bluuebunny/crossref_metadata_2025 huggingface dataset:
Persepsi Generasi Milenial Kabupaten Sidoarjo terhadap Pemberlakuan Pembatasan Sosial Berskala Besar (PSBB)
Authors: Kustanto Munari , Sholihah Fitriyatus
Published: July 2021

ENGLISHThe implementation of Large Scale Social Restriction (PSBB) is one of the efforts taken by several local governments, including Sidoarjo Regency, to break the chain of COVID-19 spread. Millennials, whose age ranged from 20 to 40 years in 2020, are interesting to be studied due to their large population. In addition, they have high proficiency in information technology. This study aimed to figure out the perception of the millennials in Sidoarjo District regarding the implementation of PSBB in that area. It utilized the google form platform to create an online questionnaire then the link was sent through WhatsApp groups. 276 Millenials were involved in this study as respondents. Quantitative and descriptive meth-od was applied to analyze the data and then presented in tables and figures. The study showed 84,78% of respondents stated that they agreed with PSBB implementation; 76,45% of respondents perceived that PSBB practice was not optimal yet; 75,00% recognized that community obedience in PSBB practice was relatively low. Millenials concluded that the factors that determined community obedience in PSBB implementation were sanctions enforcement as well as direction from law officers and the government. INDONESIAPemberlakuan PSBB (Pembatasan Sosial Berskala Besar) merupakan salah satu upaya yang ditempuh beberapa pemerintah daerah, termasuk Kabupaten Sidoarjo untuk memutus rantai persebaran virus SARS-CoV-2. Generasi milenial adalah kelompok penduduk yang berada pada rentang usia 20-40 tahun di tahun 2020. Kelompok ini menarik untuk diteliti karena dominan secara demografi dan memiliki penguasaan terhadap teknologi informasi. Penelitian ini bertujuan mengetahui persepsi generasi milenial Kabupaten Sidoarjo terhadap pemberlakuan PSBB di wilayah tersebut. Penelitian memanfaatkan platform google form untuk menyebarkan kuesioner secara daring dan link kuesioner disebar melalui grup Whatsapp. Jumlah responden yang terlibat dalam penelitian adalah 276 orang. Metode deskriptif kuantitatif digunakan untuk menganalisis data dan ditampilkan melalui tabel dan grafik. Hasil penelitian menunjukkan bahwa sebanyak 84,78% generasi milenial menyatakan setuju terhadap pemberlakuan PSBB; 76,45% memersepsikan pemberlakuan PSBB kurang optimal; dan 75,00% menyatakan kepatuhan masyara-kat dalam melaksanakan PSBB masih rendah. Generasi milenial memiliki persepsi bahwa hal-hal yang meme-ngaruhi kepatuhan masyarakat selama pemberlakuan PSBB, antara lain adanya sanksi dan arahan dari aparat kea-manan maupun pemerintah.
The Royal Site of San Lorenzo de El Escorial : problems, areas of improvement and sustainable tourism development (part 3)
Authors: Martin-Merino Mario
Published: July 2021

After having exposed and analyzed the current situation of tourism activity in San Lorenzo de El Escorial from information collected from various sources, the main problems will be identified to develop a diagnosis of tourism in the town. It is clear that these problems are an impediment to achieving sustainable tourism, and it is therefore necessary for the various competent authorities to address their resolution as soon as possible and with success. If this is not the case, there is a danger that its consequences will become chronic and that the survival of tourist activity in San Lorenzo de El Escorial will be endangered, as well as its current position as one of the most important tourist destinations in the Community of Madrid.
Students’ Identity and Mental Well-Being Among Muslims and Christians in Pakistan
Authors: Shaukat Sadia , Ayub Nadia , Hanif Tarar Amina
Published: July 2021

The identity, belongingness to the larger society as well as mental well-being of minorities in Pakistan may have suffered as a result of recent social and political attacks on Christians. The present study was aimed at finding and comparing various aspects of identity (i.e., personal, social, relational, and collective) and mental well-being among adolescents from the majority (Muslims) and minority (Christian) religious groups of Lahore district in Pakistan. The study hypothesized that adolescents of religious minorities would have a lower level of sense of aspects of identity than their dominant counterparts. The sample comprised of 414 male and female students (Muslim = 225, Christian =189) with an age range from 13 to 18years, drawn from two Muslim and two Christian schools. Data was collected using the Aspects of Identity Questionnaire (Cheek & Briggs, 2013), and Warwick–Edinburgh Mental Well-being Scale (Tennant et al., 2007). Results indicated a significant difference in the level of awareness of aspects of identity as well as well-being between majority and minority adolescents. Furthermore, within the majority group, there was also a significant gender difference in social identity and mental well-being with Muslim boys scoring higher than Muslim girls on these variables. Implications of the study are discussed.
A Methodology to Compare Biomechanical Simulations With Clinical Brain Imaging Analysis Utilizing Two Blunt Impact Cases
Authors: Tan X. Gary , Sajja Venkata Siva Sai Sujith , D’Souza Maria M. , Gupta Raj K. , Long Joseph B. , Singh Ajay K. , Bagchi Amit
Published: July 2021

