bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of a lung squamous cell carcinoma three-dimensional culture model with keratinizing structures
Authors: Kawai Shigeto , Nakano Kiyotaka , Tamai Keiichi , Fujii Etsuko , Yamada Mimori , Komoda Hiroshi , Sakumoto Hirofumi , Natori Osamu , Suzuki Masami 
Published: December 2021

AbstractTumor nests in lung squamous cell carcinoma (LUSC) have a hierarchical structure resembling squamous epithelium. The nests consist of basal-like cells on the periphery and layers of keratinocyte-like cells that differentiate towards the center of the nest, forming keratin pearls. Reproducing this spatial heterogeneity in in vitro models would be useful for understanding the biology of LUSC. Here, we established a three-dimensional (3D) culture model with a squamous epithelial structure using LUSC cell lines PLR327F-LD41 and MCC001F, established in-house. When PLR327F-LD41 cells were cultured in a mixture of Matrigel and collagen I, they generated 3D colonies (designated cancer organoids, or COs) with involucrin (IVL)-positive keratinizing cells in the center (IVLinner COs). COs with uniform size were generated by seeding PLR327F-LD41 cells in a form of small cell aggregates. Since Notch signaling induces the differentiation of squamous epithelium, we confirmed the effect of γ-secretase inhibitor in inhibiting Notch signaling in IVLinner COs. Surprisingly, γ-secretase inhibitor did not block induction of IVL-positive cells; however, cells residing between the CK5-positive basal-like layer and IVL-positive layer decreased significantly. Thus, our 3D culture model with uniform size and structure promises to be a useful tool for elucidating the biology of LUSC and for screening drug-candidates.
Postmarketing safety surveillance data reveals protective effects of botulinum toxin injections against incident anxiety
Authors: Wollmer M. Axel , Makunts Tigran , Krüger Tillmann H. C. , Abagyan Ruben 
Published: December 2021

AbstractRandomized controlled trials (RCTs) have shown an antidepressant effect of glabellar botulinum toxin (BoNT) injections. In the FDA Adverse Event Reporting System (FAERS) database, BoNT injection is associated with reduced incidence rates of depression across various non-psychiatric indications, which confirms the previous findings independently of specific expectations to an antidepressant effect of BoNT. The rationale of using BoNT to treat depression is to interrupt proprioceptive body feedback that may reinforce negative emotions. Negative emotions also occur in other mental disorders, suggesting a transdiagnostic therapeutic potential of BoNT in psychiatry. Here we report an analysis of the FAERS database, in which we found that, compared to alternative treatments, BoNT injections were associated with lower incidence of anxiety symptoms and related disorders. Among seven indications/injection sites, we found this protective effect of BoNT in cosmetic use/facial muscles, migraine/facial and head muscles, spasms and spasticity/upper and lower limbs, torticollis and neck pain/neck muscles, and sialorrhea/parotid and submandibular glands (reporting odds ratios 0.79–0.27). These findings are encouraging for possible future RCTs on the use of BoNT as a treatment for anxiety and related disorders.
Synthesis and multifaceted pharmacological activity of novel quinazoline NHE-1 inhibitors
Authors: Spasov Alexander , Ozerov Alexander , Vassiliev Pavel , Kosolapov Vadim , Gurova Natalia , Kucheryavenko Aida , Naumenko Ludmila , Babkov Denis , Sirotenko Viktor , Taran Alena , Litvinov Roman , Borisov Alexander , Klochkov Vladlen , Merezhkina Darya , Miroshnikov Mikhail , Uskov Georgy , Ovsyankina Nadezhda 
Published: December 2021

AbstractThe Na+/H+ exchanger isoform 1 (NHE-1) attracts ongoing attention as a validated drug target for the management of cardiovascular and ocular diseases owing to cytoprotective, anti-ischemic and anti-inflammatory properties of NHE-1 inhibitors. Herein we report novel NHE-1 inhibitors realized via functionalization of N1-alkyl quinazoline-2,4(1H,3H)-dione and quinazoline-4(3H)-one with N-acylguanidine or 3-acyl(5-amino-1,2,4-triazole) side chain. Lead compounds show activity in a nanomolar range. Their pharmacophoric features were elucidated with neural network modeling. Several compounds combine NHE-1 inhibition with antiplatelet activity. Compound 6b reduces intraocular pressure in rats and effectively inhibits the formation of glycated proteins. Compounds 3e and 3i inhibit pro-inflammatory activation of murine macrophages, LPS-induced interleukin-6 secretion and also exhibit antidepressant activity similar to amiloride. Hence, novel compounds represent an interesting starting point for the development of agents against cardiovascular diseases, thrombotic events, excessive inflammation, long-term diabetic complications and glaucoma.
RETRACTED ARTICLE: Human blood type influences the host-seeking behavior and fecundity of the Asian malaria vector Anopheles stephensi
Authors: Khan Shahmshad Ahmed , Kassim Nur Faeza Abu , Webb Cameron Ewart , Aqueel Muhammad Anjum , Ahmad Saboor , Malik Sadia , Hussain Taimoor 
Published: December 2021

