bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre-pregnancy weight, the rate of gestational weight gain, and the risk of early gestational diabetes mellitus among women registered in a tertiary care hospital in India
Authors: Deshpande Swapna , Kinnunen Tarja I. , Khadilkar Anuradha , Unni Jyothi , Khanijo Vandana , Donga Namrata , Kulathinal Sangita
Published: August 2023

Background

The impact of pre-pregnancy weight and the rate of gestational weight gain (GWG) together on the risk of early GDM (< 24 weeks gestation; eGDM) has not been studied in the Indian context. We aimed to study the influence of (1) pre-pregnancy weight on the risk of eGDM diagnosed in two time intervals; and (2) in addition, the rate of GWG by 12 weeks on the risk of eGDM diagnosed in 19–24 weeks.

Method

Our study utilized real-world clinical data on pregnant women routinely collected at an antenatal care clinic at a private tertiary hospital, in Pune, India. Women registering before 12 weeks of gestation (v1), with a singleton pregnancy, and having a follow-up visit between 19–24 weeks (v2) were included (n = 600). The oral glucose tolerance test was conducted universally as per Indian guidelines (DIPSI) at v1 and v2 for diagnosing eGDM. The data on the onset time of eGDM were interval censored; hence, we modeled the risk of eGDM using binomial regression to assess the influence of pre-pregnancy weight on the risk of eGDM in the two intervals. The rate of GWG by 12 weeks was added to assess its impact on the risk of eGDM diagnosed in v2.

Result

Overall, 89 (14.8%) women (age 32 ± 4 years) were diagnosed with eGDM by 24 weeks, of which 59 (9.8%) were diagnosed before 12 weeks and 30 of 541 (5.5%) women were diagnosed between 19–24 weeks. Two-thirds (66%) of eGDM were diagnosed before 12 weeks of gestation. Women’s pre-pregnancy weight was positively associated with the risk of GDM in both time intervals though the lower confidence limit was below zero in v1. The rate of GWG by 12 weeks was not observed to be associated with the risk of eGDM diagnosed between 19–24 weeks of gestation. These associations were independent of age, height, and parity.

Conclusion

Health workers may focus on pre-pregnancy weight, a modifiable risk factor for eGDM. A larger community-based study measuring weight and GDM status more frequently may be warranted to deepen the understanding of the role of GWG as a risk factor for GDM.
Serum lncRNA THRIL predicts benign and malignant pulmonary nodules and promotes the progression of pulmonary malignancies
Authors: Chen Xinyu , Zhu Xianji , Yan Wenjun , Wang Luan , Xue Dongming , Zhu Shouying , Pan Jiajun , Li Yufeng , Zhao Qixiang , Han Dong
Published: August 2023

Background

This project aimed to research the significance of THRIL in the diagnosis of benign and malignant solitary pulmonary nodules (SPNs) and to investigate the role of THRIL/miR-99a in malignant SPNs.

Methods

The study groups consisted of 169 patients with SPN and 74 healthy subjects. The differences in THRIL levels were compared between the two groups and the healthy group. The receiver operating characteristic curve (ROC) was utilized to analyze the THRIL’s significance in detecting benign and malignant SPN. Pearson correlation and binary regression coefficients represented the association between THRIL and SPN. CCK-8 assay, Transwell assay, and flow cytometry were utilized to detect the regulatory effect of THRIL silencing. The interaction between THRIL, miR-99a, and IGF1R was confirmed by the double luciferase reporter gene.

Results

There were differences in THRIL expression in the healthy group, benign SPN group, and malignant SPN group. High accuracy of THRIL in the diagnosis of benign SPN and malignant SPN was observed. THRIL was associated with the development of SPN. The expression of THRIL was upregulated and miR-99a was downregulated in lung cancer cells. The double luciferase report experiment confirmed the connections between THRIL/miR-99a/IGF1R. Silencing THRIL could suppress cell proliferation, migration, and invasion and promote cell apoptosis by binding miR-99a.

Conclusion

The detection of THRIL in serum is useful for the assessment of malignant SPN. THRIL can regulate the expression of IGF1R through miR-99a, thereby promoting the growth of lung cancer cells and inhibiting apoptosis.
Correlation analysis of aqueous humor metabolomics with myopic axial length and choroidal parameters
Authors: Shao Jiechao , Zhang Zongchan , Cai Xuecheng , Wu Xinyu , Huang Baishuang , Shen Ye , Tong Jianping
Published: August 2023

Background

To explore differential metabolites in the aqueous humor of patients with different axial lengths and their correlations with axial length and choroidal parameters.

Methods

In this study, we included 12 patients with axial lengths less than 24 mm, 11 patients with axial lengths between 24 and 26 mm, and 11 patients with axial lengths greater than 26 mm. We collected their aqueous humor samples during cataract surgery for liquid chromatography-mass spectrometry metabolomic analysis. Simultaneously, we collected relevant clinical parameters such as axial length, subfoveal choroidal thickness, and choroidal vascular index. Correlations between clinical data, differential metabolites, and clinical indicators were analyzed. In addition, we plotted receiver operating characteristic curves.

Results

The results showed that axial length was significantly negatively correlated with choroidal thickness (r=-0.7446, P < 0.0001), and that several differential metabolites were significantly correlated with certain clinical parameters. After analyzing receiver operating characteristic curves, 5-methoxytryptophol and cerulenin were found to have excellent discriminative power, demonstrating their potential as biomarkers. In the enrichment analysis, we found that the differential metabolites among each group were involved in several special pathways (Taurine and Hypotaurine Metabolism, Vitamin B6 Metabolism, Pantothenate, and coenzyme A Biosynthesis), suggesting that abnormalities in these metabolic pathways may play a role in the process of axial myopia.

