bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of efficacy and tolerability of adjuvant therapy for resected high-risk stage III-IV cutaneous melanoma: a systemic review and Bayesian network meta-analysis
Authors: Ba He , Zhu Fangyuan , Zhang Xiaoze , Mei Zubing , Zhu Yaodong 
Published: January 2023

Background: Although immune checkpoint inhibitors (ICIs) and targeted therapies have been widely used as adjuvant treatment for resected melanoma, the optimal therapy remains controversial. Therefore, we conducted this updated network meta-analysis (NMA) to assess the efficacy and tolerability of adjuvant therapies for cutaneous melanoma. Methods: PubMed, Embase, Cochrane library, and Web of Science were systematically searched for relevant literatures published in the last 30 years. Disease-free survival (DFS), overall survival (OS), and serious adverse events were considered as the efficacy and tolerability outcomes. Results: In all, 27 randomized controlled trials (RCTs) including 16,709 stage III–IV melanoma patients were enrolled in this NMA. For BRAF wild-type melanoma, our analysis showed that both nivolumab and pembrolizumab demonstrated significantly better DFS and tolerability than ipilimumab (10 mg/kg). Nivolumab, pembrolizumab, ipilimumab (3 mg/kg), and ipilimumab (10 mg/kg) all appeared to be effective in prolonging OS, but no therapy demonstrated significantly better OS than ipilimumab (10 mg/kg). Nivolumab + ipilimumab showed the best DFS, but did not appear to be effective in improving OS and ranked only seventh in tolerability. Vaccines and granulocyte-macrophage colony-stimulating factor therapies were well tolerated, but all failed to improve the DFS or OS in stage III melanoma patients. In terms of BRAF mutation-positive melanoma, ICIs (nivolumab + ipilimumab, nivolumab, pembrolizumab, ipilimumab; 10 mg/kg) exhibited comparable efficacy to dabrafenib + trametinib, and all these therapies showed significantly better DFS than placebo. Conclusion: Considering efficacy and tolerability, nivolumab and pembrolizumab seem to be preferable adjuvant therapies for patients with stage III–IV melanoma. For BRAF mutation-positive patients, more RCTs are still required to determine which is better between ICIs and targeted therapy.
Stretching, Bracing, and Devices for the Treatment of Osteoarthritis-Associated Joint Contractures in Nonoperated Joints: A Systematic Review and Meta-Analysis
Authors: Campbell T. Mark , Westby Marie , Ghogomu Elizabeth Tanjong , Fournier John , Ghaedi Bahareh Bahram , Welch Vivian 
Published: January 2023

Context: Many patients with osteoarthritis (OA) develop range of motion (ROM) restrictions in their affected joints (contractures), associated with worse outcomes and rising healthcare costs. Effective treatment guidance for lost ROM in OA-affected joints is lacking. Objective: A systematic review and meta-analysis evaluating the effectiveness of stretching and/or bracing protocols on native (nonoperated) joint ROM in the setting of radiographically diagnosed OA. Data Sources: Seven databases, English-language. Study Selection: Studies including participants with radiographically diagnosed OA in any native joint evaluating the effect of stretching or bracing on ROM. Study Design: Systematic review and meta-analysis. Level of Evidence: Level 2. Data Extraction: Two reviewers independently screened articles for inclusion and assessed risk of bias in included trials. Primary outcomes were ROM, pain, and adverse events (AEs). Results: We identified 6284 articles. A total of 9 randomized controlled trials, all evaluating the knee, met eligibility criteria. For stretching, 3 pooled studies reported total ROM, which improved by mean difference (MD) of 9.3° (95% CI 5.0°,13.5°) versus controls. Two pooled studies showed improved knee flexion ROM (MD 10.8° [7.3°,14.2°]) versus controls. Five studies were pooled for knee extension with mean improvement 9.1° [3.4°,14.8°] versus controls. Seven pooled studies showed reduced pain (standardized MD 1.9 [1.2,2.6]). One study reported improved knee extension of 3.7° [2.9°,4.5°] with use of a device. No studies used orthoses. One study reported on AEs, with none noted. Performance bias was present in all included studies, and only 3 studies clearly reported blinding of outcome assessors. Strength of evidence for primary outcomes was considered moderate. Conclusion: There was moderate-quality evidence that stretching is an effective strategy for improving knee total, flexion and extension ROM, and pain. Our findings suggest that stretching to regain joint ROM in OA is not futile and that stretching appears to be an appropriate conservative intervention to improve patient outcomes as part of a comprehensive knee OA treatment plan before arthroplasty.
Efficacy of Cryoablation on Chronic Rhinitis Management: A Systematic Review and Meta-Analysis
Authors: Young Kurtis , Bulosan Hannah , Kejriwal Sameer , Liang Jonathan , Wu Arthur W. , Tang Dennis M. , Birkeland Andrew C. , Steele Toby O. 
Published: January 2023

