bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Bending’ against straightening devices: queer lived experiences of sexuality and sexual health in Bangladesh
Authors: Alam Prima , Marston Cicely
Published: January 2023

Background

Despite global data around increased health risks among sexual and gender diverse populations, lived experiences of young lesbian, gay, bisexual, transgender, queer or questioning, and others (LGBTQ+) people are often ignored in mainstream health research. This is particularly evident in countries such as Bangladesh where the rights of sexual minorities are not recognised. This article looks at queer lived experiences of sexuality and sexual health within such a context. We use the phenomenological framework of heteronormative ‘straightening devices’ – mechanisms working to direct people towards heterosexuality, gender conformity, and procreative marriage – to identify ‘invisible’ structures upholding normative sexual behaviours and see how young people in Bangladesh navigate these in their everyday lives.

Methods

This article is based on qualitative data collected in Dhaka, Bangladesh over nine months in 2019 as part of the first author’s doctoral research. Using thematic analysis, we draw on experiences of normative sexual expectations from biographical in-depth interviews with 14 purposively sampled LGBTQ + individuals aged 18 to 24.

Results

Respondents identified heteronormative expectations around gender norms of traditional behaviour and presentation for men and women as well as parental expectations of compulsory heterosexuality through marriage. These straightening devices existed at multiple levels, including individual, interpersonal, community, and societal. The four main themes around straightening devices include marriage norms for women; harassment of feminine-presenting bodies in public spaces; heteronormative healthcare; and consequences of not embodying heteronormativity.

Conclusion

Our study highlighted young people’s everyday experiences of having to ‘bend’ to – and against – heteronormative straightening devices at home, in public spaces, and within institutions such as healthcare in Bangladesh. The exploration of queer experiences provides new insights into context-specific ways in which sexual and gender diverse people understand themselves. Further research using the framework of straightening devices can help public health professionals to identify more ‘barriers’ confronted by sexual and gender diverse young people.
Reconstruction of massive bone defects after femoral tumor resection using two new-designed 3D-printed intercalary prostheses: a clinical analytic study with the cooperative utilization of multiple technologies
Authors: Shao Xianhao , Dou Mengmeng , Yang Qiang , Li Jianmin , Zhang Ailin , Yao Yuan , Chu Qing , Li Ka , Li Zhenfeng
Published: January 2023

Background

To reconstruct massive bone defects of the femoral diaphysis and proximal end with limited bilateral cortical bone after joint-preserving musculoskeletal tumor resections, two novel 3D-printed customized intercalary femoral prostheses were applied.

Methods

A series of nine patients with malignancies who received these novel 3D-printed prostheses were retrospectively studied between July 2018 and November 2021. The proximal and diaphyseal femur was divided into three regions of interest (ROIs) according to anatomic landmarks, and anatomic measurements were conducted on 50 computed tomography images showing normal femurs. Based on the individual implant-involved ROIs, osteotomy level, and anatomical and biomechanical features, two alternative 3D-printed prostheses were designed. In each patient, Hounsfield Unit (HU) value thresholding and finite element analysis were conducted to identify the bone trabecula and calcar femorale and to determine the stress distribution, respectively. We described the characteristics of each prosthesis and surgical procedure and recorded the intraoperative data. All patients underwent regular postoperative follow-up, in which the clinical, functional and radiographical outcomes were evaluated.

Results

With the ROI division and radiographic measurements, insufficient bilateral cortical bones for anchoring the traditional stem were verified in the normal proximal femur. Therefore, two 3D-printed intercalary endoprostheses, a Type A prosthesis with a proximal curved stem and a Type B prosthesis with a proximal anchorage-slot and corresponding locking screws, were designed. Based on HU value thresholding and finite element analysis, the 3D-printed proximal stems in all prostheses maximally preserved the trabecular bone and calcar femorale and optimized the biomechanical distribution, as did the proximal screws. With the 3D-printed osteotomy guide plates and reaming guide plates, all patients underwent the operation uneventfully with a satisfactory duration (325.00 ± 62.60 min) and bleeding volume (922.22 ± 222.36 ml). In the follow-up, Harris Hip and Musculoskeletal Tumor Society scores were ameliorated after surgery (P < 0.001 and P < 0.001, respectively), reliable bone ingrowth was observed, and no major complications occurred.

Conclusions

Two novel 3D-printed femoral intercalary prostheses, which achieved acceptable overall postoperative outcomes, were used as appropriate alternatives for oncologic patients with massive bone defects and limited residual bone and increased the opportunities for joint‐preserving tumor resection. Several scientific methodologies utilized in this study may promote the clinical design proposals of 3D-printed implants.
Inclusion and diversity within medical education: a focus group study of students’ experiences
Authors: Verbree Anne-Roos , Isik Ulviye , Janssen Jeroen , Dilaver Gönül
Published: January 2023

Background/introduction

As patient populations become more diverse, it is imperative that future physicians receive proper training in order to provide the best quality of care. This study examines medical students' perceptions of how prepared they are in dealing with a diverse population and assesses how included and supported the students felt during their studies.

Methods

Four semi-structured focus groups were held with medical students across all years of the medical study program of a Dutch university. Focus group transcripts were analyzed thematically.

