bluuebunny/crossref_metadata_2025_split huggingface dataset:
The microbiome and mosquito vectorial capacity: rich potential for discovery and translation
Authors: Cansado-Utrilla Cintia , Zhao Serena Y. , McCall Philip J. , Coon Kerri L. , Hughes Grant L. 
Published: May 2021

AbstractMicrobiome research has gained considerable interest due to the emerging evidence of its impact on human and animal health. As in other animals, the gut-associated microbiota of mosquitoes affect host fitness and other phenotypes. It is now well established that microbes can alter pathogen transmission in mosquitoes, either positively or negatively, and avenues are being explored to exploit microbes for vector control. However, less attention has been paid to how microbiota affect phenotypes that impact vectorial capacity. Several mosquito and pathogen components, such as vector density, biting rate, survival, vector competence, and the pathogen extrinsic incubation period all influence pathogen transmission. Recent studies also indicate that mosquito gut-associated microbes can impact each of these components, and therefore ultimately modulate vectorial capacity. Promisingly, this expands the options available to exploit microbes for vector control by also targeting parameters that affect vectorial capacity. However, there are still many knowledge gaps regarding mosquito–microbe interactions that need to be addressed in order to exploit them efficiently. Here, we review current evidence of impacts of the microbiome on aspects of vectorial capacity, and we highlight likely opportunities for novel vector control strategies and areas where further studies are required.
The effectiveness of E-learning in continuing medical education for tuberculosis health workers: a quasi-experiment from China
Authors: Wang Zi-Yue , Zhang Li-Jie , Liu Yu-Hong , Jiang Wei-Xi , Jia Jing-Yun , Tang Sheng-Lan , Liu Xiao-Yun 
Published: May 2021

Abstract
Background
Given the context of rapid technological change and COIVD-19 pandemics, E-learning may provide a unique opportunity for addressing the challenges in traditional face-to-face continuing medical education (CME). However, the effectiveness of E-learning in CME interventions remains unclear. This study aims to evaluate whether E-learning training program can improve TB health personnel’s knowledge and behaviour in China.

Methods
This study used a convergent mixed method research design to evaluate the impact of E-learning programs for tuberculosis (TB) health workers in terms of knowledge improvement and behaviour change during the China-Gates TB Project (add the time span). Quantitative data was collected by staff surveys (baseline n = 555; final n = 757) and management information systems to measure the demographic characteristics, training participation, and TB knowledge. Difference-in-difference (DID) and multiple linear regression models were employed to capture the effectiveness of knowledge improvement. Qualitative data was collected by interviews (n = 30) and focus group discussions (n = 44) with managers, teachers, and learners to explore their learning experience.

Results
Synchronous E-learning improved the knowledge of TB clinicians (average treatment effect, ATE: 7.3 scores/100, P = 0.026). Asynchronous E-learning has a significant impact on knowledge among primary care workers (ATE: 10.9/100, P < 0.001), but not in clinicians or public health physicians. Traditional face-to-face training has no significant impact on all medical staff. Most of the learners (57.3%) agreed that they could apply what they learned to their practice. Qualitative data revealed that high quality content is the key facilitator of the behaviour change, while of learning content difficulty, relevancy, and hardware constraints are key barriers.

Conclusions
The effectiveness of E-learning in CME varies across different types of training formats, organizational environment, and target audience. Although clinicians and primary care workers improved their knowledge by E-learning activities, public health physicians didn’t benefit from the interventions.
Early life predictors of positive change during the coronavirus disease pandemic
Authors: Bleil Maria E. , Appelhans Bradley M. , Thomas Alexis S. , Gregorich Steven E. , Marquez Neal , Roisman Glenn I. , Booth-LaForce Cathryn , Crowder Kyle 
Published: May 2021

Abstract
Background
The COVID-19 pandemic is a crisis unprecedented in its size and scope. Yet studies of resilience suggest most individuals will successfully negotiate this challenge and some may even experience growth and positive change. Some evidence suggests that the capacity to enact positive change in the face of adversity may be shaped by early life experiences.

