bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic Accuracy of a Liquid Chromatography-Tandem Mass Spectrometry Assay for Rifampin-resistant Tuberculosis Drug Concentrations in a Routine Care Setting
Authors: Metcalfe John , Bacchetti Peter , Esmail Ali , Reckers Andrew , Aguilar David , Wen Anita , Huo Shu , Muyindike Winnie R. , Hahn Judith A. , Dheda Keertan , Gandhi Monica , Gerona Roy 
Published: January 2021

Abstract
BackgroundTreatment monitoring of drug-resistant tuberculosis (DR-TB) in resource-limited settings is challenging. We developed a multi-analyte assay for eleven anti-TB drugs in small hair samples as an objective metric of drug exposure. MethodsSmall hair samples were collected from participants at various timepoints during directly observed RR-TB treatment at an inpatient tertiary referral facility in South Africa (DR-TB cohort). We assessed qualitative determination (i.e., detection above limit of detection) of bedaquiline, linezolid, clofazimine, pretomanid, levofloxacin, moxifloxacin, pyrazinamide, isoniazid, ethambutol, ethionamide, and prothionamide in an LC-MS/MS index panel assay against a reference standard of inpatient treatment records. Because treatment regimens prior to hospitalization were not available, we also analyzed specificity (for all drugs except isoniazid) using an external cohort of HIV-positive patients treated for latent TB infection with daily isoniazid (HIV/LTBI cohort) in Uganda.ResultsAmong the 57 DR-TB patients (58% with pre-XDR/XDR-TB; 70% HIV-positive) contributing analyzable hair samples, the sensitivity of the investigational assay was 94% or higher for all drugs except ethionamide (58.5%, 95% confidence interval [CI], 40.7-99.9). Assay specificity was low across all tested analytes within the DR-TB cohort; conversely, assay specificity was 100% for all drugs in the HIV/LTBI cohort. ConclusionsHair drug concentrations reflect long-term exposure, and multiple successive regimens commonly employed in DR-TB treatment may result in apparent false-positive qualitative and falsely elevated quantitative hair drug levels when prior treatment histories within the hair growth window are not known.
T-cell tailored single-cell RNA barcoding and sequencing (tSCRB-seq)
Authors: Kanev Kristiyan , Roelli Patrick , Wu Ming , Wurmser Christine , Delorenzi Mauro , Pfaffl Michael W. , Zehn Dietmar 
Published: January 2021

Abstract
tSCBR-seq is a T-cell tailored plate-based single-cell RNA sequencing protocol with superior mRNA capturing efficacy and dynamic range of gene detection. This was achieved through a series of chemical modifications of the original SCBR-seq protocol published by Soumilon and colleagues [1]. The performance of the protocol was also demonstrated in the article “Proliferation-competent Tcf1+ CD8 T cells in dysfunctional populations are CD4 T cell help independent” [2].
Cryo-EM reveals the architecture of placental malaria VAR2CSA and provides molecular insight into chondroitin sulfate binding
Authors: Wang Kaituo , Dagil Robert , Lavstsen Thomas , Misra Sandeep , Spliid Charlotte , Wang Yong , Gustavsson Tobias , Sandoval Daniel , Vidal-Calvo Elena , Choudhary Swati , Agerbæk Mette , Lindorff-Larsen Kresten , Nielsen Morten , Theander Thor , Sharp Joshua , Clausen Thomas , Gourdon Pontus , Salanti Ali 
Published: January 2021

