Miracle-dz/UniFAR-FTUs huggingface dataset:
The longitudinal association of smoking behaviors with obesity risk among Chinese adults from the China Health and Nutrition Survey 1991–2015

Background Present study aims to longitudinal explore independent association of smoking status and cigarette consumption with general obesity and abdominal among Chinese adults by gender. Methods This study include 75,348 adults (35,907 males and 39,441 females) aged 18-65 years from the longitudinal data of China Health and Nutrition Survey (CHNS, 1991-2015). Multilevel mixed-effects linear and logistic regression models were performed for association analysis. Results Among males and females, heavy smokers (> 25 cigarette/d) increased from 5.5% and 0.05% in 1991 to 6.8% and 0.1% in 2015, respectively ( p < 0.001). After controlling for confounding factors, the net effect on male light (1–14 cigarette/d), moderate (15–24 cigarette/d), and heavy smokers was a significant decrease of 0.40 kg/m 2 (β: −0.40, 95% CI: − 0.48, −0.31), 0.51 kg/m 2 (β: −0.51, 95% CI: −0.60, −0.43), and 0.29 kg/m 2 (β: −0.29, 95% CI: −0.43, −0.14) in BMI, respectively. From moderate and light smokers to nonsmokers were linked with significant WC decreases of 0.87 cm (β: −0.87, 95% CI: −1.14, −0.58) and 0.86 cm (β: −0.87, 95% CI: −1.12, −0.59) in males and 1.58 cm (β: −1.58, 95% CI: −2.94, −0.22) and 1.37 cm (β: −1.37, 95% CI: −2.13, −0.59) in females, respectively. The odds ratio (95% CIs) for general obesity in males were 0.72 (0.65–0.81) for light smokers and 0.68 (0.61–0.76) for moderate smokers compared with nonsmokers. Similarly, the odds ratio (95% CIs) for abdominal obesity in males were 0.80 (0.76–0.86) for light smokers and 0.81 (0.76–0.87) for moderate smokers compared with nonsmokers. Moreover, the odds ratio (95% CIs) for abdominal obesity in females were 0.83 (0.71–0.98) for light smokers and 0.73 (0.58–0.91) for moderate smokers compared with nonsmokers.Conclusions Compared with nonsmokers, current smokers had lower BMI and WC among Chinese adults regardless of gender. Heavy smokers are more likely to be general obesity and abdominal obesity in male and abdominal obesity in female than other smokers. These findings may improve the understanding on how smoking behaviors affect fat distribution and provide scientific evidence regarding intervention in smoking and obesity by gender.
Quasi-analytical solutions of a turbulence-modeling equation on the robustness of decaying homogeneous turbulence

The present study introduces third-order quasi-analytical solutions of a turbulence-modeling equation, where the standard k − ϵ model equation is used because this model is commonly and widely used in engineering applications. These quasi-analytical solutions describe the robustness of decaying homogeneous turbulence. In the present study, decaying homogeneous turbulence influenced by a weak fluid acceleration of mean flow, which is equivalent to the small strain of the mean flow, is considered. Here, the small strain of the mean flow only slightly affects the anisotropy of the decaying homogeneous turbulence, as shown in previous experiments. Simplified governing equations are derived from the governing equations of the turbulence modeling by introducing the conditions of the small strain. Here, two nondimensional functions are introduced in order to describe the influence on the turbulent kinetic energy and its dissipation using decay laws of the turbulent kinetic energy and its dissipation. Three constants included in the quasi-analytical solutions could be obtained using observable parameters.
Stationary wavelet singular entropy based electronic tongue for classification of milk

Electronic tongue mimics human gustatory sensation and is used to characterize and discriminate beverages and foods. Feature extraction plays a key role in improving the classification accuracy by preserving the distinct characteristics while reducing high dimensionality of data generated from electronic tongue. This paper presents a new feature extraction method based on stationary wavelet singular entropy for a developed electronic tongue system to classify pasteurized cow milk. The electronic tongue consists of an array of five working electrodes along with a reference and a counter electrode to characterize milk sample. The feature extraction of acquired data is done by computing stationary wavelet transform to obtain detail and approximate coefficients at different level of decomposition. These coefficients are processed using singular value decomposition followed by calculation of entropy to obtain stationary wavelet singular entropy values. These values form the feature set and feed to two classifiers, k-nearest neighbor and back propagation artificial neural network, and their classification accuracy is evaluated with variation in their model parameters. The proposed method is compared with other wavelet transform-entropy methods in terms of classification accuracy, which indicates that the proposed method is more effective in discriminating milk samples.
Roles of Akt and ERK in mTOR-Dependent Antidepressant Effects of Vanillic Acid