Background ClariFix for posterior nasal nerve ablation has been approved for use since 2017, and this is the first study attempting to synthesize and assess the efficacy of this new device on the management of chronic rhinitis. Objective The primary objective of this meta-analysis is to assess the efficacy of ClariFix in the symptomatic management of patients with chronic rhinitis. The main outcome measure is the mean difference in the reflective total nasal symptom score (rTNSS). Methods A systematic search of Pubmed/Medline, Web of Science, and EBSCOhost was conducted from inception to May 2022. Peer-reviewed clinical trials reporting postcryotherapy rTNSS at both 1- and 3-month intervals for patients with chronic rhinitis were included. A random-effects model was utilized for meta-analysis. Study heterogeneity, bias, and overall quality were all assessed. The authors followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The primary outcome measures included mean differences in rTNSS from baseline to both 1- and 3-month postoperative time points. Secondary measures included other questionnaires including the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Results There were 5 studies that met the criteria (247 individuals). The pooled rTNSS mean difference from baseline to 1 and 3 months postoperatively was found to be −3.48 points (95% CI: −3.73 to −3.23, I2 = 0.13). and −3.50 (95% CI: −3.71 to −3.29, I2 = 0.00), respectively. The mean difference from baseline to 3 months postoperatively regarding the RQLQ was found to be −1.53 (95% CI: −1.74 to −1.31, I2 = 0.00). The most common adverse effects included facial or surgical site pain (40.4%), followed by headache (18.2%), oral numbness (11.1%), and sinusitis (4.0%). Conclusions The findings of this systematic review suggest that cryoablation with Clarifix is an effective treatment modality for chronic rhinitis. However, higher-quality randomized controlled trials will need to be performed to affirm the findings of this study.
Eosinophilia attention, diagnosis, treatment, and awareness in physicians: a cross-sectional survey
Authors: Chen Bigui , Fu Yu , Wang Zhufeng , Rong Qiuping , Zhang Qingling , Xie Jiaxing , Kong Xuetao , Jiang Mei 
Published: January 2023

Background: Patients with incidental eosinophilia is becoming increasingly common in clinical practice. But it remains challenging to diagnose and treat owing to its complex etiology. The awareness of physicians and the strategies of diagnosis and treatment toward eosinophilia are still unclear. Objective: We aimed to evaluate attention, diagnosis, treatment, and awareness of eosinophilia among physicians, as well as factors influencing clinical practice, and to find ways to improve the efficacy of this disease. Design: This is a cross-sectional survey. Methods: A cross-sectional study was conducted from 1 to 4 June 2021 in a tertiary hospital. Self-administered and validated electronic questionnaire was used to investigate the attention toward eosinophilia, the strategies of diagnosis and treatment, and the awareness in physicians. Results: A total of 607 valid questionnaires were collected, with a response rate of 84.5%. Among the responders, 65.4% of physicians claimed to be familiar with patients with eosinophilia but only 11.0% of them had read the relevant guidelines or expert consensus. Among 207 physicians who had ever diagnosed patients with eosinophilia, only 19.4% had performed detailed examinations. The accuracy of awareness questions was 1.6–53.5%, and only 26.5% of physicians had high levels of awareness. An increase in the awareness level of up to 2.82 folds was seen among physicians with factors such as job title, encountering patients with eosinophilia, linking patients’ conditions to peripheral blood eosinophil count, and paying attention to guidelines. Conclusion: This study highlighted the importance of raising awareness and knowledge of eosinophilia among physicians in China. More works on education about eosinophilia guideline are needed, which may help physicians make decision with more benefits to patients.
Identifying urban form typologies in Seoul using a new Gaussian mixture model-based clustering framework
Authors: Li Na , Quan Steven Jige 
Published: January 2023

