bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of associated femoral head fractures on surgical outcomes following osteosynthesis in posterior wall acetabular fractures
Authors: Lai Po-Ju , Lai Chih-Yang , Tseng I-Chuan , Su Chun-Yi , Yu Yi-Hsun
Published: September 2022

Background

To date, no study has compared the surgical outcomes between posterior wall acetabular fractures with and without associated femoral head fractures. Therefore, we evaluated whether an associated femoral head fracture increases the incidence of fracture sequelae, including post-traumatic osteoarthritis (PTOA) and osteonecrosis of the femoral head (ONFH), following osteosynthesis for posterior wall acetabular fractures.

Methods

This retrospective clinical study enrolled 183 patients who underwent osteosynthesis for posterior wall acetabular fractures between 2009 and 2019 at a level-1 trauma center. The incidence of PTOA, ONFH, and conversion to total hip arthroplasty (THA) was reviewed.

Results

The incidence of PTOA, ONFH, and conversion to THA following osteosynthesis were 20.2%, 15.9%, and 17.5%, respectively. The average time for conversion to THA was 18.76 ± 20.15 months (range, 1–82). The results for the comparison of patients with associated femoral head fractures and isolated posterior wall acetabular fractures were insignificant (PTOA: 27.3% vs. 15.7%,p = 0.13; ONFH: 18.2% vs. 14.3%,p = 0.58; conversion to THA: 20.4% vs. 15.7%,p = 0.52). Upon evaluating other variables, only marginal impaction negatively affected ONFH incidence (odds ratio: 2.90).

Conclusions

Our methods failed to demonstrate a significant difference in the rate of PTOA, ONFH, or conversion to THA in posterior wall acetabular fractures with and without an associated femoral head fracture. Beyond femoral head fractures, the marginal impaction of the acetabulum could have led to early sequelae.

Level of evidence

Level III
Imaging characteristics of ovarian sclerosing stromal tumor
Authors: Zhou Zhifeng , Chen Xiaoqiao , Zeng Zhibin , Zhang Fangjing , Yan Jing , Hou Gangqiang
Published: September 2022

Objectives

This study was designed to evaluate the specific imaging features of ovarian sclerosing stromal tumor (SST), improve its accuracy as well as the specificity of imaging diagnosing, and prevent overestimation of malignancy to reduce unnecessary surgical procedures.

Methods

Eight patients with magnetic resonance imaging (MRI) and six with computed tomography (CT) images were analyzed in this retrospective observational study. All the cases were confirmed by postoperative pathological examination as those of ovarian SST. Imaging and pathological features were also evaluated.

Results

All the 14 masses displayed cystic and solid components with outer surface of tumors contained a capsular and complete smooth rim. Eight tumors of MRI exhibited “lake-island” sign on T2 weighted imaging (T2WI). Two of the 6 CT cases displayed a flaky calcification. One case showed as a multiloculated cystic mass with irregularly thickened septae and the tumor wall. The solid components in other 13 masses were comb- or wheel-like enhanced. After injection of contrast agent, the solid components in 8 cases (57.1%) appeared as early enhancement, whereas the other 6 cases (42.9%) appeared as progressive enhanced, and the cystic components of all the cases had no enhancement in the whole course. Vascular flow signals or/and marked enhancement of the blood vessels were found in 12 lesions (85.7%). Pathological examination demonstrated pseudolobule patterns, round to spindle shaped cells, collagenous areas, edematous hypocellular areas and prominent vasculatures.

Conclusions

The results demonstrated that MRI with “lake-island” signs on T2WI and MRI/CT dynamic enhancement could potentially play a critical role in facilitating appropriate diagnosis preoperatively.
Better governance starts with better words: why responsible human tissue research demands a change of language
Authors: Lensink Michael A. , Jongsma Karin R. , Boers Sarah N. , Bredenoord Annelien L.
Published: September 2022

The rise of precision medicine has led to an unprecedented focus on human biological material in biomedical research. In addition, rapid advances in stem cell technology, regenerative medicine and synthetic biology are leading to more complex human tissue structures and new applications with tremendous potential for medicine. While promising, these developments also raise several ethical and practical challenges which have been the subject of extensive academic debate. These debates have led to increasing calls for longitudinal governance arrangements between tissue providers and biobanks that go beyond the initial moment of obtaining consent, such as closer involvement of tissue providers in what happens to their tissue, and more active participatory approaches to the governance of biobanks. However, in spite of these calls, such measures are being adopted slowly in practice, and there remains a strong tendency to focus on the consent procedure as the tool for addressing the ethical challenges of contemporary biobanking. In this paper, we argue that one of the barriers to this transition is the dominant language pervading the field of human tissue research, in which the provision of tissue is phrased as a ‘donation’ or ‘gift’, and tissue providers are referred to as ‘donors’. Because of the performative qualities of language, the effect of using ‘donation’ and ‘donor’ shapes a professional culture in which biobank participants are perceived as passive providers of tissue free from further considerations or entitlements. This hampers the kind of participatory approaches to governance that are deemed necessary to adequately address the ethical challenges currently faced in human tissue research. Rather than reinforcing this idea through language, we need to pave the way for the kind of participatory approaches to governance that are being extensively argued for by starting with the appropriate terminology.
EQUIP emergency: can interventions to reduce racism, discrimination and stigma in EDs improve outcomes?
Authors: Varcoe Colleen , Browne Annette J. , Perrin Nancy , Wilson Erin , Bungay Vicky , Byres David , Wathen Nadine , Stones Cheyanne , Liao Catherine , Price Elder Roberta
Published: September 2022

Background

Despite a publicly funded system, health care in Canada has been shown to be deeply inequitable, particularly toward Indigenous people. Based on research identifying key dimensions of equity-oriented health care as being cultural safety, harm reduction and trauma- and violence-informed care, an intervention to promote equity at the organizational level was tested in primary health care, refined and adapted, and tested in Emergency Departments (EDs).