Results

Students’ experiences could be categorized as follows: (1) (Minority) identities and personal motivations, (2) Understanding of diversity and an inclusive learning environment, (3) Diversity in education, (4) Experiences of exclusion, (5) Experiences of inclusion, and (6) Lack of awareness. The key findings from the focus groups were that students perceived a lack of diversity and awareness in medical education and were convinced of the need to incorporate diversity to a greater extent and were personally motivated to contribute to incorporating diversity in the curriculum. Students also shared exclusion experiences such as stereotypes and prejudices but also some inclusion experiences such as feelings of belonging.

Conclusion

Based on our findings, it is recommended that medical schools incorporate diversity education into their curriculum so that health professionals can provide the best quality of care for their diverse patient populations. This education should also ensure that all students feel included in their medical education program.
Comparison of experiences of nursing staff and patients before and after move to 100% single-bed room hospital in Australia: mixed methods
Authors: Cusack Lynette , Munt Rebecca , Verdonk Naomi , Schultz Tim , Maben Jill
Published: January 2023

Background

There is sufficient and consistent international evidence of issues reported by nurses working in single-bed room environments, requiring a design that is not only comfortable for patients but meets nurses working needs. This paper presents a comparison of nursing staff and patients experience prior to a move to 100% single-bed room hospital in 2016 (Stage 1) and actual experiences after the move in 2021 (Stage 2) in South Australia.

Method

Mixed method case study design. Survey sample of forty-two nursing staff; twelve patient interviews of their experiences of current environment and; thirteen nursing staff interviews of their experiences delivering nursing care in 100% single bed-room environment.

Results

Nurses and patients highlighted single-bed rooms contributed to patients’ privacy, confidentiality, dignity and comfort. As anticipated in Stage 1, nurses in Stage 2 reported lack of patient and staff visibility. This impacted workload, workflow and concern for patient safety.

Conclusion

Patient and nursing staff experiences are interdependent, and implications of single-bed room accommodation are complicated. Future impacts on the health system will continue to affect hospital design, which must consider nurses working needs and patient safety and comfort.
Factors associated with general practitioners' routines and comfortability with assessing female genital cutting: a cross-sectional survey
Authors: Ziyada Mai Mahgoub , Johansen R. Elise B , Berthelsen Mona , Lien Inger-Lise , Bendiksen Bothild
Published: January 2023

Background

Female genital cutting (FGC) may cause a series of health problems that require specialized healthcare. General practitioners (GPs) are gatekeepers to specialized healthcare services in Norway. To refer girls and women subjected to FGC to appropriate services, GPs need to assess whether the health problems reported by these patients are related to FGC. However, we do not know to what degree GPs assess FGC as a potential cause of the patients' health problems. We also know little about the GPs' patterns of training and knowledge of FGC and their effect on the GPs' assessment of FGC as a potential cause of health problems.

Method

We employed a cross-sectional online survey among GPs in Norway to examine: 1) patterns of received training on FGC, self-assessed knowledge, and experiences with patients with FGC-related problems and 2) the association between these three factors and the GPs' assessment of FGC as a potential cause of patients' health problems. A total of 222 GPs completed the survey. Data were analysed using binary logistic regression, where we also adjusted for sociodemographic characteristics.

Results

Two-third of the participants had received training on FGC, but only over half received training on FGC-related health problems. Over 75% of the participants stated a need for more knowledge of FGC typology and Norwegian legislation. While the majority of the participants assessed their knowledge of FGC medical codes as inadequate, this was not the case for knowledge of the cultural aspects of FGC. Female GPs were more likely to have experience with patients with FGC-related health problems than male GPs. Among GPs with experience, 46% linked health problems to FGC in patients unaware of the connection between FGC and such health problems. GPs were more likely to assess FGC as a potential cause of health problems when they had experience with patients having FGC-related problems and when they assessed their knowledge of FGC typology and FGC-related medical codes as adequate.

Conclusion

To improve their assessment of FGC as a potential cause of patients' health problems, GPs should receive comprehensive training on FGC, with particular emphasis on typology, health problems, and medical codes.
Entomological Surveillance Planning Tool (ESPT)-generated actionable evidence on human and vector behaviours optimizes present interventions and reduces exposure to Anopheles vectors in two communities of Guna Yala, Panamá
Authors: Ávila Mario I. , Vajda Élodie A. , Jeffrey Gutiérrez Eileen , Gibson Daragh , Renteria Mariela Mosquera , Presley Nicolas , O’Reilly Daniel , Tatarsky Allison , Lobo Neil F.
Published: January 2023

Background

Although most of Panamá is free from malaria, localized foci of transmission persist, including in the Guna Yala region. Government-led entomological surveillance using an Entomological Surveillance Planning Tool (ESPT) sought to answer programmatically relevant questions on local entomological drivers of transmission and gaps in protection to guide local vector control decision-making.

