bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined versus independent effects of exercise training and intermittent fasting on body composition and cardiometabolic health in adults: a systematic review and meta-analysis
Authors: Khalafi Mousa , Symonds Michael E. , Maleki Aref Habibi , Sakhaei Mohammad Hossein , Ehsanifar Mahsa , Rosenkranz Sara K.
Published: January 2024

Introduction and aim

Exercise training (Ex) and intermittent fasting (IF) are effective for improving body composition and cardiometabolic health overweight and obese adults, but whether combining Ex and IF induces additive or synergistic effects is less well established. We therefore, performed a systematic review and meta-analysis to compare the combined versus independent effects of Ex and IF on body composition and cardiometabolic health in adults.

Method

An electronic search was conducted in three main online databases including PubMed, Web of Science, and Scopus, from inception to March 9, 2023 for studies involving Ex plus IF trials versus standalone Ex and/or IF interventions in adults. Interventions had a duration of ≥ 2 weeks. Standardized (SMD) or weighted mean differences (WMD) and 95% confidence intervals were calculated in order to compare effects on body weight, body mass index (BMI), body fat lean body mass (LBM), visceral fat, and waist circumference. For cardiometabolic health, outcomes included fasting glucose, insulin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL), triglycerides (TG), high-density lipoprotein cholesterol (HDL), systolic (SBP) and diastolic (DBP) blood pressure, and VO2max/peak.

Results

Ex plus IF decreased body weight [WMD: -3.03 kg (95% CI: -3.44 to -2.61),p = 0.001], BMI [WMD: -1.12 kg.m2(95% CI: -1.28 to -0.95),p = 0.001], body fat [SMD: -0.72 (95% CI: -1.23 to -0.21),p = 0.005], visceral fat [SMD: -0.34 (95% CI: -0.63 to -0.05),p = 0.01], and waist circumference [WMD: -2.63 cm (95% CI: -4.16 to -1.11),p = 0.001] more than Ex alone. However, changes in body composition and cardiometabolic health markers were not significantly different for Ex plus IF when compared with IF alone, with the exception of VO2max/peak [SMD: 0.55 (95% CI: 0.14 to 0.97),p = 0.009].

Conclusion

We demonstrate that a combination of Ex and IF produces superior changes in body composition, but not in markers of cardiometabolic health when compared with Ex or IF alone. Ex plus IF could therefore be effective for weight and fat loss but has no additive or synergistic effects for other cardiometabolic health markers.
CircPPAP2B controls metastasis of clear cell renal cell carcinoma via HNRNPC-dependent alternative splicing and targeting the miR-182-5p/CYP1B1 axis
Authors: Zheng Zaosong , Zeng Xiangbo , Zhu Yuanchao , Leng Mengxin , Zhang Zhiyong , Wang Qiong , Liu Xiaocen , Zeng Siying , Xiao Yongyuan , Hu Chenxi , Pang Shiyu , Wang Tong , Xu Bihong , Peng Peidan , Li Fei , Tan Wanlong
Published: January 2024

Background

Renal cell carcinoma (RCC) is one of the most common malignant tumor worldwide. Metastasis is a leading case of cancer-related deaths of RCC. Circular RNAs (circRNAs), a class of noncoding RNAs, have emerged as important regulators in cancer metastasis. However, the functional effects and regulatory mechanisms of circRNAs on RCC metastasis remain largely unknown.

Methods

High-throughput RNA sequencing techniques were performed to analyze the expression profiles of circRNAs and mRNAs in highly and poorly invasive clear cell renal cell carcinoma (ccRCC) cell lines. Functional experiments were performed to unveil the regulatory role of circPPAP2B in the proliferation and metastatic capabilities of ccRCC cells. RNA pulldown, Mass spectrometry analysis, RNA methylation immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), co-immunoprecipitation (CoIP), next-generation RNA-sequencing and double luciferase experiments were employed to clarify the molecular mechanisms by which circPPAP2B promotes ccRCC metastasis.

Results

In this study, we describe a newly identified circular RNA called circPPAP2B, which is overexpressed in highly invasive ccRCC cells, as determined through advanced high-throughput RNA sequencing techniques. Furthermore, we observed elevated circPPAP2B in ccRCC tissues, particularly in metastatic ccRCC tissues, and found it to be associated with poor prognosis. Functional experiments unveiled that circPPAP2B actively stimulates the proliferation and metastatic capabilities of ccRCC cells. Mechanistically, circPPAP2B interacts with HNRNPC in a m6A-dependent manner to facilitate HNRNPC nuclear translocation. Subcellular relocalization was dependent upon nondegradable ubiquitination of HNRNPC and stabilization of an HNRNPC/Vimentin/Importin α7 ternary complex. Moreover, we found that circPPAP2B modulates the interaction between HNRNPC and splicing factors, PTBP1 and HNPNPK, and regulates pre-mRNA alternative splicing. Finally, our studies demonstrate that circPPAP2B functions as a miRNA sponge to directly bind to miR-182-5p and increase CYP1B1 expression in ccRCC.