Methods

In partnership with clinical, community and Indigenous leaders in three diverse EDs in one Canadian province, we supported direct care staff to tailor and implement the intervention. Intervention activities varied in type and intensity at each site. Survey data were collected pre- and post-intervention from every consecutive patient over age 18 presenting to the EDs (n = 4771) with 3315 completing post-visit questions in 4 waves at two sites and 3 waves (due to pandemic constraints) at the third. Administrative data were collected for 12 months pre- and 12 months post-intervention.

Results

Throughout the study period, the participating EDs were dealing with a worsening epidemic of overdoses and deaths related to a toxic drug supply, and the COVID 19 pandemic curtailed both intervention activities and data collection. Despite these constraints, staff at two of the EDs mounted equity-oriented intervention strategies; the other site was experiencing continued, significant staff shortages and leadership changeover. Longitudinal analysis using multiple regression showed non-significant but encouraging trends in patient perceptions of quality of care and patient experiences of discrimination in the ED. Subgroup analysis showed that specific groups of patients experienced care in significantly different ways at each site. An interrupted time series of administrative data showed no significant change in staff sick time, but showed a significant decrease in the percentage of patients who left without care being completed at the site with the most robust intervention activities.

Conclusions

The trends in patient perceptions and the significant decrease in the percentage of patients who left without care being completed suggest potential for impact. Realization of this potential will depend on readiness, commitment and resources at the organizational and systems levels.

Trial registration

ClinicalTrials.gov#NCT03369678 (registration date November 18, 2017).
Combined protein and transcript single-cell RNA sequencing in human peripheral blood mononuclear cells
Authors: Vallejo Jenifer , Saigusa Ryosuke , Gulati Rishab , Armstrong Suthahar Sujit Silas , Suryawanshi Vasantika , Alimadadi Ahmad , Durant Christopher P. , Ghosheh Yanal , Roy Payel , Ehinger Erik , Pattarabanjird Tanyaporn , Hanna David B. , Landay Alan L. , Tracy Russell P. , Lazar Jason M. , Mack Wendy J. , Weber Kathleen M. , Adimora Adaora A. , Hodis Howard N. , Tien Phyllis C. , Ofotokun Igho , Heath Sonya L. , Shemesh Avishai , McNamara Coleen A. , Lanier Lewis L. , Hedrick Catherine C. , Kaplan Robert C. , Ley Klaus
Published: September 2022

Background

Cryopreserved peripheral blood mononuclear cells (PBMCs) are frequently collected and provide disease- and treatment-relevant data in clinical studies. Here, we developed combined protein (40 antibodies) and transcript single-cell (sc)RNA sequencing (scRNA-seq) in PBMCs.

Results

Among 31 participants in the Women’s Interagency HIV Study (WIHS), we sequenced 41,611 cells. Using Boolean gating followed by Seurat UMAPs (tool for visualizing high-dimensional data) and Louvain clustering, we identified 50 subsets among CD4+ T, CD8+ T, B, NK cells, and monocytes. This resolution was superior to flow cytometry, mass cytometry, or scRNA-seq without antibodies. Combined protein and transcript scRNA-seq allowed for the assessment of disease-related changes in transcriptomes and cell type proportions. As a proof-of-concept, we showed such differences between healthy and matched individuals living with HIV with and without cardiovascular disease.

Conclusions

In conclusion, combined protein and transcript scRNA sequencing is a suitable and powerful method for clinical investigations using PBMCs.
Seroprevalence and risk factors of Toxoplasma gondii in urban cats from China
Authors: Xia Ningbo , Ji Nuo , Li Longjiao , Huang Yuan , Yang Congshan , Guo Xuefang , Guo Qinghong , Shen Bang , Xiao Lihua , Feng Yaoyu
Published: September 2022

Background

Toxoplasma gondii infects almost all warm-blooded animals, and cats play a crucial role in the epidemiology of T. gondii as the definitive host. Despite sporadic reports on the seroprevalence of T. gondii in domestic cats, systematic surveys are lacking and some regions remain in China uninvestigated.

Methods

A total of 1,521 serum samples were collected from 10 regions of China and analyzed by antibodies against T. gondii by ELISA with the purpose of identifying risk factors of T. gondii infection in cats across China and obtaining seroprevalence data from some previously uninvestigated areas.

Results

Antibodies to T. gondii were detected in 62 of 1,478 (4.2%) urban pet cats and in 9 of 43 (20.9%) stray cats. Among the regions examined, the prevalence was 13% in Sichuan, 12.8% in Chongqing, 6.4% in Hunan, 2.5% in Hubei and 0.9% in Guangdong. Additionally, this is the first report on the seroprevalence of T. gondii in urban pet cats from Qinghai (6.2%), Anhui (3.1%), Jiangxi (2.5%), Shaanxi (2.4%) and Ningxia (1.6%). The age and lifestyle (stray or pet) of cats were identified as the risk factors for seropositivity by multivariate analysis of the data.