Methods
In a subset of 374 participants (57% female, mean age = 29 years) in the Study of Early Child Care and Youth Development (SECCYD), a longitudinal, birth cohort, prospective models were tested to determine whether early life adversities in family and neighborhood contexts predict positive change events in response to the COVID-19 pandemic. Childhood family and neighborhood contexts were assessed using a combination of self-report questionnaires and US Census data. Adulthood positive change events (e.g., becoming more appreciative of things usually taken for granted) were assessed using the Epidemic-Pandemic Impacts Inventory (EPII).

Results
In regression analyses, neighborhood disadvantage in childhood, measured both by objective and subjective assessments, predicted a higher number of positive change events in response to the COVID-19 pandemic (β = .18, p = .004 and β = .15, p = .006, respectively). Examination of the positive change event subscales showed neighborhood disadvantage in childhood predicted increases in events related to ‘perspective taking and charitable giving’ (β = .20, p = .022 and β = .17, p = .002, respectively) and improved ‘social relationships’ (β = .18, p = .004 and β = .13, p = .020, respectively), but not to positive ‘health behaviors’ (ps > .05). All associations were independent of sociodemographic factors and childhood family dysfunction.

Conclusions
Findings suggest that neighborhood disadvantage in childhood may shape prosocial responses to stress in adulthood, potentially through early life adaptions to stress that are protective when facing adversity. There are several notable implications of the study findings. Although adversity in early life has clear negative impacts, it is possible that adversity experiences may also provide opportunities to develop adaptive strategies that foster resilience and growth when facing stress. Intervention efforts should consider leveraging such stress-adapted strengths to reduce the many negative impacts of early life adversity.
Extract of white sweet potato tuber against TNF-α-induced insulin resistance by activating the PI3K/Akt pathway in C2C12 myotubes
Authors: Shyur Lie-Fen , Varga Viola , Chen Chiao-Ming , Mu Shu-Chi , Chang Yu-Chih , Li Sing-Chung 
Published: May 2021

Abstract
Background
White sweet potato (WSP; Ipomoea batatas L. Simon No. 1) has many potential beneficial effects on metabolic control and diabetes-related insulin resistance. The improvement of insulin resistance by WSP tuber extracts on glucose uptake were not investigated in C2C12 myoblast cells.

Results
WSP tuberous ethanol extract (WSP-E) was partitioned with ethyl-acetate and water to obtain ethyl-acetate layer (WSP-EA) and water layer (WSP-EW). The WSP-EA shows the highest total phenolic contents and highest antioxidant activity by Folin-Ciocalteu and (2,2-diphenyl-1-picryl-hydrazyl-hydrate, DPPH) assay, respectively. After low concentration horse serum on differentiation inducement of C2C12 myoblasts into mature myotubes, the cells were treated with TNF-α to induce insulin resistance. WSP-EA and WSP-EW extracts increased the uptake of fluorescence glucose analogue (2-[N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino]-2-deoxy-d-glucose, 2-NBDG) in a dose-dependent manner as examined by flow cytometry. The WSP-EA enhanced glucose uptake by activation of phosphorylation of IR (pIR), IRS-1 (pIRS-1) and Akt (pAkt) involved in PI3K (phosphatidylinositol 3-kinase)/protein kinase B (Akt) pathway, also upregulated glucose transporter 4 (GLUT4) expression in myotubes.

Conclusions
WSP-EA enhanced the glucose uptake in C2C12 myotubes through upregulating the PI3K/Akt pathway. The in vitro data reveal that WSP tuber extracts has potential applications to improve insulin resistance in diabetes.
Predictive modelling for COVID-19 outbreak control: lessons from the navy cluster in Sri Lanka
Authors: Wijesekara N. W. A. N. Y. , Herath Nayomi , Kodituwakku K. A. L. C. , Herath H. D. B. , Ginige Samitha , Ruwanpathirana Thilanga , Kariyawasam Manjula , Samaraweera Sudath , Herath Anuruddha , Jayawardena Senarupa , Gamge Deepa 
Published: May 2021