AbstractThe nutritional requirements of mosquitoes include both sugar (generally derived from the nectar of flowers) and blood (humans or animals). Mosquitoes express different degrees of preferences towards hosts depending on behavioral, ecological, and physiological factors. These preferences have implications for mosquito-borne disease risk. The present study is directed to reveal the effect of the human blood groups on the fecundity and fertility of the malaria vectorAnopheles stephensi. In laboratory tests, mosquitoes were fed on ABO blood groups via artificial membrane feeders, and the level of attraction against different blood groups was tested by the electroantennogram and wind tunnel bioassay under control conditions. Results indicate that the female mosquitoes had a strong preference towards the blood group B, while in the case of females fed on O blood group had the highest digestibility rate. Overall, the human blood type had a significant impact on the fecundity and fertility of femaleAn. stephensi.The highest numbers of eggs are laid, in the case of blood group B, (mean (± SD)) 216.3 (8.81) followed by the AB, 104.06 (7.67), and O, 98.01 (7.04). In the case of blood group B, females attain the highest fertility of about 92.1 (9.98). This study provides novel insight into the ABO blood type host choice of the mosquitoes that are still partially unknown and suggests encouraging personal protection for relevant individuals within communities at risk, which is a useful tool for preventing malaria where theAn. stephensiis present as a dominant vector.
Empirical leucine-to-carbon conversion factors in north-eastern Atlantic waters (50–2000 m) shaped by bacterial community composition and optical signature of DOM
Authors: Orta-Ponce C. Pamela , Rodríguez-Ramos Tamara , Nieto-Cid Mar , Teira Eva , Guerrero-Feijóo Elisa , Bode Antonio , Varela Marta M. 
Published: December 2021

AbstractMicrobial heterotrophic activity is a major process regulating the flux of dissolved organic matter (DOM) in the ocean, while the characteristics of this DOM strongly influence its microbial utilization and fate in the ocean. In order to broaden the vertical resolution of leucine-to-carbon conversion factors (CFs), needed for converting substrate incorporation into biomass production by heterotrophic bacteria, 20 dilution experiments were performed in the North Atlantic Ocean. We found a depth-stratification in empirical CFs values from epipelagic to bathypelagic waters (4.00 ± 1.09 to 0.10 ± 0.00 kg C mol Leu−1). Our results demonstrated that the customarily used theoretical CF of 1.55 kg C mol Leu−1 in oceanic samples can lead to an underestimation of prokaryotic heterotrophic production in epi- and mesopelagic waters, while it can overestimate it in the bathypelagic ocean. Pearson correlations showed that CFs were related not only to hydrographic variables such as temperature, but also to specific phylogenetic groups and DOM quality and quantity indices. Furthermore, a multiple linear regression model predicting CFs from relatively simple hydrographic and optical spectroscopic measurements was attempted. Taken together, our results suggest that differences in CFs throughout the water column are significantly connected to DOM, and also reflect differences linked to specific prokaryotic groups.
Effect of ocular demodicosis on the stability of the tear film and the tear break up time
Authors: Sędzikowska Aleksandra , Tarkowski Witold , Moneta-Wielgoś Joanna , Grzyliński Krzysztof , Tarkowski Grzegorz , Młocicki Daniel 
Published: December 2021

AbstractThe aim of the study was to analyze the correlation between the presence of Demodex mites in the hair follicles of patients' eyelashes and the stability and break up time of the tear film assessed with the Non-Invasive Tear Break Up Times (NIBUT) method. 319 patients were included in the study (195 women, 124 men). The patients were divided into two groups: those with Demodex infestation and without visible symptoms of eyelid or eye surface diseases, and asymptomatic non-infested patients. The NIBUT analysis was performed with a 5 M keratograph (oculus). Non-invasive tests were performed to identify the first and mean values of the tear break up time. The first and mean tear break up time in the Demodex-infested group was lower than in the non-infested subjects. The difference was a highly statistically significant. There was a significant correlation with the age of the patients for the first break up time. The first break up time in both eyes decreased with the age of the Demodex-infested and non-infested patients. The NIBUT analyses indicate the impact of Demodex mites on the tear film stability. This may suggest possible association of demodicosis with dry eye syndrome.
Development of an in vitro tissue culture system for hammer coral (Fimbriaphyllia ancora) ovaries
Authors: Chiu Yi-Ling , Chang Ching-Fong , Shikina Shinya 
Published: December 2021

