bluuebunny/crossref_metadata_2025_split huggingface dataset:
Possible association between oral health and sleep duration
Authors: Han Sungjun , Jee Donghyun , Kang Yun-Jin , Park Yong-Jin , Cho Jung-Hae 
Published: December 2021

Abstract
This study was performed to investigate the association between oral health and sleep duration in South Korean subjects using 2010–2015 data from the Korean National Health and Nutrition Examination Survey (KNHANES).
Cross-sectional data on 35,599 adults over the age of 19 years who completed KNHANES were analyzed. All participants reported subjective oral health status and their daily average sleep duration using a self-reported questionnaire. Sleep duration and oral health status were divided into 3 categories: ≤5, 6–8, ≥9 h/day and good, fair, poor, respectively.
The overall prevalence of poor oral health status was 43.8%. Univariate analysis demonstrated that poor oral health status was significantly associated with age, smoking, alcohol, diabetes, education, income, depression, marital status, and sleep duration. After adjusting for covariates (age, sex, diabetes mellitus, hypertension, obesity, smoking, income, education, marital status), sleep durations of ≤5 hours (OR = 1.42; 95% CI, 1.26–1.60) and ≥9 hours (OR = 1.21; 95% CI, 1.04–1.40) were significantly associated with poor oral health, compared to a sleep duration of 6–8 hours. Short or long sleep duration was more likely to have an impact on the development of poor oral health status in men than in women. A significant relationship between sleep duration and oral health status was found in participants younger than 60 years.
This is the first report that both short and long sleep durations are significantly associated with the development of poor oral health status. The effect of short or long sleep duration on poor oral health was more significant in younger subjects and in men.
GPR116 overexpression correlates with poor prognosis in gastric cancer
Authors: Zheng Tian , Sun Mingyao , Liu Lanzai , Lan Yanfen , Wang Lihua , Lin Fan 
Published: December 2021

Abstract
The G protein-coupled receptor 116 (GPR116) is an adhesion subtype of the G protein-coupled receptor family and has been reported to be involved in tumorigenesis and cancer progression. Moreover, it has been shown to predict poor prognosis in breast and colorectal cancers. However, little is known about the role of GPR116 in gastric cancer (GC). In this study, we aimed to investigate the expression and clinical prognostic significance of GPR116 in GC.The mRNA expression levels of GPR116 in GC were analyzed using Gene Expression Omnibus and UALCAN databases, and GPR116 protein expression in GC tissues was detected using immunohistochemistry. The relationship between GPR116 expression and prognosis in patients with GC was analyzed and further validated using the Kaplan–Meier Plotter database. The correlation between GPR116 and the differentially expressed genes identified was analyzed using the LinkedOmics database. Gene set enrichment analysis was performed using WebGestalt. The results revealed that GPR116 expression was significantly upregulated in GC tissues, which was positively correlated with tumor node metastasis (TNM) staging and tumor invasion. Prognostic analysis suggested that high GPR116 expression contributed to poor overall survival in GC patients. Multivariate Cox analysis indicated that GPR116 overexpression was an independent prognostic indicator in patients with GC (HR = 1.855, 95% CI 1.021–3.370, P = .043). Enrichment analysis showed that GPR116 co-expression genes were mainly involved in extracellular matrix-receptor interaction, focal adhesion, cell adhesion, PI3K-Akt signaling, DNA replication, and cell cycle pathways. In conclusion, GPR116 was highly expressed in GC tissues and associated with poor prognosis in patients with GC, Thus GPR116 may be a novel prognostic marker and a potential therapeutic target for GC treatment.
Increased risk of bladder cancer in young adult men with hyperlipidemia
Authors: Shih Hung-Jen , Lin Ke-Hsun , Wen Yu-Ching , Fan Yen-Chun , Tsai Pei-Shan , Huang Chun-Jen 
Published: December 2021