Methods

The ESPT was used to design a sampling plan to answer priority programmatic questions about the appropriateness of Long Lasting Insecticidal Nets (LLINs) and spaces and times where humans remain exposed to Anopheles bites (gaps in protection) in the communities of Permé and Puerto Obaldía, Guna Yala. Adult Anopheles were sampled at three time points via human landing catches (HLCs) during the rainy and dry seasons (2018/2019). Human behaviour observations (HBOs) were conducted alongside HLCs to examine intervention use, indoor versus outdoor activity, and sleeping patterns. HLC and HBO data were integrated to evaluate HBO-adjusted human biting rate (HBR).

Results

A total of 7,431 adult Anopheles were collected across both sites. Of the 450 specimens molecularly confirmed to species-level, 75.5% (n = 340) were confirmed as Anopheles Nyssorhynchus albimanus, followed by Anopheles (Ny.) aquasalis. Anopheles host seeking activity was demonstrated to be primarily exophagic throughout all sampling periods and in both communities. When adjusted with HBOs, exposure to mosquito bites was predominantly indoors and overnight in Permé (Nov, Mar), compared to predominantly outdoors in Puerto Obaldía (Nov, Mar, Jul). Differences in site-specific human-vector exposure profiles were due to contrasting cultural and lifestyle practices between Permé and Puerto Obaldía (possibly partly influenced by the absence of electricity in Permé), and lower LLIN use in Permé. This evidence supported a previously planned LLIN campaign alongside a social behaviour change communication (SBCC) strategy in the Guna Yala Comarca (Jul 2019), which increased LLIN use. In turn, this led to a reduction of indoor exposure to mosquito bites, and a shift to predominant outdoor exposure to mosquito bites.

Conclusion

ESPT-based question-driven planning and the integration of HBOs, intervention, and HLC data generated evidence towards answering the programmatic questions. This evidence enabled the characterization of site-specific human-vector exposure profiles, and the quantification of remaining gaps in protection. These data also provide important insights into remaining gaps in protection that must be addressed to further reduce human exposure to mosquito bites at these sites.
Exosomes derived from human adipose mesenchymal stem cells ameliorate hepatic fibrosis by inhibiting PI3K/Akt/mTOR pathway and remodeling choline metabolism
Authors: Zhang Zilong , Shang Jin , Yang Qinyan , Dai Zonglin , Liang Yuxin , Lai Chunyou , Feng Tianhang , Zhong Deyuan , Zou Haibo , Sun Lelin , Su Yuhao , Yan Su , Chen Jie , Yao Yutong , Shi Ying , Huang Xiaolun
Published: January 2023

Liver fibrosis is a chronic liver disease with the presence of progressive wound healing response caused by liver injury. Currently, there are no approved therapies for liver fibrosis. Exosomes derived from human adipose mesenchymal stem cells (hADMSCs-Exo) have displayed a prominent therapeutic effect on liver diseases. However, few studies have evaluated therapeutic effect of hADMSCs-Exo in liver fibrosis and cirrhosis, and its precise mechanisms of action remain unclear. Herein, we investigated anti-fibrotic efficacy of hADMSCs-Exo in vitro and in vivo, and identified important metabolic changes and the detailed mechanism through transcriptomic and metabolomic profiling. We found hADMSCs-Exo could inhibit the proliferation of activated hepatic stellate cells through aggravating apoptosis and arresting G1 phase, effectively inhibiting the expression of profibrogenic proteins and epithelial-to-mesenchymal transition (EMT) in vitro. Moreover, it could significantly block collagen deposition and EMT process, improve liver function and reduce liver inflammation in liver cirrhosis mice model. The omics analysis revealed that the key mechanism of hADMSCs-Exo anti-hepatic fibrosis was the inhibition of PI3K/AKT/mTOR signaling pathway and affecting the changes of metabolites in lipid metabolism, and mainly regulating choline metabolism. CHPT1 activated by hADMSCs-Exo facilitated formation and maintenance of vesicular membranes. Thus, our study indicates that hADMSCs-Exo can attenuate hepatic stellate cell activation and suppress the progression of liver fibrosis, which holds the significant potential of hADMSCs-Exo for use as extracellular nanovesicles-based therapeutics in the treatment of liver fibrosis and possibly other intractable chronic liver diseases.

Graphical Abstract
Standardising policy and technology responses in the immediate aftermath of a pandemic: a comparative and conceptual framework
Authors: Moy Naomi , Antonini Marcello , Kyhlstedt Mattias , Fiorentini Gianluca , Paolucci Francesco
Published: January 2023

Background

The initial policy response to the COVID-19 pandemic has differed widely across countries. Such variability in government interventions has made it difficult for policymakers and health research systems to compare what has happened and the effectiveness of interventions across nations. Timely information and analysis are crucial to addressing the lag between the pandemic and government responses to implement targeted interventions to alleviate the impact of the pandemic.

Methods

To examine the effect government interventions and technological responses have on epidemiological and economic outcomes, this policy paper proposes a conceptual framework that provides a qualitative taxonomy of government policy directives implemented in the immediate aftermath of a pandemic announcement and before vaccines are implementable. This framework assigns a gradient indicating the intensity and extent of the policy measures and applies the gradient to four countries that share similar institutional features but different COVID-19 experiences: Italy, New Zealand, the United Kingdom and the United States of America.

