bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccine market and production capabilities in the Americas
Authors: Ortiz-Prado Esteban , Espín Estefanía , Vásconez Jorge , Rodríguez-Burneo Nathalia , Kyriakidis Nikolaos C. , López-Cortés Andrés 
Published: April 2021

AbstractIn the Americas, The United States of America, Canada, Mexico, and Brazil are the top vaccine producers and the countries with the leading infrastructure for biological manufacturing. The North American countries have the most demanding legislation regulating and controlling these pharmaceuticals’ distribution and production. Some Latin American countries rank in the top 20 of worldwide vaccine manufacturers, with Cuba, Brazil, México and Colombia have a self-sufficient vaccine production of 72.7%, 54,2%; 25%; and 7.7%, respectively, of the national vaccine demand. On the other hand, the rest of Latin American countries cannot satisfy their demand for vaccines, and most of their efforts are associated with the distribution within their health systems rather than in transferring technology.Based on this literature review, the results suggest an increasing growth vaccine demand, not only for their growing populations and previously established demand but also for the recently exerted pressure due to the COVID-19 pandemic.Because the American continent has a marked inequality between the hegemonic producers of vaccines, the exporters, and those that depend heavily on importing these products, this could assert technological dependence in countries with rapid population growth and jeopardize the effectiveness of the two vaccination plans.
Toxicity study and anti-trypanosomal activities of aqueous and methanol whole plant extracts of Brillantaisia owariensis on Trypanosoma brucei-induced infection in BALB/c mice
Authors: Ayawa Nafisa Garba , Ramon-Yusuf Suleiman Babatunde , Wada Yunusa Adamu , Oniye Sonnie Joshua , Shehu Dalhatu Mukhtari 
Published: April 2021

Abstract
Background
The problem of drug resistance and toxicity in trypanosomiasis is ever-increasing, thereby creating a need to search for efficacious and safer alternatives that are of plant origin. We designed the present study to assess the oral acute toxicity, and anti-trypanosomal activity of Brillantaisia owariensis in mice.

Methods
Fifty-eight BALB/c mice were used for this study. For toxicity assessment, eighteen mice were divided into two groups of nine mice each, and acute single oral administration of the aqueous and methanol whole plant extracts of B. owariensis was assessed for each group as per Lorke’s method. Mice were observed for signs of toxicity of liver and kidney organs after two weeks of oral administration. For the anti-trypanosomal activity, forty mice were divided into eight groups of five mice. Mouse in each group was inoculated with 0.1 mL containing106T. brucei /mL. Following patency of 3 days, mice were treated at different dosages of methanol and aqueous extracts. Pre-infection, post-infection, and post-treatment data for rectal temperature, body weight, parasiteamia level, packed cell volume, and daily survival were monitored.

Results
The acute oral toxicity studies (LD50) for methanol and aqueous plant extracts in this study were calculated as 3535 mg/kg/body weight, and are non-toxic. No obvious histopathologic observation in the liver and kidney tissues. The mean daily rectal temperature and mean weights of all the treated mice were restored to normal values and significant (P, 0.05) in comparison to the positive control.
Parasitaemia clearance by both extracts was suppressive. The mean PCV values were significantly increased following treatment, and there was prolonged survival especially in mice treated with methanol extracts.

Conclusion
The study concludes that the extracts of B. owariensis are relatively non-toxic with a good safety margin when administered to mice orally. Crude methanol extract exhibited better suppressive and haematinic antitrypanosomal activities than the aqueous extract, and it has a promising effect by its ability to reduce anaemia in mice challenged with T. brucei brucei, and prolonged survival.
The second pregnancy has no effect in the incidence of macrosomia: a cross-sectional survey in two western Chinese regions
Authors: Luo Li , Zeng Huan , Zeng Mao , Liu Xueqing , Xu Xianglong , Wang Lianlian , Zhao Yong 
Published: April 2021

Abstract
Background
After the implementation of the universal two-child policy in China, the increase in parity has led to an increase in adverse pregnancy outcomes. The impact of one and two fetuses on the incidence of fetal macrosomia has not been fully confirmed in China. This study aimed to explore the differences in the incidence of fetal macrosomia in first and second pregnancies in Western China after the implementation of the universal two-child policy.