Abstract
A high-cholesterol diet increases the risk of bladder cancer. The purpose of this nationwide longitudinal population-based retrospective cohort study is to investigate whether hyperlipidemia is a risk factor for bladder cancer.
Data from Taiwan National Health Insurance Database were analyzed. The primary study end point was the occurrence of newly diagnosed bladder cancer. The relative risk of bladder cancer in a hyperlipidemia cohort was compared with that in an age- and gender-matched non-hyperlipidemia cohort by using the Cox proportional hazards regression model. Cox regression analyses were further adjusted by the propensity score.
Our data revealed that the hyperlipidemia cohort (n = 33,555) had a significantly higher subsequent risk of bladder cancer than did the non-hyperlipidemia cohort (n = 33,555) (adjusted hazard ratio [HR] = 1.37, P = .005) after propensity score adjustment. Subgroup analyses revealed that men in the hyperlipidemia cohort had a significantly higher subsequent risk of bladder cancer than did those in the non-hyperlipidemia cohort (adjusted HR = 1.36, P = .040). However, the risk of bladder cancer was not significantly different between women in the hyperlipidemia cohort and those in the non-hyperlipidemia cohort. Subgroup analyses further revealed that the risk of bladder cancer was significantly higher in men aged 20 to 39 years in the hyperlipidemia cohort than in those in the non-hyperlipidemia cohort (adjusted HR = 5.45, P = .029).
In conclusion, hyperlipidemia is a risk factor for bladder cancer in young adult men.
French experience with telemedicine in inflammatory bowel disease: a patients and physicians survey
Authors: Guillo Lucas , Bonnaud Guillaume , Nahon Stéphane , Caron Bénédicte , Olympie Alain , Laurain Anne , Serrero Mélanie , Buisson Anne , Peyrin-Biroulet Laurent 
Published: December 2021

Background and aims
The use of telemedicine dramatically increased during the COVID-19 pandemic. We collected patients and physicians experience on telemedicine in the field of inflammatory bowel disease (IBD).

Methods
We conducted a nationwide survey between September 2020 and January 2021. A self-administered questionnaire was sent to participants through mailing lists of the national patients’ association and IBD expert groups.

Results
Overall, 300 patients and 110 gastroenterologists filled out the survey. On a 10 points scale of satisfaction with telemedicine, 60% of patients noted a score ≥8 and 52.7% of physicians ≥7. Patients and gastroenterologists felt that the duration of teleconsultations appeared to be shorter than in-person visits in 57.5 and 55.1% of cases, respectively. All participants agreed that telemedicine is appropriate in dedicated situations and not for flare-up consultations. For 55.1% of patients, quality of care was the same via telemedicine, whereas 51.4% of gastroenterologists believed they managed less well their patients. Lack of clinical examination being pointed out as the main limitation of telemedicine. Three-quarters of patients and gastroenterologists would agree to use telemedicine more often in the future.

Conclusion
Patients and gastroenterologists were satisfied with telemedicine and would be willing to use it in the future. However, telemedicine does not replace in-person visits and should be discussed on a case-by-case basis.
Risk of Hypersensitivity Reactions to Iopromide in Children and Elderly
Authors: Endrikat Jan , Chernova Julia , Gerlinger Christoph , Pracz Marcin , Lengsfeld Philipp , Bhatti Aasia , Michel Alexander 
Published: December 2021

Purpose
The aim of this study was to analyze the risk of hypersensitivity reactions (HSRs) to iopromide in children and elderly patients in comparison to adults.

Materials and Methods
Four observational studies were pooled and analyzed (analysis I). In addition, spontaneous reports from 1985 to 2020 from the pharmacovigilance database were evaluated (analysis II). All patients received iopromide for angiographic procedures or contrast-enhanced computed tomography in various indications. In analysis I, a nested case-control analysis, including a multivariable logistic regression model, based on pooled observational study data, was performed. Cases were defined as patients with a typical and unequivocal HSR; controls were patients without any recorded reaction. In analysis II, all spontaneous reports on HSRs after iopromide administration recorded in the pharmacovigilance database were descriptively analyzed. Exposure estimates on the size of the exposed age groups were derived from sales data and data from market research. The primary target variable was the risk of HSR to iopromide in children (<18 years) and elderly patients (≥65 years) compared with adults (≥18 to <65 years).

Results
In analysis I, a total of 132,850 patients were included (2978 children, 43,209 elderly, and 86,663 adults). Hypersensitivity reactions were significantly less frequent in children (0.47%) and elderly (0.38%) compared with adults (0.74%). The adjusted odds ratio (vs adults) for children was 0.58 (95% confidence interval, 0.34–0.98; P < 0.043), and that for the elderly was 0.51 (95% confidence interval, 0.43–0.61; P < 0.001), indicating a lower risk for both subpopulations as compared with adults. In analysis II, of the overall >288 million iopromide administrations, 5.87, 114.18, and 167.97 million administrations were administered to children, elderly, and adults, respectively. The reporting rate for HSRs in children (0.0114%) and elderly (0.0071%) was significantly lower as compared with adults (0.0143%) (P < 0.0001).

