bluuebunny/crossref_metadata_2025 huggingface dataset:
CircWalk: a novel approach to predict CircRNA-disease association based on heterogeneous network representation learning
Authors: Kouhsar Morteza , Kashaninia Esra , Mardani Behnam , Rabiee Hamid R.
Published: August 2022

Background

Several types of RNA in the cell are usually involved in biological processes with multiple functions. Coding RNAs code for proteins while non-coding RNAs regulate gene expression. Some single-strand RNAs can create a circular shape via the back splicing process and convert into a new type called circular RNA (circRNA). circRNAs are among the essential non-coding RNAs in the cell that involve multiple disorders. One of the critical functions of circRNAs is to regulate the expression of other genes through sponging micro RNAs (miRNAs) in diseases. This mechanism, known as the competing endogenous RNA (ceRNA) hypothesis, and additional information obtained from biological datasets can be used by computational approaches to predict novel associations between disease and circRNAs.

Results

We applied multiple classifiers to validate the extracted features from the heterogeneous network and selected the most appropriate one based on some evaluation criteria. Then, the XGBoost is utilized in our pipeline to generate a novel approach, called CircWalk, to predict CircRNA-Disease associations. Our results demonstrate that CircWalk has reasonable accuracy and AUC compared with other state-of-the-art algorithms. We also use CircWalk to predict novel circRNAs associated with lung, gastric, and colorectal cancers as a case study. The results show that our approach can accurately detect novel circRNAs related to these diseases.

Conclusions

Considering the ceRNA hypothesis, we integrate multiple resources to construct a heterogeneous network from circRNAs, mRNAs, miRNAs, and diseases. Next, the DeepWalk algorithm is applied to the network to extract feature vectors for circRNAs and diseases. The extracted features are used to learn a classifier and generate a model to predict novel CircRNA-Disease associations. Our approach uses the concept of the ceRNA hypothesis and the miRNA sponge effect of circRNAs to predict their associations with diseases. Our results show that this outlook could help identify CircRNA-Disease associations more accurately.
Comprehensive analysis of RNA m6A methylation in pressure overload-induced cardiac hypertrophy
Authors: Li Weidong , Xing Chenxv , Bao Limeng , Han Shengna , Luo Tianxia , Wang Zhiju , Fan Hongkun
Published: August 2022

Aim

To analyze and compare the mRNA N6-methyladenosine modifications in transverse aortic constriction induced mice hearts and normal mice hearts.

Materials and methods

Colorimetric quantification was used to probe the changes in m6A modifications in the total RNA. The expression of m6A-related enzymes was analyzed via qRT-PCR and western blotting. RNA-seq and MeRIP-seq were performed to identify genes with differences in m6A modifications or expression in the transcriptome profile.

Results

Compared with the control group, the TAC group exhibited higher m6A methylation levels. FTO and WTAP were downregulated after TAC, while METTL3 was significantly downregulated at the protein level. MeRIP-seq revealed that 1179 m6A peaks were upmethylated and 733 m6A peaks were downmethylated, and biological analysis of these genes exhibited a strong relationship with heart function.

Conclusion

Our findings provide novel information regarding m6A modification and gene expression changes in cardiac hypertrophy, which may be fundamental for further research.
Patterns and trends of antibacterial treatment in patients with urinary tract infections, 2015–2019: an analysis of health insurance data
Authors: Schmiemann Guido , Hoffmann Falk , Hamprecht Axel , Jobski Kathrin
Published: August 2022

Background

Urinary tract infections are among the most common reason for encounter and subsequent antibiotic prescriptions. Due to the risk of collateral damage and increasing resistance rates, explicit recommendations against the use of fluoroquinolones like ciprofloxacin in uncomplicated urinary tract infections have been issued. However, to what extent these recommendations were followed and if there are relevant differences between the disciplines involved (general practitioners, urologists, paediatricians and gynaecologists) are unknown.

Methods

We used anonymized data from a local statutory health insurance (SHI) company, which covered about 38% of all SHI-insured persons in the federal state of Bremen, Germany between 2015—2019. Data included demographics, outpatient diagnoses and filled prescriptions on an individual level.

Results

One-year prevalence of urinary tract infections was 5.8% in 2015 (females: 9.2%, males: 2.5%). Of all 102,715 UTI cases, 78.6% referred to females and 21.4% to males, 6.0% of cases were younger than 18 years. In females, general practitioners were the most common diagnosing speciality (52.2%), followed by urologists (20.0%) and gynaecologists (16.1%). Overall, fluoroquinolones were most often prescribed (26.3%), followed by fosfomycin (16.1%) and the combination of sulfamethoxazole and trimethoprim (14.2%). Fluoroquinolones were most often prescribed by urologists and general practitioners, while gynaecologists preferred fosfomycin. During the study period, shares of fluoroquinolones decreased from 29.4% to 8.7% in females and from 45.9% to 22.3% in males.