Conclusions

Collectively, our study provides comprehensive evidence that circPPAP2B promotes proliferation and metastasis of ccRCC via HNRNPC-dependent alternative splicing and miR-182-5p/CYP1B1 axis and highlights circPPAP2B as a potential therapeutic target for ccRCC intervention.
Treatment in certified cancer centers is related to better survival in patients with colon and rectal cancer: evidence from a large German cohort study
Authors: Bierbaum Veronika , Bobeth Christoph , Roessler Martin , Gerken Michael , Tol Kees Kleihues-van , Reissfelder Christoph , Fürst Alois , Günster Christian , Dröge Patrik , Ruhnke Thomas , Klinkhammer-Schalke Monika , Schmitt Jochen , Schoffer Olaf
Published: January 2024

Background

Certified cancer centers aim to ensure high-quality care by establishing structural and procedural standards according to evidence-based guidelines. Despite the high clinical and health policy relevance, evidence from a nation-wide study for the effectiveness of care for colorectal cancer in certified centers vs. other hospitals in Germany is still missing.

Methods

In a retrospective cohort study covering the years 2009–2017, we analyzed patient data using demographic information, diagnoses, and treatments from a nationwide statutory health insurance enriched with information on certification. We investigated whether patients with incident colon or rectal cancer did benefit from primary therapy in a certified cancer center. We used relative survival analysis taking into account mortality data of the German population and adjustment for patient and hospital characteristics via Cox regression with shared frailty for patients in hospitals with and without certification.

Results

The cohorts for colon and rectal cancer consisted of 109,518 and 51,417 patients, respectively, treated in a total of 1052 hospitals. 37.2% of patients with colon and 42.9% of patients with rectal cancer were treated in a certified center. Patient age, sex, comorbidities, secondary malignoma, and distant metastases were similar across groups (certified/non-certified) for both colon and rectal cancer. Relative survival analysis showed significantly better survival of patients treated in a certified center, with 68.3% (non-certified hospitals 65.8%) 5-year survival for treatment of colon cancer in certified (p < 0.001) and 65.0% (58.8%) 5-year survival in case of rectal cancer (p < 0.001), respectively. Cox regression with adjustment for relevant covariates yielded a lower hazard of death for patients treated in certified centers for both colon (HR = 0.92, 95% CI = 0.89–0.95) and rectal cancer (HR = 0.92, 95% CI = 0.88–0.95). The results remained robust in a series of sensitivity analyses.

Conclusions

This large cohort study yields new important evidence that patients with colorectal cancer have a better chance of survival if treated in a certified cancer center. Certification thus provides one powerful means to improve the quality of care for colorectal cancer. To decrease the burden of disease, more patients should thus receive cancer care in a certified center.
Noninvasive electrical stimulation as a neuroprotective strategy in retinal diseases: a systematic review of preclinical studies
Authors: Li Jiaxian , Zhou Wei , Liang Lina , Li Yamin , Xu Kai , Li Xiaoyu , Huang Ziyang , Jin Yu
Published: January 2024

Background

Electrical activity has a crucial impact on the development and survival of neurons. Numerous recent studies have shown that noninvasive electrical stimulation (NES) has neuroprotective action in various retinal disorders.

Objective

To systematically review the literature on in vivo studies and provide a comprehensive summary of the neuroprotective action and the mechanisms of NES on retinal disorders.

Methods

Based on the PRISMA guideline, a systematic review was conducted in PubMed, Web of Science, Embase, Scopus and Cochrane Library to collect all relevant in vivo studies on “the role of NES on retinal diseases” published up until September 2023. Possible biases were identified with the adopted SYRCLE’s tool.

Results

Of the 791 initially gathered studies, 21 articles met inclusion/exclusion criteria for full-text review. The results revealed the neuroprotective effect of NES (involved whole-eye, transcorneal, transscleral, transpalpebral, transorbital electrical stimulation) on different retinal diseases, including retinitis pigmentosa, retinal degeneration, high-intraocular pressure injury, traumatic optic neuropathy, nonarteritic ischemic optic neuropathy. NES could effectively delay degeneration and apoptosis of retinal neurons, preserve retinal structure and visual function with high security, and its mechanism of action might be related to promoting the secretion of neurotrophins and growth factors, decreasing inflammation, inhibiting apoptosis. The quality scores of included studies ranged from 5 to 8 points (a total of 10 points), according to SYRCLE’s risk of bias tool.

Conclusion

This systematic review indicated that NES exerts neuroprotective effects on retinal disease models mainly through its neurotrophic, anti-inflammatory, and anti-apoptotic capabilities. To assess the efficacy of NES in a therapeutic setting, however, well-designed clinical trials are required in the future.
LIPCAR levels in plasma-derived extracellular vesicles is associated with left ventricle remodeling post-myocardial infarction
Authors: Turkieh Annie , Beseme Olivia , Saura Ouriel , Charrier Henri , Michel Jean-Baptiste , Amouyel Philippe , Thum Thomas , Bauters Christophe , Pinet Florence
Published: January 2024

Background

Long Intergenic noncoding RNA predicting CARdiac remodeling (LIPCAR) is a long noncoding RNA identified in plasma of patients after myocardial infarction (MI) to be associated with left ventricle remodeling (LVR). LIPCAR was also shown to be a predictor of early death in heart failure (HF) patients. However, no information regarding the expression of LIPCAR and its function in heart as well as the mechanisms involved in its transport to the circulation is known. The aims of this study are (1) to characterize the transporter of LIPCAR from heart to circulation; (2) to determine whether LIPCAR levels in plasma isolated-extracellular vesicles (EVs) reflect the alteration of its expression in total plasma and could be used as biomarkers of LVR post-MI.