Conclusions

Our study identified alterations in certain metabolic pathways in different axial lengths. At the same time, we found several metabolites with significant correlation with clinical indicators, among which 5-methoxytryptophol and cerulenin were associated with axial myopia.

Clinical trial registration

Registration date:11/04/2022. Trial registration number: ChiCTR2200058575. Trial registry: The First Affiliated Hospital of the Zhejiang University School of Medicine.
Alienation from medical care policy, medical care avoidance, and the role of sex and risk perception
Authors: Xia Chun , Xu Jia , Ding Xiuzhen
Published: August 2023

Background

Medical care avoidance affects individuals’ health status. Previous studies on medical care avoidance have mainly focused on medical costs and people’s satisfaction with medical services. This study investigates whether an individual’s sense of policy alienation toward medical care policy (SPA-M) affects behavioral intention of medical care avoidance, and to what extent an intermediary variable—medical financial risk perception–mediates the relationship between SPA-M and medical care avoidance.

Methods

A cross-sectional survey was conducted involving 434 people aged 35–59 years from Wuhu, a city in China’s Anhui province. A moderated mediation model was constructed to investigate the research question and sex (biological: male and female) was used as a moderating variable between SPA-M and medical financial risk perception.

Results

We found that SPA-M significantly impacted medical care avoidance, and that medical financial risk perception played a complete mediating role in this relationship, while sex moderated the relationship between SPA-M and medical financial risk perception.

Conclusion

This study contributes to the literature by enhancing our understanding of the factors that influence behavioral intention regarding medical care avoidance, deepening our understanding of the role of SPA-M in medical care policy, and expanding the role of sex differences in the analysis of the relationship between SPA-M, medical financial risk perception, and medical care avoidance, offering implications for public and community health.
Dietary intakes of methionine, threonine, lysine, arginine and histidine increased risk of type 2 diabetes in Chinese population: does the mediation effect of obesity exist?
Authors: Liu Yuyan , Wang Huan , Liang Yuanhong , Guo Zijun , Qu Litong , Wang Ying , Zhang Chengwen , Sun Guifan , Li Yongfang
Published: August 2023

Background

Published studies have shown positive associations of branched chain and aromatic amino acids with type 2 diabetes mellitus (T2DM), and the findings remain consistent. However, the associations of other essential and semi-essential amino acids, i.e., methionine (Met), threonine (Thr), lysine (Lys), arginine (Arg) and histidine (His), with T2DM remain unknown. Obesity is an important independent risk factor for T2DM, and excessive amino acids can convert into glucose and lipids, which might underlie the associations of amino acids with obesity. Therefore, we aimed to estimate the associations between dietary intakes of these 5 amino acids and T2DM risk, as well as the mediation effects of obesity on these associations, in a Chinese population.

Methods

A total of 10,920 participants (57,293 person-years) were included, and dietary intakes of 5 amino acids were investigated using 24-h dietary recalls. Anthropometric obesity indices were measured at both baseline and the follow-up endpoints. Associations of amino acids with T2DM were estimated using COX regression models, hazard ratios (HRs) and 95% confidence intervals (95% CIs) were shown. The mediation effects of obesity indices were analyzed, and the proportion of the mediation effect was estimated.

Results

Higher intakes of the 5 amino acids were associated with increasing T2DM risk, while significant HRs were only shown in men after adjustments. No interaction by gender was found. Regression analyses using quintiles of amino acids intakes showed that T2DM risk was positively associated with amino acids intakes only when comparing participants with the highest intake levels of amino acids to those with the lowest intake levels. Adjusted correlation coefficients between amino acid intakes and obesity indices measured at follow-up endpoints were significantly positive. Mediation analyses showed that mediation effects of obesity indices existed on associations between amino acids intakes and T2DM risk, and the mediation effect of waist circumference remained strongest for each amino acid.

Conclusions

We found positive associations of dietary intakes of Met, Thr, Lys, Arg and His with increasing T2DM risk in general Chinese residents, on which the mediation effect of obesity existed. These findings could be helpful for developing more constructive guidance in the primary prevention of T2DM based on dietary interventions.
Preoperative predictors of implant size in patients undergoing total knee arthroplasty: a retrospective cohort study
Authors: Ostovar Mohsen , Jabalameli Mahmoud , Bahaeddini Mohammad Reza , Bagherifard Abolfazl , Bahardoust Mansour , Askari Alireza
Published: August 2023

Background

Traditionally, the size of total knee arthroplasty (TKA) components is predicted by preoperative radiographic templating, which is of limited accuracy. This study aimed to evaluate the role of demographic data and ankle volume in predicting implant size in TKA candidates.

Methods

In a retrospective study, 415 patients who underwent TKA at a single institution were included. The mean age of the patients was 67.5 ± 7.1 years. The mean BMI of the patients was 31.1 ± 4.7 kg/m2. TKA implants were Zimmer Biomet NexGen LPS-Flex Knee in all cases. The demographic data included age, sex, height, weight, BMI, ethnicity, and ankle volume. Ankle volume was assessed with the figure-of-eight method. Multivariate linear regression analysis was used for predicting factors of implant size.

