bluuebunny/crossref_metadata_2025 huggingface dataset:
Low thyroid function is associated with an increased risk of advanced fibrosis in patients with metabolic dysfunction-associated fatty liver disease
Authors: Fan Hong , Li Lili , Liu Zhenqiu , Zhang Pengyan , Wu Sheng , Han Xinyu , Chen Xingdong , Suo Chen , Cao Liou , Zhang Tiejun
Published: January 2023

Aims

Observational studies showed that low thyroid function may perturb liver function. We aimed to evaluate the association of low thyroid function with both metabolic dysfunction-associated fatty liver disease (MAFLD) and advanced hepatic fibrosis.

Methods

Participants who underwent abdominal ultrasonography and thyroid function test in a Chinese hospital from 2015 to 2021were enrolled. Fibrosis-4 index (FIB-4) > 2.67 and/or non-alcoholic fatty liver disease fibrosis score (NFS) > 0.676 were used to define advanced fibrosis. Descriptive analyses were performed to characterize the epidemiology of MAFLD according to levels of thyroid-stimulating hormone (TSH). The logistic regression model was applied to estimate the association of low thyroid function with MAFLD and advanced fibrosis.

Results

A total of 19,946 participants (52.78% males, mean age: 47.31 years, 27.55% MAFLD) were included, among which 14,789 were strict-normal thyroid function, 4,328 were low-normal thyroid function, 829 were subclinical hypothyroidism. TSH levels were significantly higher in MAFLD patients with a FIB-4 > 2.67 and /or NFS > 0.676 than their counterparts. The logistic regression model adjusted for age and sex showed that low-normal thyroid function increased the risk of MAFLD (odds ratio [OR] = 1.09; 95% confidence interval [CI] 1.01–1.18). Multivariable regression model adjusted for age, sex, body mass index, type 2 diabetes, and hypertension showed low-normal thyroid function increased the risk of advanced fibrosis in patients with MAFLD (FIB-4 > 2.67: OR = 1.41, 95% CI 1.02–1.93; NFS > 0.676: OR = 1.72, 95% CI 1.08–2.72).

Conclusion

Elevated TSH concentrations are associated with advanced hepatic fibrosis, even in the euthyroid state.
Deep medullary veins: a promising neuroimaging marker for mild cognitive impairment in outpatients
Authors: Chen Xiuqi , Luo Yufan , Zhang Shufan , Yang Xiaoli , Dong Zhiyuan , Wang Yilin , Wu Danhong
Published: January 2023

Background and purpose

Mild cognitive impairment is an age-dependent pre-dementia state caused by varied reasons. Early detection of MCI helps handle dementia. Vascular factors are vital for the occurrence of MCI. This study investigates the correlation between deep medullary veins and multi-dimensional cognitive outcomes.

Materials and methods

A total of 73 participants with MCI and 32 controls were enrolled. Minimum Mental State Examination and Montreal Cognitive Assessment were used to examine the global cognitive function, and different cognitive domains were measured by specific neuropsychological tests. MRI was used to assess the visibility of the DMV and other neuroimage markers.

Results

DMV score was statistically significantly higher in the MCI group compared with the control group (P = 0.009) and independently related to MCI (P = 0.007). Linear regression analysis verified that DMV score was linearly related to global cognition, memory, attention, and executive function after adjusting for cerebrovascular risk factors.

Conclusion

DMV score was independently related to the onset of MCI, and correlates with overall cognition, memory, attention, and executive function in outpatients.
PD-L1 is highly expressed in ovarian cancer and associated with cancer stem cells populations expressing CD44 and other stem cell markers
Authors: Alwosaibai Kholoud , Aalmri Salmah , Mashhour Miral , Ghandorah Salim , Alshangiti Abdulraheem , Azam Faisal , Selwi Waleed , Gharaibeh Lubna , Alatawi Yasser , Alruwaii Zainab , Alsaab Hashem O.
Published: January 2023

Background

Immune checkpoint inhibitors, including PD-L1 (programmed death ligand-1) inhibitors have well documented anticancer therapeutic effect in most types of cancers but its use in the treatment of ovarian cancer is not yet proven. The aim of our study is to explore the predictive biomarkers in ovarian cancer and its association with the outcomes. We have investigated the role of PD-L1 expressions in the tumor microenvironment cells including immune cells and cancer stem cells in different types of ovarian cancer.

Methods

A total of 119 surgical archived ovarian cancer samples were collected from the pathology department at King Fahad Specialist Hospital, Dammam, Saudi Arabia that included serous carcinomas, clear cell carcinomas, mucinous carcinomas, endometrioid carcinomas, and granulosa cell tumors. Immunohistochemistry (IHC) staining was performed using (i) PD-L1 antibodies to detect PD-L1 expressions; (ii) CD8 and CD4 to detect Tumor Infiltrating Lymphocytes (TILs); and (iii) CD44, LGR5, and ALDH2 to detect stem cell markers. The clinicopathological data were collected from patients’ medical record to investigate the association with PD-L1, TILs, and stem cells expressions.

Results

We report high PD-L1 expressions in 47.8% of ovarian cancer samples. PD-L1 expressions were detected in different types of epithelial ovarian cancer and were not associated with poor prognosis of ovarian cancer. However, determining the expression levels of TILs in the ovarian cancer tissues found that 81% (n = 97) of ovarian cancer samples have TILs that express both of CD8 and CD4 and significantly associated with high PD-L1 expressions. Interestingly, we have found that ovarian cancer tissues with high expressions of PD-L1 were associated with high expressions of stem cells expressing CD44 and LGR5.