According to the US Defense and Veterans Brain Injury Center (DVBIC) and Centers for Disease Control and Prevention (CDC), mild traumatic brain injury (mTBI) is a common form of head injury. Medical imaging data provides clinical insight into tissue damage/injury and injury severity, and helps medical diagnosis. Computational modeling and simulation can predict the biomechanical characteristics of such injury, and are useful for development of protective equipment. Integration of techniques from computational biomechanics with medical data assessment modalities (e.g., magnetic resonance imaging or MRI) has not yet been used to predict injury, support early medical diagnosis, or assess effectiveness of personal protective equipment. This paper presents a methodology to map computational simulations with clinical data for interpreting blunt impact TBI utilizing two clinically different head injury case studies. MRI modalities, such as T1, T2, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC), were used for simulation comparisons. The two clinical cases have been reconstructed using finite element analysis to predict head biomechanics based on medical reports documented by a clinician. The findings are mapped to simulation results using image-based clinical analyses of head impact injuries, and modalities that could capture simulation results have been identified. In case 1, the MRI results showed lesions in the brain with skull indentation, while case 2 had lesions in both coup and contrecoup sides with no skull deformation. Simulation data analyses show that different biomechanical measures and thresholds are needed to explain different blunt impact injury modalities; specifically, strain rate threshold corresponds well with brain injury with skull indentation, while minimum pressure threshold corresponds well with coup–contrecoup injury; and DWI has been found to be the most appropriate modality for MRI data interpretation. As the findings from these two cases are substantiated with additional clinical studies, this methodology can be broadly applied as a tool to support injury assessment in head trauma events and to improve countermeasures (e.g., diagnostics and protective equipment design) to mitigate these injuries.
Genetic and Functional Characterization of Novel Brown-Like Adipocytes Around the Lamprey Brain
Authors: Xu XiaoLuan , Ma AnQi , Li TieSong , Cui WenXue , Wang XueFeng , Li Jun , Li Qingwei , Pang Yue
Published: July 2021

During the process of vertebrate evolution, many thermogenic organs and mechanisms have appeared. Mammalian brown adipose tissue (BAT) generates heat through the uncoupling oxidative phosphorylation of mitochondria, acts as a natural defense against hypothermia and inhibits the development of obesity. Although the existence, cellular origin and molecular identity of BAT in humans have been well studied, the genetic and functional characteristics of BAT from lampreys remain unknown. Here, we identified and characterized a novel, naturally existing brown-like adipocytes at the lamprey brain periphery. Similar to human BAT, the lamprey brain periphery contains brown-like adipocytes that maintain the same morphology as human brown adipocytes, containing multilocular lipid droplets and high mitochondrion numbers. Furthermore, we found that brown-like adipocytes in the periphery of lamprey brains responded to thermogenic reagent treatment and cold exposure and that lamprey UCP2 promoted precursor adipocyte differentiation. Molecular mapping by RNA-sequencing showed that inflammation in brown-like adipocytes treated with LPS and 25HC was enhanced compared to controls. The results of this study provide new evidence for human BAT research and demonstrate the multilocular adipose cell functions of lampreys, including: (1) providing material energy and protecting structure, (2) generating additional heat and contributing to adaptation to low-temperature environments, and (3) resisting external pathogens.
Principles and Practice of Explainable Machine Learning
Authors: Belle Vaishak , Papantonis Ioannis
Published: July 2021

Artificial intelligence (AI) provides many opportunities to improve private and public life. Discovering patterns and structures in large troves of data in an automated manner is a core component of data science, and currently drives applications in diverse areas such as computational biology, law and finance. However, such a highly positive impact is coupled with a significant challenge: how do we understand the decisions suggested by these systems in order that we can trust them? In this report, we focus specifically on data-driven methods—machine learning (ML) and pattern recognition models in particular—so as to survey and distill the results and observations from the literature. The purpose of this report can be especially appreciated by noting that ML models are increasingly deployed in a wide range of businesses. However, with the increasing prevalence and complexity of methods, business stakeholders in the very least have a growing number of concerns about the drawbacks of models, data-specific biases, and so on. Analogously, data science practitioners are often not aware about approaches emerging from the academic literature or may struggle to appreciate the differences between different methods, so end up using industry standards such as SHAP. Here, we have undertaken a survey to help industry practitioners (but also data scientists more broadly) understand the field of explainable machine learning better and apply the right tools. Our latter sections build a narrative around a putative data scientist, and discuss how she might go about explaining her models by asking the right questions. From an organization viewpoint, after motivating the area broadly, we discuss the main developments, including the principles that allow us to study transparent models vs. opaque models, as well as model-specific or model-agnostic post-hoc explainability approaches. We also briefly reflect on deep learning models, and conclude with a discussion about future research directions.
A Test of Species Distribution Model Transferability Across Environmental and Geographic Space for 108 Western North American Tree Species
Authors: Charney Noah D. , Record Sydne , Gerstner Beth E. , Merow Cory , Zarnetske Phoebe L. , Enquist Brian J.
Published: July 2021