AbstractIn vitro gonad culture systems have proven useful to investigate intrinsic mechanisms of sexual reproduction in animals. Here we describe development of an in vitro culture method for coral ovaries. Mesenterial tissues containing both ovaries and mesenterial filaments were microscopically isolated from the scleractinian coral, Fimbriaphyllia ancora, and culture conditions were optimized. M199 diluted 10× (10% M199, pH 8.1) and supplemented with 25 mM HEPES and the antibiotics, ampicillin, penicillin and streptomycin, supported oocyte survival and maintained the structural integrity of ovaries during short-term culture (~ 6 days). Addition of a commercial antibiotic–antimycotic solution (Anti–Anti) and fetal bovine serum adversely affected ovary maintenance and caused tissue disintegration. Characterization of cultured ovaries showed that there is no difference in cell proliferation of ovarian somatic cells between culture Days 1 and 6. Moreover, the presence of oogonia and expression of a major yolk protein, vitellogenin, were confirmed in ovaries cultured for 6 days. This system will be useful for studying effects of a wide range of substances on coral oogenesis.
CD99 antibody disrupts T-cell acute lymphoblastic leukemia adhesion to meningeal cells and attenuates chemoresistance
Authors: Ebadi Maryam , Jonart Leslie M. , Ostergaard Jason , Gordon Peter M. 
Published: December 2021

AbstractCentral nervous system (CNS) relapse is a significant cause of treatment failure among patients with acute lymphoblastic leukemia. In prior work we found that the meninges, the thin layer of tissue that covers the brain and spinal cord, harbor leukemia cells in the CNS. Importantly, direct interactions between leukemia and meningeal cells enabled leukemia chemoresistance. Herein, we show that an antibody targeting CD99, a transmembrane protein expressed on meningeal cells and many leukemia cells, disrupts adhesion between leukemia and meningeal cells and restores sensitivity of the leukemia cells to chemotherapy. This work identifies a mechanism regulating critical intercellular interactions within the CNS leukemia niche and may lead to novel therapeutic approaches for overcoming niche-mediated chemoresistance.
Prognostic value of miR-21 for prostate cancer: a systematic review and meta-analysis
Authors: Stafford M.Y. Cynthia , Willoughby Colin E. , Walsh Colum P. , McKenna Declan J. 
Published: December 2021

Abstract
Elevated levels of miR-21 expression are associated with many cancers, suggesting it may be a promising clinical biomarker. In prostate cancer (PCa), however, there is still no consensus about the usefulness of miR-21 as an indicator of disease progression. This systematic review and meta-analysis was conducted to investigate the value of miR-21 expression as a prognostic measurement in PCa patients. Medline (Ovid), EMBASE, Web of Science, Scopus and Cochrane Library databases were systematically searched for relevant publications between 2010 to 2021. Studies exploring the relationship between miR-21 expression, PCa prognosis and clinicopathological factors were selected for review. Those reporting hazard ratio (HR) and 95% confidence intervals (CIs) were subject to meta-analyses. Fixed-effect models were employed to calculated pooled HRs and 95% CIs. Risk of bias in each study was assessed using QUIPS tool. Certainty of evidence in each meta-analysis was assessed using GRADE guidelines. A total of 64 studies were included in the systematic review. Of these, 11 were eligible for inclusion in meta-analysis. Meta-analyses revealed that high miR-21 expression was associated with poor prognosis: HR = 1.58 (95% CI = 1.19–2.09) for biochemical recurrence, MODERATE certainty; HR = 1.46 (95% CI = 1.06–2.01) for death, VERY LOW certainty; and HR = 1.26 (95% CI = 0.70–2.27) for disease progression, VERY LOW certainty. Qualitative summary revealed elevated miR-21 expression was significantly positively associated with PCa stage, Gleason score and risk groups. This systematic review and meta-analysis suggests that elevated levels of miR-21 are associated with poor prognosis in PCa patients. miR-21 expression may therefore be a useful prognostic biomarker in this disease.
Integral backstepping Lyapunov redesign control of uncertain nonlinear systems
Authors: Jalalabadi Esmaeil , Paylakhi Seyedeh Zahra , Rahimi‐kian Ashkan , Moshiri Behzad 
Published: December 2021