Conclusions

Our findings improve our understanding of seroprevalence and risk factors of T. gondii infection in cats across China, and provide useful information for the formulating of preventive and control measures against this widespread zoonotic parasite.
Association of serum levels of osteopontin and osteoprotegerin with adverse outcomes after endovascular revascularisation in peripheral artery disease
Authors: Kadoglou Nikolaos P. E. , Kapetanios Dimitrios , Korakas Emmanouil , Valsami Georgia , Tentolouris Nikolaos , Papanas Nikolaos , Lambadiari Vaia , Karkos Christos
Published: September 2022

Background

Osteoprotegerin (OPG) and osteopontin (OPN) are vascular calcification inhibitors with a known role in the atherosclerotic and inflammatory process. We investigated their relationship with adverse outcomes (restenosis/adverse cardiovascular events) after endovascular revascularisation of patients with peripheral arterial disease (PAD).

Methods

203 consecutive patients were enrolled in the PAD group (PADG) and 78 age and sex-matched subjects with less than two cardiovascular risk factors served as control group (COG). PADG underwent standard medical assessment at baseline and 12 months after the procedure. During follow up major adverse cardiovascular events (MACEs) including arterial restenosis with need for reintervention were documented and the PADG was divided accordingly into two subgroups.

Results

During 12-month follow-up, 82 MACE were recorded (MACE subgroup). The rest of 124 PAD patients remained free of MACE (non-MACE subgroup). At baseline, OPG (9.89 ± 2.85 ng/ml vs 3.47 ± 1.95 ng/ml, p < 0.001) and OPN (79.99 ± 38.29 ng/ml vs 35.21 ± 14.84 ng/ml, p < 0.001) levels were significantly higher in PADG compared to COG, as well as in MACE subgroup compared to non-MACE subgroup (13.29 ± 3.23 ng/ml vs 10.86 ± 3 ng/ml and 96.45 ± 40.12 ng/ml vs 78.1 ± 38.29 ng/ml, respectively). An independent association of PAD with OPG and OPN was found in the whole patient cohort. Although OPG and OPN were significantly related to MACE incidence in the univariate analysis, multiple logistic regression analysis failed to detect any independent predictor of MACE within the PADG.

Conclusion

Baseline high OPG and OPN levels were independently associated with PAD presence. Even higher levels of those biomarkers were detected among PAD patients with MACE, however, their prognostic role should be further clarified.
CircSMARCC1 facilitates tumor progression by disrupting the crosstalk between prostate cancer cells and tumor-associated macrophages via miR-1322/CCL20/CCR6 signaling
Authors: Xie Tao , Fu Du-jiang , Li Zhi-min , Lv Dao-jun , Song Xian-Lu , Yu Yu-zhong , Wang Chong , Li Kang-jin , Zhai Baoqian , Wu Jiacheng , Feng Ning-Han , Zhao Shan-Chao
Published: September 2022

Background

Circular RNAs (circRNAs) mediate the infiltration of tumor-associated macrophages (TAMs) to facilitate carcinogenesis and development of various types of cancers. However, the role of circRNAs in regulating macrophages in prostate cancer (PCa) remains uncertain.

Methods

Differentially expressed circRNAs in PCa were identified by RNA sequencing. The expression of circSMARCC1 was recognized and evaluated using fluorescence in situ hybridization and quantitative real-time PCR. The oncogenic role of circSMARCC1 in PCa tumor proliferation and metastasis was investigated through a series of in vitro and in vivo assays. Finally, Western blot, biotin-labeled RNA pulldown, luciferase assay, rescue experiments, and co-culture experiments with TAMs were conducted to reveal the mechanistic role of circSMARCC1.

Results

CircSMARCC1 was dramatically up-regulated in PCa cells, plasma and tissues. Overexpression of circSMARCC1 promotes tumor proliferation and metastasis both in vitro and in vivo, whereas knockdown of circSMARCC1 exerts the opposite effects. Mechanistically, circSMARCC1 regulates the expression of CC-chemokine ligand 20 (CCL20) via sponging miR-1322 and activate PI3K-Akt signaling pathway involved in the proliferation and epithelial mesenchymal transformation. More importantly, high expression of circSMARCC1 was positively associated with colonization of CD68+/CD163+/CD206+ TAMs in tumor microenvironment. In addition, overexpression of circSMARCC1 facilitates the expression of CD163 in macrophages through the CCL20-CCR6 axis, induces TAMs infiltration and M2 polarization, thereby leading to PCa progression.

Conclusions

CircSMARCC1 up-regulates the chemokine CCL20 secretion by sponging miR-1322, which is involved in the crosstalk between tumor cells and TAMs by targeting CCL20/CCR6 signaling to promote progression of PCa.
The trends in the incidence and thrombosis-related comorbidities of antiphospholipid syndrome: a 14-year nationwide population-based study
Authors: Yao Wei-Cheng , Leong Kam-Hang , Chiu Lu-Ting , Chou Po-Yi , Wu Li-Chih , Chou Chih-Yu , Kuo Chien-Feng , Tsai Shin-Yi
Published: September 2022

Background

This study aims to provide 14-year nationwide epidemiology data to evaluate the incidence ratio of APS in Taiwan and the condition of comorbidities by analyzing the National Health Insurance Research Database.