Results

Using the categorisation framework allows qualitative information to be presented, and more specifically the gradient can show the dynamic impact of policy interventions on specific outcomes. We have observed that the policy categorisation described here can be used by decision-makers to examine the impacts of major viral outbreaks such as SARS-CoV-2 on health and economic outcomes over time. The framework allows for a visualisation of the frequency and comparison of dominant policies and provides a conceptual tool to assess how dominant interventions (and innovations) affect different sets of health and non-health related outcomes during the response phase to the pandemic.

Conclusions

Policymakers and health researchers should converge toward an optimal set of policy interventions to minimize the costs of the pandemic (i.e., health and economic), and facilitate coordination across governance levels before effective vaccines are produced. The proposed framework provides a useful tool to direct health research system resources and build a policy benchmark for future viral outbreaks where vaccines are not readily available.
A multi-omic analysis reveals the esophageal dysbiosis as the predominant trait of eosinophilic esophagitis
Authors: Massimino Luca , Barchi Alberto , Mandarino Francesco Vito , Spanò Salvatore , Lamparelli Luigi Antonio , Vespa Edoardo , Passaretti Sandro , Peyrin-Biroulet Laurent , Savarino Edoardo Vincenzo , Jairath Vipul , Ungaro Federica , Danese Silvio
Published: January 2023

Background

Eosinophilic esophagitis (EoE) is a chronic immune-mediated rare disease, characterized by esophageal dysfunctions. It is likely to be primarily activated by food antigens and is classified as a chronic disease for most patients. Therefore, a deeper understanding of the pathogenetic mechanisms underlying EoE is needed to implement and improve therapeutic lines of intervention and ameliorate overall patient wellness.

Methods

RNA-seq data of 18 different studies on EoE, downloaded from NCBI GEO with faster-qdump (https://github.com/ncbi/sra-tools), were batch-corrected and analyzed for transcriptomics and metatranscriptomics profiling as well as biological process functional enrichment. The EoE TaMMA web app was designed with plotly and dash. Tabula Sapiens raw data were downloaded from the UCSC Cell Browser. Esophageal single-cell raw data analysis was performed within the Automated Single-cell Analysis Pipeline. Single-cell data-driven bulk RNA-seq data deconvolution was performed with MuSiC and CIBERSORTx. Multi-omics integration was performed with MOFA.

Results

The EoE TaMMA framework pointed out disease-specific molecular signatures, confirming its reliability in reanalyzing transcriptomic data, and providing new EoE-specific molecular markers including CXCL14, distinguishing EoE from gastroesophageal reflux disorder. EoE TaMMA also revealed microbiota dysbiosis as a predominant characteristic of EoE pathogenesis. Finally, the multi-omics analysis highlighted the presence of defined classes of microbial entities in subsets of patients that may participate in inducing the antigen-mediated response typical of EoE pathogenesis.

Conclusions

Our study showed that the complex EoE molecular network may be unraveled through advanced bioinformatics, integrating different components of the disease process into an omics-based network approach. This may implement EoE management and treatment in the coming years.
Lipolysis and gestational diabetes mellitus onset: a case-cohort genome-wide association study in Chinese
Authors: Zhang Miao , Li Qing , Wang Kai-Lin , Dong Yao , Mu Yu-Tong , Cao Yan-Min , Liu Jin , Li Zi-Heng , Cui Hui-Lu , Liu Hai-Yan , Hu An-Qun , Zheng Ying-Jie
Published: January 2023

Background

Genetic knowledge of gestational diabetes mellitus (GDM) in Chinese women is quite limited. This study aimed to identify the risk factors and mechanism of GDM at the genetic level in a Chinese population.

Methods

We conducted a genome-wide association study (GWAS) based on single nucleotide polymorphism (SNP) array genotyping (ASA-CHIA Bead chip, Illumina) and a case-cohort study design. Variants including SNPs, copy number variants (CNVs), and insertions-deletions (InDels) were called from genotyping data. A total of 2232 pregnant women were enrolled in their first/second trimester between February 2018 and December 2020 from Anqing Municipal Hospital in Anhui Province, China. The GWAS included 193 GDM patients and 819 subjects without a diabetes diagnosis, and risk ratios (RRs) and their 95% confidence intervals (CIs) were estimated by a regression-based method conditional on the population structure. The calling and quality control of genotyping data were performed following published guidelines. CNVs were merged into CNV regions (CNVR) to simplify analyses. To interpret the GWAS results, gene mapping and overexpression analyses (ORAs) were further performed to prioritize the candidate genes and related biological mechanisms.

Results

We identified 14 CNVRs (false discovery rate corrected P values < 0.05) and two suggestively significant SNPs (P value < 0.00001) associated with GDM, and a total of 19 candidate genes were mapped. Ten genes were significantly enriched in gene sets related to lipase (triglyceride lipase and lipoprotein lipase) activity (LIPF, LIPK, LIPN, and LIPJ genes), oxidoreductase activity (TPH1 and TPH2 genes), and cellular components beta-catenin destruction complex (APC and GSK3B genes), Wnt signalosome (APC and GSK3B genes), and lateral element in the Gene Ontology resource (BRCA1 and SYCP2 genes) by two ORA methods (adjusted P values < 0.05).