Methods
A total of 1598 pregnant women from three hospitals were investigated by means of a cross-sectional study from August 2017 to January 2018. Participants were recruited by convenience and divided into first and second pregnancy groups. These groups included 1094 primiparas and 504 women giving birth to their second child. Univariate and multivariate logistic regression analyses were performed to discuss the differences in the incidence of fetal macrosomia in first and second pregnancies.

Results
No significant difference was found in the incidence of macrosomia in the first pregnancy group (7.2%) and the second pregnancy group (7.1%). In the second-time pregnant mothers, no significant association was found between the macrosomia of the second child (5.5%) and that of the first child (4.7%). The multivariate logistic regression model showed that mothers older than 30 years are not likely to give birth to children with macrosomia (odds ratio (OR) 0.6, 95% confidence interval (CI) 0.4,0.9).

Conclusions
The incidence of macrosomia in Western China is might not be affected by the birth of the second child and is not increased by low parity.
Excess epicardial fat volume in women is a novel risk marker for microvascular dysfunction, which may be a contributing factor in the atypical chest pain syndrome
Authors: El Shahawy Mahfouz , Tucker Susan , Izadi Lillee , Sabatini Antonella , Mohan Sukanya 
Published: April 2021

Abstract
Background
Excess epicardial fat volume (EFV) has been recently implicated in cardiovascular structural and functional abnormalities. It has been associated with abnormal microvascular stiffness (as reflected by radial artery waveform; C2), which may result in microvascular dysfunction and contribute to the atypical chest pain syndrome without obstructive coronary artery disease (CAD). Women have been statistically shown to present with atypical chest pain more often than men and specifically without obstructive CAD. The aim of this study is to assess whether excess EFV in female subjects is associated with significant microvascular dysfunction (i.e., C2), in subjects without obstructive CAD.

Results
We screened 596 asymptomatic subjects, ages 20–79, using the Early Cardiovascular Health Risk Scoring System (ECVHRS), which has been reported. Out of the 596 total subjects, 230 subjects had a CACS. Out of these 230 subjects, 77 subjects (45 females; 32 males) had a 0 CACS. The 45 females from this cohort were the subjects of this study, and they were further categorized into 3 groups: group 1 (normal EFV, non-obese female subjects; n=16), females with ECVHRS < 3 and ACC/AHA risk score < 5%; group 2 (n = 9), females with elevated EFV and no abdominal visceral obesity; and group 3 (n=20), females with elevated EFV and abdominal visceral obesity. The average EFV was determined to be 72±20 cm3 among group 1, which indicates the values for normal EFV. The results in group 2 indicate that excess EFV is contributing to the development of microvascular dysfunction, resulting in abnormal micro-arterial (C2) elasticity (p< 0.00001), increase in resting blood pressure (p =0.0001), an abnormal rise in blood pressure (BP) at rest and post-mild protocol exercise (PME) (p = < 0.00001), and abnormal increase in carotid intima-media thickness (CIMT) (p = 0.000164).

Conclusion
Excess EFV appears to be not only a novel cardiovascular risk marker, but also the culprit for other cardiovascular risk markers. Based on these findings, elevated EFV may contribute to the development of the atypical chest pain syndrome in females without obstructive CAD. Additionally, EFV is emerging as a potential clinically relevant significant cardiovascular risk biomarker and may become a target to reduce cardiovascular morbidity and mortality.
Semi-quantitative CT severity scoring as a predictor of development of post-COVID syndrome
Authors: Saad Mohammad A. , El Khateeb Ahmed F. , Ahmed Mona I. , Magdy Ahmed M. 
Published: April 2021

Abstract
Background
Following COVID-19 pandemic, clinical description focused on the clinical presentation of patients in the acute stage of the disease. More recently, data have emerged that some patients continue to experience symptoms related to COVID-19 after the acute phase of infection has subsided (post-COVID syndrome). Although characteristics of post-COVID syndrome have been well described, less is known about the possible invitations during acute illnesses that can predict such syndrome. Our study is a prospective study aiming at assessment of CT severity scoring in the acute phase of COVID-19 pneumonia as a predictor for development of post-COVID syndrome in recovering patients.

