bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial epidemiologic analysis of the liver cancer and gallbladder cancer incidence and its determinants in South Korea
Authors: Jang Jieun , Yoo Dae-Sung , Chun Byung Chul 
Published: November 2021

Abstract
Background
There have been reports on regional variation in prevalence of hepatitis B and C, and Clonorchis sinensis (C. sinensis) infection, which indicates potential of spatial variation in liver cancer and gallbladder cancer incidence in Korea. Therefore, we aimed to assess the regional variation of liver and gallbladder cancer incidence and its determinants based on the regional distribution of risk factors, including hepatitis B infection in Korea.

Methods
This study used an ecological study design and district-level cancer incidence statistics generated by the National Cancer Center. Spatial clusters of liver and gallbladder cancer incidence were detected based on spatial scan statistics using SaTScan™ software. We set the size of maximum spatial scanning window of 25 and 35% of the population at risk for analyses of liver and gallbladder cancer, respectively. Significance level of 0.05 was used to reject the null hypothesis of no cluster. We fitted the Besag-York-Mollie model using integrated nested Laplace approximations to assess factors that influence the regional variation in cancer incidence.

Results
Spatial clusters with high liver cancer incidence rates were detected in the southwestern and southeastern regions of Korea. High gallbladder cancer incidence rates are clustered in the southeastern region. Regional liver cancer incidence can be accounted for the prevalence of high household income (coefficient, − 0.10; 95% credible interval [CI], − 0.18 to − 0.02), marital status (coefficient, − 0.14; 95% CI, − 0.25 to − 0.03), the incidence of hepatitis B (coefficient, 0.87; 95% CI, 0.29 to 1.44), and liver cancer screening (coefficient, 0.06; 95% CI, 0.00 to 0.12), while gallbladder cancer incidence was related to the prevalence of high household income (coefficient, − 0.03; 95% CI, − 0.05 to 0.00) and living close to a river with a high prevalence of liver fluke infection (coefficient, 0.55; 95% CI, 0.14 to 0.96).

Conclusions
This study demonstrated geographic variation in liver and gallbladder cancer incidence, which can be explained by determinants such as hepatitis B, income, marital status, and living near a river.
Solitary multicystic lesion lung cancer: two case reports and review of the literature
Authors: Tang Xi , Liu Gang , Tan Xianglan , Liu Chengjun , Xiang Jin , Jiang Yu 
Published: November 2021

Abstract
Background
Lung cancer associated with cystic airspaces, especially solitary multicystic lesion lung cancer, is a rare disease (a rare imaging performance of non-small cell lung cancer). It is difficult to diagnose owing to the lack of a clear definition; therefore, diagnosis of these neoplastic lesions remains challenging.

Case presentation
We outlined two cases of elderly Chinese men who were admitted to the hospital with a solitary multicystic lesion of the lung and subsequent surgical resection, confirming a diagnosis of adenocarcinoma.

Conclusions
For solitary pulmonary cystic airspaces (especially solitary multicystic lung lesions), it is important to properly recognise their imaging features. Due to the possibility of malignancies, timely surgery is an effective treatment strategy for early diagnosis.
Preliminary development of a questionnaire to measure the extra-pulmonary symptoms of severe asthma
Authors: de Felice Giulio , Hyland Michael E. , Lanario Joseph W. , Antonacci Yuri , Jones Rupert C. , Masoli Matthew 
Published: November 2021

Abstract
Background
Research into the effects of asthma treatments on the extra-pulmonary symptoms of severe asthma is limited by the absence of a suitable questionnaire. The aim was to create a questionnaire suitable for intervention studies by selecting symptoms that are statistically associated with asthma pathology and therefore may improve when pathology is reduced.

Methods
Patients attending a specialist asthma clinic completed the 65-item General Symptom Questionnaire (GSQ-65), a questionnaire validated for assessing symptoms of people with multiple medically unexplained symptoms. Lung function (FEV1%) and cumulative oral corticosteroids (OCS) calculated from maintenance dose plus exacerbations were obtained from clinic records. Pathology was represented by the two components of a principal component analysis (PCA) of FEV1% and OCS. LASSO regression was used to select symptoms that had high coefficients with these two principal components and occurred frequently in severe asthma.