Seoul, the capital city of South Korea, has diverse urban forms developed through its complex history. Previous studies show limitations of strong subjectivity and difficulty in scalability in identifying typical Seoul urban forms with expert knowledge. Data-driven approach offers an opportunity to address those challenges, but previous studies often focused on direct applications of clustering algorithms to a given area with diverse methods and workflows, lacking a systematic framework. This study addressed these issues by developing a new form clustering framework to systematically identify form typologies at a large scale and demonstrated its application in Seoul. With a 500 m × 500 m grid as the basic spatial unit and twelve urban form attributes as learning features, 14 clusters were identified using the Gaussian mixture model. These clusters were further translated into form typologies following a semantic typology naming system, with representative form samples identified. The resulting typologies were then verified and validated through comparisons with previous studies. Their relationships with zoning classes were also examined, emphasizing their role in urban planning and design. Results suggest this new framework is an effective and promising way to identify urban form typologies in complex urban environments to better support urban planning and management.
LRP6/filamentous-actin signaling facilitates osteogenic commitment in mechanically induced periodontal ligament stem cells
Authors: Wang Jixiao , Yang Huiqi , Ma Xiaobei , Liu Jiani , Li Lan , Chen Lei , Wei Fulan 
Published: January 2023

AbstractBackgroundMechanotransduction mechanisms whereby periodontal ligament stem cells (PDLSCs) translate mechanical stress into biochemical signals and thereby trigger osteogenic programs necessary for alveolar bone remodeling are being deciphered. Low-density lipoprotein receptor-related protein 6 (LRP6), a Wnt transmembrane receptor, has been qualified as a key monitor for mechanical cues. However, the role of LRP6 in the mechanotransduction of mechanically induced PDLSCs remains obscure.MethodsThe Tension System and tooth movement model were established to determine the expression profile of LRP6. The loss-of-function assay was used to investigate the role of LRP6 on force-regulated osteogenic commitment in PDLSCs. The ability of osteogenic differentiation and proliferation was estimated by alkaline phosphatase (ALP) staining, ALP activity assay, western blotting, quantitative real-time PCR (qRT-PCR), and immunofluorescence. Crystalline violet staining was used to visualize cell morphological change. Western blotting, qRT-PCR, and phalloidin staining were adopted to affirm filamentous actin (F-actin) alteration. YAP nucleoplasmic localization was assessed by immunofluorescence and western blotting. YAP transcriptional response was evaluated by qRT-PCR. Cytochalasin D was used to determine the effects of F-actin on osteogenic commitment and YAP switch behavior in mechanically induced PDLSCs.ResultsLRP6 was robustly activated in mechanically induced PDLSCs and PDL tissues. LRP6 deficiency impeded force-dependent osteogenic differentiation and proliferation in PDLSCs. Intriguingly, LRP6 loss caused cell morphological aberration, F-actin dynamics disruption, YAP nucleoplasmic relocation, and subsequent YAP inactivation. Moreover, disrupted F-actin dynamics inhibited osteogenic differentiation, proliferation, YAP nuclear translocation, and YAP activation in mechanically induced PDLSCs.ConclusionsWe identified that LRP6 in PDLSCs acted as the mechanosensor regulating mechanical stress-inducible osteogenic commitment via the F-actin/YAP cascade. Targeting LRP6 for controlling alveolar bone remodeling may be a prospective therapy to attenuate relapse of orthodontic treatment.
Global transcriptome profiling reveals differential regulatory, metabolic and hormonal networks during somatic embryogenesis in Coffea arabica
Authors: Awada Rayan , Lepelley Maud , Breton David , Charpagne Aline , Campa Claudine , Berry Victoria , Georget Frédéric , Breitler Jean-Christophe , Léran Sophie , Djerrab Doâa , Martinez-Seidel Federico , Descombes Patrick , Crouzillat Dominique , Bertrand Benoît , Etienne Hervé 
Published: January 2023

Abstract
Background
Somatic embryogenesis (SE) is one of the most promising processes for large-scale dissemination of elite varieties. However, for many plant species, optimizing SE protocols still relies on a trial and error approach. We report the first global scale transcriptome profiling performed at all developmental stages of SE in coffee to unravel the mechanisms that regulate cell fate and totipotency.

