bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of CD8+ T cell epitopes through proteasome cleavage site predictions
Authors: Gomez-Perosanz Marta , Ras-Carmona Alvaro , Lafuente Esther M. , Reche Pedro A. 
Published: December 2020

Abstract
Background
We previously introduced PCPS (Proteasome Cleavage Prediction Server), a web-based tool to predict proteasome cleavage sites using n-grams. Here, we evaluated the ability of PCPS immunoproteasome cleavage model to discriminate CD8+ T cell epitopes.

Results
We first assembled an epitope dataset consisting of 844 unique virus-specific CD8+ T cell epitopes and their source proteins. We then analyzed cleavage predictions by PCPS immunoproteasome cleavage model on this dataset and compared them with those provided by a related method implemented by NetChop web server. PCPS was clearly superior to NetChop in term of sensitivity (0.89 vs. 0.79) but somewhat inferior with regard to specificity (0.55 vs. 0.60). Judging by the Mathew’s Correlation Coefficient, PCPS predictions were overall superior to those provided by NetChop (0.46 vs. 0.39). We next analyzed the power of C-terminal cleavage predictions provided by the same PCPS model to discriminate CD8+ T cell epitopes, finding that they could be discriminated from random peptides with an accuracy of 0.74. Following these results, we tuned the PCPS web server to predict CD8+ T cell epitopes and predicted the entire SARS-CoV-2 epitope space.

Conclusions
We report an improved version of PCPS named iPCPS for predicting proteasome cleavage sites and peptides with CD8+ T cell epitope features. iPCPS is available for free public use at https://imed.med.ucm.es/Tools/pcps/.
Three redescriptions in Tintinnopsis (Protista: Ciliophora: Tintinnina) from coastal waters of China, with cytology and phylogenetic analyses based on ribosomal RNA genes
Authors: Bai Yang , Wang Rui , Song Wen , Li Lifang , Santoferrara Luciana F. , Hu Xiaozhong 
Published: December 2020

Abstract
Background
The taxonomy of tintinnine ciliates is vastly unresolved because it has traditionally been based on the lorica (a secreted shell) and it has only recently incorporated cytological and molecular information. Tintinnopsis, the most speciose tintinnine genus, is also the most problematic: it is known to be non-monophyletic, but it cannot be revised until more of its species are studied with modern methods.

Results
Here, T. hemispiralis Yin, 1956, T. kiaochowensis Yin, 1956, and T. uruguayensis Balech, 1948, from coastal waters of China, were studied. Lorica and cell features were morphometrically investigated in living and protargol-stained specimens, and sequences of three ribosomal RNA (rRNA) loci were phylogenetically analyzed. The three species show a complex ciliary pattern (with ventral, dorsal, and posterior kineties and right, left, and lateral ciliary fields), but differ in lorica morphology, details of the somatic ciliature and rRNA gene sequences. Tintinnopsis hemispiralis is further distinguished by a ciliary tuft (a ribbon of very long cilia originated from the middle portion of the ventral kinety and extending out of the lorica) and multiple macronuclear nodules. Both T. kiaochowensis and T. uruguayensis have two macronuclear nodules, but differ in the number of somatic kineties and the position of the posterior kinety. Two neotypes are fixed for T. hemispiralis and T. kiaochowensis to stabilize the species names objectively, mainly because of the previous unavailability of type materials. By phylogenetic analysis and comparison with closely-related species, we infer that the ciliary tuft and details such as the commencement of the rightmost kinety in the lateral ciliary field are synapomorphies that may help clarify the systematics of Tintinnopsis-like taxa.