Results
A total of 192 symptomatic COVID-19 patients between April 2020 and October 2020 were enrolled in this single-center study, and high-resolution chest CT examinations were evaluated for CT severity scoring. Data were matched with the long-term clinical outcome. CT severity score was significantly higher in patients who developed post-COVID symptoms (p < 0.001). A CT score of > 7 was associated with an increased risk and was found to be predictive of condition development with sensitivity (95.9%), specificity (96%), positive predictive value (95.92%), negative predictive value (96%), and accuracy (95.96%).

Conclusions
CT severity scoring can help in predicting the long-term outcome of COVID-19 patients with cutoff value of CT-SSS > 7 showing highest sensitivity and specificity for predicting development of post-COVID syndrome.
Post-COVID-19 pneumonia lung fibrosis: a worrisome sequelae in surviving patients
Authors: Ali Rasha Mostafa Mohamed , Ghonimy Mai Bahgat Ibrahim 
Published: April 2021

AbstractBackgroundProgressive fibrotic lung disease is one of the possible consequences of COVID-19 pulmonary pneumonia, and it is one of the most worrying long-term complications. Pulmonary fibrosis is associated with non-reversible lung dysfunction. The long-term lung changes of previous COVID-19 infection still not completely understood and should be included in further studies. The aim of this study is the early detection and prediction of patients whom may develop such serious complication, thus giving a chance for early introduction of anti-fibrotic drugs.ResultsFrom April 2020 to December 2020, 80 patients in Cairo, Egypt, who have clinical manifestations and confirmed COVID-19 by PCR, were evaluated by follow-up MDCT. CT image analysis was processed including comparative study using follow-up data (different radiological signs and residual fibrotic changes). Although there was no specific cause for post-COVID-19 lung fibrosis, there were some predicting factors such as old age, cigarette smoking, high CT severity score, and long-term mechanical ventilation.ConclusionEarly detection of potential cases of post-COVID-19 pulmonary fibrosis may give a chance to prevent or at least modify such disabling complication.
Establishing diagnostic thresholds for Alzheimer's disease in adults with Down syndrome: the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS)
Authors: Beresford-Webb Jessica A. , Mak Elijah , Grigorova Monika , Daffern Samuel J. , Holland Anthony J. , Zaman Shahid H. 
Published: April 2021

Background
Diagnosis of prodromal Alzheimer's disease and Alzheimer's disease dementia in people with Down syndrome is a major challenge. The Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS) has been validated for diagnosing prodromal Alzheimer's disease and Alzheimer's disease dementia, but the diagnostic process lacks guidance.

Aims
To derive CAMDEX-DS informant interview threshold scores to enable accurate diagnosis of prodromal Alzheimer's disease and Alzheimer's disease dementia in adults with Down syndrome.

Method
Psychiatrists classified participants with Down syndrome into no dementia, prodromal Alzheimer's disease and Alzheimer's disease dementia groups. Receiver operating characteristic analyses assessed the diagnostic accuracy of CAMDEX-DS informant interview-derived scores. Spearman partial correlations investigated associations between CAMDEX-DS scores, regional Aβ binding (positron emission tomography) and regional cortical thickness (magnetic resonance imaging).

Results
Diagnostic performance of CAMDEX-DS total scores were high for Alzheimer's disease dementia (area under the curve (AUC), 0.998; 95% CI 0.953–0.999) and prodromal Alzheimer's disease (AUC = 0.954; 95% CI 0.887–0.982) when compared with healthy adults with Down syndrome. When compared with those with mental health conditions but no Alzheimer's disease, CAMDEX-DS Section B scores, denoting memory and orientation ability, accurately diagnosed Alzheimer's disease dementia (AUC = 0.958; 95% CI 0.892–0.984), but were unable to diagnose prodromal Alzheimer's disease. CAMDEX-DS total scores exhibited moderate correlations with cortical Aβ (r ~ 0.4 to 0.6, P ≤ 0.05) and thickness (r ~ −0.4 to −0.44, P ≤ 0.05) in specific regions.