Conclusions

Despite a clear trend toward a more guideline adherent prescription pattern, there is still room for improvement regarding the use of second-line antibiotics especially fluoroquinolones. The choice of antibiotics prescribed differs between specialities with higher uptake of guideline-recommended antibiotics by gynaecologists, mainly because of higher prescription shares of fosfomycin.
Inflammatory biomarkers and risk of breast cancer among young women in Latin America: a case-control study
Authors: Fontvieille Emma , His Mathilde , Biessy Carine , Navionis Anne-Sophie , Torres-Mejía Gabriela , Ángeles-Llerenas Angélica , Alvarado-Cabrero Isabel , Sánchez Gloria Inés , Navarro Edgar , Cortes Yorlany Rodas , Porras Carolina , Rodriguez Ana Cecilia , Garmendia Maria Luisa , Soto José Luis , Moyano Leonor , Porter Peggy L. , Lin Ming Gang , Guenthoer Jamie , Romieu Isabelle , Rinaldi Sabina ,   PRECAMA team, Tejeda Jenny , Lazcano María Felix , Franco Libia Zulema , Jaramillo Roberto , Angel Alberto , Ossa Carlos Andres , Arias William H. , Bedoya Gabriel , Cock-Rada Alicia , Echeverri Carolina , Herazo Fernando , Díaz-Yunez Israel , Hernández Angel , Cortes Bernal , Gonzalez Paula , Ocampo Rebecca , Guillen Diego , Loría Viviana , Vial Catalina , Diaz Lizette , Donato Elizabeth , Donn Thomas , Wirtala Kelly , Loucks Hailey
Published: August 2022

Background

Breast cancer incidence is increasing rapidly in Latin America, with a higher proportion of cases among young women than in developed countries. Studies have linked inflammation to breast cancer development, but data is limited in premenopausal women, especially in Latin America.

Methods

We investigated the associations between serum biomarkers of chronic inflammation (interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), leptin, adiponectin) and risk of premenopausal breast cancer among 453 cases and 453 matched, population-based controls from Chile, Colombia, Costa Rica, and Mexico. Odds ratios (OR) were estimated using conditional logistic regression models. Analyses were stratified by size and hormonal receptor status of the tumors.

Results

IL-6 (ORper standard deviation (SD) = 1.33 (1.11–1.60)) and TNF-α (ORper SD = 1.32 (1.11–1.58)) were positively associated with breast cancer risk in fully adjusted models. Evidence of heterogeneity by estrogen receptor (ER) status was observed for IL-8 (P-homogeneity = 0.05), with a positive association in ER-negative tumors only. IL-8 (P-homogeneity = 0.06) and TNF-α (P-homogeneity = 0.003) were positively associated with risk in the largest tumors, while for leptin (P-homogeneity = 0.003) a positive association was observed for the smallest tumors only.

Conclusions

The results of this study support the implication of chronic inflammation in breast cancer risk in young women in Latin America. Largest studies of prospective design are needed to confirm these findings in premenopausal women.
Bi-columnar locking plate fixation through a combined medial and lateral approach for the treatment of low transcondylar fractures of the distal humerus in the elderly
Authors: Park Sam-Guk , Seok Hyun-Gyu
Published: August 2022

Background

Low transcondylar fractures (LTFs) of the distal humerus are relatively uncommon elbow injuries in elderly patients after low-energy injuries. Although there is still debate regarding the method of fixation, several surgeons prefer bi-columnar fixation using pre-contoured locking plates. However, posterior approaches, which are usually used to perform the above procedure, have disadvantages, such as ulnar nerve neuropathy, damage to the extensor mechanism, and the need for general anesthesia. To solve these problems, the authors designed a combined medial and lateral approach. The purpose of this study was to present the outcomes of bi-columnar internal fixation through a combined medial and lateral approach for the treatment of LTFs of the distal humerus in the elderly. 

Methods

A total of 46 patients diagnosed with distal humeral fractures between May 2017 and April 2020 were included. Thirty patients were excluded, and 16 patients who underwent open reduction and internal fixation by the medial and lateral approach were selected. We carried out all the surgeries under brachial plexus anesthesia. The clinical outcomes were assessed based on the visual analog scale (VAS) score, Mayo elbow performance score (MEPS), disabilities of the arm, shoulder, and hand (DASH) score, and range of motion (ROM) of the elbow joint. Standardized radiographs were obtained at 3, 6, and 12 months after surgery and at the last follow-up visit to evaluate for bony union and to check for complications, such as ulnar nerve neuropathy and heterotopic ossification.

Results

The mean age was 81 years (range, 65–91 years). Bony union was achieved in 15 out of 16 patients. The mean VAS score was 2.1 (range, 0–6), the mean MEPS was 84.4 (range, 70–100), and the mean DASH score was 20.6 (range, 9.5–33.6). There were three complications including reduction loss, skin necrosis, and stiffness of the elbow. There was no ulnar nerve neuropathy. The post-operative ROM was 100 degrees or higher in all cases, which did not cause any impairment in daily life.

Conclusion

LTFs of the distal humerus in the elderly can yield satisfactory results with bi-columnar internal fixation through a combined medial and lateral approach.
Knowledge, practice and perceived barriers towards chemotherapy induced nausea and vomiting in prophylaxis guideline adherence among nurses in oncology units at selected hospitals, in Addis Ababa, Ethiopia, a cross-sectional study
Authors: Gebre Deneke , Murugan Rajalakshmi , Bizuwork Ketema , Wurjine Teshome Habte
Published: August 2022

Background

Chemotherapy-induced emesis can be prevented by the use of recommended guidelines for antiemetic regimens but a research study indicates that in Ethiopia the use of standard antiemetic drug guidelines is very limited.

Objectives

To assess knowledge, practice, and perceived barriers towards chemotherapy-induced nausea and vomiting in prophylaxis guideline adherence among nurses in oncology units.