Results
RNA-seq of 48 samples (12 developmental stages × 4 biological replicates) generated 90 million high quality reads per sample, approximately 74% of which were uniquely mapped to the Arabica genome. First, the statistical analysis of transcript data clearly grouped SE developmental stages into seven important phases (Leaf, Dedifferentiation, Primary callus, Embryogenic callus, Embryogenic cell clusters, Redifferentiation and Embryo) enabling the identification of six key developmental phase switches, which are strategic for the overall biological efficiency of embryo regeneration. Differential gene expression and functional analysis showed that genes encoding transcription factors, stress-related genes, metabolism-related genes and hormone signaling-related genes were significantly enriched. Second, the standard environmental drivers used to control SE, i.e. light, growth regulators and cell density, were clearly perceived at the molecular level at different developmental stages. Third, expression profiles of auxin-related genes, transcription factor-related genes and secondary metabolism-related genes were analyzed during SE. Gene co-expression networks were also inferred. Auxin-related genes were upregulated during dedifferentiation and redifferentiation while transcription factor-related genes were switched on from the embryogenic callus and onward. Secondary metabolism-related genes were switched off during dedifferentiation and switched back on at the onset of redifferentiation. Secondary metabolites and endogenous IAA content were tightly linked with their respective gene expression. Lastly, comparing Arabica embryogenic and non-embryogenic cell transcriptomes enabled the identification of biological processes involved in the acquisition of embryogenic capacity.

Conclusions
The present analysis showed that transcript fingerprints are discriminating signatures of cell fate and are under the direct influence of environmental drivers. A total of 23 molecular candidates were successfully identified overall the 12 developmental stages and can be tested in many plant species to optimize SE protocols in a rational way.
Comparison of State-of-the-Art Neural Network Survival Models with the Pooled Cohort Equations for Cardiovascular Disease Risk Prediction
Authors: Deng Yu , Liu Lei , Jiang Hongmei , Peng Yifan , Wei Yishu , Zhou Zhiyang , Zhong Yizhen , Zhao Yun , Yang Xiaoyun , Yu Jingzhi , Lu Zhiyong , Kho Abel , Ning Hongyan , Allen Norrina B. , Wilkins John T. , Liu Kiang , Lloyd-Jones Donald M. , Zhao Lihui 
Published: January 2023

Abstract
Background
The Pooled Cohort Equations (PCEs) are race- and sex-specific Cox proportional hazards (PH)-based models used for 10-year atherosclerotic cardiovascular disease (ASCVD) risk prediction with acceptable discrimination. In recent years, neural network models have gained increasing popularity with their success in image recognition and text classification. Various survival neural network models have been proposed by combining survival analysis and neural network architecture to take advantage of the strengths from both. However, the performance of these survival neural network models compared to each other and to PCEs in ASCVD prediction is unknown.

Methods
In this study, we used 6 cohorts from the Lifetime Risk Pooling Project (with 5 cohorts as training/internal validation and one cohort as external validation) and compared the performance of the PCEs in 10-year ASCVD risk prediction with an all two-way interactions Cox PH model (Cox PH-TWI) and three state-of-the-art neural network survival models including Nnet-survival, Deepsurv, and Cox-nnet. For all the models, we used the same 7 covariates as used in the PCEs. We fitted each of the aforementioned models in white females, white males, black females, and black males, respectively. We evaluated models’ internal and external discrimination power and calibration.

Results
The training/internal validation sample comprised 23216 individuals. The average age at baseline was 57.8 years old (SD = 9.6); 16% developed ASCVD during average follow-up of 10.50 (SD = 3.02) years. Based on 10 × 10 cross-validation, the method that had the highest C-statistics was Deepsurv (0.7371) for white males, Deepsurv and Cox PH-TWI (0.7972) for white females, PCE (0.6981) for black males, and Deepsurv (0.7886) for black females. In the external validation dataset, Deepsurv (0.7032), Cox-nnet (0.7282), PCE (0.6811), and Deepsurv (0.7316) had the highest C-statistics for white male, white female, black male, and black female population, respectively. Calibration plots showed that in 10 × 10 validation, all models had good calibration in all race and sex groups. In external validation, all models overestimated the risk for 10-year ASCVD.