Methods

Nineteen thousand one hundred sixty-three patients newly diagnosed as having APS during the 2000–2013 period and 76,652 controls (with similar distributions of age and sex) were analyzed.

Results

The incidence of APS increased from 4.87 to 6.49 per 10,000 person-years in the Taiwan population during 2000–2013. The incidence of APS increased with age after 20 years old, especially in the female population, and it rose rapidly after age over 60 years old. In addition, APS cohorts presented a higher proportion of diabetes mellitus, hypertension, hyperlipidemia, stroke, heart failure, atrial fibrillation, myocardial infarction, PAOD, chronic kidney disease, COPD, deep vein thrombosis, pulmonary embolism, SLE, rheumatoid arthritis, Sjogren’s syndrome, and polymyositis.

Conclusions

Our study indicated an increasing trend in APS incidence among the Taiwanese population and a relationship between APS and potential comorbidities. This large national study found that the APS risk is heavily influenced by sex and age. Thus, the distinctive sex and age patterns might be constructive given exploring potential causal mechanisms. Furthermore, our findings indicate that clinicians should have a heightened awareness of the probability of APS, especially in women in certain age groups presenting with symptoms of APS.
Understanding the policy dynamics of COVID-19 vaccination in Ghana through the lens of a policy analytical framework
Authors: Atinga Roger A. , Koduah Augustina , Abiiro Gilbert Abotisem
Published: September 2022

Background

Ghana became the first African country to take delivery of the first wave of the AstraZeneca/Oxford vaccine from the COVAX facility. But why has this promising start of the vaccination rollout not translated into an accelerated full vaccination of the population? To answer this question, we drew on the tenets of a policy analytical framework and analysed the diverse interpretations, issue characteristics, actor power dynamics and political context of the COVID-19 vaccination process in Ghana.

Methods

We conducted a rapid online review of media reports, journal articles and other documents on debates and discussions of issues related to framing of the vaccination rollout, social constructions generated around vaccines, stakeholder power dynamics and political contentions linked to the vaccination rollout. These were complemented by desk reviews of parliamentary reports.

Results

The COVID-19 vaccination was mainly framed along the lines of public health, gender-centredness and universal health coverage. Vaccine acquisition and procurement were riddled with politics between the ruling government and the largest main opposition party. While the latter persistently blamed the former for engaging in political rhetoric rather than a tactical response to vaccine supply issues, the former attributed vaccine shortages to vaccine nationalism that crowded out fair distribution. The government’s efforts to increase vaccination coverage to target levels were stifled when a deal with a private supplier to procure 3.4 million doses of the Sputnik V vaccine collapsed due to procurement breaches. Amidst the vaccine scarcity, the government developed a working proposal to produce vaccines locally which attracted considerable interest among pharmaceutical manufacturers, political constituents and donor partners. Regarding issue characteristics of the vaccination, hesitancy for vaccination linked to misperceptions of vaccine safety provoked politically led vaccination campaigns to induce vaccine acceptance.

Conclusions

Scaling up vaccination requires political unity, cohesive frames, management of stakeholder interests and influence, and tackling contextual factors promoting vaccination hesitancy.
From raw data to a score: comparing quantitative methods that construct multi-level composite implementation strength scores of family planning programs in Malawi
Authors: Pattnaik Anooj , Mohan Diwakar , Zeger Scott , Kanyuka Mercy , Kachale Fannie , Marx Melissa A.
Published: September 2022

Background

Data that capture implementation strength can be combined in multiple ways across content and health system levels to create a summary measure that can help us to explore and compare program implementation across facility catchment areas. Summary indices can make it easier for national policymakers to understand and address variation in strength of program implementation across jurisdictions. In this paper, we describe the development of an index that we used to describe the district-level strength of implementation of Malawi’s national family planning program.

Methods

To develop the index, we used data collected during a 2017 national, health facility and community health worker Implementation Strength Assessment survey in Malawi to test different methods to combine indicators within and then across domains (4 methods—simple additive, weighted additive, principal components analysis, exploratory factor analysis) and combine scores across health facility and community health worker levels (2 methods—simple average and mixed effects model) to create a catchment area-level summary score for each health facility in Malawi. We explored how well each model captures variation and predicts couple-years protection and how feasible it is to conduct each type of analysis and the resulting interpretability.

Results

We found little difference in how the four methods combined indicator data at the individual and combined levels of the health system. However, there were major differences when combining scores across health system levels to obtain a score at the health facility catchment area level. The scores resulting from the mixed effects model were able to better discriminate differences between catchment area scores compared to the simple average method. The scores using the mixed effects combination method also demonstrated more of a dose–response relationship with couple-years protection.

Conclusions

The summary measure that was calculated from the mixed effects combination method captured the variation of strength of implementation of Malawi’s national family planning program at the health facility catchment area level. However, the best method for creating an index should be based on the pros and cons listed, not least, analyst capacity and ease of interpretability of findings. Ultimately, the resulting summary measure can aid decision-makers in understanding the combined effect of multiple aspects of programs being implemented in their health system and comparing the strengths of programs across geographies.
Performance evaluation of antigen detection rapid diagnostic test (Ag-RDT) for COVID-19 diagnosis in a primary healthcare center during the Shanghai COVID-19 quarantine period
Authors: Dong Lan , Li Wen-Fang , Jiang Ying
Published: September 2022

Background

Rapid and accurate detection of SARS-CoV-2 infection is the cornerstone of prompt patient care. However, the reliability of the antigen rapid diagnostic test (Ag-RDT) in the diagnosis of SARS-CoV-2 infection remains inconclusive.