Methods

A cross-sectional study design was conducted among 81 oncology nurses selected in the two public hospitals of Addis Ababa, from March 1 to 30, 2020. The study participants were selected by using the population census method from the source population of nurses in oncology units. Data has collected by using semi-structured questionnaires with the self-administrated method. Data were analyzed by using Statistical Package for the Social Sciences software version 24. Descriptive statistics and logistic regression including bivariate and multivariate were conducted to examine the association between independent and outcome variables. The level of significance was determined at a p-value < 0.05 and a 95% confidence interval.

Result

Seventy-nine nurses participated with a 96% of response rate. All participants were aged greater than 24 with a mean age of 28.8 ± 6 years and nearly two-thirds of the respondents (60.8%) were females. Nurses were not trained in chemotherapy-induced nausea and vomiting management shows 54.4%. nurses’ knowledge of chemotherapy-induced nausea and vomiting prophylaxis Guidelines was 78.5%. The means score of oncology nurses’ practice toward guideline recommendation was 41.8%. Knowledge of nurses associated with the use of chemotherapy-induced nausea and vomiting prophylaxis guideline recommendations working in the outpatient department, inpatient ward, and chemotherapy administration unit has a significant association with chemotherapy-induced nausea and vomiting management knowledge. In the multiple logistic regression analysis, nurses who have trained for chemotherapy-induced nausea and vomiting management were 1.64-fold more aware than those who were not trained.

Conclusion

The study reveals that nurses working in the oncology unit of the study hospitals have a poor practice of Chemotherapy-Induced Nausea and Vomiting. Therefore, recommended providing Training for the Nurses working in the oncology unit and encourage them to apply standard guidelines.
Nectin-4 promotes osteosarcoma progression and metastasis through activating PI3K/AKT/NF-κB signaling by down-regulation of miR-520c-3p
Authors: Liu Yongheng , Li Guanghao , Zhang Yan , Li Lili , Zhang Yanting , Huang Xiaoyu , Wei Xianfu , Zhou Peng , Liu Ming , zhao Gang , Feng Jinyan , Wang Guowen
Published: August 2022

Purpose

Nectin-4 is specifically up-regulated in various tumors, exert crucial effects on tumor occurrence and development. Nevertheless, the role and molecular mechanism of Nectin-4 in osteosarcoma (OS) are rarely studied.

Methods

The expression of Nectin-4 and its relationship with clinical characteristics of OS were investigated using OS clinical tissues, tissue microarrays, TCGA, and GEO databases. Moreover, the effect of Nectin-4 on cell growth and mobility was detected by CCK-8, colony formation, transwell, and wound-healing assays. The RT-qPCR, Western blotting, and luciferase reporter assays were performed to explore molecular mechanisms through which Nectin-4 mediates the expression of miR-520c-3p, thus modulating PI3K/AKT/NF-κB signaling. In vivo mice models constructed by subcutaneous transplantation and tail vein injection were used to validate the functional roles of Nectin-4 and miR-520c-3p.

Results

Nectin-4 displayed a higher expression in OS tumor tissues compared with normal tissues, and its overexpression was positively associated with tumor stage and metastasis in OS patients. Functionally, Nectin-4 enhanced OS cells growth and mobility in vitro. Mechanistically, Nectin-4 down-regulated the levels of miR-520c-3p that directly targeted AKT-1 and P65, thus leading to the stimulation of PI3K/AKT/NF-κB signaling. In addition, the expression of miR-520c-3p was apparently lower in OS tissues than in normal tissues, and its low expression was significantly related to tumor metastasis. Furthermore, ectopic expression of miR-520c-3p markedly blocked the effect of Nectin-4 on OS cell growth and mobility. Knockdown of Nectin-4 could suppress the tumorigenesis and metastasis in vivo, which could be remarkably reversed by miR-520c-3p silencing.

Conclusions

Nectin-4 as an oncogene can promote OS progression and metastasis by activating PI3K/AKT/NF-κB signaling via down-regulation of miR-520c-3p, which could represent a novel avenue for identifying a potential therapeutic target for improving patient outcomes.
The geospatial and conceptual configuration of the natural environment impacts the association with health outcomes and behavior in children and adolescents
Authors: Nigg Carina , Niessner Claudia , Burchartz Alexander , Woll Alexander , Schipperijn Jasper
Published: August 2022

Background

Studies investigating associations between natural environments and health outcomes or health behaviors in children and adolescents yielded heterogenous results to date. This may be the result of different geospatial configurations of the natural environment and confounding characteristics of the study population. Thus, we investigated how the relationship between the natural environment and mental health, muscular fitness, and physical activity varies depending on the geospatial configuration of nature and children’s and adolescents’ characteristics.

Methods

Data were derived from the German Motorik-Modul (MoMo) cohort study (2018–2020) that investigates physical activity, muscular fitness, and health parameters in a national sample of children and adolescents (N = 2843) between four and 17 years (Mage = 10.46 ± 3.49 years; 48.3% girls). Mental health was assessed via questionnaire, muscular fitness via standing long jump, and physical activity with 7-day accelerometer measurement. Using geographic information systems, land cover, and land use data, three different nature definitions were applied. Both circular buffers (100–1000 m) and street-network buffers (1000–5000 m) were created for each of the nature definitions. Associations were explored with linear regression models, and interaction analysis was used to investigate how those relationships vary by gender, age, and socio-economic status.