Abstract
Malaria during pregnancy remains a major health problem in Plasmodium falciparum endemic areas. Parasite-infected red blood cells sequester in the placenta through interaction between parasite-expressed protein VAR2CSA and the glycosaminoglycan chondroitin sulfate A (CS) abundantly present in the intervillous space. Placental malaria can have severe consequences for both mother and child by causing maternal anemia, low birth weight and stillbirth. Several VAR2CSA-based vaccines have been developed and clinically tested but they have failed to induce an antibody response that effectively inhibits placental adhesion of different genetic variants of VAR2CSA. The interaction between VAR2CSA and CS represents a unique case of an evolution-driven high-affinity interaction between a protein and an oncofetal carbohydrate. Here, we report cryo-EM structures of the VAR2CSA ectodomain up to 3.1 Å resolution revealing an overall V-shaped architecture and a complex domain organization. Notably, the surface displays a single significantly electropositive patch, compatible with binding of negatively charged CS. Using molecular docking and molecular dynamics simulations as well as comparative hydroxyl radical protein foot-printing of VAR2CSA in complex with placental CS, we identify the CS-binding groove, intersecting with the positively charged patch of the central VAR2CSA structure. We identify distinctive conserved structural features upholding the macro-molecular domain complex and CS binding capacity of VAR2CSA as well as divergent elements possibly allowing immune escape at or near the CS binding site. These observations enable rational design of second-generation placental malaria vaccines eliciting broadly VAR2CSA-reactive antibodies and novel cancer therapies.
The Socioecological Model as a Framework for Exploring Factors Influencing Childhood Immunization Uptake in Lagos State, Nigeria
Authors: Olaniyan Abisola , Isiguzo Chinwoke , Hawk Mary 
Published: January 2021

Abstract
Background

Nigeria is one of the ten countries globally that accounts for 62% of under- and unvaccinated children worldwide. Despite several governmental and non-governmental agencies' interventions, Nigeria has yet to achieve significant gains in childhood immunization coverage. This study identifies intrapersonal, interpersonal, organizational, community, and policy-level factors that influence childhood immunization uptake from various stakeholders' perspectives using the Socioecological Model (SEM).
Methods

Using the Socioecological Model as a guiding framework, we conducted ten focus group sessions with mothers/caregivers and community leaders residing in Lagos state and nine semi-structured interviews with healthcare workers who provide routine immunization services in Lagos state primary healthcare facilities. We performed a qualitative analysis of focus groups and semi-structured interviews using deductive coding methods.
Results

The study sample included 44 mothers/caregivers and 24 community leaders residing in Lagos State, Nigeria, and 18 healthcare workers (routine immunization focal persons) working in the primary healthcare setting in Lagos state. Study participants discussed factors at the each level of the SEM that influence childhood immunization uptake, including intrapersonal (caregivers’ immunization knowledge, caregivers’ welfare and love of child/ren), interpersonal (role of individual relationships and social networks), organizational (geographical and financial access to health facilities, health facilities attributes, staff coverage, and healthcare worker attributes), community (community outreaches and community resources), and policy-level (free immunization services and provision of child immunization cards) that influence childhood immunization uptake. Several factors were intertwined, such as healthcare workers’ education of caregivers on immunization and caregivers' knowledge of vaccination.
Conclusions

The reciprocity of the findings from the different Socioecological Model levels emphasizes the importance of developing multi-pronged interventions that operate at multiple levels of the SEM. Our results can inform the design of culturally appropriate and effective interventions to address Nigeria's suboptimal immunization coverage.
Maternal Periconceptional Folic Acid Supplementation and the Risk of Non-Syndromic Oral Clefts in Offspring: A Population-Based Case-Control Study in Chengdu, China
Authors: Xu Wenli , Yi Ling , Deng Changfei , Zhao Ziling , Zhou Tianjin , Zhang Gang , Ran Longrong , Ren Zhihong , Zhao Shunxia , Liu Hanmin , Dai Li 
Published: January 2021

Abstract
Maternal periconceptional folic acid supplementation (FAS) has been documented to be associated with decreased risk of nonsyndromic oral clefts (NsOC). However, the results remain inconclusive. In this population-based case-control study of 807 singletons affected by NsOC and 8070 healthy neonates who were born between October 2010 and September 2015 in Chengdu, China, we examined the association of maternal FAS with the risk of nonsyndromic cleft lip with or without cleft palate (NsCL/P), and cleft palate (NsCP). Unconditional logistic regression analysis was used to estimate the crude and adjusted odds ratios (ORs) and 95% confidential intervals (CI). Significant associations were found between maternal periconceptional FAS and decreased risk of NsCL/P (aOR = 0.41, 95% CI: 0.33–0.51). This protective effect was also detected for NsCL (aOR = 0.42, 95% CI: 0.30–0.58) and NsCLP (aOR = 0.41, 95% CI: 0.31–0.54). Both maternal FAS started before and after the last menstrual period (LMP) were negatively associated with NsCL/P (before LMP, aOR = 0.43, 95% CI: 0.33–0.56; after LMP, aOR = 0.41, 95% CI: 0.33–0.51). The association between NsCP and maternal FAS initiating before LMP was significant (aOR = 0.52, 95% CI: 0.30–0.90), but the statistical power seemed weak due to limited number of NsCP cases. The findings suggest that maternal periconceptional FAS can reduce the risk of each subtype of NsCL/P in offspring, while the potential effect on NsCP needs further investigations.
Hyperbaric Oxygen Suppressed Tumor Progression through Improvement of Tumor Hypoxia and Induction of Tumor Apoptosis in Lung Cancer
Authors: Chen Shao-Yuan , Tsuneyama Koichi , Yen Mao-Hsiung , Lee Jiunn-Tay , Chen Jiun-Liang , Huang Shih-Ming 
Published: January 2021

