Miracle-dz/UniFAR-FTUs huggingface dataset:
Procedure-Related Complications of Left Bundle Branch Pacing: A Single-Center Experience

Background: Although left bundle branch pacing (LBBP) has emerged as a novel physiological pacing strategy with a low and stable threshold, its safety has not been well-documented. In the present study, we included all the patients with procedure-related complications at our centre to estimate these LBBP cases with unique complications. Methods: We enrolled 612 consecutive patients who received the procedure in Zhongshan Hospital, Fudan University, between January 2018 and July 2020. Regular follow-ups were conducted (at 1, 3, and 6 months in the first year and every 6–12 months from the second year), and the clinical data of the patients with complications were collected and analyzed. Results: With a mean follow-up period of 12.32 ± 5.21 months, procedure-related complications were observed in 10 patients (1.63%) that included two postoperative septum perforations (2/612, 0.33%), two postoperative lead dislodgements (2/612, 0.33%), four intraoperative septum injuries (4/612, 0.65%), and two intraoperative lead fractures (2/612, 0.33%). Pacing parameters were stable during follow-up, and no major complications were observed after lead repositioning in the cases of septum perforation and lead dislodgement. Conclusion: The incidence of procedure-related complications for LBBP, namely postoperative septum perforation, postoperative lead dislodgement, intraoperative septum injury, and intraoperative lead fracture, were low. No adverse clinical outcomes were demonstrated after successful repositioning of the lead and appropriate treatment.
Substrate Inhibition of 5β-Δ4-3-Ketosteroid Dehydrogenase in Sphingobium sp. Strain Chol11 Acts as Circuit Breaker During Growth With Toxic Bile Salts

In contrast to many steroid hormones and cholesterol, mammalian bile salts are 5β-steroids, which leads to a bent structure of the steroid core. Bile salts are surface-active steroids excreted into the environment in large amounts, where they are subject to bacterial degradation. Bacterial steroid degradation is initiated by the oxidation of the A-ring leading to canonical Δ4-3-keto steroids with a double bond in the A-ring. For 5β-bile salts, this Δ4-double bond is introduced into 3-keto-bile salts by a 5β-Δ4-ketosteroid dehydrogenase (5β-Δ4-KSTD). With the Nov2c019 protein from bile-salt degrading Sphingobium sp. strain Chol11, a novel 5β-Δ4-KSTD for bile-salt degradation belonging to the Old Yellow Enzyme family was identified and named 5β-Δ4-KSTD1. By heterologous production in Escherichia coli, 5β-Δ4-KSTD function could be shown for 5β-Δ4-KSTD1 as well as the homolog CasH from bile-salt degrading Rhodococcus jostii RHA1. The deletion mutant of 5β-Δ4-kstd1 had a prolonged lag-phase with cholate as sole carbon source and, in accordance with the function of 5β-Δ4-KSTD1, showed delayed 3-ketocholate transformation. Purified 5β-Δ4-KSTD1 was specific for 5β-steroids in contrast to 5α-steroids and converted steroids with a variety of hydroxy groups regardless of the presence of a side chain. 5β-Δ4-KSTD1 showed a relatively low Km for 3-ketocholate, a very high specific activity and pronounced substrate inhibition. With respect to the toxicity of bile salts, these kinetic properties indicate that 5β-Δ4-KSTD1 can achieve fast detoxification of the detergent character as well as prevention of an overflow of the catabolic pathway in presence of increased bile-salt concentrations.
Optimal Surgery Type and Adjuvant Therapy for T1N0M0 Lung Large Cell Neuroendocrine Carcinoma

