bluuebunny/crossref_metadata_2025 huggingface dataset:
SCSilicon: a tool for synthetic single-cell DNA sequencing data generation
Authors: Feng Xikang , Chen Lingxi
Published: May 2022

Background

Single-cell DNA sequencing is getting indispensable in the study of cell-specific cancer genomics. The performance of computational tools that tackle single-cell genome aberrations may be nevertheless undervalued or overvalued, owing to the insufficient size of benchmarking data. In silicon simulation is a cost-effective approach to generate as many single-cell genomes as possible in a controlled manner to make reliable and valid benchmarking.

Results

This study proposes a new tool, SCSilicon, which efficiently generates single-cell in silicon DNA reads with minimum manual intervention. SCSilicon automatically creates a set of genomic aberrations, including SNP, SNV, Indel, and CNV. Besides, SCSilicon yields the ground truth of CNV segmentation breakpoints and subclone cell labels. We have manually inspected a series of synthetic variations. We conducted a sanity check of the start-of-the-art single-cell CNV callers and found SCYN was the most robust one.

Conclusions

SCSilicon is a user-friendly software package for users to develop and benchmark single-cell CNV callers. Source code of SCSilicon is available at https://github.com/xikanfeng2/SCSilicon.
Identification of functionally important miRNA targeted genes associated with child obesity trait in genome-wide association studies
Authors: Song Melinda , Yu Jiaqi , Li Binze , Dong Julian , Gao Jeslyn , Shang Lulu , Zhou Xiang , Bai Yongsheng
Published: May 2022

Background

Genome-wide association studies (GWAS) have uncovered thousands of genetic variants that are associated with complex human traits and diseases. miRNAs are single-stranded non-coding RNAs. In particular, genetic variants located in the 3’UTR region of mRNAs may play an important role in gene regulation through their interaction with miRNAs. Existing studies have not been thoroughly conducted to elucidate 3’UTR variants discovered through GWAS. The goal of this study is to analyze patterns of GWAS functional variants located in 3’UTRs about their relevance in the network between hosting genes and targeting miRNAs, and elucidate the association between the genes harboring these variants and genetic traits.

Methods

We employed MIGWAS, ANNOVAR, MEME, and DAVID software packages to annotate the variants obtained from GWAS for 31 traits and elucidate the association between their harboring genes and their related traits. We identified variants that occurred in the motif regions that may be functionally important in affecting miRNA binding. We also conducted pathway analysis and functional annotation on miRNA targeted genes harboring 3’UTR variants for a trait with the highest percentage of 3’UTR variants occurring.

Results

The Child Obesity trait has the highest percentage of 3’UTR variants (75%). Of the 16 genes related to the Child Obesity trait, 5 genes (ETV7, GMEB1, NFIX, ZNF566, ZBTB40) had a significant association with the term DNA-Binding (p < 0.05). EQTL analysis revealed 2 relevant tissues and 10 targeted genes associated with the Child Obesity trait.

In addition, Red Blood Cells (RBC), Hemoglobin (HB), and Package Cell Volume (PCV) have overlapping variants. In particular, thePIM1variant occurred inside the HB Motif region 37,174,641–37,174,660, andLUC7L3variant occurred inside RBC Motif region 50,753,918–50,753,937.

Conclusion

Variants located in 3’UTR can alter the binding affinity of miRNA and impact gene regulation, thus warranting further annotation and analysis. We have developed a bioinformatics bash pipeline to automatically annotate variants, determine the number of variants in different categories for each given trait, and check common variants across different traits. This is a valuable tool to annotate a large number of GWAS result files.
B-assembler: a circular bacterial genome assembler
Authors: Huang Fengyuan , Xiao Li , Gao Min , Vallely Ethan J. , Dybvig Kevin , Atkinson T. Prescott , Waites Ken B. , Chong Zechen
Published: May 2022

Background

Accurate bacteria genome de novo assembly is fundamental to understand the evolution and pathogenesis of new bacteria species. The advent and popularity of Third-Generation Sequencing (TGS) enables assembly of bacteria genomes at an unprecedented speed. However, most current TGS assemblers were specifically designed for human or other species that do not have a circular genome. Besides, the repetitive DNA fragments in many bacterial genomes plus the high error rate of long sequencing data make it still very challenging to accurately assemble their genomes even with a relatively small genome size. Therefore, there is an urgent need for the development of an optimized method to address these issues.

Results

We developed B-assembler, which is capable of assembling bacterial genomes when there are only long reads or a combination of short and long reads. B-assembler takes advantage of the structural resolving power of long reads and the accuracy of short reads if applicable. It first selects and corrects the ultra-long reads to get an initial contig. Then, it collects the reads overlapping with the ends of the initial contig. This two-round assembling procedure along with optimized error correction enables a high-confidence and circularized genome assembly. Benchmarked on both synthetic and real sequencing data of several species of bacterium, the results show that both long-read-only and hybrid-read modes can accurately assemble circular bacterial genomes free of structural errors and have fewer small errors compared to other assemblers.

Conclusions

B-assembler provides a better solution to bacterial genome assembly, which will facilitate downstream bacterial genome analysis.
Methylated Septin9 has moderate diagnostic value in colorectal cancer detection in Chinese population: a multicenter study
Authors: Lu Dong-cheng , Zhang Qi-fang , Li Li , Luo Xian-ke , Liang Bin , Lu Yi-han , Hu Bang-li , Jiang Hai-xing
Published: May 2022

Background

The detection rate of methylated Septin9 (mSEPT9) in colorectal cancer (CRC) is varied greatly across the studies. This study aimed to evaluate the diagnostic ability of mSEPT9 in CRC, and compare the diagnostic efficacy with fecal immunochemical test (FIT).

