bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping the effectiveness of integrating mental health in HIV programs: a scoping review
Authors: Conteh Ndeshiteelela K , Latona Ashley , Mahomed Ozayr
Published: April 2023

Introduction

Mental health and substance abuse issues are increasing among HIV-positive people, and it negatively impacts health outcomes like engagement, retention in HIV care, and adherence to ART. Thus, national ART programs must include mental health management. The scoping review sought to map evidence on the efficacy of combining HIV and mental health care.

Methods

The Arksey and O’Malley methodological framework was used to map the existing research on integrating HIV and mental health services to identify knowledge gaps. Two independent reviewers screened articles for inclusion. Studies on HIV-mental health integration were considered. We searched numerous sources, extracted data, and summarized publications by integration model and patient outcomes.

Results

Twenty-nine articles met the criteria for this scoping review. Twenty-three studies were from high-income countries, with only six from low and middle-income countries in Africa (Zimbabwe 1, Uganda 3, South Africa 1, and Tanzania 1). Most of the literature discussed single-facility integration although multi-facility and integrated care through a case manager was researched as well. There was a reduction in depression, alcohol use, increased social function, decreased self-reported stigma, decreased psychiatric symptoms, and improved mood in PLHIV who received cognitive behavioral therapy in settings implementing integrated care. When providing integrated mental health services to PLHIV, healthcare workers reported feeling more comfortable discussing mental illness. Personnel in the mental health field reported less stigma and increased PLHIV referrals for mental health services due to integrated HIV and mental health care.

Conclusion

According to the research, integrating mental health services into HIV care improves the diagnosis and treatment of depression and other mental disorders related to substance abuse in PLHIV.
Insurance status and traumatized patients’ outcomes: a report from the national trauma registry of Iran
Authors: Isazadehfar Khatereh , Salamati Payman , Zafarghandi Mohammad Reza , Rahimi-Movaghar Vafa , Khormali Moein , Baigi Vali
Published: April 2023

Background

Trauma care is one of the most expensive medical procedures that is significantly affected by factors like insurance status. Providing medical care to injured patients has a significant impact on patients’ prognosis. This study examined whether insurance status was associated with different outcomes, including hospital length of stay (HLOS), mortality, and Intensive Care Unit (ICU) admission.

Methods

This prospective study analyzed the data of traumatized patients who had been registered in the National Trauma Registry of Iran (NTRI), and hospitalized at Sina Hospital, Tehran, Iran, from March 22, 2016, to February 8, 2021. Given the type of insurance, the insured patients were classified as basic, road traffic, and foreign nationality. The outcomes of in-hospital death, ICU admission, and HLOS between insured and uninsured patients, and then different insurance statuses, were compared using regression models.

Result

A total of 5014 patients were included in the study. 49% of patients (n = 2458) had road traffic insurance, 35.2% (n = 1766) basic insurance, 10.5% (n = 528) were uninsured, and 5.2% (n = 262) had foreign nationality insurance. The mean age of patients with basic, road traffic insurance, foreign nationality, and uninsured patients was 45.2 (SD = 22.3), 37.8 (SD = 15.8), 27.8 (SD = 13.3), and 32.4 (SD = 11.9) years, respectively. There was a statistically significant association between insurance status and mean age. Based on these results, the mean age of patients with basic insurance was higher than other groups (p < 0.001). Additionally, 85.6% of the patients were male, with male to female ratio of 9.64 in road traffic insurance, 2.99 in basic insurance, 14.4 in foreign nationality, and 16 in uninsured patients. There was no statistically significant difference between in-hospital mortality in insured and uninsured patients, 98 (2.3%) vs. 12 (2.3%), respectively. The odds of in-hospital mortality in uninsured patients were 1.04 times the odds of in-hospital death in insured patients [Crude OR: 1.04, 95%CI: 0.58 to 1.90]. Multiple logistic regression showed that after adjusting for age, sex, ISS, and Cause of trauma, the odds of in-hospital death in uninsured patients were 2.97 times the odds of in-hospital death in insured patients [adjusted OR: 2.97, 95%CI: 1.43 to 6.21].

Conclusion

This study shows that having insurance can change the ICU admission, death, and HLOS in traumatized patients. The results of this study can provide essential data for national health policy for minimizing the disparities among different insurance statuses and proper use of medical resources.
Barriers to breast and cervical cancer screening uptake among Black, Asian, and Minority Ethnic women in the United Kingdom: evidence from a mixed-methods systematic review
Authors: Bolarinwa Obasanjo Afolabi , Holt Nicole
Published: April 2023

Background

Cancer is currently the leading cause of mortality globally, with new cancer cases estimated at 19.3 million and almost 10 million deaths in 2020. Specifically, breast and cervical cancer incidence and mortality prevalence among women of the minority group or marginalised populations in Europe have continued to be a public health concern due to the low uptake of cancer screening. Thus, this study utilised a mixed-method systematic review to identify barriers to breast and cervical screening uptake among Black, Asian, and Minority Ethnic women in the United Kingdom.

Methods

Databases including PubMed, CINAHL, British Nursing Index, Web of Science, EMBASE, and Scopus databases, were systematically searched for studies on barriers to breast and cervical screening uptake among Black, Asian, and Minority Ethnic women in the United Kingdom published in English between January 2010 to July 2022. This mixed-method systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in reporting the included studies’ results. The cluster mapping approach was used to identify and classify the barriers into themes.