Methods

Since expression of LIPCAR is restricted to human species and the limitation of availability of cardiac biopsy samples, serum-free conditioned culture media from HeLa cells were first used to characterize the extracellular transporter of LIPCAR before validation in EVs isolated from human cardiac biopsies (non-failing and ischemic HF patients) and plasma samples (patients who develop or not LVR post-MI). Differential centrifugation at 20,000g and 100,000g were performed to isolate the large (lEVs) and small EVs (sEVs), respectively. Western blot and nanoparticle tracking (NTA) analysis were used to characterize the isolated EVs. qRT-PCR analysis was used to quantify LIPCAR in all samples.

Results

We showed that LIPCAR is present in both lEVs and sEVs isolated from all samples. The levels of LIPCAR are higher in lEVs compared to sEVs isolated from HeLa conditioned culture media and cardiac biopsies. No difference of LIPCAR expression was observed in tissue or EVs isolated from cardiac biopsies obtained from ischemic HF patients compared to non-failing patients. Interestingly, LIPCAR levels were increased in lEVs and sEVs isolated from MI patients who develop LVR compared to patients who did not develop LVR.

Conclusion

Our data showed that large EVs are the main extracellular vesicle transporter of LIPCAR from heart into the circulation independently of the status, non-failing or HF, in patients. The levels of LIPCAR in EVs isolated from plasma could be used as biomarkers of LVR in post-MI patients.
Myeloid leukemia-derived galectin-1 downregulates CAR expression to hinder cytotoxicity of CAR T cells
Authors: Li Chuo , Zuo Shiyu , Shan Lingling , Huang Huifang , Cui Haidong , Feng Xiaoming
Published: January 2024

Background

Chimeric antigen receptor (CAR) T cells have shown significant activity in B-lineage malignancies. However, their efficacy in myeloid leukemia has not been successful due to unclear molecular mechanisms.

Methods

We conducted in vitro and in vivo experiments to investigate whether myeloid leukemia cells directly induce CAR down-regulation. Furthermore, we designed a CD33 CARKR in which all lysines in the cytoplasmic domain of CAR were mutated to arginine and verified through in vitro experiments that it could reduce the down-regulation of surface CARs and enhance the killing ability. Transcriptome sequencing was performed on various AML and ALL cell lines and primary samples, and the galectin-1-specific inhibitory peptide (anginex) successfully rescued the killing defect and T-cell activation in in vitro assays.

Results

CAR down-regulation induced by myeloid leukemia cells under conditions of low effector-to-tumor ratio, which in turn impairs the cytotoxicity of CAR T cells. In contrast, lysosomal degradation or actin polymerization inhibitors can effectively alleviate CAR down-regulation and restore CAR T cell-mediated anti-tumor functions. In addition, this study identified galectin-1 as a critical factor used by myeloid leukemia cells to induce CAR down-regulation, resulting in impaired T-cell activation.

Conclusion

The discovery of the role of galectin-1 in cell surface CAR down-regulation provides important insights for developing strategies to restore anti-tumor functions.
Predicting quetiapine dose in patients with depression using machine learning techniques based on real-world evidence
Authors: Hao Yupei , Zhang Jinyuan , Yu Jing , Yu Ze , Yang Lin , Hao Xin , Gao Fei , Zhou Chunhua
Published: January 2024

Background

Being one of the most widespread, pervasive, and troublesome illnesses in the world, depression causes dysfunction in various spheres of individual and social life. Regrettably, despite obtaining evidence-based antidepressant medication, up to 70% of people are going to continue to experience troublesome symptoms. Quetiapine, as one of the most commonly prescribed antipsychotic medication worldwide, has been reported as an effective augmentation strategy to antidepressants. The right quetiapine dose and personalized quetiapine treatment are frequently challenging for clinicians. This study aimed to identify important influencing variables for quetiapine dose by maximizing the use of data from real world, and develop a predictive model of quetiapine dose through machine learning techniques to support selections for treatment regimens.

Methods

The study comprised 308 depressed patients who were medicated with quetiapine and hospitalized in the First Hospital of Hebei Medical University, from November 1, 2019, to August 31, 2022. To identify the important variables influencing the dose of quetiapine, a univariate analysis was applied. The prediction abilities of nine machine learning models (XGBoost, LightGBM, RF, GBDT, SVM, LR, ANN, DT) were compared. Algorithm with the optimal model performance was chosen to develop the prediction model.

Results

Four predictors were selected from 38 variables by the univariate analysis (p < 0.05), including quetiapine TDM value, age, mean corpuscular hemoglobin concentration, and total bile acid. Ultimately, the XGBoost algorithm was used to create a prediction model for quetiapine dose that had the greatest predictive performance (accuracy = 0.69) out of nine models. In the testing cohort (62 cases), a total of 43 cases were correctly predicted of the quetiapine dose regimen. In dose subgroup analysis, AUROC for patients with daily dose of 100 mg, 200 mg, 300 mg and 400 mg were 0.99, 0.75, 0.93 and 0.86, respectively.

Conclusions

In this work, machine learning techniques are used for the first time to estimate the dose of quetiapine for patients with depression, which is valuable for the clinical drug recommendations.
Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion: a case report
Authors: Duan Rong , He Xiaojuan , Ma Xiaojing , Huang Fengbo , Hu Xiangrong
Published: January 2024

Background

Cutaneous Melanocytic Tumor with CRTC1::TRIM11 Fusion (CMTCT) represents a novel and rare entity in the realm of dermatological oncology, characterized by distinct melanocytic differentiation. This particular tumor type has yet to be officially recognized by the World Health Organization (WHO). CMTCT is generally perceived as a tumor with a relatively indolent nature; however, it is not devoid of metastatic potential. Therefore, ensuring complete surgical excision of the tumor, coupled with rigorous long-term follow-up, is paramount for patient management. In this context, we report the case of an 18-year-old female patient who presented with a dull red nodule on her left leg. Initial surgical intervention led to a pathological diagnosis of CMTCT, but it was determined that the tumor had not been fully excised. Consequently, a second surgical procedure was undertaken to achieve complete removal of the tumor. During a follow-up period of six months post-surgery, the patient showed no signs of local recurrence or metastasis, indicating a successful outcome.