Results

The relationship between the three outcomes and the natural environment varied considerably depending on the nature definition, buffer size, and buffer type, as well as socio-demographic characteristics. Specifically, when comparing youth with a high socio-economic status to those with a medium socio-economic status, smaller circular buffer distances were related to less physical activity, but larger street-network buffer distances were related to greater mental health problems. Distinct relationships also occurred for youth with low socio-economic status in those relationships, with the pattern being less clear.

Conclusions

For future health research studies that investigate the role of the natural environment, we argue for the development of an a-priori model that integrates both geospatial considerations (nature definition, buffer type, and buffer size) and conceptual considerations (health outcome/behavior, sample characteristics) based on potentially underlying mechanisms that link the natural environment and the health outcome or behavior under investigation to theoretically underpin the geospatial configuration of the natural environment.
Injectable pH-responsive hydrogel for combinatorial chemoimmunotherapy tailored to the tumor microenvironment
Authors: Gu Jun , Zhao Gang , Yu Jiangkun , Xu Pei , Yan Jiabin , Jin Zhengshuai , Chen Sheng , Wang Yong , Zhang Leshuai W. , Wang Yangyun
Published: August 2022

Although combination chemoimmunotherapy shows promising clinical results for cancer treatment, this approach is largely restricted by variable objective response rate and severe systemic adverse effects of immunotherapeutic antibody and chemotherapeutic drugs. Therefore, an in situ-formed therapeutic silk-chitosan composite scaffold is fabricated in this study to allow local release of the chemotherapeutic drug doxorubicin (DOX) and JQ1 (small molecular inhibitor used for the extraterminal protein BRD4 and bromodomain) with control release kinetics. DOX-JQ1@Gel contains a pH-degradable group that releases therapeutics in a weak acidic tumor microenvironment. The released DOX could directly kill tumor cells or lead to immunogenic cell death, thereby triggering the response of antitumor immunity. Meanwhile, chemotherapy-triggered antigen release and JQ1-mediated PD-L1 checkpoint blockade cumulatively contribute to trigger the response of antitumor immunity. Finally, the DOX-JQ1@Gel is locally injected to evaluate its synergistic cancer therapeutic effect, which is expected to improve objective response rate of immunotherapy and minimize systemic side effects.

Graphical Abstract
Mechanisms of chemotherapeutic resistance and the application of targeted nanoparticles for enhanced chemotherapy in colorectal cancer
Authors: Guo Yu , Wang Min , Zou Yongbo , Jin Longhai , Zhao Zeyun , Liu Qi , Wang Shuang , Li Jiannan
Published: August 2022

Colorectal cancer is considered one of the major malignancies that threaten the lives and health of people around the world. Patients with CRC are prone to post-operative local recurrence or metastasis, and some patients are advanced at the time of diagnosis and have no chance for complete surgical resection. These factors make chemotherapy an indispensable and important tool in treating CRC. However, the complex composition of the tumor microenvironment and the interaction of cellular and interstitial components constitute a tumor tissue with high cell density, dense extracellular matrix, and high osmotic pressure, inevitably preventing chemotherapeutic drugs from entering and acting on tumor cells. As a result, a novel drug carrier system with targeted nanoparticles has been applied to tumor therapy. It can change the physicochemical properties of drugs, facilitate the crossing of drug molecules through physiological and pathological tissue barriers, and increase the local concentration of nanomedicines at lesion sites. In addition to improving drug efficacy, targeted nanoparticles also reduce side effects, enabling safer and more effective disease diagnosis and treatment and improving bioavailability. In this review, we discuss the mechanisms by which infiltrating cells and other stromal components of the tumor microenvironment comprise barriers to chemotherapy in colorectal cancer. The research and application of targeted nanoparticles in CRC treatment are also classified.
Mechanisms of action for stigma reduction among primary care providers following social contact with service users and aspirational figures in Nepal: an explanatory qualitative design
Authors: Kaiser Bonnie N. , Gurung Dristy , Rai Sauharda , Bhardwaj Anvita , Dhakal Manoj , Cafaro Cori L. , Sikkema Kathleen J. , Lund Crick , Patel Vikram , Jordans Mark J. D. , Luitel Nagendra P. , Kohrt Brandon A.
Published: August 2022

Background

There are increasing initiatives to reduce mental illness stigma among primary care providers (PCPs) being trained in mental health services. However, there is a gap in understanding how stigma reduction initiatives for PCPs produce changes in attitudes and clinical practices. We conducted a pilot randomized controlled trial of a stigma reduction intervention in Nepal: REducing Stigma among HealthcAre Providers (RESHAPE). In a previous analysis of this pilot, we described differences in stigmatizing attitudes and clinical behaviors between PCPs receiving a standard mental health training (mental health Gap Action Program, mhGAP) vs. those receiving an mhGAP plus RESHAPE training. The goal of this analysis is to use qualitative interview data to explain the quantitative differences in stigma outcomes identified between the trial arms.

Methods

PCPs were randomized to either standard mental health training using mhGAP led by mental health specialists or the experimental condition (RESHAPE) in which service users living with mental illness shared photographic recovery narratives and participated in facilitated social contact. Qualitative interviews were conducted with PCPs five months post-training (n = 8, standard mhGAP training; n = 20, RESHAPE). Stigmatizing attitudes and clinical practices before and after training were qualitatively explored to identify mechanisms of change.