Results

Multivariate linear regression analysis showed that the Sex (β:1.41, P < 0.001), height (β:0.058, P < 0.001), ankle volume (β:0.11, P < 0.001), and Age (β:0.017, P = 0.004) were significant predictors of tibial component size. Sex (β:0.89, P < 0.001), height (β:0.035, P < 0.001), and ankle volume(β:0.091, P < 0.001) were significant predictors of femoral component size in the multivariate analysis.

Conclusion

Demographic data, adjunct with the ankle volume, could provide a promising model for preoperative prediction of the size of tibial and femoral components in TKA candidates.
Epigenetic instability caused by absence of CIZ1 drives transformation during quiescence cycles
Authors: Dobbs Olivia G. , Wilson Rosemary H. C. , Newling Katherine , Ainscough Justin F.-X. , Coverley Dawn
Published: August 2023

Background

Cip1-interacting zinc finger protein 1 (CIZ1) forms RNA-dependent protein assemblies that stabilise epigenetic state, notable at the inactive X chromosome in females. CIZ1 has been linked with a range of human cancers and in mice genetic deletion of CIZ1 manifests as hyperproliferative lymphoid lineages in females. This suggests that its role in maintenance of epigenetic stability is linked with disease.

Results

Here, we show that male and female CIZ1-null primary murine fibroblasts have reduced H4K20me1 and that this compromises nuclear condensation on entry to quiescence. Global transcriptional repression remains intact in condensation-deficient CIZ1-null cells; however, a subset of genes linked with chromatin condensation and homology-directed DNA repair are perturbed. Failure to condense is phenotypically mimicked by manipulation of the H4K20me1 methyltransferase, SET8, in WT cells and partially reverted in CIZ1-null cells upon re-expression of CIZ1. Crucially, during exit from quiescence, nuclear decondensation remains active, so that repeated entry and exit cycles give rise to expanded nuclei susceptible to mechanical stress, DNA damage checkpoint activation, and downstream emergence of transformed proliferative colonies.

Conclusions

Our results demonstrate a role for CIZ1 in chromatin condensation on entry to quiescence and explore the consequences of this defect in CIZ1-null cells. Together, the data show that CIZ1’s protection of the epigenome guards against genome instability during quiescence cycles. This identifies loss of CIZ1 as a potentially devastating vulnerability in cells that undergo cycles of quiescence entry and exit.
Potential value of ctDNA monitoring in metastatic HR + /HER2 − breast cancer: longitudinal ctDNA analysis in the phase Ib MONALEESASIA trial
Authors: Chiu Joanne , Su Fei , Joshi Mukta , Masuda Norikazu , Ishikawa Takashi , Aruga Tomoyuki , Zarate Juan Pablo , Babbar Naveen , Balbin O. Alejandro , Yap Yoon-Sim
Published: August 2023

Background

There is increasing interest in the use of liquid biopsies, but data on longitudinal analyses of circulating tumor DNA (ctDNA) remain relatively limited. Here, we report a longitudinal ctDNA analysis of MONALEESASIA, a phase Ib trial evaluating the efficacy and safety of ribociclib plus endocrine therapy (ET) in Asian patients with hormone receptor–positive, human epidermal growth factor receptor-2–negative advanced breast cancer.

Methods

MONALEESASIA enrolled premenopausal and postmenopausal Japanese and postmenopausal non-Japanese Asian patients. All patients received ribociclib with ET (letrozole, fulvestrant, or tamoxifen with goserelin). ctDNA was analyzed using a targeted next-generation sequencing panel of 572 cancer-related genes and correlated by best overall response (BOR).

Results

Five hundred seventy-four cell-free DNA samples from 87 patients were tested. The most frequently altered genes at baseline included PIK3CA (29%) and TP53 (22%). Treatment with ribociclib plus ET decreased ctDNA in most patients at the first on-treatment time point, regardless of dose or ET partner. Patients with partial response and stable disease had lower ctDNA at baseline that remained low until data cutoff if no progressive disease occurred. Most patients with progressive disease as the best response had higher ctDNA at baseline that remained high at the end of treatment. For patients with partial response and stable disease with subsequent progression, ctDNA increased towards the end of treatment in most patients, with a median lead time of 83 days (14–309 days). In some patients with BOR of partial response who experienced disease progression later, specific gene alterations and total ctDNA fraction increased; this was sometimes observed concurrently with the development of new lesions without a change in target lesion size. Patients with alterations in PIK3CA and TP53 at baseline had shorter median progression-free survival compared with patients with wild-type PIK3CA and TP53, 12.7 and 7.3 months vs 19.2 and 19.4 months, respectively (P = .016 and P = .0001, respectively).

Conclusions

Higher ctDNA levels and PIK3CA and TP53 alterations detected at baseline were associated with inferior outcomes. On-treatment ctDNA levels were associated with different patterns based on BOR. Longitudinal tracking of ctDNA may be useful for monitoring tumor status and detection of alterations with treatment implications.

Trial registration

ClinicalTrials.gov NCT02333370. Registered on January 7, 2015.
The associations of dietary patterns with depressive and anxiety symptoms: a prospective study
Authors: Chen Han , Cao Zhi , Hou Yabing , Yang Hongxi , Wang Xiaohe , Xu Chenjie
Published: August 2023

Background

Diet is increasingly recognized as an important risk factor for mental health. However, evidence regarding the association between diet pattern and depressive and anxiety symptoms is limited. We aimed to investigate the associations of dietary patterns characterized by a set of nutrients of interest with depressive and anxiety symptoms.