Abstract
Tumor cells have long term been recognized as a relative contraindication to hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer growth. However, in an oxygen deficit condition, tumor cells are more progressive and have the potentials to be metastatic. HBOT increasing in oxygen partial pressure may benefit tumor suppression. In this study, we investigated the effects of HBOT on solid tumors, such as lung cancer. Non-small cell human lung carcinoma A549-cell-transferred severe combined immunodeficiency mice (SCID) mice were selected as an in vivo model to detect the potential mechanism of HBOT in lung tumors. HBOT not only improved tumor hypoxia but also suppressed tumor growth in murine xenograft tumor models. In vitro, HBOT suppressed the growth of A549 cells in a time-dependent manner and immediately downregulated the expression of p53 protein after HBOT in A549 cells. Our results demonstrated that HBOT improved tissue vasculogenesis, tumor hypoxia and potentially target apoptosis to lung cancer cells in murine xenograft tumor models. HBOT will merit further cancer therapy as an adjuvant treatment for lung cancer.
Flavor Disorder Is Associated with Obstructive Sleep Apnea: A Nationwide Population-Based Cohort Study
Authors: Tsao Chien-Han , Huang Hsin-Hsin , Hung Yao-Min , Hung  , Wei James Cheng-Chung , Wen Wei-Sheng , Wang Yu-Hsun , Huang Kuo-Shu 
Published: January 2021

Abstract
Background: Flavor sensation was the joint perception of smell and taste sensation was associated with the pleasure of life. Obstructive sleep apnea (OSA) had been demonstrated the presence of upper airway remodeling which altered sensory and motor function due to hypoxia or snore vibration. This study aims to investigate whether OSA is associated with the risk of flavor disorder (FD). Methods: We conducted a nationwide cohort study using the Taiwan National Health Insurance Research Database, one million subjects were sampled with data collected from 1999 to 2013 and 9,191 identified diagnosed OSA patients were included. Each patient was matched with non-OSA controls from the general population by propensity score matching (1:1) based on age, gender, hypertension, hyperlipidemia, ankylosing spondylitis, and Charlson comorbidity index, 8,037 OSA and an equal number of non-OSA subjects were used to compared in this study. The incidence of FD was assessed at the end of 2013 and cumulative incidences, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Results: The adjusted HR (aHR)of FD for the OSA group was 2.082-fold (95% CI = 1.149–3.773, p=0.0155) higher than non-OSA group. The stratified analyses revealed aHR of FD for the hyperlipidemia group was 2.264-fold (95% CI = 1.061–4.832, p=0.035). Subgroup analysis showed the subjected of female OSA had more risk to develop FD (aHR:2.345, 95% CI = 1.026–5.357, p=0.043). Conclusion: A higher risk of developing FD was found among the newly diagnosed OSA cohort during the longer than 10-year follow-up period
Prevalence of Orthodontic Malocclusion in School Children in the North East of Slovenia: Retrospective Epidemiology Study
Authors: Egic Boris 
Published: January 2021

