Miracle-dz/UniFAR-FTUs huggingface dataset:
Circulation Pathways and Exports of Arctic River Runoff Influenced by Atmospheric Circulation Regimes

River runoff supplies the Arctic Ocean with a large amount of freshwater and land-derived material, so it is important for both the physical and biogeochemical marine environment. In this study, we used wind perturbation simulations to elucidate the response of the circulation pathways and exports of Arctic river runoff to different atmospheric circulation regimes. Specifically, wind perturbations representing the negative and positive phases of the Arctic Oscillation and Beaufort High modes were imposed over the Arctic Ocean separately in different sensitivity experiments. In addition, some combinations of the two modes were also considered in sensitivity experiments. By comparing these experiments with a control simulation, we revealed the impact of different wind perturbations. The atmospheric circulation regimes influence the Arctic surface geostrophic currents through changing the halosteric height, which is associated with the changes in spatial distribution of surface freshwater. The circulation pathways of river runoff, and Pacific and Atlantic derived surface waters are mainly determined by the surface geostrophic currents. The positive (negative) Arctic Oscillation reduces (increases) freshwater storage and sea surface height in the Makarov and Eurasian basins, thus strengthening (weakening) the cyclonic circulation and weakening (strengthening) the anticyclonic circulation; Accordingly, the Eurasian runoff leaves the Siberian shelf at more eastern (western) locations, and has an enhanced export through the Fram Strait (Canadian Arctic Archipelago). The positive (negative) Beaufort High increases (reduces) freshwater storage and sea surface height in the Amerasian Basin, thus strengthening (weakening) the anticyclonic circulation; Accordingly, the Eurasian runoff export through the Fram Strait and the Mackenzie River runoff export through the Canadian Arctic Archipelago are reduced (increased). The positive Arctic Oscillation increases freshwater available to the Beaufort Gyre, which can be efficiently accumulated there in the presence of a positive Beaufort High forcing. The impact of the Beaufort High mode on the location of the Transpolar Drift Stream and runoff circulation pathways is stronger with a positive Arctic Oscillation than with a neutral Arctic Oscillation state. Our results also showed that Eurasian runoff can only have a relatively small contribution to freshwater accumulation in the Beaufort Gyre region.
The Effects of Repetitive Use and Pathological Remodeling on Channelrhodopsin Function in Cardiomyocytes

Aim: Channelrhodopsins (ChRs) are a large family of light-gated ion channels with distinct properties, which is of great importance in the selection of a ChR variant for a given application. However, data to guide such selection for cardiac optogenetic applications are lacking. Therefore, we investigated the functioning of different ChR variants in normal and pathological hypertrophic cardiomyocytes subjected to various illumination protocols. Methods and Results: Isolated neonatal rat ventricular cardiomyocytes (NRVMs) were transduced with lentiviral vectors to express one of the following ChR variants: H134R, CatCh, ReaChR, or GtACR1. NRVMs were treated with phenylephrine (PE) to induce pathological hypertrophy (PE group) or left untreated [control (CTL) group]. In these groups, ChR currents displayed unique and significantly different properties for each ChR variant on activation by a single 1-s light pulse (1 mW/mm2: 470, 565, or 617 nm). The concomitant membrane potential (Vm) responses also showed a ChR variant-specific profile, with GtACR1 causing a slight increase in average Vm during illumination (Vplateau: −38 mV) as compared with a Vplateau > −20 mV for the other ChR variants. On repetitive activation at increasing frequencies (10-ms pulses at 1–10 Hz for 30 s), peak currents, which are important for cardiac pacing, decreased with increasing activation frequencies by 17–78% (p < 0.05), while plateau currents, which are critical for arrhythmia termination, decreased by 10–75% (p < 0.05), both in a variant-specific manner. In contrast, the corresponding Vplateau remained largely stable. Importantly, current properties and Vm responses were not statistically different between the PE and CTL groups, irrespective of the variant used (p > 0.05). Conclusion: Our data show that ChR variants function equally well in cell culture models of healthy and pathologically hypertrophic myocardium but show strong, variant-specific use-dependence. This use-dependent nature of ChR function should be taken into account during the design of cardiac optogenetic studies and the interpretation of the experimental findings thereof.
Incidence and Risk Factors of Postpartum Hemorrhage in China: A Multicenter Retrospective Study