Methods

The analyses included a total of 126,819 participants in the UK Biobank who had completed at least two dietary questionnaires. Dietary data were obtained through 24-h dietary assessment at baseline between 2006 and 2010 and four rounds of online follow-ups between 2011 and 2012. Reduced rank regression was applied to derive dietary patterns (DPs) explaining variability in energy density, free sugars, saturated fat, and fiber intakes. Depressive and anxiety symptoms were measured by the Patient Health Questionnaire-9 and General Anxiety Disorder-7 between 2016 and 2017, respectively. Logistic regression models were performed to investigate the associations between dietary patterns and depressive and anxiety symptoms.

Results

During a mean follow-up of 7.6 years, 2746 cases of depressive symptoms and 2202 cases of anxiety symptoms were recorded. Three major DPs were derived, explaining 74% of the variation in nutrients hypothesized to be related to depressive and anxiety symptoms. DP1 was characterized by high intakes of chocolate, confectionery, butter, and low vegetable/fruit intakes. Compared to the lowest quintile of DP1, the odds ratio (95% confidence interval) of depressive symptoms for Q2–Q5 was 0.82 (0.72–0.93), 0.86 (0.76–0.98), 1.02 (0.90–1.15), and 1.17 (1.03–1.32), respectively. Compared to the lowest quintile of DP1, the odds ratio (95% CI) of anxiety symptoms for Q2–Q5 was 0.84 (0.73–0.97), 0.91 (0.79–1.05), 1.01 (0.88–1.15), and 1.18 (1.03–1.35), respectively. DP2 featured high intakes of sugar-sweetened beverages, added sugars, and low intakes of butter/cheese but showed no significant links to depressive or anxiety symptoms. DP3 was characterized by high butter and milk desserts and low alcohol/bread intakes. Compared to the lowest quintile of DP3, the odds ratio (95% CI) of depressive symptoms for Q2–Q5 was 0.90 (0.79–1.01), 1.00 (0.88–1.13), 1.06 (0.94–1.20), and 1.17 (1.03–1.32), respectively. Compared to the lowest quintile of DP3, the odds ratio (95% CI) of anxiety symptoms for Q2–Q5 was 0.90 (0.78–1.04), 1.05 (0.91–1.20), 1.02 (0.89–1.17), and 1.21 (1.05–1.38), respectively.

Conclusions

A DP characterized by high intakes of chocolate and confectionery, butter, high-fat cheese, added sugars, along with low intakes of fresh fruit and vegetables, is associated with a higher risk of depressive and anxiety symptoms.
The moderating impact of neighborhood walkability on mHealth interventions to increase moderate to vigorous physical activity for insufficiently active adults in a randomized trial
Authors: McEntee Mindy L. , Hurley Jane C. , Phillips Christine B. , Hooker Steven P. , Todd Michael , Frank Lawrence D. , Adams Marc A.
Published: August 2023

Background

Ecological models suggest that interventions targeting specific behaviors are most effective when supported by the environment. This study prospectively examined the interactions between neighborhood walkability and an mHealth intervention in a large-scale, adequately powered trial to increase moderate-to-vigorous physical activity (MVPA).

Methods

Healthy, insufficiently active adults (N = 512) were recruited purposefully from census block groups ranked on walkability (high/low) and socioeconomic status (SES, high/low). Participants were block-randomized in groups of four to WalkIT Arizona, a 12-month, 2 × 2 factorial trial evaluating adaptive versus static goal setting and immediate versus delayed financial reinforcement delivered via text messages. Participants wore ActiGraph GT9X accelerometers daily for one year. After recruitment, a walkability index was calculated uniquely for every participant using a 500-m street network buffer. Generalized linear mixed-effects hurdle models tested for interactions between walkability, intervention components, and phase (baseline vs. intervention) on: (1) likelihood of any (versus no) MVPA and (2) daily MVPA minutes, after adjusting for accelerometer wear time, neighborhood SES, and calendar month. Neighborhood walkability was probed at 5th, 25th, 50th, 75th, and 95th percentiles to explore the full range of effects.

Results

Adaptive goal setting was more effective in increasing the likelihood of any MVPA and daily MVPA minutes, especially in lower walkable neighborhoods, while the magnitude of intervention effect declined as walkability increased. Immediate reinforcement showed a greater increase in any and daily MVPA compared to delayed reinforcement, especially relatively greater in higher walkable neighborhoods.

Conclusions

Results partially supported the synergy hypotheses between neighborhood walkability and PA interventions and suggest the potential of tailoring interventions to individuals’ neighborhood characteristics.

Trial Registration

Preregistered at clinicaltrials.gov (NCT02717663).
HCC prediction models in chronic hepatitis B patients receiving entecavir or tenofovir: a systematic review and meta-analysis
Authors: Xu Xiaolan , Jiang Lushun , Zeng Yifan , Pan Liya , Lou Zhuoqi , Ruan Bing
Published: August 2023

Background

Our study aimed to compare the predictive performance of different hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B patients receiving entecavir or tenofovir, including discrimination, calibration, negative predictive value (NPV) in low-risk, and proportion of low-risk.

Methods

We conducted a systematic literature research in PubMed, EMbase, the Cochrane Library, and Web of Science before January 13, 2022. The predictive performance was assessed by area under receiver operating characteristic curve (AUROC), calibration index, negative predictive value, and the proportion in low-risk. Subgroup and meta-regression analyses of discrimination and calibration were conducted. Sensitivity analysis was conducted to validate the stability of the results.

