needs but with limited effectiveness evidence. Environmental Enrichment (EE) is an animal model intervention for many neurodevelopmental disorders, including CP, with considerable positive effects. This case report defines the “HEP®” (Homeostasis-Enrichment-Plasticity) approach, which is based upon principles of EE and ecological theories of development, and describes its’ use to promote the developmental and functional skills of an infant with CP.Methods: Parent interviews and assessment data were completed before and after intervention. Data was gathered by developmental history, systematic observation of behaviors in the clinical setting and at home, Beck Anxiety Inventory (BAI), Infant-Toddler Symptom Checklist, the Sensory Profile Infant/Toddler, Peabody Developmental Motor Scales-2, Gross Motor Function Measurement-88 (GMFM-88), the Gross Motor Function Classification System (GMFCS) and Pediatric Evaluation of Disability Inventory (PEDI). The HEP® approach intervention was implemented one time per week for 12 months.Results: Following the HEP® approach intervention, self regulation and sensory processing scores improve to typical performance ranges. GMFM-88 total score improved from 45/264 to 123/264. The Peabody found all Gross Motor (54 to 110), Fine Motor (65 to 117) and Total Motor Quotient (119 to 227) scores increased significantly after intervention. Post- intervention observations showed significant gross motor progress with movement fromGMFCS Level IV to Level I. Performance on the Functional Skills Scales and Caregiver Assistance Scales of PEDI also demonstrated significant gains.Conclusions: A definition and detailed description of the HEP® approach intervention is presented here for the first time. The case report demonstrated preliminary evidence for the effectiveness of the HEP® approach on self-regulation, sensory processing, motor development, functional skills, and caregiver assistance with an infant with CP. Additional studies are needed to validate the findings.
Sexual Dysfunction After Partial Penectomy for Penile Cancer: Updated Report from A Vietnamese Patient Cohort
Authors: Nguyen Quang , Bui Van-Quang , Vo Hoang-Long
Published: April 2022

Objectives
This study sought to evaluate sexual dysfunction of patients who underwent partial penectomy for carcinoma of the penis.
Method
We included the individuals who aged 18 years and older and received the treatment with partial penectomy for penile carcinoma. Information on sexual function after partial penectomy were evaluated to be erectile dysfunction, premature ejaculation, frequency of sexual intercourse within one month, time to have sex again, delayed ejaculation, decreased sexual desire, partners’s attitudes toward sex, and partner’s sexual avoidance.
Results
Between January 2016 and December 2019, there were 22 eligible patients who received the treatment with partial penectomy, with the mean age at operation of 50.3 ± 11.6 years. Three (13.6%) patients had phimosis and one (4.5%) patient had genital warts. 17 patients were fully monitored postoperatively, 2 patients died and 3 patients were uncontactable. In 17 patients who were followed up after partial penectomy in this study, 13 of them had sexual intercourse after surgery (76.5%), when there were four patients who did not have sex again after surgery. There was significant decrease in the mean frequency of sexual intercourse within one month pre-operatively compared to post-operatively (7.6 ± 2.2 times vs. 3.4 ± 2.1 times). The average time to have sex again after surgery was 92.8 ± 92.5 days. In the sample of 13 patients having sexual intercourse again after partial penectomy, most them were no erectile dysfunction (n = 11; 84.6%). The degree of erectile dysfunction was mild in one patient (7.7%) and, mild to moderate in one patient (7.7%). There were delayed ejaculation in 12 (92.3%) patients and decreased sexual desire in 11 (64.7%) patients. 13 (76.5%) patients reported partners’s disappointed attitudes toward sex after surgery. 9 (69.2%) patients reported partner’s sexual avoidance after partial penectomy.
Conclusions
Besides the sexual dysfunction of penile carcinoma patients after partial penectomy was known, our preliminary findings suggest that notable sexual problems that patients experiencing after surgery were decreased frequency of sexual intercourse and satisfaction of both patient and partner.
Modeling and control of a CDPM-based Smart Crane
Authors: GUESMI Fatma , Azouz Naoufel , NEJI Jamel
Published: April 2022

