bluuebunny/crossref_metadata_2025_split huggingface dataset:
The People’s War Against Pandemic: protocol for a randomized control trial based on a virtual interactive training system intervention to improve the emergency preparedness of public for major emerging infectious diseases
Authors: Luo Yue , Wei Wei , Li Mei , Ren Jianlan , Zheng Yu , Huang Yongli , Chen Yanhua 
Published: June 2023

Abstract
Background
The frequent occurrence and increasing severity of major emerging infectious diseases (MEIDs) have posed considerable public health, economic and social issues worldwide. The emergency preparedness of public is inadequate to respond to and recover from MEIDs. Due to the limitation of time, space and resources, it is also difficult to carry out large-scale emergency preparedness training related to MEIDs. Then we developed a virtual interactive training system to improve emergency preparedness of public, including preparation of legal compliance, emergency knowledge, emergency capacity, economic estimation, material reserve and physical and mental health.

Methods
A protocol for conducting a randomized controlled trail to evaluate the People’s War against Pandemic, a virtual interactive training system aimed to improve emergency preparedness of public for MEIDs. During the intervention, participants need to complete the storyline task at least once a day, watch at least one article and one video in the knowledge corner, and complete a retest of wrong choices in the intelligent evaluation module. The primary outcome is emergency preparedness of public for MEIDs. The secondary outcome is prevention and control knowledge of MEIDs.

Discussion
The People’s War Against Pandemic may be an effective approach to provide public with a panoramic understanding of the response to MEIDs, so as to promote their comprehensive preparation and finally achieve effective response.

Trial registration
This study was funded in 2021 and registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200060919) in June 2022. Recruitment and enrollment of participants began in July 2022.
Sensitivity to thyroid hormone indices are associated with papillary thyroid carcinoma in Chinese patients with thyroid nodules
Authors: Sun Jie , Liu Jie , Wu Ting-ting , Gu Zhi-yuan , Zhang Xiao-wen 
Published: June 2023

Abstract
Background
The association between thyroid hormone sensitivity and thyroid cancer is unknown, and we aimed to investigate the association between sensitivity to thyroid hormone indices and papillary thyroid carcinoma (PTC) in Chinese patients with thyroid nodules (TNs).

Methods
A total of 1,998 patients undergoing thyroid surgery due to TNs from Nanjing Drum Tower Hospital were included in this study. We evaluated central sensitivity to thyroid hormones, such as thyroid stimulating hormone index (TSHI), TSH T4 resistance index (TT4RI), thyroid feedback quantile-based index (TFQI), and parametric thyroid feedback quantile-based Index (PTFQI). Peripheral sensitivity to thyroid hormone was evaluated by FT3 to FT4 ratio. Multivariate logistic regression analysis was performed to evaluate the association between sensitivity to thyroid hormone indices and PTC risk.

Results
The results showed that central indices of thyroid hormone sensitivity, including TSHI, TT4RI, TFQI, and PTFQI, were positively associated with PTC risk. For each SD increase in TSHI, TT4RI, TFQI, and PTFQI, the odds ratios (OR, 95% CI) of PTC were 1.31 (1.18–1.46), 1.01 (1.01–1.02), 1.94 (1.45–2.60), and 1.82 (1.41–2.34), respectively. On the other hand, the association between peripheral sensitivity to thyroid hormone and PTC was significantly negative. For each SD increase in FT3/FT4 ratio, the OR (95% CI) of PTC was 0.18 (0.03–0.96), and a negative correlation was found between FT3/FT4 ratio and TNM staging of PTC.

Conclusions
Sensitivity to thyroid hormone indices could be used as new indicators for predicting PTC in Chinese patients with TNs. Future researches are still needed to confirm our findings.
Comparison of therapies of white spot lesions: a systematic review and network meta-analysis
Authors: Xie Zunxuan , Yu Lei , Li Sining , Li Jianing , Liu Yuyan 
Published: June 2023