Conclusions

PD-L1 is highly expressed in the serous type of ovarian carcinomas and the overall expression of PD-L1 is not associated with poor survival rate. Furthermore, PD-L1 expressions are strongly associated with TILs and stem cell markers in ovarian cancer. Inhibiting the PD-L1 using immune checkpoint inhibitors might downregulate stem cell population that known to be associated with cancer recurrence.
The efficacy of small molecule anti-angiogenic drugs in previously treated Thymic carcinoma
Authors: Guan Yelan , Gu Xiaodong , Si Jinfei , Xiang Jing , Wei Jingwen , Hao Yue , Wang Wenxian , Sun Yan
Published: January 2023

Background

Antiangiogenic drugs have shown initial efficacy in the treatment of advanced thymic carcinomas (TCs); however, data are limited. In this study, we provide real-world data relating to the efficacy of antiangiogenic drugs for the treatment of patients with TCs.

Methods

We retrospectively collected data on clinical progress after first-line chemotherapy in TCs patients who were treated with small molecule antiangiogenic drugs at our institution between January 2010 and December 2021. Tumor response was evaluated according to version 1.1 of the Response Evaluation Criteria in Solid Tumors. Progression free survival and overall survival were calculated using the Kaplan-Meier method.

Results

Of the 17 patients enrolled, 13 (76.5%) received apatinib and four (23.5%) anlotinib monotherapy with an objective response rate of 23.5%. Eleven (64.7%) patients had stable disease. The median follow-up period was 46.0 months (95% confidence interval [CI], 33.0–59.0 months). The median progression survival and overall survival were 7.9 months (95% CI, 6.5–9.3) and 47.0 months (95% CI, 35.4–58.6), respectively. In the 13 patients receiving apatinib, the median PFS was 7.0 months (95% CI, 5.0–9.0), compared with 8.0 months (95% CI, 2.7–13.3 months) for patients in the anlotinib group (P = 0.945). The most common grade 3 adverse events (AEs) were hypertension (n = 3, 23.1%), followed by proteinuria and hand-foot syndrome (HFS, n = 2, 15.4%). There were no grade 4 AEs although eight patients (47.1%) required mid-course discontinuation.

Conclusion

For refractory TCs, small molecule antiangiogenic drugs are efficacious as second- or post-line treatments. The toxicity of antiangiogenic therapy is manageable.
Inference of core needle biopsy whole slide images requiring definitive therapy for prostate cancer
Authors: Tsuneki Masayuki , Abe Makoto , Ichihara Shin , Kanavati Fahdi
Published: January 2023

Background

Prostate cancer is often a slowly progressive indolent disease. Unnecessary treatments from overdiagnosis are a significant concern, particularly low-grade disease. Active surveillance has being considered as a risk management strategy to avoid potential side effects by unnecessary radical treatment. In 2016, American Society of Clinical Oncology (ASCO) endorsed the Cancer Care Ontario (CCO) Clinical Practice Guideline on active surveillance for the management of localized prostate cancer.

Methods

Based on this guideline, we developed a deep learning model to classify prostate adenocarcinoma into indolent (applicable for active surveillance) and aggressive (necessary for definitive therapy) on core needle biopsy whole slide images (WSIs). In this study, we trained deep learning models using a combination of transfer, weakly supervised, and fully supervised learning approaches using a dataset of core needle biopsy WSIs (n=1300). In addition, we performed an inter-rater reliability evaluation on the WSI classification.

Results

We evaluated the models on a test set (n=645), achieving ROC-AUCs of 0.846 for indolent and 0.980 for aggressive. The inter-rater reliability evaluation showed s-scores in the range of 0.10 to 0.95, with the lowest being on the WSIs with both indolent and aggressive classification by the model, and the highest on benign WSIs.

Conclusion

The results demonstrate the promising potential of deployment in a practical prostate adenocarcinoma histopathological diagnostic workflow system.
A delta-radiomic lymph node model using dynamic contrast enhanced MRI for the early prediction of axillary response after neoadjuvant chemotherapy in breast cancer patients
Authors: Liu Shasha , Du Siyao , Gao Si , Teng Yuee , Jin Feng , Zhang Lina
Published: January 2023

Background

The objective of this paper is to explore the value of a delta-radiomic model of the axillary lymph node (ALN) using dynamic contrast-enhanced (DCE) MRI for early prediction of the axillary pathological complete response (pCR) of breast cancer patients after neoadjuvant chemotherapy (NAC).

Methods

A total of 120 patients with ALN-positive breast cancer who underwent breast MRI before and after the first cycle of NAC between October 2018 and May 2021 were prospectively included in this study. Patients were divided into a training (n = 84) and validation (n = 36) cohort based on the temporal order of their treatments. Radiomic features were extracted from the largest slice of targeted ALN on DCE-MRI at pretreatment and after one cycle of NAC, and their changes (delta-) were calculated and recorded. Logistic regression was then applied to build radiomic models using the pretreatment (pre-), first-cycle(1st-), and changes (delta-) radiomic features separately. A clinical model was also built and combined with the radiomic models. The models were evaluated by discrimination, calibration, and clinical application and compared using DeLong test.