AbstractThis paper intends to design an integral backstepping Lyapunov redesign controller (IBLRC) for various uncertain strict‐feedback‐form nonlinear systems. The pros and cons of backstepping Lyapunov redesign resulted in the design idea. An integral term is incorporated in conventional backstepping with Lyapunov redesign to indirectly decrease chattering and steady‐state error of a reference signal tracking when unknown static parameters and matched and unmatched dynamic uncertainties exist. The closed‐loop system is mathematically confirmed as stable in a Lyapunov frame, and we ultimately reach uniformly semi‐global boundedness of all signals. Simulation results of the proposed IBLRC are juxtaposed with those of the classic backstepping with the Lyapunov redesign. The proposed IBLRC realizes excellent tracking and enhanced robust performance than the BLRC for time‐varying and step tracking references.
Clinical and Obstetric Aspects of Pregnant Women with COVID-19: A Systematic Review
Authors: Bastos Sarah Nilkece Mesquita Araújo Nogueira , Barbosa Bárbara Louise Freire , Cruz Larisse Giselle Barbosa , Souza Rayza Pereira de , Silva Melo Simone Santos e , Luz Caroline Camargo Bandeira da Silveira 
Published: December 2021

Abstract
Objective To analyze the clinical and obstetric aspects of pregnant women with COVID-19.
Methods A systematic literature review in the MEDLINE/PubMed, LILACS, SCIELO, and CNKI databases was performed from March to May 2020, with the descriptors: Pregnancy; 2019-nCov; Coronavirus; SARS-Cov-2, Covid-19. Of those chosen were original titles, without language and period restriction and that addressed pregnant women with a clinical and/or laboratory diagnosis of COVID-19. Revisions, editorials, and duplicate titles were excluded. The Newcastle-Ottawa (NOS) and Murad et al. scales were used to assess the quality of the studies.
Results We included 34 articles with 412 pregnant women infected with severe acute respiratory syndrome (SARS-Cov-2), with an average age of 27.5 years of age and 36.0 gestational weeks. The most common symptom was fever (205 [49.7%]), and 89 (21.6%) pregnant women progressed to severe viral pneumonia. Laboratory tests showed an increase in C-reactive protein (154 [37.8%]), and radiological tests showed pneumonia with peripheral ground-glass pattern (172 [51.4%]). Emergency cesarean delivery was indicated for most pregnant women, and the most common gestational complication was premature rupture of ovarian membranes (14 [3.4%;]). We detected 2 (0.5%) neonatal deaths, 2 (0.5%) stillbirths, and 1 (0.2%) maternal death.
Conclusion Pregnant women with COVID-19 presented a clinical picture similar to that of non-infected pregnant women, with few obstetric or neonatal repercussions. There was a greater indication of cesarean deliveries before the disease aggravated, and there was no evidence of vertical transmission of the infection.
Overview of the Effect of Complementary Medicine on Treating or Mitigating the Risk of Endometriosis
Authors: Mirzaee Firoozeh , Ahmadi Atefeh 
Published: December 2021

Abstract
Objective Endometriosis is a hormone-dependent chronic inflammatory disease with symptoms such as pelvic pain, which affect the physical, emotional, and social health of women in reproductive age. The current overview article aims to explore the effect of complementary medicine on the treatment or in mitigating the risk of endometriosis.
Methods This is an overview article done in Iran. Two separate researchers systematically searched 3 databases (Medline, Scopus, and Cochrane Central Register Trials) until September 2020. The methodological quality of each study was assessed using the assessment of multiple systematic reviews (AMSTAR) tool.
Results The results of two reviews suggested that physical activity, tobacco smoking, diet, coffee and caffeine intake had no effect on mitigating the risk of endometriosis or improving its treatment, but acupuncture successfully reduced pain and related marker (serum CA-125) levels.
Conclusion As endometriosis is an annoying disease with many complications and is hard to diagnose and treat, related studies in complementary medicine can help patients with endometriosis. Based on the relevant literature review, among the complementary medicine available for the treatment or to mitigate the risk of endometriosis, only acupuncture seems to alleviate the pain of endometriosis.
Intermittent versus Continuous Catheterization and Differences in the Evolution of Labor: Systematic Review and Meta-analysis
Authors: Reis Inês , Cunha Sara , Martins Matilde , Sousa Luísa , Seixas Adérito , Rasteiro Cátia 
Published: December 2021