Conclusions

Genes related to lipolysis, redox reaction, and proliferation of islet β-cells are associated with GDM in Chinese women. Energy metabolism, particularly lipolysis, may play an important role in GDM aetiology and pathology, which needs further molecular studies to verify.
Home-based brain–computer interface attention training program for attention deficit hyperactivity disorder: a feasibility trial
Authors: Lim Choon Guan , Soh Chui Pin , Lim Shernice Shi Yun , Fung Daniel Shuen Sheng , Guan Cuntai , Lee Tih-Shih
Published: January 2023

Background

Attention deficit hyperactivity disorder (ADHD) is a prevalent child neurodevelopmental disorder that is treated in clinics and in schools. Previous trials suggested that our brain–computer interface (BCI)-based attention training program could improve ADHD symptoms. We have since developed a tablet version of the training program which can be paired with wireless EEG headsets. In this trial, we investigated the feasibility of delivering this tablet-based BCI intervention at home.

Methods

Twenty children diagnosed with ADHD, who did not receive any medication for the preceding month, were randomised to receive the 8-week tablet-based BCI intervention either in the clinic or at home. Those in the home intervention group received instructions before commencing the program and got reminders if they were lagging on the training sessions. The ADHD Rating Scale was completed by a blinded clinician at baseline and at week 8. Adverse events were monitored during any contact with the child throughout the trial and at week 8.

Results

Children in both groups could complete the tablet-based intervention easily on their own with minimal support from the clinic therapist or their parents (at home). The intervention was safe with few reported adverse effects. Clinician-rated inattentive symptoms on the ADHD-Rating Scale reduced by 3.2 (SD 6.20) and 3.9 (SD 5.08) for the home-based and clinic-based groups respectively, suggesting that home-based intervention was comparable to clinic-based intervention.

Conclusions

This trial demonstrated that the tablet version of our BCI-based attention training program can be safely delivered to children in the comfort of their own home.

Trial registration This trial is registered at clinicaltrials.gov as NCT01344044
Transient inhibition of microsomal prostaglandin E synthase-1 after status epilepticus blunts brain inflammation and is neuroprotective
Authors: Yasmen Nelufar , Sluter Madison N. , Li Lexiao , Yu Ying , Jiang Jianxiong
Published: January 2023

Status epilepticus (SE) in humans is characterized by prolonged convulsive seizures that are generalized and often difficult to control. The current antiseizure drugs (ASDs) aim to stop seizures quickly enough to prevent the SE-induced brain inflammation, injury, and long-term sequelae. However, sole reliance on acute therapies is imprudent because prompt treatment may not always be possible under certain circumstances. The pathophysiological mechanisms underlying the devastating consequences of SE are presumably associated with neuroinflammatory reactions, where prostaglandin E2 (PGE2) plays a pivotal role. As the terminal synthase for pathogenic PGE2, the microsomal prostaglandin E synthase-1 (mPGES-1) is rapidly and robustly induced by prolonged seizures. Congenital deletion of mPGES-1 in mice is neuroprotective and blunts gliosis following chemoconvulsant seizures, suggesting the feasibility of mPGES-1 as a potential antiepileptic target. Herein, we investigated the effects of a dual species mPGES-1 inhibitor in a mouse pilocarpine model of SE. Treatment with the mPGES-1 inhibitor in mice after SE that was terminated by diazepam, a fast-acting benzodiazepine, time-dependently abolished the SE-induced PGE2 within the brain. Its negligible effects on cyclooxygenases, the enzymes responsible for the initial step of PGE2 biosynthesis, validated its specificity to mPGES-1. Post-SE inhibition of mPGES-1 also blunted proinflammatory cytokines and reactive gliosis in the hippocampus and broadly prevented neuronal damage in a number of brain areas. Thus, pharmacological inhibition of mPGES-1 by small-molecule inhibitors might provide an adjunctive strategy that can be implemented hours after SE, together with first-line ASDs, to reduce SE-provoked brain inflammation and injury.
TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability
Authors: Chen Xintian , Yong Hongmei , Chen Miaolei , Deng Chuyin , Wang Pengfei , Chu Sufang , Li Minle , Hou Pingfu , Zheng Junnian , Li Zhongwei , Bai Jin
Published: January 2023

Background

Metabolic reprogramming is a hallmark of various cancers. Targeting metabolic processes is a very attractive treatment for cancer. Renal cell carcinoma (RCC) is a type of metabolic disease, and the lipidomic profile of RCC is significantly altered compared with that of healthy tissue. However, the molecular mechanism underlying lipid metabolism regulation in RCC is not clear.

Methods

The XF long-chain fatty acid oxidative stress test kits were used to assess the dependence on long-chain fatty acids and mitochondrial function after knockdown TRIM21 in RCC cells. The effect of TRIM21 on the lipid content in RCC cells was determined by metabolomics analysis, Oil Red O staining, and cellular Nile red staining. qRT-PCR and western blot were used to explore the relationship between TRIM21 and lipogenesis, and then the key molecule sterol regulatory element binding transcription factor 1 (SREBF1) was identified to interact with TRIM21 by immunoprecipitation, which was also identified in an orthotopic model. Subsequently, the relevance and clinical significance of TRIM21 and SREBF1 were analyzed by The Cancer Genome Atlas (TCGA) database, and 239 tissues were collected from RCC patients.