Methods

We conducted a field evaluation of Ag-RDT performance during the Shanghai Coronavirus disease 2019 (COVID-19) quarantine and screened 7225 individuals visiting our Emergency Department. 83 asymptomatic SARS-CoV-2 (+) individuals were enrolled in the current study. Simultaneously, Ag-RDT was performed to evaluate its testing performance.

Results

For the Ag-RDT(−) cases, the average cycle threshold (Ct) values of the N gene were 27.26 ± 4.59, which were significantly higher than the Ct value (21.9 ± 4.73) of the Ag-RDT(+) individuals (p < 0.0001). The overall sensitivity of Ag-RDT versus that of RT-PCR was 43.37%. The Ag-RDT(+) individuals regarding the N gene’s Ct value were 16 cases in the < 20 range, 12 in 20–25, 5 in 25–30, and 3 in 30–35. The corresponding sensitivity was 84.21%, 52.17%, 21.74% and 16.67%, respectively. Meanwhile, sampling had a straight specificity of 100% regardless of the Ct value.

Conclusions

The Ag-RDT were extremely sensitive in asymptomatic COVID-19 individuals with a Ct value < 20.
A meta-analysis of colchicine in prevention of atrial fibrillation following cardiothoracic surgery or cardiac intervention
Authors: Zhao Hong , Chen Yueming , Mao Min , Yang Jun , Chang Jing
Published: September 2022

Background

Postoperative atrial fibrillation (POAF) is the most common complication after cardiothoracic surgery or cardiac intervention. Colchicine is an anti-inflammatory agent that was associated with improved cardiovascular outcomes. However, its effect on POAF prevention was inconsistent across studies. Therefore, the aim of this meta-analysis was to evaluate the efficacy of colchicine in prevention of POAF.

Methods

We searched PubMed, Embase, ClinicalTrials.gov, Cochrane Library database and Google Scholar for randomized controlled trials (RCTs), using terms "atrial fibrillation” and “colchicine". The primary end point was the occurrence of clinically diagnosed atrial fibrillation. The relative risk (RR) and 95% confidence interval (CI) were evaluated. Estimates were pooled using DerSimonian-Laird random-effects model. We also performed subgroup analyses based on the duration and dose of colchicine treatment.

Results

A total of 9 RCTs were included in this meta-analysis, enrolling a total of 2031 patients. Colchicine significantly reduces the incidence of POAF (RR 0.62; 95% CI, 0.52–0.74, P < 0.001, I2 = 0%). Subgroup analyses indicated that the protective effect of colchicine on POAF was almost the same (P = 0.71) in the long-duration group (RR 0.60; 95% CI, 0.48–0.75, P < 0.001, I2 = 0%) and the short-duration group (RR 0.65; 95% CI, 0.49–0.86, P < 0.001, I2 = 0%).

Conclusion

Colchicine is effective in preventing the occurrence of POAF. The efficacy of colchicine cannot be slightly increased over treatment duration, with no obvious adverse reactions.
APE1 redox function is required for activation of Yes-associated protein 1 under reflux conditions in Barrett’s-associated esophageal adenocarcinomas
Authors: Ballout Farah , Lu Heng , Chen Lei , Sriramajayam Kannappan , Que Jianwen , Meng Zhipeng , Wang Timothy C. , Giordano Silvia , Zaika Alexander , McDonald Oliver , Peng Dunfa , El-Rifai Wael
Published: September 2022

Background

Esophageal adenocarcinoma (EAC) is characterized by poor prognosis and low survival rate. Chronic gastroesophageal reflux disease (GERD) is the main risk factor for the development of Barrett’s esophagus (BE), a preneoplastic metaplastic condition, and its progression to EAC. Yes-associated protein 1 (YAP1) activation mediates stem-like properties under cellular stress. The role of acidic bile salts (ABS) in promoting YAP1 activation under reflux conditions remains unexplored.

Methods

A combination of EAC cell lines, transgenic mice, and patient-derived xenografts were utilized in this study. mRNA expression and protein levels of APE1 and YAP1 were evaluated by qRT-PCR, western blot, and immunohistochemistry. YAP1 activation was confirmed by immunofluorescence staining and luciferase transcriptional activity reporter assay. The functional role and mechanism of regulation of YAP1 by APE1 was determined by sphere formation assay, siRNA mediated knockdown, redox-specific inhibition, and co-immunoprecipitation assays.

Results

We showed that YAP1 signaling is activated in BE and EAC cells following exposure to ABS, the mimicry of reflux conditions in patients with GERD. This induction was consistent with APE1 upregulation in response to ABS. YAP1 activation was confirmed by its nuclear accumulation with corresponding up-regulation of YAP1 target genes. APE1 silencing inhibited YAP1 protein induction and reduced its nuclear expression and transcriptional activity, following ABS treatment. Further investigation revealed that APE1-redox-specific inhibition (E3330) or APE1 redox-deficient mutant (C65A) abrogated ABS-mediated YAP1 activation, indicating an APE1 redox-dependent mechanism. APE1 silencing or E3330 treatment reduced YAP1 protein levels and diminished the number and size of EAC spheroids. Mechanistically, we demonstrated that APE1 regulated YAP1 stability through interaction with β-TrCP ubiquitinase, whereas APE1-redox-specific inhibition induced YAP1 poly-ubiquitination promoting its degradation.

