bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractColorectal 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

Abstract
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

Abstract
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

Abstract
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

AbstractIntroductionLife-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.ObjectiveThe 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.MethodsThis 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.FindingsData 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 conclusionAs 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

AbstractThe 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

Abstract

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.

Summary
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

Abstract
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

Abstract
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

AbstractInside 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

AbstractIn 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.