Vanillic acid, an oxidized form of vanilla, is a flavoring agent with a creamy odor. Several studies have reported the neuroprotective effects of vanillic acid, which are predominantly associated with anti-inflammatory and antioxidative properties. The anti-inflammatory and antioxidative properties may result from Akt or ERK signaling activation. The activation of the mammalian target of rapamycin (mTOR), a key downstream target of Akt and ERK signaling, is a crucial therapeutic target for treating depression. However, the antidepressant effects of vanillic acid remain unknown. The present study applied the forced swim test (FST) to investigate the antidepressant effects of vanillic acid and its association with Akt, ERK, and mTOR signaling and upstream α-amino-3-hydroxy-5-methyl-4-isoxazolepropionaic acid receptor (AMPAR) in the prefrontal cortex (PFC) of mice. Vanillic acid demonstrated antidepressant effects by significantly reducing behavioral despair in the FST. None of the treatments changed locomotor activity. Additionally, vanillic acid increased AMPAR throughput, Akt, and mTOR signaling but not ERK signaling in the PFC. NBQX (an AMPAR blocker), MK 2206 (an Akt blocker), and rapamycin (an mTOR blocker) used in pretreatment attenuated the antidepressant effects of vanillic acid, but SL327 (an ERK inhibitor) did not. The immunochemical results indicated that the antidepressant effects of vanillic acid depend on the AMPAR–Akt–mTOR signaling transduction pathway. Our findings reveal an Akt-dependent, but ERK-independent, the mechanism underlying the antidepressant effects of vanillic acid, which may be beneficial for some patients with depression.
Comparison of Functional and Radiological Outcomes of Tears Involving the Subscapularis: Isolated Subscapularis Versus Combined Anterosuperior Rotator Cuff Tears

Background: Few studies have compared the clinical and radiological characteristics and outcomes in isolated subscapularis (SSC) and combined anterosuperior (AS) rotator cuff tears (RCTs). Furthermore, risk factors for retear after SSC repair and the effect of preoperative fatty degeneration require further evaluation. Purpose: To compare the functional and radiological outcomes of isolated SSC with combined AS RCTs after arthroscopic repair and to determine the risk factors for SSC retear in these 2 groups. Study Design: Cohort study; Level of evidence, 3. Methods: Data from 30 patients in the isolated SSC group were compared with data from 110 patients in the combined AS group. All patients underwent primary arthroscopic rotator cuff repair between 2010 and 2016. Clinical outcomes were assessed through use of the visual analog scale for pain, American Shoulder and Elbow Surgeons score, and Simple Shoulder Test at a mean follow-up of 26.7 months (range, 24-96 months). SSC tendon integrity was examined via magnetic resonance imaging, computed tomography arthrogram, or ultrasonography at least 1 year after surgery. Results: The isolated SSC group had a greater proportion of males and the patients were younger compared with the combined AS group (both P < .050). The incidence of trauma was high but not significantly different between groups (56.7% vs 40.9%; P = .180). Clinical outcome measures and radiological outcomes in terms of retear were not statistically different between both groups (16.7% vs 8/5%; P = .337). The optimal cutoff values for the risk of SSC tendon retear in both groups were 19-mm retraction and 16-mm superoinferior dimension (P = .048). Unfavorable preoperative fatty degeneration of the SSC muscle (grades 3 and 4) was a significant risk factor for retear (odds ratio, 9.8; P < .001). Conclusion: Isolated SSC and combined AS RCTs were comparable except for patient age and sex; both had a high incidence of traumatic history. The current data suggest that the risk factors for retear after SSC repair in RCTs involving the SSC were tear size greater than 19 mm of retraction and unfavorable fatty degeneration (grade 3 or higher) of the SSC muscle.
T-cells with a single tumor antigen-specific T-cell receptor can be generated in vitro from clinically relevant stem cell sources