Conclusions
CAMDEX-DS total score accurately diagnoses Alzheimer's disease dementia and prodromal Alzheimer's disease in healthy adults with Down syndrome.
Uptake of KRAS Testing and Anti-EGFR Antibody Use for Colorectal Cancer in the VA
Authors: Becker Daniel J. , Lee Kyung M. , Lee Steve Y. , Lynch Kristine E. , Makarov Danil V. , Sherman Scott E. , Morrissey Christy D. , Kelley Michael J. , Lynch Julie A. 
Published: April 2021

PURPOSEAdvances in precision oncology, including RAS testing to predict response to epidermal growth factor receptor monoclonal antibodies (EGFR mAbs) in colorectal cancer (CRC), can extend patients’ lives. We evaluated uptake and clinical use of KRAS molecular testing, guideline recommended since 2010, in the Veterans Affairs Healthcare System (VA).MATERIALS AND METHODSWe conducted a retrospective cohort study of patients with stage IV CRC diagnosed in the VA 2006-2015. We gathered clinical, demographic, molecular, and treatment data from the VA Corporate Data Warehouse and 29 commercial laboratories. We performed multivariable analyses of associations between patient characteristics, KRAS testing, and EGFR mAb treatment.RESULTSAmong 5,943 patients diagnosed with stage IV CRC, only 1,053 (17.7%) had KRAS testing. Testing rates increased from 2.3% in 2006 to 28.4% in 2013. In multivariable regression, older patients (odds ratio, 0.17; 95% CI, 0.09 to 0.32 for ≥ age 85 v < 45 years) and those treated in the Northeast and South regions were less likely, and those treated at high-volume CRC centers were more likely to have KRAS testing (odds ratio, 2.32; 95% CI, 1.48 to 3.63). Rates of potentially guideline discordant care were high: 64.3% (321/499) of KRAS wild-type (WT) went untreated with EGFR mAb and 8.8% (401/4,570) with no KRAS testing received EGFR mAb. Among KRAS-WT patients, survival was better for patients who received EGFR mAb treatment (29.6 v 18.8 months; P < .001).CONCLUSIONWe found underuse of KRAS testing in advanced CRC, especially among older patients and those treated at lower-volume CRC centers. We found high rates of potentially guideline discordant underuse of EGFR mAb in patients with KRAS-WT tumors. Efforts to understand barriers to precision oncology are needed to maximize patient benefit.
Loss of CREB Coactivator CRTC1 in SF1 Cells Leads to Hyperphagia and Obesity by High-fat Diet But Not Normal Chow Diet
Authors: Matsumura Shigenobu , Ishikawa Fuka , Sasaki Tsutomu , Terkelsen Mike Krogh , Ravnskjaer Kim , Jinno Tomoki , Tanaka Jin , Goto Tsuyoshi , Inoue Kazuo 
Published: April 2021

Abstract
Cyclic adenosine monophosphate responsive element–binding protein-1-regulated transcription coactivator-1 (CRTC1) is a cytoplasmic coactivator that translocates to the nucleus in response to cyclic adenosine monophosphate. Whole-body knockdown of Crtc1 causes obesity, resulting in increased food intake and reduced energy expenditure. CRTC1 is highly expressed in the brain; therefore, it might play an important role in energy metabolism via the neuronal pathway. However, the precise mechanism by which CRTC1 regulates energy metabolism remains unknown. Here, we showed that mice lacking CRTC1, specifically in steroidogenic factor-1 expressing cells (SF1 cells), were sensitive to high-fat diet (HFD)-induced obesity, exhibiting hyperphagia and increased body weight gain. The loss of CRTC1 in SF1 cells impaired glucose metabolism. Unlike whole-body CRTC1 knockout mice, SF1 cell-specific CRTC1 deletion did not affect body weight gain or food intake in normal chow feeding. Thus, CRTC1 in SF1 cells is required for normal appetite regulation in HFD-fed mice. CRTC1 is primarily expressed in the brain. Within the hypothalamus, which plays an important role for appetite regulation, SF1 cells are only found in ventromedial hypothalamus. RNA sequencing analysis of microdissected ventromedial hypothalamus samples revealed that the loss of CRTC1 significantly changed the expression levels of certain genes. Our results revealed the important protective role of CRTC1 in SF1 cells against dietary metabolic imbalance.
Other ways of communicating the pandemic - memes and stickers against COVID-19: a systematic review
Authors: Moya-Salazar Jeel , Cañari Betsy , Gomez-Saenz Lucía , Contreras-Pulache Hans 
Published: April 2021