AbstractObjectiveWhite spot lesions (WSLs), the earliest evidence of enamel demineralization, are considered amenable to intervention to achieve a remineralized or arrested state of caries. The management of WSLs is quite challenging, and there is no definitive cure as yet. We performed a network meta-analysis to assess the efficacy of seven therapies for WSLs and gave a hierarchy of them.Materials and methodsWe systematically searched the PubMed, EMBASE, Cochrane, and Web of Science databases (last search: July 2022) to identify all relevant studies. We limited our search to studies published in English. Randomized controlled designed in vitro/clinical trials related to the efficacy of the seven therapies for WSLs were included. Data extraction was performed independently by two reviewers. The risk of bias (ROB) 2.0 tool from Cochrane and a previous in vitro methodological tool will be used for the quality assessment. Variations in quantitative light-induced fluorescence (QLF), laser fluorescence (LF), and lesions area were the primary outcome measures. Standard mean difference (SMD) was used as the effect size for the Network meta-analysis (NMA). Consistency and inconsistency tests were conducted. The hierarchy of 7 treatment effects was evaluated using surface probabilities under cumulative ranking (SUCRA). Publication bias was evaluated using a bias plot.ResultsForty-two articles were included in the systematic review. Thirty-one of them, with a total of 1906 participants, were included in the network meta-analysis. The studies owned a low and moderate risk of bias. This analysis does not suffer from significant inconsistency. The difference between 4 groups ‘self-assembled peptide (SAP) P11-4’, ‘P11-4 + Fluoride Varnish (FV)’, ‘Resin Infiltration (RI)’, ‘casein phosphor peptides-amorphous calcium fluoride phosphate (CPP-ACFP)’ and the 'Control' group was found to be statistically significant. Compared to the ‘FV’ and ‘casein phosphor peptides-amorphous calcium phosphate (CPP-ACP)’ groups, the ‘P11-4 + FV” group and ‘RI” group made a significant difference. The hierarchy was evident in the SUCRA values of 7 therapies. P11-4 + FV and RI were considered effective therapies compared to the control group or the FV group (gold standard group).ConclusionsThe available evidence suggests that resin infiltration and P11-4 in combination with fluoride varnish had advantages over gold standard (FV). The effect of tricalcium phosphate-based drugs and fluoride is not very noticeable. Overall, drugs based on P11-4 and resin infiltration will be better therapies. Using more than two drugs in combination also would increase efficacy.
Suid alphaherpesvirus 1 of wild boar origin as a recent source of Aujeszky’s disease in carnivores in Germany
Authors: Freuling Conrad M. , Hlinak Andreas , Schulze Christoph , Sehl-Ewert Julia , Wysocki Patrick , Szentiks Claudia A. , Schmitt Klaus , Wohlsein Peter , Kluth Gesa , Reinhardt Ilka , Mettenleiter Thomas C. , Müller Thomas 
Published: June 2023

AbstractBackgroundThe high susceptibility of carnivores to Suid Alphaherpesvirus 1 [SuAHV1, synonymous pseudorabies virus (PrV)], renders them inadvertent sentinels for the possible occurrence of Aujeszky’s disease (AD) in domestic and wild swine populations. The aim of this study was to epidemiologically analyse the occurrence of PrV infections in domestic and wild animals in Germany during the last three decades and to genetically characterise the causative PrV isolates.MethodsPrV in dogs was detected using standard virological techniques including conventional and real time PCR, virus isolation or by immunohistochemistry. Available PrV isolates were characterized by partial sequencing of the open gC reading frame and the genetic traits were compared with those of archived PrV isolates from carnivores and domestic pigs from Germany before the elimination of AD in the domestic pig population.ResultsDuring 1995 and 2022, a total of 38 cases of AD in carnivores, e.g. dogs and red foxes, were laboratory confirmed. Sequencing and subsequent phylogenetic analysis of PrV isolates established a strong connection between AD cases in carnivores and the occurrence of PrV infections in European wild boars in the end phase of and after elimination of AD from the domestic pig population. While PrV infections occur at low numbers but regularly in hunting dogs, interestingly, PrV was not observed in grey wolves in Germany. In none of 682 dead-found grey wolves and wolf-dog hybrids tested from Germany during 2006–2022 could PrV infection be detected by molecular means.ConclusionsAlthough PrV has been eliminated from domestic pigs, spillover infections in domestic and wild carnivores should always be expected given the endemic presence of PrV in wild pig populations. Since detection of PrV DNA and virus in carnivores is sporadic even in areas with high seroprevalence of PrV in wild pigs, it may not reflect the full diversity of PrV.
Differentiating people who use cannabis heavily through latent class analysis
Authors: Alvarez-Roldan Arturo , García-Muñoz Teresa , Gamella Juan F. , Parra Iván , Duaso Maria J. 
Published: June 2023

