bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating socioeconomic disparities in lung cancer diagnosis, treatment and mortality: an Italian cohort study
Authors: Servadio Michela , Rosa Alessandro C. , Addis Antonio , Kirchmayer Ursula , Cozzi Ilaria , Michelozzi Paola , Cipelli Riccardo , Heiman Franca , Davoli Marina , Belleudi Valeria
Published: June 2024

Background

Lung cancer is one of the most lethal cancers worldwide and patient clinical outcomes seem influenced by their socioeconomic position (SEP). Since little has been investigated on this topic in the Italian context, our aim was to investigate the role of SEP in the care pathway of lung cancer patients in terms of diagnosis, treatment and mortality.

Methods

This observational retrospective cohort study included patients discharged in the Lazio Region with a lung cancer diagnosis between 2014 and 2017. In the main analysis, educational level was used as SEP measure. Multivariate models, adjusted for demographic and clinical variables, were applied to evaluate the association between SEP and study outcomes, stratified for metastatic (M) and non-metastatic (NM) cancer. We defined a diagnosis as 'delayed' when patients received their initial cancer diagnosis after an emergency department admission. Access to advanced lung cancer treatments (high-cost, novel and innovative treatments) and mortality were investigated within the 24-month period post-diagnosis. Moreover, two additional indicators of SEP were examined in the sensitivity analysis: one focusing on area deprivation and the other on income-based exemption.

Results

A total of 13,251 patients were identified (37.3% with metastasis). The majority were males (> 60%) and over half were older than 70 years. The distribution of SEP levels among patients was as follow: 31% low, 29% medium–low, 32% medium–high and 7% high. As SEP increased, the risks of receiving a delayed diagnosis ((high vs low: M: OR = 0.29 (0.23–0.38), NM: OR = 0.20 (0.16–0.25)) and of mortality ((high vs low M: OR = 0.77 (0.68–0.88) and NM: 0.61 (0.54–0.69)) decreased. Access to advanced lung cancer treatments increased in accordance with SEP only in the M cohort (high vs low: M: OR = 1.57 (1.18–2.09)). The primary findings were corroborated by sensitivity analysis.

Conclusions

Our study highlighted the need of public health preventive and educational programs in Italy, a country where the care pathway of lung cancer patients, especially in terms of diagnosis and mortality, appears to be negatively affected by SEP level.
Oral appliance therapy vs. positional therapy for managing positional obstructive sleep apnea; a systematic review and meta-analysis of randomized control trials
Authors: Mohamed Abdelrahman MA , Mohammed Omar Magdy , Liu Shanshan , Al-balaa Maher , Al-warafi Leena Ali , Peng Song Juan , Qiao Yi Qiang
Published: June 2024

Aim

To assess the efficacy of positional therapy and oral appliance therapy for the management of positional obstructive sleep apnea.

Methods

We searched PubMed, Web of Science, Cochrane, and SCOPUS for relevant clinical trials. Quality assessment of the included trials was evaluated according to Cochrane’s risk of bias tool. We included the following outcomes: The apnea-hypopnea index (AHI), AHI non-supine, AHI supine, sleep efficiency, percentage of supine sleep, Adherence (≥ 4 h/night, ≥ 5 days/week), Oxygen desaturation Index, Arousal Index, Epworth Sleepiness Scale score (ESS), Mean SpO2, and Functional Outcomes of Sleep Questionnaire.

Results

The AHI non-supine and the ESS scores were significantly lower in the OAT cohort than in the PT cohort. The PT cohort was associated with a significantly decreased percentage of supine sleep than the OAT cohort (MD= -26.07 [-33.15, -19.00], P = 0.0001). There was no significant variation between PT cohort and OAT cohort regarding total AHI, AHI supine, ODI, sleep efficiency, arousal index, FOSQ, adherence, and mean SpO2.

Conclusion

Both Positional Therapy and Oral Appliance Therapy effectively addressed Obstructive Sleep Apnea. However, Oral Appliance Therapy exhibited higher efficiency, leading to increased supine sleep percentage and more significant reductions in the Apnea Hypopnea Index during non-supine positions, as well as lower scores on the Epworth Sleepiness Scale.
Psychological status of pregnant women during the omicron pandemic outbreak in China
Authors: Bao Shuting , Chen Bangwu , Zhu Shuqi , Hu Ying , Lee Chee Shin , Du Mengkai , Zhou Menglin , Fan Danfeng , Xie Biao , Gu Huimin , Liang Zhaoxia
Published: June 2024

Background

Pregnant women faced great challenges and psychological and physiological changes of varying degrees during the omicron epidemic outbreak. It is important to recognize the potential impact of these challenges on the mental health of pregnant women and to provide appropriate resources and support to mitigate their effects.

Method

By using the convenience sampling approach, a total of 401 pregnant women from two hospitals of different grades in two cities were included in the survey. The cross-sectional survey was conducted by basic characteristics, Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-9), Insomnia Severity Index (ISI) and self-made questionnaire.

Results

Insomnia affected 207 participants (51.6%), depression affected 160 participants (39.9%) and anxiety affected 151 participants (37.7%). Moreover, pregnant women in provincial capital city were more likely to experience anxiety, depression and insomnia than those in county-level city (P < 0.01). Pregnant women’s anxiety, depression and insomnia were positively correlated with the severity of COVID-19 infection (P < 0.05). However, COVID-19 infection had no appreciable impact on maternal demand for termination of pregnancy and cesarean section (P > 0.05).