Results

We identified ten prediction models in 23 studies. The pooled 3-, 5-, and 10-year AUROC varied from 0.72 to 0.84, 0.74 to 0.83, and 0.76 to 0.86, respectively. REAL-B, AASL-HCC, and HCC-RESCUE achieved the best discrimination. HCC-RESCUE, PAGE-B, and mPAGE-B overestimated HCC development, whereas mREACH-B, AASL-HCC, REAL-B, CAMD, CAGE-B, SAGE-B, and aMAP underestimated it. All models were able to identify people with a low risk of HCC accurately. HCC-RESCUE and aMAP recognized over half of the population as low-risk. Subgroup analysis and sensitivity analysis showed similar results.

Conclusion

Considering the predictive performance of all four aspects, we suggest that HCC-RESCUE was the best model to utilize in clinical practice, especially in primary care and low-income areas. To confirm our findings, further validation studies with the above four components were required.
Global serum profiling: an opportunity for earlier cancer detection
Authors: Sala Alexandra , Cameron James M. , Brennan Paul M. , Crosbie Emma J. , Curran Tom , Gray Ewan , Martin-Hirsch Pierre , Palmer David S. , Rehman Ihtesham U. , Rattray Nicholas J. W. , Baker Matthew J.
Published: August 2023

The advances in cancer research achieved in the last 50 years have been remarkable and have provided a deeper knowledge of this disease in many of its conceptual and biochemical aspects. From viewing a tumor as a ‘simple’ aggregate of mutant cells and focusing on detecting key cell changes leading to the tumorigenesis, the understanding of cancer has broadened to consider it as a complex organ interacting with its close and far surroundings through tumor and non-tumor cells, metabolic mechanisms, and immune processes. Metabolism and the immune system have been linked to tumorigenesis and malignancy progression along with cancer-specific genetic mutations. However, most technologies developed to overcome the barriers to earlier detection are focused solely on genetic information. The concept of cancer as a complex organ has led to research on other analytical techniques, with the quest of finding a more sensitive and cost-effective comprehensive approach. Furthermore, artificial intelligence has gained broader consensus in the oncology community as a powerful tool with the potential to revolutionize cancer diagnosis for physicians. We herein explore the relevance of the concept of cancer as a complex organ interacting with the bodily surroundings, and focus on promising emerging technologies seeking to diagnose cancer earlier, such as liquid biopsies. We highlight the importance of a comprehensive approach to encompass all the tumor and non-tumor derived information salient to earlier cancer detection.
The effect of a customised digital adherence tool on HIV treatment outcomes in young people living with HIV (YPLHIV) in Blantyre, Malawi: a protocol for a randomised controlled trial
Authors: Msosa Takondwa Charles , Swai Iraseni , Sumari-de Boer Marion , Ngowi Kennedy , F. Rinke de Wit Tobias , Aarnoutse Rob , Nliwasa Marriott
Published: August 2023

Background

People living with HIV (PLHIV) have to take lifelong antiretroviral treatment, which is often challenging. Young people living with HIV (YPLHIV) have the lowest viral load suppression rates in Malawi and globally, mostly due to poor treatment adherence. This is a result of complex interactions of multiple factors unique to this demographic group. The use of digital health interventions, such as real-time medication monitor (RTMM)-based digital adherence tools (DATs), could improve ART adherence in YPLHIV and subsequently improve viral load suppression which in turn could lead to reduced HIV-associated morbidity and mortality.

Aim

To provide the evidence base for a digital adherence intervention to improve treatment outcomes in YPLHIV on ART.

Objectives

1. The primary objective is to determine the efficacy of a customised DAT compared to the standard of care in improving ART adherence in YPLHIV.

2. The secondary objective is to determine the efficacy of the customised DAT compared to the standard of care in improving viral load suppression in YPLHIV.

Methodology

This will be a parallel open-label randomised control controlled two-arm trial in which non-adherent YPLHIV in selected ART facilities in Blantyre will be randomised in a 1:1 ratio to a customised DAT and standard care arms and followed up for 9 months. The primary outcome is the proportion adherent at 9 months (> = 95% by pill count), and the secondary outcome is the proportion with viral load suppressed at 9 months (< 200 copies/ml).

Discussion

There is a paucity of good quality evidence on effective digital health interventions to improve ART adherence and viral load suppression in YPLHIV globally and particularly in HIV high-burden settings like Malawi. This study will provide good-quality evidence on the effectiveness of a customised DAT in improving ART adherence and viral load suppression in this important demographic.

Trial registration

The trial has been registered in the Pan African Clinical Trials Registry number: PACTR202303867267716 on 23 March 2023 and can be accessed through the following URL: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=25424. All items from the WHO Trial Registration Data Set are described in this manuscript.
Effects of multimodal exercise program on postural balance in patients with chronic obstructive pulmonary disease: study protocol for a randomized controlled trial
Authors: Daros dos Santos Tamires , Pasqualoto Adriane Schmidt , Cardoso Dannuey Machado , Da Cruz Ivana Beatrice Mânica , Moresco Rafael Noal , Ferreira da Silveira Aron , Martins de Albuquerque Isabella
Published: August 2023

Background

Evidence has shown that patients with chronic obstructive pulmonary disease present significant deficits in the control of postural balance when compared to healthy subjects. In view of this, it is pertinent to investigate the effects of different therapeutic strategies used alone or in association with pulmonary rehabilitation with the potential to improve postural balance and other outcomes with clinical significance in patients with chronic obstructive pulmonary disease. This study will investigate the effects of an 8-week (short-term) multimodal exercise program [inspiratory muscle training (IMT) plus neuromuscular electrical stimulation (NMES)] on postural balance in patients with chronic obstructive pulmonary disease enrolled in a pulmonary rehabilitation program compared to individualized addition of IMT or NMES to pulmonary rehabilitation or standard pulmonary rehabilitation.