Results

Thirteen eligible studies were included in this current review. Seven of the thirteen studies used quantitative cross-sectional research design, while six used qualitative cross-sectional research design. These studies were conducted across the United Kingdom. Five themes were developed from the cluster mapping, and thirty-four sub-theme barriers to the uptake of breast and cervical cancer screening among Black, Asian, and Minority Ethnic women in the United Kingdom were identified. The developed themes in relation to the barriers include; socio-demographic characteristics, health service delivery, cultural, religious & language, the gap in knowledge & awareness, and emotional, sexual & family support.

Conclusion

The study concluded that barriers in socio-demographic characteristics, health service delivery, cultural, religious and language, the gap in knowledge & awareness, and emotional, sexual & family support were identified as non-uptake of breast and cervical cancer screening among Black, Asian, and Minority Ethnic women in the United Kingdom. Reducing or eliminating these barriers would improve the benefits of timely breast and cervical cancer screening in the United Kingdom.
Prevalence, trends and associated factors of malaria in the Shai-Osudoku District Hospital, Ghana
Authors: Tetteh Jessica Ashiakie , Djissem Patrick Elorm , Manyeh Alfred Kwesi
Published: April 2023

Background

Even though malaria is easily preventable and treatable, it continues to have a devastating impact on people’s health and livelihoods around the world. Sub-Saharan Africa carries a disproportionately high share of the global malaria burden. This study seeks to assess the prevalence, trends and factors associated with malaria in the Shai-Osudoku District Hospital, Ghana.

Methods

A cross-sectional study was conducted to determine the prevalence, trend, and factors associated with malaria in the Shai-Osudoku District Hospital; a 10-month secondary data was extracted from February to November 2020. The extracted data were entered into Epi Data version 6 and analysed using STATA version 16. Descriptive analysis was performed to determine the prevalence, trend and socio-demographic characteristics of study participants. Simple logistic regression at a 95% confidence level was performed to investigate socio-demographic factors associated with malaria infection. Tables and charts with summary statistics were used to present the results.

Results

Secondary data from 3896 individuals were included in the study. The age of the participants range from 0.8 to 101 years with a mean age of 32.5. The estimated prevalence of malaria during the study period is 20.9%. A majority (79.1%) of the participants who presented signs and symptoms of malaria were negative after testing. The prevalence of malaria cases increased progressively from 6.7 to 55.4% across the ten months. The simple logistic regression at a 95% confidence level revealed that age group, sex, residential status, religion, occupation and marital status were statistically significantly associated with malaria. The results shows that persons who tested positive for malaria were mostly treated with artemether-lumefantrine (46.1%), some malaria positive cases were given artesunate injection (11.6%), dihydroartemisinin-piperaquine (16.2%) and oral artemether-lumefantrine (6.5%). Surprisingly 19.6% of the malaria-positive cases were not given any form of malaria medication.

Conclusion

Factors found to influence malaria infection in the Shai-Osudoku District Hospital include participant’s age, sex, residential status, religious affiliation occupation and marital status. The findings of this study showed that malaria remains a serious public health problem in the Shai Osudoku District Hospital. The information obtained from this study can guide the implementation of malaria prevention, control and elimination strategies in Ghana.
A novel protein encoded by circINSIG1 reprograms cholesterol metabolism by promoting the ubiquitin-dependent degradation of INSIG1 in colorectal cancer
Authors: Xiong Li , Liu Hua-shan , Zhou Chi , Yang Xin , Huang Liang , Jie Hai-qing , Zeng Zi-wei , Zheng Xiao-bin , Li Wen-xin , Liu Zhan-zhen , Kang Liang , Liang Zhen-xing
Published: April 2023

Background

Hypoxia is a hallmark of solid tumors and leads to the metabolic reprogramming of cancer cells. The role of epigenetic regulation between hypoxia and aberrant cholesterol metabolism in colorectal cancer (CRC) remains elusive.

Methods

Hypoxia-responsive circular RNAs (circRNAs) were identified by high throughput RNA sequencing between CRC cells cultured under normoxia or hypoxia. The protein-coding potential of circINSIG1 was identified by polysome profiling and LC–MS. The function of circINSIG1 was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses.

Results

A novel hypoxia-responsive circRNA named circINSIG1 was identified, which was upregulated in CRC tissues and correlated with advanced clinical stages and poor survival. Mechanistically, circINSIG1 encoded a 121 amino acid protein circINSIG1-121 to promote K48-linked ubiquitination of the critical cholesterol metabolism regulator INSIG1 at lysine 156 and 158 by recruiting CUL5-ASB6 complex, a ubiquitin E3 ligase complex, thereby inducing cholesterol biosynthesis to promote CRC proliferation and metastasis. The orthotopic xenograft tumor models and patient-derived xenograft models further identified the role of circINSIG1 in CRC progression and potential therapeutic target of CRC.