AbstractBackgroundPeople who use cannabis daily or near-daily vary considerably in their daily dosage and use frequency, impacting both experienced effects and adverse consequences. This study identified heavy cannabis user groups according to consumption patterns and factors associated with class membership.MethodsWe conducted a cross-sectional study of 380 Spanish residents (61.8% male; average age = 30.3 years) who had used cannabis ≥ 3 days/week throughout the past year. Participants were recruited through chain referral and cannabis social clubs. We applied latent class analysis (LCA) to cluster participants according to use intensity. LCA indicators included frequency of weekly cannabis use, joints smoked each day, cannabis dosage, and if cannabis was consumed throughout the day or only at specific times. Associations between class membership and socio-demographics, use patterns, motives, supply sources, adverse outcomes, and use of other substances were measured using ANOVA and chi-squared tests. Multinomial regression identified the factors associated with latent class membership.ResultsThree latent classes (moderately heavy: 21.8%, heavy: 68.2%, very heavy: 10%) had average weekly cannabis intakes of 2.4, 5.5, and 18.3 g, respectively. Very heavy users were older ($${\chi }^{2}$$=17.77,p < 0.01), less educated$${(\chi }^{2}$$=36.80,p < 0.001), and had used cannabis for longer (F = 4.62,p = 0.01). CAST scores (F = 26.51,p < 0.001) increased across the classes. The prevalence of past-month alcohol use was lower among the heaviest users ($${\chi }^{2}$$=5.95,p = 0.05). Cannabis was usually obtained from a club by very heavy users ($${\chi }^{2}$$=20.95,p < 0.001).ConclusionsPeople who use cannabis heavily present three groups according to frequency and quantity of cannabis consumption. Use intensity is associated with increased cannabis-related problems. Differences among heavy users must be considered in harm reduction interventions in cannabis clubs and indicated prevention.
Expanding potential targets of herbal chemicals by node2vec based on herb–drug interactions
Authors: Zhang Dai-yan , Cui Wen-qing , Hou Ling , Yang Jing , Lyu Li-yang , Wang Ze-yu , Linghu Ke-Gang , He Wen-bin , Yu Hua , Hu Yuan-jia 
Published: June 2023

AbstractBackgroundThe identification of chemical–target interaction is key to pharmaceutical research and development, but the unclear materials basis and complex mechanisms of traditional medicine (TM) make it difficult, especially for low-content chemicals which are hard to test in experiments. In this research, we aim to apply the node2vec algorithm in the context of drug-herb interactions for expanding potential targets and taking advantage of molecular docking and experiments for verification.MethodsRegarding the widely reported risks between cardiovascular drugs and herbs,Salvia miltiorrhiza(Danshen, DS) andLigusticum chuanxiong(Chuanxiong, CX), which are widely used in the treatment of cardiovascular disease (CVD), and approved drugs for CVD form the new dataset as an example. Three data groups DS-drug, CX-drug, and DS-CX-drug were applied to serve as the context of drug-herb interactions for link prediction. Three types of datasets were set under three groups, containing information from chemical-target connection (CTC), chemical-chemical connection (CCC) and protein–protein interaction (PPI) in increasing steps. Five algorithms, including node2vec, were applied as comparisons. Molecular docking and pharmacological experiments were used for verification.ResultsNode2vec represented the best performance with average AUROC and AP values of 0.91 on the datasets “CTC, CCC, PPI”. Targets of 32 herbal chemicals were identified within 43 predicted edges of herbal chemicals and drug targets. Among them, 11 potential chemical-drug target interactions showed better binding affinity by molecular docking. Further pharmacological experiments indicated caffeic acid increased the thermal stability of the protein GGT1 and ligustilide and low-content chemical neocryptotanshinone induced mRNA change of FGF2 and MTNR1A, respectively.ConclusionsThe analytical framework and methods established in the study provide an important reference for researchers in discovering herb–drug interactions, alerting clinical risks, and understanding complex mechanisms of TM.
Clinical and genetic spectrum of GSD type 6 in Korea
Authors: Hahn Jong Woo , Lee Heerah , Seong Moon Woo , Kang Gyeong Hoon , Moon Jin Soo , Ko Jae Sung 
Published: June 2023

Abstract
Background
Glycogen storage disease type VI (GSD VI) is a rare disease in which liver glycogen metabolism is impaired by mutations in the glycogen phosphorylase L (PYGL). This study aimed to examine the clinical features, genetic analyses, and long-term outcomes of patients with GSD VI in Korea.