Methods

326 subjects from four centers were prospectively recruited, including 179 CRC and 147 non-CRC subjects. The plasma was collected for mSEPT9 and CEA, AFP, CA125, CA153 and CA199 test, and fecal samples for FIT tests. Sensitivity, specificity and area under the curve (AUC) of receiver operating characteristic curve were calculated to evaluate the diagnostic value of each biomarker.

Results

The positive rate in mSEPT9 and FIT, and the level of CEA, CA125 and CA199 were significantly higher in CRC compared with non-CRC subjects. The mSEPT9 positive rate was not associated with TNM stage and tumor stage. The sensitivity, specificity and AUC of mSEPT9 in diagnostic CRC were 0.77, 0.88 and 0.82, respectively, while the value in FIT was 0.88, 0.80 and 0.83, respectively. mSEPT9 and FIT have higher AUC value than that of CEA, CA125 and CA199. Combination of both mSEPT9 and FIT positive increased sensitivity and AUC to 0.98 and 0.83, respectively, but the specificity was declined. mSEPT9 has a slightly low sensitivity in diagnosis of colon cancer (0.87) compared with rectal cancer (0.93).

Conclusion

mSEPT9 demonstrated moderate diagnostic value in CRC detection, which was similar to the FIT but superior to the CEA, CA125 and CA199. Combination of mSEPT9 and FIT further improved diagnostic sensitivity in CRC.

Trial registration: ChiCTR2000038319.
Characteristics of acute kidney injury and its impact on outcome in patients with acute-on-chronic liver failure
Authors: Huang Yue , Cai Junjun , Ha Fushuang , Guo Beichen , Xin Shaojie , Duan Zhongping , Han Tao
Published: May 2022

Objective

Acute kidney injury (AKI) is a common and life-threatening complication of liver failure. The purpose of this study is to construct a nomogram and online calculator to predict the development of hospital-acquired acute kidney injury (HA-AKI) in patients with acute-on-chronic liver failure (ACLF), which may contribute to the prognosis of ACLF.

Methods

574 ACLF patients were evaluated retrospectively. AKI was defined by criteria proposed by International Club of Ascites (ICA) and divided into community-acquired and hospital-acquired AKI (CA-AKI and HA-AKI). The difference between CA-AKI and HA-AKI, factors associated with development into and recovered from AKI periods. The risk factors were identified and nomograms were developed to predict the morbidity of HA-AKI in patients with ACLF.

Results

Among 574 patients, 217(37.8%) patients had AKI, CA-AKI and HA-AKI were 56 (25.8%) and 161 (74.2%) respectively. The multivariate logistic regression model (KP-AKI) for predicting the occurrence of HA-AKI were age, gastrointestinal bleeding, bacterial infections, albumin, total bilirubin, blood urea nitrogen and prothrombin time. The AUROC of the KP-AKI in internal and external validations were 0.747 and 0.759, respectively. Among 217 AKI patients, 81(37.3%), 96(44.2%) and 40(18.4%) patients were with ICA-AKI stage progression, regression and fluctuated in-situ, respectively. The 90-day mortality of patients with AKI was 55.3% higher than non-AKI patients 21.6%. The 90-day mortality of patients with progression of AKI was 88.9%, followed by patients with fluctuated in-situ 40% and regression of AKI 33.3%.

Conclusions

The nomogram constructed by KP-AKI can be conveniently and accurately in predicting the development of HA-AKI, and AKI can increase the 90-day mortality significantly in ACLF patients.

Trial registration Chinese clinical trials registry: ChiCTR1900021539.
Sleep characteristic profiles and the correlation with spectrum of metabolic syndrome among older adult: a cross-sectional study
Authors: Liu Xin , Huang Limei , Wu Qiang , Chen Yingwei , Chen Xiuqin , Chen Hao , Gao Junling , Xiao Qianyi
Published: May 2022

Background

Metabolic Syndrome (MetS) is a common health problem among older adults. Previous studies have revealed the relationship between sleep duration as well as global sleep status and MetS.

Objectives

This study aims to examine the association between the specific sleep characteristic and MetS as well as MetS components among community-dwelling old adults.

Methods

This cross-sectional study included 1499 community residents aged ≥ 60 years. Sleep characteristics were assessed using the Pittsburgh Sleep Quality Index (PSQI) and bed/rise time of the residents. Logistic regression analysis and multiple linear regression analysis were used to examine the associations between sleep characteristics and MetS as well as MetS components. A generalized additive model was built to assess the smooth relationship between triglyceride (TG) levels and sleep duration.

Results

Of the 1499 participants, 449 (30.0%) had MetS, and 443 (29.6%) had poor sleep quality. The rise time was found to be associated with MetS (> 6:00 vs. 5:00 ~ 6:00: adjusted OR (95%) = 1.77 (1.17–2.69), P = 0.007). For the MetS components, a U-shaped relationship was first revealed for sleep duration and TG levels (EDF = 1.85, P < 0.001). Furthermore, significant associations also included the associations of subjective sleep quality and daytime dysfunction with hypertension, the associations of sleep efficiency and rise time with hyperglycemia, the associations of rise time with TG levels, and the association of bedtime with waist circumference.