Case presentation

An 18-year-old female patient noticed a dull red nodule on her left leg three years ago, which exhibited slow growth over time. She underwent a subcutaneous tumor resection. Histological examination under high-power magnification revealed that the neoplasm consisted of epithelioid cells arranged in nests, fascicles, bundles, or sheets. The tumor cells had round or ovoid nuclei with prominent nucleoli and visible mitotic figures. Notably, areas resembling nevus cell clusters were observed. Immunohistochemical analysis confirmed melanocytic differentiation. Next-generation sequencing (NGS) identified a CRTC1::TRIM11 fusion, and fluorescence in situ hybridization (FISH) for CRTC1 confirmed rearrangement. Consequently, a diagnosis of cutaneous melanocytic tumor with CRTC1::TRIM11 fusion was established.

Conclusions

CMTCT is a rare tumor characterized by melanocytic differentiation. In this case, the tumor predominantly comprised epithelioid cells with localized nevus cell clusters. The expression of melanocyte markers could easily lead to a misdiagnosis as cutaneous melanoma. However, several distinguishing features were noted: the tumor was not connected to the epidermis, exhibited low cellular heterogeneity and proliferation index, and showed minimal cellular atypia. Additionally, tests for EWSR1 rearrangement (FISH) and BRAF V600E mutation (PCR-ARMS) were negative.This case underscores the importance of a comprehensive diagnostic approach when clinical, microscopic, immunohistochemical, and molecular findings do not align. The presence of nevus cell clusters morphology in the tumor cells enhances our understanding of this disease’s histological spectrum and aids in avoiding misdiagnosis or missed diagnosis.
Compressive buttress compared with off-axial screw fixation for vertical femoral neck fractures in young adults: a prospective, randomized controlled trial
Authors: Yin Bo-hao , Liu Chen-jun , Sherrier Matthew C. , Sun Hui , Zhang Wei
Published: January 2024

Background

To compare the clinical outcomes of compressive buttress screw (CBS) fixation, a novel screw fixation strategy, to off-axial screw fixation (off-axial partial threaded cannulated screw, OPTCS) for vertical femoral neck fractures (FNFs) in young adults.

Methods

A total of 146 adults younger than 55 years old with high-energy Pauwels type III FNFs were randomized to receive CBS fixation or OPTCS fixation. Primary outcomes were complication rates, including fixation failure, fracture nonunion, and avascular necrosis of the femoral head (ANFH) at 24 months after treatment. Fixation loosening, femoral neck shortening and varus collapse, patient function and quality of life using the Harris hip score (HHS), and EuroQol-5 dimensional-5 levels (EQ-5D-5L) questionnaire (including EQ-5D-5L and EQ-VAS) were assessed as secondary outcomes at 24 months.

Results

CBS and OPTCS fixation groups were similar with regard to demographics at baseline. At 24 months, patients in the CBS fixation cohort had a significantly lower rate of fixation failure (10.5% vs. 25.0%, p = 0.041) and fracture nonunion (1.8% vs. 18.3%, p = 0.003) compared with patients who received OPTCS fixation. There was no difference in rate of ANFH (7.0% vs. 11.7%, p = 0.389) between groups. Additionally, patients managed with CBS fixation showed significantly less fixation loosening (19.3% vs. 58.3%, p < 0.001), less severe femoral neck shortening and varus collapse (10.5% vs. 25.0%, p = 0.007), higher HHS (93 vs. 83, p = 0.001) and more excellent grade (68.4% vs. 36.7%, p = 0.008), higher EQ-5D-5L (0.814 vs, 0.581, p < 0.001) and EQ-VAS (85 vs. 80, p = 0.002).

Conclusion

CBS screw fixation confers significantly lower complication rate in addition to higher functional and quality of life outcomes for young adults with high-energy FNF compared with OPTCS fixation.

Trial registration

This prospective, randomized controlled trial was approved by the institutional review board of our center, Ethics Committee of Shanghai sixth people's Hospital, and registered at www.chictr.org.cn (Approval Number: ChiCTR1900026283; Registered 29 September 2019—Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=43164).
Placement of stent grafts with different calibers into the true and false lumens of anastomotic aneurysms after descending aortic replacement for aortic dissection
Authors: Uehara Hiroo , Uchiyama Masateru , Imazuru Tomohiro
Published: January 2024

Anastomotic aneurysms present as a life-threatening emergency after descending aortic replacement for aortic dissection. Thoracic endovascular aneurysm repair (TEVAR) has been performed since the early 2000s for complicated cases in which re-thoracotomy cannot be adopted. We report the case of a 57-year-old male patient, during a 5-year follow-up after descending aortic replacement for aortic dissection, developed aneurysm expansion around the false lumen on the peripheral side of the artificial graft. Considering the risk and the patient’s desires, we opted to perform TEVAR with different calibers into the true and false lumens “modified kissing stents technique”. His postoperative course was uneventful without any complications. This case highlights the utility of the modified kissing stents technique for anastomotic aneurysms after descending aortic replacement for aortic dissection using stent grafts with different calibers into the true and false lumens.
Emotion dysregulation and psychopathological symptoms in non-clinical adolescents: The mediating role of boredom and social media use
Authors: Iannattone Sara , Mezzalira Selene , Bottesi Gioia , Gatta Michela , Miscioscia Marina
Published: January 2024

Background

Emotion dysregulation, boredom, and problematic social media use are well-known vulnerability factors for psychopathology during adolescence; nevertheless, the interplay between these factors remains underinvestigated in the literature. Therefore, the present cross-sectional study aimed to explore the mediating role of boredom and problematic social media use in the relations between emotion dysregulation and both internalizing and externalizing problems in a non-clinical group of Italian adolescents.