Conclusion

Pregnant women frequently suffer from anxiety disorder, depression and insomnia as a result of the omicron pandemic in China. During this period, the community and medical professionals should provide more psychological counseling, conduct health education and offer virtual prenatal care to pregnant women (particularly in the provincial capital city).
Unraveling the treatment effects of huanglian jiedu decoction on drug-induced liver injury based on network pharmacology, molecular docking and experimental validation
Authors: Xie Yaochen , Gong Shuchen , Wang Lingkun , Yang Zhaoxu , Yang Chen , Li Guilin , Zha Huiyan , Lv Shuying , Xiao Boneng , Chen Xiaoyu , Di Zhenning , He Qiaojun , Wang Jincheng , Weng Qinjie
Published: June 2024

Huanglian Jiedu Decoction (HJD) is a well-known Traditional Chinese Medicine formula that has been used for liver protection in thousands of years. However, the therapeutic effects and mechanisms of HJD in treating drug-induced liver injury (DILI) remain unknown. In this study, a total of 26 genes related to both HJD and DILI were identified, which are corresponding to a total of 41 potential active compounds in HJD. KEGG analysis revealed that Tryptophan metabolism pathway is particularly important. The overlapped genes from KEGG and GO analysis indicated the significance of CYP1A1, CYP1A2, and CYP1B1. Experimental results confirmed that HJD has a protective effect on DILI through Tryptophan metabolism pathway. In addition, the active ingredients Corymbosin, and Moslosooflavone were found to have relative strong intensity in UPLC-Q-TOF-MS/MS analysis, showing interactions with CYP1A1, CYP1A2, and CYP1B1 through molecule docking. These findings could provide insights into the treatment effects of HJD on DILI.
Exploring the potential of Huangqin Tang in breast cancer treatment using network pharmacological analysis and experimental verification
Authors: Zhao Ziqiao , Zhu Yongxia , Long Fangyi , Ma Yu , Tang Qing , Wang Ting
Published: June 2024

Aims of this study

This study aims to investigate the potential of Huangqin Tang (HQT), a traditional Chinese medicine formulation, in the treatment of breast cancer (BC) through a comprehensive approach integrating network pharmacology, molecular docking, and experimental validation.

Methods

Chemical composition and target information of HQT were collected using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Disease-related target genes were obtained from the GeneCards database. Network pharmacological analysis, including construction of compound-disease-target networks and protein-protein interaction networks, was performed. Molecular docking simulations were conducted to evaluate the binding affinity between HQT components and key targets. Experimental validation was carried out using cell viability assays, clone formation assays, flow cytometry, Western blotting, and pathway analysis.

Results

A total of 210 candidate targets were identified. Network analysis revealed STAT3, AKT1, MAPK3 etc. as central targets. Enrichment analysis suggested HQT may exert anti-tumor effects through regulating lipid metabolism and inflammation related pathways. Molecular docking showed that the key compounds baicalein, wogonin, kaempferol and quercetin all bound effectively to MAPK1. The binding of baicalein to IL6 and naringenin to TNF-α was also relatively stable. The experimental results demonstrated that HQT effectively inhibited the proliferation of breast cancer cells, with IC50 values of 2.334 mg/mL and 1.749 mg/mL in MCF-7 cells at 24 h and 48 h, and IC50 values of 1.286 mg/mL and 1.496 mg/mL in MDA-MB-231 cells at 24 h and 48 h, respectively. Furthermore, HQT induced cell cycle arrest at the G2/M phase in breast cancer cells and downregulated the expression of related proteins including CDK1, Cyclin B1, CDK2, and Cyclin E. Additionally, HQT promoted apoptosis in breast cancer cells by upregulating the expression of Bak and CC-3, while downregulating the expression of Bcl-2. Notably, HQT also exhibited regulatory effects on the HIF-1 signaling pathway.

Conclusions

This study provides insights into the potential multi-component and multi-target mechanisms of HQT against BC, suggesting it may achieve therapeutic effects through regulating inflammatory response and cancer-related pathways via the identified active compounds and targets. The findings highlight the importance of integrating traditional medicine with modern approaches for the development of novel cancer therapies.
Evaluating the impact of an educational intervention on the history of racism in America for teaching structural competency to medical academicians
Authors: Glenn Jason E. , Bridges Kristina M. , Boye-Doe Kakra , Taylor LesLee , Peltzer Jill N. , Alexander Shawn Leigh , Binion Danielle , Schuette Matthew , Francis Carrie L. , McGee Jerrihlyn L.
Published: June 2024

Background

A challenge facing many Academic Health Centers (AHCs) attempting to revise health professions education to include the impact of racism as a social and structural determinant of health (SSDoH) is a lack of broad faculty expertise to reinforce and avoid undermining learning modules addressing this topic. To encourage an institutional culture that is in line with new anti-racism instruction, we developed a six-part educational series on the history of racism in America and its impact on contemporary health inequities for teaching structural competency to health professions academicians.

Methods

We developed a six-hour elective continuing education (CE) series for faculty and staff with the following objectives: (1) describe and discuss race as a social construct; (2) describe and discuss the decolonization of the health sciences and health care; (3) describe and discuss the history of systemic racism and structural violence from a socio-ecological perspective; and (4) describe and discuss reconciliation and repair in biomedicine. The series was spread over a six-month period and each monthly lecture was followed one week later by an open discussion debriefing session. Attendees were assessed on their understanding of each objective before and after each series segment.