Results
100 patients provided data. PCA revealed two components, one where FEV1% and OCS were inversely related and another where they were directly related. LASSO regression revealed 39 symptoms with non-zero coefficients on one or more of the two principal components from which 16 symptoms were selected for the GSQ-A on the basis of magnitude of coefficient and frequency. Asthma symptoms measured by asthma control questionnaires were excluded. The GSQ-A correlated 0.33 and − 0.34 (p = 0.001) with the two principal components.

Conclusion
The GSQ-A assesses the frequency of 16 heterogenous non-respiratory symptoms that are associated with asthma severity using the statistical combination of FEV1% and OCS.
Interstitial lung disease is a dominant feature in patients with circulating myositis-specific antibodies
Authors: Misra Abhinav K. , Wong Nathan L. , Healey Terrance T. , Lally Edward V. , Shea Barry S. 
Published: November 2021

AbstractBackgroundMany patients with polymyositis (PM) or dermatomyositis (DM) have circulating myositis-specific antibodies (MSAs). Interstitial lung disease (ILD) is a common manifestation of PM/DM, and it can even precede the onset of characteristic muscle or skin manifestations. Furthermore, there appear to be some patients with ILD and circulating MSAs who do not develop muscle or skin disease even after prolonged follow-up. We sought to determine whether ILD is equally or more common than myositis or dermatitis at the time of initial detection of MSAs.MethodsWe identified all patients found to have circulating MSAs at our institution over a 4-year period and assessed for the presence of lung, muscle, and skin disease at the time of initial detection of MSAs. Among those found to have ILD, we compared demographic and clinical features, chest CT scan findings, and outcomes between those with PM/DM-associated ILD and those with ILD but no muscle or skin disease.ResultsA total of 3078 patients were tested for MSAs, and of these 40 were positive. Nine different MSAs were detected, with anti-histidyl tRNA synthetase (anti-Jo-1) being the most common (35% of MSAs). Among patients with positive MSAs, 86% were found to have ILD, compared to 39% and 28% with muscle and skin involvement, respectively (p < 0.001). Fifty percent of all MSA-positive patients had isolated ILD, with no evidence of muscle or skin disease. Those with isolated ILD were more likely to be older and have fibrotic changes on chest CT, less likely to receive immunomodulatory therapy, and had worse overall survival.ConclusionsIn this study we found that individuals with circulating MSAs were more likely to have ILD than classic muscle or skin manifestations of PM/DM at the time of initial detection of MSAs. Our findings suggest that the presence of ILD should be considered a disease-defining manifestation in the presence of MSAs and incorporated into classification criteria for PM/DM.
Modified high-flow nasal cannula oxygen therapy versus conventional oxygen therapy in patients undergoing bronchoscopy: a randomized clinical trial
Authors: Wang Rui , Li Hai-Chao , Li Xu-Yan , Tang Xiao , Chu Hui-Wen , Yuan Xue , Tong Zhao-Hui , Sun Bing 
Published: November 2021

Abstract
Background
Hypoxemia frequently occurs during bronchoscopy. High-flow nasal cannula (HFNC) oxygen therapy may be a feasible alternative to prevent the deterioration of gas exchange during bronchoscopy. With the convenience of clinical use in mind, we modified an HFNC using a single cannula. This clinical trial was designed to test the hypothesis that a modified HFNC would decrease the proportion of patients with a single moment of peripheral arterial oxygen saturation (SpO2) < 90% during bronchoscopy.

Methods
In this single-center, prospective randomized controlled trial, hospitalized patients in the respiratory department in need of diagnostic bronchoscopy were randomly assigned to a modified HFNC oxygen therapy group or a conventional oxygen therapy (COT) group. The primary outcome was the proportion of patients with a single moment of SpO2 < 90% during bronchoscopy.