Results

Among the three radiomic models, the ALN delta-radiomic model performed the best with AUCs of 0.851 (95% CI: 0.770–0.932) and 0.822 (95% CI: 0.685–0.958) in the training and validation cohorts, respectively. The clinical model yielded moderate AUCs of 0.742 (95% CI: 0.637–0.846) and 0.723 (95% CI: 0.550–0.896), respectively. After combining clinical features to the delta-radiomics model, the efficacy of the combined model (AUC = 0.932) in the training cohort was significantly higher than that of both the delta-radiomic model (Delong p = 0.017) and the clinical model (Delong p < 0.001) individually. Additionally, in the validation cohort, the combined model had the highest AUC (0.859) of any of the models we tested although this was not statistically different from any other individual model’s validation AUC. Calibration and decision curves showed a good agreement and a high clinical benefit for the combined model.

Conclusion

This preliminary study indicates that ALN-based delta-radiomic model combined with clinical features is a promising strategy for the early prediction of downstaging ALN status after NAC. Future axillary MRI applications need to be further explored.
Prevalence and factors associated with Diabetes retinopathy among type 2 diabetic patients at Northwest Amhara Comprehensive Specialized Hospitals, Northwest Ethiopia 2021
Authors: Zegeye Alebachew Ferede , Temachu Yemataw Zewdu , Mekonnen Chilot Kassa
Published: January 2023

Introduction

The worldwide prevalence of Diabetic Retinopathy was recently estimated to be 34.6%. The prevalence of diabetic retinopathy in developed nations has been thoroughly investigated, and risk factors are well understood. However, there is a shortage of information in the study areas about the prevalence and contributing factors of diabetic retinopathy among type two diabetes patients.

Objective

The aim of this study was to assess the prevalence of diabetic retinopathy and associated factor among type 2 diabetic patients who were on follow up services at northwest Amhara comprehensive specialized hospitals diabetic care units.

Method

An institutional based cross-sectional study was conducted at northwest Amhara comprehensive specialized hospitals from October 15 to November 15, 2021, among 496 diabetes patients. Systematic random sampling technique was used. Data were collected by utilizing a semi-structured questionnaire and a direct Topcon retinal camera inspection. Then data were coded, entered, and exported to SPSS version 23 from EPI-Data version 4.6. All variables with P-value < 0.25 in the binary logistic regression analyses were included in the multivariable regression analysis. The degree of association was interpreted by using the adjusted odds ratio with 95% confidence intervals, and the significance level was declared at P-value < 0.05. The Hosmer–Lemeshow test was used to check the fitness of the model.

Result

The prevalence of diabetic retinopathy among type two diabetes patients was 36.3%. Sex [AOR = 3.25, 95% CI (1.80, 6.68)], visiting health institution [AOR = 0.027, 95% CI (0.003, 0.253)], educational level [AOR = 4.23, 95% CI (1.09, 16.47)], glycemic control [AOR = 0.099, 95% CI (0.02, 0.49)], hypertension status (AOR = 2.56, 95% CI (1.01, 6.45)] were significantly associated with diabetic retinopathy.

Conclusion

In this study less than half of diabetic patients had diabetic retinopathy. Sex, visiting health institution, educational level, glycemic control, and hypertension status were significantly associated with diabetic retinopathy.
Neuro-ophthalmologic symptoms after coronavirus disease 2019 vaccination: a retrospective study
Authors: Kang Kyumin , Lee Se Youp , Lee Dong Cheol
Published: January 2023

Background

There have been several studies on inflammatory ophthalmic diseases; however, few studies have reported neuro-ophthalmological symptoms, such as diplopia and ocular motor nerve palsy, after coronavirus disease 2019 (COVID-19) vaccination. Therefore, this study aimed to report neuro-ophthalmological symptoms in patients after COVID-19 vaccination.

Methods

This was a retrospective study based on the medical records of 10 patients who visited our ophthalmology clinic in 2021 with symptoms, such as diplopia (nine patients) and decreased visual acuity (one patient), and showed findings, such as ocular motor nerve palsy, after vaccination against COVID-19.

Results

One patient had third nerve palsy, two had sixth nerve palsy, and five had fourth nerve palsy. One patient complained of subjective binocular diplopia but all test results were normal. One patient presented with decreased visual acuity accompanied by a sudden increase in intraocular pressure and orbital cellulitis in the other eye. The symptoms improved gradually in most patients. Compared with previous studies, this study reported three cases of antiplatelet therapy that was initiated due to the older age of the patients and underlying diseases.

Conclusion

As COVID-19 vaccines can cause neuro-ophthalmological diseases, such as ocular motor nerve palsy, patients’ age and underlying diseases should be considered while administering them.
Comparison between the CASIA SS-1000 and Pentacam in measuring corneal curvatures and corneal thickness maps
Authors: Feldman Robert M. , Kim Gene , Chuang Alice Z. , Shiraishi Atsushi , Okamoto Keiichiro , Tsukamoto Makoto
Published: January 2023

Purpose

To compare the intra-device repeatability and inter-device reproducibility between two anterior segment imaging instruments, the CASIA SS-1000 (Tomey Corp., Nagoya, Japan) and Pentacam (OCULUS, Arlington, WA) in measuring anterior segment parameters.

Methods

Single-center, prospective clinical trial. Participants ≥20 years of age were included. One eye was randomly selected, each imaged by three CASIA SS-1000 devices and three Pentacam devices by three different examiners. Each photographer operated a pair of devices, one CASIA SS-1000 and one Pentacam. The image order for each participant was determined by a random permutation table. Three images were taken from each device. A total of 18 images were taken for each eye. Ratios of the standard deviations, referenced as (CASIA/Pentacam), were calculated to compare the repeatability and reproducibility of the two imaging instruments.