Results

We found significant increases in knowledge and understanding of each objective as the series progressed. Attendees reported that the series helped them grapple with their discomfort in a constructive manner. Self-selected attendees were overwhelmingly women (81.8%), indicating a greater willingness to engage with this material than men.

Conclusions

The series provides a model for AHCs looking to promote anti-racism and structural competency among their faculty and staff.
Perspectives of researchers, science policy makers and research ethics committee members on the feedback of individual genetic research findings in African genomics research
Authors: Musvipwa Faith , Wonkam Ambroise , Berkman Benjamin , de Vries Jantina
Published: June 2024

Background

Genetic research can yield information that is unrelated to the study’s objectives but may be of clinical or personal interest to study participants. There is an emerging but controversial responsibility to return some genetic research results, however there is little evidence available about the views of genomic researchers and others on the African continent.

Methods

We conducted a continental survey to solicit perspectives of researchers, science policy makers and research ethics committee members on the feedback of individual genetic research findings in African genomics research.

Results

A total of 110 persons participated in the survey with 51 complete and 59 incomplete surveys received. Data was summarised using descriptive analysis. Overall, our respondents believed that individual genetic research results that are clinically actionable should be returned to study participants apparently because participants have a right to know things about their health, and it might also be a means for research participation to be recognized. Nonetheless, there is a need for development of precise guidance on how to return individual genetic research findings in African genomics research.

Discussion

Participants should receive information that could promote a healthier lifestyle; only clinically actionable findings should be returned, and participants should receive all important information that is directly relevant to their health. Nevertheless, detailed guidelines should inform what ought to be returned. H3Africa guidelines stipulate that it is generally considered good practice for researchers to feedback general study results, but there is no consensus about whether individual genomic study results should also be fed back. The decision on what individual results to feedback, if any, is very challenging and the specific context is important to make an appropriate determination.
Community health workers’ dissemination of COVID-19 information and services in the early pandemic response: a systematic review
Authors: Oliver Jane , Ferdinand Angeline , Kaufman Jessica , Allard Nicole , Danchin Margie , Gibney Katherine B.
Published: June 2024

Background

Community health workers (CHWs) had important roles mitigating the impact of the COVID-19 pandemic in vulnerable communities. We described how CHWs supported the dissemination of COVID-19 information and services during the early pandemic response.

Methods

Online article searches were conducted across five scientific databases, with review article reference lists hand searched to identify grey/unpublished literature. Articles were included if they reported on a program that engaged CHWs and aimed to prevent/control COVID-19.

Results

Nineteen relevant programs were identified from 18 included articles. CHWs were widely engaged in the pandemic response, especially in low- and middle-income countries and in vulnerable communities. CHWs’ ability to effectively disseminate COVID-19 information/services was enabled by community trust and understanding community needs. CHWs were often underfunded and required to work in difficult conditions. Pre-existing services incorporating CHWs rapidly adapted to the new challenges brought by the pandemic.

Conclusions

We recommend establishing programs that employ CHWs to disseminate health information and services in communities at-risk of misinformation and poor health outcomes during non-pandemic times. CHWs are well-placed to deliver interventions should an infectious disease outbreak arise. Having pre-existing trusted relationships between CHWs and community members may help protect vulnerable groups, including when outbreaks occur.
Molecular characterisation of fowl adenovirus associated with hydropericardium hepatitis syndrome in broiler and layer breeders in Azerbaijan
Authors: Bayraktar Erhan , Aydin Ozge , Tali Hasan Emre , Yilmaz Semaha Gul , Yilmaz Aysun , Turan Nuri , Bamac Ozge Erdogan , Ozturk Akay , Erdem Altug , Kelleci Metin , Sadeyen Jean-Remy , Chang Pengxiang , Yilmaz Huseyin , Iqbal Munir
Published: June 2024

Background

Fowl adenovirus-4 is a causative agent of hydropericardium hepatitis syndrome (HHS) in chickens and has been frequently reported from many countries. Fowl adenoviruses cause severe disease and mortality in broiler and layer breeders in Azerbaijan. Therefore, in this study, pathological lesions and the dissemination of fowl adenovirus-4 into the visceral organs of infected birds were investigated as well as molecular characterisation of detected strains. For this, liver, heart and spleen from 20 necropsied chickens originated from a broiler breeder flock and a layer breeder flock were embeded on the FTA cards and the samples were analysed for adenovirus-DNA by PCR and sequencing.

Results

The findings of necropsy in both broiler and layer breeder chickens were similar, and the liver was severely effected showing hepatitis, and the heart with hydropericardium lesions. The kidneys were swollen with haemorrhages and small white foci on the surface of the spleens were noted. Intestinal congestion and ecchymotic hemorrhages were also observed in some birds. Fowl adenovirus-4-DNA was detected by PCR in all collected organs of 20 birds. The sequence analysis revealed that fowl adenovirus-4 present in Azerbaijan and close similarity of the hexon genes of the adenoviruses existing in the Middle East, North America, far east and Indian subcontinent were determined by phylogenetic analysis. However, sequence diversity was detected from the adenovirus strains circulating in Europe, North and South America.