Results

PCPs in both training arms described changes in knowledge, skills, and confidence in providing mental healthcare. PCPs in both arms described a positive feedback loop, in which discussing mental health with patients encouraged more patients to seek treatment and open up about their illness, which demonstrated for PCPs that mental illness can be treated and boosted their clinical confidence. Importantly, PCPs in the RESHAPE arm were more likely to describe a willingness to treat mental health patients and attributed this in part to social contact with service users during the training.

Conclusions

Our qualitative research identified testable mechanisms of action for stigma reduction and improving clinical behavior: specifically, recovery stories from service users and social engagement led to greater willingness to engage with patients about mental illness, triggering a feedback loop of more positive experiences with patients who benefit from mental healthcare, which further reinforces willingness to deliver mental healthcare.

Trial registration ClinicalTrials.gov identifier, NCT02793271
Estimation of the impact of three different bioinformatic pipelines on sheep nemabiome analysis
Authors: Baltrušis Paulius , Halvarsson Peter , Höglund Johan
Published: August 2022

Background

Next-generation sequencing (NGS) has provided an alternative strategy to study the composition of nematode communities with increased resolution and sensitivity. However, the handling and processing of gigabytes worth of amplicon sequence data produced by an NGS platform is still a major hurdle, limiting the use and adoption of faster and more convenient analysis software.

Methods

In total 32 paired, fecal samples from Swedish sheep flocks were cultured and the larvae subsequently harvested subjected to internal transcribed spacer 2 (ITS2) amplicon sequencing using the PacBio platform. Samples were analyzed with three different bioinformatic pipelines, i.e. the DADA2, Mothur and SCATA pipelines, to determine species composition and richness.

Results

For the the major species tested in this study (Haemonchus contortus, Teladorsagia circumcinta and Trichostrongylus colubriformis) neither relative abundances nor species diversity differed significantly between the three pipelines, effectively showing that all three analysis pipelines, although different in their approaches, yield nearly identical outcomes. In addition, the samples analyzed here had especially high frequencies of H. contortus (90–95% across the three pipelines) both before and after sample treatment, followed by T. circumcinta (3.5–4%). This shows that H. contortus is the parasite of primary importance in contemporary Swedish sheep farms struggling with anthelmintic resistance. Finally, although on average a significant reduction in egg counts was achieved post-treatment, no significant shifts in major species relative frequencies occurred, indicating highly rigid community structures at sheep farms where anthelmintic resistance has been reported.

Conclusions

The findings presented here further contribute to the development and application of NGS technology to study nemabiome compositions in sheep, in addition to expanding our understanding about the most recent changes in parasite species abundances from Swedish sheep farms struggling with anthelmintic resistance.

Graphical Abstract
Limited evidence for blood eQTLs in human sexual dimorphism
Authors: Porcu Eleonora , Claringbould Annique , Weihs Antoine , Lepik Kaido ,   BIOS Consortium, Richardson Tom G. , Völker Uwe , Santoni Federico A. , Teumer Alexander , Franke Lude , Reymond Alexandre , Kutalik Zoltán
Published: August 2022

Background

The genetic underpinning of sexual dimorphism is very poorly understood. The prevalence of many diseases differs between men and women, which could be in part caused by sex-specific genetic effects. Nevertheless, only a few published genome-wide association studies (GWAS) were performed separately in each sex. The reported enrichment of expression quantitative trait loci (eQTLs) among GWAS-associated SNPs suggests a potential role of sex-specific eQTLs in the sex-specific genetic mechanism underlying complex traits.

Methods

To explore this scenario, we combined sex-specific whole blood RNA-seq eQTL data from 3447 European individuals included in BIOS Consortium and GWAS data from UK Biobank. Next, to test the presence of sex-biased causal effect of gene expression on complex traits, we performed sex-specific transcriptome-wide Mendelian randomization (TWMR) analyses on the two most sexually dimorphic traits, waist-to-hip ratio (WHR) and testosterone levels. Finally, we performed power analysis to calculate the GWAS sample size needed to observe sex-specific trait associations driven by sex-biased eQTLs.

Results

Among 9 million SNP-gene pairs showing sex-combined associations, we found 18 genes with significant sex-biased cis-eQTLs (FDR 5%). Our phenome-wide association study of the 18 top sex-biased eQTLs on >700 traits unraveled that these eQTLs do not systematically translate into detectable sex-biased trait-associations. In addition, we observed that sex-specific causal effects of gene expression on complex traits are not driven by sex-specific eQTLs. Power analyses using real eQTL- and causal-effect sizes showed that millions of samples would be necessary to observe sex-biased trait associations that are fully driven by sex-biased cis-eQTLs. Compensatory effects may further hamper their detection.

Conclusions

Our results suggest that sex-specific eQTLs in whole blood do not translate to detectable sex-specific trait associations of complex diseases, and vice versa that the observed sex-specific trait associations cannot be explained by sex-specific eQTLs.
Emotional upheaval, the essence of anticipatory grief in mothers of children with life threatening illnesses: a qualitative study
Authors: Najafi Kazem , Shirinabadi Farahani Azam , Rassouli Maryam , Alavi Majd Hamid , Karami Maryam
Published: August 2022

Introduction

Life-threatening illnesses in childhood are considered a crisis for the whole family, especially for the mother, which leads to experiencing different degrees of grief and emotional-behavioral problems.