Conclusions
We demonstrated the use of the state-of-the-art neural network survival models in ASCVD risk prediction. Neural network survival models had similar if not superior discrimination and calibration compared to PCEs.
The role of social circle COVID-19 illness and vaccination experiences in COVID-19 vaccination decisions: an online survey of the United States population
Authors: Skidmore Mark 
Published: January 2023

Abstract
Background
Around the world, policymakers have clearly communicated that COVID-19 vaccination programs need to be accepted by a large proportion of the population to allow life return to normal. However, according to the Center for Disease Control, about 31% of the United States population had not completed the primary vaccination series as of November 2022.

Aims
The primary aim of this work is to identify the factors associated by American citizens with the decision to be vaccinated against COVID-19. In addition, the proportion of fatal events from COVID-19 vaccinations was estimated and compared with the data in the VAERS database.

Methods
An online survey of COVID-19 health experiences was conducted. Information was collected regarding reasons for and against COVID-19 inoculations, experiences with COVID-19 illness and COVID-19 inoculations by survey respondents and their social circles. Logit regression analyses were carried out to identify factors influencing the likelihood of being vaccinated.

Results
A total of 2840 participants completed the survey between December 18 and 23, 2021. 51% (1383 of 2840) of the participants were female and the mean age was 47 (95% CI 46.36–47.64) years. Those who knew someone who experienced a health problem from COVID-19 were more likely to be vaccinated (OR: 1.309, 95% CI 1.094–1.566), while those who knew someone who experienced a health problem following vaccination were less likely to be vaccinated (OR: 0.567, 95% CI 0.461–0.698). 34% (959 of 2840) reported that they knew at least one person who had experienced a significant health problem due to the COVID-19 illness. Similarly, 22% (612 of 2840) of respondents indicated that they knew at least one person who had experienced a severe health problem following COVID-19 vaccination. With these survey data, the total number of fatalities due to COVID-19 inoculation may be as high as 278,000 (95% CI 217,330–332,608) when fatalities that may have occurred regardless of inoculation are removed.

Conclusion
Knowing someone who reported serious health issues either from COVID-19 or from COVID-19 vaccination are important factors for the decision to get vaccinated. The large difference in the possible number of fatalities due to COVID-19 vaccination that emerges from this survey and the available governmental data should be further investigated.
Adherence to recommended physical activity restrictions due to threatened preterm delivery – a descriptive multi-center study
Authors: Bendix Jane M. , Backhausen Mette G. , Hegaard Hanne K. , Rom Ane Lilleoere , Molsted Stig , Lokkegaard Ellen C. L. 
Published: January 2023

Abstract
Background
Threatened preterm delivery is a serious obstetrical complication and has for decades been prescribed physical activity restrictions (AR). Adherence to the recommended level of physical AR is however unknown. This study aimed to assess the objectively measured different physical positions and activities of pregnant women recommended AR due to threatened preterm delivery complications, compared to a reference group of uncomplicated pregnant women without restrictions, and to explore if admission status influenced adherence to AR.

Methods
A Danish descriptive, clinical multi-center study included singleton pregnancies between 22–33 gestational weeks admitted to an antenatal ward or during midwife consultations either prescribed AR due to threatened preterm delivery or uncomplicated controls without restrictions. For seven days participants wore two tri-axial accelerometric SENS® monitors. Accelerometric data included time spent in five different positions, activities, and step counts. At inclusion demographic and obstetric information was collected.

Results
Seventy-two pregnant women participated; 31% were prescribed strict AR, 15% moderate, 3% light, 8% unspecified, and 43% had no AR. Strict AR participants rested in the supine/lateral position for 17.7 median hours/day (range:9.6–24.0); sat upright 4.9 h/day (0.11–11.7); took 1,520steps/day (20–5,482), and 64% were inpatients. Moderate AR participants rested in the supine/lateral position for 15.1 h/day (11.5–21.6); sat upright 5.6 h/day (2.0–9.3); took 3,310steps/day (467–6,968), and 64% were outpatients. Participants with no AR rested 10.5 h/day (6.3–15.4) in supine/lateral position; sat upright 7.6 h/day (0.1–11.4) and took 9,235steps/day (3,225–20,818). Compared to no restrictions, participants with strict or moderate AR spent significant more time in physical resting positions and took significant fewer mean steps. Among strict AR admission status did not alter time spent in the physical positions, nor the step count.

Conclusions
Overall, participants adhered highly to the recommended AR. However, discriminating between strict and moderate AR recommendations did not alter how physical resting positions and activities were carried out. The admission status did not influence how participants adhered to strict AR.