bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time to death and its predictors among adult patients with COVID-19: A retrospective cohort study in Ethiopia
Authors: Atamenta Tegene , Cherie Amsale , Alemu Wudma 
Published: January 2023

BackgroundCoronavirus (COVID-19) disease affected people throughout the globe and has become a severe threat to the health and wellbeing of the global community. Time to death and predictors of mortality vary across settings. So far, no or few related studies have been undertaken in Ethiopia. Studying the time to death from COVID-19 and its predictors is essential to understand the characteristics of the disease and thereby contribute to the identification of indicators for early detection and initiation of treatment. Therefore, this study aimed to estimate time to death and its predictors among adults with COVID-19 in Ethiopia.MethodsA retrospective follow-up study was conducted among 602 adults with COVID-19 attending Eka Kotebe General Hospital, COVID-19 Treatment Center, between 13 March 2020 and 13 November 2020. The data were entered by Epi-data version 4.2 while the analysis was carried out using STATA version 16. A Kaplan–Meier survivor curve was computed to estimate the survival probabilities. A log-rank test was used to compare the difference in survival curves. Cox proportional hazard models were fitted to identify the predictors of time to death.ResultsThe overall median time to death was 21 days. Older adults (aged ≥65 years) [adjusted hazard ratio (AHR) 2.22, 95% confidence interval (CI) 1.02–4.86], being men (AHR 3.04, 95% CI 1.61–5.74), shortness of breathing at admission (AHR 2.29, 95% CI 1.16–4.54), comorbidity (AHR 2.23, 95% CI 1.04–4.80), diabetes mellitus (AHR 2.31, 95% CI 1.30–4.08), altered cardiac function (AHR 2.07, 95% CI 1.21–3.43), and baseline white blood cell count of greater than 10 (103/µl) (AHR 2.62, 95% CI 1.55–4.44) were independent predictors of COVID-19 mortality.ConclusionMale sex, older adults, shortness of breathing at admission, patients with comorbidities, and higher blood cell count were significant predictors of time to death from COVID-19. Therefore, concerned stakeholders should focus on those predictors of mortality and design interventions accordingly to enhance the survival of patients with COVID-19.
Identification and validation of a muscle failure index to predict prognosis and immunotherapy in lung adenocarcinoma through integrated analysis of bulk and single-cell RNA sequencing data
Authors: Gu Xuyu , Cai Lubing , Luo Zhiwen , Shi Luze , Peng Zhen , Sun Yaying , Chen Jiwu 
Published: January 2023

BackgroundIt was previously reported that the production of exerkines is positively associated with the beneficial effects of exercise in lung adenocarcinoma (LUAD) patients. This study proposes a novel scoring system based on muscle failure-related genes, to assist in clinical decision making.MethodsA comprehensive analysis of bulk and single cell RNA sequencing (scRNA-seq) of early, advanced and brain metastatic LUAD tissues and normal lung tissues was performed to identify muscle failure-related genes in LUAD and to determine the distribution of muscle failure-related genes in different cell populations. A novel scoring system, named MFI (Muscle failure index), was developed and validated. The differences in biological functions, immune infiltration, genomic alterations, and clinical significance of different subtypes were also investigated.ResultsFirst, we conducted single cell analysis on the dataset GSE131907 and identified eight cell subpopulations. We found that four muscle failure-related genes (BDNF, FNDC5, IL15, MSTN) were significantly increased in tumor cells. In addition, IL15 was widely distributed in the immune cell population. And we have validated it in our own clinical cohort. Then we created the MFI model based on 10 muscle failure-related genes using the LASSO algorithm, and MFI remained an independent prognostic factor of OS in both the training and validation cohorts. Moreover, we generated MFI in the single-cell dataset, in which cells with high MFI received and sent more signals compared to those with low MFI. Biological function analysis of both subtypes revealed stronger anti-tumor immune activity in the low MFI group, while tumor cells with high MFI had stronger metabolic and proliferative activity. Finally, we systematically assessed the immune cell activity and immunotherapy responses in LUAD patients, finding that the low MFI group was more sensitive to immunotherapy.ConclusionOverall, our study can improve the understanding of the role of muscle failure-related genes in tumorigenesis and we constructed a reliable MFI model for predicting prognosis and guiding future clinical decision making.
Immunogenicity and reactogenicity of accelerated regimens of fractional intradermal COVID-19 vaccinations
Authors: Niyomnaitham Suvimol , Atakulreka Suparat , Wongprompitak Patimaporn , Copeland Katherine Kradangna , Toh Zheng Quan , Licciardi Paul V. , Srisutthisamphan Kanjana , Jansarikit Laddawan , Chokephaibulkit Kulkanya 
Published: January 2023