Conclusions

circINSIG1 presents an epigenetic mechanism which provides insights into the crosstalk between hypoxia and cholesterol metabolism, and provides a promising therapeutic target for the treatment of CRC.
The “Great Debate” at Immunotherapy Bridge 2022, Naples, November 30th–December 1st, 2022
Authors: Ascierto Paolo A. , Brentjens Renier , Khleif Samir N. , Odunsi Kunle , Rezvani Katayoun , Ruella Marco , Sullivan Ryan J. , Fox Bernard A. , Puzanov Igor
Published: April 2023

The 2022 Immunotherapy Bridge congress (November 30–December 1, Naples, Italy) featured a Great Debate session which addressed three contemporary topics in the field of immunotherapy. The debates included counterpoint views from leading experts and considered whether adoptive cell therapy (ACT) has a role in the treatment of solid tumors, the use of peripheral/blood biomarkers versus tumor microenvironment biomarkers for cancer immunotherapy and the role of chimeric antigen receptor T cell versus natural killer cell therapy. As is the tradition in the Immunotherapy Bridge Great Debates, speakers are invited by the meeting Chairs to express one side of the assigned debate and the opinions given may not fully reflect their own personal views. Audiences voted in favour of either side of the topic both before and after each debate.
Network pharmacology identifies fisetin as a treatment for osteoporosis that activates the Wnt/β-catenin signaling pathway in BMSCs
Authors: Liang Guihong , Zhao Jinlong , Pan Jianke , Yang Yuan , Dou Yaoxing , Yang Weiyi , Zeng Lingfeng , Liu Jun
Published: April 2023

Background

Although fisetin may exist widely in many natural herbs, its anti-OP mechanism is still unclear. The aim of this study is to explore the molecular anti-osteoporosis (OP) mechanism of fisetin based on network pharmacology and cell experiments.

Methods

The target of fisetin was extracted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The targets of OP were obtained by DisGeNET, GeneCards and the Comparative Toxicogenomics Database, and the targets of fisetin in OP were screened by cross-analysis. The protein–protein interaction (PPI) network was constructed by STRING, and the core targets were obtained. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on common targets via the Database for Annotation, Visualization and Integrated Discovery. Finally, an in vitro cell experiment was used to verify the anti-OP effect and mechanism of fisetin.

Results

There are 44 targets of fisetin related to the treatment of OP. The PPI results suggest that CTNNB1, CCND1, TP53, JUN, and AKT1 are the core targets. A total of 259 biological process, 57 molecular function and 26 cell component terms were obtained from GO enrichment analysis. The results of KEGG pathway enrichment analysis suggested that fisetin treatment of OP may be related to the Wnt signaling pathway, estrogen signaling pathway, PI3K-Akt signaling pathway and other signaling pathways. In vitro cell experiments showed that fisetin significantly increased the expression levels of ALP, collagen I, osteopontin and RUNX2 in bone marrow mesenchymal stem cells (BMSCs) (p < 0.05). Fisetin also increased the gene expression levels of Wnt3 and β-catenin (CTNNB1) in BMSCs, which indicates that fisetin can regulate the Wnt/β-catenin signaling pathway and promote the osteogenic differentiation of BMSCs.

Conclusions

Fisetin acts on multiple targets and pathways in the treatment of OP; mechanistically, it regulates the Wnt/β-catenin signaling pathway, which promotes the osteogenic differentiation of BMSCs and maintains bone homeostasis. The results of this study provide a theoretical basis for further study on the complex anti-OP mechanism of fisetin.
Modifiable risk factors in women at high risk of breast cancer: a systematic review
Authors: Cohen Sarah Y. , Stoll Carolyn R. , Anandarajah Akila , Doering Michelle , Colditz Graham A.
Published: April 2023

Background

Modifiable risk factors (alcohol, smoking, obesity, hormone use, and physical activity) affect a woman’s breast cancer (BC) risk. Whether these factors affect BC risk in women with inherited risk (family history, BRCA1/2 mutations, or familial cancer syndrome) remains unclear.

Methods

This review included studies on modifiable risk factors for BC in women with inherited risk. Pre-determined eligibility criteria were used and relevant data were extracted.

Results

The literature search resulted in 93 eligible studies. For women with family history, most studies indicated that modifiable risk factors had no association with BC and some indicated decreased (physical activity) or increased risk (hormonal contraception (HC)/menopausal hormone therapy (MHT), smoking, alcohol). For women with BRCA mutations, most studies reported no association between modifiable risk factors and BC; however, some observed increased (smoking, MHT/HC, body mass index (BMI)/weight) and decreased risk (alcohol, smoking, MHT/HC, BMI/weight, physical activity). However, measurements varied widely among studies, sample sizes were often small, and a limited number of studies existed.

Conclusions

An increasing number of women will recognize their underlying inherited BC risk and seek to modify that risk. Due to heterogeneity and limited power of existing studies, further studies are needed to better understand how modifiable risk factors influence BC risk in women with inherited risk.
A desert lncRNA HIDEN regulates human endoderm differentiation via interacting with IMP1 and stabilizing FZD5 mRNA
Authors: Lu Pei , Yang Jie , Li Mao , Wen Shanshan , Zhang Tianzhe , Yan Chenchao , Liu Ran , Xiao Yu , Wang Xinghuan , Jiang Wei
Published: April 2023

Background

Extensive studies have revealed the function and mechanism of lncRNAs in development and differentiation, but the majority have focused on those lncRNAs adjacent to protein-coding genes. In contrast, lncRNAs located in gene deserts are rarely explored. Here, we utilize multiple differentiation systems to dissect the role of a desert lncRNA,HIDEN(humanIMP1-associated "desert" definitiveendoderm lncRNA), in definitive endoderm differentiation from human pluripotent stem cells.