Conclusion
The redescriptions of three poorly known Tintinnopsis species, namely T. hemispiralis, T. kiaochowensis, and T. uruguayensis firstly revealed their ciliary patterns and rRNA sequences. This study expands knowledge and database of tintinnines and helps in identifying potential synapomorphies for future taxonomic rearrangements.
Asymptomatic malaria and hepatitis B do not influence cytokine responses of persons involved in chronic sedentary activities
Authors: Anabire Nsoh Godwin , Aryee Paul Armah , Ziblim Zulka , Suurbaar Jonathan , Ansah Felix , Helegbe Gideon Kofi 
Published: December 2020

AbstractBackgroundChronic Sedentary lifestyles have been linked to increased odds of stress, elevated anxiety and diminished wellbeing, inducing cytokine production and predispose to hypertension and other cardiovascular diseases. In endemic areas,Plasmodium falciparumand hepatitis B virus (HBV) infections can trigger pro-inflammatory cytokine responses. However, the impact of these infections on cytokine response profiles in individuals engaged in chronic sedentary activities is unknown. This study was aimed at addressing these concerns using a predominantly sedentary population of traders in the Tamale metropolis of Ghana.MethodFour hundred respondents were categorized, based on their number of working years (< or ≥ 5 years) and number of working hours per day (< or ≥ 10 h), into sedentary (≥5 years + ≥ 10 h)and non-sedentary (≥ 5 years + < 10 h, < 5 years + ≥ 10 h and <  5 years + < 10 h)groups. The participants were tested forP. falciparumand HBV infections using polymerase chain reaction. Blood pressure and cytokines responses were measured. Associations and comparison analysis between variables were determined, and test statistics withp < 0.05were considered statistically significant.ResultsInfection status included: un-infected (93.5%),P. falciparummono-infected (1.0%), HBV mono-infected (3.0%) orP. falciparum/HBV co-infected (2.5%). Majority of the participants, 57.0% (n = 228) were involved in chronic sedentary life style. That notwithstanding, sedentary lifestyle was independent of the infection groups(χ2 = 7.08, p = 0.629).Hypertension was diagnosed in 53.8% of respondents and was independent of infection status(X2 = 6.33, p = 0.097).Pro-inflammatory(TNF-α, IL-1β, IL-6, IL-8 and IL-12)and anti-inflammatory(IL-10, IL-7 and IL-13)cytokine responses were similar among individuals with different sedentary working time and between hypertensive and non-hypertensive individuals(p > 0.05 for all comparisons).Among individuals with different infection status, pro-inflammatory (TNF-α; p = 0.290, IL-1β; p = 0.442, IL-6; p = 0.686, IFN-γ; p = 0.801, IL-8; p = 0.546, IL-12; p = 0.154)and anti-inflammatory (IL-10; p = 0.201, IL-7; p = 0.190, IL-13; p = 0.763)cytokine responses were similar.ConclusionOur data suggest that asymptomatic infections ofP. falciparumand HBV together with a high prevalence of hypertension did not have any significant impact on cytokine response profiles among predominantly sedentary traders in the Tamale metropolis of Ghana.
Protocol for iGrow (Infant Growth and Development Study): biopsychosocial predictors of childhood obesity risk at 2 years
Authors: Leerkes Esther M. , Buehler Cheryl , Calkins Susan D. , Shriver Lenka H. , Wideman Laurie 
Published: December 2020

AbstractBackgroundChildhood obesity remains a significant public health problem. To date, most research on the causes and correlates of obesity has focused on a small number of direct predictors of obesity rather than testing complex models that address the multifactorial nature of the origins of obesity in early development. We describe the rationale and methods of iGrow (Infant Growth and Development Study) which will test multiple pathways by which (a) prenatal maternal psychobiological risk predicts infant weight gain over the first 6 months of life, and (b) this early weight gain confers risk for obesity at age 2. Infant hormonal and psychobiological risk are proposed mediators from prenatal risk to early weight gain, though these are moderated by early maternal sensitivity and obesogenic feeding practices. In addition, higher maternal sensitivity and lower obesogenic feeding practices are proposed predictors of adaptive child self-regulation in the second year of life, and all three are proposed to buffer/reduce the association between high early infant weight gain and obesity risk at age 2.MethodsiGrow is a prospective, longitudinal community-based study of 300 diverse mothers and infants to be followed across 5 data waves from pregnancy until children are age 2. Key measures include (a) maternal reports of demographics, stress, well-being, feeding practices and child characteristics and health; (b) direct observation of maternal and infant behavior during feeding, play, and distress-eliciting tasks during which infant heart rate is recorded to derive measures of vagal withdrawal; (c) anthropometric measures of mothers and infants; and (d) assays of maternal prenatal blood and infant saliva and urine. A host of demographic and other potential confounds will be considered as potential covariates in structural equation models that include tests of mediation and moderation. Efforts to mitigate the deleterious effects of COVID-19 on study success are detailed.DiscussionThis study has the potential to inform (1) basic science about early life processes casually related to childhood obesity and (2) development of targeted intervention and prevention approaches that consider mother, infant, and family risks and resources.
Spatial-temporal patterns of malaria incidence in Uganda using HMIS data from 2015 to 2019
Authors: Kigozi Simon P. , Kigozi Ruth N. , Sebuguzi Catherine M. , Cano Jorge , Rutazaana Damian , Opigo Jimmy , Bousema Teun , Yeka Adoke , Gasasira Anne , Sartorius Benn , Pullan Rachel L. 
Published: December 2020