Conclusions

The different sleep characteristics were associated with different MetS components.
Monocyte count and soluble markers of monocyte activation in people living with HIV and uninfected controls
Authors: Knudsen Andreas D. , Bouazzi Randa , Afzal Shoaib , Gelpi Marco , Benfield Thomas , Høgh Julie , Thomsen Magda Teresa , Trøseid Marius , Nordestgaard Børge G. , Nielsen Susanne D.
Published: May 2022

Background

Monocytes play an important role in inflammation, and monocytosis and monocyte activation are features of chronic inflammation. We aimed to investigate if HIV status was associated with monocyte count and monocyte activation and to assess the relationship between monocyte count and monocyte activation markers and HIV-related factors.

Methods

Persons living with HIV (PLWH) with measured monocyte count and sCD14 and sCD163 were included from the Copenhagen Comorbidity in HIV infection (COCOMO) study and matched 1:5 on sex and age with uninfected controls. In addition, 74 uninfected individuals from COCOMO with measured sCD14 and sCD163 were included. Identical protocols and equipment were used to determine monocyte counts and monocyte activation in PLWH and uninfected controls. Linear regression adjusted for age, sex, smoking and waist-to-hip-ratio was used to analyze the association between possible risk factors and monocyte outcomes.

Results

We included 871 PLWH and 4355 uninfected controls. PLWH had − 0.021 [− 0.031 − 0.011] × 109/L) lower monocyte count than uninfected controls, and in adjusted analyses HIV status was independently associated with − 0.035 [− 0.045, − 0.025] × 109/L lower monocyte count. In contrast, PLWH had higher sCD163 and sCD14 concentrations than uninfected controls. After adjustment, HIV-status was associated with higher sCD14 and sCD163 concentrations (588 [325, 851] ng/ml, and 194 [57, 330] ng/ml, respectively).

Conclusion

PLWH had lower monocyte counts than controls, but the absolute difference was small, and any clinical impact is likely limited. In contrast, concentrations of monocyte activation markers, previously implicated as drivers of non-AIDS comorbidity, were higher in PLWH than in controls.
Safety and effectiveness of eribulin in Japanese patients with soft tissue sarcoma including rare subtypes: a post-marketing observational study
Authors: Kawai Akira , Narahara Hiroyuki , Takahashi Shunji , Nakamura Tomoki , Kobayashi Hiroshi , Megumi Yasunori , Matsuoka Toshiyuki , Kobayashi Eisuke
Published: May 2022

Background

Soft tissue sarcomas (STSs) are a heterogeneous group of cancers with over 100 described subtypes. While these cancers are infrequent, the prognosis is quite poor, particularly for those with stage IV metastatic disease. Patients for whom curative resection is difficult or those with recurrent metastatic disease are treated with chemotherapy, although the options are very limited. Eribulin is an approved treatment of all STS subtypes in Japan. Efficacy and safety data for the treatment of rare STS subtypes other than liposarcoma and leiomyosarcoma (L-type sarcomas) are limited. This nationwide, multicenter, prospective, post-marketing observational study was conducted to assess the real-world effectiveness and safety of eribulin in Japanese patients with STS.

Methods

Patients with all types of STS and who consented to eribulin treatment were eligible to participate. The observation period was 1 year, starting at treatment initiation, and clinical outcomes were followed up for 2 years after initiating treatment. The primary endpoint was overall survival (OS). Additional outcomes included time-to-treatment failure (TTF), objective response rate (ORR), disease control rate (DCR), and safety. ORR and DCR were evaluated using imaging findings. Effectiveness results were analyzed both for all patients and by STS subtype.

Results

A total of 256 patients were enrolled; 252 and 254 were included in the effectiveness and safety analysis set, respectively. Most patients (83.1%) received an initial eribulin dose of 1.4 mg/m2 (standard dose). Respective median OS (95% confidence interval [CI]) was 10.8 (8.5–13.1), 13.8 (10.1–22.3) and 6.5 (5.7–11.1) months for all, L-type, and non-L-type subtypes. The respective median TTF (95% CI) was 2.5 (2.1–2.8), 2.8 (2.3–3.7), and 2.2 (1.6–2.6) months. The ORR and DCR were 8.1 and 42.6%, respectively. Adverse drug reactions (ADRs) and serious ADRs were reported for 83.5 and 18.9% of patients, respectively. The main ADRs were associated with myelosuppression. No significant difference was observed in the incidence of ADRs for patients ≥65 versus <65 years old.

Conclusions

Eribulin demonstrated effectiveness and a manageable safety profile for patients with STS, although the effectiveness of eribulin was not demonstrated for some non-L-type subtypes.

Trial registration

NCT03058406 (ClinicalTrials.gov).
Low level of Fibrillarin, a ribosome biogenesis factor, is a new independent marker of poor outcome in breast cancer
Authors: Nguyen Van Long Flora , Lardy-Cleaud Audrey , Carène Dimitri , Rossoni Caroline , Catez Frédéric , Rollet Paul , Pion Nathalie , Monchiet Déborah , Dolbeau Agathe , Martin Marjorie , Simioni Valentin , Bray Susan , Le Beherec Doris , Mosele Fernanda , Bouakka Ibrahim , Colombe-Vermorel Amélie , Odeyer Laetitia , Diot Alexandra , Jordan Lee B. , Thompson Alastair M. , Jamen Françoise , Dubois Thierry , Chabaud Sylvie , Michiels Stefan , Treilleux Isabelle , Bourdon Jean-Christophe , Pérol David , Puisieux Alain , André Fabrice , Diaz Jean-Jacques , Marcel Virginie
Published: May 2022

Background

A current critical need remains in the identification of prognostic and predictive markers in early breast cancer. It appears that a distinctive trait of cancer cells is their addiction to hyperactivation of ribosome biogenesis. Thus, ribosome biogenesis might be an innovative source of biomarkers that remains to be evaluated.