Objective

The present study is conducted with the aim of explaining the concept of anticipatory grief from the perspective of the mothers of the children with life-threatening illnesses.

Methods

This qualitative study is part of a sequential exploratory research for model development in the field of anticipatory grief, which was conducted using conventional content analysis method. The data were collected through in-depth semi-structured interviews with 19 mothers of the children with life-threatening illnesses living in Shiraz and Tehran, who were selected through purposive sampling with maximum variation. When data saturation were achieved, the data were codified by MAXQDA-10 software and analyzed using Graneheim and Lundman’s approach.

Findings

Data analysis resulted in the identification of 8 subcategories including shock, irritability, fear of losing, feeling guilty, uncertainty, hopelessness, loneliness and isolation, and mourning without a coffin, all forming the major theme emotional upheaval.

Discussion and conclusion

As the result of being in a situation of imminent and possible loss of her child, the mother experiences different responses of sadness and sorrow and suffers the consequences the core of which is consisted of emotional upheaval. Therefore, by explaining the behaviors related to anticipatory grief, efficient and effective interventions can be designed to improve coping among this group of mothers.
Evaluation of mood disorder questionnaire positivity and associated factors in a population-based screening study
Authors: Konuk Numan , Karaahmet Elif , Angın Ülkem , Kılıç Alperen , Kökrek Zekeriya
Published: August 2022

The Mood Disorders Questionnaire (MDQ) is a 3-item scale that is frequently used in bipolar disorders (BD) screening and questions the symptoms of BD, its effect on functionality, and the coexistence of symptoms. The aim of this study is to evaluate the prevalence of positive screening of the MDQ among general population and to investigate the associated risk factors.

In this cross-sectional study, the sample was randomly selected from household data to represent the city population. A total of 432 participants were asked to fill in MDQ, CAGE (cutting down, annoyance by criticism, guilty feeling, and eye-openers) questionnaire, which consists of four clinical interview questions proven to aid in the diagnosis of alcoholism, and clinical and sociodemographic data form.

The Cronbach’s alpha value of our current study was 0.813 for MDQ. The prevalence of MDQ positivity was found 7.6%. The estimated prevalence rate of bipolar disorders varied between 0.3 and 13.4% according to different cut-off values. Multivariate logistic regression models showed that the presence of possible alcohol addiction, shift work history, and body mass index (BMI) were statistically significant predictors of MDQ positivity.

The prevalence of MDQ positivity found is similar to studies in literature. Keeping in mind that psychometric properties of the MDQ, positive screen results should be cautiously interpreted due to the presence of other risk factors and comorbidities.
Immunoscore Is Prognostic in Low-Risk and High-Risk Stage III Colon Carcinomas Treated With Adjuvant Infusional Fluorouracil, Leucovorin, and Oxaliplatin in a Phase III Trial
Authors: Sinicrope Frank A. , Shi Qian , Catteau Aurelie , Poage Graham M. , Zemla Tyler J. , Mlecnik Bernhard , Benson Al B. , Gill Sharlene , Goldberg Richard M. , Kahlenberg Morton S. , Nair Suresh G. , Shields Anthony F. , Smyrk Thomas C. , Galon Jerome , Alberts Steven R.
Published: August 2022

PURPOSE

The recommended duration of adjuvant fluoropyrimidine and oxaliplatin chemotherapy for patients with stage III colon cancer is based on tumor classification into clinically low-risk (T1-3 N1) and high-risk (T4 or N2) groups. We determined whether Immunoscore can enhance prognostication within these risk groups.

MATERIALS AND METHODS

Patients with stage III colon carcinomas (N = 600) were randomly selected from the infusional fluorouracil, leucovorin, and oxaliplatin arm of adjuvant trial NCCTG N0147 (Alliance for Clinical Trials in Oncology). Tumors were evaluated for Immunoscore that quantifies CD3+ and CD8+ T-cell densities in the tumor center and invasive margin by digital image analysis. Disease-free survival (DFS) by Immunoscore was analyzed using a multivariable Cox regression model in each risk group with adjustment for covariates including KRAS, BRAF V600E, and mismatch repair status.

RESULTS

Of 559 cancers with Immunoscore data, 299 (53.5%) were classified as clinically low-risk (T1-3 N1) and 260 (46.5%) as clinically high-risk (T4 and/or N2). Among patients with low-risk tumors, those with Immunoscore-Low versus Immunoscore-High tumors had significantly worse 5-year DFS rates (77.5% v 91.8%; hazard ratio, 1.70; 95% CI, 1.03 to 2.79; P = .037). Among patients with high-risk tumors, those with Immunoscore-Low versus Immunoscore-High tumors also had significantly worse DFS (55.3% v 70.3%; hazard ratio, 1.65; 95% CI, 1.11 to 2.47; P = .013). Tumors that were low-risk/Immunoscore-Low had similar outcomes as did tumors that were high-risk/Immunoscore-High ( P = .174). Prognostication was significantly improved in multivariable models where Immunoscore was added to clinical risk parameters and limited biomarkers (likelihood ratio test P = .0003).