As part of the development of Large Capacity Airships, this paper presents the design and the mathematical model of an innovative smart crane CHAYA-SC, based on the principle of Cable Driven Parallel Manipulators as well as its stabilization. This crane is mounted on the airship hold and intended for handling at altitude. The highest level of precision is required. Thus, the model developed includes the oscillations as well as the transverse and longitudinal vibrations of the heavy cable supporting the load to be handled. The highly nonlinear partial differential equations (PDE) and the ordinary derivative equations (ODE) that govern the motion of the system are obtained via the Lagrange equations coupled with a modal synthesis. As a first validation of the modeling, a simple control vector is applied to stabilize the airship and its load under the effect of a squall. Numerical simulations are presented at the end of the paper to show the efficiency of the design.
Empowerment training to support service user involvement in mental health system strengthening in rural Ethiopia: a mixed-methods pilot study
Authors: Abayneh Sisay , Lempp Heidi , Rai Sauharda , Girma Eshetu , Getachew Medhanit , Alem Atalay , Kohrt Brandon A. , Hanlon Charlotte
Published: April 2022

BackgroundIncreased service user involvement is recommended to improve weak mental health systems in low-and middle-income countries (LMICs). However, involvement is rarely implemented and interventions to support involvement are sparse. In this study we evaluated the acceptability, feasibility and perceived outcomes of an empowerment and training program for service users and health professionals to facilitate service user involvement in mental health system strengthening in rural Ethiopia.MethodsREducing Stigma among HealthcAreProvidErs (RESHAPE) is a training curriculum for service users, their caregivers and aspirational health workers, which uses PhotoVoice methodology, to prepare them in participation of mental health systems strengthening in LMICs. We delivered the RESHAPE training augmented with empowerment content developed in Ethiopia. The interactive face-to-face training was delivered to service users and caregivers (over 10 days), and health professionals (one day) separately. The study was an uncontrolled, convergent mixed-methods design. The quantitative data consisted of process data, satisfaction questionnaire, and a retrospective pre-test survey. Qualitative data included exit and follow-up in-depth interviews with the service users. Descriptive statistics were performed for quantitative data, and qualitative data were thematically analysed. The findings were integrated through triangulation for convergent themes following analysis.Results12 service users, 12 caregivers and 18 health professionals were enrolled, and completed the training. Participants valued the content and delivery process; the standard of the training program met their expectations and participation led to positive gains in understanding about mental illness, stigma, service-user involvement and human rights. The qualitative findings identified positive impacts, including increased self-confidence, sense of empowerment, social - and perceived therapeutic benefits.ConclusionsWe found that the RESHAPE training with added content for Ethiopia, delivered using the PhotoVoice methodology, is feasible, acceptable and of value to develop and implement training programmes which can empower service users to be involved in mental health system strengthening in this setting. Further study to assess the impact on health systems strengthening is warranted.
Neuroecotoxicology: Effects of Environmental Heavy Metal Exposure on the Brain of African Giant Rats and the contribution of Vanadium to the Neuropathology, Part 1
Authors: Usende Ifukibot Levi , Olopade James , Azeez Idris Ayodeji , Andrioli Anna , Bankole Oluwamolakun O , Olopade Funmilayo E , Nafady Allam A , Bentivoglio Marina
Published: April 2022