Abstract
Objective To evaluate the differences between bladder emptying options (permanent catheterization and intermittent bladder emptying/spontaneous urination) regarding the effects on labor length, need of operative vaginal deliveries, and cesarean section rate.
Data Sources The search was conducted in MEDLINE, Scopus, Web of Science, and The Cochrane Central Register of Controlled Trials databases.
Selection of Studies The survey returned 964 studies. A total of 719 studies were evaluated by title and abstract, of which 4 were selected for inclusion.
Data Collection All references were inserted in the Rayyan QCRI tool (Rayyan Systems Inc., Cambridge, MA, USA). The full text of the selected articles was obtained so we could later decide whether or not to include them in this systematic review.
Data Synthesis No differences were found in the number of instrumented deliveries or in cesarean section rate between groups.
Conclusions After evaluating the studies performed on the topic, we concluded that there is no clear advantage to either method, although continuous catheterization was associated with a greater occurrence of eutocic births. In the remaining outcomes, there were no differences between catheterization types.
Uterine Artery Pulsatility Index as a Pre-eclampsia Predictor in the 3 Trimesters in Women with Singleton Pregnancies
Authors: Guzmán Yuly Natalia , Uriel Montserrat , Ramírez Alexandra Porras , Romero Ximena Carolina 
Published: December 2021

AbstractObjective To evaluate the mean uterine artery pulsatility index (UtAPI) in each trimester of pregnancy as a predictor of early or late pre-eclampsia (PE) in Colombian pregnant women.Methods The UtAPI was measured in singleton pregnancies in each trimester. Uterine artery pulsatility index as predictor of PE was evaluated by odds ratio (OR), receiver operating characteristic (ROC) curves, and Kaplan-Meier diagram.Results Analysis in the 1st and 3rd trimester showed that abnormal UtAPI was associated with early PE (OR: 5.99: 95% confidence interval [CI]: 1.64–21.13; and OR: 10.32; 95%CI: 2.75–42.49, respectively). Sensitivity and specificity were 71.4 and 79.6%, respectively, for developing PE (area under the curve [AUC]: 0.922). The Kaplan-Meier curve showed that a UtAPI of 0.76 (95%CI: 0.58–1.0) in the 1st trimester was associated with early PE, and a UtAPI of 0.73 (95%CI: 0.55–0.97) in the 3rd trimester was associated with late PE.Conclusion Uterine arteries proved to be a useful predictor tool in the 1st and 3rd trimesters for early PE and in the 3rd trimester for late PE in a pregnant population with high prevalence of PE.
School-based HPV Vaccination: The Challenges in a Brazilian Initiative
Authors: Teixeira Julio Cesar , Vianna Mariana Silva Castro , Vale Diama Bhadra , Arbore Daniella Moretti , Perini Thais Helena Wilmers , Couto Tulio Jose Tomass , Neto Jose Pedroso , Zeferino Luiz Carlos 
Published: December 2021

Abstract
Objective The present study assesses the implementation and the impact after 2 years of a school-based human papillomavirus (HPV) vaccination program in a Brazilian city.
Methods A prospective study assessing the implementation of the program, offering quadrivalent HPV vaccine in two annual doses to girls and boys aged from 9 to 10 years old. The program was started in the city of Indaiatuba, state of São Paulo, Brazil, in 2018, and had authorization from the National Immunization Program. The number of HPV vaccine first doses applied and the coverage in 2018 was calculated and compared to the year 2017. There were described events that have influenced the results.
Results The program invited 4,878 children through schools (87.1% of the target population), and 7.5% refused vaccination. Several concurrent events required or competed for health professionals of the vaccination teams. The coverage of the first dose (between 9 and 10 years old) was 16.1% in 2017 and increased to 50.5% in 2018 (p < 0.0001). The first dose in all ages increased 78% in 2018 compared with 2017 (6,636/3,733). Competing demands over the program continued in 2019, and the first dose coverage dropped (26.9%). For 2020, a municipal law instituted school-based vaccination and the creation of dedicated teams for vaccination, and these strategies are waiting to be tested.
Conclusion School-based annual HPV vaccination in children between 9 and 10 years old was feasible and increased vaccination coverage, regardless of gender, although the program was vulnerable to competing events.