Predictions from species distribution models (SDMs) are commonly used in support of environmental decision-making to explore potential impacts of climate change on biodiversity. However, because future climates are likely to differ from current climates, there has been ongoing interest in understanding the ability of SDMs to predict species responses under novel conditions (i.e., model transferability). Here, we explore the spatial and environmental limits to extrapolation in SDMs using forest inventory data from 11 model algorithms for 108 tree species across the western United States. Algorithms performed well in predicting occurrence for plots that occurred in the same geographic region in which they were fitted. However, a substantial portion of models performed worse than random when predicting for geographic regions in which algorithms were not fitted. Our results suggest that for transfers in geographic space, no specific algorithm was better than another as there were no significant differences in predictive performance across algorithms. There were significant differences in predictive performance for algorithms transferred in environmental space with GAM performing best. However, the predictive performance of GAM declined steeply with increasing extrapolation in environmental space relative to other algorithms. The results of this study suggest that SDMs may be limited in their ability to predict species ranges beyond the environmental data used for model fitting. When predicting climate-driven range shifts, extrapolation may also not reflect important biotic and abiotic drivers of species ranges, and thus further misrepresent the realized shift in range. Future studies investigating transferability of process based SDMs or relationships between geodiversity and biodiversity may hold promise.
Experimental and Genomic Evaluation of the Oestrogen Degrading Bacterium Rhodococcus equi ATCC13557
Authors: Harthern-Flint Sarah L. , Dolfing Jan , Mrozik Wojciech , Meynet Paola , Eland Lucy E. , Sim Martin , Davenport Russell J.
Published: July 2021

Rhodococcus equi ATCC13557 was selected as a model organism to study oestrogen degradation based on its previous ability to degrade 17α-ethinylestradiol (EE2). Biodegradation experiments revealed that R. equi ATCC13557 was unable to metabolise EE2. However, it was able to metabolise E2 with the major metabolite being E1 with no further degradation of E1. However, the conversion of E2 into E1 was incomplete, with 11.2 and 50.6% of E2 degraded in mixed (E1-E2-EE2) and E2-only conditions, respectively. Therefore, the metabolic pathway of E2 degradation by R. equi ATCC13557 may have two possible pathways. The genome of R. equi ATCC13557 was sequenced, assembled, and mapped for the first time. The genome analysis allowed the identification of genes possibly responsible for the observed biodegradation characteristics of R. equi ATCC13557. Several genes within R. equi ATCC13557 are similar, but not identical in sequence, to those identified within the genomes of other oestrogen degrading bacteria, including Pseudomonas putida strain SJTE-1 and Sphingomonas strain KC8. Homologous gene sequences coding for enzymes potentially involved in oestrogen degradation, most commonly a cytochrome P450 monooxygenase (oecB), extradiol dioxygenase (oecC), and 17β-hydroxysteroid dehydrogenase (oecA), were identified within the genome of R. equi ATCC13557. These searches also revealed a gene cluster potentially coding for enzymes involved in steroid/oestrogen degradation; 3-carboxyethylcatechol 2,3-dioxygenase, 2-hydroxymuconic semialdehyde hydrolase, 3-alpha-(or 20-beta)-hydroxysteroid dehydrogenase, 3-(3-hydroxy-phenyl)propionate hydroxylase, cytochrome P450 monooxygenase, and 3-oxosteroid 1-dehydrogenase. Further, the searches revealed steroid hormone metabolism gene clusters from the 9, 10-seco pathway, therefore R. equi ATCC13557 also has the potential to metabolise other steroid hormones such as cholesterol.
Identification of a Genetically Linked but Functionally Independent Two-Component System Important for Cell Division of the Rice Pathogen Burkholderia glumae
Authors: Marunga Joan , Goo Eunhye , Kang Yongsung , Hwang Ingyu
Published: July 2021

Bacterial two-component regulatory systems control the expression of sets of genes to coordinate physiological functions in response to environmental cues. Here, we report a genetically linked but functionally unpaired two-component system (TCS) comprising the sensor kinase GluS (BGLU_1G13350) and the response regulator GluR (BGLU_1G13360), which is critical for cell division in the rice pathogen Burkholderia glumae BGR1. The gluR null mutant, unlike the gluS mutant, formed filamentous cells in Lysogeny Broth medium and was sensitive to exposure to 42°C. Expression of genes responsible for cell division and cell-wall (dcw) biosynthesis in the gluR mutant was elevated at transcription levels compared with the wild type. GluR-His bound to the putative promoter regions of ftsA and ftsZ is involved in septum formation, indicating that repression of genes in the dcw cluster by GluR is critical for cell division in B. glumae. The gluR mutant did not form filamentous cells in M9 minimal medium, whereas exogenous addition of glutamine or glutamate to the medium induced filamentous cell formation. These results indicate that glutamine and glutamate influence GluR-mediated cell division in B. glumae, suggesting that GluR controls cell division of B. glumae in a nutrition-dependent manner. These findings provide insight into how the recognition of external signals by TCS affects the sophisticated molecular mechanisms involved in controlling bacterial cell division.
Case Report: Mitochondrial Encephalomyopathy Presents as Epilepsy, Ataxia, and Dystonia With a Rare Mutation in MT-TW
Authors: Wang Shuang , Miao Jing , Feng Jiachun
Published: July 2021