Abstract
Background
As global progress to reduce malaria transmission continues, it is increasingly important to track changes in malaria incidence rather than prevalence. Risk estimates for Africa have largely underutilized available health management information systems (HMIS) data to monitor trends. This study uses national HMIS data, together with environmental and geographical data, to assess spatial-temporal patterns of malaria incidence at facility catchment level in Uganda, over a recent 5-year period.

Methods
Data reported by 3446 health facilities in Uganda, between July 2015 and September 2019, was analysed. To assess the geographic accessibility of the health facilities network, AccessMod was employed to determine a three-hour cost-distance catchment around each facility. Using confirmed malaria cases and total catchment population by facility, an ecological Bayesian conditional autoregressive spatial-temporal Poisson model was fitted to generate monthly posterior incidence rate estimates, adjusted for caregiver education, rainfall, land surface temperature, night-time light (an indicator of urbanicity), and vegetation index.

Results
An estimated 38.8 million (95% Credible Interval [CI]: 37.9–40.9) confirmed cases of malaria occurred over the period, with a national mean monthly incidence rate of 20.4 (95% CI: 19.9–21.5) cases per 1000, ranging from 8.9 (95% CI: 8.7–9.4) to 36.6 (95% CI: 35.7–38.5) across the study period. Strong seasonality was observed, with June–July experiencing highest peaks and February–March the lowest peaks. There was also considerable geographic heterogeneity in incidence, with health facility catchment relative risk during peak transmission months ranging from 0 to 50.5 (95% CI: 49.0–50.8) times higher than national average. Both districts and health facility catchments showed significant positive spatial autocorrelation; health facility catchments had global Moran’s I = 0.3 (p < 0.001) and districts Moran’s I = 0.4 (p < 0.001). Notably, significant clusters of high-risk health facility catchments were concentrated in Acholi, West Nile, Karamoja, and East Central – Busoga regions.

Conclusion
Findings showed clear countrywide spatial-temporal patterns with clustering of malaria risk across districts and health facility catchments within high risk regions, which can facilitate targeting of interventions to those areas at highest risk. Moreover, despite high and perennial transmission, seasonality for malaria incidence highlights the potential for optimal and timely implementation of targeted interventions.
COVID-19: a National Survey on perceived level of knowledge, attitude and practice among frontline healthcare Workers in Nepal
Authors: Tamang Nira , Rai Punam , Dhungana Siddhartha , Sherchan Binod , Shah Bikash , Pyakurel Prajjwal , Rai Saroj 
Published: December 2020