AbstractIn response to an outbreak of coronavirus disease 2019 (COVID-19) within a cluster of Navy personnel in Sri Lanka commencing from 22nd April 2020, an aggressive outbreak management program was launched by the Epidemiology Unit of the Ministry of Health. To predict the possible number of cases within the susceptible population under four social distancing scenarios, the COVID-19 Hospital Impact Model for Epidemics (CHIME) was used. With increasing social distancing, the epidemiological curve flattened, and its peak shifted to the right. The observed or actually reported number of cases was above the projected number of cases at the onset; however, subsequently, it fell below all predicted trends. Predictive modelling is a useful tool for the control of outbreaks such as COVID-19 in a closed community.
Gut microbiota of frugo-folivorous sifakas across environments
Authors: Greene Lydia K. , Blanco Marina B. , Rambeloson Elodi , Graubics Karlis , Fanelli Brian , Colwell Rita R. , Drea Christine M. 
Published: May 2021

AbstractBackgroundCaptive animals, compared to their wild counterparts, generally harbor imbalanced gut microbiota owing, in part, to their altered diets. This imbalance is particularly striking for folivores that fundamentally rely on gut microbiota for digestion, yet rarely receive sufficient dietary fiber in captivity. We examine the critically endangered Coquerel’s sifaka (Propithecus coquereli), an anatomically specialized, rather than facultative, folivore that consumes a seasonal frugo-folivorous diet in the wild, but is provisioned predominantly with seasonal foliage and orchard vegetables in captivity. Using amplicon and metagenomic sequencing applied to fecal samples collected from two wild and one captive population (each comprising multiple groups), we clarify how dietary variation underlies the perturbational effect of captivity on the structure and function of this species’ gut microbiota.ResultsThe gut microbiota of wild sifakas varied by study population, most notably in community evenness and in the abundance of diet-associated microbes fromPrevotellaeceaeandLachnospiraceae. Nevertheless, the differences among wild subjects were minor compared to those evident between wild and captive sifakas: Unusually, the consortia of captive sifakas were the most diverse, but lacked representation of endemicBacteroidetesand metagenomic capacity for essential amino-acid biosynthesis. Instead, they were enriched for complex fiber metabolizers from theFirmicutesphylum, for archaeal methanogens, and for several metabolic pathways putatively linked to plant fiber and secondary compound metabolism.ConclusionsThe relatively minor differences in gut microbial structure and function between wild sifaka populations likely reflect regional and/or temporal environmental variability, whereas the major differences observed in captive conspecifics, including the loss of endemic microbes, but gain in low-abundance taxa, likely reflect imbalanced or unstable consortia. Indeed, community perturbation may not necessarily entail decreased community diversity. Moreover, signatures of greater fiber degradation indicate that captive sifakas consume a more fibrous diet compared to their wild counterparts. These results do not mirror those typically reported for folivores and herbivores, suggesting that the direction and strength of captivity-induced ‘dysbiosis’ may not be universal across species with similar feeding strategies. We propose that tailored, species-specific dietary interventions in captivity, aimed at better approximating naturally foraged diets, could functionally ‘rewild’ gut microbiota and facilitate successful management of diverse species.
Predictive factors of ovarian response to GnRH antagonist stimulation protocol: AMH and age are potential candidates
Authors: Laqqan Mohammed M. , Yassin Maged M. 
Published: May 2021

Abstract
Background
Prediction of ovarian response prior to the ovarian stimulation cycle is useful in determining the optimal starting dose of recombinant follicle-stimulating hormone (r-FSH). This study was designed to (I) evaluate which of the following parameters (age, AMH, and FSH) can be used as a predictor of ovarian response to GnRH antagonist stimulation protocol, (II) determine the cutoff value of AMH and age for predicting poor and high ovarian response, and (III) investigate the relationship between age, AMH level, and other clinical parameters. It is a retrospective study. A total of 318 women with a mean age of 28.2 ± 5.9 years old were included in this study. Hormone levels (FSH, LH, PRL, E2, and AMH) and the number of collected oocytes were determined. Based on the number of retrieved oocytes, the participants were divided into three groups: poor response (oocytes < 4, n= 51), normal response (oocytes 4–14, n= 192), and high response (oocytes > 14, n= 75).