Results

We show that desert lncRNAs are highly expressed with cell-stage-specific patterns and conserved subcellular localization during stem cell differentiation. We then focus on the desert lncRNAHIDENwhich is upregulated and plays a vital role during human endoderm differentiation. We find depletion ofHIDENby either shRNA or promoter deletion significantly impairs human endoderm differentiation.HIDENfunctionally interacts with RNA-binding protein IMP1 (IGF2BP1), which is also required for endoderm differentiation. Loss ofHIDENor IMP1 results in reduced WNT activity, and WNT agonist rescues endoderm differentiation deficiency caused by the depletion ofHIDENor IMP1. Moreover,HIDENdepletion reduces the interaction between IMP1 protein andFZD5mRNA and causes the destabilization ofFZD5mRNA, which is a WNT receptor and necessary for definitive endoderm differentiation.

Conclusions

These data suggest that desert lncRNAHIDENfacilitates the interaction between IMP1 andFZD5mRNA, stabilizingFZD5mRNA which activates WNT signaling and promotes human definitive endoderm differentiation.
A study protocol for the randomized controlled trial SAFIR FAMILY TALK: a selective primary preventive intervention vs. service as usual for children of parents with mental illness
Authors: Nielsen Signe S. , Mikkelsen Lisbeth J. , Quaade Nikolaj , Gladstone Tracy R. G. , Beardslee William R. , Bonnemose Katrina , Rosenberg Nicole K. , Hjorthøj Carsten , Thorup Anne A. E. , Nordentoft Merete , Ranning Anne
Published: April 2023

Background

Children of parents with mental illness have an increased risk of developing mental illness themselves throughout their lifespan. This is due to genetic factors but also environmental disadvantages during childhood associated with parental mental illness. Selective primary preventive interventions for the children are recommended to mitigate risk factors and strengthen protective factors, but large-scale, longitudinal studies are needed. This study aims to investigate the effect of the Family Talk Preventive Intervention in a cohort of children and their parents with mental illness.

Methods

The study is a randomized controlled trial with 286 planned families with at least one parent with any mental illness and at least one child aged 7 to 17 years. It will be carried out in the mental healthcare system in the Capital Region of Denmark. Families will be referred from hospitals and municipalities. The children and parents will be assessed at baseline and then randomized and allocated to either the Family Talk Preventive Intervention or service as usual. The intervention group will be assigned to Family Talk Preventive Intervention, a manualized programme consisting of ~ seven sessions for the family, including psychoeducation about parental mental illness and resilience in children, stimulating dialogue between family members and creating a common family narrative. The study period for both groups will be 12 months. Follow-up assessments will be conducted after 4 months and 12 months. The primary outcomes are the children’s level of functioning, parental sense of competence and family functioning.

Discussion

Given the prevalence of transgenerational transmission of mental illness, a systematic approach to prevention is needed in the mental healthcare setting. This study provides valuable knowledge on the Family Talk Preventive Intervention with a large sample size, inclusion of any parental mental illness and examination of the primary outcomes.

Trial registration

ClinicalTrials.gov NCT05615324. Registered on 26 October 2022. Retrospectively registered.
Glutathione peroxidase 3 is a novel clinical diagnostic biomarker and potential therapeutic target for neutrophils in rheumatoid arthritis
Authors: Chen Tao , Zhou Zhen , Peng Minge , Hu Huifang , Sun Rui , Xu Jiayi , Zhu Chenxi , Li Yanhong , Zhang Qiuping , Luo Yubin , Yang Bin , Dai Lunzhi , Liu Yi , Muñoz Luis E. , Meng Liesu , Herrmann Martin , Zhao Yi
Published: April 2023

Background

Neutrophils have a critical role in the pathogenesis of rheumatoid arthritis (RA) with immune system dysfunction. However, the molecular mechanisms of this process mediated by neutrophils still remain elusive. The purpose of the present study is to identify hub genes in neutrophils for diagnosis and treatment of RA utilizing publicly available datasets.

Methods

Gene expression profiles were downloaded from the Gene Expression Omnibus, and batch-corrected and normalized expression data were obtained using the ComBat package. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were used to conduct significantly functional analysis and crucial pathways. The resulting co-expression genes modules and hub genes were generated based on the weighted gene co-expression network analysis and visualization by Cytoscape. Flow cytometry was conducted to detect reactive oxygen species (ROS) levels in neutrophils.

Results

Neutrophils underwent transcriptional changes in synovial fluid (SF) of RA patients, different from peripheral blood of healthy controls or patients with RA. Especially, glycolysis, HIF-1 signaling, NADH metabolism, and oxidative stress were affected. These hub genes were strongly linked with classical glycolysis-related genes (ENO1, GAPDH, and PKM) responsible for ROS production. The antioxidant enzyme glutathione peroxidase 3 (GPX3), a ROS scavenger, was first identified as a hub gene in RA neutrophils. Neutrophils from patients with autoinflammatory and autoimmune diseases had markedly enhanced ROS levels, most notably in RA SF.