AbstractBackgroundThe aim of this study was to determine the knowledge, attitude and practice (KAP) regarding the COVID-19 among frontline healthcare workers (F-HCWs) working at different hospitals in Nepal and to identify the factors significantly associated with KAP.MethodsWe used a web-based survey, and a convenience sampling method was adopted to collect data from 603 F-HCWs working at different hospitals in Nepal during the first week of June 2020. A self-administered questionnaire was utilized to assess the KAP perceived by the F-HCWs. It was divided into 4-parts consisting of 30-items, demographic characteristics (10-items), knowledge (10-items), attitude (5-items), and practice (5-items). It consisted of both multiple-choice questions and Likert scale items questionnaire.ResultsAmong the participants, 76% reported adequate knowledge, 54.7% reported positive attitude, and 78.9% reported appropriate practice. Statistically significant differences regarding the perceived level of knowledge among F-HCWs were observed among independent variables, including age, gender, level of education, marital status, profession, work experience, source of information, infection prevention and control (IPC) training, and online course(p < 0.05). Similarly, statistically significant differences regarding the attitude among F-HCWs were observed among independent variables, including age, gender, level of education, profession, and online course(p < 0.05). Moreover, only 2-independent variables, including the profession and online course, showed statistically significant differences with practice(p < 0.05). Pearson correlation analysis showed a significant association between knowledge, attitude and practice at the level ofp = 0.01. The factors significantly associated with adequate knowledge were male gender, nurse and doctor, websites and IPC training. Similarly, factors significantly associated with positive attitude were online course related to COVID-19 only. Moreover, factors significantly associated with appropriate practice were master’s degree or above and online course related to COVID-19.ConclusionsF-HCWs reported adequate overall knowledge with a positive attitude and adopted the appropriate practice. The experienced F-HCWs with higher education and who received IPC training and online course regarding COVID-19 had better KAP. So, the stakeholders must arrange the educational programs and training for F-HCWs for better preparedness tackling with COVID-19.
Competition for nutritional resources masks the true frequency of bacterial mutants
Authors: Neves Henrique Iglesias , Machado Gabriella Trombini , Ramos Taíssa Cristina dos Santos , Yang Hyun Mo , Yagil Ezra , Spira Beny 
Published: December 2020

AbstractBackgroundIt is widely assumed that all mutant microorganisms present in a culture are able to grow and form colonies, provided that they express the features required for selection. Unlike wild-typeEscherichia coli, PHO-constitutive mutants overexpress alkaline phosphatase and hence can hydrolyze glycerol-2-phosphate (G2P) to glycerol and form colonies on plates having G2P as the sole carbon source. These mutations mostly occur in thepstoperon. However, the frequency of PHO-constitutive colonies on the G2P selective plate is exceptionally low.ResultsWe show that the rate in which spontaneous PHO-constitutive mutations emerge is about 8.0 × 10−6/generation, a relatively high rate, but the growth of most existing mutants is inhibited by their neighboring wild-type cells. This inhibition is elicited only by non-mutant viable bacteria that can take up and metabolize glycerol formed by the mutants. Evidence indicates that the few mutants that do form colonies derive from microclusters of mutants on the selective plate. A mathematical model that describes the fate of the wild-type and mutant populations under these circumstances supports these results.ConclusionThis scenario in which neither the wild-type nor the majority of the mutants are able to grow resembles an unavoidable “tragedy of the commons” case which results in the collapse of the majority of the population. Cooperation between rare adjacent mutants enables them to overcome the competition and eventually form mutant colonies. The inhibition of PHO-constitutive mutants provides an example of mutant frequency masked by orders of magnitude due to a competition between mutants and their ancestral wild-type cells. Similar “tragedy of the commons-like” cases may occur in other settings and should be taken into consideration while estimating true mutant frequencies and mutation rates.
Oxidative stress mediates thalidomide-induced pain by targeting peripheral TRPA1 and central TRPV4
Authors: De Logu Francesco , Trevisan Gabriela , Marone Ilaria Maddalena , Coppi Elisabetta , Padilha Dalenogare Diéssica , Titiz Mustafa , Marini Matilde , Landini Lorenzo , Souza Monteiro de Araujo Daniel , Li Puma Simone , Materazzi Serena , De Siena Gaetano , Geppetti Pierangelo , Nassini Romina 
Published: December 2020

Abstract
Background
The mechanism underlying the pain symptoms associated with chemotherapeutic-induced peripheral neuropathy (CIPN) is poorly understood. Transient receptor potential ankyrin 1 (TRPA1), TRP vanilloid 4 (TRPV4), TRPV1, and oxidative stress have been implicated in several rodent models of CIPN-evoked allodynia. Thalidomide causes a painful CIPN in patients via an unknown mechanism. Surprisingly, the pathway responsible for such proalgesic response has not yet been investigated in animal models.