Conclusions

This study indicates the impact of fowl adenovirus-4 on the poultry health and production, and improved disease control and prevention strategies are necessary to reduce the HHS disease in chickens in Azerbaijan.
OLFM4 promotes the progression of intestinal metaplasia through activation of the MYH9/GSK3β/β-catenin pathway
Authors: Wei Hongfa , Li Wenchao , Zeng Leli , Ding Ni , Li Kuan , Yu Hong , Jiang Fei , Yin Haofan , Xia Yu , Deng Cuncan , Cai Nan , Chen Xiancong , Gu Liang , Chen Huanjie , Zhang Feiran , He Yulong , Li Jia , Zhang Changhua
Published: June 2024

Background

Intestinal metaplasia (IM) is classified into complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM). Patients diagnosed with IIM face an elevated susceptibility to the development of gastric cancer, underscoring the critical need for early screening measures. In addition to the complexities associated with diagnosis, the exact mechanisms driving the progression of gastric cancer in IIM patients remain poorly understood. OLFM4 is overexpressed in several types of tumors, including colorectal, gastric, pancreatic, and ovarian cancers, and its expression has been associated with tumor progression.

Methods

In this study, we used pathological sections from two clinical centers, biopsies of IM tissues, precancerous lesions of gastric cancer (PLGC) cell models, animal models, and organoids to explore the role of OLFM4 in IIM.

Results

Our results show that OLFM4 expression is highly increased in IIM, with superior diagnostic accuracy of IIM when compared to CDX2 and MUC2. OLFM4, along with MYH9, was overexpressed in IM organoids and PLGC animal models. Furthermore, OLFM4, in combination with Myosin heavy chain 9 (MYH9), accelerated the ubiquitination of GSK3β and resulted in increased β-catenin levels through the Wnt signaling pathway, promoting the proliferation and invasion abilities of PLGC cells.

Conclusions

OLFM4 represents a novel biomarker for IIM and could be utilized as an important auxiliary means to delimit the key population for early gastric cancer screening. Finally, our study identifies cell signaling pathways involved in the progression of IM.
Association of plasma high-density lipoprotein cholesterol level with risk of stress urinary incontinence in women: a retrospective study
Authors: Xu Wenning , Zheng Baojia , Su Lili , Xiang Yali
Published: June 2024

Background

Studies have found that high density lipoprotein cholesterol (HDL-C) levels are linked to a variety of diseases. However, evidence for the relationship between stress urinary incontinence (SUI) and HDL-C remain limited.

Methods

590 eligible women were enrolled. Basic characteristic, gynecological examinations and blood sampling were collected. The examination of the possible link between HDL-C and SUI was done using univariate and multivariate logistic regression. Feature importance ranking and Receiver operating characteristic (ROC) curves were performed to further evaluate the association between HDL-C and SUI in women.

Results

A significant association was found between HDL-C and SUI in women, revealing higher HDL-C levels were related to a lower risk of SUI (OR 0.238; 95%CI: 0.091–0.623; P < 0.01) after adjustment for potential key confounders. The AUC for the SUI predicted by the combined HDL-C was 0.845 (95%CI: 0.798–0.891, P < 0.001). The feature importance ranking revealed that vaginal delivery, HDL-C were the top two important factors.

Conclusions

HDL-C levels were correlated with the development of SUI. In addition to physical and surgical treatments, HDL-C may offer the possibility of potential targeted treatment and prevention of SUI afterwards.
Plasma exosomes from patients with active thyroid-associated orbitopathy induce inflammation and fibrosis in orbital fibroblasts
Authors: Wei Li , Huang Qinying , Tu Yunhai , Song Shihan , Zhang Xiaobo , Yu Bo , Liu Yufen , Li Ziwei , Huang Qing , Chen Lili , Liu Bo , Xu Shenglan , Li Tong , Liu Xiyuan , Hu Xiaozhou , Liu Weijie , Chi Zai-Long , Wu Wencan
Published: June 2024

Background

The pathogenesis of thyroid-associated orbitopathy (TAO) remains incompletely understand. The interaction between immunocytes and orbital fibroblasts (OFs) play a critical role in orbital inflammatory and fibrosis. Accumulating reports indicate that a significant portion of plasma exosomes (Pla-Exos) are derived from immune cells; however, their impact upon OFs function is unclear.

Methods

OFs were primary cultured from inactive TAO patients. Exosomes isolated from plasma samples of patients with active TAO and healthy controls (HCs) were utilized for functional and RNA cargo analysis. Functional analysis in thymocyte differentiation antigen-1+ (Thy-1+) OFs measured expression of inflammatory and fibrotic markers (mRNAs and proteins) and cell activity in response to Pla-Exos. RNA cargo analysis was performed by RNA sequencing and RT-qPCR. Thy-1+ OFs were transfected with miR-144-3p mimics/inhibitors to evaluate its regulation of inflammation, fibrosis, and proliferation.

Results

Pla-Exos derived from active TAO patients (Pla-ExosTAO−A) induced stronger production of inflammatory cytokines and hyaluronic acid (HA) in Thy-1+ OFs while inhibiting their proliferation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and single sample gene set enrichment analysis (ssGSEA) suggested that the difference in mRNA expression levels between Pla-ExosTAO−A and Pla-ExosHC was closely related to immune cells. Differential expression analysis revealed that 62 upregulated and 45 downregulated miRNAs in Pla-ExosTAO−A, with the elevation of miR-144-3p in both Pla-Exos and PBMCs in active TAO group. KEGG analysis revealed that the target genes of differentially expressed miRNA and miR-144-3p enriched in immune-related signaling pathways. Overexpression of the miR-144-3p mimic significantly upregulated the secretion of inflammatory cytokines and HA in Thy-1+ OFs while inhibiting their proliferation.