Results

In all, 66 participants with a mean age of 46.4 years (±21.7) were enrolled in the study. All repeatability ratios and intra-device variability were less than 1 (anterior corneal curvature: flat = 0.86, steep = 0.85; posterior corneal curvature: flat = 0.43, steep = 0.61; and map: thinnest = 0.22; central = 0.24, 2 mm = 0.26, 4 mm = 0.27, and 6 mm = 0.30). All reproducibility ratios, which measure the inter-device variability, were less than 1 (anterior corneal curvature: flat = 0.58, steep = 0.73; posterior corneal curvature: flat = 0.25, steep = 0.31; and pachymetry map: thinnest = 0.20; central = 0.20; 2 mm = 0.20; 4 mm = 0.19; and 6 mm = 0.22). A ratio of less than 1 indicates that the CASIA SS-1000 has more consistent measurements.

Conclusions

The CASIA SS-1000 was found to have better repeatability and reproducibility compared to the Pentacam for both corneal curvature and pachymetry maps. This greater consistency may require further study to determine whether the decreased variability can be translated into improved clinical results.
Relationships between physical activity, body image, BMI, depression and anxiety in Chinese college students during the COVID-19 pandemic
Authors: Han Bing , Du Guoli , Yang Yashu , Chen Jiping , Sun Guoxiao
Published: January 2023

Background

Both depression and anxiety are worldwide burden that is not being abated with our current knowledge and treatment of the condition. Numerous clinical trials have supported that physical activity (PA) can reduce the depression and anxiety in adolescents, but little is known about its mechanism of action. Therefore, the study objectives were to explore the potential relationship between physical activity and depression and anxiety from the perspective of body image and body mass index (BMI), and to provide an important reference for future self-esteem education and health promotion intervention.

Methods

The participants in this study were 251 Chinese college students between 17 and 22 years old. Participants completed the International Physical Activity Questionnaire-Short Form (IPAQ-SF), the Body Image Questionnaire (BIQ), the Self-rating Depression Scale (SDS) and the Self-rating Anxiety Scale (SAS). A descriptive and correlational approach was used, using the PROCESS macro for Statistical Package for the Social Sciences (SPSS).

Results

(1) Physical activity was significantly negatively correlated with both depression and anxiety (t = -0.216, p < 0.001; t = -0.184, p < 0.01). (2) Body image had a significant moderating effect on the relationship between physical activity and anxiety among college students, but there was no moderating effect between depression and physical activity. BMI has no moderating effect on the two interrelationships.

Conclusion

There is only body image that moderates the relationship between anxiety and physical activity.
Transbronchial cryobiopsy in unexplained, severe ARDS: a single center retrospective case series
Authors: Eisenmann Stephan , Lambrecht Nina , Dießel Linda , Busse Christin , Nuding Sebastian , Vogt Alexander
Published: January 2023

Background

Acute respiratory distress syndrome (ARDS) deptics an acute form of lung infjury with often severe respiratory impairment that requires invasive mechanical ventilation. Since ARDS can be caused by several distinct etiologies, correct characterization is desired and frequently challenging. Surgical lung biopsy was previously reported to be of additive value. We describe our institutional experience using transbronchial cryobiopsy (TBCB) for further characterization of severe and unexplained ARDS cases.

Case presentation

We retrospectively collected data of TBCB in patients with unexplained ARDS, whether with or without ECMO-support. Between 2019 and 2020 TBCB was performed in eight patients. Decision for the intervention was decided in multidisciplinary discussion. Five patients were treated with ECMO. The median duration of invasive ventilation before TBCB was 24 days. TBCB was performed in one segment, that was prophylactically occluded by Watanabe spigot or swab after the procedure. Histology results and their contribution to further therapeutic decisions were analyzed. Histology revealed five diffuses alveolar damage, one acute fibrinoid organizing pneumonia, one cryptogenic organizing pneumonia and one lung cancer. All results contributed to the decision of further management. While no pneumothorax or severe endobronchial bleeding occurred, two delayed hematothoraces needed surgical treatment. No patients died due to TBCB.

Conclusion

TBCB is feasible in ARDS even during ECMO treatment. Histologic results can play a significant role in therapeutic and ethic discussion to guide the patients’ care. Side effects should be considered and monitored.
Association between psoriasis and lung cancer: two-sample Mendelian randomization analyses
Authors: Wang Xiuqing , Wang Xiulan , Wang Hongkang , Yang Mingxing , Dong Wen , Shao Dan
Published: January 2023

Background

Observational studies reported an association between psoriasis and risk of lung cancer. However, whether psoriasis is causally associated with lung cancer is unclear.

Methods

Genetic summary data of psoriasis were retrieved from two independent genome-wide association studies (GWAS). Genetic information of lung cancer was retrieved from GWAS of International Lung Cancer Consortium. A set of quality control steps were conducted to select instrumental tools. We performed two independent two-sample Mendelian randomization (MR) analyses and a meta-analysis based on the two independent MR estimates to assess the causal relationship between psoriasis and lung cancer (LUCA) as well as its subtypes, squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD).

Results

Between-SNP heterogeneity was present for most MR analyses, whereas horizontal pleiotropy was not detected for all MR analyses. Multiplicative random-effect inverse variance weighted (IVW-MRE) method was therefore selected as the primary MR approach. Both IVW-MRE estimates from the two independent MR analyses suggested that there was no significant causal relationship between psoriasis and LUCA as well as its histological subtypes. Sensitivity analyses using other four MR methods gave similar results. Meta-analysis of the two IVW-MRE derived MR estimates yielded an odds ratio (OR) of 1.00 (95% CI 0.95–1.06) for LUCA, 1.01 (95% CI 0.93–1.08) for LUSC, and 0.97 (95% CI 0.90–1.06) for LUAD.