Increased exploitation of minerals has led to pollution of confined environments as documented in Nigeria Niger Delta. Information on the effects on brain of such exposure is limited. Due to its exploratory activities, the African giant rat (Cricetomys gambianus) (AGR) provides a unique model for neuroecotoxicological research to determine levels of animal and human exposure to different pollutants. This study aims to unravel neuropathological features of AGR sampled from three agro-ecological zones of Nigeria. Fifteen AGR were sampled according to previously determined data on heavy metal exposure: high vanadium, high lead, and low metals. Eighteen AGR were collected from low metal zone and divided into two groups. Control group received vehicle while SMV exposed group received 3mg/kg sodium metavanadate (SMV) intraperitoneally for 14days. Brain immunohistochemical analyses were conducted, and ultrastructural changes were studied in experimentally exposed group. Results showed significant loss of tyrosin hydroxylase, parvalbumin, orexin-A and melanin concentration hormone containing neuronal populations in brains obtained from high vanadium and high lead zones and in experimentally intoxicated SMV groups. Similarly, significant decrease numbers of dendritic arborations; extracellular matrix density, perineuronal nets; astrocytes and microglia activations are documented in same groups. Ultrastructural studies revealed mass denudation, cilia loss, disintegration of ependymal layer and intense destructions of myelin sheaths in SMV exposed group. These are the first “neuroecotoxicological” findings in distinct neuronal cells. The implications of these findings are highly relevant for human population living in these areas, not only in Nigeria but also in similarly polluted areas elsewhere in the world.
Evaluation of the Mineral composition, Phytochemical and Proximate Constituents of three Culinary Spices in Nigeria: A Comparative Study
Authors: Evuen Uduenevwo Francis , Okolie Ngozi Paulinus , Apiamu Augustine
Published: April 2022

A comparative assessment of the quantitative mineral composition, phytochemical and proximate constituents of Xylopia aethiopica (fruits), Piper guineense (seeds) and Rhaphiostylis beninensis (roots) was done using standard protocols. Mineral analysis of the culinary spices revealed significant differences (p < 0.05) in the Magnesium, Zinc, Iron, Selenium, Copper, Calcium, Manganese, Molybdenum, Potassium and Sodium contents of the spices. The respective concentrations of Iron and Selenium (16.03 ± 0.01, 0.25 ± 0.01 mg/L) in R. beninensis were the highest and lowest of all mineral elements evaluated in the three spices. Similarly, the carbohydrate and moisture contents (81.24 ± 0.25%, 0.71 ± 0.01%) of R. beninensis were the highest and lowest among all proximate parameters evaluated in the three spices. However, the Fibre contents of R. beninensis and P. guineense and the ash contents of P. guineense and X. aethiopica respectively, showed no significant differences (p > 0.05). Moreover, flavonoid and oxalate concentrations (4.04 ± 0.09%, 0.25 ± 0.04%) in X. aethiopica were the highest and lowest of phytochemicals in the three spices respectively. Nevertheless, there were no significant differences (p > 0.05) in the tannin content of P. guineense and X. aethiopica spices respectively. Similar trends were observed between the oxalate contents of R. beninensis and X. aethiopica, the phytate contents of R. beninensis and P. guineense and the saponin contents of the three spices respectively. These results indicate that the spices are notable sources of essential nutrients and phytochemicals. Therefore, they are possible candidates in the search for natural ingredients to formulate drugs and nutraceuticals by pharmaceutical industries.
Vision Transformer based System for Fruit Quality Evaluation
Authors: Kumar Tanushri , R Shivani
Published: April 2022

Purpose Fruit quality assessment is one of the most pressing issues in the farming industry. Agriculturists would benefit significantly from the capacity to recognize the freshness of fruits, as it will allow them to optimize the harvesting stage and avoid reaping either underdeveloped or overdeveloped natural products. Productivity has decreased due to a lack of low-cost technology and equitable access. Despite large-scale agricultural mechanization in some parts of the country, most agricultural operations are still carried out by hand with simple instruments. The goal of this research is to automate the task of evaluating fruit quality. Methods Transformers were first presented in the field of natural language processing, and they offer dramatic performance improvements over existing models in NLP like as LSTMs and GRU. The Vision Transformer, or ViT, is an image classification model that uses a Transformer-like design over image patches. Results Vision transformer exhibited far superior results compared to CNN models. The models were evaluated on various metrics and the vision transformer model generated the highest accuracy compared to convolutional neural network models such as InceptionNet and EfficientNet. Conclusions Vision Transformers exhibited superior performance in fruit quality evaluation compared to traditional CNN model approaches. For future works, this model can be used to develop an efficient quality control system Automation of the quality prediction process can greatly reduce food and agricultural produce wastage.
Rapid detection of bovine rotavirus A by isothermal reverse transcription recombinase polymerase amplification assays
Authors: Liu Yuelin , Liu Libing , Wang Jinfeng , Sun Xiaoxia , Gao Yaxin , Yuan Wanzhe , Wang Jianchang , Li Ruiwen
Published: April 2022