Method

721 students (64.6% girls; Mage = 15.49 years ± 1.82) were involved and completed self-report tools assessing emotion dysregulation, boredom, problematic social media use, and psychopathological symptoms. Path analysis was used to test whether boredom and problematic social media use mediated the relation between emotion dysregulation and psychopathology, distinguishing between internalizing and externalizing problems.

Results

Path models showed that emotion dysregulation predicted both internalizing and externalizing problems, as well as boredom and problematic social media use. Importantly, boredom mediated the associations between emotion dysregulation and both psychopathological dimensions, while problematic social media use mediated only the relation with externalizing problems.

Conclusions

Our results highlight that the influence of emotion dysregulation on psychopathology can manifest through different paths, leading to specific symptomatology based on interactions between various variables. In particular, boredom seems to be a transdiagnostic factor for psychopathology in adolescence, whereas problematic social media use would be a dimension-specific factor. The practical implications of these findings are discussed.
Association between maternal polycystic ovarian syndrome undergoing assisted reproductive technology and pregnancy complications and neonatal outcomes: a systematic review and meta-analysis
Authors: Ban Miaomiao , Sun Yifei , Chen Xiaojing , Zhou Xiaoqian , Zhang Yiyuan , Cui Linlin
Published: January 2024

Background

Polycystic ovarian syndrome (PCOS) is recognized as the most prevalent endocrine disorder among women of reproductive age. While the utilization of assisted reproductive technology (ART) has resulted in favorable outcomes for infertility treatment in PCOS patients, the inherent pathophysiological features of the condition give rise to complications and consequences during pregnancy and delivery for both the mother and offspring. This study was to assess the correlation between maternal PCOS and various pregnancy complications and neonatal outcomes undergone ART.

Methods

A systematic search was conducted on PubMed, EmBase, and the Cochrane Library to identify observational studies that investigated the association between PCOS and the risk of various pregnancy complications and neonatal outcomes, including gestational diabetes mellitus (GDM), hypertension in pregnancy (PIH), preeclampsia (PE), preterm birth, abortion, congenital malformations (CA), small for gestational age (SGA), large for gestational age (LGA), low birth weight (LBW), macrosomia, neonatal intensive care unit (NICU) admission and birth weight. Eligible studies were selected based on predetermined inclusion and exclusion criteria. The meta-analysis was conducted using Review Manager and Stata software, with odds ratios (ORs) or mean difference (MD), confidence intervals (CIs), and heterogeneity (I2) being calculated. The search was conducted up to March 2023.

Results

A total of 33 studies with a combined sample size of 92,810 participants were identified. The findings indicate that PCOS is significantly associated with an increased risk of GDM (OR 1.51, 95% CI:1.17–1.94), PIH (OR 1.72, 95% CI:1.25–2.39), PE (OR 2.12, 95% CI:1.49–3.02), preterm birth (OR 1.29, 95% CI:1.21–1.39), and LBW (OR 1.29, 95% CI:1.14–1.47). In subgroup analyses, the risks of GDM (OR 1.80, 95% CI:1.23–2.62) and abortion (OR 1.41, 95% CI:1.08–1.84) were elevated in fresh embryo transferred (ET) subgroup, whereas elevated risk of PE (OR 1.82, 95% CI:1.17–2.83) and preterm birth (OR 1.31, 95% CI:1.21–1.42) was identified in frozen ET subgroup. Whatever with or without hyperandrogenism, patients with PCOS had a higher risk in preterm birth (OR 1.69, 95% CI: 1.31–2.18; OR 1.24, 95% CI:1.02–1.50) and abortion (OR 1.38, 95% CI:1.12–1.71; OR 1.23, 95% CI:1.06–1.43).

Conclusion

Our findings suggest that individuals with PCOS undergone ART are at a notably elevated risk for experiencing pregnancy complications and unfavorable neonatal outcomes. Nevertheless, to establish a definitive association between PCOS and pregnancy-related outcomes, it is necessary to conduct extensive prospective, blinded cohort studies and effectively control for confounding variables.
No evidence for a diminished ovarian reserve among patients with hypertensive disorders of pregnancy: a case control study
Authors: van Bree Bo E. , Jorissen Laura M. , Pattinaja Désirée A.P.M. , Bons Judith A.P. , Spaanderman Marc E.A. , Valkenburg Olivier , van Golde Ron J.T.
Published: January 2024

Background

Existing evidence suggests a relation between cardiovascular dysfunction and diminished ovarian reserve. While it is known that pre-existent cardiovascular dysfunction is also associated with the development of preeclampsia (PE) during pregnancy, we hypothesize that signs of diminished ovarian reserve may occur more frequently among women with a history of hypertensive disorders of pregnancy (HDP). The aim of our study was therefore to analyse if women with a history of HDP show signs of diminished ovarian reserve, represented by lower anti-Mullarian hormone (AMH) levels, compared to controls. For this retrospective observational case control study, patients included women with a history of HDP, whereas controls constituted of women with a history of an uncomplicated pregnancy. The study was conducted in a tertiary referral centre in which all women underwent a one-time cardiovascular and metabolic assessment. Ovarian reserve and markers of cardiovascular function were evaluated, adjusted for age and body mass index (BMI) using linear regression analyses.