Mitochondrial diseases are a group of common inherited disorders caused by mutations in nuclear DNA or mitochondrial DNA (mtDNA); the clinical phenotype of diseases caused by mutant mtDNA is challenging owing to heteroplasmy of mtDNA and may delay diagnosis and treatment. Herein, we report the case of an adult male who slowly developed epilepsy, ataxia, dystonia, impaired cognition, and hearing impairment over 14 years in the absence of clinical myopathy. His lactate level was normal. Brain computed tomography showed calcifications of the bilateral basal ganglia, thalamus, and cerebellar dentate nuclei. Magnetic resonance imaging revealed multiple lesions in the bilateral internal capsule and periventricular areas, which were hypointense on T1-weighted images and hyperintense on T2-weighted images. The first blood genetic test result was negative. Two years later, a muscle biopsy was performed. Succinate dehydrogenase (SDH) staining showed several ragged blue fibers and atypical strongly SDH-reactive vessels. Cytochrome C oxidase (COX) staining revealed abundant COX-deficient fibers. mtDNA testing of blood and muscle revealed a rare m.5549G>A mutation in the MT-TW gene. It was heteroplasmic, with 5.4% mutant mtDNA in the blood and 61.5% in the muscle. The patient was diagnosed with mitochondrial encephalomyopathy and treated with levetiracetam instead of valproate to reduce possible mitochondrial toxicity. After receiving anti-epileptic drugs and mitochondrial supplements, the patient remained clinically stable. For mitochondrial disease, when mutant mtDNA is not detected in blood, muscle biopsy should be performed in routine analysis, and it should be genetically tested, even if there are no manifestations of myopathy.
Development and Validation of a Prognostic Nomogram for Colorectal Cancer Patients With Synchronous Peritoneal Metastasis
Authors: Yang Zifeng , Li Yong , Qin Xiusen , Lv Zejian , Wang Huaiming , Wu Deqing , Yuan Zixu , Wang Hui
Published: July 2021

Purpose

Synchronous peritoneal metastasis (S-PM) is considered a poor prognostic factor for colorectal cancer (CRC) and there is no nomogram to predict the survival of these patients. In this study, we aimed to use a multicenter data to identify the factors associated with S-PM of CRC to construct a nomogram for predicting the overall survival (OS) of these patients.

Methods

CRC patients with S-PM from two medical centers were enrolled between September 2007 and June 2017. Multivariate analysis was used to identify independent factors associated with OS for the nomogram to predict the 1-, 2-, and 3-year OS rates in the development group. The concordance index (C-index), calibration plot, relative operating characteristic (ROC) curve with area under the curve (AUC) were calculated to evaluate the performance of the nomogram in both the development and an external validation group.

Results

277 CRC patients with S-PM in the development group and 68 patients in the validation group were eligible for this study. In multivariate analysis of development group, age, carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and chemotherapy were independent variables for OS, based on which the nomogram was built. The C-index of the nomogram in the development and validation group was 0.701 (95% Cl, 0.666–0.736) and 0.716 (95% Cl, 0.622–0.810); demonstrating good discriminative ability. The calibration plots showed satisfactory consistency between actual observation and nomogram-predicted OS probabilities in the development and external validation group. The nomogram showed good predictive accuracy for 1-, 2-, and 3-year OS rates in both groups with AUC >0.70. An online dynamic webserver was also developed for increasing the ease of the nomogram.

Conclusions

We developed and validated a predictive nomogram with good discriminative and high accuracy to predict the OS in CRC patients with S-PM.
Downregulation of miR-135b-5p Suppresses Progression of Esophageal Cancer and Contributes to the Effect of Cisplatin
Authors: Di Yuzhu , Jiang Yanan , Shen Xiuyun , Liu Jing , Gao Yang , Cai Huimin , Sun Xiaoli , Ning Dandan , Liu Bing , Lei Jiaji , Jin Shizhu
Published: July 2021

Esophageal cancer (EC) is one of the commonest human cancers, which accompany high morbidity. MicroRNAs (miRNAs) play a pivotal role in various cancers, including EC. Our research aimed to reveal the function and mechanism of miR-135b-5p. Our research identified that miR-135b-5p was elevated in EC samples from TCGA database. Correspondingly real-time PCR assay also showed the miR-135b-5p is also higher expressed in Eca109, EC9706, KYSE150 cells than normal esophageal epithelial cells (Het-1A). CCK8, Edu, wound healing, Transwell assay, and western blot demonstrated miR-135b-5p inhibition suppresses proliferation, invasion, migration and promoted the apoptosis in Eca109 and EC9706 cells. Moreover, the miR-135b-5p inhibition also inhibited xenograft lump growth. We then predicted the complementary gene of miR-135b-5p using miRTarBase, TargetScan, and DIANA-microT. TXNIP was estimated as a complementary gene for miR-135b-5p. Luciferase report assay verified the direct binding site for miR-135b-5p and TXNIP. Real-time PCR and western blot assays showed that the inhibition of miR-135b-5p remarkably enhanced the levels of TXNIP in Eca109 and EC9706 cells. Furthermore, cisplatin (cis-diamminedichloroplatinum II, DDP) decreased miR-135b-5p expression and increased TXNIP expression. Enhanced expression of miR-135b-5p attenuated the inhibitory ability of cisplatin (cis-diamminedichloroplatinum II, DDP) in Eca109 cells, accompanied by TXNIP downregulation. In conclusion, the downregulation of miR-135b-5p suppresses the progression of EC through targeting TXNIP. MiR-135b-5p/TXNIP pathway contributes to the anti-tumor effect of DDP. These findings may provide new insight into the treatment of EC.
18F-Fluoride PET/CT Imaging of Medication-Related Osteonecrosis of the Jaw in Conservative Treatment—A Case Report
Authors: Reinert Christian Philipp , Pfannenberg Christina , Gatidis Sergios , la Fougère Christian , Nikolaou Konstantin , Hoefert Sebastian
Published: July 2021

Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect in antiresorptive treatment. Treatment of MRONJ is considered primarily conservative with oral mouth rinses and antibiotics but may demand surgery, depending on the complaints and general condition of the patient, the extent of the necrosis, and the overall prognosis with respect to the underlying disease. A 77 year old female patient with invasive ductal breast cancer and bone metastases was treated with intravenous bisphosphonate (BP) zoledronic acid. During therapy, she developed MRONJ in the mandible with severe pain. Clinical examination revealed confluent exposed bone of the lower left jaw and a fistula at the right molar region. The panoramic radiograph revealed a mandibular osseous involvement with diffuse radiopaque areas between radiolucent areas. For preoperative planning, 18F-fluoride positron emission tomography/computed tomography (PET/CT) of the jaw was performed, showing substantially increased 18F-fluoride uptake in regions 38 to 47 of the mandible with a focal gap in region 36 (area of clinically exposed bone). CT revealed medullary sclerosis and cortical thickening with confluent periosteal reaction and focal cortical erosion in the regions 37 to 42, whereas the regions 43 to 47 were only subtly sclerotic without cortical thickening. After systemic antibiotic therapy with sultamicillin following significant symptom and pain relief, 18F-fluoride PET/CT imaging was performed again after 5 months. No changes in either CT and PET were observed in regions 38 to 42, whereas the bony sclerosis was slightly increased in regions 43 to 47 with a slight reduction of 18F-fluoride uptake. 18F-fluoride PET/CT showed no significant changes assessing the extent of MRONJ prior and after systemic antibiotic therapy, providing no evidence that conservative treatment reduced the extent of the MRONJ-affected jawbone. The additional information of 18F-fluoride PET enables to identify the true extent of MRONJ which may be underestimated by CT imaging alone. Patients with MRONJ undergoing conservative treatment could benefit because additional imaging may be avoided as the pre-therapeutic 18F-fluoride PET/CT delivers all information needed for further treatment. Our findings support the recommendation of a surgical approach as long-term antibiotics cannot downsize the extent of MRONJ.
Near-Infrared Fluorescent Agent for In Vitro Screening of Endometrial Cancer and Precancerous Lesions
Authors: Liang Dongxin , Tuo Xiaoqian , Wang Qing , Zhao Lanbo , Zhang Kailu , Wang Yiran , Feng Xue , Yin Panyue , Guo Lin , Liu Yu , Wang Lei , Han Lu , An Ruifang , Li Qiling
Published: July 2021

The lack of cytopathologists delays the advancement of screening for endometrial cancer. It was urgent to develop a new dye for rapid diagnosis. Our study aimed to synthesize a targeted folate receptor-α near-infrared (NIR) fluorescent agent, folic acid-zwitterionic NIR fluorophore (ZW-FA), and explore the feasibility for screening of endometrial cancer and precancerous change. Folic acid was conjugated with zwitterionic NIR fluorophore. The preparation of ZW-FA was validated by 1H NMR, mass spectrometric, ultraviolet spectra and fluorescence spectra. ZW-FA was incubated with endometrial cytology samples obtained from patients who underwent dilation and curettage or total hysterectomy. Diagnostic utility was calculated by applying laser confocal microscope, Image-J and statistical models, such as enumeration, receiver operating characteristic curve, logistic regression, support vector machine and decision tree were used. The purity of ZW-FA was > 95% determined by 1H NMR. ZW-FA had the strongest absorption peak at 633 nm in ultraviolet spectra. Photostability of ZW-FA was over 8 hours. In clinical validation, a total of 92 patients were enrolled. The cut-off value of ZW-FA was 49 in enumeration, which was used to distinguish the type of samples. Indicators about diagnostic utility are as follows: sensitivity 90.77%, specificity 62.96%, false-positive rate 37.04%, false-negative rate 9.23%, positive predictive value 85.51% and negative predictive value 73.91%. The samples processed by ZW-FA did not affect further Hematoxylin-Eosin staining and pathological diagnosis. It was an effective cytologic strategy for in vitro diagnosis of endometrial cancer and precancerous change by using ZW-FA.

Clinical Trial Registration

http://www.chictr.org.cn/index.aspx, identifier ChiCTR1800020123.
Model-Based Meta-Analysis in Psoriasis: A Quantitative Comparison of Biologics and Small Targeted Molecules
Authors: He Huan , Wu Wenwen , Zhang Yi , Zhang Meng , Sun Ning , Zhao Libo , Wang Xiaoling
Published: July 2021

Background: The response time-course information of biologics and small targeted molecules for the treatment of moderate to severe plaque psoriasis which helps clinicians to understand the onset of action and maintenance of effect are unclear. Quantitative information about the efficacy comparation of different systemic agents are needed.

Methods: Model-based meta-analysis was conducted and longitudinal models were developed by applying two clinical end points commonly reported in the clinical trials of psoriasis: the proportion of patients achieving ≥75% reduction from baseline Psoriasis Area and Severity Index score (PASI75) and the proportion of patients achieving ≥90% reduction from baseline Psoriasis Area and Severity Index score (PASI90).