Background The appropriate treatment strategy for T1N0M0 lung large cell neuroendocrine carcinoma (LCNEC) was not well illustrated. We evaluated the efficacy of different surgery types and adjuvant therapy on patients with T1N0M0 LCNEC. Methods Patients diagnosed T1N0M0 LCNEC from 2004 to 2016 were identified in the surveillance, epidemiology, and end results (SEER) database. Clinical characteristics, treatment and survival data were collected. The efficacy of surgery type and adjuvant therapy stratified by tumor size was assessed. Overall survival(OS) was evaluated by the Kaplan-Meier method, and relevant survival variables were identified by the Cox proportional hazard model. Results From 2004 to 2016, 425 patients were included in this study, 253 (59.5%) patients received lobectomy, and 236 (55.5%) patients had 4 or more lymph nodes removed. Patients received lobectomy had better survival than those received sublobar resection(P=0.000). No matter tumor size less than 2 cm or 2 to 3 cm, lobectomy was significantly prolonged survival. Compared with no lymph nodes removed, lymph nodes dissection was associated with more remarkable OS(P<0.000). 4 or more regional lymph nodes dissection predicted better OS compared with 1 to 3 regional lymph nodes dissection(P=0.014). After surgery, adjuvant chemotherapy did not contribute to extended survival in patients with tumor less than 2 cm(P=0.658), and possibly for tumor 2 to 3 cm(P=0.082). Multivariate analysis showed that age and lobectomy were independent prognostic factors(P=0.000). Conclusion Our results suggest that lobectomy and lymph nodes dissection were associated with significantly better survival. Extensive regional lymph node dissection(4 or more) was more effective in prolonging survival than 1 to 3 lymph nodes dissection. Adjuvant chemotherapy was not associated with extended survival for tumor less than 2 cm, and possibly for tumor 2 to 3 cm.
Absent Exercise-Induced Improvements in Fat Oxidation in Women With Polycystic Ovary Syndrome After High-Intensity Interval Training

Background: Polycystic ovary syndrome (PCOS) and metabolic inflexibility are linked to insulin resistance, and women with PCOS appear to be metabolic inflexible in the rested, insulin-stimulated state. Exercise training is a primary lifestyle intervention in PCOS. Exercise training improves whole-body fat oxidation during submaximal exercise in healthy women, yet little is known about the effect on this outcome in women with PCOS. Methods: We measured whole-body fat oxidation rates during sub maximal exercise before and after 16 weeks of high-intensity interval training (HIT) in women with PCOS randomly allocated to either: low- or high-volume HIT (n = 41; low-volume HIT, 10 × 1 min work bouts at maximal, sustainable intensity and high-volume HIT, 4 × 4 min work bouts at 90–95% of maximal heart rate) or non-exercise control (n = 23), and in women without PCOS (Non-PCOS) allocated to low- or high volume HIT (n = 15). HIT was undertaken three times weekly. In a subset of women with and without PCOS, we measured mitochondrial respiration in abdominal and gluteal subcutaneous adipose tissue using high-resolution respirometry, as well as fat cell sizes in these tissues. Results: At baseline, women with PCOS had lower whole-body fat oxidation and mitochondrial respiration rates in abdominal adipose tissue compared to Non-PCOS. Peak oxygen uptake (mL/min/kg) increased in women with PCOS (~4%, p = 0.006) and Non-PCOS (~6%, p = 0.003) after 16 weeks of HIT. Whole-body fat oxidation only improved in Non-PCOS after HIT. No changes were observed in mitochondrial respiration and cell size in abdominal and gluteal adipose tissue after HIT in either group of women. Conclusion: We observed exercise-induced improvements in whole-body fat oxidation during submaximal exercise in Non-PCOS, but not in women with PCOS, after 16 weeks of HIT, suggesting metabolic inflexibility in women with PCOS. Clinical Trial Registration: www.clinicaltrials. gov, identifier NCT02419482 and NCT02943291.
Effect of Ketamine on Human Neurochemistry in Posterior Cingulate Cortex: A Pilot Magnetic Resonance Spectroscopy Study at 3 Tesla