Results
Eight hundred and twelve patients were randomized to the modified HFNC (n = 406) or COT (n = 406) group. Twenty-four patients were unable to cooperate or comply with bronchoscopy. Thus, 788 patients were included in the analysis. The proportion of patients with a single moment of SpO2 < 90% during bronchoscopy in the modified HFNC group was significantly lower than that in the COT group (12.5% vs. 28.8%, p < 0.001). There were no significant differences in the fraction of inspired oxygen between the two groups. The lowest SpO2 during bronchoscopy and 5 min after bronchoscopy in the modified HFNC group was significantly higher than that in the COT group. Multivariate analysis showed that a baseline forced vital capacity (FVC) < 2.7 L (OR, 0.276; 95% CI, 0.083–0.919, p = 0.036) and a volume of fluid instilled > 60 ml (OR, 1.034; 95% CI, 1.002–1.067, p = 0.036) were independent risk factors for hypoxemia during bronchoscopy in the modified HFNC group.

Conclusions
A modified HFNC could decrease the proportion of patients with a single moment of SpO2 < 90% during bronchoscopy. A lower baseline FVC and large-volume bronchoalveolar lavage may predict desaturation during bronchoscopy when using a modified HFNC.
Trial registration ClinicalTrials. Gov: NCT02606188. Registered 17 November 2015.
Obstructive sleep apnoea and 12-month weight loss in adults with class 3 obesity attending a multidisciplinary weight management program
Authors: Kobuch Sophie , Tsang Fiona , Chimoriya Ritesh , Gossayn Daniel , O’Brien Sarah , Jamal Javeria , Laks Leon , Tahrani Abd , Kormas Nic , Piya Milan K 
Published: November 2021

Abstract
Background
Although there is a strong association between obesity and obstructive sleep apnoea (OSA), the effects of OSA and CPAP therapy on weight loss are less well known. The aim of this study in adults with class 3 obesity attending a multidisciplinary weight management program was to assess the relationship between OSA and CPAP usage, and 12-month weight change.

Methods
A retrospective cohort study of all patients commencing an intensive multidisciplinary publicly funded weight management program in Sydney, Australia, between March 2018 and March 2019. OSA was diagnosed using laboratory overnight sleep studies. Demographic and clinical data, and use of CPAP therapy was collected at baseline and 12 months. CPAP use was confirmed if used ≥4 h on average per night on download.

Results
Of the 178 patients who joined the program, 111 (62.4 %) completed 12 months in the program. At baseline, 63.1 % (n=70) of patients had OSA, of whom 54.3 % (n=38) were using CPAP. The non-OSA group had more females compared to the OSA with CPAP group and OSA without CPAP group (90.2 % vs. 57.9 % and 62.5 %, respectively; p=0.003), but there were no significant baseline differences in BMI (50.4±9.3 vs. 52.1±8.7 and 50.3±9.5 kg/m2, respectively; p=0.636). There was significant weight loss across all three groups at 12 months. However, there were no statistically significant differences across groups in the percentage of body weight loss (OSA with CPAP: 6.3±5.6 %, OSA without CPAP: 6.8±6.9 %, non-OSA: 7.2±6.5 %; p=0.844), or the proportion of patients who achieved ≥5 % body weight loss (OSA with CPAP: 57.9 %, OSA without CPAP: 59.4 %, non-OSA: 65.9 %; p=0.743). In patients with T2DM, there was a significant reduction in HbA1c from baseline to 12 months (7.8±1.7 % to 7.3±1.4 %, p=0.03), with no difference between groups (p=0.997).

Conclusions
This multidisciplinary weight management program resulted in significant weight loss at 12 months, regardless of OSA diagnosis or CPAP use in adults with class 3 obesity. Larger studies are needed to further investigate the effects of severity of OSA status and CPAP use in weight management programs. Until completed, this study suggests that the focus should remain on implementing lifestyle changes and weight management regardless of OSA status.
Identification of de novo mutations for ARID1B haploinsufficiency associated with Coffin–Siris syndrome 1 in three Chinese families via array-CGH and whole exome sequencing
Authors: Lu Guanting , Peng Qiongling , Wu Lianying , Zhang Jian , Ma Liya 
Published: November 2021

Abstract
Background
Coffin–Siris syndrome (CSS) is a multiple malformation syndrome characterized by intellectual disability associated with coarse facial features, hirsutism, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. CSS represents a small group of intellectual disability, and could be caused by at least twelve genes. The genetic background is quite heterogenous, making it difficult for clinicians and genetic consultors to pinpoint the exact disease types.