Abstract
Background: Dental malocclusions exhibit the third-highest prevalence among oral pathologies. The occlusion is evaluated in primary, mixed and permanent dentition. Most orthodontic patients were treated in the early permanent dentition. Early detection of dental anomalies is important to prevent complications and can have short-term and long-term benefits. The epidemiological data on the prevalence of malocclusion is an important determinant in planning appropriate levels of orthodontic services. Dentists have the responsibility to recognize, diagnose, and manage or refer to abnormalities. Data from researches showed that is the incidence of malocclusions from 11% to 93%. The study aim is to find out, the prevalence and species of malocclusion of school children in 4 school years, how they are registered by general dentists.Results: The research was conducted in 4 consecutive school years on schoolchildren from 1. to 9. class. Dentists have registered the presence and type of malocclusion. They are made statistical data percentage of children with malocclusion and percentage of representation malocclusion and statistical difference between genders. The percentage of malocclusion was the lowest in the 1. class. The highest percentage of malocclusion was in 7. class. The most common types of malocclusion were deep bite, crowding cross bite and II class of Angle's. The upper lateral incisive was the most common missing tooth (aplasia).Conclusion: The high percentage of malocclusion at the end of school (15-year-old) about 50% and the low number of children in orthodontic therapy.
Mechanism of Cellular Production and in Vivo Seeding Effects of Hexameric β-Amyloid Assemblies
Authors: Vrancx Céline , Vadukul Devkee M , Contino Sabrina , Suelves Nuria , D'Auria Ludovic , Perrin Florian , Pesch Vincent van , Hanseeuw Bernard , Quinton Loïc , Kienlen-Campard Pascal 
Published: January 2021

Abstract
BackgroundThe β-amyloid peptide (Aβ) plays a key role in Alzheimer’s disease. After its production by catabolism of the amyloid precursor protein (APP) through the action of presenilin 1 (PS1)- or presenilin 2 (PS2)-dependent γ-secretases, monomeric Aβ can assemble in oligomers. In a pathological context, this eventually leads to the formation of fibrils, which deposit in senile plaques. Many studies suggest that Aβ toxicity is related to its soluble oligomeric intermediates. Among these, our interest focuses on hexameric Aβ, which acts as a nucleus for Aβ self-assembly.MethodsBiochemical analyses were used to identify hexameric Aβ in a wide range of models; cell lines, cerebrospinal fluid from cognitively impaired patients and transgenic mice exhibiting human Aβ pathology (5xFAD). We isolated this assembly and assessed both its effect on primary neuron viability in vitro, and its contribution to amyloid deposition in vivo following intracerebral injection. In both cases, we used wild-type mice (C57BL/6) to mimic an environment where hexameric Aβ is present alone and 5xFAD mice to incubate hexameric Aβ in a context where human Aβ species are pre-existing. Using CRISPR-Cas9, we produced stable knockdown human cell lines for either PS1 or PS2 to elucidate their contribution to the formation of hexameric Aβ.ResultsIn WT mice, we found that neither in vitro or in vivo exposure to hexameric Aβ was sufficient to induce cytotoxic effects or amyloid deposition. In 5xFAD mice, we observed a significant increase in neuronal death in vitro following exposure to 5μM hexameric Aβ, as well as a 1.47-fold aggravation of amyloid deposition in vivo. At the cellular level, we found hexameric Aβ in extracellular vesicles and observed a strong decrease in its excretion when PS2 was knocked down by 60%.ConclusionsOur results indicate the absence of cytotoxic effects of cell-derived hexameric Aβ by itself, but its capacity to aggravate amyloid deposition by seeding other Aβ species. We propose an important role for PS2 in the formation of this particular assembly in vesicular entities, in line with previous reports linking the restricted location of PS2 in acidic compartments to the production of more aggregation-prone Aβ.
Debridement and Bone Graft Fusion via the Lateral Extracavitary Approach Combined with Lateral and Posterior Screw-Rod Fixation in Treatment of Thoracic Spinal Tuberculosis: A Retrospective Study of 38 Cases
Authors: Zhou Jianwei , Li Shaoping , Guan Xiaoli , Lei Shuanhu , Wang Yuliang 
Published: January 2021

