bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating adipokine levels and preeclampsia: A bidirectional Mendelian randomization study
Authors: Chen Xiaoyan , Liu Zhaoming , Cui Jingen , Chen Xiaolan , Xiong Jing , Zhou Wei 
Published: August 2022

Background: Several observational studies have demonstrated that significantly rising circulating adipokine levels are pervasive in preeclampsia or eclampsia disorder (or preeclampsia toxemia (PET)). However, it remains unclear whether this relationship is causal. In this study, we sought to elucidate the causal effects of circulating adipokine levels on PET.Methods: Summary-level data and independent genetic variants strongly associated with common adipokine molecule (adiponectin, leptin, resistin, sOB-R, and PAI-1) levels were drawn from public genome-wide association study (GWASs). Additionally, the corresponding effects between instrumental variables and PET outcomes were acquired from the FinnGen consortium, including 4,743 cases and 136,325 controls of European ancestry. Subsequently, an inverse-variance weighted (IVW) approach was applied for the principal two-sample Mendelian randomization (MR) and multivariable MR (MVMR) analyses. Various complementary sensitivity analyses were then carried out to determine the robustness of our models.Results: The results of the IVW method did not reveal any causal relationship shared across genetically predisposed adipokine levels and PET risk (for adiponectin, OR = 0.86, 95% CI: 0.65–1.13, p = 0.274). Additionally, no significant associations were identified after taking into account five circulating adipokines in MVMR research. Complementary sensitivity analysis also supported no significant associations between them. In the reverse MR analysis, genetically predicted PET risk showed a suggestive association with elevating PAI-1 levels by the IVW method (Beta = 0.120, 95% CI: 0.014, 0.227, p = 0.026). Furthermore, there were no strong correlations between genetic liability to PET and other adipokine levels (p &gt; 0.05).Conclusion: Our MR study did not provide robust evidence supporting the causal role of common circulating adipokine levels in PET, whereas genetically predicted PET may instrumentally affect PAI-1 levels. These findings suggest that PAI-1 may be a useful biomarker for monitoring the diagnosis or therapy of PET rather than a therapeutic target for PET.
Clinical Utility of Medical Exome Sequencing: Expanded Carrier Screening for Patients Seeking Assisted Reproductive Technology in China
Authors: Tong Keya , He Wenbin , He Yao , Li Xiurong , Hu Liang , Hu Hao , Lu Guangxiu , Lin Ge , Dong Chang , Zhang Victor Wei , Du Juan , Liu Dongyun 
Published: August 2022

Purpose: Expanded carrier screening (ECS) is an effective method to identify at-risk couples (ARCs) and avoid birth defects. This study aimed to reveal the carrier spectrum in the Chinese population and to delineate an expanded carrier gene panel suitable in China.Methods: Medical exome sequencing (MES), including 4,158 disease-causing genes, was offered to couples at two reproductive centers. It was initially used as a diagnostic yield for potential patients and then used for ECS. Clinical information and ECS results were retrospectively collected.Results: A total of 2,234 couples, representing 4,468 individuals, underwent MES. In total, 254 individuals showed genetic disease symptoms, and 56 of them were diagnosed with genetic diseases by MES. Overall, 94.5% of them were carriers of at least one disease-causing variant. The most prevalent genes were GJB2 for autosomal recessive disorders and G6PD for X-linked diseases. The ARC rate was 9.80%, and couples were inclined to undergo preimplantation genetic testing when diseases were classified as “profound” or “severe.”Conclusion: This study provided insight to establish a suitable ECS gene panel for the Chinese population. Disease severity significantly influenced reproductive decision-making. The results highlighted the importance of conducting ECS for couples before undergoing assisted reproductive technology.
The differential expression and effects of Drosha on metamorphosis of Japanese flounder (paralichthys olivaceus)
Authors: Zhang Hongmei , Xu Zhaobin , Xu Junxiao , Wei Zhenlin , Shi Zhiyi 
Published: August 2022