Results: A total of 80 trials of thirteen biological agents and four small targeted molecules covering 235 treatment arms and 40323 patients with moderate to severe plaque psoriasis were included in this analysis. The drugs were divided into five classes of biologics and three classes of small molecules. Two longitudinal models of PASI75 and PASI90 were used to describe the time-varying drug effect and dose-effect relationship. The typical response-time courses for PASI75 and PASI90 increased over time and finally reached to the platform. For PASI75 end point at week 12, of all the therapeutic drugs, risankizumab administered as 150 mg at week 0, week 4, and q12w showed the most efficacious with PASI75 was 85.95% (95%CI, 75.71–92.60%), followed by ixekizumab administered as 160 mg at week 0, and q4w with PASI75 was 85.9% (95%CI, 76.12–92.79%). As for PASI90 end point at week 12, ixekizumab 160 mg at week 0, and q4w showed the greatest percentage of person achieved PASI90 (67.2%; 95%CI, 49.91–77.2%), followed by risankizumab 150 mg at week 0, week 4, and q12w (65.5%; 95%CI, 47.8–75.7%). What’s more, the risankizumab provided the highest response of PASI90 at week 16 and week 24.

Conclusions: This study provided a quantitative efficacy comparation of 17 systemic agents for psoriasis in term of efficacy only and that safety was not considered. Risankizumab and ixekizumab showed superiority for both the two end points.
Comparative Efficacy and Acceptability of Anti-inflammatory Agents on Major Depressive Disorder: A Network Meta-Analysis
Authors: Hang Xiaoyi , Zhang Yijie , Li Jingjing , Li Zhenzhen , Zhang Yi , Ye Xuanhao , Tang Qisheng , Sun Wenjun
Published: July 2021

Background: With the growing importance of research about the association between neuroinflammation and major depressive disorder (MDD), anti-inflammatory agents have been used as a new antidepressant therapy in clinical practice. We conducted a network meta-analysis (NMA) with up-to-date evidence to compare different anti-inflammatory agents for improving the treatment of MDD patients.

Methods: To identify eligible randomized clinical trials, four databases (i.e, the Cochrane Library, Web of Science, PubMed and Embase) were searched from inception date to May 31, 2020. Anti-inflammatory agents were defined as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, cytokine inhibitors, statins, pioglitazone, minocycline, N-acetylcysteine (NAC) and omega-3 fatty acid (Omega-3 FA). The main outcomes of this NMA were efficacy, acceptability and remission rate. Risk ratio (RR) was adopted for dichotomous outcomes, and the confidence interval (CI) was set at 95%. STATA 14.0 and R 3.6.3 were used to conduct the NMA. The study protocol was registered with PROSPERO (CRD42020182531).

Results: A total of 39 studies, involving 2871 participants, were included in quantitative data synthesis. For efficacy, NSAIDs (RR=0.50, 95%CI: 0.26-0.73) and pioglitazone (RR=0.45, 95%CI: 0.20-0.84) were more favorable than placebo. With respect to acceptability, NSAIDs were more acceptable than placebo (RR=0.89, 95%CI: 0.77-0.99) and minocycline (RR=1.22, 95%CI: 1.03-1.49). For remission, NSAIDs were more superior than placebo (RR=0.48, 95%CI: 0.27-0.79) and Omega-3 FA (RR=2.01, 95%CI: 1.09-3.90), while NACs were more favorable than placebo (RR=0.39, 95%CI: 0.13-0.99). Based on the surface under the cumulative ranking curve (SUCRA) value, corticosteroids (0.86) were the best anti-inflammatory agent for MDD patients in terms of efficacy, but the head-to-head comparisons for the efficacy of glucocorticoids and other agents were not statistically significant. As for acceptability, NSAIDs (0.81) were much better than other anti-inflammatory agents. Besides, NAC (0.80) was the best anti-inflammatory agent in the terms of remission.

Conclusions: In summary, we found that corticosteroids were more superior than other agents in terms of efficacy according to the SUCRA value. However, this result must be interpreted with caution because the head-to-head comparisons for the efficacy of glucocorticoids and other agents did not reach statistical significance. NSAIDs were recommended for acceptability and NAC for remission rate.
Distinct Embryonic Origin and Injury Response of Resident Stem Cells in Craniofacial Muscles
Authors: Cheng Xu , Shi Bing , Li Jingtao
Published: July 2021