IntroductionThis phase I study explored the immunogenicity and reactogenicity of accelerated, Q7 fractional, intradermal vaccination regimens for COVID-19.MethodsParticipants (n = 60) aged 18-60 years, naïve to SARS-CoV-2 infection or vaccination, were randomly allocated into one of four homologous or heterologous accelerated two-dose, two-injection intradermal regimens seven days apart:(1) BNT162b2-BNT162b2(n= 20),(2) ChAdOx1- BNT162b2 (n = 20), (3) CoronaVac-ChAdOx1 (n = 10), and (4) ChAdOx1-ChAdOx1 (n = 10). CoronaVac and ChAdOx1 were 20%, and BNT162b2 17%, of their standard intramuscular doses (0.1 mL and 0.05 mL per injection, respectively). Humoral immune responses were measured through IgG response towards receptor binding domains (RBD-IgG) of ancestral SARS-CoV-2 spike protein and pseudovirus neutralization tests (PVNT50). Cellular immune responses were measured using ELISpot for ancestral protein pools.ResultsImmunogenicity was highest in regimen (2), followed by (1), (4), and (3) 2 weeks after the second dose (P &lt; 0.001 for anti-RBD-IgG and P= 0.01 for PVNT50). Each group had significantly lower anti-RBD IgG (by factors of 5.4, 3.6, 11.6, and 2.0 for regimens (1) to (4), respectively) compared to their respective standard intramuscular regimens (P &lt; 0.001 for each). Seroconversion rates for PVNT50 against the ancestral strain were 75%, 90%, 57% and 37% for regimens (1) to (4), respectively. All participants elicited ELISpot response to S-protein after vaccination. Adverse events were reportedly mild or moderate across cohorts.DiscussionWe concluded that accelerated, fractional, heterologous or homologous intradermal vaccination regimens of BNT162b2 and ChAdOx1 were well tolerated, provided rapid immune priming against SARS-CoV-2, and may prove useful for containing future outbreaks.
A multi-epitope vaccine GILE against Echinococcus Multilocularis infection in mice
Authors: Zhou Pei , Zhou Zhen , Huayu Meiduo , Wang Lei , Feng Lin , Xiao Yang , Dai Yao , Xin Mingyuan , Tang Feng , Li Runle 
Published: January 2023

IntroductionThe objective of this study is to construct a multi-epitope vaccine GILE containing B-cell and T-cell epitopes against Echinococcus Multilocularis (E. multilocularis) infection based on the dominant epitopes of E. multilocularis EMY162, LAP, and GLUT1.MethodsThe structure and hydrophobicity of GILE were predicted by SWISSMODEL, pyMOL, SOPMA and VMD, and its sequence was optimized by Optimum™ Codon. The GILE gene was inserted into pCzn1 and transformed into Escherichia coli Arctic express competent cells. IPTG was added to induce the expression of recombinant proteins. High-purity GILE recombinant protein was obtained by Ni-NTA Resin. BALB/c mice were immunized with GILE mixed with Freund’s adjuvant, and the antibody levels and dynamic changes in the serum were detected by ELISA. Lymphocyte proliferation was detected by MTS. The levels of IFN-g and IL-4 were detected by ELISpot and flow cytometry (FCM). T cells were detected by FCM. The growth of hepatic cysts was evaluated by Ultrasound and their weights were measured to evaluate the immune protective effect of GILE.ResultsThe SWISS-MODEL analysis showed that the optimal model was EMY162 95-104―LAP464-479―LAP495-510―LAP396-410―LAP504-518―EMY162112-126. The SOPMA results showed that there were Alpha helix (14.88%), Extended strand (26.25%), Beta turn (3.73%) and Random coil (45.82%) in the secondary structure of GILE. The restriction enzyme digestion and sequencing results suggested that the plasmid pCzn1-GILE was successfully constructed. The SDSPAGE results indicated that the recombinant protein was 44.68 KD. The ELISA results indicated that mice immunized with GILE showed higher levels of serum antibodies compared to the PBS group. The FCM and ELISpot results indicated that mice immunized with GILE secreted more IFN-g and IL-4. Immunization with GILE also led to a significant decrease in the maximum diameter and weight of cysts and stimulated the production of CD4+ and CD8+ T Cell.DiscussionA multi-epitope vaccine GILE with good immunogenicity and antigenicity has been successfully constructed in this study, which may provide important theoretical and experimental bases for the prevention and treatment of E. multilocularis infection.
Effect of immunostimulation with bacterial lysate on the clinical course of allergic rhinitis and the level of γδT, iNKT and cytotoxic T cells in children sensitized to grass pollen allergens: A randomized controlled trial
Authors: Janeczek Kamil , Kowalska Wioleta , Zarobkiewicz Michał , Suszczyk Dorota , Mikołajczyk Marek , Markut-Miotła Ewa , Morawska-Michalska Izabela , Bakiera Adrian , Tomczak Aleksandra , Kaczyńska Agnieszka , Emeryk Andrzej , Roliński Jacek , Piotrowska-Weryszko Krystyna 
Published: January 2023