Methods
Array-Comparative Genomic Hybridization (array-CGH) and whole exome sequencing (WES) were applied for three trios affected with intellectual disability and clinical features similar with those of Coffin–Siris syndrome. Sanger sequencing was used to verify the detected single-nucleotide variants (SNVs).

Results
All of the three cases were female with normal karyotypes of 46, XX, born of healthy, non-consanguineous parents. A 6q25 microdeletion (arr[hg19]6q25.3(155,966,487–158,803,979) × 1) (2.84 Mb) (case 1) and two loss-of-function (LoF) mutations of ARID1B [c.2332 + 1G > A in case 2 and c.4741C > T (p.Q1581X) in case 3] were identified. All of the three pathogenic abnormalities were de novo, not inherited from their parents. After comparison of publicly available microdeletions containing ARID1B, four types of microdeletions leading to insufficient production of ARID1B were identified, namely deletions covering the whole region of ARID1B, deletions covering the promoter region, deletions covering the termination region or deletions covering enhancer regions.

Conclusion
Here we identified de novo ARID1B mutations in three Chinese trios. Four types of microdeletions covering ARID1B were identified. This study broadens current knowledge of ARID1B mutations for clinicians and genetic consultors.
Control of the expiratory flow in a lung model and in healthy volunteers with an adjustable flow regulator: a combined bench and randomized crossover study
Authors: Schmidt Johannes , Martin Anna , Wenzel Christin , Weber Jonas , Wirth Steffen , Schumann Stefan 
Published: November 2021

Abstract
Background
Pursed-lips breathing (PLB) is a technique to attenuate small airway collapse by regulating the expiratory flow. During mandatory ventilation, flow-controlled expiration (FLEX), which mimics the expiratory flow course of PLB utilizing a digital system for measurement and control, was shown to exert lung protective effects. However, PLB requires a patient’s participation and coordinated muscular effort and FLEX requires a complex technical setup. Here, we present an adjustable flow regulator to mimic PLB and FLEX, respectively, without the need of a patient’s participation, or a complex technical device.

Methods
Our study consisted of two parts: First, in a lung model which was ventilated with standard settings (tidal volume 500 ml, respiratory rate 12 min−1, positive end-expiratory pressure (PEEP) 5 cmH2O), the possible reduction of the maximal expiratory flow by utilizing the flow regulator was assessed. Second, with spontaneously breathing healthy volunteers, the short-term effects of medium and strong expiratory flow reduction on airway pressure, the change of end-expiratory lung volume (EELV), and breathing discomfort was investigated.

Results
In the lung model experiments, expiratory flow could be reduced from − 899 ± 9 ml·s−1 down to − 328 ± 25 ml·s−1. Thereby, inspiratory variables and PEEP were unaffected. In the volunteers, the maximal expiratory flow of − 574 ± 131 ml·s−1 under baseline conditions was reduced to − 395 ± 71 ml·s−1 for medium flow regulation and to − 266 ± 58 ml·s−1 for strong flow regulation, respectively (p < 0.001). Accordingly, mean airway pressure increased from 0.6 ± 0.1 cmH2O to 2.9 ± 0.4 cmH2O with medium flow regulation and to 5.4 ± 2.4 cmH2O with strong flow regulation, respectively (p < 0.001). The EELV increased from baseline by 31 ± 458 ml for medium flow regulation and 320 ± 681 ml for strong flow regulation (p = 0.033). The participants rated breathing with the flow regulator as moderately uncomfortable, but none rated breathing with the flow regulator as intolerable.

Conclusions
The flow regulator represents an adjustable device for application of a self-regulated expiratory resistive load, representing an alternative for PLB and FLEX. Future applications in spontaneously breathing patients and patients with mandatory ventilation alike may reveal potential benefits.
Trial registration: DRKS00015296, registered on 20th August, 2018; URL: https://www.drks.de/drks_web/setLocale_EN.do.
Sex differences in the non-linear association between BMI and LDL cholesterol in middle-aged and older adults: findings from two nationally representative surveys in China
Authors: Li Haibin , Ma Jiahui , Zheng Deqiang , Li Xia , Guo Xiuhua , Wang Jing , Su Pixiong 
Published: November 2021

Abstract
Background
The relationship between body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C) has not been clearly elucidated in middle-aged and older adults. This study aimed to evaluate the non-linear dose-response relationship between BMI and LDL-C in males and females.