Drosha is critical for producing mature microRNAs (miRNAs) from their precursor molecules and small interfering RNAs (siRNAs). Although Drosha has been well characterized in most vertebrate species, identifying the Japanese flounder Drosha has remained elusive. In this study, we cloned the Japanese flounder Drosha gene, which has 4,122 nucleotides (nt), including a 5’-untranslated region (UTR) of 14 nt, a 3’-UTR of 230 nt, and a 3,879 nt open reading frame (ORF) encodes a 1,292 amino acid polypeptide. Then, we analyzed the conservation and phylogenetic evolution of Drosha in some species. Real-time quantitative PCR revealed that Drosha mRNA is highly expressed in the brain, and a lower amount of mRNA was also found in muscle than in other tissues. Drosha plays a vital role in controlling flounder development and metabolism, and its mRNA levels were relatively high at 36 dph (days post-hatching) in the period of metamorphosis and growth of the Japanese flounder. Drosha expression showed in advance with a peak at 23 dph following TH (thyroid hormone) treatment. To further investigate the role of Drosha in metamorphosis, we performed siRNA knockdown of Drosha in flounder embryonic cells (FEC) cells. The result shows that the Drosha-specific siRNA significantly down-regulated Drosha mRNA and miR-1,133,17,214,181a,181b levels, while primary miRNA (pri-miRNA) levels were not significantly different from negative control (NC). These results suggest that Drosha plays a vital role in Japanese flounder development and metamorphosis through processing to produce mature miRNAs, providing essential information for further studying of the part of the Drosha gene in the Japanese flounder development.
A nomogram for predicting 10-year cancer specific survival in patients with pathological T3N0M0 rectal cancer
Authors: Liu Shuang , Yang Shanfei , Yu Haina , Luo Huilong , Chen Gong , Gao Yuanhong , Sun Rui , Xiao Weiwei 
Published: August 2022

BackgroundThe pathological T3N0M0 (pT3N0M0) rectal cancer is the earliest stage and has the best prognosis in the locally advanced rectal cancer, but the optimal treatment remains controversial. A reliable prognostic model is needed to discriminate the high-risk patients from the low-risk patients, and optimize adjuvant chemotherapy (ACT) treatment decisions by predicting the likelihood of ACT benefit for the target population.Patients and methodsWe gathered and analyzed 276 patients in Sun Yat-sen University Cancer Center from March 2005 to December 2011. All patients underwent total mesorectal excision (TME), without preoperative therapy, and were pathologically proven pT3N0M0 rectal cancer with negative circumferential resection margin (CRM). LASSO regression model was used for variable selection and risk factor prediction. Multivariable cox regression was used to develop the predicting model. Optimum cut-off values were determined using X-Tile plot analysis. The 10-fold cross-validation was adopted to validate the model. The performance of the nomogram was evaluated with its calibration, discrimination and clinical usefulness.ResultsA total of 188 patients (68.1%) had ACT and no patients had adjuvant radiotherapy. Age, monocyte percentage, carbohydrate antigen 19–9, lymph node dissection numbers and perineural invasion (PNI) were identified as significantly associated variables that could be combined for an accurate prediction risk of Cancer Specific Survival (CSS) for pT3N0M0 patients. The model adjusted for CSS showed good discrimination with a C-index of 0.723 (95% CI: 0.652–0.794). The calibration curves showed that the nomogram adjusted for CSS was able to predict 3-, 5-, and 10-year CSS accurately. The corresponding predicted probability was used to stratify high and low-risk patients (10-year CSS: 69.1% vs. 90.8%, HR = 3.815, 95%CI: 2.102–6.924, P &lt; 0.0001). ACT improved overall survival (OS) in the low-risk patients (10-year OS: 91.9% vs. 83.3%, HR = 0.338, 95% CI: 0.135–0.848, P &lt; 0.0001), while it did not exhibit a significant benefit in the high-risk patients.ConclusionThe present study showed that age, monocyte percentage, carbohydrate antigen 19–9, lymph node dissection numbers and PNI were independent prognostic factors for pT3N0M0 rectal cancer patients. A nomogram based on these prognostic factors effectively predicts CSS in patients, which can be conveniently used in clinical practice. ACT may improve overall survival in the low-risk patients. But the benefit of ACT was not seen in the high-risk patients.
Effect of exercise intervention on social distance in middle-aged and elderly patients with chronic low back pain
Authors: Weng Lin-Man , Wang Rui , Yang Qi-Hao , Chang Tian-Tian , Wu Cheng-Cheng , Li Wen-Long , Du Shu-Hao , Wang Yu-Chen , Wang Xue-Qiang 
Published: August 2022