Conclusions
Hypersensitivity reactions to iopromide were significantly less frequent in children and elderly compared with adults.
Development of a Prognostic Model for Predicting Multiple Sclerosis After Optic Neuritis: A Secondary Analysis of Data From the Optic Neuritis Treatment Trial
Authors: Luo Wenjing , Deng Xinlei , Xu Xiaoyu , Song Ruitong , Luo Meifeng , Moss Heather E. , Du Yi 
Published: December 2021

Background:
Optic neuritis can be the initial manifestation of multiple sclerosis (MS). The purpose of this study was to develop a prognostic model for predicting the risk of MS development among patients with optic neuritis.

Methods:
The data from 388 patients with optic neuritis were retrieved from the Optic Neuritis Treatment Trial (ONTT). Cox proportional hazards regression analysis was used to develop a prognostic model. The performance of the model was assessed by using Harrell's C-index and calibration curves. The rates of MS development were estimated using the Kaplan–Meier method.

Results:
Among the enrolled subjects, a total of 154 (39.7%) patients developed clinically definite MS during a median follow-up period of 15.8 years (interquartile range, 7.2–16.9 years). The factors associated with the development of MS were the presence of brain lesions as on baseline MRI, previous nonspecific neurologic symptoms, commencing low-dose corticosteroids treatment, ocular pain, and absence of optic disc/peripapillary hemorrhage. After incorporating these 5 factors into the prognostic model, a C-index of 0.72 (95% confidence interval [CI], 0.69–0.76) and good calibration curves were obtained. The C-index of the model was significantly higher than the C-indexes of any single factor (P < 0.001 in all cases). The model was able to stratify the ONTT patient cohort into 3 risk groups with significantly different intergroup rates of developing MS (rates for developing MS within a 15-year period: high-risk group, 75.7% [95% CI, 65.6%–82.9%], intermediate-risk group, 44.7% [95% CI, 31.4%–55.4%]; and low-risk group, 20.8% [95% CI, 14.2%–26.8%]; log-rank P < 0.001).

Conclusions:
This prognostic model had a better prediction ability when compared with the standard practice that relies solely on using brain lesions on MRI. It can, therefore, help guide decision-making to initiate earlier disease-modifying therapy for patients with optic neuritis at risk of developing MS.
Third COVID-19 Vaccine Dose Boosts Neutralising Antibodies in Poor Responders
Authors: Lake Douglas F. , Roeder Alexa J. , Gonzalez-Moa Maria J. , Koehler Megan , Kaleta Erin , Jasbi Paniz , Vanderhoof John , McKechnie Davis , Forman Jack , Edwards Baylee , Seit-Nebi Alim , Svarovsky Sergei 
Published: December 2021

ABSTRACTObjectiveTo determine if poor responders to COVID-19 RNA vaccines (<50% neutralisation) after two doses would remain poor responders, or if a third dose could elicit high levels of NAbs.DesignClinical follow-up studySettingAcademic and medical institutions in USAParticipants269 healthy individuals ranging in age from 19 to 80 (Average age = 51; 165 females and 104 males) who received either BNT162b2 (Pfizer) or mRNA1273 (Moderna) vaccines.Main Outcome MeasuresNAb levels were measured: i) 2-4 weeks after a second vaccine dose, ii) 2-4 months after the second dose, iii) within 1-2 weeks prior to a third dose and iv) 2-4 weeks after a third RNA vaccine dose.ResultsIn 269 study participants, percent neutralisation ranged from 0% to 99% 2-4 weeks after a second vaccine dose. The majority of vaccine recipients (154/269, 57%) demonstrated NAb levels at ≥75% 2-4 weeks after their second dose. Our study also revealed that 25% of vaccine recipients did not neutralise above 50% (Median neutralisation = 21%, titers <1:80) within a month after their second dose. We called these individuals “vaccine poor responders” (VPRs). Twenty-three VPRs ranging in age from 31 to 79 (10 males, 13 females, average age = 62.5) independently obtained a third dose of either BNT162b2 or mRNA-1273 vaccine 1-8 months (average = 5 months) after their second dose. Within a month after their third dose, poor responders showed an average 20-fold increase in NAb levels (range 46%-99%).ConclusionsThe results suggest that poor responders are not permanently poor responders; they can generate high NAb levels with an additional vaccine dose–independent of mRNA vaccine manufacturer. Previous reports indicate that NAb levels decline much more rapidly than clinical protection from hospitalisation and disease, but that does not account for vaccine recipients who never generated high levels of NAbs after two doses. It is possible that poor responders are a source of breakthrough infections. Although it is not known what levels of NAbs protect from infection or disease, many vaccine recipients in high-risk professions may wish to keep peripheral NAb levels high, limiting infection, asymptomatic viral replication, and potential transmission.
A robust and adaptive framework for interaction testing in quantitative traits between multiple genetic loci and exposure variables
Authors: Hecker Julian , Prokopenko Dmitry , Moll Matthew , Lee Sanghun , Kim Wonji , Qiao Dandi , Voorhies Kirsten , Kim Woori , Vansteelandt Stijn , Hobbs Brian D. , Cho Michael H. , Silverman Edwin K. , Lutz Sharon M. , DeMeo Dawn L. , Weiss Scott T. , Lange Christoph 
Published: December 2021