Conclusion

Our results do not support a genetic association between psoriasis and lung cancer and its subtypes. More population-based and experimental studies are warranted to further dissect the complex correlation between psoriasis and lung cancer.
Comparison between functional lung volume measurement and segment counting for predicting postoperative pulmonary function after pulmonary resection in lung cancer patients
Authors: Fan Zheyuan , Zhao Shilei , Wang Ling , Li Fengzhou , Wang Jin , Gu Chundong
Published: January 2023

Background

Functional lung volume (FLV) obtained from computed tomography images was a breakthrough for lung imaging and functional assessment. We compared the accuracy of the FLV measurement method and the segment-counting (SC) method in predicting postoperative pulmonary function.

Methods

A total of 113 patients who underwent two thoracoscopic surgeries were enrolled in our study. We predicted postoperative pulmonary function by the FLV measurement method and the SC method. Novel formulas based on the FLV measurement method were established using linear regression equations between the factors affecting pulmonary function and the measured values.

Results

The predicted postoperative forced vital capacity (ppoFVC) and forced expiratory volume in 1 s (ppoFEV1) measured by the 2 methods showed high concordance between the actual postoperative forced vital capacity (postFVC) and the forced expiratory volume in 1 s (postFEV1) [r = 0.762, P < 0.001 (FLV method) and r = 0.759, P < 0.001 (SC method) for FVC; r = 0.790, P < 0.001 (FLV method) and r = 0.795, P < 0.001 (SC method) for FEV1]. Regression analysis showed that the measured preoperative pulmonary function parameters (FVC, FEV1) and the ratio of reduced FLV to preoperative FLV were significantly associated with the actual postoperative values and could predict these parameters (all P < 0.001). The feasibility of using these equations [postFVC = 0.8 × FVC − 0.784 × ΔFLV/FLV + 0.283 (R2 = 0.677, RSD = 0.338), postFEV1 = 0.766 × FEV1 − 0.694 × ΔFLV/FLV + 0.22 (R2 = 0.743, RSD = 0.265)] to predict the pulmonary function parameters after wedge resection was also verified.

Conclusions

The new FLV measurement method is valuable for predicting postoperative pulmonary function in patients undergoing lung resection surgery, with accuracy and consistency similar to those of the conventional SC method.
Dietary energy density, metabolic parameters, and blood pressure in a sample of adults with obesity
Authors: Pour-Abbasi Mohammad-Sadegh , Nikrad Negin , Farhangi Mahdieh Abbasalizad , Vahdat Sahar , Jafarzadeh Faria
Published: January 2023

Background

Several previous studies revealed the role of dietary energy density (DED) in developing obesity and related disorders. However, the possible role of DED in triggering cardiometabolic risk factors of individuals with obesity has not been studied yet. This study aimed to evaluate the association between DED and anthropometric parameters, blood pressure, and components of metabolic syndrome (MetS) (such as glycemic markers, lipid profile, and blood pressure) among individuals with obesity.

Methods

In this cross-sectional study, we included 335 adults with obesity (BMI ≥ 30 kg/m2) aged 20–50 years in Tabriz and Tehran, Iran. Dietary intake was assessed by a validated semi-quantitative Food Frequency Questionnaire (FFQ), including 168 food items; then, DED was calculated. MetS was defined based on the guidelines of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III). Enzymatic methods were used to assess serum lipids, glucose, and insulin concentrations. Blood pressure was measured by sphygmomanometer and body composition by bioelectrical impedance analysis (BIA).

Results

Participants in the higher tertiles of DED had more intake of carbohydrate, dietary fat, saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and meat, fish, poultry (MFP). Increasing the DED in both methods had no association with systolic blood pressure (SBP), fasting blood sugar (FBS), low-density lipoprotein cholesterol (LDL-C), insulin, triglyceride (TG), and homeostatic model assessment of insulin resistance (HOMA-IR) even after adjustment for confounders. However, diastolic blood pressure (DBP) decreased in second tertile of DED I (β = 0.921,P = 0.004). The quantitative insulin-sensitivity check index (QUICKI) in second tertile of both DED methods had significant positive association with DED. In the second tertile of DED II, while total cholesterol (TC) significantly decreased (P crude = 0.036, P adjusted = 0.024), high-density lipoprotein cholesterol (HDL-C) increased (β = 1.096,p = 0.03). There was no significant changes in biochemical parameters in third tertile of DED I and II even after adjustment for covariates. Also, higher tertiles of DED was associated with reduced prevalence of MetS.

Conclusion

High DED was associated with lower levels of blood pressure and TC but elevated levels of HDL and QUICKI independent of such confounders as age, BMI, sex, and physical activity. Further longitudinal studies are warranted to better elucidate casual associations.
Increasing palliative care capacity in primary care: study protocol of a cluster randomized controlled trial of the CAPACITI training program
Authors: Seow Hsien , Bainbridge Daryl , Winemaker Samantha , Stajduhar Kelli , Pond Gregory , Kortes-Miller Kathy , Marshall Denise , Kilbertus Frances , Myers Jeff , Steinberg Leah , Incardona Nadia , Levine Oren , Pereira Jose
Published: January 2023

Background

Primary care providers play a critical role in providing early palliative care to their patients. Despite the availability of clinical education on best practices in palliative care, primary care providers often lack practical guidance to help them operationalize this approach in practice. CAPACITI is a virtual training program aimed at providing practical tips, strategies, and action plans to provide an early palliative approach to care. The entire program consists of 12 sessions (1 h each), divided evenly across three modules: (1) Identify and Assess; (2) Enhance Communication Skills; (3) Coordinate for Ongoing Care. We report the protocol for our planned evaluation of CAPACITI on its effectiveness in helping primary care providers increase their identification of patients requiring a palliative approach to care and to strengthen other core competencies.