Background
Bovine rotavirus A (BRVA) is considered to be the most common pathogen of severe diarrhea in cattle worldwide, which could lead to the death of newborn calves and cause the significant economic losses to the cattle industry. As a novel isothermal nucleic acid amplification technique, recombinase polymerase amplification (RPA) has been applied widely for the rapid detection of different important pathogens in human and animals.
Results
Targeting the VP6 gene of BRVA, an RT-RPA assay based on the fluorescence monitoring (real-time RT-RPA) and an RT-RPA assay combined with a lateral flow strip (LFS RT-RPA) were successfully developed. The RT-RPA assays allowed the exponential amplification of the target fragment in 20 minutes. After incubation of the LFS RT-RPA on a metal bath at 40°C, the results were displayed on the lateral flow strip within 5 min, while real-time RT-RPA allowed the real-time observation of the results in Genie III at 42°C. Both of the two assays showed high specificity for BRVA without any cross-reaction with the other tested pathogens causing diarrhea in cattle. With the standard RNA of BRVA serving as a template, the limit of detection for real-time RT-RPA and LFS RT-RPA were 1.4 × 102 copies per reaction and 1.4 × 101 copies per reaction, respectively. In the 134 fecal samples collected from cattle with diarrhea, the BRVA RNA positive rate were 45.52% (61/134) and 46.27% (62/134) in real-time RT-RPA and LFS RT-RPA, respectively. Compared to a previously published real-time PCR, the real-time RT-RPA and LFS RT-RPA showed a diagnostic specificity of 100%, diagnostic sensitivity of 98.39% and 100%, and a kappa coefficient of 0.985 and 1.0, respectively.
Conclusions
In this study, BRVA was successfully detected in cattle fecal samples by the developed real-time RT-RPA and LFS RT-RPA assays. The developed RT-RPA assays had great potential for the rapid detection of BRVA in under-equipped diagnostic laboratory and the point-of-need diagnosis at quarantine stations and farms, which is of great importance to control BRVA-associated diarrhea in cattle herds.
Orally bioavailable Bruton’s tyrosine kinase proteolysis-targeting chimeras active against wild-type and C481 mutant BTKs in murine hematology models
Authors: Lim Ye Seul , Yoo Sun-Mi , Patil Vineet , Kim Han Wool , Kim Hyun-Hwi , Suh Beomseon , Park Ji Youn , Jeong Na-rae , Park Chi Hoon , Ryu Je Ho , Lee Byung-Hoon , Kim Pilho , Lee Song Hee
Published: April 2022