Conclusion

Pla-Exos derived from patients with active TAO were immune-active, which may be a long-term stimulus casual for inflammatory and fibrotic progression of TAO. Our finding suggests that Pla-Exos could be used as biomarkers or treatment targets in TAO patients.
Unravelling the role of intratumoral bacteria in digestive system cancers: current insights and future perspectives
Authors: Lu Weiqin , Aihaiti Aihemaitijiang , Abudukeranmu Paziliya , Liu Yajun , Gao Huihui
Published: June 2024

Recently, research on the human microbiome, especially concerning the bacteria within the digestive system, has substantially advanced. This exploration has unveiled a complex interplay between microbiota and health, particularly in the context of disease. Evidence suggests that the gut microbiome plays vital roles in digestion, immunity and the synthesis of vitamins and neurotransmitters, highlighting its significance in maintaining overall health. Conversely, disruptions in these microbial communities, termed dysbiosis, have been linked to the pathogenesis of various diseases, including digestive system cancers. These bacteria can influence cancer progression through mechanisms such as DNA damage, modulation of the tumour microenvironment, and effects on the host’s immune response. Changes in the composition and function within the tumours can also impact inflammation, immune response and cancer therapy effectiveness. These findings offer promising avenues for the clinical application of intratumoral bacteria for digestive system cancer treatment, including the potential use of microbial markers for early cancer detection, prognostication and the development of microbiome-targeted therapies to enhance treatment outcomes. This review aims to provide a comprehensive overview of the pivotal roles played by gut microbiome bacteria in the development of digestive system cancers. Additionally, we delve into the specific contributions of intratumoral bacteria to digestive system cancer development, elucidating potential mechanisms and clinical implications. Ultimately, this review underscores the intricate interplay between intratumoral bacteria and digestive system cancers, underscoring the pivotal role of microbiome research in transforming diagnostic, prognostic and therapeutic paradigms for digestive system cancers.
Citrobacter rodentium infection impairs dopamine metabolism and exacerbates the pathology of Parkinson’s disease in mice
Authors: He Yongtao , Zhao Jiayin , Ma Yuanyuan , Yan Xin , Duan Yufei , Zhang Xiaoshuang , Dong Hongtian , Fang Rong , Zhang Yunhe , Li Qing , Yang Ping , Yu Mei , Fei Jian , Huang Fang
Published: June 2024

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder with indistinct etiology and ill-defined pathophysiology. Intestinal inflammation involved in the pathogenesis of PD, but the underlying mechanism is not fully understood. Citrobacter rodentium (C.R) is a gram-negative bacterium that can be used to induce human inflammatory bowel disease in mice. Here, we investigated whether the proinflammatory effects caused by C.R infection initiate PD-like injury and/or exacerbate PD pathology and extensively studied the underlying mechanism. Mice were gavaged once with C.R and monitored for several pathological features at 9 days post infection. The results showed that C.R delivery in mice induced IBD-like symptoms, including significant weight loss, increased fecal water content, an impaired intestinal barrier, intestinal hyperpermeability and inflammation, and intestinal microbiota disturbances. Notably, C.R infection modified dopamine (DA) metabolism in the brains of both male and female mice. Subsequently, a single high dose of MPTP or normal saline was administered at 6 days post infection. At 3 days after MPTP administration, the feces were collected for 16 S rRNA analysis, and PD-like phenotypes and mechanisms were systemically analyzed. Compared with C.R or MPTP injection alone, the injection of C.R and MPTP combined worsened behavioral performance. Moreover, such combination triggered more severe dopaminergic degeneration and glial cell overactivation in the nigrostriatal pathway of mice. Mechanistically, the combination of C.R and MPTP increased the expression of TLR4 and NF-κB p65 in the colon and striatum and upregulated proinflammatory cytokine expression. Therefore, C.R infection-induced intestinal inflammation can impair dopamine metabolism and exacerbate PD pathological processes.
Magnitude and risk factors of mother-to-child transmission of HIV among HIV-exposed infants after Option B+ implementation in Ethiopia: a systematic review and meta-analysis
Authors: Facha Wolde , Tadesse Takele , Wolka Eskinder , Astatkie Ayalew
Published: June 2024

Background

Mother-to-child transmission (MTCT) of the human immunodeficiency virus (HIV) remains a major public health challenge in Ethiopia. The objective of this review was to assess the pooled magnitude of MTCT of HIV and its risk factors among mother-infant pairs who initiated antiretroviral therapy (ART) after Option B+ in Ethiopia.

Methods

A systematic search of literature from PubMed, Hinari, African Journals Online (AJOL), Science Direct, and Google Scholar databases was conducted from June 11, 2013 to August 1, 2023. The authors used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to guide the article selection process and reporting. Observational studies that reported the magnitude and/or risk factors on MTCT of HIV among mother-infant pairs who initiated ART after the implementation of Option B+ in Ethiopia were included. We applied a random-effect model meta-analysis to estimate the overall pooled magnitude and risk factors of MTCT of HIV. A funnel plot and Egger’s regression test were employed to check publication bias, and heterogeneity was assessed using I2 statistics. The protocol was registered in the PROSPERO database with registration ID number CRD42022325938.

Result

Eighteen published articles on the magnitude of MTCT and 16 published articles on its risk factors were included in this review. The pooled magnitude of MTCT of HIV after the Option B+ program in Ethiopia was 4.05% (95% CI 3.09, 5.01). Mothers who delivered their infants at home [OR: 9.74; (95% CI: 6.89–13.77)], had not been on ART intervention [OR: 19.39; (95% CI: 3.91–96.18)], had poor adherence to ART [OR: 7.47; (95% CI: 3.40–16.45)], initiated ART during pregnancy [OR: 5.09; (95% CI: 1.73–14.97)], had WHO clinical stage 2 and above [OR: 4.95; (95% CI: 1.65–14.88]], had a CD4 count below 350 at enrolment [OR: 5.78; (95% CI: 1.97–16.98], had no or low male partner involvement [OR: 5.92; (95% CI: 3.61–9.71]] and whose partner was not on ART [OR: 8.08; (95% CI: 3.27–19.93]] had higher odds of transmitting HIV to their infants than their counterparts.