Background: Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality worldwide but the incidence and its risk factors in China is limited. The objective of this study is to investigate the incidence and the risk factors of PPH in Chinese women. Methods: A multi-center retrospective study of pregnant women at ≥28 weeks of gestation was conducted. Logistic regression was used to identify potential risk factors of PPH and receiver operating characteristic curve was used to evaluate the predictive performance of the identified risk factors. Subgroup analysis focusing on the number of fetus and the mode of delivery was conducted. Results: A total of 99,253 pregnant women were enrolled and 804 (0.81%) experienced PPH. The subgroup analysis revealed that the incidence of PPH was 0.75, 2.65, 1.40, and 0.31% in singletons, twin pregnancies, cesarean sections, and vaginal deliveries, respectively. Placenta previa and placenta accreta were the predominant risk factors of PPH in the overall population and all subgroups. A twin pregnancy was a risk factor for PPH regardless of the mode of delivery. Obesity, and multiparity were risk factors for PPH in both singletons and cesarean section cases, but the latter predicted a reduced probability of PPH in vaginal deliveries. Macrosomia was associated with increased risk of PPH in singletons or vaginal deliveries. In women who delivered vaginally, preeclampsia was associated with a higher risk of PPH. The areas under the curve for the overall cohort, singletons, twin pregnancies, cesarean section cases, and vaginal deliveries were 0.832 (95% confidence interval [CI] 0.813–0.851), 0.824 (95% CI 0.803–0.845), 0.686 (95% CI 0.617–0.755), 0.854 (95% CI 0.834–0.874), and 0.690 (95% CI 0.646–0.735), respectively. Conclusions: The risk factors of PPH varied slightly based on the number of fetuses and the mode of delivery, while placenta previa and placenta accreta were the two major risk factors. A combination of the identified risk factors yielded a satisfactory predictive performance in determining PPH in the overall cohort, singletons pregnancies, and women who delivered by cesarean section, whereas the performance was moderate in twin pregnancies and in women delivering vaginally.
Central Venous Disease Increases the Risk of Microbial Colonization in Hemodialysis Catheters

Objectives: Tunneled-cuffed catheters (TCCs) are widely used in maintenance hemodialysis patients. However, microbial colonization in catheters increases the likelihood of developing various complications, such as catheter-related infection (CRI), catheter failure, hospitalization, and death. Identification of the risk factors related to microorganism colonization may help us reduce the incidence of these adverse events. Therefore, a retrospective analysis of patients who underwent TCC removal was conducted. Methods: From a pool of 389 adult patients, 145 were selected for inclusion in the study. None of the patients met the diagnostic criteria for CRI within 30 days before recruitment. The right internal jugular vein was the unique route evaluated. The catheter removal procedure was guided by digital subtraction angiography. Catheter tips were collected for culture. Biochemical and clinical parameters were collected at the time of catheter removal. Results: The average age of this cohort was 55.46 ± 17.25 years. A total of 45/145 (31.03%) patients were verified to have a positive catheter culture. The proportions of gram-positive bacteria, gram-negative bacteria, and fungi were 57.8, 28.9, and 13.3%, respectively. History of CRI [odds ratio (OR) = 2.44, 95% confidence interval (CI) 1.09 to 5.49], fibrin sheath (OR = 2.93, 95% CI 1.39–6.19), white blood cell (WBC) count ≥5.9 × 109/l (OR = 2.31, 95% CI 1.12–4.77), moderate (OR = 4.87, 95% CI 1.61–14.78) or severe central venous stenosis (CVS) (OR = 4.74, 95% CI 1.16–19.38), and central venous thrombosis (CVT) (OR = 3.41, 95% CI 1.51–7.69) were associated with a significantly increased incidence of microbial colonization in a univariate analysis. Central venous disease (CVD) elevated the risk of microbial colonization, with an OR of 3.37 (1.47–7.71, P = 0.004). A multivariate analysis showed that both CVS and CVT were strongly associated with catheter microbial colonization, with ORs of 3.06 (1.20–7.78, P = 0.019) and 4.13 (1.21–14.05, P = 0.023), respectively. As the extent of stenosis increased, the relative risk of catheter microbial colonization also increased. In patients with moderate and severe stenosis, a sustained and significant increase in OR from 5.13 to 5.77 was observed. Conclusions: An elevated WBC count and CVD can put hemodialysis patients with TCCs at a higher risk of microbial colonization, even if these patients do not have the relevant symptoms of infection. Avoiding indwelling catheters is still the primary method for preventing CRI.
Lipid Accumulation Product Combined With Urine Glucose Excretion Improves the Efficiency of Diabetes Screening in Chinese Adults