BackgroundThere are many drugs for allergic rhinitis (AR), however, these drugs show variable clinical effectiveness and some side effects. Therefore, new methods of AR pharmacotherapy are being sought.ObjectivesThe objectives of this study were to evaluate the efficacy of polyvalent mechanical bacterial lysate (PMBL) therapy in improving the clinical course of grass pollen-induced AR (seasonal AR, SAR) in children and its effect on changes in the blood level of the γδT, iNKT and cytotoxic T cell subsets.MethodsFifty children with SAR were enrolled in this study and were randomly assigned to either the PMBL group or the placebo group. The severity of SAR symptoms was assessed using the total nasal symptom score (TNSS) and visual analogue scale (VAS). During two visits (V1, V2), peak nasal inspiratory flow (PNIF) was measured and peripheral blood was collected for immunological analyses. The study also included 2 telephone contacts (TC1, TC2).ResultsThe severity of the nasal symptoms of SAR on the TNSS scale was revealed to have a significantly lower impact in the PMBL group vs the placebo group at measuring points TC1 and V2 (p = 0.01, p = 0.009, respectively). A statistically significantly lower mean severity of nasal symptoms of SAR on the VAS scale was recorded for children in the PMBL group compared to the placebo group at measuring points TC1, V2 and TC2 (p = 0.04, p = 0.04, p = 0.03, respectively). The compared groups do not show significant differences in terms of PNIF values at individual measuring points. There were no statistically significant changes in immune variables. For both groups, there was a statistically significant association between the level of Th1-like γδT cells and the severity of SAR symptoms expressed on the TNSS scale (p = 0.03) – the lower the level of Th1-like γδT cells, the higher the TNSS value.ConclusionAdministration of sublingual PMBL tablets during the grass pollen season proves to have a high efficacy in alleviating SAR symptoms in children sensitized to grass pollen allergens. Th1-like γδT cells may be used as potential markers for SAR severity in children.Clinical trial registrationClinicalTrials.gov, identifier (NCT04802616).
Discovery of pyrazolopyrrolidinones as potent, broad-spectrum inhibitors of Leishmania infection
Authors: Kavouris John A. , McCall Laura-Isobel , Giardini Miriam A. , De Muylder Geraldine , Thomas Diane , Garcia-Pérez Adolfo , Cantizani Juan , Cotillo Ignacio , Fiandor Jose M. , McKerrow James H. , De Oliveira Camila I. , Siqueira-Neto Jair L. , González Silvia , Brown Lauren E. , Schaus Scott E. 
Published: January 2023

IntroductionLeishmaniasis is a parasitic disease that affects more than 1 million people worldwide annually, predominantly in resource-limited settings. The challenge in compound development is to exhibit potent activity against the intracellular stage of the parasite (the stage present in the mammalian host) without harming the infected host cells. We have identified a compound series (pyrazolopyrrolidinones) active against the intracellular parasites of Leishmania donovani and L. major; the causative agents of visceral and cutaneous leishmaniasis in the Old World, respectively.MethodsIn this study, we performed medicinal chemistry on a newly-discovered antileishmanial chemotype, with over 100 analogs tested. Studies included assessments of antileishmanial potency, toxicity towards host cells, and in vitro ADME screening of key drug properties.Results and discussionMembers of the series showed high potency against the deadliest form, visceral leishmaniasis (approximate EC50 ≥ 0.01 µM without harming the host macrophage up to 10.0 µM). In comparison, the most efficient monotherapy treatment for visceral leishmaniasis is amphotericin B, which presents similar activity in the same assay (EC50 = 0.2 µM) while being cytotoxic to the host cell at 5.0 µM. Continued development of this compound series with the Discovery Partnership with Academia (DPAc) program at the GlaxoSmithKline Diseases of the Developing World (GSK DDW) laboratories found that the compounds passed all of GSK’s criteria to be defined as a potential lead drug series for leishmaniasis.ConclusionHere, we describe preliminary structure-activity relationships for antileishmanial pyrazolopyrrolidinones, and our progress towards the identification of candidates for future in vivo assays in models of visceral and cutaneous leishmaniasis.
Heterogeneity in diagnostic characters across ecoregions: A case study with Botrynema (Hydrozoa: Trachylina: Halicreatidae)
Authors: Montenegro Javier , Collins Allen G. , Hopcroft Russell R. , Questel Jennifer M. , Thuesen Erik V. , Bachtel Tiffany S. , Bergman Leah A. , Sangekar Mehul N. , Drazen Jeffrey C. , Lindsay Dhugal J. 
Published: January 2023