Methods

Here, fibrillarin (FBL) was used as a surrogate marker of ribosome biogenesis due to its essential role in the early steps of ribosome biogenesis and its association with poor prognosis in breast cancer when overexpressed. Using 3,275 non-metastatic primary breast tumors, we analysed FBL mRNA expression levels and protein nucleolar organisation. Usage of TCGA dataset allowed transcriptomic comparison between the different FBL expression levels-related breast tumours.

Results

We unexpectedly discovered that in addition to breast tumours expressing high level of FBL, about 10% of the breast tumors express low level of FBL. A correlation between low FBL mRNA level and lack of FBL detection at protein level using immunohistochemistry was observed. Interestingly, multivariate analyses revealed that these low FBL tumors displayed poor outcome compared to current clinical gold standards. Transcriptomic data revealed that FBL expression is proportionally associated with distinct amount of ribosomes, low FBL level being associated with low amount of ribosomes. Moreover, the molecular programs supported by low and high FBL expressing tumors were distinct.

Conclusion

Altogether, we identified FBL as a powerful ribosome biogenesis-related independent marker of breast cancer outcome. Surprisingly we unveil a dual association of the ribosome biogenesis FBL factor with prognosis. These data suggest that hyper- but also hypo-activation of ribosome biogenesis are molecular traits of distinct tumors.
Assessment of the masseter stiffness in patients during conservative therapy for masticatory muscle disorders with shear wave elastography
Authors: Olchowy Anna , Seweryn Piotr , Olchowy Cyprian , Wieckiewicz Mieszko
Published: May 2022

Background

The complex structure of the stomatognathic system plays a vital role in chewing, digestion, speaking, breathing, facial expression and swallowing. Its complexity is the primary reason for creating multidisciplinary teams to manage temporomandibular disorders (TMD). We aimed to assess the masseter stiffness in patients undergoing conservative therapy for masticatory muscle disorders and evaluate the efficacy of manual therapy and stabilization occlusal splint in the treatment of masticatory muscle disorders.

Methods

This uncontrolled prospective cohort study included 35 patients with masticatory muscle disorders. The study lasted for eight weeks. The patients were treated with manual therapy and stabilization occlusal splint and evaluated using shear wave elastography of the masseter muscles and patient-reported outcome measures (PROMs) to assess pain, anxiety, quality of sleep, satisfaction with life and perceived stress.

Results

After the treatment, the stiffness of both masseter muscles decreased significantly (by 4.21 kPa). The patients reported a significant reduction in pain. At baseline, the median scores ranged from 5 to 8; after treatment, they ranged from 0 to 1 (p < 0.0001). The patients also reported significant improvement in terms of all patient-reported outcome measures. The reduction in stiffness corresponded to the improvement in pain and PROMs, as shown by correlations which were insignificant for all measures.

Conclusions

Conservative therapy of masticatory muscle disorders involving manual therapy and stabilization occlusal splint is effective. It reduces the masseter stiffness as objectively shown in shear wave elastography and improves subjective PROMs scores, including numerical pain assessment and selected questionnaires. Shear wave elastography has the potential for broad application in clinical practice to monitor masticatory muscle disorders treatment effects due to its objectivity and non-invasive character. Further research is recommended on larger patient populations and longer follow-up.

Trial registration

The study was registered at clinicaltrials.gov (NCT03844854). First posted date: 19/02/2019.
A comparative study of two robotic thyroidectomy procedures: transoral vestibular versus bilateral axillary-breast approach
Authors: He Qingqing , Zhu Jian , Li Xiaolei , Wang Meng , Wang Gang , Zhou Peng , Wang Dan , Liu Changrui , Zheng Luming , Zhuang Dayong , Fan Ziyi , Yu Fang , Ma Yunhan , Cao Xianjiao , Wang Suai , Yue Tao , Hu Jinzhi
Published: May 2022

Objective

To compare the surgical outcomes between the transoral-vestibular robotic thyroidectomy (TOVRT) and bilateral axillo-breast approach robotic thyroidectomy (BABART).

Methods

A total of 99 patients with papillary thyroid carcinoma but no distant metastasis were enrolled in this study from May 2020 to April 2021. Lobectomy or total thyroidectomy with central lymph node dissection were performed in all cases. All 99 patients were received an ultrasound guided fine needle aspiration biopsy prior to surgical intervention, out of which 49 patients underwent TOVRT, while rest 50 patients underwent BABART. During the procedure, intraoperative neuromonitoring system was used and all recurrent laryngeal nerves (RLNs) were preserved, additionally for TOVRT procedure, three intraoral ports or right axillary fold incision was used to allow for fine countertraction of tissue for radical oncological dissection. The clinical data including age, gender, height, weight, BMI, primary tumor size, number of central lymph node removed, central lymph node metastasis, operating time, total hospital stays, postoperative hospital stays, total postoperative drainage volume, postoperative pain score, cosmetic effect and complications were recorded and analyzed.

Results

There were no significant differences in gender, height, weight, BMI and removed central lymph nodes between the two groups (P > 0.05). Patients accepted TOVRT were younger and had smaller primary tumor size than those who accepted BABART. The TOVRT group had a longer surgical time than the BABART group, but with smaller postoperative drainage volume and superior cosmetic effect (under visual analogue scale, VAS) (P < 0.05). There was no significant difference in lymph node metastasis, hospital stay and postoperative pain score (under numerical rating scale, NRS) between the two groups (P > 0.05). Last but not least, certain peculiar complications were observed in TOVRT group: paresthesia of the lower lip and the chin (one case), surgical site infection (one case) and skin burn (one case).