Results

163 patients and 81 controls were included over a time span of 3 years. No signs of diminished ovarian reserve i.e. lower AMH level were observed in the patient group versus controls. A subgroup analysis even showed higher AMH levels in late onset HDP as compared to controls (2.8 vs. 2.0 µg/L, p = 0.025). As expected, cardiovascular function markers were significantly less favourable in the patient group compared to controls; higher levels of systolic blood pressure (BP) (5%), diastolic BP (4%), triglycerides (29%), glucose (4%) and insulin levels (81%) (all p < 0.05), whereas high density lipid (HDL) cholesterol was 12% lower (NS).

Conclusions

Despite unfavourable cardiovascular risk profile, the present study does not substantiate the hypothesis that women with HDP show accelerated ovarian ageing as compared to healthy parous controls. Although HDP patients should be warned about their cardiovascular health, they shouldn’t be concerned about unfavourable ovarian reserve status.
Identification and validation of senescence-related genes in polycystic ovary syndrome
Authors: Jiang Danni , Xu Yang , Yang Lin , Li Pengfei , Han Xiaojuan , Li Qianni , Yang Yang , Chao Lan
Published: January 2024

Background

Polycystic ovary syndrome (PCOS) is an exceedingly intractable issue affecting female endocrine and reproductive health. However, the etiology and intricate pathological mechanisms of PCOS remain unclear. Nowadays, aging was found to share multiple common pathological mechanisms with PCOS, which causes probing into the pathogenesis of PCOS from senescence. However, no bioinformatics analyses have specifically focused on connection between PCOS and ovarian aging.

Methods

Differentially expressed aging-related genes in PCOS were identified and then analyzed using function enrichment method. Hub genes were determined based on multiple algorithms, and expression validation of hub genes was performed in both datasets and experiments (human granulosa-like tumor cell line, KGN; human Granulosa Cell, hGCs). Finally, a transcription factor-miRNA-gene network of hub genes was constructed.

Results

Here, we identified 73 aging-related differential expression genes (ARDEGs) by intersecting DEGs in PCOS and senescence-related gene set. Furthermore, we performed biological functions and potential pathways of ARDEGs and potential hub genes were also screened by multiple algorithms. From the perspective of immune dysfunction, we analyzed the correlation between PCOS and immune cells. Finally, TF-miRNA-gene networks were constructed. Finally, TF-miRNA-gene networks were constructed.

Conclusions

Our work aimed to elucidate the relation between PCOS and cellular senescence based on bioinformatics strategy, deepening the understanding of mechanisms and to seek for novel therapy strategies for improving reproductive lifespan and female health. Exploring the potential molecular mechanism of cell aging in PCOS is expected to bring a new breakthrough for PCOS diagnosis and therapy strategies. And this, might deepen our understanding about intricate mechanisms of ovarian aging.
Green synthesis of silver nanoparticles and its environmental sensor ability to some heavy metals
Authors: Ibrahim Nesma H. , Taha Gharib M. , Hagaggi Noura Sh. A. , Moghazy Marwa A.
Published: January 2024

This study marks a pioneering effort in utilizing Vachellia tortilis subsp. raddiana (Savi) Kyal. & Boatwr., (commonly known as acacia raddiana) leaves as both a reducing and stabilizing agent in the green “eco-friendly” synthesis of silver nanoparticles (AgNPs). The research aimed to optimize the AgNPs synthesis process by investigating the influence of pH, temperature, extract volume, and contact time on both the reaction rate and the resulting AgNPs' morphology as well as discuss the potential of AgNPs in detecting some heavy metals. Various characterization methods, such as UV–vis spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), infrared spectroscopy (IR), Zeta sizer, EDAX, and transmitting electron microscopy (TEM), were used to thoroughly analyze the properties of the synthesized AgNPs. The XRD results verified the successful production of AgNPs with a crystallite size between 20 to 30 nm. SEM and TEM analyses revealed that the AgNPs are primarily spherical and rod-shaped, with sizes ranging from 8 to 41 nm. Significantly, the synthesis rate of AgNPs was notably higher in basic conditions (pH 10) at 70 °C. These results underscore the effectiveness of acacia raddiana as a source for sustainable AgNPs synthesis. The study also examined the AgNPs' ability to detect various heavy metal ions colorimetrically, including Hg2+, Cu2+, Pb2+, and Co2+. UV–Vis spectroscopy proved useful for this purpose. The color of AgNPs shifts from brownish-yellow to pale yellow, colorless, pale red, and reddish yellow when detecting Cu2+, Hg2+, Co2+, and Pb2+ ions, respectively. This change results in an alteration of the AgNPs' absorbance band, vanishing with Hg2+ and shifting from 423 to 352 nm, 438 nm, and 429 nm for Cu2+, Co2+, and Pb2+ ions, respectively. The AgNPs showed high sensitivity, with detection limits of 1.322 × 10–5 M, 1.37 × 10–7 M, 1.63 × 10–5 M, and 1.34 × 10–4 M for Hg2+, Cu2+, Pb2+, and Co2+, respectively. This study highlights the potential of using acacia raddiana for the eco-friendly synthesis of AgNPs and their effectiveness as environmental sensors for heavy metals, showcasing strong capabilities in colorimetric detection.
Minimal aromatic aldehyde reduction (MARE) yeast platform for engineering vanillin production
Authors: Mo Qiwen , Yuan Jifeng
Published: January 2024

Background

Vanillin represents one of the most widely used flavoring agents in the world. However, microbial synthesis of vanillin is hindered by the host native metabolism that could rapidly degrade vanillin to the byproducts.