BackgroundIncreased social distance is one of the manifestations of social impairment. Chronic low back pain (CLBP) is one of factors associated with increased social distance and social withdrawal. Exercise therapy is an effective means to social impairment. However, whether exercise could reduce social distance in patients with CLBP remains unknown. This study aimed to investigate the effect of exercise on social distance in middle-aged and elderly patients with CLBP.MethodsThe longitudinal intervention recruited 29 middle-aged and elderly patients with CLBP from various communities in Yangpu District, Shanghai, China. The participants received exercise intervention for 8 weeks. The assessments were conducted before and after the intervention, including social distance, pain intensity, unpleasantness of pain, Roland-Morris Questionnaire (RMDQ), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS). Intention to treat analysis was performed.ResultsAfter the 8-week exercise intervention, the social distance of patients with CLBP was shorter than that before intervention and showed significant difference (p &lt; 0.05). The scores of pain intensity, unpleasantness of pain, RMDQ, SAS, and SDS also decreased and were significantly different between pre- and post-intervention (p &lt; 0.05). In addition, the social distance, pain intensity, unpleasantness of pain, RMDQ, SAS, and SDS scores of the moderate CLBP group decreased more after the intervention compared with those of the mild CLBP group.ConclusionThe 8-week exercise intervention cannot only shorten the social distance in middle-aged and elderly patients with CLBP but also relieve pain, disability, and negative emotions.
Diastolic blood pressure predicts enlarged vertebral venous plexus and intracranial pressure in patients with bilateral transverse sinus stenosis
Authors: Li Min , Gao Xiaogang , Liu Fengwei , Sun Jingkun , Xia Ning , Meng Ran , Ji Xunming 
Published: August 2022

BackgroundBilateral transverse sinus stenosis (BTSS) is associated with intracranial hypertension. Enlarged vertebral venous plexus (EVVP) refers to a compensation mechanism against elevated intracranial pressure (ICP) in patients with BTSS. This study aims to investigate the influencing factors of EVVP.MethodsPatients with BTSS were prospectively recruited from the neurology department and neurosurgery department of Xuanwu Hospital Capital Medical University from January 2020 to December 2021.ResultsA total of 37 patients were enrolled with a mean age of 45.42 ± 15.64 years. Women tend to be more susceptible to BTSS. The most common co-morbid disease was hypertension. The most common clinical manifestations were visual disorders, headaches, and tinnitus. BMI and DBP were significantly higher in BTSS patients without EVVP than those with EVVP. Multivariate analysis revealed that diastolic blood pressure (DBP) was negatively correlated with EVVP. In addition, a positive correlation between DBP and the ICP was also observed. A DBP of 81.5 mmHg was calculated as the cutoff value for the presence of EVVP. BTSS patients with DBP ≤ 81.5 mmHg had a higher incidence of EVVP and a lower ICP compared to those with DBP &gt; 81.5 mmHg.ConclusionsDBP was identified as an independent predictor of EVVP. DBP was lower (≤81.5 mmHg) in patients with EVVP and therefore was associated with a lower ICP in patients with BTSS.
Spatiotemporal analysis of regional TIA trends
Authors: Kawai Andrew , Hui Samuel , Beare Richard , Srikanth Velandai K. , Sundararajan Vijaya , Ma Henry , Phan Thanh G. 
Published: August 2022

BackgroundThere has been a decline in the stroke incidence across high income countries but such knowledge exists at Country or State rather than areal unit level such local government area (LGA). In this disease mapping study, we evaluate if there are local hot spots or temporal trends in TIA rate. Such knowledge will be of help in planning healthcare service delivery across regions.MethodsLinked hospital discharge data (Victorian Admitted Episodes Dataset or VAED) was used to collect TIA (defined by ICD-10-AM codes G450-G459) cases from 2001 to 2011. The State of Victoria is the second most populous state in Australia, with a population of 6.7 million and can be divided into 79 administrative units or LGA. The data is anonymized and contains residence of the patient in terms of LGA but not exact location. The date of the TIA event when the patient is admitted to hospital is provided in the dataset. The number of TIAs per year was aggregated for each LGA. Standardized TIA ratios were calculated by dividing actual over expected cases for each LGA per year. We used Integrated Nested Laplace Approximation (INLA) to perform spatial and spatiotemporal regression, adjusting for hypertension, sex and population, age (≥60), and socio-economic status (SES) decile within the LGA. The final model was chosen based on the lowest the Deviance Information Criterion (DIC) and Watanabe-Akaike information criteria (WAIC).ResultsChoropleth maps showed a higher standardized TIA ratios in North-West rural region. Compared to the baseline model (DIC 13,159, WAIC 13,261), adding in a spatial random effect significantly improved the model (DIC 6,463, WAIC 6,667). However, adding a temporal component did not lead to a significant improvement (DIC 6,483, WAIC 6,707).ConclusionOur finding suggests a statically significant spatial component to TIA rate over regional areas but no temporal changes or yearly trends. We propose that such exploratory method should be followed by evaluation of reasons for regional variations and which in turn can identify opportunities in primary prevention of stroke, and stroke care.
Nitrogen balance and outcomes in critically ill patients: A systematic review and meta-analysis
Authors: Zhu Yi-Bing , Yao Yan , Xu Yuan , Huang Hui-Bin 
Published: August 2022