Conclusion

Our findings established a novel function of APE1 in EAC progression elucidating druggable molecular vulnerabilities via targeting APE1 or YAP1 for the treatment of EAC.
The role of oxidative stress in ovarian aging: a review
Authors: Yan Fei , Zhao Qi , Li Ying , Zheng Zhibo , Kong Xinliang , Shu Chang , Liu Yanfeng , Shi Yun
Published: September 2022

Ovarian aging refers to the process by which ovarian function declines until eventual failure. The pathogenesis of ovarian aging is complex and diverse; oxidative stress (OS) is considered to be a key factor. This review focuses on the fact that OS status accelerates the ovarian aging process by promoting apoptosis, inflammation, mitochondrial damage, telomere shortening and biomacromolecular damage. Current evidence suggests that aging, smoking, high-sugar diets, pressure, superovulation, chemotherapeutic agents and industrial pollutants can be factors that accelerate ovarian aging by exacerbating OS status. In addition, we review the role of nuclear factor E2-related factor 2 (Nrf2), Sirtuin (Sirt), mitogen-activated protein kinase (MAPK), protein kinase B (AKT), Forkhead box O (FoxO) and Klotho signaling pathways during the process of ovarian aging. We also explore the role of antioxidant therapies such as melatonin, vitamins, stem cell therapies, antioxidant monomers and Traditional Chinese Medicine (TCM), and investigate the roles of these supplements with respect to the reduction of OS and the improvement of ovarian function. This review provides a rationale for antioxidant therapy to improve ovarian aging.
CTCF and cohesin promote focal detachment of DNA from the nuclear lamina
Authors: van Schaik Tom , Liu Ning Qing , Manzo Stefano G. , Peric-Hupkes Daan , de Wit Elzo , van Steensel Bas
Published: September 2022

Background

Lamina-associated domains (LADs) are large genomic regions that are positioned at the nuclear lamina. It has remained largely unclear what drives the positioning and demarcation of LADs. Because the insulator protein CTCF is enriched at LAD borders, it was postulated that CTCF binding could position some LAD boundaries, possibly through its function in stalling cohesin and hence preventing cohesin invading into the LAD. To test this, we mapped genome–nuclear lamina interactions in mouse embryonic stem cells after rapid depletion of CTCF and other perturbations of cohesin dynamics.

Results

CTCF and cohesin contribute to a sharp transition in lamina interactions at LAD borders, while LADs are maintained after depletion of these proteins, also at borders marked by CTCF. CTCF and cohesin may thus reinforce LAD borders, but do not position these. CTCF binding sites within LADs are locally detached from the lamina and enriched for accessible DNA and active histone modifications. Remarkably, despite lamina positioning being strongly correlated with genome inactivity, this DNA remains accessible after the local detachment is lost following CTCF depletion. At a chromosomal scale, cohesin depletion and cohesin stabilization by depletion of the unloading factor WAPL quantitatively affect lamina interactions, indicative of perturbed chromosomal positioning in the nucleus. Finally, while H3K27me3 is locally enriched at CTCF-marked LAD borders, we find no evidence for an interplay between CTCF and H3K27me3 on lamina interactions.

Conclusions

These findings illustrate that CTCF and cohesin are not primary determinants of LAD patterns. Rather, these proteins locally modulate NL interactions.
Utilization of preventive services in a systemic lupus erythematosus population-based cohort: a Lupus Midwest Network (LUMEN) study
Authors: Chevet Baptiste , Figueroa-Parra Gabriel , Yang Jeffrey X. , Hocaoglu Mehmet , Osei-Onomah Shirley-Ann , Hulshizer Cassondra A. , Gunderson Tina M. , Cornec Divi , Barbour Kamil E. , Greenlund Kurt J. , Crowson Cynthia S. , Duarte-García Alí
Published: September 2022

Background

Systemic lupus erythematosus (SLE) is a disease that can lead to damage of multiple organs and, along with certain treatments, increase the risk of developing cancer, cardiovascular disease, diabetes, osteoporosis, and infections. Preventive services are particularly important in patients with SLE to mitigate the aforementioned risks. We aimed to evaluate the trends of preventive services utilization in patients with systemic lupus erythematosus, compared with non-SLE population.

Methods

All ≥19-year-old patients in the Lupus Midwest Network (LUMEN) registry, a population-based cohort, with SLE on January 1, 2015, were included and matched (1:1) by sex, age, race, and county to non-SLE comparators. Among both groups, we compared the rates of screenings for breast and cervical cancer, hypertension, hyperlipidemia, diabetes mellitus, and osteoporosis as well as immunizations.