Results

Here, we report that the industrial workhorse Saccharomyces cerevisiae was engineered by systematic deletion of oxidoreductases to improve the vanillin accumulation. Subsequently, we harnessed the minimal aromatic aldehyde reduction (MARE) yeast platform for de novo synthesis of vanillin from glucose. We investigated multiple coenzyme-A free pathways to improve vanillin production in yeast. The vanillin productivity in yeast was enhanced by multidimensional engineering to optimize the supply of cofactors (NADPH and S-adenosylmethionine) together with metabolic reconfiguration of yeast central metabolism. The final yeast strain with overall 24 genetic modifications produced 365.55 ± 7.42 mg l−1 vanillin in shake-flasks, which represents the best reported vanillin titer from glucose in yeast.

Conclusions

The success of vanillin overproduction in budding yeast showcases the great potential of synthetic biology for the creation of suitable biocatalysts to meet the requirement in industry. Our work lays a foundation for the future implementation of microbial production of aromatic aldehydes in budding yeast.

Graphical Abstract
Combining a prioritization strategy and functional studies nominates 5’UTR variants underlying inherited retinal disease
Authors: Dueñas Rey Alfredo , del Pozo Valero Marta , Bouckaert Manon , Wood Katherine A , Van den Broeck Filip , Daich Varela Malena , Thomas Huw B , Van Heetvelde Mattias , De Bruyne Marieke , Van de Sompele Stijn , Bauwens Miriam , Lenaerts Hanne , Mahieu Quinten , Josifova Dragana ,   Genomics England Research Consortium, Rivolta Carlo , O’Keefe Raymond T , Ellingford Jamie , Webster Andrew R , Arno Gavin , Ayuso Carmen , De Zaeytijd Julie , Leroy Bart P , De Baere Elfride , Coppieters Frauke
Published: January 2024

Background

5’ untranslated regions (5’UTRs) are essential modulators of protein translation. Predicting the impact of 5’UTR variants is challenging and rarely performed in routine diagnostics. Here, we present a combined approach of a comprehensive prioritization strategy and functional assays to evaluate 5’UTR variation in two large cohorts of patients with inherited retinal diseases (IRDs).

Methods

We performed an isoform-level re-analysis of retinal RNA-seq data to identify the protein-coding transcripts of 378 IRD genes with highest expression in retina. We evaluated the coverage of their 5’UTRs by different whole exome sequencing (WES) kits. The selected 5’UTRs were analyzed in whole genome sequencing (WGS) and WES data from IRD sub-cohorts from the 100,000 Genomes Project (n = 2397 WGS) and an in-house database (n = 1682 WES), respectively. Identified variants were annotated for 5’UTR-relevant features and classified into seven categories based on their predicted functional consequence. We developed a variant prioritization strategy by integrating population frequency, specific criteria for each category, and family and phenotypic data. A selection of candidate variants underwent functional validation using diverse approaches.

Results

Isoform-level re-quantification of retinal gene expression revealed 76 IRD genes with a non-canonical retina-enriched isoform, of which 20 display a fully distinct 5’UTR compared to that of their canonical isoform. Depending on the probe design, 3–20% of IRD genes have 5’UTRs fully captured by WES. After analyzing these regions in both cohorts, we prioritized 11 (likely) pathogenic variants in 10 genes (ARL3, MERTK, NDP, NMNAT1, NPHP4, PAX6, PRPF31, PRPF4, RDH12, RD3), of which 7 were novel. Functional analyses further supported the pathogenicity of three variants. Mis-splicing was demonstrated for the PRPF31:c.-9+1G>T variant. The MERTK:c.-125G>A variant, overlapping a transcriptional start site, was shown to significantly reduce both luciferase mRNA levels and activity. The RDH12:c.-123C>T variant was found in cis with the hypomorphic RDH12:c.701G>A (p.Arg234His) variant in 11 patients. This 5’UTR variant, predicted to introduce an upstream open reading frame, was shown to result in reduced RDH12 protein but unaltered mRNA levels.

Conclusions

This study demonstrates the importance of 5’UTR variants implicated in IRDs and provides a systematic approach for 5’UTR annotation and validation that is applicable to other inherited diseases.
Uterine rupture in the first trimester: a case report and review of the literature
Authors: Mutiso Steve Kyende , Oindi Felix Mwembi , Mundia Debbie Muthoni
Published: January 2024

Background

Uterine rupture is a rare complication that can occur in the first trimester of pregnancy. It can lead to serious maternal morbidity or mortality, which is mostly due to catastrophic bleeding. First trimester uterine rupture is rare; hence, diagnosis can be challenging as it may be confused with other causes of early pregnancy bleeding such as an ectopic pregnancy. We present a case of first trimester scar dehiscence and conduct a literature review of this rare condition.