Conclusion

This review showed that the pooled magnitude of MTCT of HIV among mother-infant pairs who initiated ART after the Option B + program in Ethiopia is at the desired target of the WHO, which is less than 5% in breastfeeding women. Home delivery, lack of male partner involvement, advanced HIV-related disease, lack of PMTCT intervention, and poor ARV adherence were significant risk factors for MTCT of HIV in Ethiopia.
Vertebral HU value and the pectoral muscle index based on chest CT can be used to opportunistically screen for osteoporosis
Authors: Wang Xiong-Yi , Pan Sheng , Liu Wei-Feng , Wang Yi-Ke , Yun Si-Min , Xu You-Jia
Published: June 2024

Background

Existing studies have shown that computed tomography (CT) attenuation and skeletal muscle tissue are strongly associated with osteoporosis; however, few studies have examined whether vertebral HU values and the pectoral muscle index (PMI) measured at the level of the 4th thoracic vertebra (T4) are strongly associated with bone mineral density (BMD). In this study, we demonstrate that vertebral HU values and the PMI based on chest CT can be used to opportunistically screen for osteoporosis and reduce fracture risk through prompt treatment.

Methods

We retrospectively evaluated 1000 patients who underwent chest CT and DXA scans from August 2020–2022. The T4 HU value and PMI were obtained using manual chest CT measurements. The participants were classified into normal, osteopenia, and osteoporosis groups based on the results of dual-energy X-ray (DXA) absorptiometry. We compared the clinical baseline data, T4 HU value, and PMI between the three groups of patients and analyzed the correlation between the T4 HU value, PMI, and BMD to further evaluate the diagnostic efficacy of the T4 HU value and PMI for patients with low BMD and osteoporosis.

Results

The study ultimately enrolled 469 participants. The T4 HU value and PMI had a high screening capacity for both low BMD and osteoporosis. The combined diagnostic model—incorporating sex, age, BMI, T4 HU value, and PMI—demonstrated the best diagnostic efficacy, with areas under the receiver operating characteristic curve (AUC) of 0.887 and 0.892 for identifying low BMD and osteoporosis, respectively.

Conclusions

The measurement of T4 HU value and PMI on chest CT can be used as an opportunistic screening tool for osteoporosis with excellent diagnostic efficacy. This approach allows the early prevention of osteoporotic fractures via the timely screening of individuals at high risk of osteoporosis without requiring additional radiation.
The influence of low-dose s-ketamine on postoperative delirium and cognitive function in older adults undergoing thoracic surgery
Authors: Wang Yujia , Ma Bingqiang , Wang Chaochang , Wang Yingqi , Liu Aijia , Hang Lihua
Published: June 2024

Background

Postoperative delirium (POD) and cognitive dysfunction (POCD) are common complications following thoracic surgery, particularly in patients aged 65 years and above. These complications can significantly affect recovery and increase healthcare costs. This study investigates the effects of low-dose S-ketamine on reducing POD and POCD in this patient demographic.

Methods

In this retrospective cohort study, medical records of patients aged ≥ 65 years who underwent elective thoracic surgery from January 2019 to August 2023 were reviewed. Patients were categorized into S-ketamine and Control groups based on intraoperative S-ketamine exposure. POD was assessed using the Confusion Assessment Method (CAM), while cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) at baseline, 1 week, 1 month, and 6 months post-surgery. Intraoperative and postoperative parameters, including hemodynamic stability, blood loss, pain scores, and ICU stay length, were also recorded.

Results

The study comprised 140 participants, with 70 in each group. The S-ketamine group demonstrated a significantly lower incidence of POD at 7 days post-surgery (12.0% vs. 26.7%, P < 0.001), and reduced POCD at 1 month (18.7% vs. 36.0%, P < 0.05) and 6 months (10.7% vs. 21.3%, P < 0.05). The Ketamine group had a significantly higher median MoCA score compared to the Control group both at 1 month (P = 0.021) and 6 months (P = 0.007). Adverse events, such as infection, bleeding, and respiratory failure, showed no significant differences between the groups, suggesting a safe profile for S-ketamine.

Conclusion

Administering low-dose S-ketamine during thoracic surgery in patients aged 65 years and above significantly reduces the incidence of POD and POCD, highlighting its neuroprotective potential. These findings advocate for the inclusion of S-ketamine in anesthetic protocols to improve postoperative outcomes and reduce healthcare costs in this patient population.
Lasofoxifene as a potential treatment for aromatase inhibitor-resistant ER-positive breast cancer
Authors: Lainé Muriel , Greene Marianne E , Kurleto Justyna D , Bozek Grazyna , Leng Tiffany , Huggins Rosemary J , Komm Barry S , Greene Geoffrey L
Published: June 2024

Background

Breast cancers treated with aromatase inhibitors (AIs) can develop AI resistance, which is often driven by estrogen receptor-alpha (ERα/ESR1) activating mutations, as well as by ER-independent signaling pathways. The breast ER antagonist lasofoxifene, alone or combined with palbociclib, elicited antitumor activities in a xenograft model of ER + metastatic breast cancer (mBC) harboring ESR1 mutations. The current study investigated the activity of LAS in a letrozole-resistant breast tumor model that does not have ESR1 mutations.