Conclusion

Transoral-vestibular robotic thyroidectomy is safe and feasible for certain patients, which could be considered an alternative approach for patients who require no scarring on their neck.
Impact of anxiety, depression and disease-related distress on long-term glycaemic variability among subjects with Type 1 diabetes mellitus
Authors: Déniz-García Alejandro , Díaz-Artiles Alba , Saavedra Pedro , Alvarado-Martel Dácil , Wägner Ana M. , Boronat Mauro
Published: May 2022

Background

Anxiety, depression, and disease-related distress are linked to worse overall glycaemic control, in terms of HbA1c. This study was aimed to evaluate whether traits of these emotional disorders are associated with long-term glycaemic variability in subjects with Type 1 diabetes.

Methods

Longitudinal retrospective study. Six-year HbA1c data (2014–2019) from 411 subjects with Type 1 diabetes who had participated in a previous study to design a diabetes-specific quality of life questionnaire in the year 2014 were included. Scores for Spanish versions of the Hospital Anxiety and Depression Scale (HADS) and Problem Areas in Diabetes (PAID) scale were obtained at baseline, along with sociodemographic and clinical data. Long-term glycaemic variability was measured as the coefficient of variation of HbA1c (HbA1c-CV). The association between HADS and PAID scores and HbA1c-CV was analysed with Spearman correlations and multiple regression models, both linear and additive, including other covariates (age, sex, diabetes duration time, type of treatment, baseline HbA1c, use of anxiolytic or antidepressant drugs, education level and employment status).

Results

Scores of depression, anxiety and distress were positively and significantly correlated to HbA1c-CV in univariate analyses. Multiple regression study demonstrated an independent association only for diabetes distress score (p < 0.001). Age, diabetes duration time, baseline HbA1c, education level and employment status were also significantly associated with HbA1c-CV. However, when subjects were analyzed separately in two age groups, distress scores were associated with HbA1c-CV only among those aged 25 years or older, while anxiety scores, but not distress, were associated with HbA1c-CV among those younger than 25 years.

Conclusions

Psychological factors, particularly disease-related distress and anxiety, are associated with long-term glycaemic variability in subjects with Type 1 diabetes.
Body mass index at baseline directly predicts new-onset diabetes and to a lesser extent incident cardio-cerebrovascular events, but has a J-shaped relationship to all-cause mortality
Authors: Bae Yoon-Jong , Shin Sang-Jun , Kang Hee-Taik
Published: May 2022

Objective

The prevalence of diabetes mellitus (DM), cardio-cerebrovascular diseases (CCVDs) has increased during recent decades. We aimed to investigate the relationship between body mass index (BMI) and each of several outcomes (DM, CCVDs, or mortality) based on the Korean National Health Insurance Service-Health Screening cohort.

Methods

BMI was categorized as appropriate for Asian populations, into underweight (< 18.5 kg/m2), normal (18.5–< 23 kg/m2), overweight (23–< 25 kg/m2), grade 1 obesity (25–< 30 kg/m2), grade 2 obesity (30–< 35 kg/m2), and grade 3 obesity (≥35 kg/m2). In addition, BMI was further stratified into one unit. Multivariate Cox proportional hazards regression analyses were conducted to examine the association between BMI category and the primary outcomes (DM, CCVDs, or mortality).

Results

A total of 311,416 individuals were included. The median follow-up was 12.5 years. Compared to normal BMI, underweight, overweight, and grade 1–3 obese individuals had a higher risk of the primary outcomes (hazard ratio [95% confidence intervals] 1.293 [1.224–1.365], 1.101 [1.073–1.129], 1.320 [1.288–1.353], 1.789 [1.689–1.897], and 2.376 [2.019–2.857], respectively, in men and 1.084 [1.010–1.163], 1.150 [1.116–1.185], 1.385 [1.346–1.425], 1.865 [1.725–2.019], and 2.472 [2.025–3.028], respectively, in women). Setting the reference BMI to 20–< 21 kg/m2 and categorizing into one unit increment, BMI was associated with the primary outcomes in a J-shaped manner in both sexes. The risk of DM increased with higher BMI in both sexes, while all-cause mortality decreased in men with a BMI 21–< 31 kg/m2 and women with BMI 22–< 30 kg/m2.

Conclusions

BMI was associated with all-cause mortality in a J-shaped manner in both sexes, while it was associated with risk of DM in a dose-response relationship. The relationship between BMI and the primary outcomes was J-shaped.
Mentoring in palliative medicine in the time of covid-19: a systematic scoping review
Authors: Goh Sherill , Wong Ruth Si Man , Quah Elaine Li Ying , Chua Keith Zi Yuan , Lim Wei Qiang , Ng Aubrey Ding Rui , Tan Xiu Hui , Kow Cheryl Shumin , Teo Yao Hao , Lim Elijah Gin , Pisupati Anushka , Chong Eleanor Jia Xin , Kamal Nur Haidah Ahmad , Tan Lorraine Hui En , Tay Kuang Teck , Ong Yun Ting , Chiam Min , Lee Alexia Sze Inn , Chin Annelissa Mien Chew , Mason Stephen , Krishna Lalit Kumar Radha
Published: May 2022

Introduction

The redeployment of mentors and restrictions on in-person face-to-face mentoring meetings during the COVID-19 pandemic has compromised mentoring efforts in Palliative Medicine (PM). Seeking to address these gaps, we evaluate the notion of a combined novice, peer-, near-peer and e-mentoring (CNEP) and interprofessional team-based mentoring (IPT) program.