Background
Bruton’s tyrosine kinase (BTK) is an important signaling hub that activates the B-cell receptor (BCR) signaling cascade. BCR activation can contribute to the growth and survival of B-cell lymphoma or leukemia. The inhibition of the BCR signaling pathway is critical for blocking downstream events and treating B-cell lymphomas. Herein, we report potent and orally available proteolysis-targeting chimeras (PROTACs) that target BTK to inactivate BCR signaling.
Methods
Fluorescence resonance energy transfer signals were used to assess BTK and cereblon (CRBN) ternary complex formation with Mab anti-6His-Eu cryptate and Mab anti-glutathione-S-transferase-XL665. BTK and CRBN binding activities were investigated using in vitro target binding assays. Subsequently, SDS-PAGE and western blotting of whole cell lysates was performed, followed by immunofluorescence analysis of TMD-8 cells. ELISA was performed in TMD-8 cells treated with 0.01 µM PROTAC, ibrutinib, acalabrutinib, ARQ-531, Binder, or MT-802 to measure CCL3 and CCL4 levels. Tandem ubiquitin-binding elements pull-down assay was used to characterize UBX-382 in Ramos cells. Various cells treated with inhibitor or PROTAC were assessed for proliferation and viability. Wild-type- or BTK-transfected cells were transplanted in CB17/SCID mice and the established tumors were assessed using immunohistochemistry.
Results
Of the PROTACs tested, UBX-382 showed superior degradation activity for wild-type (WT) and mutant BTK proteins in a single-digit nanomolar range of DC50 in DLBCL cell line. UBX-382 was effective on seven out of eight known BTK mutants in in vitro experiment and was highly effective in inhibiting tumor growth in murine xenograft models harboring WT or C481S mutant BTK-expressing TMD-8 cells over ibrutinib, ARQ-531, and MT-802. Remarkably, oral dosing of UBX-382 for less than 2-weeks led to complete tumor regression in 3 and 10 mg/kg groups in murine xenograft models. UBX-382 also provoked the cell-type-dependent and selective degradation of CRBN neo-substrates in various hematological cancer cells.
Conclusions
These results suggest that UBX-382 treatment is a promising therapeutic strategy for B-cell-related blood cancers with improved efficacy and diverse applicability.
Gliclazide prevents irradiation-induced cardiotoxicity and lung injury through inhibiting Oxidative Stress: a biochemical and histopathological study
Authors: Amiri Fereshteh Talebpour , Arzani Sourosh , Farzipour Soghra , Hosseinimehr Seyed Jalal
Published: April 2022

Background
Cardiotoxicity and lung injury are two of the main side effects of oxidative stress following radiotherapy in patients with thoracic region cancer. Gliclazide (GLZ) as an antihyperglycemic drug has antioxidant, anti-inflammatory, and anti-apoptotic activities. This study aimed to evaluate the effect of GLZ in cardiotoxicity and lung injury induced by irradiation (IR).
Materials and methods
In this experimental study, Sixty-four mice were divided into eight groups: control, GLZ (5, 10, and 25 mg/kg), IR (6 Gy), and IR + GLZ (in three doses). GLZ was administrated for 8 consecutive successive days and mice were exposed with IR on the 9th day of study. On the 10th day of study, tissue biochemical assay and at 14th day of study, histopathological assay were performed to evaluate for cardiotoxicity and lung injury.
Results
The findings revealed that IR induces atypical features in heart and lung histostructure, and oxidative stress (an increase of MDA, PC levels, and decrease of GSH content) in these tissues. GLZ administration preserved heart and lung damages and improves oxidative stress markers in mice.
Conclusion
Data have authenticated that GLZ could protect heart and lung histostructure against oxidative stress-induced injury through inhibiting oxidative stress.
TIGIT is Positively Associated with Advanced Human Glioma and Displays an Immunosuppressive Microenvironment
Authors: Qandouci Ahmed , Ghouzlani Amina , Kone Abdou-Samad , Lakhdar Abdelhakim , Badou Abdallah
Published: April 2022