CONCLUSION

Immunoscore can refine patient prognosis beyond clinical risk group classification, suggesting its potential utility for adjuvant decision making.
Thyroid, Diet, and Alternative Approaches
Authors: Larsen Dana , Singh Sargun , Brito Maria
Published: August 2022

Background

Increasingly, patients are asking their physicians about the benefits of dietary and alternative approaches to manage their diseases, including thyroid disease. We seek to review the evidence behind several of the vitamins, minerals, complementary medicines, and elimination diets that patients are most commonly using for the treatment of thyroid disorders.

Several trace elements are essential to normal thyroid function, and their supplementation has been studied in various capacities. Iodine supplementation has been implemented on national scales through universal salt iodization with great success in preventing severe thyroid disease, but can conversely cause thyroid disorders when given in excess. Selenium and zinc supplementation has been found to be beneficial in specific populations with otherwise limited generalizability. Other minerals, such as vitamin B12, low-dose naltrexone, and ashwagandha root extract, have little to no evidence of any impact on thyroid disorders. Avoidance of gluten and dairy has positive impacts only in patients with concomitant sensitivities to those substances, likely by improving absorption of levothyroxine. Avoidance of cruciferous vegetables and soy has little proven benefit in patients with thyroid disorders.

Conclusion

While many patients are seeking to avoid conventional therapy and instead turn to alternative and dietary approaches to thyroid disease management, many of the most popular approaches have no proven benefit or have not been well studied. It is our responsibility to educate our patients about the evidence for or against benefit, potential harms, or dearth of knowledge behind these strategies.
A Historical Portrait of Female Economists' Coauthorship Networks
Authors: Hengel Erin , Phythian-Adams Sarah Louisa
Published: August 2022

This article describes how women have contributed to the research published in influential general interest journals between 1940 and 2019. The share of women published in these journals follows a U-shaped curve that troughs in the late 1970s—a decline possibly related to an increase in the number of papers being published as well as a rise in coauthoring. By the late 1970s and early 1980s, however, the share of women began increasing again, largely thanks to a rise in mixed-gendered papers. Coauthorship between women, on the other hand, was almost nonexistent until around 2010. A decade-by-decade comparison of men's and women's coauthorship networks suggests female-female networks in the most recent decade in our data (2010–19) roughly resemble male networks from earlier decades (1940–69) and highlight the key role prominent individuals play in network formation. We hypothesize that the recent growth in papers by female teams may signal that research by women collaborating with other women is receiving greater recognition in the field.
The Queen of the Social Sciences: The Reproduction of a [White] “Man's Field”
Authors: Cohen Jennifer
Published: August 2022

Economics reproduces itself as a [white] man's field through resistance to demographic and epistemic diversity. Although some resistance is expressed by anonymous individuals, they are neither the sole nor the primary source. Resistance is internal to the discipline; it is structural. It is present in the vertical organization of the profession, the seemingly neutral forms of evaluation that institutionalize gender bias, and the marginalization of certain topics and critical perspectives. Because resistance is structural, even if individuals do not discriminate, the discipline will remain resistant to diversity.

The conceptualization of work as paid employment alone reflects gender ideology and plays a key role in the devalorization of unpaid work—those who do it and research about it. Concepts and methods from feminist political economy link the orthodox conceptualization of work, and the value system underpinning it, to the experiences of women economists between 1970 and the present. I find that economics remains a “man's field” through structural resistance to women economists, through interpreting women's economic activities as marginal to the “real business” of economics, and by delegitimizing feminist research about those activities. The delegitimization of feminists' paid work as economists functionally devalues women's unpaid work in economic thought. Because economic thought is influential outside the economics discipline, the delegitimization of feminist economic research devalues women's unpaid work outside the discipline as well.

Efforts to “fix” structural resistance to diversity without addressing the devalorization of the gendered work required to reproduce people are likely to have limited impacts. They may contribute to demographic diversity, but demographic diversity will not automatically translate into theoretical diversity in a discipline that marginalizes critical thought. Diversity, equity, and inclusion efforts should ensure that nonwhite and nonmen economists have pathways to advancement with scope for academic freedom. This is especially necessary when their intellectual contributions challenge the value systems and the unequal power relations that economic orthodoxy reinforces.
Who Makes the City? Beijing's Urban Villages as Sites of Ideological Contestation
Authors: Hayward Jane , Jakimów Małgorzata
Published: August 2022

Inside Beijing are hundreds of urban villages. Originally farming villages, now engulfed by urban expansion, they persist due to China's segregated urban-rural property system. Inhabitants are often still classed as peasants, despite being inside the city. Since most have had their agricultural land requisitioned for urban construction, they instead build multiple extensions to their houses to rent to rural migrants seeking cheap accommodation. In some cases, village populations have increased tenfold as migrants have flooded in, causing cramped conditions and overloading village infrastructure. Urban villages have in recent years emerged as key sites of ideological and political contestation. For local officials and planners envisioning gleaming world cities brimming with advanced technology and highly skilled workers, these are dirty and backward “urban cancers,” enclaves of the “low-end population,” and obstacles to their visions of the city as embodiment of global modernity. An opposing set of scholars and policy makers view these villages as essential to city life, channels for low-cost labor to service urban elites, and gateways to modernity for those formerly excluded. Within the urban villages, groups of migrant-activists defy the statist vision of the city. Through cultural performances and visual representations, they struggle to promote an urban modernity in which they are included as active participants. This article explores how Beijing's urban villages constitute a key site of ideological contestation over what the city should be, and whom urban life is for.
The Dark Side of the Miracle: Spectacular and Precarious Accumulation in an Urban Village under Siege (A Photo Essay)
Authors: Lam Tong
Published: August 2022