Methods

A Systematic Evidence Based Approach (SEBA) guided systematic scoping review was carried out to study accounts of CNEP and IPT from articles published between 1st January 2000 and 28th February 2021. To enhance trustworthiness, concurrent thematic and content analysis of articles identified from structured database search using terms relating to interprofessional, virtual and peer or near-peer mentoring in medical education were employed to bring together the key elements within included articles.

Results

Fifteen thousand one hundred twenty one abstracts were reviewed, 557 full text articles were evaluated, and 92 articles were included. Four themes and categories were identified and combined using the SEBA’s Jigsaw and Funnelling Process to reveal 4 domains - characteristics, mentoring stages, assessment methods, and host organizations. These domains suggest that CNEP’s structured virtual and near-peer mentoring process complement IPT’s accessible and non-hierarchical approach under the oversight of the host organizations to create a robust mentoring program.

Conclusion

This systematic scoping review forwards an evidence-based framework to guide a CNEP-IPT program. At the same time, more research into the training and assessment methods of mentors, near peers and mentees, the dynamics of mentoring interactions and the longitudinal support of the mentoring relationships and programs should be carried out.
Can a multitiered copayment system affect people’s healthcare-seeking behavior? A case study of Wenzhou, China
Authors: Ge Lizheng , Zhang Xiangyang , Huang Yunyun , Xu Tingke , Zhao Qianru , Zhu Tingting , Pan Jingye , Chen Chun
Published: May 2022

Background

Facilitating the primary health care (PHC) system and maintaining people’s reasonable healthcare-seeking behavior are key to establishing a sustainable healthcare system. China has employed a multitiered copayment system/medical insurance differentiated payment policies to incentivize the public to utilize PHC services through its hierarchical medical care system; however, most people still prefer visiting tertiary care hospitals. We question whether the quality gap in healthcare services reduces the effect of the multitiered copayment system, which is considered an important factor in the lack of reform in the Chinese healthcare system. Thus, we explore the effect and influencing factors of the multitiered copayment system that drives primary healthcare-seeking behavior under the current situation with a large quality gap. We also consider the hypothetical situation of a reduced gap in the future.

Methods

This study used the hypothetical quality improvement scenario to elicit people’s hypothetical behaviors, and a multistage stratified cluster random sampling method. This preliminary study was conducted in 2016 using 1829 individuals from four regions of Wenzhou in Zhejiang Province: Ouhai, Ruian, Yongjia, and Taishun. A descriptive statistical analysis, chi-square analysis, Fisher’s exact test, and multinomial logistic regression model were performed to introduce the effect of the multitiered copayment system, and to explore the factors affecting the selection of PHC institutions at pre- and post-change phases.

Result

The results show that compared with the large quality gap phase, the number of respondents who believed the multitiered copayment system had an effect on their selection of PHC institutions after the equalization of healthcare services quality increased threefold (from 14.0% to 50.8%). Moreover, the main determinants in people’s selection of PHC institutions changed from age and needs variables (self-rated health status) to age, needs variables (self-rated health status) and enabling variables (distance to a medical care facility).

Conclusion

The results indicate limited initial effects of the multitiered copayment system. However, they become more pronounced after the equalization of healthcare services quality. This study confirms that changes in the quality gap in healthcare services influence the effect of the multitiered copayment system. Hence, reducing this gap can help achieve the intended outcome of the tiered healthcare insurance schedule.
Association between circulating vitamin E and ten common cancers: evidence from large-scale Mendelian randomization analysis and a longitudinal cohort study
Authors: Xin Junyi , Jiang Xia , Ben Shuai , Yuan Qianyu , Su Li , Zhang Zhengdong , Christiani David C. , Du Mulong , Wang Meilin
Published: May 2022

Background

The association between vitamin E and cancer risk has been widely investigated by observational studies, but the findings remain inconclusive. Here, we aimed to evaluate the causal effect of circulating vitamin E on the risk of ten common cancers, including bladder, breast, colorectal, esophagus, lung, oral and pharynx, ovarian, pancreatic, prostate, and kidney cancer.

Methods

A Mendelian randomization (MR) analytic framework was applied to data from a cancer-specific genome-wide association study (GWAS) comprising a total of 297,699 cancer cases and 304,736 controls of European ancestry. Three genetic instrumental variables associated with circulating vitamin E were selected. Summary statistic-based methods of inverse variance weighting (IVW) and likelihood-based approach, as well as the individual genotyping-based method of genetic risk score (GRS) were used. Multivariable IVW analysis was further performed to control for potential confounding effects. Furthermore, the UK Biobank cohort was used as external validation, supporting 355,543 European participants (incident cases ranged from 437 for ovarian cancer to 4882 for prostate cancer) for GRS-based estimation of circulating vitamin E, accompanied by a one-sample MR analysis of dietary vitamin E intake underlying the time-to-event analytic framework.

Results

Specific to cancer GWAS, we found that circulating vitamin E was significantly associated with increased bladder cancer risk (odds ratios [OR]IVW = 6.23, PIVW = 3.05×10-3) but decreased breast cancer risk (ORIVW = 0.68, PIVW = 8.19×10-3); however, the significance of breast cancer was dampened (Pmultivariable IVW > 0.05) in the subsequent multivariable MR analysis. In the validation stage of the UK Biobank cohort, we did not replicate convincing causal effects of genetically predicted circulating vitamin E concentrations and dietary vitamin E intake on the risk of ten cancers.