Methods
From January 2002 to November 2022, we retrospectively reviewed patients diagnosed with GSD VI using a gene panel at Seoul National University Hospital. We investigated the clinical profile, liver histology, molecular diagnosis, and long-term outcomes of patients with GSD VI.

Results
Five patients were included in the study. The age at onset was 18–30 months (median, 21 months), and current age was 3.7–17 years (median, 11 years). All patients showed hepatomegaly, elevated liver transaminase activity, and hypertriglyceridaemia. Hypercholesterolaemia and fasting hypoglycaemia occurred in 60% and 40% of patients, respectively. Ten variants of PYGL were identified, of which six were novel: five missense (p.[Gly607Val], p.[Leu445Pro], p.[Gly695Glu], p.[Val828Gly], p.[Tyr158His]), and one frameshift (p.[Arg67AlafsTer34]). All patients were treated with a high-protein diet, and four also received corn starch. All patients showed improved liver function tests, hypertriglyceridaemia, hepatomegaly, and height z score.

Conclusions
The GSD gene panel is a useful diagnostic tool for confirming the presence of GSD VI. Genetic heterogeneity was observed in all patients with GSD VI. Increased liver enzyme levels, hypertriglyceridaemia, and height z score in patients with GSD VI improved during long-term follow-up.
Ultrasound findings in Kaposi sarcoma patients: overlapping sonographic features with disseminated tuberculosis
Authors: Huson Michaela Aurelia Maria , Kumwenda Tapiwa , Gumulira Joe , Rambiki Ethel , Wallrauch Claudia , Heller Tom 
Published: June 2023

Abstract
Background
Focused Assessment with Sonography for HIV-associated TB (FASH) is a diagnostic tool for extra-pulmonary tuberculosis (TB) in symptomatic patients with advanced HIV. As Kaposi’s sarcoma (KS) is also prevalent in this patient population, changes due to KS may mimic TB findings and clinical interpretation of target FASH findings can be challenging. We aimed to describe sonographic findings in patients with KS.

Methods
We performed a prospective observational study at Lighthouse clinic at Kamuzu Central Hospital, Lilongwe, Malawi, in consecutive patients with newly diagnosed KS, without known diagnosis of TB, referred for paclitaxel treatment. All patients underwent FASH and abdominal ultrasound to assess for effusions and changes in liver and spleen, as well as systematic sonographic assessment for lymphadenopathy.

Results
We included 30 patients. We found inguinal lymph nodes using ultrasound in 20 patients; in 3 (10%) additionally abdominal lymph nodes were found. Pathological effusions were seen in eight patients (27%): pericardial effusion in one (3%), pleural effusion in six (20%) and ascites in four (13%) patients. We found focal spleen lesions in three (10%) patients. Most of these lesions were echogenic, but in one patient, we saw hypoechoic lesions with an echogenic center. In three (10%) patients an unusual “sponge-like pattern” of the splenic vasculature was found. Six (20%) patients had echogenic focal lesions in the liver resembling hemangiomas, individual lesions showing a hypoechoic center. In two patients echogenic portal fields were seen.

Conclusions
The majority of patients with newly diagnosed KS demonstrate sonographic features of disease, predominantly lymphadenopathy. Effusions were observed in a significant minority, as well as focal lesions in liver or spleen, which commonly resemble hemangiomas, but hypoechoic lesions were also observed and can easily be mistaken for extra-pulmonary TB. A 'sponge-like pattern' of the spleen should not be confused with micro-abscesses. In conclusion, this case series illustrates the diverse nature of ultrasound features in patients with KS, which can be difficult to distinguish from other opportunistic diseases, including TB.
Sexual dimorphism in mitochondrial dysfunction and diabetes mellitus: evidence from a population-based cohort study
Authors: Wang Shanjie , Guo JunChen , Liu Xiaoxuan , Tian Wei , Zhang Yiying , Wang Ye , Liu Yige , E. Mingyan , Fang Shaohong 
Published: June 2023

Abstract
Background
Pathophysiological mechanisms underlying sex-based differences in diabetes remain poorly understood. Mitochondrial metabolite methylmalonic acid (MMA) accumulation reflects mitochondrial dysfunction which is involved in sex-specific pathophysiological responses biologically. We aimed to investigate the sex-specific associations between mortality risk and MMA in adults with the presence or absence of type 2 diabetes.