AbstractThe identification and understanding of gene-environment interactions can provide insights into the pathways and mechanisms underlying complex diseases. However, testing for gene-environment interaction remains a challenge since statistical power is often limited, the specification of environmental effects is nontrivial, and such misspecifications can lead to false positive findings. To address the lack of statistical power, recent methods aim to identify interactions on an aggregated level using, for example, polygenic risk scores. While this strategy increases power to detect interactions, identifying contributing key genes and pathways is difficult based on these global results.Here, we propose RITSS (Robust Interaction Testing using Sample Splitting), a gene-environment interaction testing framework for quantitative traits that is based on sample splitting and robust test statistics. RITSS can incorporate multiple genetic variants and/or multiple environmental factors. Using sample splitting, a screening step enables the selection and combination of potential interactions into scores with improved interpretability, based on the user’s unrestricted choices for statistical/machine learning approaches. In the testing step, the application of robust test statistics minimizes the susceptibility of the results to main effect misspecifications.Using extensive simulation studies, we demonstrate that RITSS controls the type 1 error rate in a wide range of scenarios. In an application to lung function phenotypes and human height in the UK Biobank, RITSS identified genome-wide significant interactions with subcomponents of genetic risk scores. While the contributing single variant interactions are moderate, our analysis results indicate interesting interaction patterns that result in strong aggregated signals that provide further insights into gene-environment interaction mechanisms.
MAL suppresses OSCC tumorigenesis by maintaining epithelial cell differentiation
Authors: Zhu Xueqin , Liu Zheqi , Qi Shengcai , Zou Xin , Lu Tingwei , Ke Xing , Qin Xing , Wang Xiaoning , Yan Ming , Xu Qin , Zhang Jianjun , Wang Xu , Zhang Zhen , Cao Wei , Wu Xiangbing , Chen Wantao 
Published: December 2021

AbstractOral squamous cell carcinoma (OSCC) is widely recognized as an optimal model for precise medicine guided molecular biomarkers of cancer, however, few clinical practices were applied till now. Based on the data from our own studies and published papers, it was found that the expression of MAL was significantly decreased in epithelial cancer as compared with normal tissues, and exhibited a opposite association with pathological grade. To study the molecular events related to deficiency of MAL during carcinogenesis, occurrence and development, a Mal knockout mouse model was constructed and consistently reproduced and bred. The Mal knockout mice are highly vulnerable to tumor induction by carcinogen of 4NQO, evidenced by their extremely earlier carcinogenesis, higher incidence, and more aggressive growth. Analysis of scRNA-seq data indicated that Mal knockout mice lost the ability in maintaining epithelial cell differentiation and get more prone to carcinogen with a remarkably higher incidence of epithelial malignancy. Further analyses identified putative co-functional genes of MAL, including DSG1, AQP3 and S100A8, which are key factors in maintaining epithelial cell differentiation. To conclude, the current study exhibits the clinical significance and explains the tumor suppressing function of MAL. The results also suggest the potential of MAL and its co-functional genes being biomarkers for designing the prevention and/or differentiation therapy strategies in OSCC.SignificanceMAL is found to be strongly opposite with tumor pathological grade from clinical and in vivo studies in OSCC. We propose MAL and its co-functional genes, including DSG1, AQP3 and S100A8, as key factors in maintaining epithelial cell differentiation and are valuable targets for designing prevention and differentiation therapy strategies in OSCC.
Non-zero Mean Alpha Oscillations are Evident in Computational Model and Empirical Data
Authors: Studenova Alina A. , Villringer Arno , Nikulin Vadim V. 
Published: December 2021