Craniofacial muscles emerge as a developmental novelty during the evolution from invertebrates to vertebrates, facilitating diversified modes of predation, feeding and communication. In contrast to the well-studied limb muscles, knowledge about craniofacial muscle stem cell biology has only recently starts to be gathered. Craniofacial muscles are distinct from their counterparts in other regions in terms of both their embryonic origin and their injury response. Compared with somite-derived limb muscles, pharyngeal arch-derived craniofacial muscles demonstrate delayed myofiber reconstitution and prolonged fibrosis during repair. The regeneration of muscle is orchestrated by a blended source of stem/progenitor cells, including myogenic muscle satellite cells (MuSCs), mesenchymal fibro-adipogenic progenitors (FAPs) and other interstitial progenitors. Limb muscles host MuSCs of the Pax3 lineage, and FAPs from the mesoderm, while craniofacial muscles have MuSCs of the Mesp1 lineage and FAPs from the ectoderm-derived neural crest. Both in vivo and in vitro data revealed distinct patterns of proliferation and differentiation in these craniofacial muscle stem/progenitor cells. Additionally, the proportion of cells of different embryonic origins changes throughout postnatal development in the craniofacial muscles, creating a more dynamic niche environment than in other muscles. In-depth comparative studies of the stem cell biology of craniofacial and limb muscles might inspire the development of novel therapeutics to improve the management of myopathic diseases. Based on the most up-to-date literature, we delineated the pivotal cell populations regulating craniofacial muscle repair and identified clues that might elucidate the distinct embryonic origin and injury response in craniofacial muscle cells.
Sleep, Anxiety, and Academic Performance: A Study of Adolescents From Public High Schools in China
Authors: Zhang Xiaoning , Dimitriou Dagmara , Halstead Elizabeth J.
Published: July 2021

Purpose: Sleep is essential for optimal learning across the developmental pathways. This study aimed to (1) explore whether school start and end times and screen time influenced sleep disturbances in adolescents during the lockdown in China and (2) investigate if sleep disturbances at night and sleep-related impairment (daytime fatigue) influenced adolescents' academic performance and anxiety levels.

Methods: Ninety-nine adolescents aged 15–17 years old were recruited from two public schools in Baishan City Jilin Province, China. An online questionnaire was distributed including questions on adolescents' demographics, screen time habits, academic performance, anxiety level, sleep disturbances, and sleep-related impairment.

Results: Adolescents who started school earlier and ended school later had a greater severity of sleep disturbances and sleep-related impairment compared with students who started school later and finished earlier. Adolescents who engaged in screen time at bedtime were more likely to have a greater severity of sleep-related impairment than students who reported no screen time use at bedtime. Adolescents who had a greater severity of sleep disturbances had higher anxiety and higher academic achievements than adolescents with less sleep disturbances. Finally, 79.7% of adolescents reported their total sleep duration as <8 h.

Conclusions: Adolescents are experiencing sleep disturbances to manage academic demands during COVID-19, which in turn is having a wider impact on their mental health. Many schools internationally have continued to provide online education to students, longitudinal studies on how COVID-19 has influenced adolescents sleep and mental health would be beneficial in understanding the impact of the pandemic.
Lexical and Structural Cues to Discourse Processing in First and Second Language
Authors: Crible Ludivine , Wetzel Mathis , Zufferey Sandrine
Published: July 2021

Discourse connectives are lexical items like “but” and “so” that are well-known to influence the online processing of the discourse relations they convey. Yet, discourse relations like causality or contrast can also be signaled by other means than connectives, such as syntactic structures. So far, the influence of these alternative signals for discourse processing has been comparatively under-researched. In particular, their processing in a second language remains entirely unexplored. In a series of three self-paced reading experiments, we compare the reading patterns of contrastive relations by native French-speakers and non-native speakers of French with English as a first language. We focus on the effect of syntactic parallelism and how it interacts with different types of connectives. We test whether native and non-native readers equally recruit parallelism to process contrast in combination with or without a connective (Experiment 1), with a frequent vs. infrequent connective (Experiment 2) and with an ambiguous vs. unambiguous connective (Experiment 3), thus varying the explicitness and ease of retrieval of the contrast relation. Our results indicate that parallelism plays an important role for both groups of readers, but that it is a more prominent cue for non-native speakers, while its effect is modulated by task difficulty for native participants.
A Framework for Cervical Cancer Elimination in Low-and-Middle-Income Countries: A Scoping Review and Roadmap for Interventions and Research Priorities
Authors: Shin Michelle B. , Liu Gui , Mugo Nelly , Garcia Patricia J. , Rao Darcy W. , Broshkevitch Cara J. , Eckert Linda O. , Pinder Leeya F. , Wasserheit Judith N. , Barnabas Ruanne V.
Published: July 2021

The World Health Organization announced an ambitious call for cervical cancer elimination worldwide. With existing prevention and treatment modalities, cervical cancer elimination is now within reach for high-income countries. Despite limited financing and capacity constraints in low-and-middle-income countries (LMICs), prevention and control efforts can be supported through integrated services and new technologies. We conducted this scoping review to outline a roadmap toward cervical cancer elimination in LMICs and highlight evidence-based interventions and research priorities to accelerate cervical cancer elimination. We reviewed and synthesized literature from 2010 to 2020 on primary and secondary cervical cancer prevention strategies. In addition, we conducted expert interviews with gynecologic and infectious disease providers, researchers, and LMIC health officials. Using these data, we developed a logic model to summarize the current state of science and identified evidence gaps and priority research questions for each prevention strategy. The logic model for cervical cancer elimination maps the needs for improved collaboration between policy makers, production and supply, healthcare systems, providers, health workers, and communities. The model articulates responsibilities for stakeholders and visualizes processes to increase access to and coverage of prevention methods. We discuss the challenges of contextual factors and highlight innovation needs. Effective prevention methods include HPV vaccination, screening using visual inspection and HPV testing, and thermocoagulation. However, vaccine coverage remains low in LMICs. New strategies, including single-dose vaccination could enhance impact. Loss to follow-up and treatment delays could be addressed by improved same-day screen-and-treat technologies. We provide a practical framework to guide cervical cancer elimination in LMICs. The scoping review highlights existing and innovative strategies, unmet needs, and collaborations required to achieve elimination across implementation contexts.
Population-Based Prevalence of Oral Conditions as a Basis for Planning Community-Based Interventions: An Epidemiological Study From Rural Burkina Faso
Authors: Clauss Alexandra , Sie Ali , Zabre Pascal , Schmoll Jörg , Sauerborn Rainer , Listl Stefan
Published: July 2021

Objectives: The purpose of the present study was to: (i) provide timely data on dental caries and periodontal conditions in rural Burkina Faso; (ii) identify the oral health practices carried out in this population, and (iii) to prioritize evidence-based interventions at the community level.