Methods

A cluster randomized controlled trial evaluating two modes of CAPACITI program delivery: 1) self-directed learning, consisting of online access to program materials; and 2) facilitated learning, which also includes live webinars where the online materials are presented and discussed. The primary outcomes are 1) percent of patients identified as requiring palliative care (PC), 2) timing of first initiation of PC, and self-reported PC competency (EPCS tool). Secondary outcomes include self-reported confidence in PC, practice change, and team collaboration (AITCS-II tool), as well as qualitative interviews. Covariates that will be examined are readiness for change (ORCA tool), learning preference, and team size.

Primary care teams representing interdisciplinary providers, including physicians, nurse practitioners, registered nurses, care coordinators, and allied health professionals will be recruited from across Canada. The completion of all three modules is expected to take participating teams a total of six months.

Discussion

CAPACITI is a national trial aimed at behavior change in primary care providers. This research will help inform future palliative care educational initiatives for generalist health care providers. Specifically, our findings will examine the effectiveness of the two models of education delivery and the participant experience associated with each modality.

Trial registration

ClinicalTrials.gov NCT05120154.
Coordinated reprogramming of renal cancer transcriptome, metabolome and secretome associates with immune tumor infiltration
Authors: Poplawski Piotr , Alseekh Saleh , Jankowska Urszula , Skupien-Rabian Bozena , Iwanicka-Nowicka Roksana , Kossowska Helena , Fogtman Anna , Rybicka Beata , Bogusławska Joanna , Adamiok-Ostrowska Anna , Hanusek Karolina , Hanusek Jan , Koblowska Marta , Fernie Alisdair R. , Piekiełko-Witkowska Agnieszka
Published: January 2023

Background

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. The molecules (proteins, metabolites) secreted by tumors affect their extracellular milieu to support cancer progression. If secreted in amounts detectable in plasma, these molecules can also serve as useful, minimal invasive biomarkers. The knowledge of ccRCC tumor microenvironment is fragmentary. In particular, the links between ccRCC transcriptome and the composition of extracellular milieu are weakly understood. In this study, we hypothesized that ccRCC transcriptome is reprogrammed to support alterations in tumor microenvironment. Therefore, we comprehensively analyzed ccRCC extracellular proteomes and metabolomes as well as transcriptomes of ccRCC cells to find molecules contributing to renal tumor microenvironment.

Methods

Proteomic and metabolomics analysis of conditioned media isolated from normal kidney cells as well as five ccRCC cell lines was performed using mass spectrometry, with the following ELISA validation. Transcriptomic analysis was done using microarray analysis and validated using real-time PCR. Independent transcriptomic and proteomic datasets of ccRCC tumors were used for the analysis of gene and protein expression as well as the level of the immune infiltration.

Results

Renal cancer secretome contained 85 proteins detectable in human plasma, consistently altered in all five tested ccRCC cell lines. The top upregulated extracellular proteins included SPARC, STC2, SERPINE1, TGFBI, while downregulated included transferrin and DPP7. The most affected extracellular metabolites were increased 4-hydroxy-proline, succinic acid, cysteine, lactic acid and downregulated glutamine. These changes were associated with altered expression of genes encoding the secreted proteins (SPARC, SERPINE1, STC2, DPP7), membrane transporters (SLC16A4, SLC6A20, ABCA12), and genes involved in protein trafficking and secretion (KIF20A, ANXA3, MIA2, PCSK5, SLC9A3R1, SYTL3, and WNTA7). Analogous expression changes were found in ccRCC tumors. The expression of SPARC predicted the infiltration of ccRCC tumors with endothelial cells. Analysis of the expression of the 85 secretome genes in > 12,000 tumors revealed that SPARC is a PanCancer indicator of cancer-associated fibroblasts’ infiltration.

Conclusions

Transcriptomic reprogramming of ccRCC supports the changes in an extracellular milieu which are associated with immune infiltration. The proteins identified in our study represent valuable cancer biomarkers detectable in plasma.
Estimating population ITN access at council level in Tanzania
Authors: Koenker Hannah , Worges Matt , Yukich Joshua , Gitanya Peter , Chacky Frank , Lazaro Samwel , Mwalimu Charles Dismas , Aaron Sijenunu , Ibrahim Raya , Abbas Faiza , Khamis Mwinyi , Mwingizi Deodatus , Dadi David , Selby Ato , Serbantez Naomi , Msangi Lulu , Loll Dana , Kamala Benjamin
Published: January 2023

Background

Since 2013, the National Malaria Control Programme in mainland Tanzania and the Zanzibar Malaria Elimination Programme have implemented mass insecticide-treated net (ITN) distribution campaigns, routine ITN distribution to pregnant women and infants, and continuous distribution through primary schools (mainland) and community leaders (Zanzibar) to further malaria control efforts. Mass campaigns are triggered when ITN access falls below 40%. In this context, there is a need to monitor ITN access annually to assess whether it is below threshold and inform quantification of ITNs for the following year. Annual estimates of access are needed at the council level to inform programmatic decision-making.