Results

TRIM21 silencing attenuated the dependence of RCC cells on fatty acids, and enhanced lipid accumulation in RCC cells. TRIM21 overexpression significantly decreased lipid contents by decreasing the expression of lipogenic enzymes via ubiquitination-mediated degradation of SREBF1. SREBF1 is critical for TRIM21-mediated lipogenesis inhibition in vitro and in vivo. Moreover, TRIM21 expression is negatively correlated with SREBF1 expression, and TRIM21-SREBF1 is a reliable combinational biomarker for RCC prognosis.

Conclusion

The findings from this study reveal a novel pathway through which TRIM21 inhibits the lipid metabolism process of RCC and shed light on the development of targeted metabolic treatment and prognosis diagnosis of RCC.
Studies on the mechanism of Toxoplasma gondii Chinese 1 genotype Wh6 strain causing mice abnormal cognitive behavior
Authors: Tao Qing , Yang Di , Qin Kunpeng , Liu Lei , Jin Mengmeng , Zhang Famin , Zhu Jinjin , Wang Jie , Luo Qingli , Du Jian , Yu Li , Shen Jilong , Chu Deyong
Published: January 2023

Background

Alzheimer's disease presents an abnormal cognitive behavior. TgCtwh6 is one of the predominant T. gondii strains prevalent in China. Although T. gondii type II strain infection can cause host cognitive behavioral abnormalities, we do not know whether TgCtwh6 could also cause host cognitive behavioral changes. So, in this study, we will focus on the effect of TgCtwh6 on mouse cognitive behavior and try in vivo and in vitro to explore the underlying mechanism by which TgCtwh6 give rise to mice cognitive behavior changes at the cellular and molecular level.

Methods

C57BL/6 mice were infected orally with TgCtwh6 cysts. From day 90 post-infection on, all mice were conducted through the open field test and then Morris water maze test to evaluate cognitive behavior. The morphology and number of cells in hippocampus were examined with hematoxylin-eosin (H&E) and Nissl staining; moreover, Aβ protein in hippocampus was determined with immunohistochemistry and thioflavin S plaque staining. Synaptotagmin 1, apoptosis-related proteins, BACE1 and APP proteins and genes from hippocampus were assessed by western blotting or qRT-PCR. Hippocampal neuronal cell line or mouse microglial cell line was challenged with TgCtwh6 tachyzoites and then separately cultured in a well or co-cultured in a transwell device. The target proteins and genes were analyzed by immunofluorescence staining, western blotting and qRT-PCR. In addition, mouse microglial cell line polarization state and hippocampal neuronal cell line apoptosis were estimated using flow cytometry assay.

Results

The OFT and MWMT indicated that infected mice had cognitive behavioral impairments. The hippocampal tissue assay showed abnormal neuron morphology and a decreased number in infected mice. Moreover, pro-apoptotic proteins, as well as BACE1, APP and Aβ proteins, increased in the infected mouse hippocampus. The experiments in vitro showed that pro-apoptotic proteins and p-NF-κBp65, NF-κBp65, BACE1, APP and Aβ proteins or genes were significantly increased in the infected HT22. In addition, CD80, pro-inflammatory factors, notch, hes1 proteins and genes were enhanced in the infected BV2. Interestingly, not only the APP and pro-apoptotic proteins in HT22, but also the apoptosis rate of HT22 increased after the infected BV2 were co-cultured with the HT22 in a transwell device.

Conclusions

Neuron apoptosis, Aβ deposition and neuroinflammatory response involved with microglia polarization are the molecular and cellular mechanisms by which TgCtwh6 causes mouse cognitive behavioral abnormalities.

Graphical Abstract
TRPA1 as a potential factor and drug target in scleroderma: dermal fibrosis and alternative macrophage activation are attenuated in TRPA1-deficient mice in bleomycin-induced experimental model of scleroderma
Authors: Mäki-Opas Ilari , Hämäläinen Mari , Moilanen Eeva , Scotece Morena
Published: January 2023

Background

Systemic sclerosis is a rheumatoid disease best known for its fibrotic skin manifestations called scleroderma. Alternatively activated (M2-type) macrophages are normally involved in the resolution of inflammation and wound healing but also in fibrosing diseases such as scleroderma. TRPA1 is a non-selective cation channel, activation of which causes pain and neurogenic inflammation. In the present study, we investigated the role of TRPA1 in bleomycin-induced skin fibrosis mimicking scleroderma.

Methods

Wild type and TRPA1-deficient mice were challenged with intradermal bleomycin injections to induce a scleroderma-mimicking disease. Macrophages were investigated in vitro to evaluate the underlying mechanisms.

Results

Bleomycin induced dermal thickening and collagen accumulation in wild type mice and that was significantly attenuated in TRPA1-deficient animals. Accordingly, the expression of collagens 1A1, 1A2, and 3A1 as well as pro-fibrotic factors TGF-beta, CTGF, fibronectin-1 and YKL-40, and M2 macrophage markers Arg1 and MRC1 were lower in TRPA1-deficient than wild type mice. Furthermore, bleomycin was discovered to significantly enhance M2-marker expression particularly in the presence of IL-4 in wild type macrophages in vitro, but not in macrophages harvested from TRPA1-deficient mice. IL-4-induced PPARγ-expression in macrophages was increased by bleomycin, providing a possible mechanism behind the phenomenon.