Conclusions

This large-scale population study upon data from cancer-specific GWAS and a longitudinal biobank cohort indicates plausible non-causal associations between circulating vitamin E and ten common cancers in the European populations. Further studies regarding ancestral diversity are warranted to validate such causal associations.
Evaluating agreement between bodies of evidence from randomized controlled trials and cohort studies in medical research: a meta-epidemiological study
Authors: Bröckelmann Nils , Balduzzi Sara , Harms Louisa , Beyerbach Jessica , Petropoulou Maria , Kubiak Charlotte , Wolkewitz Martin , Meerpohl Joerg J. , Schwingshackl Lukas
Published: May 2022

Background

Randomized controlled trials (RCTs) and cohort studies are the most common study design types used to assess the treatment effects of medical interventions. To evaluate the agreement of effect estimates between bodies of evidence (BoE) from randomized controlled trials (RCTs) and cohort studies and to identify factors associated with disagreement.

Methods

Systematic reviews were published in the 13 medical journals with the highest impact factor identified through a MEDLINE search. BoE-pairs from RCTs and cohort studies with the same medical research question were included. We rated the similarity of PI/ECO (Population, Intervention/Exposure, Comparison, Outcome) between BoE from RCTs and cohort studies. The agreement of effect estimates across BoE was analyzed by pooling ratio of ratios (RoR) for binary outcomes and difference of mean differences for continuous outcomes. We performed subgroup analyses to explore factors associated with disagreements.

Results

One hundred twenty-nine BoE pairs from 64 systematic reviews were included. PI/ECO-similarity degree was moderate: two BoE pairs were rated as “more or less identical”; 90 were rated as “similar but not identical” and 37 as only “broadly similar”. For binary outcomes, the pooled RoR was 1.04 (95% CI 0.97–1.11) with considerable statistical heterogeneity. For continuous outcomes, differences were small. In subgroup analyses, degree of PI/ECO-similarity, type of intervention, and type of outcome, the pooled RoR indicated that on average, differences between both BoE were small. Subgroup analysis by degree of PI/ECO-similarity revealed high statistical heterogeneity and wide prediction intervals across PI/ECO-dissimilar BoE pairs.

Conclusions

On average, the pooled effect estimates between RCTs and cohort studies did not differ. Statistical heterogeneity and wide prediction intervals were mainly driven by PI/ECO-dissimilarities (i.e., clinical heterogeneity) and cohort studies. The potential influence of risk of bias and certainty of the evidence on differences of effect estimates between RCTs and cohort studies needs to be explored in upcoming meta-epidemiological studies.
The correlation between promoter hypermethylation of VDR, CLDN, and CasR genes and recurrent stone formation
Authors: Khatami Fatemeh , Gorji Alireza , Khoshchehreh Mahdi , Mashhadi Rahil , Pishkuhi Mahin Ahmadi , Khajavi Alireza , Shabestari Alireza Namazi , Aghamir Seyed Mohammad Kazem
Published: May 2022

Objectives

Recurrent Kidney stone formation is a main medical problem imposing a significant burden on both healthcare and the economy worldwide. Environmental and genetic factors have been linked to a bigger risk of kidney stone formation. We aim to assess the role of methylation on recurrent stone formation in three target genes.

Methods

We aimed to check the association between promoter hypermethylation vitamin D receptor (VDR), calcium-sensing receptor (CaSR), and claudin 14 (CLDN14) genes in recurrent kidney stones. We enrolled 30 consecutive recurrent kidney stone formers (age 18–60 years) (cases) and 30 age and gender-matched controls.3. To identify promoter methylation, two target regions from each candidate gene were bisulfited after blood collection and DNA extraction. Methylation quantification was done through methylation-specific high resolution melting (MS-HRM).

Results

The mean age of the patients and controls (mean ± SD) was 49.58 ± 14.23 years and BMI 36.12 ± 2.72. The methylation status in all six target regions was meaningfully different between the stone-former group and controls when methylation was considered in three clusters of unmethylated, methylated, and hypermethylated. A higher effect in VDR and CLDN was observed compare to CasR (p-value < 0.001, and < 0.005 versus p-value < 0.256).

Conclusions

Methylation as an important epigenetic mechanism should be considered more in recurrent stone formations. Promoter hypermethylation of VRD and CLDN genes may have an essential role in recurrent kidney stones formations.
Consumption of flavonoids and risk of hormone-related cancers: a systematic review and meta-analysis of observational studies
Authors: Liu Fubin , Peng Yu , Qiao Yating , Huang Yubei , Song Fengju , Zhang Ming , Song Fangfang
Published: May 2022

Background

Flavonoids seem to have hormone-like and anti-hormone properties so that the consumption of flavonoids may have potential effects on hormone-related cancers (HRCs), but the findings have been inconsistent so far. This meta-analysis was aimed to explore the association between flavonoids intake and HRCs risk among observational studies.

Methods

Qualified articles, published on PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) from January 1999 to March 2022 and focused on relationships between flavonoids (total, subclass of and individual flavonoids) and HRCs (breast, ovarian, endometrial, thyroid, prostate and testicular cancer), were retrieved for pooled analysis. Random effects models were performed to calculate the pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Funnel plots and Begg’s/Egger’s test were used to evaluate the publication bias. Subgroup analyses and sensitivity analyses were conducted to explore the origins of heterogeneity.