Results
Here, we reveal that a single systemic administration of thalidomide and its derivatives, lenalidomide and pomalidomide, elicits prolonged (~ 35 days) mechanical and cold hypersensitivity in C57BL/6J mouse hind paw. Pharmacological antagonism or genetic deletion studies indicated that both TRPA1 and TRPV4, but not TRPV1, contribute to mechanical allodynia, whereas cold hypersensitivity was entirely due to TRPA1. Thalidomide per se did not stimulate recombinant and constitutive TRPA1 and TRPV4 channels in vitro, which, however, were activated by the oxidative stress byproduct, hydrogen peroxide. Systemic treatment with an antioxidant attenuated mechanical and cold hypersensitivity, and the increase in oxidative stress in hind paw, sciatic nerve, and lumbar spinal cord produced by thalidomide. Notably, central (intrathecal) or peripheral (intraplantar) treatments with channel antagonists or an antioxidant revealed that oxidative stress-dependent activation of peripheral TRPA1 mediates cold allodynia and part of mechanical allodynia. However, oxidative stress-induced activation of central TRPV4 mediated the residual TRPA1-resistant component of mechanical allodynia.

Conclusions
Targeting of peripheral TRPA1 and central TRPV4 may be required to attenuate pain associated with CIPN elicited by thalidomide and related drugs.
Tripeptidyl peptidase I promotes human endometrial epithelial cell adhesive capacity implying a role in receptivity
Authors: Santos Leilani L. , Ling Cheuk Kwan , Dimitriadis Evdokia 
Published: December 2020

AbstractThe endometrium undergoes cyclic remodelling throughout the menstrual cycle in preparation for embryo implantation which occurs in a short window during the mid-secretory phase. It is during this short ‘receptive window’ that the endometrial luminal epithelium acquires adhesive capacity permitting blastocysts firm adhesion to the endometrium to establish pregnancy. Dysregulation in any of these steps can compromise embryo implantation resulting in implantation failure and infertility. Many factors contribute to these processes including TGF-β, LIF, IL-11 and proteases. Tripeptidyl peptidase 1 (TPP1) is a is a lysosomal serine-type protease however the contribution of the TPP1 to receptivity is unknown. We aimed to investigate the role of TPP1 in receptivity in humans.In the current study, TPP1 was expressed in both epithelial and stromal compartments of the endometrium across the menstrual cycle. Expression was confined to the cytoplasm of luminal and glandular epithelial cells and stromal cells. Staining of mid-secretory endometrial tissues of women with normal fertility and primary unexplained infertility showed reduced immunostaining intensity of TPP1 in luminal epithelial cells of infertile tissues compared to fertile tissues. By contrast, TPP1 levels in glandular epithelial and stromal cells were comparable in both groups in the mid-secretory phase. Inhibition of TPP1 using siRNA compromised HTR8/SVneo (trophoblast cell line) spheroid adhesion on siRNA-transfected Ishikawa cells (endometrial epithelial cell line) in vitro. This impairment was associated with decreased sirtuin 1 (SIRT1), BCL2 and p53 mRNA and unaltered, CD44, CDH1, CDH2, ITGB3, VEGF A, OSTEOPONTIN, MDM2, CASP4, MCL1, MMP2, ARF6, SGK1, HOXA-10, LIF, and LIF receptor gene expression between treatment groups. siRNA knockdown of TPP1 in primary human endometrial stromal cells did not affect decidualization nor the expression of decidualization markers prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1). Taken together, our data strongly suggests a role for TPP1 in endometrial receptivity via its effects on epithelial cell adhesion and suggests reduced levels associated with unexplained infertility may contribute to implantation failure.