Abstract
BackgroundThoracic spinal tuberculosis is still common, and surgical treatment can rapidly relieve pain, correct deformity, reduce bone loss and prevent further damage to neurological function. We have practiced an efficient and safe surgical method.MethodsFrom January 2013 to April 2019, 38 patients with thoracic spinal TB were included in our study. Debridement and bone grafting were performed via the lateral extracavitary approach, combined with two different fixation method. Data from these cases were analyzed retrospectively.ResultsThe average surgical duration was 297.0±68.4 min, average intraoperative blood loss was 702.6±252.0 ml, postoperative hospital stay was 11.1±3.6 d, and C-reaction protein (CRP) and erythrocyte sedimentation rate (ESR) of all the patients decreased to normal levels at the last follow-up. The average Visual Analog Scale (VAS) score was 7.5±1.6 preoperatively and 0.6±0.8 at the last follow-up, which was significantly reduced compared with that before surgery. The average kyphosis correction was 6.3±4.7° and the angle loss was 1.4±1.6°. Neurological functions of all cases were significantly improved According to the American Spinal Injury Association (ASIA) classification. Solid fusion was observed in all cases at the last follow-up. One patient presented sinus tract formation at the incision site and the other two patients had rupture of the parietal pleura intraoperatively. No severe complications such as spinal cord injury or great vessel injury were found in all patients.ConclusionsDebridement and bone graft fusion via the posterolateral extracavitary approach combined with two fixation methods can both achieve high efficacy in the treatment of thoracic spinal TB. Lateral single screw-rod fixation is more suitable for patients with single-segment lower thoracic lesions and high stability, with less blood loss and shorter surgical duration. Posterior pedicle screw fixation has higher strength, and is more suitable for patients with multi-segment lesions, poor stability and complex conditions.
A Systematic Review and Meta-analysis of Direct Anterior Approach Versus Posterolateral Approach in Total Hip Arthroplasty
Authors: Xie Honghua , Long Junyangxi , Li Shuzhen 
Published: January 2021

Abstract
Background: To evaluate the difference of clinical results between DAA and PLA in primary THA.Methods: The PubMed , Embase and the Cochrane Library were searched by computer to collect and compare clinical randomized controlled trials of primary THA through DAA and PLA. The clinical outcome measures include operation time, total blood loss, acetabular abduction angle, acetabular anteversion angle, Harris hip score and postoperative dislocation rate. The Revman 5.3 software provided by the Cochrane Collaborat Network was used for Meta analysis of the data.Results: A total of 654 patients were included in 8 studies, including 328 patients in DAA group and 326 patients in PLA group. Meta-combined results, The number of acetabular abduction angle in DAA group is smaller than that in PLA group [MD =-0.87, 95%CI(-1.69 ~-0.04), p = 0.04], and the number of acetabular anteversion angle in DAA group is also smaller than that in PLA group [MD =-4.25, 95%CI(-4.96 ~-3.54), p < 0.00001], the differences are statistically significant. 6 weeks after operation, the Harris hip score of DAA was higher than that of PLA [MD = 5.35, 95%CI(2.38 ~ 8.32), P = 0.0004], and the difference was statistically significant. For the total Harris hip score , DAA is higher than PLA, and the difference is statistically significant [MD = 2.3, 95%CI (0.19 ~ 4.41), P = 0.03]; However, other results were not statistically significant.Conclusion: Compared with PLA, DAA can accelerate postoperative rehabilitation of patients, and at the same time can obtain better acetabular prosthesis location.
Cytotoxicity of Insects (T. Molitor, G. Bimaculatis, S. Gregaria and A. Domesticus) in A Simulated Gastrointestinal Digestion/Human Intestinal Cell Model
Authors: Dobermann Darja , Scheers Nathalie 
Published: January 2021

Abstract
Insects as an alternative nutritional source for protein and other nutrients has gained increasing attention in the last decade. On the other hand, insects produce several compounds toxic to human cells associated with e.g. antitumoral activity and as such has been proposed as tentative anti-cancer agents. In this work, we used a combined simulated gastrointestinal digestion and human absorptive cell model, Caco-2, common in nutritional studies but also in cancer research, to investigate cytotoxicity of common insect species in a simulated oral intake setting. Caco-2 cells were exposed to various concentrations of digested insects (Gryllus bimaculatus, Schistocerca gregaria, Tenebrio molitor, Acheta domesticus) which showed a significant decrease in survival and viability in response to the digests. T. molitor affected the viability of Caco-2 cells the most, compared to the other species. Notable effects on protein expression of several calcium homeostasis and cell response related proteins, FOSB, BANK1 and EGFL7, a metabolic homeostasis oxidative stress response related protein, FOXO1, and an apoptosis related protein, H0-1/HM0X/HSP32 was identified. We conclude that these insect species were cytotoxic to the intestinal cells in a simulated oral intake setting.