IntroductionBotrynema, a genus of medusozoans in the trachyline family Halicreatidae, currently contains two species: B. brucei and B. ellinorae, distinguished by the presence or absence, respectively, of an apical knob as a diagnostic character. However, no study has corroborated if these taxonomic diagnoses have a biological and evolutionary basis. Therefore, in this study we attempted to address the question “do the two nominal species in the genus Botrynema represent independent phylogenetic lineages, or two phenotypic variants of a single species?MethodsIn this study we took advantage of legacy collections from different research expeditions across the globe from 2000 to 2021 to study the phylogenetics and taxonomy of the genus Botrynema.ResultsB. brucei and B. ellinorae present partially overlapping vertical distributions in the Arctic and as a whole in the Arctic the genus seems to be limited to the Atlantic water masses. The phylogenetic reconstruction based on the concatenated alignment corroborates the validity of the family Halicreatidae and of genus Botrynema as monophyletic groups. However no clear differentiation was found between the two presently accepted species, B. ellinorae and B. brucei.DiscussionBased on the evidence we gathered, we conclude that while the genus Botrynema does contain at least two species lineages, these lineages are not concordant with current species definitions. The species B. ellinorae is reassigned as a subspecies of B. brucei and diagnostic characters are provided.
An analysis of neurovascular disease markers in the hippocampus of Tupaia chinensis at different growth stages
Authors: Ouyang Yiqiang , Zhang Ying , Guo Xiaoping , Li Jiafu , Ao Qingqing , Guo Songchao , Zhang Mingyuan , Sun Junming 
Published: January 2023

IntroductionIt is considered thatTupaia chinensiscan replace laboratory primates in the study of nervous system diseases. To date, however, protein expression in the brain ofTupaia chinensishas not been fully understood.MethodThree age groups ofT. chinensis-15 days, 3 months and 1.5 years—were selected to study their hippocampal protein expression profiles.ResultsA significant difference was observed between the 15-day group and the other two age groups, where as there were no significant differences between the 3-month and 1.5-year age groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that differentially expressed proteins could be enriched in several pathways related to neurovascular diseases, such as metabolic pathways for Alzheimer's disease (AD), Huntington's disease, Parkinson's disease, and other diseases. The KEGG enrichment also showed that relevant protein involved in oxidative phosphorylation in the hippocampus ofT. chinensisfor 15days were downregulated, and ribosomal proteins (RPs) were upregulated, compared to those in the hippocampus of the other two age groups.DiscussionIt was suggested that when the hippocampus ofT. chinensisdeveloped from day 15 to 3 months, the expression of oxidatively phosphorylated proteins and RPs would vary over time. Meanwhile, the hippocamppal protein expression profile ofT. chinensisafter 3 months had become stable. Moreover, the study underlines that, during the early development of the hippocampus ofT. chinensis, energy demand increases while protein synthesis decreases. The mitochondria ofT. chinensischanges with age, and the oxidative phosphorylation metabolic pathway of mitochondria is closely related to neurovascular diseases, such as stroke and cerebral ischemia.
Spatial rehabilitation using virtual auditory space training paradigm in individuals with sensorineural hearing impairment
Authors: Nisha Kavassery Venkateswaran , Uppunda Ajith Kumar , Kumar Rakesh Trinesh 
Published: January 2023