Conclusion

This research recognized hub genes and explored the characteristics of neutrophils in RA. Our findings suggest that the novel hub gene GPX3 is involved in the neutrophil-driven oxidative stress-mediated pathogenesis of RA. It has the potency to be a target for neutrophil-directed RA therapy.
Preliminary insights into patient preparedness for knee or hip arthroplasty: a descriptive survey study
Authors: Naylor Justine M , Harris Ian A , Joon Sidhant , Boland Robert , Brady Bernadette , Ogul Shaniya , Mittal Rajat
Published: April 2023

Objective

Knowledge-based preparedness for surgery is achieved through education. It is unclear which of brief or extended education programs prior to knee or hip arthroplasty provides better patient preparedness. Using the Patient Preparedness for Surgery survey, we investigated whether people awaiting arthroplasty attending a hospital that provided education over multiple visits via a pre-surgery management program (‘Extended’) report superior preparedness compared to those attending a hospital in the same health district that only provides education at the pre-admission clinic assessment (‘Brief’).

Results

A consecutive sample of 128 people (n = 101, ‘Extended’, n = 27 ‘Brief’) completed the anonymized survey. COVID-19 related service disruptions undermined the sample size, reducing statistical power. The pre-specified superiority of the Extended program (a relative 20% more reporting ‘agree’/’strongly agree’) was not observed for ‘Overall preparedness’ [95% (Extended) vs. 89% (Brief), p = 0.36]. Between-group differences exceeding 20% relative superiority were observed for three preparedness sub-domains [‘Alternatives explained’ (52 vs. 33%, p = 0.09); ‘Prepared for home’ (85 vs. 57%, p < 0.01); ‘Recall of complications’ (42 vs 26%, p = 0.14)]. The preliminary findings suggest an extended education program potentially yields better patient-reported preparedness in some preparedness sub-domains, but not all.
Comparative analysis of active networks reveals the changes of key proteins and their interactions under different oxygen levels in Shewanella oneidensis MR-1
Authors: Xiong Chenwu , Tong Hua , He Xiaoqing , Ding Dewu
Published: April 2023

Purpose

The extracellular electron transfer (EET) capability enables electroactive microorganisms have a wide range of applications in energy production, wastewater treatment, bioremediation and chemical synthesis. Because the oxygen levels will sharply affect the EET process, we integrated transcriptome changes under different oxygen levels with protein–protein interaction (PPI) network to study the specific changes under these conditions in a typical electroactive microorganismShewanella oneidensisMR-1 (S. oneidensisMR-1).

Methods

First, the mRNA expression data ofS. oneidensisMR-1 under different oxygen levels were integrated into its PPI network to construct the active protein networks. Then, we studied the changes of key proteins and their interactions by comparative analysis of multiple pairs of active networks.

Results

The analysis of node centrality and its changes in the active networks under high and low oxygen levels shows that most of the key nodes in the network are ribosomes or proteins closely related to ribosomes. The results of our centrality versus centrality change analysis of nodes show that the two proteins FlgB and PetA are the largest changed proteins. Among these proteins, the FlgB protein is the structural component of flagella, while PetA protein is closely related to cytochromec. Furthermore, we also analyzed the changes in protein–protein interactions in the active networks under different oxygen levels, identified the key interactions in each pair of active networks, and finally screened out the key interaction Tig-RplX that exists in three pairs of active networks.

Conclusion

Our results indicate that the translational processes of proteins and the corresponding translation efficiency may play an important role before and after the activation of the EET process ofS. oneidensisMR-1. Furthermore, this study can also provide some guidance for identifying key proteins and interactions under different conditions for this species.
Differential costs for the non-adult ADHD population in Catalonia
Authors: Mora Toni , Puig-Junoy Jaume , Jacobs Rowena , Cid Jordi
Published: April 2023

Attention-Deficit/Hyperactivity Disorder (ADHD) is young children’s most common mental health disorder. We aim to provide causal estimates of the differential costs for the non-adult population with ADHD. We used longitudinal administrative data covering the non-adult population over five years and different healthcare providers (general practitioners, hospitalisations and emergency departments, visits to mental healthcare centres—day-care or hospitals) of 1,101,215 individuals in Catalonia (Spain). We also include the consumption of pharmaceuticals and cognitive therapies. We instrumented ADHD diagnosis by the probability of being diagnosed by the most visited healthcare provider based on individual monthly visits to the provider in which this visit was related to ADHD and the density of professionals in the different mental health providers. After using matching procedures to include a proper control group, we estimated two-part and finite mixture models. Our results indicate that ADHD children and adolescents displayed 610€ higher annual health direct costs compared to not diagnosed counterparts. We provide average costs disentangling the sample by age boundaries, gender, and comorbidities to offer values for cost-effective analyses and incremental costs after diagnosis, which is around 400€. A significant differential annual direct health cost for the non-adult population with ADHD is determined, which will be helpful for cost-effectiveness analysis and complete cost-of-illness studies.
The hindgut microbiome contributes to host oxidative stress in postpartum dairy cows by affecting glutathione synthesis process
Authors: Gu Fengfei , Zhu Senlin , Hou Jinxiu , Tang Yifan , Liu Jian-Xin , Xu Qingbiao , Sun Hui-Zeng
Published: April 2023

Background

Dairy cows are susceptible to postpartum systemic oxidative stress (OS), which leads to significant production loss and metabolic disorders. The gut microbiota has been linked to host health and stress levels. However, to what extent the gut microbiota is associated with postpartum OS remains unknown. In this study, the contribution of the fecal microbiota to postpartum systemic OS and its underlying mechanisms were investigated by integrating 16S rRNA gene sequencing, metagenomics, and metabolomics in postpartum dairy cattle and by transplanting fecal microbiota from cattle to mice.