Methods

Letrozole-resistant, MCF7 LTLT cells tagged with luciferase-GFP were injected into the mammary duct inguinal glands of NSG mice (MIND model; 6 mice/group). Mice were randomized to vehicle, lasofoxifene ± palbociclib, fulvestrant ± palbociclib, or palbociclib alone 2–3 weeks after cell injections. Tumor growth and metastases were monitored with in vivo and ex vivo luminescence imaging, terminal tumor weight measurements, and histological analysis. The experiment was repeated with the same design and 8–9 mice in each treatment group.

Results

Western blot analysis showed that the MCF7 LTLT cells had lower ERα and higher HER2 expressions compared with normal MCF7 cells. Lasofoxifene ± palbociclib, but not fulvestrant, significantly reduced primary tumor growth versus vehicle as assessed by in vivo imaging of tumors at study ends. Percent tumor area in excised mammary glands was significantly lower for lasofoxifene plus palbociclib versus vehicle. Ki67 staining showed decreased overall tumor cell proliferation with lasofoxifene ± palbociclib. The lasofoxifene + palbociclib combination was also associated with significantly fewer bone metastases compared with vehicle. Similar results were observed in the repeat experiment.

Conclusions

In a mouse model of letrozole-resistant breast cancer with no ESR1 mutations, reduced levels of ERα, and overexpression of HER2, lasofoxifene alone or combined with palbociclib inhibited primary tumor growth more effectively than fulvestrant. Lasofoxifene plus palbociclib also reduced bone metastases. These results suggest that lasofoxifene alone or combined with a CDK4/6 inhibitor may offer benefits to patients who have ER-low and HER2-positive, AI-resistant breast cancer, independent of ESR1 mutations.
Lomustine with or without reirradiation for first progression of glioblastoma, LEGATO, EORTC-2227-BTG: study protocol for a randomized phase III study
Authors: Preusser Matthias , Kazda Tomáš , Le Rhun Emilie , Sahm Felix , Smits Marion , Gempt Jens , Koekkoek Johan AF , Monti Angelo F , Csanadi Marcell , Pitter János György , Bulbek Helen , Fournier Beatrice , Quoilin Caroline , Gorlia Thierry , Weller Michael , Minniti Giuseppe ,   on behalf of the European Organisation for Research, Treatment of Cancer (EORTC) Brain Tumor Group
Published: June 2024

Background

Chemotherapy with lomustine is widely considered as standard treatment option for progressive glioblastoma. The value of adding radiotherapy to second-line chemotherapy is not known.

Methods

EORTC-2227-BTG (LEGATO, NCT05904119) is an investigator-initiated, pragmatic (PRECIS-2 score: 34 out of 45), randomized, multicenter phase III trial in patients with first progression of glioblastoma. A total of 411 patients will be randomized in a 1:1 ratio to lomustine (110 mg/m2 every 6 weeks) or lomustine (110 mg/m2 every 6weeks) plus radiotherapy (35 Gy in 10 fractions). Main eligibility criteria include histologic confirmation of glioblastoma, isocitrate dehydrogenase gene (IDH) wild-type per WHO 2021 classification, first progression at least 6 months after the end of prior radiotherapy, radiologically measurable disease according to RANO criteria with a maximum tumor diameter of 5 cm, and WHO performance status of 0–2. The primary efficacy endpoint is overall survival (OS) and secondary endpoints include progression-free survival, response rate, neurocognitive function, health-related quality of life, and health economic parameters. LEGATO is funded by the European Union’s Horizon Europe Research program, was activated in March 2024 and will enroll patients in 43 sites in 11 countries across Europe with study completion projected in 2028.

Discussion

EORTC-2227-BTG (LEGATO) is a publicly funded pragmatic phase III trial designed to clarify the efficacy of adding reirradiation to chemotherapy with lomustine for the treatment of patients with first progression of glioblastoma.

Trial registration

ClinicalTrials.gov NCT05904119. Registered before start of inclusion, 23 May 2023
Multi-task transfer learning for the prediction of entity modifiers in clinical text: application to opioid use disorder case detection
Authors: Almudaifer Abdullateef I. , Covington Whitney , Hairston JaMor , Deitch Zachary , Anand Ankit , Carroll Caleb M. , Crisan Estera , Bradford William , Walter Lauren A. , Eaton Ellen F. , Feldman Sue S. , Osborne John D.
Published: June 2024

Background

The semantics of entities extracted from a clinical text can be dramatically altered by modifiers, including entity negation, uncertainty, conditionality, severity, and subject. Existing models for determining modifiers of clinical entities involve regular expression or features weights that are trained independently for each modifier.

Methods

We develop and evaluate a multi-task transformer architecture design where modifiers are learned and predicted jointly using the publicly available SemEval 2015 Task 14 corpus and a new Opioid Use Disorder (OUD) data set that contains modifiers shared with SemEval as well as novel modifiers specific for OUD. We evaluate the effectiveness of our multi-task learning approach versus previously published systems and assess the feasibility of transfer learning for clinical entity modifiers when only a portion of clinical modifiers are shared.

Results

Our approach achieved state-of-the-art results on the ShARe corpus from SemEval 2015 Task 14, showing an increase of 1.1% on weighted accuracy, 1.7% on unweighted accuracy, and 10% on micro F1 scores.