Background To compare the efficacy of lipid accumulation product (LAP) and urine glucose excretion (UGE) in predicting diabetes and evaluate whether the combination of LAP and UGE would help to improve the efficacy of using LAP alone or UGE alone in identifying diabetes. Methods Data from 7485 individuals without prior history of diabetes who participated in a cross-sectional survey in Jiangsu, China, were analyzed. Each participant underwent an oral glucose-tolerance test. Operating characteristic curves (ROC) and logistic regression analyses were used to evaluate the performance of LAP and UGE in identification of newly diagnosed diabetes (NDM) and prediabetes (PDM). Results For subjects with NDM, the area under the ROC curve was 0.72 for LAP and 0.85 for UGE, whereas for PDM, these values were 0.62 and 0.61, respectively. Furthermore, LAP exhibited a comparable sensitivity with UGE in detecting NDM (76.4% vs 76.2%, p = 0.31). In predicting PDM, LAP showed a higher sensitivity than UGE (66.4% vs 42.8%, p < 0.05). The combination of LAP and UGE demonstrated a significantly higher sensitivity than that of LAP alone and UGE alone for identification of NDM (93.6%) and PDM (80.1%). Moreover, individuals with both high LAP and high UGE had significantly increased risk of NDM and PDM than those with both low LAP and low UGE. Conclusions The combination of LAP and UGE substantially improved the efficacy of using LAP and using UGE alone in detecting diabetes, and may be a novel approach for mass screening in the general population.
Glutamatergic Neurotransmission Controls the Functional Lateralization of the mPFC in the Modulation of Anxiety Induced by Social Defeat Stress in Male Mice

The rodent medial prefrontal cortex (mPFC) is anatomically divided into cingulate (Cg1), prelimbic (PrL), and infralimbic (IL) subareas. The left and right mPFC (L and RmPFC) process emotional responses induced by stress-related stimuli, and LmPFC and RmPFC inhibition elicit anxiogenesis and anxiolysis, respectively. Here we sought to investigate (i) the mPFC functional laterality on social avoidance/anxiogenic-like behaviors in male mice subjected to chronic social defeat stress (SDS), (ii) the effects of left prelimbic (PrL) inhibition (with local injection of CoCl2) on the RmPFC glutamatergic neuronal activation pattern (immunofluorescence assay), and (iii) the effects of the dorsal right mPFC (Cg1 + PrL) NMDA receptor blockade (with local injection of AP7) on the anxiety induced by left dorsal mPFC inhibition in mice exposed to the elevated plus maze (EPM). Results showed that chronic SDS induced anxiogenic-like behaviors followed by the rise of ΔFosB labeling and by ΔFosB + CaMKII double-labeling bilaterally in the Cg1 and IL subareas of the mPFC. Chronic SDS also increased ΔFosB and by ΔFosB + CaMKII labeling only on the right PrL. Also, the left PrL inhibition increased cFos + CaMKII labeling in the contralateral PrL and IL. Moreover, anxiogenesis induced by the left PrL inhibition was blocked by NMDA receptor antagonist AP7 injected into the right PrL. These findings suggest the lateralized control of the glutamatergic neurotransmission in the modulation of emotional-like responses in mice subjected to chronic SDS.
Cost-Effectiveness Analysis of Nivolumab Plus Ipilimumab for Advanced Non-Small-Cell Lung Cancer