Methods
Data was obtained from two nationally representative surveys in China—the China Health and Nutrition Survey (CHNS, 2009) and China Health and Retirement Longitudinal Study (CHARLS, 2011–2012). To evaluate the sex differences in the association between BMI and LDL-C, the generalized additive models with a smooth function for continuous BMI and smooth-factor interaction for sexes with BMI were used. Segmented regressions were fitted to calculate the slopes with different estimated breakpoints among females and males.

Results
A total of 12,273 participants (47.1% male) aged 45 to 75 years were included. The generalized additive models revealed that a non-linear relationship between BMI and LDL-C level in both sexes after adjustment for age, residence, education levels, marital status, drinking, smoking status, and cohort (CHNS or CHARLS). Slopes of the association between BMI and LDL-C association changed at BMI 20.3 kg/m2 (95% CI: 18.8 to 21.8) in females and 27.1 kg/m2 (95% CI: 25. 8 to 28.4) in males. Below these BMI breakpoints, LDL-C levels increased 1.84 (95% CI: 1.45 to 2.31) in males and 3.49 (95% CI: 1.54 to 5.45) mg/dL per kg/m2 in females. However, LDL-C levels declined − 1.50 (95% CI: − 2.92 to − 0.09) mg/dL per kg/m2 above BMI of 27.1 kg/m2 in males. The non-linear association BMI and LDL-C in males and females was varied by cohort source, age groups, and the number of metabolic syndrome criteria.

Conclusions
In the Chinese middle aged and older adults, the BMI and LDL-C relationship was inverted U-shaped with a high level of LDL-C at a BMI of 27.1 kg/m2 in males, and an approximately linear association was observed in females.
How cancer cells remodel lipid metabolism: strategies targeting transcription factors
Authors: Jeong Do-Won , Lee Seulbee , Chun Yang-Sook 
Published: November 2021

AbstractReprogramming of lipid metabolism has received increasing recognition as a hallmark of cancer cells because lipid dysregulation and the alteration of related enzyme profiles are closely correlated with oncogenic signals and malignant phenotypes, such as metastasis and therapeutic resistance. In this review, we describe recent findings that support the importance of lipids, as well as the transcription factors involved in cancer lipid metabolism. With recent advances in transcription factor analysis, including computer-modeling techniques, transcription factors are emerging as central players in cancer biology. Considering the limited number and the crucial role of transcription factors associated with lipid rewiring in cancers, transcription factor targeting is a promising potential strategy for cancer therapy.
Triglyceride glucose-body mass index in identifying high-risk groups of pre-diabetes
Authors: Jiang Chunyuan , Yang Ruijuan , Kuang Maobin , Yu Meng , Zhong Mingchun , Zou Yang 
Published: November 2021

Abstract
Background
Triglyceride glucose-body mass index (TyG-BMI) has been recommended as an alternative indicator of insulin resistance. However, the association between TyG-BMI and pre-diabetes remains to be elucidated.

Methods
More than 100,000 subjects with normal glucose at baseline received follow-up. The main outcome event of concern was pre-diabetes defined according to the diagnostic criteria recommended by the American Diabetes Association (ADA) in 2018 and the World Health Organization (WHO) in 1999. A Cox proportional hazard regression model was used to evaluate the role of TyG-BMI in identifying people at high risk of pre-diabetes.

Results
At a mean observation period of 3.1 years, the incidence of pre-diabetes in the cohort was 3.70 and 12.31% according to the WHO and ADA diagnostic criteria for pre-diabetes, respectively. The multivariate Cox regression analysis demonstrated that TyG-BMI was independently positively correlated with pre-diabetes, and there was a special population dependence phenomenon. Among them, non-obese people, women and people under 50 years old had a significantly higher risk of TyG-BMI-related pre-diabetes (P-interaction< 0.05).

Conclusions
These findings suggest that a higher TyG-BMI significantly increases an individual’s risk of pre-diabetes, and this risk is significantly higher in women, non-obese individuals, and individuals younger than 50 years of age.