Methods

This is a randomized, single-blind, 4-parallel-group trial. Forty patients with chronic obstructive pulmonary disease will be included prospectively to this study during a pulmonary rehabilitation program. Patients will be randomly assigned to one of four groups: multimodal exercise program (IMT + NMES + pulmonary rehabilitation group) or (IMT + pulmonary rehabilitation group) or (NMES + pulmonary rehabilitation group) or standard pulmonary rehabilitation group. Patients will receive two sessions per week for 8 weeks. The primary outcome will be static postural balance and secondary outcomes will include as follows: static and dynamic postural balance, fear of falling, muscle strength and endurance (peripheral and respiratory), functional capacity, health-related quality of life, muscle architecture (quadriceps femoris and diaphragm), and laboratory biomarkers.

Discussion

This randomized clinical trial will investigate the effects of adding of short-term multimodal exercise program, in addition to pulmonary rehabilitation program, in postural balance in patients with chronic obstructive pulmonary disease enrolled in a pulmonary rehabilitation. Furthermore, this randomized control trial will enable important directions regarding the effectiveness of short-term intervention as part of the need to expand the focus of pulmonary rehabilitation to include balance management in chronic obstructive pulmonary disease patients which will be generated.

Trial registration

ClinicalTrials.gov NCT04387318. Registered on May 13, 2020.
Differences in the position of endometriosis-associated and non-associated ovarian cancer relative to the uterus
Authors: Saida Tsukasa , Mori Kensaku , Ishiguro Toshitaka , Saida Yukihisa , Satoh Toyomi , Nakajima Takahito
Published: August 2023

Background

Preoperative assessment of the histological type of ovarian cancer is essential to determine the appropriate treatment strategy. Tumor location may be helpful in this regard. The purpose of this study was to compare the position of endometriosis-associated (EAOCs) and non-associated (non-EAOCs) ovarian cancer relative to the uterus using MRI.

Methods

This retrospective study included patients with pathologically confirmed malignant epithelial ovarian tumors who underwent MRI at our hospital between January 2015 and January 2023. T2-weighted images of the sagittal and axial sections of the long axis of the uterine body were used for the analysis. Three blinded experienced radiologists independently interpreted the images and assessed whether the ovarian tumor was attached to the uterus, and the angle between the uterus and the tumor was measured. The presence of attachment and the measured angles were compared for each histology. In addition, the angles between EAOCs, including endometrioid carcinomas (ECs) and clear cell carcinomas (CCCs), were compared with non-EAOCs.

Results

In total, 184 women (mean age, 56 years; age range, 20–91 years) were evaluated. High-grade serous carcinomas (HGSCs) were significantly smaller than the others and had significantly less uterine attachment than CCCs (p < 0.01 for all readers). According to the mean of the measured angles, CCCs were positioned significantly more posteriorly than HGSCs and mucinous carcinomas (p < 0.02), and EAOCs were positioned significantly more posteriorly to the uterus than non-EAOCs (p < 0.01).

Conclusion

HGSCs are often not attached to the uterus, and EAOCs are positioned more posteriorly to the uterus than non-EAOCs.

Critical relevance statement

High-grade serous carcinomas were often not attached to the uterus, and endometriosis-associated ovarian cancers were positioned more posteriorly to the uterus than non-endometriosis-associated ovarian cancers.

Key points

• The position of the ovarian tumor can be determined using MRI.

• High-grade serous carcinomas had less attachment to the uterus.

• Endometriosis-associated cancers were positioned more posteriorly to the uterus.

• The location of ovarian tumors is helpful in estimating histology.

Graphical abstract
Symptomatic calcified chronic subdural hematoma in an elderly patient: a case report
Authors: Tefera Esayas Adefirs , Assefa Mezgebu Alemneh , Molla Yohannis Derbew
Published: August 2023

Introduction

Calcified chronic subdural hematoma is a rare and infrequent diagnosis made in clinical practice according to the literature. Calcification of chronic subdural hematoma is found more frequently in children and young adults than in the aged. The proposed mechanism of calcification may involve poor circulation and absorption in the subdural space together with intravascular thrombosis and prolonged existence of the hematoma in the subdural space.

Clinical presentation

An 84-year-old Ethiopian male patient presented with progressive right-sided body weakness of 8-month duration. The weakness started in the right lower extremity and progressively involved the upper extremity. Associated with the above complaint, he had had also a globalized headache of the same duration. Pre- and post-contrast brain computed tomography scans showed a right hemispheric extra-axial collection that crossed the suture line, with a maximum depth of 2.3 cm. Subsequently, craniotomy and hematoma evacuation were carried out and the patient was discharged improved.