Objective: This study evaluated the cost-effectiveness of nivolumab plus ipilimumab vs. chemotherapy in the first-line setting for patients with advanced non-small-cell lung cancer (NSCLC) from the US payer perspective. Materials and methods: A Markov model wasdeveloped to evaluate the cost and effectiveness of nivolumab plus ipilimumab vs. chemotherapy in the first-line treatment of advanced NSCLC. The survival benefits of nivolumab plus ipilimumab were based on the results of the CheckMate 227 trial. The main endpoints of the model were cost, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER). Univariable and probabilistic sensitivity analyses were conducted to assess model uncertainty. Additonal subgroup analyses were also performed. Results: nivolumab plus ipilimumab produced a gain of 0.62 QALYs, at a cost of $104238 per QALY. The variables that had the greatest influence on the ICER were body weight and overall survival (OS) hazard ratio (HR). The probability of nivolumab plus ipilimumab being cost-effectiveness compared to chemotherapy is 50.7 and 66.2% when the willingness-to-pay (WTP) value is $ 100,000 and $ 150,000 per QALY. The results of subgroup analyses showed the ICER remained below $150,000/QALY regardless of the PD-L1 expression level. Conclusions: nivolumab plus ipilimumab was estimated to be cost-effective compared with chemotherapy for patients with advanced NSCLC at a WTP threshold from 100,000/QALY to 150,000/QALY.
Brain Function Network: Higher Order vs. More Discrimination

Brain functional network (BFN) has become an increasingly important tool to explore individual differences and identify neurological/mental diseases. For estimating a “good” BFN (with more discriminative information for example), researchers have developed various methods, in which the most popular and simplest is Pearson's correlation (PC). Despite its empirical effectiveness, PC only encodes the low-order (second-order) statistics between brain regions. To model high-order statistics, researchers recently proposed to estimate BFN by conducting two sequential PCs (denoted as PC2 in this paper), and found that PC2-based BFN can provide additional information for group difference analysis. This inspires us to think about (1) what will happen if continuing the correlation operation to construct much higher-order BFN by PCn (n>2), and (2) whether the higher-order correlation will result in stronger discriminative ability. To answer these questions, we use PCn-based BFNs to predict individual differences (Female vs. Male) as well as identify subjects with mild cognitive impairment (MCI) from healthy controls (HCs). Through experiments, we have the following findings: (1) with the increase of n, the discriminative ability of PCn-based BFNs tends to decrease; (2) fusing the PCn-based BFNs (n>1) with the PC1-based BFN can generally improve the sensitivity for MCI identification, but fail to help the classification accuracy. In addition, we empirically find that the sequence of BFN adjacency matrices estimated by PCn (n = 1,2,3,⋯ ) will converge to a binary matrix with elements of ± 1.
Development and Validation of a Prediction Model for Elevated Arterial Stiffness in Chinese Patients With Diabetes Using Machine Learning