Results

A strong link was found between fecal microbial composition and postpartum OS, with an explainability of 43.1%. A total of 17 significantly differential bacterial genera and 19 species were identified between cows with high (HOS) and low OS (LOS). Among them, 9 genera and 16 species showed significant negative correlations with OS, and Marasmitruncus and Ruminococcus_sp._CAG:724 had the strongest correlations. The microbial functional analysis showed that the fecal microbial metabolism of glutamine, glutamate, glycine, and cysteine involved in glutathione synthesis was lower in HOS cows. Moreover, 58 significantly different metabolites were identified between HOS and LOS cows, and of these metabolites, 19 were produced from microbiota or cometabolism of microbiota and host. Furthermore, these microbial metabolites were enriched in the metabolism of glutamine, glutamate, glycine, and cysteine. The mice gavaged with HOS fecal microbiota had significantly higher OS and lower plasma glutathione peroxidase and glutathione content than those orally administered saline or LOS fecal microbiota.

Conclusions

Integrated results suggest that the fecal microbiota is responsible for OS and that lower glutathione production plays a causative role in HOS. These findings provide novel insights into the mechanisms of postpartum OS and potential regulatory strategies to alleviate OS in dairy cows.
Long term worsening of amyloid pathology, cerebral function, and cognition after a single inoculation of beta-amyloid seeds with Osaka mutation
Authors: Célestine Marina , Jacquier-Sarlin Muriel , Borel Eve , Petit Fanny , Perot Jean-Baptiste , Hérard Anne-Sophie , Bousset Luc , Buisson Alain , Dhenain Marc
Published: April 2023

Alzheimer’s disease (AD) is characterized by intracerebral deposition of abnormal proteinaceous assemblies made of amyloid-β (Aß) peptides or tau proteins. These peptides and proteins induce synaptic dysfunctions that are strongly correlated with cognitive decline. Intracerebral infusion of well-defined Aβ seeds from non-mutated Aβ1-40 or Aβ1-42 peptides can increase Aβ depositions several months after the infusion. Familial forms of AD are associated with mutations in the amyloid precursor protein (APP) that induce the production of Aβ peptides with different structures. The Aβ Osaka (Aβosa mutation (E693Δ)) is located within the Aβ sequence and thus the Aβosa peptides have different structures and properties as compared to non-mutated Aβ1-42 peptides (Aβwt). Here, we wondered if a single exposure to this mutated Aβ can worsen AD pathology as well as downstream events including cognition, cerebral connectivity and synaptic health several months after the inoculation. To answer this question we inoculated Aβ1-42-bearing Osaka mutation (Aβosa) in the dentate gyrus of APPswe/PS1dE9 mice at the age of two months. Their cognition and cerebral connectivity were analyzed at 4 months post-inoculation by behavioral evaluation and functional MRI. Aβ pathology as well as synaptic density were evaluated by histology. The impact of Aβosa peptides on synaptic health was also measured on primary cortical neurons. Remarkably, the intracerebral administration of Aβosa induced cognitive and synaptic impairments as well as a reduction of functional connectivity between different brain regions, 4 months post-inoculation. It increased Aβ plaque depositions and increased Aβ oligomers. This is the first study showing that a single, sporadic event as Aβosa inoculation can worsen the fate of the pathology and clinical outcome several months after the event. It suggests that a single inoculation of Aβ regulates a large cascade of events for a long time.

Graphical Abstract
Effect of transcutaneous auricular vagal nerve stimulation on the fatigue syndrome in patients with gastrointestinal cancers — FATIVA: a randomized, placebo-controlled pilot study protocol
Authors: Gierthmuehlen Mortimer , Höffken Nadine , Timmesfeld Nina , Schmieder Kirsten , Reinacher-Schick Anke
Published: April 2023

Background

Cancer-related fatigue (CRF) is defined as a “distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning.” CRF is frequently observed in cancer patients even before the initiation of tumor therapy. Its cause is not clear, but in addition to primary effects of therapy, a tumor-induced elevated level of inflammatory cytokines may play a role. Transcutaneous auricular vagal nerve stimulation (taVNS) is a noninvasive way to activate central nervous pathways and modulate pain perception and the immune system. It has positive effects on autoimmune conditions and can also improve fatigue associated with Sjogren’s syndrome. It is the main purpose of this feasibility study to investigate the feasibility of daily taVNS against CRF. Therefore, the stimulation protocol of the newly introduced smartphone app of the manufacturer is evaluated. Additionally, the effect taVNS on CRF and quality of life (QoL) shall be evaluated.