Methods: Leaning on WHO recommendations for oral health epidemiological studies, clinical examinations and questionnaire-based surveys were conducted in two different age groups (adolescents: 15–19 years old; adults: 35–44 years old) in the health district of Nouna, Burkina Faso. Caries and tooth status were assessed according to the DMFT Index. The periodontal status was assessed by a modified Community Periodontal Index on all teeth present and measuring the level of attachment-loss of six index teeth. Questionnaire items specifically included utilization of oral health care and oral health behaviors.

Results: The prevalence of untreated caries was 38% in adolescents and 73% in adults. In terms of periodontal health, 21% of adolescents and 61% of adults had an attachment loss ≥4 mm. Ninety seven percent of adolescents had not attended a dentist in the previous year and 78% of adults had never seen a dentist in their life. About one third of adolescents and adults cleaned their teeth less often than once per day with equal proportions of toothbrushes and traditional chewing sticks made of tree branches. Fluoride toothpaste was used by <10% of study participants. Almost half of the examined people reported to drink a sugar-sweetened beverage at least once a day.

Conclusions: Dental caries and periodontitis are highly prevalent in rural Burkina Faso. These findings highlight the key relevance of epidemiological data for identifying people's oral health needs as basis for developing, testing, and implementing oral health interventions and programs. Special emphasis should be put on the design and evaluation of community-based interventions.
Evaluating Young People's Ability to Sustain an Evidence-Based Social Accountability Approach to Improve Adolescent Sexual and Reproductive Health in Ntcheu, Malawi
Authors: Mgoli Mwale Patience , Msiska Thumbiko , Wako Etobssie , Chinkhota Kriss , Munthali Tapiwa , Rodriguez Mariela , Shato Thembekile , Laterra Anne , Sebert Kuhlmann Anne
Published: July 2021

The Community Score Card© (CSC), a social accountability approach, brings together community members, service providers, and local government officials to identify issues, prioritize, and plan actions to improve local health services. In addition, young people in Ntcheu, Malawi have been using the CSC approach to mobilize their communities to bring change across varying issues of importance to them. An earlier cluster randomized trial in Ntcheu showed the CSC effectively increased reproductive health behaviors, improved satisfaction with services, and enhanced the coverage and quality of services. Building upon this evidence of effectiveness, this study aims to evaluate if and how young people were able to sustain implementation of the CSC, and the improvements it brings, approximately 2.5 years after the randomized trial ended. As part of a larger evaluation of CSC sustainability in Ntcheu, we conducted 8 focus groups across 5 health catchment areas with 109 members of mixed-gender youth groups (58 females and 51 males, ages 14–29 years) who continued to engage with the CSC. Audio recordings were transcribed, translated into English, and coded in Dedoose using an a priori codebook augmented with emergent codes and a constant comparative approach. Although the 8 youth groups were still actively using the CSC, they had made some adaptations. While the CSC in Ntcheu initially focused on maternal health, young people adopted the approach for broader sexual and reproductive topics important to them such as child marriages and girls' education. To enable sustainability, young people trained each other in the CSC process; they also requested more formal facilitation training. Young people from Ntcheu recommended nationwide scale-up of the CSC. Young people organically adopted the CSC, which enabled them to highlight issues within their communities that were a priority to them. This diffusion among young people enabled them to elevate their voice and facilitate a process where they hold local government officials, village leaders, and services providers accountable for actions and the quality of healthcare services. Young people organized and sustained the CSC as a social accountability approach to improve adolescent sexual and reproductive health in their communities more than 2.5 years after the initial effectiveness trial ended.
The Effects of Incorrect Occlusion Cues on the Understanding of Barehanded Referencing in Collaborative Augmented Reality
Authors: Li Yuan , Hu Donghan , Wang Boyuan , Bowman Doug A. , Lee Sang Won
Published: July 2021

In many collaborative tasks, the need for joint attention arises when one of the users wants to guide others to a specific location or target in space. If the collaborators are co-located and the target position is in close range, it is almost instinctual for users to refer to the target location by pointing with their bare hands. While such pointing gestures can be efficient and effective in real life, performance will be impacted if the target is in augmented reality (AR), where depth cues like occlusion may be missing if the pointer’s hand is not tracked and modeled in 3D. In this paper, we present a study utilizing head-worn AR displays to examine the effects of incorrect occlusion cues on spatial target identification in a collaborative barehanded referencing task. We found that participants’ performance in AR was reduced compared to a real-world condition, but also that they developed new strategies to cope with the limitations of AR. Our work also identified mixed results of the effect of spatial relationships between users.