Results

We included 440 SLE patients and 430 non-SLE comparators. The probability of breast cancer screening among women with SLE was similar to comparators (hazard ratio [HR] 1.09, 95% CI 0.85–1.39), while cervical cancer screening was lower (HR 0.75, 95% CI 0.58–0.96). Hypertension screening was higher among patients with SLE (HR 1.35, 95% CI 1.13–1.62); however, hyperlipidemia screening was similar to comparators (HR 1.16, 95% CI 0.96–1.41). Diabetes and osteoporosis screenings were more likely to be performed for SLE patients than for comparators (HR 2.46, 95% CI 2.11–2.87; and HR 3.19, 95% CI 2.31–4.41; respectively). Influenza and pneumococcal immunizations were higher among SLE patients (HR 1.31, 95% CI 1.12–1.54; and HR 2.06, 95% CI 1.38–3.09; respectively), while zoster vaccination was similar (HR 1.17, 95% CI 0.81–1.69).

Conclusions

The trends of utilization of preventive services by SLE patients vary according to screening or vaccine compared with the general population. Considering these differences, we demonstrate an opportunity for improvement, particularly in cervical cancer, hyperlipidemia, and osteoporosis screenings and vaccinations.
Robustness under parameter and problem domain alterations of Bayesian optimization methods for chemical reactions
Authors: Khondaker Rubaiyat Mohammad , Gow Stephen , Kanza Samantha , Frey Jeremy G , Niranjan Mahesan
Published: September 2022

The related problems of chemical reaction optimization and reaction scope search concern the discovery of reaction pathways and conditions that provide the best percentage yield of a target product. The space of possible reaction pathways or conditions is too large to search in full, so identifying a globally optimal set of conditions must instead draw on mathematical methods to identify areas of the space that should be investigated. An intriguing contribution to this area of research is the recent development of the Experimental Design for Bayesian optimization (EDBO) optimizer [1]. Bayesian optimization works by building an approximation to the true function to be optimized based on a small set of simulations, and selecting the next point (or points) to be tested based on an acquisition function reflecting the value of different points within the input space. In this work, we evaluated the robustness of the EDBO optimizer under several changes to its specification. We investigated the effect on the performance of the optimizer of altering the acquisition function and batch size, applied the method to other existing reaction yield data sets, and considered its performance in the new problem domain of molecular power conversion efficiency in photovoltaic cells. Our results indicated that the EDBO optimizer broadly performs well under these changes; of particular note is the competitive performance of the computationally cheaper acquisition function Thompson Sampling when compared to the original Expected Improvement function, and some concerns around the method’s performance for “incomplete” input domains.
Hydrocephalus: historical analysis and considerations for treatment
Authors: Hochstetler Alexandra , Raskin Jeffrey , Blazer-Yost Bonnie L.
Published: September 2022

Hydrocephalus is a serious condition that affects patients of all ages, resulting from a multitude of causes. While the etiologies of hydrocephalus are numerous, many of the acute and chronic symptoms of the condition are shared. These symptoms include disorientation and pain (headaches), cognitive and developmental changes, vision and sleep disturbances, and gait abnormalities. This collective group of symptoms combined with the effectiveness of CSF diversion as a surgical intervention for many types of the condition suggest that the various etiologies may share common cellular and molecular dysfunctions. The incidence rate of pediatric hydrocephalus is approximately 0.1–0.6% of live births, making it as common as Down syndrome in infants. Diagnosis and treatment of various forms of adult hydrocephalus remain understudied and underreported. Surgical interventions to treat hydrocephalus, though lifesaving, have a high incidence of failure. Previously tested pharmacotherapies for the treatment of hydrocephalus have resulted in net zero or negative outcomes for patients potentially due to the lack of understanding of the cellular and molecular mechanisms that contribute to the development of hydrocephalus. Very few well-validated drug targets have been proposed for therapy; most of these have been within the last 5 years. Within the last 50 years, there have been only incremental improvements in surgical treatments for hydrocephalus, and there has been little progress made towards prevention or cure. This demonstrates the need to develop nonsurgical interventions for the treatment of hydrocephalus regardless of etiology. The development of new treatment paradigms relies heavily on investment in researching the common molecular mechanisms that contribute to all of the forms of hydrocephalus, and requires the concerted support of patient advocacy organizations, government- and private-funded research, biotechnology and pharmaceutical companies, the medical device industry, and the vast network of healthcare professionals.
Adoption of artificial insemination technology and its intensity of use in Eastern Tigray National Regional State of Ethiopia
Authors: Gebre Yemane Hailu , Gebru Gebrehiwot Weldegebrial , Gebre Kahsa Tadel
Published: September 2022

Background

The study was focused on the adoption and intensity of adoption of artificial insemination (AI) Technology in Saesie-tsaedaemba District of Tigray Region, Ethiopia. AI is one of the most important and valuable dairy technology that has been used for genetic improvement for several years in the study area. However, there was little empirical information about major factors affecting adoption decision and intensity of AI in the study area. The purpose of this study was to evaluate the status of AI technology adoption and its intensity and to identify major factors influencing the adoption and intensity of use of AI technology.

Methods

A multistage sampling technique was applied to select study sites and sample households. A structured interview was used to collect data from a total of 204 sample farmers. Besides, key informants interview was used to triangulate, validate, and enrich the findings of the household interview.

Results

Results of the tobit model regression revealed that households’ level of literacy, milk yield, income, training, access to extension service, mobile ownership, supplementation of concentrated feed and hybrid cattle ownership were found to have a positive and statistically significant relationship with adoption and intensity of AI technology, whereas distance to farmer training centre (FTC) office had shown a negative relationship.