Conclusions

In conclusion, the results indicate that interfering TRPA1 attenuates fibrotic and inflammatory responses in bleomycin-induced scleroderma. Therefore, TRPA1-blocking treatment could potentially alleviate M2 macrophage driven diseases like systemic sclerosis and scleroderma.
The beneficial effect on cognition of noninvasive brain stimulation intervention in patients with dementia: a network meta-analysis of randomized controlled trials
Authors: Tseng Ping-Tao , Chen Yen-Wen , Zeng Bing-Yan , Zeng Bing-Syuan , Hung Chao-Ming , Sun Cheuk-Kwan , Cheng Yu-Shian , Stubbs Brendon , Carvalho Andre F. , Brunoni Andre R. , Su Kuan-Pin , Tu Yu-Kang , Wu Yi-Cheng , Chen Tien-Yu , Lin Pao-Yen , Liang Chih-Sung , Hsu Chih-Wei , Chu Che-Sheng , Suen Mein-Woei , Li Cheng-Ta
Published: January 2023

Background

Dementia [i.e., Alzheimer disease (AD)], the most common neurodegenerative disease, causes profound negative impacts on executive function and quality of life. Available pharmacological treatments often fail to achieve satisfactory outcomes. Noninvasive brain stimulation (NIBS) techniques, which focally modify cortical function and enhance synaptic long-term potentiation, are potentially beneficial for the cognition in patients with AD. The aim of the current network meta-analysis (NMA) was to evaluate the efficacy and safety of different NIBS interventions in patients with AD through NMA.

Methods

Only randomized controlled trials (RCTs) examining NIBS interventions in patients with AD had been included. All NMA procedures were performed under the frequentist model. The primary and secondary outcomes were changes in cognitive function and quality of life, respectively.

Results

Nineteen RCTs (639 participants) were included. The mean treatment and follow-up durations were 5.7 and 10.5 weeks, respectively. The combination of cathodal tDCS of the left dorsolateral prefrontal cortex and anodal tDCS over the right supraorbital region (c-tDCS-F3 + a-tDCS-Fp2) was associated with a significant beneficial effect on cognition compared with sham controls (standardized mean difference=2.43, 95% confidence interval=0.61–4.26, n=12 and 11). It was also associated with the greatest beneficial effect on cognition among all the investigated NIBS approaches. All the methods were well tolerated with regard to the safety profile, as reflected in the rates of adverse events or local discomfort, as well as acceptability, as indicated by dropout rate.

Conclusions

The present findings provide evidence of the benefits of NIBS, especially tDCS, for beneficial effect on cognition in patients with AD. However, because of few studies included, this effect was not replicated yet in the other studies. Therefore, future larger-scale and longer follow-up duration RCTs should be warranted.

Trial registration

PROSPERO CRD42020209516. The current study had been approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center (TSGHIRB No. B-109-29).
Joint hybrid-precoding design for MU-MISO systems with a subconnected architecture
Authors: Bahingayi Eduard E. , Lee Kyungchun
Published: January 2023

In this study, we propose a joint hybrid-precoding algorithm for multiuser multiple-input single-output downlink systems. Specifically, we consider that the base station employs an energy-efficient hybrid-precoding subconnected (SC) architecture with fixed equal subarrays (FESA) (SC-FESA). Optimizing the analog precoding matrix in an SC-FESA architecture is challenging due to its unique constraint structure. In this study, to maximize system sum rate, we propose an efficient method to transform the system’s sum-rate optimization problem into a continuous and differentiable objective function wherein only the nonzero elements of the analog precoding matrix are optimized. For the formulated problem, we develop an alternating optimization (AO) approach to jointly optimize the digital and analog precoders in succession by maximizing the system’s sum rate. Specifically, in the proposed AO method, when the digital precoder is fixed, we employ the Riemannian conjugate gradient algorithm to generate the analog precoder. Furthermore, when the analog precoder is fixed, we use the minimum mean squared error method to obtain the digital precoder. Numerical simulation results show that the proposed AO algorithm improves the sum rate and energy efficiency of the SC-FESA architecture compared to existing algorithms.
Using computer-based habit versus chess-based cognitive remediation training as add-on therapy to modify the imbalance between habitual behavior and cognitive control in tobacco use disorder: protocol of a randomized controlled, fMRI study
Authors: Karl Damian , Wieland Alfred , Shevchenko Yury , Grundinger Nadja , Machunze Noah , Gerhardt Sarah , Flor Herta , Vollstädt-Klein Sabine
Published: January 2023

Background

Although the vast majority of smokers are aware of the enormous preventable health hazards caused by smoking, only a small percentage of smokers manage to remain abstinent in the long term. One possible explanation for this discrepancy lies in the inflexibility of addictive behavior and associated disadvantageous decision‐making. According to a dual‐process theory of decision‐making, two distinct decision systems can be identified. One slow deliberate system based on desirable expectations of outcome value described as goal‐directed behavior and a fast reflexive system based on habitual instrumental behavior and driven by reinforcement experienced in the past. In the course of addiction development, an imbalance occurs between habitual behavior and goal-directed. The present study aims to investigate the modifiability of the balance between habitual and goal-directed behavior at the neurobiological and behavioral level in smokers using two different novel add-on therapies. We hypothesize that both interventions change the balance between goal-directed and habitual behavior, but by different mechanisms. Whereas a cognitive remediation treatment should directly improve cognitive control, in contrast an implicit priming task should affect the early processing and the emotional valence of smoking and smoking cues.