Methods

An age-structured stock and flow model was used to predict annual net crops from council-level distribution data in Tanzania from 2012 to 2020 parameterized with a Tanzania-specific net median lifespan of 2.15 years. Annual nets-per-capita (NPC) was calculated by dividing each annual net crop by mid-year council projected population. A previously fit nonparametric conditional quantile function for the proportion of the population with access to an ITN (ITN access) as a function of NPC was used to predict ITN access at the council level based on the predicted NPC value. These estimates were compared to regional-level ITN access from large household surveys.

Results

For regions with the same ITN strategy for all councils, predicted council-level ITN access was consistent with regional-level survey data for 79% of councils. Regions where ITN strategy varied by council had regional estimates of ITN access that diverged from the council-specific estimates. Predicted ITN access reached 60% only when “nets issued as a percentage of the council population” (NPP) exceeded 15%, and approached 80% ITN access when NPP was at or above 20%.

Conclusion

Modelling ITN access with country-specific net decay rates, council-level population, and ITN distribution data is a promising approach to monitor ITN coverage sub-regionally and between household surveys in Tanzania and beyond.
Quantitative proteomics analysis revealed the potential role of lncRNA Ftx in cardiomyocytes
Authors: Sun Xiangfei , Jiang Ying , Li Qingbao , Tan Qi , Dong Mingliang , Cai Bi’e , Zhang Di , Zhao Qi
Published: January 2023

Objective

This study aims to decode the proteomic signature of cardiomyocytes in response to lncRNA Ftx knockdown and overexpression via proteomic analysis, and to study the biological role of lncRNA Ftx in cardiomyocytes. 

Methods

The expression level of the lncRNA Ftx in cardiomyocytes cultured in vitro was intervened, and the changes in protein levels in cardiomyocytes were quantitatively detected by liquid chromatography-mass spectrometry. The key molecules and pathways of the lncRNA-Ftx response were further examined by GO, KEGG, and protein interaction analysis.

Results

A total of 2828 proteins are quantified. With a 1.5-fold change threshold, 32 upregulated proteins and 49 downregulated proteins are identified in the lncRNA Ftx overexpression group, while 67 up-regulated proteins and 54 down-regulated proteins are identified in the lncRNA Ftx knockdown group. Functional clustering analysis of differential genes revealed that the lncRNA Ftx is involved in regulating cardiomyocyte apoptosis and ferroptosis and improving cellular energy metabolism. In addition, Hub genes such as ITGB1, HMGA2, STAT3, GSS, and LPCAT3 are regulated downstream by lncRNA Ftx.

Conclusion

This study demonstrates that lncRNA Ftx plays a vital role in cardiomyocytes and may be involved in the occurrence and development of various myocardial diseases. It provides a potential target for clinical protection of the myocardium and reversal of myocardial fibrosis.
Predictors of virologic outcome among people living with HIV who continue a protease inhibitor-based antiretroviral regimen following virologic failure with no or limited resistance
Authors: Salata Robert A. , Grinsztejn Beatriz , Ritz Justin , Collier Ann C. , Hogg Evelyn , Gross Robert , Godfrey Catherine , Kumarasamy Nagalingeswaran , Kanyama Cecilia , Mellors John W. , Wallis Carole L. , Hughes Michael D. ,   the ACTG A5288 Study Team
Published: January 2023

Background

Treatment management after repeated failure of antiretroviral therapy (ART) is difficult due to resistance and adherence challenges. For people who have failed non-nucleoside reverse transcriptase inhibitor-(NNRTI-) and protease inhibitor-(PI-) based regimens with no or limited resistance, remaining on PI-based ART is an option. Using data from an ART strategy trial (A5288) in low/middle-income countries which included this option, we explored whether predictors can be identified distinguishing those who experienced further virologic failure from those who achieved and maintained virologic suppression.

Methods

A5288 enrolled people with confirmed HIV-1 RNA ≥ 1000 copies/mL after ≥ 24 weeks of PI-based ART and prior failure on NNRTI-based ART. This analysis focused on the 278 participants with no resistance to the PI being taken and no or limited nucleoside reverse transcriptase inhibitor (NRTI) resistance, who continued their PI with flexibility to change NRTIs. Proportional hazards models were used to evaluate predictors of virologic failure during follow-up (VF: confirmed HIV-1 RNA ≥ 1000 copies/mL at ≥ 24 weeks of follow-up).

Results

56% of participants were female. At study entry, median age was 40 years, time on ART 7.8 years, CD4 count 169 cells/mm3, HIV-1 RNA 20,444 copies/mL; and 37% had NRTI resistance. The estimated proportion experiencing VF increased from 39% at week 24 to 60% at week 96. In multivariable analysis, significant predictors at study entry of VF were higher HIV-1 RNA (adjusted hazard ratio: 2.20 for ≥ 10,000 versus < 10,000 copies/mL), lower age (1.96 for < 30 versus ≥ 30 years), NRTI resistance (1.74 for present versus absent), lower CD4 count (1.73 for < 200 versus ≥ 200 cells/mm3), and shorter ART duration (1.62 for < 10 versus ≥ 10 years). There was a strong trend in proportion with VF at week 96 with the number of these five risk factors that a participant had, varying from 8% for zero, to 31%, 40%, 73%, and 100% for one, two, three, and four/five. Only 13% of participants developed new NRTI or PI resistance mutations.