ObjectiveNitrogen balance (NB) is a commonly used nutrition indicator in clinical practice, while its relation to the interpretation of protein malnutrition and outcomes in critically ill patients remains unclear. This study aimed to evaluate the impact of NB on prognosis in such a patient population.MethodsWe searched for relevant studies in PubMed, EMBASE, and the Cochrane Database up to May 10, 2022. Meta-analyses were performed to evaluate the relationship between NB (initial, final, or absolute change of NB levels) and prognosis and important clinical outcomes in critically ill patients. Pooled odds ratios (ORs) and mean differences (MDs) together with their 95% confidence intervals (CIs) were calculated. We also conducted subgroup analyses to explore the sources of heterogeneity.ResultsEight studies with 1,409 patients were eligible. These studies were moderate to high quality. When pooled, the initial NB was comparable between the survival and non-survival groups (five studies, MD 1.20, 95% CI, −0.70 to 3.11, I2 = 77%; P = 0.22), while a significantly higher final NB in the survival group than that in the death group (two studies, MD 3.69, 95% CI, 1.92–5.46, I2 = 55%; P &lt; 0.0001). Two studies provided the absolute change of NB over time and suggested survival patients had more increased NB (MD 4.16 g/day, 95% CI, 3.70–4.61, I2 = 0%; P &lt; 0.00001). Similarly, for studies utilizing multivariate logistic regression, we found an improved NB (four studies, OR 0.85, 95% CI, 0.73–0.99, I2 = 61%; P = 0.04) but not an initial NB (two studies, OR 0.92, 95% CI 0.78–1.08, I2 = 55%; P = 0.31) was significantly associated the risk of all-cause mortality. These results were further confirmed in subgroup analyses. In addition, patients with improved NB had more protein and calorie intake and a similar length of stay in hospital than those without.ConclusionsOur results suggested that an improved NB but not the initial NB level was associated with all-cause mortality in critically ill patients. This highlights the requirement for dynamic monitoring of NB during nutrition treatment. Further randomized clinical trials examining the impact of NB-guided protein intake on clinical outcomes in critically ill patients are warranted.Systematic review registrationINPLASY202250134, https://doi.org/10.37766/inplasy2022.5.0134.
Multimodality imaging in lobular breast cancer: Differences in mammography, ultrasound, and MRI in the assessment of local tumor extent and correlation with molecular characteristics
Authors: Dołęga-Kozierowski Bartosz , Lis Michał , Marszalska-Jacak Hanna , Koziej Mateusz , Celer Marcin , Bandyk Małgorzata , Kasprzak Piotr , Szynglarewicz Bartłomiej , Matkowski Rafał 
Published: August 2022

IntroductionInvasive lobular breast cancer (ILC) is a diagnostic challenge due to the diversity of morphological features. The objective of the study was to investigate the presentation and local extent of ILC using various imaging techniques and to assess the correlation between imaging and molecular profile.Materials and methodsWe reviewed 162 consecutive patients with ILC found on vacuum-assisted biopsy, who underwent evaluation of the lesion morphology and extent using ultrasound (US), mammography (MMG), and magnetic resonance imaging (MRI). Radiographic features were compared with ILC intrinsic subtype based on the expression of Ki-67 and estrogen, progesterone, and HER2 receptors.ResultsA total of 113 mass lesions and 49 non-mass enhancements (NMEs) were found in MRI. Masses were typically irregular and spiculated, showing heterogeneous contrast enhancement, diffusion restriction, and type III enhancement curve. NMEs presented mainly as the area of focal or multiregional distribution with heterogeneous or clumped contrast enhancement, diffusion restriction, and type III enhancement curve. Lesion extent significantly varied between MRI and MMG/ultrasonography (USG) (P &lt; 0.001) but did not differ between MGF and ultrasonography (USG). The larger the ILC, the higher the disproportion when lesion extent in MRI was compared with MMG (P &lt; 0.001) and ultrasonography (USG) (P &lt; 0.001). In the study group, there were 97 cases of luminal A subtype (59.9%), 54 cases of luminal B HER2− (33.3%), nine cases of luminal B HER2+ (5.5%), and two cases of triple negative (1.2%). The HER2 type was not found in the study group. We did not observe any significant correlation between molecular profile and imaging.ConclusionMRI is the most effective technique for the assessment of ILC local extent, which is important for optimal treatment planning. Further studies are needed to investigate if the intrinsic subtype of ILC can be predicted by imaging features on MRI.
Deep learning models for predicting the survival of patients with chondrosarcoma based on a surveillance, epidemiology, and end results analysis
Authors: Yan Lizhao , Gao Nan , Ai Fangxing , Zhao Yingsong , Kang Yu , Chen Jianghai , Weng Yuxiong 
Published: August 2022