AbstractOscillations and evoked responses are two main types of neuronal activity recorded non-invasively with EEG/MEG. Although typically studied separately, they might in fact represent the same neuronal process. One possibility to unite them is to demonstrate that neuronal oscillations have non-zero mean which would indicate that stimulus- or task-triggered amplitude modulation of oscillations will unavoidably lead to the generation of evoked responses. We validated this mechanism using computational modelling and analysis of a large EEG data set. With a biophysical model, we indeed demonstrated that the mean of alpha oscillations is non-zero for a wide range of model parameters. In EEG data we detected non-zero mean alpha oscillations in about 96% of the participants. Furthermore, using complementary neuronal-ensemble modelling, we provided an explanation for the previously observed discrepancies between evoked responses and oscillatory amplitude changes after stimulus presentation. Overall, our results provide strong support for the unification of neuronal oscillations and evoked responses.
Sex-specific Stress and Behavioural Responses to Human Experimenters in Rats
Authors: Faraji Jamshid , Ambeskovic Mirela , Sauter Nevyn , Toly Jaxson , Whitten Kera , Lopes Nayara Antunes , Olson David M. , Metz Gerlinde A. S. 
Published: December 2021

AbstractThe sex of the experimenter may cause stress in animal models and be a major confounding factor in preclinical research. We studied the effects of the sex of the experimenter on female and male rat anxiety behaviours using thigmotaxis in the open field test, anxiety-induced changes in brain and back temperature using infra-red thermography, and alterations in plasma concentrations of stress hormones, corticosterone and oxytocin. Female rats displayed consistently exacerbated anxiety-related behaviours along with increased infrared cutaneous temperature during repeated exposure to male experimenters. Experimental stress further intensified thermal responses to a male experimenter, especially in female rats. These behavioural responses to a male experimenter in females were associated with higher circulating corticosterone and lower oxytocin levels. Similar responses were induced by a T-shirt worn by a human male. These findings suggest that emotional and physiological responses of female rats to a male experimenter are influenced by visual and olfactory cues. These results emphasize the need to standardize and report experimenter sex throughout a study to avoid ambiguity in interpretation of the results.
Age-related differences in the neural network interactions underlying the predictability gain
Authors: Rysop Anna Uta , Schmitt Lea-Maria , Obleser Jonas , Hartwigsen Gesa 
Published: December 2021

AbstractSpeech comprehension is often challenged by increased background noise, but can be facilitated via the semantic context of a sentence. This predictability gain relies on an interplay of language-specific semantic and domain-general brain regions. However, age-related differences in the interactions within and between semantic and domain-general networks remain poorly understood. Using functional neuroimaging, we investigated commonalities and differences in network interactions enabling processing of degraded speech in healthy young and old participants. Participants performed a sentence repetition task while listening to sentences with high and low predictable endings and varying intelligibility. Stimulus intelligibility was adjusted to individual hearing abilities. Older adults showed an undiminished behavioural predictability gain. Likewise, both groups recruited a similar set of semantic and cingulo-opercular brain regions. However, we observed age-related differences in effective connectivity for high predictable speech of increasing intelligibility. Young adults exhibited stronger connectivity between regions of the cingulo-opercular network and between left insula and the posterior middle temporal gyrus. Moreover, these interactions were excitatory in young adults but inhibitory in old adults. Finally, the degree of the inhibitory influence between cingulo-opercular regions was predictive of the behavioural sensitivity towards changes in intelligibility for high predictable sentences in older adults only. Our results demonstrate that the predictability gain is relatively preserved in older adults when stimulus intelligibility is individually adjusted. While young and old participants recruit similar brain regions, differences manifest in underlying network interactions. Together, these results suggest that ageing affects the network configuration rather than regional activity during successful speech comprehension under challenging listening conditions.