Background Arterial stiffness assessed by pulse wave velocity is a major risk factor for cardiovascular diseases. The incidence of cardiovascular events remains high in diabetics. However, a clinical prediction model for elevated arterial stiffness using machine learning to identify subjects consequently at higher risk remains to be developed. Methods Least absolute shrinkage and selection operator and support vector machine-recursive feature elimination were used for feature selection. Four machine learning algorithms were used to construct a prediction model, and their performance was compared based on the area under the receiver operating characteristic curve metric in a discovery dataset (n = 760). The model with the best performance was selected and validated in an independent dataset (n = 912) from the Dryad Digital Repository (https://doi.org/10.5061/dryad.m484p). To apply our model to clinical practice, we built a free and user-friendly web online tool. Results The predictive model includes the predictors: age, systolic blood pressure, diastolic blood pressure, and body mass index. In the discovery cohort, the gradient boosting-based model outperformed other methods in the elevated arterial stiffness prediction. In the validation cohort, the gradient boosting model showed a good discrimination capacity. A cutoff value of 0.46 for the elevated arterial stiffness risk score in the gradient boosting model resulted in a good specificity (0.813 in the discovery data and 0.761 in the validation data) and sensitivity (0.875 and 0.738, respectively) trade-off points. Conclusion The gradient boosting-based prediction system presents a good classification in elevated arterial stiffness prediction. The web online tool makes our gradient boosting-based model easily accessible for further clinical studies and utilization.
Dl-3-n-Butylphthalide Ameliorates Diabetic Nephropathy by Ameliorating Excessive Fibrosis and Podocyte Apoptosis

Diabetic nephropathy (DN) is a common diabetes associated complication. Thus, it is important to understand the pathological mechanism of DN and find the appropriate therapeutic strategy for it. Dl-3-n-Butylphthalide (DL-NBP) has anti-inflammatory and antioxidant effects, and been widely used for the treatment of stroke and cardiovascular diseases. In this study, we selected three different doses (20, 60, and 120 mg⋅kg−1 d−1) of DL-NBP and attempted to elucidate its role and molecular mechanism underlying DN. We found that DL-NBP, especially at the dose of 60 or 120 mg⋅kg−1 d−1, could significantly ameliorate diabetes-induced elevated blood urea nitrogen (BUN) and creatinine level, and alleviate renal fibrosis. Additionally, the elevated expressions of collagen and α-smooth muscle actin (α-SMA) in the kidney from db/db mice were found to be significantly suppressed after DL-NBP treatment. Furthermore, mechanistic studies revealed that DL-NBP inhibits pro-inflammatory cytokine levels, thereby ameliorating the development of renal fibrosis. Moreover, we found that DL-NBP could not only reduce the endoplasmic reticulum stress (ERS), but also suppress activation of the renin-angiotensin system to inhibit vascular endothelial growth factor (VEGF) level, which subsequently reduces the podocyte apoptosis in kidney of db/db mice. In a word, our findings suggest that DL-NBP may be a potential therapeutic drug in the treatment of DN.
A Review of the Clinician’s Role in Women’s Weight Management and Implications for Women’s Health and Pregnancy Outcomes

Importance Ten years have passed since the Institute of Medicine (IOM) released its recommendations for gestational weight gain (GWG), based on a woman's prepregnancy body mass index. Despite this, the majority of women do not gain the appropriate gestational weight; most women gain too much weight, and a small but substantial number gain too little. Objectives We review the literature concerning GWG, the opinions and practices of clinicians in managing their patients' weight, and how these practices are perceived by patients. We also review several randomized control trials that investigate the efficacy of clinical intervention in managing GWG. Evidence Acquisition A literature review search was conducted with no limitations on the number of years searched. Results The number of clinicians who are aware of and use the IOM recommendations has increased, but the prevalence of inappropriate GWG has not decreased. Clinicians report feeling less than confident in their ability to have an impact on their patients' weight gain, and there are discrepancies between what clinicians and patients report regarding counseling. Many randomized control trials demonstrate a beneficial impact of clinical intervention, highlighting the importance of collaboration and technology to provide educational information and support throughout a pregnancy. Conclusions Pregnancy provides an opportunity for clinicians to have open and direct conversations with their patients about their weight. Providing clinicians with the tools, skillset, and confidence to assist in the management of GWG is essential to the health of women and their children, and warrants further investigation. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives After completing this review, clinicians should be better able to identify risk factors of inappropriate GWG and associated complications; summarize current literature on how both clinicians and patients perceive GWG; explain how to assess appropriate GWG on an individual basis based on IOM recommendations; and describe methods to help women achieve appropriate GWG.