Ketamine is a powerful glutamatergic long-lasting antidepressant, efficient in intractable major depression. Whereas ketamine’s immediate psychomimetic side-effects were linked to glutamate changes, proton MRS (1H-MRS) showed an association between the ratio of glutamate and glutamine and delayed antidepressant effect emerging ∼2 h after ketamine administration. While most 1H-MRS studies focused on anterior cingulate, recent functional MRI connectivity studies revealed an association between ketamine’s antidepressant effect and disturbed connectivity patterns to the posterior cingulate cortex (PCC), and related PCC dysfunction to rumination and memory impairment involved in depressive pathophysiology. The current study utilized the state-of-the-art single-voxel 3T sLASER 1H-MRS methodology optimized for reproducible measurements. Ketamine’s effects on neurochemicals were assessed before and ∼3 h after intravenous ketamine challenge in PCC. Concentrations of 11 neurochemicals, including glutamate (CRLB ∼ 4%) and glutamine (CRLB ∼ 13%), were reliably quantified with the LCModel in 12 healthy young men with between-session coefficients of variation (SD/mean) <8%. Also, ratios of glutamate/glutamine and glutamate/aspartate were assessed as markers of synaptic function and activated glucose metabolism, respectively. Pairwise comparison of metabolite profiles at baseline and 193 ± 4 min after ketamine challenge yielded no differences. Minimal detectable concentration differences estimated with post hoc power analysis (power = 80%, alpha = 0.05) were below 0.5 μmol/g, namely 0.39 μmol/g (∼4%) for glutamate, 0.28 μmol/g (∼10%) for Gln, ∼14% for glutamate/glutamine and ∼8% for glutamate/aspartate. Despite the high sensitivity to detect between-session differences in glutamate and glutamine concentrations, our study did not detect delayed glutamatergic responses to subanesthetic ketamine doses in PCC.
How Positively Valenced Health Messages can Foster Information Selection: Evidence from Two Experiments

Objective: Positively valenced appeals have received comparably less attention than negative appeals. However, messages utilizing negative emotions have been repeatedly criticized, and research has demonstrated the beneficial effects of applying positive emotionally-charged messages. Therefore, this study investigates the impact and effectiveness of positive to negative messages. Design: In two studies (N 1 = 108, N 2 = 355), participants were exposed to one video about healthy eating and exercising, which was manipulated concerning valence (positive vs. negative). Main Outcome Measures: We assessed efficacy perceptions and attitudes toward healthy eating and exercising as well as participants’ selection of topic-related information on a mock-up website immediately after message exposure. Results: A positive emotional experience led to stronger efficacy perceptions, which promoted attitudes toward the displayed behavior but not information selection (Study 1). A more diverse sample in a follow-up replication (Study 2) substantiated these findings. Additionally, it demonstrated that being affected by a health issue has a decisive influence on the selection of information. In particular, a higher BMI negatively influenced information selection when efficacy perceptions were high. Conclusion: The study demonstrates the double-edged nature of strengthening efficacy expectations, as they can promote healthy attitudes and provide affected individuals with a false sense of security.
PPAR γ Prevents Neuropathic Pain by Down-Regulating CX3CR1 and Attenuating M1 Activation of Microglia in the Spinal Cord of Rats Using a Sciatic Chronic Constriction Injury Model