In spite of their informal and substandard nature, Chinese urban villages are actually part of the infrastructure that institutionalizes and normalizes China's uneven development by providing cheap dormitory-style accommodations to the country's vast army of unskilled rural migrants who flock to cities as precarious laborers. This extended photo essay uses an urban village renewal project in the southern city Guangzhou to analyze the politics of eviction, demolition, resistance, and gentrification in light of the region's shift from low-value to high-tech industries. When urban villagers appropriated ideas of tradition, lineage, and socialist collectivism to fight against the government and the developer, their purpose was to acquire greater compensation and even symbolic capital in order to secure an urban middle-class future for themselves. In the process, however, they have further foreclosed the futures of many rural migrants whose survival in the city rely on cheap accommodation in these slum-like enclaves, even though survival in this context often implies dull and dead-end jobs with little prospect of social mobility. Drawing on the author's visual project called Where There Is No Room for Fiction, the selected photographs here provide a visual ethnographic account of the contested landscape of an urban village under siege. As well, these images explore the possibility of a critical aesthetics in order to engage the official vision of urban modernity that is saturated with spectacle and speculation.
Early Diagnosis and Surgical Intervention Within 3 Weeks From Symptom Onset Are Associated With Prolonged Survival of Patients With Glioblastoma
Authors: Kawauchi Daisuke , Ohno Makoto , Miyakita Yasuji , Takahashi Masamichi , Yanagisawa Shunsuke , Omura Takaki , Yoshida Akihiko , Kubo Yuko , Igaki Hiroshi , Ichimura Koichi , Narita Yoshitaka
Published: August 2022

BACKGROUND:

Glioblastoma (GBM) is a rapidly growing and most life-threatening malignant brain tumor. The significance of early treatment to the clinical outcomes of patients with GBM is unclear.

OBJECTIVE:

To determine whether early diagnosis and surgery improve the preoperative and postoperative Karnofsky performance status (KPS) and prognosis of patients with GBM.

METHODS:

Data of isocitrate dehydrogenase-wildtype patients with GBM treated at our institution between January 2010 and December 2019 were reviewed. Patients were classified into early or late diagnosis groups with a threshold of 14 days from initial symptoms. In addition, patients were divided into early, intermediate, and late surgery groups with thresholds of 21 and 35 days. Representative symptoms and patient prognoses were examined.

RESULTS:

Of 153 patients, 72 and 81 were classified into the early and late diagnosis groups. The median tumor volume was significantly smaller in the former group. The proportion of patients with preoperative KPS scores

90 was 48.6% and 29.6% in the early and late diagnosis groups (P = .016). The early, intermediate, and late surgery groups included 43, 24, and 86 patients. The median overall survival was significantly longer in the early surgery group than in the late surgery group (28.4 vs 18.7 months, P = .006). Multivariate analysis demonstrated that significant predictors of shorter survival included extent of tumor resection (partial or biopsy), preoperative and postoperative KPS

60, and O6-methylguanine-DNA-methyltransferase promoter status (unmethylated).

CONCLUSION:

Early diagnosis within 2 weeks and surgical interventions within 3 weeks from the symptom onset are associated with prolonged patient survival. Early GBM treatment will benefit patients with GBM.
Comparison of Fusion versus Nonunion After 4-Level and 5-Level Anterior Cervical Diskectomy and Fusion With Anterior Plate Fixation
Authors: Bakare Adewale A. , Smitherman Adam D. , Fontes Ricardo B. V. , O'Toole John E. , Deutsch Harel , Traynelis Vincent C.
Published: August 2022

BACKGROUND:

Nonunion remains a concern in multilevel anterior cervical discectomy and fusion (ACDF), yet there are limited data on nonunion after 4 to 5-level ACDF. In fact, the largest series on 4-level or 5-level ACDF focused specifically on the swallowing outcomes.

OBJECTIVE:

To assess nonunion after 4 to 5-level ACDF.

METHODS:

Forty-one patients treated with 4 to 5-level ACDF with minimum of 12-month radiographic follow-up were retrospectively reviewed. Nonunion was found in 25 patients (61%) and 42 levels (25%) and complete fusion in 16 (39%) patients and 126 levels (75%). The 2 groups were further compared.

RESULTS:

One-level nonunion was by far the most common pattern compared with multilevel nonunion. Nonunion occurred more frequently at the caudal than the cranial or middle segments (P < .0001). There were significantly more subsidence (P < .0001) and screw fractures/pullouts (P < .0001) in the nonunion compared with the fusion group. The symptomatic patients were significantly younger than the asymptomatic patients (P = .044). The symptomatic levels were significantly more than asymptomatic levels (P = .048). Equal proportion of patients implanted with allograft and polyetheretherketone had nonunion. However, there were markedly more nonunion than fused levels with allograft and more fused than nonunion levels with polyetheretherketone (P = .023). The reoperation rate was 24.4% and mostly due to nonunion. There were no reoperations within 90 days of the primary surgery.

CONCLUSION:

The nonunion rate for 4-level and 5-level ACDF may be higher than previously reported. Symptomatic nonunion remains a major reason for reoperation after multilevel ACDF. Baseline characteristics that negatively affect fusion may be obviated by careful patient selection.