Methods

Thirty adult patients with gastrointestinal tumors during or after treatment, relevant CRF (Hornheide questionnaire) and life expectancy > 1 year, are enrolled. Patients are randomized to treatment or sham arm and be informed that they will either feel the stimulation or not. Treatment group will receive left-sided tragus above-threshold stimulation with 25 Hz, 250 µs pulse width, and 28-s/32-s on/off paradigm for 4 h throughout the day for 4 weeks. Sham group will receive no stimulation via a nonfunctional electrode. A daily stimulation protocol with time and average intensity is automatically created by a smartphone app connected to the stimulator via Bluetooth®. Multidimensional Fatigue Inventory-20, Short-Form 36 and Beck Depression Inventory questionnaires will be filled out before and after 4 weeks of stimulation.

Discussion

Primarily, the patients’ daily stimulation time and intensity will be evaluated through the electronic protocol after 4 weeks. Secondarily, the effect of taVNS on cancer-related fatigue and QoL will be measured through the questionnaires. As taVNS seems to modulate inflammatory cytokines, this noninvasive method may — if accepted by the patients — be a promising adjunct in the treatment of cancer-related fatigue.

Trial registration

The study was approved by local ethics committee (21–7395) and registered at the DRKS database (DRKS00027481).
Beyond gender mainstreaming: transforming humanitarian action, organizations and culture
Authors: Gupta Geeta Rao , Grown Caren , Fewer Sara , Gupta Reena , Nowrojee Sia
Published: April 2023

The United Nations and major humanitarian organizations have made policy commitments to promote gender equality and empower women and girls. This study assesses the extent to which humanitarian responses have met these commitments based on reviews of gender mainstreaming, textual analysis of policy and program cycle documents, and interviews with humanitarian actors. The analysis reveals that while gender mainstreaming may raise awareness and make fixes at the margins, its focus has been limited to altering internal processes rather than emphasizing results for women and men and girls and boys. Our study also analyzes the cultural and institutional context in which gender mainstreaming takes place. The culture of humanitarian organizations has been characterized as hierarchical and driven by a short-term crisis response with a distinctly macho style of functioning, which is misaligned with gender mainstreaming. We propose replacing gender mainstreaming with a results-focused approach rooted in behavioral science that uses evidence of the conscious and non-conscious drivers of human behavior to address problems, alongside other efforts to change the internal culture of humanitarian organizations.
DNA polymerase κ suppresses inflammation and inflammation-induced mutagenesis and carcinogenic potential in the colon of mice
Authors: Hakura Atsushi , Sui Hajime , Seki Yuki , Sonoda Jiro , Yoshida Yusaku , Takagi Hisayoshi , Yokose Shigeo , Matsuda Tomonari , Asakura Shoji , Nohmi Takehiko
Published: April 2023

Background

Chronic inflammation induces DNA damage and promotes cell proliferation, thereby increasing the risk of cancer. DNA polymerase κ (Pol κ), involved in translesion DNA synthesis, counteracts mutagenesis induced by inflammation in the colon of mice. In the present study, we examined whether Pol κ suppressed inflammation-induced colon tumorigenesis by treating inactivated Polk knock-in (Polk−/−) mice with dextran sulfate sodium (DSS), an inducer of colon inflammation.

Results

Male and female Polk−/− and Polk+/+ mice were administered 2% DSS in drinking water for six consecutive days, succeeded via a recovery period of 16 days, followed by 2% DSS for another two days. DSS treatment strongly induced colitis, and the severity of colitis was higher in Polk−/− mice than in Polk+/+ mice. The mice were sacrificed after 19 weeks from the initiation of the first DSS treatment and subjected to pathological examination and mutation analysis. DSS treatment induced colonic dysplasia, and the multiplicity of dysplasia was higher in Polk−/− mice than in Polk+/+mice. Some of the dysplasias in Polk−/− mice exhibited β-catenin-stained nucleus and/or cytoplasm. Mutation frequencies in the gpt reporter gene were increased by DSS treatment in Polk−/− mice, and were higher than those in Polk+/+ mice.

Conclusions

Pol κ suppresses inflammation and inflammation-induced dysplasia as well as inflammation-induced mutagenesis. The possible mechanisms by which Pol κ suppresses colitis- and colitis-induced dysplasia are discussed.
Are there placebo or nocebo effects in balancing performance?
Authors: Horváth Áron , Szabo Attila , Gál Vera , Suhaj Csilla , Aranyosy Blanka , Köteles Ferenc
Published: April 2023

Placebo and nocebo effects could influence the perceived, actual, or both postural stabilities. Therefore, this experiment examined whether postural stability is susceptible to placebo and nocebo effects. Driven by expectations, these cognitions could influence the motor stability of people in physical rehabilitation and those with motion instability. We randomly assigned 78 participants to a placebo, nocebo, or control group. Then, we applied a sham sports cream with positive, negative, or neutral instructions about its impact on balance. Next, we tested postural stability with a modified version of the Modified Clinical Test of Sensory Interaction in Balance, including standard, proprioceptive, visual, and vestibular tests before and after the intervention. Further, we measured expected and perceived performance with visual analog scales and assessed trait anxiety, change in state anxiety, optimism, holistic thinking, persistence, and cooperation with questionnaires. The intervention did not affect actual test performances; similarly, trait and state variables and expectations did not have an impact. Furthermore, the experimental manipulation and trait and state variables did not significantly affect perceived performance. However, the association between expectation and perceived performance was strong (ϱ = 0.627, p < 0.001). These findings suggest that postural stability is not susceptible to placebo and nocebo influences. Still, there is a dissociation between objective and subjective performance, showing that expectations impact perceived but not actual performance, which could fuel motivation in rehabilitation settings.
Tirzepatide as Monotherapy Improved Markers of Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes (SURPASS-1)
Authors: Lee Clare J , Mao Huzhang , Thieu Vivian T , Landó Laura Fernández , Thomas Melissa K
Published: April 2023