Case presentation

A 39-year-old African patient with four previous hysterotomy scars presented with severe lower abdominal pain at 11 weeks of gestation. She had two previous histories of third trimester uterine rupture in previous pregnancies with subsequent hysterotomies and repair. She underwent a diagnostic laparoscopy that confirmed the diagnosis of a 10 cm anterior wall uterine rupture. A laparotomy and repair of the rupture was subsequently done.

Conclusion

In conclusion, the case presented adds to the body of evidence of uterine scar dehiscence in the first trimester. The risk factors, clinical presentation, diagnostic imaging, and management outlined may help in early identification and management of this rare but life threatening condition.
The association of vasoactive-inotropic score and surgical patients’ outcomes: a systematic review and meta-analysis
Authors: Sun Yan-ting , Wu Wei , Yao Yun-tai
Published: January 2024

Background

The objective of this study is to conduct a systematic review and meta-analysis examining the relationship between the vasoactive-inotropic score (VIS) and patient outcomes in surgical settings.

Methods

Two independent reviewers searched PubMed, Web of Science, EMBASE, Scopus, Cochrane Library, Google Scholar, and CNKI databases from November 2010, when the VIS was first published, to December 2022. Additional studies were identified through hand-searching the reference lists of included studies. Eligible studies were those published in English that evaluated the association between the VIS and short- or long-term patient outcomes in both pediatric and adult surgical patients. Meta-analysis was performed using RevMan Manager version 5.3, and quality assessment followed the Joanna Briggs Institute (JBI) Critical Appraisal Checklists.

Results

A total of 58 studies comprising 29,920 patients were included in the systematic review, 34 of which were eligible for meta-analysis. Early postoperative VIS was found to be associated with prolonged mechanical ventilation (OR 5.20, 95% CI 3.78–7.16), mortality (OR 1.08, 95% CI 1.05–1.12), acute kidney injury (AKI) (OR 1.26, 95% CI 1.13–1.41), poor outcomes (OR 1.02, 95% CI 1.01–1.04), and length of stay (LOS) in the ICU (OR 3.50, 95% CI 2.25–5.44). The optimal cutoff value for the VIS as an outcome predictor varied between studies, ranging from 10 to 30.

Conclusion

Elevated early postoperative VIS is associated with various adverse outcomes, including acute kidney injury (AKI), mechanical ventilation duration, mortality, poor outcomes, and length of stay (LOS) in the ICU. Monitoring the VIS upon return to the Intensive Care Unit (ICU) could assist medical teams in risk stratification, targeted interventions, and parent counseling.

Systematic review registration

PROSPERO CRD42022359100.
A knowledge-graph based text summarization scheme for mobile edge computing
Authors: Yu Zheng , Wu Songyu , Jiang Jielin , Liu Dongqing
Published: January 2024

As the demand for edge services intensifies, text, being the most common type of data, has seen a significant expansion in data volume and an escalation in processing complexity. Furthermore, mobile edge computing (MEC) service systems often faces challenges such as limited computational capabilities and difficulties in data integration, requiring the development and implementation of more efficient and lightweight methodologies for text data processing. To swiftly extract and analysis vital information from MEC text data, an automatic generation scheme of multi-document text summarization based on knowledge graph is proposed in this paper, named KGCPN. For the text data from MEC devices and applications, the natural language processing technology is used to execute the data pre-processing steps, which transforms the MEC text data into a computationally tractable and semantically comprehensible format. Then, the knowledge graph of multi-document text is constructed by integrating the relationship paths and entity descriptions. The nodes and edges of the knowledge graph serve to symbolize the semantic relationships within the text, and the Graph Convolution Neural network (GCN) is used to understand the text and learn the semantic representation. Finally, a pointer-generator network model accepts the encoding information from GCN and automatically generate a general text summarization. The experimental results indicate that our scheme can effectively facilitate the smart pre-processing and integration of MEC data.
Utilizing neurodegenerative markers for the diagnostic evaluation of amyotrophic lateral sclerosis
Authors: Klíčová Kateřina , Mareš Jan , Menšíková Kateřina , Kaiserová Michaela , Friedecký David , Kaňovský Petr , Strnad Miroslav , Matěj Radoslav
Published: January 2024

Background

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive deterioration of upper and lower motor neurons. A definitive diagnostic test or biomarker for ALS is currently unavailable, leading to a diagnostic delay following the onset of initial symptoms. Our study focused on cerebrospinal fluid (CSF) concentrations of clusterin, tau protein, phosphorylated tau protein, and beta-amyloid1–42 in ALS patients and a control group.

Methods

Our study involved 54 ALS patients and 58 control subjects. Among the ALS patients, 14 presented with bulbar-onset ALS, and 40 with limb-onset ALS. We quantified biomarker levels using enzyme-linked immunosorbent assay (ELISA) and compared the results using the Mann–Whitney U-test.

Results

Significant elevations in neurodegenerative markers, including tau protein (p < 0.0001), phosphorylated tau protein (p < 0.0001), and clusterin (p = 0.038), were observed in ALS patients compared to controls. Elevated levels of tau protein and phosphorylated tau protein were also noted in both bulbar and limb-onset ALS patients. However, no significant difference was observed for beta-amyloid1–42. ROC analysis identified tau protein (AUC = 0.767) and p-tau protein (AUC = 0.719) as statistically significant predictors for ALS.

Conclusion

Our study demonstrates that neurodegenerative marker levels indicate an ongoing neurodegenerative process in ALS. Nonetheless, the progression of ALS cannot be predicted solely based on these markers. The discovery of a specific biomarker could potentially complement existing diagnostic criteria for ALS.