ABSTRACT Chimeric antigen receptor (CAR) T-cells have shown great promise in the treatment of B-cell malignancies. For acute myeloid leukemia (AML), however, the optimal target surface antigen has yet to be discovered. Alternatively, T-cell receptor (TCR)-redirected T-cells target intracellular antigens, marking a broader territory of available target antigens. Currently, adoptive TCR T-cell therapy uses peripheral blood lymphocytes for the introduction of a transgenic TCR. However, this can cause graft-versus-host disease, due to mispairing of introduced and endogenous TCR chains. Therefore, we started from hematopoietic stem and progenitor cells (HSPC), that do not express a TCR yet, isolated from healthy donors, patients in remission after chemotherapy and AML patients at diagnosis. Using the OP9-DL1 in vitro co-culture system and agonist selection, TCR-transduced HSPC develop into mature tumor antigen-specific T-cells with only one TCR. We show here that this approach is feasible with adult HSPC from clinically relevant sources, albeit with slower maturation and lower cell yield compared to cord blood HSPC. Moreover, cryopreservation of HSPC does not have an effect on cell numbers or functionality of the generated T-cells. In conclusion, we show here that it is feasible to generate TA-specific T-cells from HSPC from adult healthy donors and patients and we believe these T-cells could be of use as a very valuable form of patient-tailored T-cell immunotherapy.
Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Titration Study of Methylphenidate Hydrochloride Extended-Release Capsules (Aptensio XR) in Preschool Children with Attention-Deficit/Hyperactivity Disorder

Objectives: To assess the efficacy and safety of a methylphenidate hydrochloride extended-release capsule (MPH-MLR) formulation in treating attention-deficit/hyperactivity disorder (ADHD) in preschool children. Methods: Children aged 4 to <6 years with qualifying ADHD Rating Scale Fourth Edition (ADHD-RS-IV) Preschool Version scores (≥90th percentile for age/gender) participated in four behavior management training (BMT) sessions or immediately entered (based on investigator assessment of symptom severity or previous participation) into a 6-week, open-label, flexible MPH-MLR dose optimization phase. After BMT, children with <30% improvement in ADHD-RS-IV score and ≥3 score on the Clinical Global Impression—Improvement (CGI-I) scale also entered the open-label period. All children began the open-label period with MPH-MLR 10 mg once daily; weekly adjustments permitted once-daily maximum of up to 40 mg. Children with ≥30% improvement in ADHD-RS-IV total score and a CGI-I score of 1–2 at open-label completion were randomized to their optimized dose of MPH-MLR or placebo for 2 weeks (double blind [DB]). Safety measures included adverse events (AEs), vital signs, and electrocardiograms. Results: Open-label enrollment was 119 children. Mean (SD) ADHD-RS-IV total scores at open-label start and open-label end was 40.8 (10.4) and 19.5 (11.1), respectively. Ninety children were enrolled in the DB phase. Mean (SD) ADHD-RS-IV total scores for the MPH-MLR and placebo group were similar at DB beginning and was 25.8 (14.6) and 34.9 (14.1), respectively, at DB end. Mean change from baseline in ADHD-RS-IV total score during DB was significantly greater in children randomized to placebo compared with MPH-MLR; least squares mean change difference from baseline was −11.2, p = 0.002. During open-label dosing, the most common AEs (≥10%) were decreased appetite, decreased weight, insomnia, hypertension, emotional disorder, and affect lability. Conclusion: Results demonstrate MPH-MLR efficacy in preschool children and a safety profile consistent with known AEs of methylphenidate when used for ADHD.
EMT-related gene expression is positively correlated with immunity and may be derived from stromal cells in osteosarcoma