Context

Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for treatment of type 2 diabetes (T2D). SURPASS-1, a phase 3 trial of tirzepatide monotherapy in people with early T2D, enables evaluating effects of tirzepatide on pancreatic beta-cell function and insulin sensitivity (IS) without other background antihyperglycemic medications.

Objective

Explore changes in biomarkers of beta-cell function and IS with tirzepatide monotherapy.

Design

Post hoc analyses of fasting biomarkers with analysis of variance and mixed model repeated measures.

Setting

Forty-seven sites in 4 countries.

Patients

Four hundred seventy-eight T2D participants.

Intervention

Tirzepatide (5, 10, 15 mg), placebo.

Main Outcome Measure(s)

Analyze biomarkers of beta-cell function and IS at 40 weeks.

Results

At 40 weeks, markers of beta-cell function improved with tirzepatide monotherapy vs placebo with reductions from baseline in fasting proinsulin levels (49-55% vs −0.6%) and in intact proinsulin/C-peptide ratios (47-49% vs −0.1%) (P < .001, all doses vs placebo). Increases from baseline in homeostatic model assessment for beta-cell function (computed with C-peptide) (77-92% vs −1.4%) and decreases in glucose-adjusted glucagon levels (37-44% vs +4.8%) were observed with tirzepatide vs placebo (P < .001, all doses vs placebo). IS improved as indicated by reductions from baseline in homeostatic model assessment for insulin resistance (9-23% vs +14.7%) and fasting insulin levels (2-12% vs +15%), and increases in total adiponectin (16-23% vs −0.2%) and insulin-like growth factor binding protein 2 (38-70% vs +4.1%) with tirzepatide vs placebo at 40 weeks (P ≤ .031, all doses vs placebo, except for fasting insulin levels with tirzepatide 10 mg).

Conclusions

As monotherapy for early T2D, tirzepatide achieved significant improvements in biomarkers of both pancreatic beta-cell function and IS.
“Mediterranization,” or the “Sexual Question” in the North of the City
Authors: Milne Anna-Louise
Published: April 2023

Taking its lead from contemporary debates about the “crisis” that is the masculinization of the Barbès-La Chapelle-Stalingrad triangle in northern Paris, this article considers the processes whereby this district has been both “southernized” (“Mediterranization”) and “sexualized” while also being yoked into the modernizing, infrastructural dynamics of a “global city” (Sassen 1991). It relates these debates to the longer history of labor migration, structural inequality and the exceptionalist policing of sexual politics under colonial rule and into the period of decolonization. In so doing it establishes the context for reviewing Gramsci's southern question through the prism of his writing on “the sexual question.” Where Gramsci posits “a new feminine personality,” largely occluding the forms of female subaltern labor, the discussion here looks to the work of two young female artists, the photographer Randa Maroufi's 2019 series Les Intruses and the filmmaker Louise Mootz's 2019 work Jungle, to explore this terrain. In so doing, it proposes that their negotiation of and with urban form, which itself reflects the complex history of containment and porosity in this environment, displaces “the South” from a polarity with the North and situates the female body in its work, play and pleasure, but also in the confrontation with the violence of the street and of gender norms, as the locus of a radical shaping of the intersection between the southern/sexual question.
Zika virus-induces metabolic alterations in fetal neuronal progenitors that could influence in neurodevelopment during early pregnancy
Authors: Gilbert-Jaramillo Javier , Purnama Ujang , Molnár Zoltán , James William S.
Published: April 2023

Cortical development consists of an orchestrated process in which progenitor cells exhibit distinct fate restrictions regulated by time-dependent activation of energetic pathways. Thus, the hijacking of cellular metabolism by Zika virus (ZIKV) to support its replication may contribute to damage in the developing fetal brain. Here, we showed that ZIKV replicates differently in two glycolytically distinct pools of cortical progenitors derived from human induced pluripotent stem cells (hiPSCs), which resemble the metabolic patterns of quiescence (early hi-NPCs) and immature brain cells (late hi-NPCs) in the forebrain. This differential replication alters the transcription of metabolic genes in both pools of cortical progenitors but solely upregulates the glycolytic capacity of early hi-NPCs. Analysis using Imagestream® revealed that, during early stages of ZIKV replication, in early hi-NPCs there is an increase in lipid droplet abundance and size. This stage of ZIKV replication significantly reduced the mitochondrial distribution in both early and late hi-NPCs. During later stages of ZIKV replication, late hi-NPCs show reduced mitochondrial size and abundance. The finding that there are alterations of cellular metabolism during ZIKV infection which are specific to pools of cortical progenitors at different stages of maturation may help to explain the differences in brain damage over each trimester.