Background Previous studies have proved that peripheral nerve injury is involved in the pathogenesis of neuropathic pain (NP). The peripheral nerve injury primes spinal M1 microglia phenotype and produces pro-inflammatory cytokines, which are responsible for neurotoxic and neuronal hyper-excitable outcomes. Spinal peroxisome proliferator-activated receptor gamma (PPAR γ) has been shown to play an anti-inflammatory role in the development of NP. However, the role of PPAR γ in attenuating the pathological pathway of spinal microgliosis is still unknown. Methods Sprague-Dawley rats (male, aged 8–10 weeks) were randomly divided into three groups, i.e., a control group, a NP group, and a NP + lentivirus encoding PPAR γ (LV-PPAR γ) group. The sciatic chronic constriction injury (CCI) model was used to induce NP in rats. Pain behavior was assessed by monitoring the rat hind-paw withdrawal threshold to mechanical stimuli and withdrawal latency to radiant heat. The LV-PPAR γ was intrathecally infused 1 day before CCI. Western blot analysis and real-time qPCR were used to detect the microglia phenotypic molecules and CX3CR1 expression in the spinal cord. In vitro, BV-2 microglia cells were transfected with LV-PPAR γ and incubated with lipopolysaccharides (LPS), and the levels of M1 microglia phenotypic molecules and CX3CR1 in BV-2 microglia cells were assessed by western blot analysis, real-time qPCR, and enzyme-linked immunosorbent assay. Results Preoperative intrathecal infusion of LV-PPAR γ attenuated pain in rats 7 days post-CCI. The M1-microglia marker, CX3CR1, and pro-inflammatory signaling factors were increased in the spinal cord of CCI rats, while the preoperative intrathecal infusion of LV-PPAR γ attenuated these changes and increased the expression of IL-10. In vitro, the overexpression of PPAR γ in BV-2 cells reduced LPS-induced M1 microglia polarization and the levels of CX3CR1 and pro-inflammatory cytokines. Conclusion Intrathecal infusion of LV-PPAR γ exerts a protective effect on the development of NP induced by CCI in rats. The overexpression of PPAR γ may produce both analgesic and anti-inflammatory effects due to inhibition of the M1 phenotype and CX3CR1 signaling pathway in spinal microglia.
The Role of Comparisons in Judgments of Loneliness

Loneliness—perceived social isolation—is defined as a discrepancy between existing social relationships and desired quality of relationships. Whereas most research has focused on existing relationships, we consider the standards against which people compare them. Participants who made downward social or temporal comparisons that depicted their contact with others as better (compared to other people’s contact or compared to the past) reported less loneliness than participants who made upward comparisons that depicted their contact with others as worse (Study 1–3). Extending these causal results, in a survey of British adults, upward social comparisons predicted current loneliness, even when controlling for loneliness at a previous point in time (Study 4). Finally, content analyses of interviews with American adults who lived alone showed that social and temporal comparisons about contact with others were both prevalent and linked to expressed loneliness (Study 5). These findings contribute to understanding the social cognition of loneliness, extend the effects of comparisons about social connection to the important public health problem of loneliness, and provide a novel tool for acutely manipulating loneliness.
A Phase II Randomized Clinical Trial and Mechanistic Studies Using Improved Probiotics to Prevent Oral Mucositis Induced by Concurrent Radiotherapy and Chemotherapy in Nasopharyngeal Carcinoma

Earlier evidence has proven that probiotic supplements can reduce concurrent chemoradiotherapy (CCRT)-induced oral mucositis (OM) in nasopharyngeal cancer (NPC). The incidence of severe OM (grade 3 or higher) was the primary endpoint in this study. We first enrolled 85 patients with locally advanced NPC who were undergoing CCRT. Of them, 77 patients were finally selected and randomized (1:1) to receive either a probiotic cocktail or placebo. To investigate the protective effects and the mechanism of probiotic cocktail treatment on OM induced by radiotherapy and chemotherapy, we randomly divided the rats into the control (C) group, the model (M) group, and the probiotic (P) group. After treatment, samples from the tongue, blood, and fecal and proximal colon tissues on various days (7th, 14th, and 21st days) were collected and tested for the inflammatory response, cell apoptosis, intestinal permeability, and intestinal microbial changes. We found that patients taking the probiotic cocktail showed significantly lower OM. The values of the incidence of 0, 1, 2, 3, and 4 grades of OM in the placebo group and in the probiotic cocktail group were reported to be 0, 14.7, 38.2, 32.4, and 14.7% and 13.9, 36.1, 25, 22.2, and 2.8%, respectively. Furthermore, patients in the probiotic cocktail group showed a decrease in the reduction rate of CD3+ T cells (75.5% vs. 81%, p < 0.01), CD4+ T cells (64.53% vs. 79.53%, p < 0.01), and CD8+ T cells (75.59 vs. 62.36%, p < 0.01) compared to the placebo group. In the rat model, the probiotic cocktail could ameliorate the severity of OM, decrease the inflammatory response, cause cell apoptosis and intestinal permeability, and restore the structure of gut microbiota to normalcy. In conclusion, the modified probiotic cocktail significantly reduces the severity of OM by enhancing the immune response of patients with NPC and modifying the structure of gut microbiota. Clinical Trial Registration: The Clinical Trial Registration should be the NCT03112837.
Protective Effects of Deferoxamine on Vestibulotoxicity in Gentamicin-Induced Bilateral Vestibulopathy Rat Model