Background Osteosarcoma is the most common type of bone cancer in children and young adults. Recent studies have shown a correlation between epithelial–mesenchymal transition (EMT)-related gene expression and immunity in human cancers. Here, we investigated the relationship among EMT, immune activity, stromal activity and tumor purity in osteosarcoma. Methods We defined EMT gene signatures and evaluated immune activity and stromal activity based on the gene expression and clinical data from three independent microarray datasets. These factors were evaluated by single sample Gene Set Enrichment Analyses and the ESTIMATE tool. Finally, we analyzed the key source of EMT gene expression in osteosarcoma using microarray datasets from the Gene Expression Omnibus and human samples that we collected. Results EMT-related gene expression was positively correlated with immune and stromal activity in osteosarcoma. Tumor purity was negatively correlated with EMT, immune activity and stromal cells. We further demonstrated that high EMT gene expression could significantly predict poor overall survival (OS) and recurrence-free survival (RFS) in osteosarcoma patients, while high immune activity cannot. However, combining these factors could have further prognostic value for osteosarcoma patients in terms of OS and RFS. Finally, we found that stromal cells may serve as a key source of EMT gene expression in osteosarcoma. Conclusion The results of this study reveal that the expression of EMT genes and immunity are positively correlated, but these signatures convey disparate prognostic information. Furthermore, the results indicate that EMT-related gene expression may be derived from stromal rather than epithelial cancer cells.
Expression of TIM3/VISTA checkpoints and the CD68 macrophage-associated marker correlates with anti-PD1/PDL1 resistance: implications of immunogram heterogeneity

ABSTRACT Although immunotherapies have achieved remarkable salutary effects among subgroups of advanced cancers, most patients do not respond. We comprehensively evaluated biomarkers associated with the “cancer-immunity cycle” in the pan-cancer setting in order to understand the immune landscape of metastatic malignancies as well as anti-PD-1/PD-L1 inhibitor resistance mechanisms. Interrogation of 51 markers of the cancer-immunity cycle was performed in 101 patients with diverse malignancies using a clinical-grade RNA sequencing assay. Overall, the immune phenotypes demonstrated overexpression of multiple checkpoints including VISTA (15.8% of 101 patients), PD-L2 (10.9%), TIM3 (9.9%), LAG3 (8.9%), PD-L1 (6.9%) and CTLA4 (3.0%). Additionally, aberrant expression of macrophage-associated markers (e.g. CD68 and CSF1R; 11-23%), metabolic immune escape markers (e.g. ADORA2A and IDO1; 9-16%) and T-cell priming markers (e.g. CD40, GITR, ICOS and OX40; 4-31%) were observed. Most tumors (87.1%, 88/101) expressed distinct immune portfolios, with a median of six theoretically actionable biomarkers (pharmacologically tractable by Food and Drug Administration approved agents [on- or off-label] or with agents in clinical development). Overexpression of TIM-3, VISTA and CD68 were significantly associated with shorter progression-free survival (PFS) after anti-PD-1/PD-L1-based therapies (among 39 treated patients) (all P < .01). In conclusion, cancer-immunity cycle biomarker evaluation was feasible in diverse solid tumors. High expression of alternative checkpoints TIM-3 and VISTA and of the macrophage-associated markers CD68 were associated with significantly worse PFS after anti-PD-1/PD-L1-based therapies. Most patients had distinct and complex immune expression profiles suggesting the need for customized combinations of immunotherapy.
Multidimensional evaluation of the TRMM 3B43V7 satellite-based precipitation product in mainland China from 1998–2016

This study evaluates the applicability of the Tropical Rain Measurement Mission (TRMM) 3B43V7 product for use throughout mainland China. Four statistical metrics were used based on the observations made by rain gauges; these metrics were the correlation coefficient (R), the relative bias (RB), the root mean square error (RMSE) and Nash-Sutcliffe efficiency (NSE), and they were chosen to evaluate the performance of the 3B43V7 product at temporal and spatial scales. The results revealed that 3B43V7 performed satisfactorily on all timescales (R > 0.9 and NSE > 0.86); however, it overestimated the results when compared with the rain gauge observations in certain circumstances (RB = 9.7%). Monthly estimates from 3B43V7 were in agreement with rain gauge observations. 3B43V7 can effectively capture the seasonal patterns of precipitation characteristics over mainland China. However, 3B43V7 tends to register a greater overestimation of precipitation in the winter (RB = 14%) than in other seasons while showing greater consistency with the observations made by rain gauges during dry periods. The 3B43V7 product performs well in the eastern part of mainland China, while its performance is poor in the western part of mainland China. In terms of altitude, 3B43V7 performs satisfactorily in areas with moderate to low altitudes (when altitude < 3,500 m, R > 0.9, NSE > 0.8 and RB < 10.2%) but RB values increase with altitude. Overall, 3B43V7 had a favorable performance throughout mainland China.
Upregulated expression of pyruvate kinase M2 mRNA predicts poor prognosis in lung adenocarcinoma