PurposeThe present study aimed to quantify the effects of spatial training using virtual sources on a battery of spatial acuity measures in listeners with sensorineural hearing impairment (SNHI).MethodsAn intervention-based time-series comparison design involving 82 participants divided into three groups was adopted. Group I (n = 27, SNHI-spatially trained) and group II (n = 25, SNHI-untrained) consisted of SNHI listeners, while group III (n = 30) had listeners with normal hearing (NH). The study was conducted in three phases. In the pre-training phase, all the participants underwent a comprehensive assessment of their spatial processing abilities using a battery of tests including spatial acuity in free-field and closed-field scenarios, tests for binaural processing abilities (interaural time threshold [ITD] and level difference threshold [ILD]), and subjective ratings. While spatial acuity in the free field was assessed using a loudspeaker-based localization test, the closed-field source identification test was performed using virtual stimuli delivered through headphones. The ITD and ILD thresholds were obtained using a MATLAB psychoacoustic toolbox, while the participant ratings on the spatial subsection of speech, spatial, and qualities questionnaire in Kannada were used for the subjective ratings. Group I listeners underwent virtual auditory spatial training (VAST), following pre-evaluation assessments. All tests were re-administered on the group I listeners halfway through training (mid-training evaluation phase) and after training completion (post-training evaluation phase), whereas group II underwent these tests without any training at the same time intervals.Results and discussionStatistical analysis showed the main effect of groups in all tests at the pre-training evaluation phase, with post hoc comparisons that revealed group equivalency in spatial performance of both SNHI groups (groups I and II). The effect of VAST in group I was evident on all the tests, with the localization test showing the highest predictive power for capturing VAST-related changes on Fischer discriminant analysis (FDA). In contrast, group II demonstrated no changes in spatial acuity across timelines of measurements. FDA revealed increased errors in the categorization of NH as SNHI-trained at post-training evaluation compared to pre-training evaluation, as the spatial performance of the latter improved with VAST in the post-training phase.ConclusionThe study demonstrated positive outcomes of spatial training using VAST in listeners with SNHI. The utility of this training program can be extended to other clinical population with spatial auditory processing deficits such as auditory neuropathy spectrum disorder, cochlear implants, central auditory processing disorders etc.
The relationship between intake of fruits, vegetables and dairy products with overweight and obesity in a large sample in Iran: Findings of STEPS 2016
Authors: Nouri Mehran , Shateri Zainab , Faghih Shiva 
Published: January 2023

BackgroundThe present study aimed to investigate the association between fruits and vegetables (FVs) and dairy product intake with body weight based on the data from the nationwide Stepwise approach to surveillance (STEPS) survey in Iran.MethodsSTEPS is a national-based cross-sectional study conducted on 3,0541 people selected by stratified cluster random sampling in Iran from April to November 2016. The outcome of the current study was body mass index (BMI) which was classified as normal weight, underweight, overweight, and obese. Also, as exposure variables, dietary intakes of fruits, vegetables and dairy products were extracted from the STEPS questionnaires. Multinomial logistic regression was used to evaluate the association between dairy products, FVs consumption, and BMI category in the crude and adjusted models.ResultsIn the adjusted model, we observed 41% [odd ratio (OR) = 0.59; 95% confidence intervals (CI): 0.50, 0.68, P &lt; 0.001], 27% (OR = 0.73; 95% CI: 0.62, 0.84,P&lt; 0.001), and 26% (OR = 0.74; 95% CI: 0.63, 0.87,P&lt; 0.001) lower odds of being overweight, and 46% (OR = 0.54; 95% CI: 0.46, 0.64,P&lt; 0.001), 29% (OR = 0.71; 95% CI: 0.60, 0.84,P&lt; 0.001), and 21% (OR = 0.79; 95% CI: 0.65, 0.95,P= 0.014) decrease in obesity odds among the participants who consumed 1, 2, and more than 2 servings of fruits per day in comparison to less than one serving, respectively. Also, we observed participants who consumed 1, 2, and more than 2 servings in comparison to less than one serving of dairy products per day had 31% (OR = 0.69; 95% CI: 0.58, 0.81,P&lt; 0.001), 23% (OR = 0.77; 95 %CI: 0.65, 0.91,P= 0.002), and 21% (OR = 0.79; 95% CI: 0.67, 0.94,P= 0.011) lower odds of being overweight and 47% (OR = 0.53; 95% CI: 0.44, 0.64,P&lt; 0.001), 36% (OR = 0.64; 95% CI: 0.53, 0.77,P&lt; 0.001), and 32% (OR = 0.68; 95% CI: 0.56, 0.83,P&lt; 0.001) lower odds of obesity, respectively. In addition, compared to participants who consumed less than 2 servings of vegetables per day, participants who consumed 2, 3, and more than 3 servings had 40% (OR = 0.60; 95% CI: 0.47, 0.76,P&lt; 0.001), 29% (OR = 0.71; 95% CI: 0.56, 0.90,P= 0.006), and 26% (OR = 0.74; 95% CI: 0.57, 0.96,P= 0.027) lower odds of being overweight, respectively. Furthermore, we observed 36% lower odds of obesity among participants who ate 2 servings of vegetables per day compared to less than 2 serving (OR = 0.64; 95% CI: 0.49, 0.84,P= 0.002).ConclusionOur findings showed that intake of FVs and dairy products is associated with a healthier weight status in adults. Further studies are needed to confirm these findings.