Conclusion

A simple count of five predictors might have value for identifying risk of continued VF. Novel antiretroviral and adherence support interventions are needed to improve virologic outcomes for higher risk individuals.
Comparison of cortical versus cancellous bone fixation in tendon-to-bone healing with a rat trans-calcaneal suture model for Achilles tendon sleeve avulsion
Authors: Gao Shang , Hu Chao , Wang Yunjiao , Zhang Jiqiang , Tang Kanglai
Published: January 2023

Background

Trans-calcaneal suture technique is an economical and effective method for repairing Achilles tendon sleeve avulsion. Whether cancellous bone fixation upon this technique could accelerate tendon-to-bone healing is unknown. The purpose of this study is to compare the effect of cortical versus cancellous bone fixation on tendon–bone healing with a novel rat trans-calcaneal suture model.

Methods

Trans-calcaneal suture treatment was carried out on the right hindlimb in male Sprague–Dawley rats (N = 80). They were randomly divided into the cortical group (Achilles fixed to the calcaneal cortical bone, n = 40) and the cancellous group (Achilles fixed to the calcaneal cancellous bone, n = 40). Gait analysis and immunohistochemistry were performed 1, 4, 7, and 14 days after the operation. Gross observation, biomechanical analysis, micro-CT, and histological analysis were performed 4 and 8 weeks after surgery. Independent-samples t tests were used for comparison between groups.

Results

At 1, 4, and 7 days, the swing time of the affected limb in the cancellous group decreased, while the duty cycle, the maximum contact area, the print area, and the mean intensity increased significantly. The cross-sectional area of the tendon–bone junction in the cancellous group was smaller, and the failure load and stiffness were higher 4 weeks after the operation. The cancellous group showed more proportion of new bone and a relatively well-organized and dense connective tissue interface with better fibrocartilage-like tissue at 4 weeks after the operation. The ratio of ED2 + macrophages in the cancellous group was significantly higher than in the cortical group on 1, 4, 7, and 14 days. There were no significant differences in gait at 2 weeks, in appearance, biomechanics, new bone formation, and histology at 8 weeks after surgery between the two groups.

Conclusion

In the new rat trans-calcaneal suture model, cancellous fixation can accelerate tendon-to-bone healing in the early stage, which perhaps is related to the abundant bone marrow tissue in the cancellous bone that modulates the inflammatory processes.
FGF23 promotes proliferation, migration and invasion by regulating miR-340-5p in osteosarcoma
Authors: Fang Lun , Li Zhongzhe , Yu Beilei , Zhou Lu
Published: January 2023

Background

Increasing evidences have been indicated that FGF23 is associated with the biological behavior of malignant tumors, but its role in osteosarcoma and the specific mechanism need to be elucidated. The purpose of this study is to investigate the effects of FGF23 on the proliferation, migration and invasion of osteosarcoma cells, and the possible molecular mechanisms.

Methods

Western blot was used to detect differences in FGF23 expression in osteosarcoma cells MG-63 and U2-OS and osteoblasts hFOB1.19. FGF23-overexpressing adenoviruses and FGF-silencing plasmids were transfected into osteosarcoma cells, and transfection efficiency was verified using Western blot. MTT and colony formation assays were performed to detect osteosarcoma cell proliferation. Cell cycle was measured by flow cytometry. Scratch assay, holographic imaging cell analyzer Holomonitor ® M4 and transwell were applied to detect cell migration and invasion. Dual-luciferase reporter assay was performed to validate the interaction between FGF23 and miR-340-5p. Changes in miR-340-5p mRNA levels were measured by QRT-PCR.

Results

FGF23 is highly expressed in osteosarcoma cells compared to hFOB1.19. Overexpression of FGF23 significantly promoted the proliferation, migration and invasion of MG-63 and U2-OS cells. MiR-340-5p is a target of FGF23. Transfection of miR-340-5p mimics reversed the promoting effects of FGF23 on proliferation, migration and invasion of MG-63 and U2-OS cells.

Conclusion

FGF23 promotes osteosarcoma cell proliferation, migration and invasion by targeting miR-340-5p gene expression.
Attaining competency and proficiency in minimally invasive mitral valve repair: a learning curve assessment using cumulative sum analysis
Authors: Shu Yue , Zheng Yin , He Shuwu , Du Yiping , Zhu Dan , Shi Zhensu
Published: January 2023

Objective

To evaluate the learning curve of minimally invasive mitral valvuloplasty (MVP).

Background

Minimally invasive MVP is characterized by minimal trauma, minimal bleeding, and short postoperative recovery time. The learning curve of any new procedure needs to be evaluated for learning and replication. However, minimally invasive mitral valve technique is a wide-ranging concept, no further analysis of the outcomes and learning curve of minimally invasive Mitral valvuloplasty has been performed.

Methods

One hundred and fifty consecutive patients who underwent minimally invasive MVP alone without concurrent surgery were evaluated. Using cardiopulmonary bypass (CPB) time and aortic clamping (AC) time as evaluation variables, we visualized the learning curve for minimally invasive MVP using cumulative sum analysis. We also analyzed important postoperative variables such as postoperative drainage, duration of mechanical ventilation, ICU stay and postoperative hospital stay.

Results

The slope of the fitted curve was negative after 75 procedures, and the learning curve could be crossed after the completion of the 75th procedure when AC and CPB time were used as evaluation variables. And as the number of surgical cases increased, CPB, AC, postoperative drainage, duration of mechanical ventilation, ICU stay and postoperative hospital stay all showed different degrees of decrease. The incidence of postoperative adverse events is similar to conventional Mitral valvuloplasty.

Conclusion

Compared to conventional MVP, minimally invasive MVP provides the same satisfactory surgical results and stabilization can be achieved gradually after completion of the 75th procedure.