Methods

We will conduct a randomized controlled study in treatment-seeking individuals with tobacco use disorder applying either chess-based cognitive remediation training (N = 30) or implicit computer-based habit-modifying training (N = 30) as add on therapy compared to the standard smoking cessation group therapy (N = 30) only. We will address neurobiological and neuropsychological correlates associated with craving, reward devaluation, cue reactivity and attentional bias. In addition, various effects of treatment and prediction of treatment outcome will be examined using behavioral and neural measures.

Discussion

The present study will apply different examination methods such as functional magnetic resonance imaging, neuropsychological tests, and self-report before and after the interventions. This allows the identification of intervention-specific mechanisms and therefore potential neurobiology-based specific treatment targets for individuals with Tobacco Use Disorder.

Trial registration: Registered at clinicaltrials.gov/ct2/show/NCT03764969 (05 December 2018).
Active learning and education 4.0 for complex thinking training: analysis of two case studies in open education
Authors: Patiño Azeneth , Ramírez-Montoya María Soledad , Buenestado-Fernández Mariana
Published: January 2023

This article focuses on empirically analyzing the final products designed by 147 academics from 11 countries who participated in an international open education movement workshop by answering the research questions “What are the techno-pedagogical components of the products designed by the participants to encourage the open educational movement? and what practice of the open educational movement is being executed?” The article starts with a conceptual basis that describes the concepts of Active learning, Education 4.0, Complex Thinking and Open Education. It presents (1) the case study methodology on which this research is based, (2) two case studies on open education, (3) a game-based intervention proposal to support instructors in training university students in complex thinking skills based on Education 4.0 technologies and game-based learning principles, (4) and a discussion of the findings and opportunities for further work in the area. The findings of this study reveal that (A) the use of emerging and 4.0 technologies in initiatives of the open education movement continue to increase; (B) most of the open education initiatives designed by academics participating in the workshops were focused on the production of OER; and (C) inclusive access to education and continuing professional development of teachers is a constant concern addressed in open education initiatives. The results of this research suggest that training and development interventions implying the creation or design of open education initiatives should focus on encouraging all kinds of open education practices (i.e. use, production, dissemination and mobilization).
Pivot shift intraoperative quantitative assessment using a smartphone accelerometer in ACL deficient knees
Authors: Soudé Guillaume , De Villeneuve Bargemon Jean‐Baptiste , Khakha Raghbir , Pithioux Martine , Argenson Jean‐Noël , Ollivier Matthieu , Jacquet Christophe
Published: January 2023

Purpose

The Pivot Shift (PS) test is a complex clinical sign that assesses the internal rotation and anterior tibial translation, which occurs abnormally in ACL deficient‐knees. Because of the high inter‐observer variability, different devices have been designed to characterize this complex movement in quantitative variables. The objective of this pilot study is to validate the reproducibility of intraoperative quantitative assessment of the PS with a smartphone accelerometer.

Methods

Twelve ACL‐injured knees were included and compared with the contralateral uninjured side. The PS was measured by two independent observers utilizing a smartphone accelerometer and graded according to the IKDC classification. Measurements were taken preoperatively, intraoperatively and postoperatively. Intraoperative readings were taken during each stage of reconstruction or repair of meniscoligamentous lesions including meniscal lesions, ramp lesions, ACL reconstruction and lateral tenodesis. Reproducibility of the measurements were evaluated according to an intraclass correlation coefficient (ICC).

Results

The intra‐observer reliability was good for the first examiner and excellent for the second examiner, with the ICC 0.89 [0.67, 0.98] p < 0,001 and ICC 0.97 [0.91, 1.0] p < 0,001 respectively. The inter‐observer reliability was excellent between the two observers with the ICC 0.99 [0.97, 1.0] p < 0,001. The mean tibial acceleration measured 3.45 m.s2 (SD = 1.71) preoperatively on the injured knees and 1.03 m.s2 (SD = 0.36) on the healthy knees, demonstrating a significant difference following univariate analysis p < 0.001. Postoperatively, no significant difference was observed between healthy and reconstructed knees The magnitudes of tibial acceleration values were correlated with the PS IKDC grade.

Conclusion

The smartphone accelerometer is a reproducible device to quantitatively assess the internal rotation and anterior tibial translation during ACL reconstruction surgery. The measurements are influenced by the different surgical steps. Other larger cohort studies are needed to evaluate the specific impact of each step of the ACL reconstruction and meniscal repair on this measurement. An external validation using other technologies are needed to validate the reliability of this device to assess the PS test.

Level of evidence

Level IV, case series, pilot study.