Conclusions

We show that learned weights from our shared model can be effectively transferred to a new partially matched data set, validating the use of transfer learning for clinical text modifiers.
Tumour-specific phosphorylation of serine 419 drives alpha-enolase (ENO1) nuclear export in triple negative breast cancer progression
Authors: Marshall Morgan L , Fung Kim YC , Jans David A , Wagstaff Kylie M
Published: June 2024

Background

The glycolytic enzyme alpha-enolase is a known biomarker of many cancers and involved in tumorigenic functions unrelated to its key role in glycolysis. Here, we show that expression of alpha-enolase correlates with subcellular localisation and tumorigenic status in the MCF10 triple negative breast cancer isogenic tumour progression model, where non-tumour cells show diffuse nucleocytoplasmic localisation of alpha-enolase, whereas tumorigenic cells show a predominantly cytoplasmic localisation. Alpha-enolase nucleocytoplasmic localisation may be regulated by tumour cell-specific phosphorylation at S419, previously reported in pancreatic cancer.

Results

Here we show ENO1 phosphorylation can also be observed in triple negative breast cancer patient samples and MCF10 tumour progression cell models. Furthermore, prevention of alpha-enolase-S419 phosphorylation by point mutation or a casein kinase-1 specific inhibitor D4476, induced tumour-specific nuclear accumulation of alpha-enolase, implicating S419 phosphorylation and casein kinase-1 in regulating subcellular localisation in tumour cell-specific fashion. Strikingly, alpha-enolase nuclear accumulation was induced in tumour cells by treatment with the specific exportin-1-mediated nuclear export inhibitor Leptomycin B. This suggests that S419 phosphorylation in tumour cells regulates alpha-enolase subcellular localisation by inducing its exportin-1-mediated nuclear export. Finally, as a first step to analyse the functional consequences of increased cytoplasmic alpha-enolase in tumour cells, we determined the alpha-enolase interactome in the absence/presence of D4476 treatment, with results suggesting clear differences with respect to interaction with cytoskeleton regulating proteins.

Conclusions

The results suggest for the first time that tumour-specific S419 phosphorylation may contribute integrally to alpha-enolase cytoplasmic localisation, to facilitate alpha-enolase’s role in modulating cytoskeletal organisation in triple negative breast cancer. This new information may be used for development of triple negative breast cancer specific therapeutics that target alpha-enolase.
Optimum solution of $(k,\gimel )$-Hilfer FDEs by $\mathcal{A}$-condensing operators and the incorporated measure of noncompactness
Authors: Khokhar Gurpreet Kaur , Patel Deepesh Kumar , Patle Pradip Ramesh , Samei Mohammad Esmael
Published: June 2024

The notion of $\mathcal{A}$
A
-condensing operators via the measure of noncompactness is proposed, which retains the existing classes of condensing operators. Results concerning the existence of the best proximity point (pair) of cyclic (noncyclic) $\mathcal{A}$
A
-condensing operators along with the coupled best proximity-point theorem for cyclic $\mathcal{A}$
A
-condensing operators have been formulated. An application to a $(k, \gimel )$
(
k
,
ℷ
)
-Hilfer fractional differential equation of order $2< p<3$
2
<
p
<
3
, type $q\in [0,1]$
q
∈
[
0
,
1
]
satistfying some boundary conditions is presented. The paper is the first to investigate the optimum solution of such a generalized fractional differential equation. The hypothesis involved in the investigation is independent of the incorporated measure of noncompactness, thereby making our result better in application than that present in the literature. Moreover, added numerical examples validate the theoretical conclusions.
Patient eligibility for trials with imaging response assessment at the time of molecular tumor board presentation
Authors: Mansour Nabeel , Heinrich Kathrin , Zhang Danmei , Winkelmann Michael , Ingenerf Maria , Gold Lukas , Klambauer Konstantin , Rudelius Martina , Klauschen Frederick , von Bergwelt-Baildon Michael , Ricke Jens , Heinemann Volker , Westphalen C. Benedikt , Kunz Wolfgang G.
Published: June 2024

Purpose

To assess the eligibility of patients with advanced or recurrent solid malignancies presented to a molecular tumor board (MTB) at a large precision oncology center for inclusion in trials with the endpoints objective response rate (ORR) or duration of response (DOR) based on Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).

Methods

Prospective patients with available imaging at the time of presentation in the MTB were included. Imaging data was reviewed for objectifiable measurable disease (MD) according to RECIST v1.1. Additionally, we evaluated the patients with MD for representativeness of the identified measurable lesion(s) in relation to the overall tumor burden.

Results

262 patients with different solid malignancies were included. 177 patients (68%) had MD and 85 (32%) had non-measurable disease (NMD) at the time point of MTB presentation in accordance with RECIST v1.1. MD was not representative of the overall tumor burden in eleven patients (6%). The main reasons for NMD were lesions with longest diameter shorter than 10 mm (22%) and non-measurable peritoneal carcinomatosis (18%). Colorectal cancer and malignant melanoma displayed the highest rates of MD (> 75%). In contrast, gastric cancer, head and neck malignancies, and ovarian carcinoma had the lowest rates of MD (< 55%). In case of MD, the measurable lesions were representative of the overall tumor burden in the vast majority of cases (94%).

Conclusion

Approximately one third of cancer patients with advanced solid malignancies are not eligible for treatment response assessment in trials with endpoints ORR or DOR at the time of MTB presentation. The rate of patients eligible for trials with imaging endpoints differs significantly based on the underlying malignancy and should be taken under consideration during the planning of new precision oncology trials.