Background: In the midst of the coronavirus disease 2019 (COVID-19) pandemic, there are many ways to communicate hygiene measures, such as memes and stickers that are widely used on social networks. We carried out a systematic review in order to determine the impact of stickers and memes as tools to face the COVID-19 pandemic, following the PRISMA guide. Methods: The search was carried out in scientific databases (MEDLINE / PubMed, ScientiDirect, Scielo, LILACS, and Latindex), and in public pre-publication servers (bioRxiv, SocArXiv, medRxiv and Preprints). The publications were identified using the terms (((meme) OR (sticker)) AND ((COVID-19) OR (SARS-COV-2)) AND (WhatsApp)) and the corresponding translations for Spanish and Portuguese. Results: In the initial search, 8434 studies were obtained, 7749 in Preprints, 446 in SocArXiv, 145 in ScientDirect, 82 in medRxiv, and 12 in PubMed. No studies were found in LILACS, Latindex, Scielo, or bioRxiv. Of the 51 studies included as eligible, all were eliminated for not meeting the study inclusion criteria. The majority (40 studies) were eliminated as studies were publications related to the social aspects related to COVID-19, but did not develop an analysis of stickers or memes. Conclusions: No studies were identified that met the inclusion criteria related to the role of stickers and memes as tools to face the COVID-19 pandemic. More studies are needed to estimate its role as a means of communication in health.
Impact of Plasmodium falciparum small-sized extracellular vesicles on host peripheral blood mononuclear cells
Authors: Mwangi Shaban J. , Gwela Agnes , Mwikali Kioko , Bargul Joel L. , Nduati Eunice W. , Ndungu Francis M. , Bejon Philip , Rayner Julian C. , Abdi Abdirahman I. 
Published: April 2021

Background: Exagerated immune activation has a key role in the pathogenesis of malaria. During blood-stage infection, Plasmodium falciparum can interact directly with host immune cells through infected red blood cells (PfiRBCs), or indirectly by the release of extracellular vesicles (EVs). Here, we compared the impact of PfiRBCs and P. falciparum small-sized EVs (PfsEVs, also known as exosomes) from a Kenyan clinical isolate (PfKE12) adapted to short-term laboratory culture conditions on host peripheral blood mononuclear cells (PBMC). Methods: PfsEVs were isolated from cell-free culture-conditioned media by ultracentrifugation while mature trophozoite PfiRBCs were purified by magnetic column separation. The PfsEVs and the PfiRBCs were co-cultured for 18 hours with PBMC. Cellular responses were quantified by cell surface expression of activation markers (CD25, CD69) and cytokine/chemokine levels in the supernatant. Results: Relative to negative control conditions, PfsEVs induced CD25 expression on CD4+, CD19+ and CD14+ cells, while PfiRBCs induced on CD19+ and CD14+ cells. Both PfsEVs and PfiRBCs induced CD69 on CD4+, CD8+ and CD19+ cells. In addition, PfiRBCs induced higher expression of CD69 on CD14+ cells. CD69 induced by PfiRBCs on CD4+ and CD19+ cells was significantly higher than that induced by PfsEVs. Secretion of MIP1α, MIP1β, GM-CSF, IL-6, IL-8, and TNFα were significantly induced by both PfsEVs and PfiRBCs whereas MCP-1, IL-10, IL-17α were preferentially induced by PfsEVs and IP-10 and IFN-γ by PfiRBCs. Prior exposure to malaria (judged by antibodies to schizont extract) was associated with lower monocyte responses to PfsEVs. Conclusions: PfsEVs and PfiRBCs showed differential abilities to induce secretion of IL-17α and IFN-γ, suggesting that the former are better at inducing Th17, whilst the latter induce Th1 immune responses respectively. Prior exposure to malaria significantly reduces the ability of PfsEVs to activate monocytes, suggesting immune tolerance to PfsEVs may play a role in naturally acquired anti-disease immunity.