Conclusion

The most common symptom of calcified chronic subdural hematoma is headache followed by lethargy, confusion, memory impairment weakness, and seizures. A diminished level of consciousness is relatively common and motor deficits are usually manifested as hemiparesis or gait disturbance. Most calcified chronic subdural hematomas can be diagnosed by computed tomography or magnetic resonance imaging and differentiated from the usual chronic subdural hematoma by imaging studies and gross pathology. Surgical treatment is advised in symptomatic patients when feasible, and often results in neurological improvement. Here we presented a patient with an uncommon calcified chronic subdural hematoma, which was successfully evacuated, resulting in a good recovery.
SDF-1 and NOTCH signaling in myogenic cell differentiation: the role of miRNA10a, 425, and 5100
Authors: Mierzejewski Bartosz , Grabowska Iwona , Michalska Zuzanna , Zdunczyk Kamila , Zareba Franciszek , Irhashava Aliksandra , Chrzaszcz Marta , Patrycy Magdalena , Streminska Wladyslawa , Janczyk-Ilach Katarzyna , Koblowska Marta , Iwanicka-Nowicka Roksana , Gromadka Agnieszka , Kowalski Kamil , Ciemerych Maria Anna , Brzoska Edyta
Published: August 2023

Background

Skeletal muscle regeneration is a complex process regulated by many cytokines and growth factors. Among the important signaling pathways regulating the myogenic cell identity are these involving SDF-1 and NOTCH. SDF-1 participates in cell mobilization and acts as an important chemoattractant. NOTCH, on the other hand, controls cell activation and myogenic determination of satellite cells. Knowledge about the interaction between SDF-1 and NOTCH signaling is limited.

Methods

We analyzed two populations of myogenic cells isolated from mouse skeletal muscle, that is, myoblasts derived from satellite cells (SCs) and muscle interstitial progenitor cells (MIPCs). First, microRNA level changes in response to SDF-1 treatment were analyzed with next-generation sequencing (NGS). Second, myogenic cells, i.e., SC-derived myoblasts and MIPCs were transfected with miRNA mimics, selected on the basis of NGS results, or their inhibitors. Transcriptional changes, as well as proliferation, migration, and differentiation abilities of SC-derived myoblasts and MIPCs, were analyzed in vitro. Naive myogenic potential was assessed in vivo, using subcutaneous engrafts and analysis of cell contribution to regeneration of the skeletal muscles.

Results

SDF-1 treatment led to down-regulation of miR10a, miR151, miR425, and miR5100 in myoblasts. Interestingly, miR10a, miR425, and miR5100 regulated the expression of factors involved in the NOTCH signaling pathway, including Dll1, Jag2, and NICD. Furthermore, miR10a, miR425, and miR5100 down-regulated the expression of factors involved in cell migration: Acta1, MMP12, and FAK, myogenic differentiation: Pax7, Myf5, Myod, Mef2c, Myog, Musk, and Myh3. However, these changes did not significantly affect myogenic cell migration or fusion either in vitro or in vivo, except when miR425 was overexpressed, or miR5100 inhibitor was used. These two molecules increased the fusion of MIPCs and myoblasts, respectively. Furthermore, miR425-transfected MIPC transplantation into injured skeletal muscle resulted in more efficient regeneration, compared to control cell transplantation. However, skeletal muscles that were injected with miR10a transfected myoblasts regenerated less efficiently.

Conclusions

SDF-1 down-regulates miR10a, miR425, and miR5100, what could affect NOTCH signaling, differentiation of myogenic cells, and their participation in skeletal muscle regeneration.
Fibroblast-to-cardiomyocyte lactate shuttle modulates hypertensive cardiac remodelling
Authors: Wei Tong , Guo Yuetong , Huang Chenglin , Sun Mengwei , Zhou Bin , Gao Jing , Shen Weili
Published: August 2023

Background

Cardiac fibroblasts (CFs) and cardiomyocytes are the major cell populations in the heart. CFs not only support cardiomyocytes by producing extracellular matrix (ECM) but also assimilate myocardial nutrient metabolism. Recent studies suggest that the classical intercellular lactate shuttle may function in the heart, with lactate transported from CFs to cardiomyocytes. However, the underlying mechanisms regarding the generation and delivery of lactate from CFs to cardiomyocytes have yet to be explored.

Results

In this study, we found that angiotensin II (Ang II) induced CFs differentiation into myofibroblasts that, driven by cell metabolism, then underwent a shift from oxidative phosphorylation to aerobic glycolysis. During this metabolic conversion, the expression of amino acid synthesis 5-like 1 (GCN5L1) was upregulated and bound to and acetylated mitochondrial pyruvate carrier 2 (MPC2) at lysine residue 19. Hyperacetylation of MPC2k19 disrupted mitochondrial pyruvate uptake and mitochondrial respiration. GCN5L1 ablation downregulated MPC2K19 acetylation, stimulated mitochondrial pyruvate metabolism, and inhibited glycolysis and lactate accumulation. In addition, myofibroblast-specific GCN5L1-knockout mice (GCN5L1fl/fl: Periostin-Cre) showed reduced myocardial hypertrophy and collagen content in the myocardium. Moreover, cardiomyocyte-specific monocarboxylate transporter 1 (MCT1)-knockout mice (MCT1fl/fl: Myh6-Cre) exhibited blocked shuttling of lactate from CFs to cardiomyocytes and attenuated Ang II-induced cardiac hypertrophy.

Conclusions

Our findings suggest that GCN5L1-MPC2 signalling pathway alters metabolic patterns, and blocking MCT1 interrupts the fibroblast-to-cardiomyocyte lactate shuttle, which may attenuate cardiac remodelling in hypertension.

Graphical Abstract
Meta-analysis of preclinical measures of efficacy in immune checkpoint blockade therapies and comparison to clinical efficacy estimates
Authors: Tenorio-Pedraza Juan Miguel , Lippert Jörg , Burghaus Rolf , Scheerans Christian
Published: August 2023

Background

Despite the successes of checkpoint inhibitors targeting T-cell receptors, clinical efficacy is highly cancer-dependent and subject to high inter-individual variability in treatment outcome. The ability to predict the clinical success in different cancer indications is therefore an important capability for successful clinical development. In this meta-analysis, the main goal was to identify factors that modified the clinical efficacy estimates of checkpoint blockade therapies derived from preclinical animal data to improve the robustness and reliability of such estimates.