Conclusions

Adoption of context-based AI technology plays a paramount importance in achieving farm household's food security. The extension system should give more emphasis to the capacity building which is pivotal for introducing, adoption, and scaling out of best practices of dairy technologies. Besides the effort of the government, the participation of the private sector in AI technology is important to achieve wider adoption of AI technology.
Experimental Evaluation of Effect Factors on Seismic Performance of Concrete Columns Reinforced with HTRB630 High-Strength Steel Bars
Authors: Sun Chuanzhi , Zhuang Mei-Ling , Dong Bo
Published: September 2022

HTRB630 steel bar is a new type of high-strength steel bars. To study the seismic performance and promote the application of concrete columns reinforced with HTRB630 high-strength steel bars, the pseudo-static test of 10 concrete columns reinforced with HTRB630 high-strength steel bars and 3 concrete columns reinforced with HRB400 was carried out. Test specimens were divided into five categories according to concrete grade, reinforcement strength, and degree of confinement. The effect of concrete strength (C45 and C60), axial load ratio (0.1 and 0.25), equal strength substitution of longitudinal reinforcements (HTRB630 and HRB400), equal strength and volume substitution of stirrups (HTRB630 and HRB400), equal strength substitution of confined reinforcements (HTRB630 and HRB400) on the seismic performance are analyzed and discussed from the failure mode, hysteresis loops, skeleton curves, lateral strength, ductility, energy dissipation capacity, stiffness and strength degradation. The failure mode of each specimen was bending failure. Reducing of the axial lo ratio or increasing the strength of reinforcements, the seismic performance of the specimen could be improved. C60 concrete can improve the seismic performance of HTRB630 reinforced columns. The lateral strength of the concrete column specimen with HTRB630 reinforcements was slightly increased, and the ductility and energy dissipation capacity were reduced, the stiffness degradation was more gradual, the strength degradation coefficient was greater than 0.94, but still met the requirements of the code for seismic design of buildings (GB50011-2010).
Metabolic cross-talk within the bone marrow milieu: focus on multiple myeloma
Authors: Oudaert Inge , Van der Vreken Arne , Maes Anke , De Bruyne Elke , De Veirman Kim , Vanderkerken Karin , Menu Eline
Published: September 2022

Cancer cells are well-known for their capacity to adapt their metabolism to their increasing energy demands which is necessary for tumor progression. This is no different for Multiple Myeloma (MM), a hematological cancer which develops in the bone marrow (BM), whereby the malignant plasma cells accumulate and impair normal BM functions. It has become clear that the hypoxic BM environment contributes to metabolic rewiring of the MM cells, including changes in metabolite levels, increased/decreased activity of metabolic enzymes and metabolic shifts. These adaptations will lead to a pro-tumoral environment stimulating MM growth and drug resistance In this review, we discuss the identified metabolic changes in MM and the BM microenvironment and summarize how these identified changes have been targeted (by inhibitors, genetic approaches or deprivation studies) in order to block MM progression and survival.
Impaired mitochondria of Tregs decreases OXPHOS-derived ATP in primary immune thrombocytopenia with positive plasma pathogens detected by metagenomic sequencing
Authors: Zhan Yanxia , Cao Jingjing , Ji Lili , Zhang Miaomiao , Shen Qi , Xu Pengcheng , Zhuang Xibing , Qin Shanshan , Hua Fanli , Sun Lihua , Li Feng , Chen Hao , Cheng Yunfeng
Published: September 2022

Background

Primary immune thrombocytopenia (ITP) is an autoimmune disease. Some ITP patients are associated with pathogen infection undetected with conventional technologies. Investigating the changes of T cells and potential metabolic mechanism are important for better understanding of ITP.

Methods

The study enrolled 75 newly diagnosed ITP patients. The pathogens of patients were detected by metagenomic next-generation sequencing (mNGS). Plasma lipids were measured by liquid chromatography-mass spectrometry (LC–MS). CD4 T cell and CD8 T cell were analyzed using flow cytometry. Mitochondrial reactive oxygen species (ROS) and mitochondrial membrane potential were measured by flow cytometry. Seahorse XF real-time ATP rate assay was used to investigate the change of cellular metabolism.

Results

Positive plasma pathogens were detected in seven ITP patients. Of them, 5 (71.4%) positive pathogen-ITP patients were no response (NR) after first-line treatment with corticosteroids. Regulatory T cells (Tregs) increased significantly in positive pathogen-ITP patients compared to negative pathogen-ITP patients and healthy controls (HC). Mitochondrial membrane potential of Th17 and Tregs were decreased in positive pathogen-ITP and negative pathogen-ITP patients, compared to HC (all p < 0.05). The overall metabolism flux of positive pathogen-ITP patients was decreased, as compared to HC (p = 0.004), of them a higher proportion of glycolysis-derived ATP and a smaller proportion of oxidative phosphorylation (OXPHOS)-derived ATP were found in Tregs. The ATP rate index of Tregs was decreased significantly in positive pathogen-ITP patients compared to negative pathogen-ITP patients and HC (p < 0.05).

Conclusions

Impaired mitochondria function of Tregs in positive pathogen-ITP patients caused a decrease of OXPHOS-derived ATP and overall metabolism flux that might be the cause of steroid resistance in ITP patients.