Methods
This cohort study included 24,164 adults (12,123 females and 12,041 males) from the NHANES study during 1999–2014. Both sexes were separately categorized as those with no diabetes, prediabetes, undiagnosed diabetes, and diagnosed diabetes. Circulating MMA level was measured at baseline by mass-spectrometric detection. Mortality status was ascertained from baseline until December 31, 2015.

Results
During a median follow-up of 11.1 years, 3375 deaths were documented. Males had a particularly higher mortality than females in adults with diagnosed diabetes compared to differences in those with no diabetes, prediabetes and undiagnosed diabetes (sex differences in mortality rate per 1000 person-years across diabetic status: 0.62, 1.44, 5.78, and 9.77, p < 0.001). Notably, the sex-specific difference in associations between MMA and mortality was significant only in adults with diagnosed diabetes (p for interaction = 0.028), not in adults with no diabetes and prediabetes. Adjusted HRs (95%CIs) per doubling of MMA for all-cause mortality were 1.19 (1.04–1.37) in females with diagnosed diabetes versus 1.58 (1.36–1.86) in male counterparts. In addition, MMA levels had an insignificant or weak correlation with sex hormone profiles at baseline, regardless of diabetes status and sex.

Conclusions
Sex difference in mortality risk was especially significant in diagnosed type 2 diabetes. Increasing equivalent exposure to mitochondrial metabolite MMA was associated with a greater excess risk of future mortality in males with diabetes than in females.
Evaluation of recurrence risk for patients with stage I invasive lung adenocarcinoma manifesting as solid nodules based on 18F-FDG PET/CT, imaging signs, and clinicopathological features
Authors: Zheng Xuan , Lin Jie , Xie Jiageng , Jiang Jia , Lan Junping , Ji Xiaowei , Tang Kun , Zheng Xiangwu , Liu Jinjin 
Published: June 2023

Abstract
Background
Stage I lung adenocarcinoma is a heterogeneous group. Previous studies have shown the prognostic evaluation value of PET/CT in this cohort; however, few studies focused on stage I invasive adenocarcinoma manifesting as solid nodules. This study aimed to evaluate the recurrence risk for patients with stage I invasive lung adenocarcinoma manifesting as solid nodules based on 18F-FDG PET/CT, CT imaging signs, and clinicopathological parameters.

Methods
We retrospectively enrolled 230 patients who underwent 18F-FDG PET/CT examination between January 2013 and July 2019. Metabolic parameters: maximum standard uptake value (SUVmax), mean standard uptake value, tumor metabolic volume (MTV), and total tumor glucose digestion were collected. Kaplan–Meier method was used to evaluate recurrence-free survival (RFS), and the multivariate Cox proportional hazards model was used to determine the independent risk factors associated with RFS. The time-dependent receiver operating characteristic curve (ROC) method was used to calculate the optimal cutoff value of metabolic parameters.

Results
The 5-year RFS rate for all patients was 71.7%. Multivariate Cox analysis revealed that the International Association for the Study of Lung Cancer Pathology Committee (IASLC) pathologic grade 3 [Hazard ratio (HR), 3.96; 95% Confidence interval (CI), 1.11–14.09], the presence of cavity sign (HR 5.38; 95% CI 2.23–12.96), SUVmax (HR 1.23; 95% CI 1.13–1.33), and MTV (HR 1.05; 95% CI 1.01–1.08) were potential independent prognostic factors for RFS. Patients with IASLC grade 3, the presence of cavity sign, SUVmax > 3.9, or MTV > 5.4 cm3 were classified as high risk, while others were classified as low risk. There was a significant difference in RFS between the high-risk and low-risk groups (HR 6.04; 95% CI 2.17–16.82, P < 0.001), and the 5-year RFS rate was 94.1% for the low-risk group and 61.3% for the high-risk group.

Conclusions
We successfully evaluate the recurrence risk of patients with stage I invasive adenocarcinoma manifesting as solid nodules for the first time. The 5-year RFS rate in the high-risk group was significantly lower than in the low-risk group (61.3% vs. 94.1%). Our study may aid in optimizing therapeutic strategies and improving survival benefits for those patients.