BackgroundAccurate prediction of prognosis is critical for therapeutic decisions in chondrosarcoma patients. Several prognostic models have been created utilizing multivariate Cox regression or binary classification-based machine learning approaches to predict the 3- and 5-year survival of patients with chondrosarcoma, but few studies have investigated the results of combining deep learning with time-to-event prediction. Compared with simplifying the prediction as a binary classification problem, modeling the probability of an event as a function of time by combining it with deep learning can provide better accuracy and flexibility.Materials and methodsPatients with the diagnosis of chondrosarcoma between 2000 and 2018 were extracted from the Surveillance, Epidemiology, and End Results (SEER) registry. Three algorithms—two based on neural networks (DeepSurv, neural multi-task logistic regression [NMTLR]) and one on ensemble learning (random survival forest [RSF])—were selected for training. Meanwhile, a multivariate Cox proportional hazards (CoxPH) model was also constructed for comparison. The dataset was randomly divided into training and testing datasets at a ratio of 7:3. Hyperparameter tuning was conducted through a 1000-repeated random search with 5-fold cross-validation on the training dataset. The model performance was assessed using the concordance index (C-index), Brier score, and Integrated Brier Score (IBS). The accuracy of predicting 1-, 3-, 5- and 10-year survival was evaluated using receiver operating characteristic curves (ROC), calibration curves, and the area under the ROC curves (AUC).ResultsA total of 3145 patients were finally enrolled in our study. The mean age at diagnosis was 52 ± 18 years, 1662 of the 3145 patients were male (53%), and mean survival time was 83 ± 67 months. Two deep learning models outperformed the RSF and classical CoxPH models, with the C-index on test datasets achieving values of 0.832 (DeepSurv) and 0.821 (NMTLR). The DeepSurv model produced better accuracy and calibrated survival estimates in predicting 1-, 3- 5- and 10-year survival (AUC:0.895-0.937). We deployed the DeepSurv model as a web application for use in clinical practice; it can be accessed through https://share.streamlit.io/whuh-ml/chondrosarcoma/Predict/app.py.ConclusionsTime-to-event prediction models based on deep learning algorithms are successful in predicting chondrosarcoma prognosis, with DeepSurv producing the best discriminative performance and calibration.
Validation of the Gait Disorientation Test in children with concussion
Authors: Alkathiry Abdulaziz A. , Alsubaie Saud F. , Alsalaheen Bara A. , Whitney Susan L. 
Published: August 2022

BackgroundMild traumatic brain injury (mTBI) or concussion is a complex injury that is difficult to diagnose and assess. There are negative impacts on cognition, balance, and mobility after a concussion. The Gait Disorientation Test (GDT) is an objective measure that assesses a person's balance ability by comparing the walking time with eyes open and the walking time with eyes closed in a standardized walking task. The purpose of this study was to assess the validity and the diagnostic properties of the GDT in children with concussions.MethodsThirty-six children with concussions, and 91 controls aged between 9 and 18 years old participated in the study. Participants completed demographics, the GDT, the Functional Gait Assessment (FGA), the Pediatric Vestibular Symptom Questionnaire (PVSQ), and the Pediatric Visually Induced Dizziness Questionnaire (PVID).ResultsChildren with concussions showed higher (worse) GDT scores (M = 2.18 ± 1.93 s) than healthy controls (M = 1.13 ± 0.95 s), which was statistically significant (P = 0.014).ConclusionThe GDT was able to distinguish between children with concussions and healthy controls. Given the simplicity of the GDT, it can be used to assist in discriminating between children with and without concussion.