Background Pyruvate kinase M2 (PKM2) is critical regulator contributing to Warburg effect. However, the expression pattern and prognostic value of PKM2 remain unknown in lung adenocarcinoma (LUAD). The aim of this study is to clarify the prognostic value of PKM2 via intergrated bioinformatics analysis. Methods Firstly, mRNA expression levels of PKM2 in LUAD were systematically analyzed using the ONCOMINE and TCGA databases. Then, the association between PKM2 expression and clinical parameters was investigated by UALCAN. The Kaplan–Meier Plotter was used to assess the prognostic significance of PKM2. Finally, the relationship between PKM2 expression and its genetic and epigenetic changes was evaluated with MEXPRESS and MethHC database. Results Pooled analysis showed that PKM2 is frequently upregulated expression in LUAD. Subsequently, PKM2 expression was identified to be positively associated with tumor stage and lymph node metastasis and also strongly correlated with worse OS (P = 2.80e−14), PPS (P = 0.022), FP (P = 1.30e−6) and RFS (P = 3.41e−8). Importantly, our results demonstrated that over-expressed PKM2 is associated with PKM2 hypomethylation and copy number variations (CNVs). Conclusion This study confirms that over-expressed PKM2 in LUAD is associated with poor prognosis, suggesting that PKM2 might act as a promising prognostic biomarker and novel therapeutic target for LUAD.
ESD with double clips and rubber band traction of neoplastic lesions developed in the appendiceal orifice is effective and safe

Abstract Background and study aims Endoscopic submucosal dissection (ESD) of superficial colorectal lesions in close proximity to the appendiceal orifice (L-PAO) was shown to be feasible except in case of deep invasion into the appendix (type 3 of Toyonaga’s classification). This study aimed to determine the outcomes of ESD with double clip and rubber band traction (DCT-ESD) of L-PAO including a majority of type 3. Patients and methods We reviewed retrospectively all consecutive DCT-ESD of L-PAO performed in 3 French centers. Each lesion was described according to Toyonaga’s classification and type 0 lesions were excluded. The primary outcome was en bloc and R0 resection rates for L-PAO. Morbidity and salvage surgery were recorded. Results A total of 32 patients underwent DCT-ESD; 22 lesions (68.8 %) were type 3, including 11 with previous appendectomy (34.4 %). Median lesion size was 35 mm range (10–110 mm) and median duration of resection was 47 min range (10–230 min). We achieved 100 % of En bloc resection exclusively with DCT-ESD and 90.6 % of histological R0 resection rate. Per-procedure, 11 perforations occurred and were all immediately closed with clips. Overall, 3 patients (10.7 %) underwent surgery without stoma (2 complications related and 1 incomplete resection). No death occurred. Conclusion ESD of lesions deeply invading appendiceal orifice is feasible with the help of a traction system. Technical success by endoscopy avoiding surgery was achieved in 90.6 % of cases.
Overexpression of microRNA-155 enhances the efficacy of dendritic cell vaccine against breast cancer

ABSTRACT MicroRNA 155 (miR-155) plays important roles in the regulation of the development and functions of a variety of immune cells. We previously revealed a vital role of miR-155 in regulating the function of dendritic cells (DCs) in breast cancer. miR-155 deficiency in DCs impaired their maturation, migration, cytokine production, and ability to activate T cells. In the current study, to exploit the therapeutic value of miR-155 for breast cancer, we examined the impact of overexpression of miR-155 on antitumor responses generated by DC vaccines. We boosted miR-155 expression in DCs by generating a miR-155 transgenic mouse strain (miR-155tg) or using lentivirus transduction. DCs overexpressing miR-155 exhibited enhanced functions in response to tumor antigens. Using miR-155 overexpressing DCs, we generated a DC vaccine and found that the vaccine resulted in enhanced antitumor immunity against established breast cancers in mice, demonstrated by increased effector T cells in the mice, suppressed tumor growth, and drastically reduced lung metastasis. Our current study suggests that in future DC vaccine development for breast cancer or other solid tumors, introducing forced miR155 overexpression in DCs via various approaches such as viral transduction or nanoparticle delivery, as well as including other adjuvant agents such as TLR ligands or immune stimulating cytokines, may unleash the full therapeutic potential of the DC vaccines.