Results

All included studies were rated as medium or high quality. Higher consumption of flavonols (OR = 0.85, 95% CI: 0.76–0.94), flavones (OR = 0.85, 95% CI: 0.77–0.95) and isoflavones (OR = 0.87, 95% CI: 0.82–0.92) was associated with a decreased risk of women-specific cancers (breast, ovarian and endometrial cancer), while the higher intake of total flavonoids was linked to a significantly elevated risk of prostate cancer (OR = 1.11, 95% CI: 1.02–1.21). A little evidence implied that thyroid cancer risk was augmented with the higher intake of flavones (OR = 1.24, 95% CI: 1.03–1.50) and flavanones (OR = 1.31, 95% CI: 1.09–1.57).

Conclusions

The present study suggests evidence that intake of total flavonoids, flavonols, flavones, flavanones, flavan-3-ols and isoflavones would be associated with a lower or higher risk of HRCs, which perhaps provides guidance for diet guidelines to a certain extent.

Trial registration

This protocol has been registered on PROSPERO with registration number CRD42020200720.
Advancing urban health equity in the United States in an age of health care gentrification: a framework and research agenda
Authors: Cole Helen V. S. , Franzosa Emily
Published: May 2022

Background

Access to health care has traditionally been conceptualized as a function of patient socio-demographic characteristics (i.e., age, race/ethnicity, education, health insurance status, etc.) and/or the system itself (i.e., payment structures, facility locations, etc.). However, these frameworks typically do not take into account the broader, dynamic context in which individuals live and in which health care systems function.

Purpose

The growth in market-driven health care in the U.S. alongside policies aimed at improving health care delivery and quality have spurred health system mergers and consolidations, a shift toward outpatient care, an increase in for-profit care, and the closure of less profitable facilities. These shifts in the type, location and delivery of health care services may provide increased access for some urban residents while excluding others, a phenomenon we term “health care gentrification.“ In this commentary, we frame access to health care in the United States in the context of neighborhood gentrification and a concurrent process of changes to the health care system itself.

Conclusions

We describe the concept of health care gentrification, and the complex ways in which both neighborhood gentrification and health care gentrification may lead to inequitable access to health care. We then present a framework for understanding health care gentrification as a function of dynamic and multi-level systems, and propose ways to build on existing models of health care access and social determinants of health to more effectively measure and address this phenomenon. Finally, we describe potential strategies applied researchers might investigate that could prevent or remediate the effects of health care gentrification in the United States.
Effect of bevacizumab combined with chemotherapy on SDF-1 and CXCR4 in epithelial ovarian cancer and its prognosis
Authors: Ma Chunyan
Published: May 2022

Background

The effect of bevacizumab combined with chemotherapy on the expression of stromal cell-derived factor-1 (SDF-1) and receptor CXCR4 in epithelial ovarian cancer tumor cells and its prognosis are unknown. Our work aimed to investigate the effect of chemotherapy +/− bevacizumab on these markers and the impact of this treatment modality in clinical outcomes.

Methods

Altogether 68 patients with epithelial ovarian cancer who were treated with chemotherapy in our hospital from June 2018 to June 2019 were selected. It was an open-labeled and controlled clinical trial (ethical approval no. 20180435). The patients were grouped according to their admission order. Patients treated with paclitaxel and carboplatin were included in group A, while patients treated with bevacizumab, paclitaxel, and carboplatin were included in group B. qRT-PCR was used to detect the changes of SDF-1 and CXCR4 before and after chemotherapy. Various clinical indicators of patients in the two groups were recorded to analyze the clinical efficacy, and safety of different treatment modalities and the prognosis of the two groups was analyzed.

Results

The relative expression of SDF-1 and CXCR4 was positively correlated with epithelial ovarian cancer stages (P<0.00). Together, SDF-1 and CXCR4 were positively correlated in epithelial ovarian cancer staging (P<0.001). SDF-1 and CXCR4 in both groups after chemotherapy were significantly decreased (P<0.001), and the downregulation of SDF-1 and CXCR4 expression in group B was significantly higher than that in group A after chemotherapy (P<0.001). No significant difference in the metastasis rates of the two groups before chemotherapy was observed (P>0.05), but the recurrence rate after 1 year was lower in group B than in group A (P<0.05).

Conclusion

Adding bevacizumab diminished the expression of related cancer markers SDF-1 and CXCR4 more than chemotherapy alone in patients with epithelial ovarian cancer. Furthermore, better rates of recurrence with no concerns regarding adverse drug reactions or quality of life were seen in bevacizumab plus chemotherapy group.
Small molecules of herbal origin for osteoarthritis treatment: in vitro and in vivo evidence
Authors: Zhang Penghui , Li Kaihu , Kamali Amir , Ziadlou Reihane , Ahmad Paras , Wang Xinluan , Richards R. Geoff , Alini Mauro , Basoli Valentina , Li Zhen , Grad Sibylle
Published: May 2022

Osteoarthritis (OA) is one of the most common musculoskeletal degenerative diseases and contributes to heavy socioeconomic burden. Current pharmacological and conventional non-pharmacological therapies aim at relieving the symptoms like pain and disability rather than modifying the underlying disease. Surgical treatment and ultimately joint replacement arthroplasty are indicated in advanced stages of OA. Since the underlying mechanisms of OA onset and progression have not been fully elucidated yet, the development of novel therapeutics to prevent, halt, or reverse the disease is laborious. Recently, small molecules of herbal origin have been reported to show potent anti-inflammatory, anti-catabolic, and anabolic effects, implying their potential for treatment of OA. Herein, the molecular mechanisms of these small molecules, their effect on physiological or pathological signaling pathways, the advancement of the extraction methods, and their potential clinical translation based on in vitro and in vivo evidence are comprehensively reviewed.