Results
A significant increase has been found in AMH level and number of retrieved oocytes and mature oocytes from low to normal and high ovarian response group (P < 0.001). Also, the age in the poor ovarian response group was significantly greater than normal and high ovarian response groups (P < 0.001). A significant positive correlation has been found between the number of retrieved oocytes and mature oocytes and level of AMH (P < 0.001). The receiver operating characteristic (ROC) curves showed that both AMH and age had the highest accuracy in the prediction of poor ovarian response with a cutoff value < 1.45 and > 31.5 years, respectively. Additionally, the ROC analysis has shown that the AMH had the highest accuracy, followed by age in the prediction of high ovarian response with a cutoff value > 3.55 and < 27.5 years, respectively.

Conclusions
This study demonstrates that AMH level and women’s age may be used as potential predictors of ovarian response to GnRH antagonist stimulation protocol.
Direct Comparison of the Prediction of the Unbound Brain-to-Plasma Partitioning Utilizing Machine Learning Approach and Mechanistic Neuropharmacokinetic Model
Authors: Kosugi Yohei , Mizuno Kunihiko , Santos Cipriano , Sato Sho , Hosea Natalie , Zientek Michael 
Published: May 2021

AbstractThe mechanistic neuropharmacokinetic (neuroPK) model was established to predict unbound brain-to-plasma partitioning (Kp,uu,brain) by considering in vitro efflux activities of multiple drug resistance 1 (MDR1) and breast cancer resistance protein (BCRP). Herein, we directly compare this model to a computational machine learning approach utilizing physicochemical descriptors and efflux ratios of MDR1 and BCRP-expressing cells for predicting Kp,uu,brain in rats. Two different types of machine learning techniques, Gaussian processes (GP) and random forest regression (RF), were assessed by the time and cluster-split validation methods using 640 internal compounds. The predictivity of machine learning models based on only molecular descriptors in the time-split dataset performed worse than the cluster-split dataset, whereas the models incorporating MDR1 and BCRP efflux ratios showed similar predictivity between time and cluster-split datasets. The GP incorporating MDR1 and BCRP in the time-split dataset achieved the highest correlation (R2 = 0.602). These results suggested that incorporation of MDR1 and BCRP in machine learning is beneficial for robust and accurate prediction. Kp,uu,brain prediction utilizing the neuroPK model was significantly worse compared to machine learning approaches for the same dataset. We also investigated the predictivity of Kp,uu,brain using an external independent test set of 34 marketed drugs. Compared to machine learning models, the neuroPK model showed better predictive performance with R2 of 0.577. This work demonstrates that the machine learning model for Kp,uu,brain achieves maximum predictive performance within the chemical applicability domain, whereas the neuroPK model is applicable more widely beyond the chemical space covered in the training dataset.
Scientific research and innovation response to the COVID-19 pandemic in Peru
Authors: Moya-Salazar Jeel , Gomez-Saenz Lucia , Cañari Betsy , Contreras-Pulache Hans 
Published: May 2021

Background: COVID-19 has shaken countries at all levels, putting public health at risk. Global efforts have allocated funding for the development of research for the development of vaccines, digital tools, epidemiologic, social, and economic studies. Although these efforts have been developed worldwide, not all countries have prioritized the same topics, and may have a different impact on solving problems and containing the spread of COVID-19. Methods: A descriptive study was conducted with secondary data of "Special Projects COVID-19” in order to analyze the prioritization of proposals and projects to Peruvian needs in the face of pandemic. Two calls were made by the Peruvian research council (CONCyTec); the first with five areas and second with seven. The global amounts financed by each call were 342,857 USD (1,200,000 soles) and 700,000 USD (1,750,000 soles), respectively. Results: A total of 1,101 research projects were presented, 600 (54.5%) in the first call. In this call, 176 (29.3%) projects were from the technological development and innovation and 29 were winners (with a global budget of 1,711,907.25 USD /6,077,270.75 soles). In the second call, 120 (23.9%) projects were from the area of Social and economic research and 21 were winners (global budget of 1,284,002.25 USD/558,208.55 soles) (p=0.043). The largest proportion of winning projects in both calls was 12 (41.4%) in Technological developments and innovation, then five (17.2%) each in telehealth and mobile health, and epidemiological and social studies. Across both calls, 214 (55.8%) and 160 (51.9%) projects were of private organizations and universities, respectively. Conclusions: This research shows ~2% of rapid response "Special Projects COVID-19” were financed by the CONCyTec call with over a million dollars of funds. Although the main topics were technological innovation, detection systems, and vaccines, these priorities have not had a global impact on the epidemiological development of the pandemic in Peru.
Case Report: SARS-CoV-2 as an unexpected causal agent of isolated febrile hepatitis
Authors: Filippidis Paraskevas , van Ouwenaller Francois , Cerutti Alberto , Geiger-Jacquod Anaïs , Sempoux Christine , Pantaleo Giuseppe , Moradpour Darius , Lamoth Frederic 
Published: May 2021