Methods

To this end, animal studies testing checkpoint inhibitors (anti-PD-1, anti-PD-L1, anti-CTLA-4) were identified in PubMed ranging from 1.01.2000 to 31.12.2018. The eligibility criteria included the reporting of the Kaplan–Meier estimates of survival and the number of mice used in each experiment. A mixed-effects model was fitted to the preclinical and clinical data separately to determine potential sources of bias and heterogeneity between studies.

Results

A total of 160 preclinical studies comprising 13,811 mice were selected, from which the hazard ratio (HR) and the median survival ratio (MSR) were calculated. Similarly, clinical Phase III studies of checkpoint inhibitors were identified in PubMed and the ClinicalTrials.gov database ranging from 1.01.2010 to 31.12.2020. This resulted in 62 clinical studies representing 43,135 patients subjected to 8 therapies from which overall survival (OS) and progression-free survival (PFS) hazard ratios were obtained. Using a mixed-effects model, different factors were tested to identify sources of variability between estimates. In the preclinical data, the tumor cell line and individual study were the main factors explaining the heterogeneity. In the clinical setting, the cancer type was influential to the inter-study variability. When using the preclinical estimates to predict clinical estimates, the cancer-type specific estimates of treatment effect using the MSRs better approximated the observed clinical estimates than the HR-derived predictions.

Conclusions

This has strong implications on the design of ICB preclinical studies with respect to sample size determination, selection of cancer cell lines and labs to run the experiments and the choice of efficacy measure.
Patient experience of spontaneous intracranial hypotension (SIH): qualitative interviews for concept elicitation
Authors: Amrhein Timothy J. , McFatrich Molly , Ehle Kate , Malinzak Michael D. , Gray Linda , Kranz Peter G. , Weant E. Hope , Zigler Christina K.
Published: August 2023

Background & objectives

Spontaneous intracranial hypotension (SIH) is an underdiagnosed and debilitating condition caused by a spinal cerebrospinal fluid (CSF) leak. Although SIH can lead to substantial morbidity and disability, little data exists about patients’ perspectives. Without hearing directly from patients, our understanding of the full experience of having SIH is limited, as is our ability to identify and use appropriate patient-reported outcome measures (PROMs) within clinical care and research. The purpose of this study was to conduct qualitative interviews with confirmed SIH patients to fully describe their experiences and identify relevant concepts to measure.

Methods

Patients were recruited from an SIH specialty clinic at a large, U.S.-based healthcare center. Patients undergoing an initial consultation who were ≥ 18 years old, English-speaking, met the International Classification of Headache Disorders-3 criteria for SIH, and had a brain MRI with contrast that was positive for SIH were eligible to participate. During semi-structured qualitative interviews with a trained facilitator, participants were asked to describe their current SIH symptoms, how their experiences with SIH had changed over time, and the aspects of SIH that they found most bothersome. Analysts reviewed the data, created text summaries, and wrote analytic reports.

Results

Fifteen participants completed interviews. Common symptoms reported by patients included headache, tinnitus, ear fullness/pressure/pain, and neck or interscapular pain. Patients reported that their symptoms worsened over the course of their day and with activity. The most bothersome aspect of SIH was disruption to daily activities and limits to physical activities/exercise, which were severe. With regard to symptoms, the most bothersome and impactful included physical pain and discomfort (including headache), as well as fatigue.

Conclusions

Patients reported a diverse set of symptoms that were attributed to SIH, with devastating impacts on functioning and high levels of disability. Researchers considering use of PROMs for SIH should consider inclusion of both symptom scales and aspects of functioning, and future work should focus on evaluating the validity of existing measures for this patient population using rigorous qualitative and quantitative methods in diverse samples. Additionally, these data can be used to assist clinicians in understanding the impacts of SIH on patients.
IPACK block with spinal anesthesia compared to fentanyl-based spinal anesthesia for postoperative analgesia following arthroscopic meniscectomy: a randomized, prospective study
Authors: Aboelsuod Mohamed Abdelgawad Abdelhalim , Abdalla Abdalla Mohamed , Elbadawy Mohamed Ahmed , Yahia Othman Saad-eldien
Published: August 2023

Background

Local anesthesia and intrathecal narcotics are utilized to provide postoperative analgesia. IPACK (infiltration between the knee capsule and popliteal artery) is a new localized analgesic approach for knee surgery. This randomized study aimed to compare fentanyl-based spinal anesthesia and IPACK block-based spinal anesthesia for postoperative analgesia in patients undergoing arthroscopic meniscectomy.

Results

In group F, the VAS (visual analog scale) was higher than in group I, whereas the total amount of morphine was lower in group I (P < .05). In group F (3.92 ± 1.54), the initial painkiller request occurred earlier than in group I (8.82 ± 0.44). In addition, total morphine administrated in group F (20.81 ± 0.69) was significantly higher than in group I (9.54 ± 0.73) (P < .05). Group I had a higher level of patient satisfaction 24 h after surgery than group F (P < .05). In the current study, there were no significant adverse effects linked to the use of fentanyl. Moreover, no complications associated with the IPACK block were detected.

Conclusions

The combination of IPACK block and hyperbaric bupivacaine spinal anesthesia is an effective treatment for initial postoperative pain following arthroscopic meniscectomy, according to the findings of this study. IPACK block prolongs postoperative analgesia more than intrathecal fentanyl.

Trial registration

This study was registered with Clinical Trials Registry (NCT05833776).