Background: Diffuse glioma is a malignant human brain cancer that is hard to overcome. This represents a high risk of mortality. The current challenge is limited to the control of tumor progression and survival improvement.Immunotherapy consists of stimulating the immune system in order to eliminate the non-self-elements that damage the human body, including cancer cells. However, in human glioma, the current immunotherapeutic targets did not show significant benefit. In this study, we aimed at evaluating the expression and potential role of a new immunosuppressive molecule, TIGIT in glioma patients. Patients and Methods: A cohort of 667 patients from the TCGA database along with a cohort of 53 Moroccan patients, were analyzed in order to assess the role of TIGIT in human glioma progression and to estimate whether blocking this immune checkpoint molecule would be of a potential therapeutic benefit.Real time RT-PCR from fresh human biopsies and bioinformatics approaches were both used in this study. Results: Our results showed that high expression of TIGIT had prognostic value with some known clinical glioma risk factors such as sex, age and mutation status. High expression of TIGIT was positively associated with an advanced grade of glioma. Moreover, elevated levels of TIGIT were correlated to higher rates of FoxP3, a regulatory T-cell marker that reflects a strong immunosuppressive microenvironment. Interestingly, TIGIT showed strong association with Treg cell-secreted cytokines (TGF-beta and IL-10), supporting the likely involvement of TIGIT in the exhaustion of the intra-tumoral immune cells. Finally, elevated rates of TIGIT were significantly associated to elevated rates of other inhibitory immune checkpoint molecules (PD-1, VISTA and Tim-3) in human glioma patients.Conclusions: TIGIT blockade might be of valuable therapeutic benefit in patients with advanced gliomas.
Incidence and risk factors for early and late reoperation following lumbar fusion surgery
Authors: Wang Shuaikang , Wang Peng , Li Xiang-yu , Kong Chao , Cui Peng , Lu Shi-bao
Published: April 2022

Study Design. Retrospective Cohort StudyPurpose. The aim of our study was to determine the rates and indications of reoperations following primary lumbar fusion, as well as the independent risk factors for early and late reoperation.Methods. We retrospectively reviewed patients who underwent lumbar fusion surgery between January 2017 and September 2020. All patients were followed up for more than 1 year. Characteristics, laboratory tests, primary diagnosis and surgery-related variables were compared among the early reoperation (< three months), the late reoperation (> three months) and the non-reoperation groups. Multivariable logistic regression analysis was used to identify independent risk factors for early and late reoperations.Results. Of 877 patients included in our studies, 34 patients underwent early reoperation, and 35 patients underwent late reoperation. The cumulative reoperation rate was about 3.9% (95%CI, 2.6%-5.2%) at three months,5.6% (95%CI, 4.1%–7.1%) at 1 year and 7.1% (95%CI 5.4%–8.8%) at 2 years. Multivariable analysis indicated that osteoporosis (odds ratio [OR] 3.8, 95%CI 1.3-10.9, p=0.01) and diabetes (OR 2.2, 95%CI 1.1-4.5, p=0.03) were independently associated with early reoperation and multilevel fusion (OR 2.4, 95%CI 1.0-5.5, p=0.03) was independently associated with late reoperation.Conclusions. The most common reasons for early reoperation and late operation were surgical site infection and adjacent segment diseases, respectively. Osteoporosis and diabetes were independent risk factors for early reoperation and multilevel fusion was independent risk factor for late reoperation. Surgeons should pay more attention to these patients and future studies should consider the effects of follow-up periods on results.
Optimal Design of Circuit Breaker Based on Flower Pollination Algorithm
Authors: LI Guodong , XIE Min , TIAN Yunhe
Published: April 2022

The flower pollination algorithm is a new meta-heuristic algorithm that simulates the pollination behavior of flowers in nature. Aiming at the problem that the basic flower pollination algorithm is easy to fall into the local optimum and the later convergence speed is slow, the "adaptive-mutation catfish" flower pollination algorithm is proposed, Introduce the adaptive step size in the global pollination stage, introduce the mutation strategy and catfish effect in the local pollination stage, and use the classic test function to analyze the performance of the improved algorithm. The improved flower pollination algorithm is applied to the high breaking and comprehensive optimization design of the circuit breaker, the mathematical model of the high breaking and comprehensive optimization of the circuit breaker is constructed, and the optimal design method of the circuit breaker based on the flower pollination algorithm is given. The results show that the circuit breaker optimization design method based on flower pollination algorithm is feasible, and the improved flower pollination algorithm is effective.