Background: Respiratory symptoms and pneumonia are the predominant features of Coronavirus disease 2019 (COVID-19) due to emerging SARS-CoV-2 virus, but extrapulmonary manifestations are also observed. For instance, some degree of liver injury has been described among patients requiring hospital admission for severe COVID-19. However, acute febrile hepatitis as an initial or predominant manifestation of COVID-19 has been rarely reported. Case presentation: A 34-year-old man without underlying medical conditions presented with fever of unknown origin for two weeks in the absence of respiratory symptoms or other complaints. Laboratory testing revealed isolated acute hepatitis, for which an extensive microbiological work-up did not reveal identification of the causal agent. PCR testing for SARS-CoV-2 on a nasopharyngeal swab was negative on two occasions and initial serology for SARS-CoV-2 (at 15 days from symptoms onset) was also negative. However, repeated SARS-CoV-2 serological testing at 30 days demonstrated seroconversion leading to the diagnosis of COVID-19-related hepatitis. The patient's condition progressively improved, while transaminases steadily declined and eventually returned back to normal within 30 days. Conclusions: We describe here a unique case of SARS-CoV-2 isolated febrile hepatitis in a young and previously healthy man, which was diagnosed by demonstration of seroconversion, while PCR screening was negative. This case report highlights the role of repeated serological testing for the diagnosis of extrapulmonary manifestations of COVID-19.
The impact of COVID-19 on clinical research: the PIPPRA and MEDRA experience
Authors: Larkin Louise , Raad Tala , Moses Anusha , Fraser Alexander , Gallagher Stephen , Appel Esbensen Bente , Glynn Liam , Griffin Anne , Tierney Audrey C , Kennedy Norelee 
Published: May 2021

Background: Coronavirus disease 2019 (COVID-19) has had a significant impact on clinical research. This paper aims to provide an insight into how the COVID-19 pandemic, associated public health restrictions and international guidance on the conduct of clinical research impacted two clinical rheumatology research trials - the Physiotherapist-led Intervention to Promote Physical Activity in Rheumatoid Arthritis (PIPPRA) and the MEDiterranean diet in Rheumatoid Arthritis (MEDRA) projects. Methods: The March 2019 public health restrictions imposed to mitigate the risk of COVID-19 occurred at a time when PIPPRA was in the process of delivering assessment and intervention on a face-to-face basis (n=48) and MEDRA had commenced recruitment. Participants in PIPPRA and MEDRA had a diagnosis of rheumatoid arthritis, with some being immunosuppressed and thus at a higher risk for COVID-19. The decision-making processes of both trials is outlined to demonstrate the required amendments to continue in the context of the COVID-19 pandemic. Results: Amendments to PIPPRA and MEDRA trial protocols were agreed and received ethical and funder approval. Both trials switched from a face-to-face delivery to a telehealth using online platforms. The PIPPRA study was paused for five months (April-August 2020), resulting in n=33 (60%) deviations from assessment protocol. MEDRA switched from face-to-face to online recruitment with 20% (n=35/44) deviation in recruitment. Of the n=18 participants who consented to participating in a face-to-face trial, just n=2 (11%) opted to engage with telehealth delivery of the intervention. MEDRA assessment and intervention deviations were 100% as no sessions were completed as planned in 2020. Conclusions: The COVID-19 pandemic has severely impacted the PIPPRA and MEDRA clinical trials. Moving face-to-face clinical research to telehealth delivery may not be the panacea it is purported to be. Our experiences may be of benefit to researchers, clinicians, and funders in seeking to continue clinical research during a global pandemic.