Introduction: Administration of aminoglycoside (AG) antibiotics is one of the most common causes of ototoxicity. This study aimed to determine the protective effects of deferoxamine, an iron-chelating agent, on vestibulotoxicity using an intratympanic gentamicin injection (ITGM)-induced bilateral vestibulopathy rat model. Methods: Fifteen Sprague-Dawley rats were randomly assigned to the ITGM only (n = 5), the ITGM combined with intramuscular deferoxamine (DFO) injection (ITGM+DFO, n = 5), or the intratympanic normal saline (control, n = 5) group. The rats in the ITGM+DFO group received intramuscular injection of 150 mg/kg of deferoxamine at 30, 90, and 150 min after the ITGM. The vestibular function was evaluated using the rotarod and open field test every 3 days after the injection until Day 16 when the rats were subjected to histological changes. Results: The rats in the ITGM only group began to show significantly impaired vestibular function 2 days after ITGM into both ears. In contrast, the vestibular function was maintained in the control and ITGM+DFO groups without a difference throughout the experiments. The rats in the ITGM only group showed a near-complete loss of the type I and II hair cells and a collapse of the sensory epithelium in both the saccule and utricle. In contrast, the rats in the ITGM+DFO and control groups showed a relatively well-preserved sensory epithelium including the hair cells, cilia, and otolith layer. Conclusion: This study provides experimental evidence for preventive effects of iron-chelating agents on AG-induced vestibulotoxicity. Simultaneous administration of iron-chelating agents may be considered when using ototoxic agents, especially in those considered to be vulnerable to toxic damage of the inner ear.
PRRSV Promotes MARC-145 Cells Entry Into S Phase of the Cell Cycle to Facilitate Viral Replication via Degradation of p21 by nsp11

Porcine reproductive and respiratory syndrome virus (PRRSV) remains one of the most economically significant pathogens that seriously affect the global swine industry. Despite sustained efforts, the factors that affect PRRSV replication in host cells are far from being fully elucidated and thus warrants further investigation. In this study, we first demonstrated that PRRSV infection can cause downregulation of endogenous p21 protein in MARC-145 cells in a virus dose-dependent manner. Next, we analyzed the effect of p21 knockdown by RNA interference on cell cycle progression using flow cytometric analysis, and found that knockdown of p21 promotes MARC-145 cells entry into S phase of the cell cycle. Interestingly, we further discovered PRRSV infection is also able to promote MARC-145 cells entry into the S phase. Subsequently, we synchronized MARC-145 cells into G0/G1, S and G2/M phases, respectively, and then determined PRRSV replication in these cells. Results here show that the MARC-145 cells synchronized into the S phase exhibited the highest viral titer among the cells synchronized to different phases. Additionally, to reliably analyze the potential role of endogenous p21 protein in PRRSV replication, we constructed a p21 gene-knockout MARC-145 cell line (p21−/−) using CRISPR/Cas9 technology and evaluated its capability to support PRRSV replication. Our results indicate that knockout of p21 is conducive to PRRSV replication in MARC-145 cells. Furthermore, through construction of a series of eukaryotic plasmids expressing each of individual PRRSV proteins combined with cell transfection, we demonstrated that the nonstructural protein 11 (nsp11) of PRRSV mediates p21 degradation, which was further confirmed by generating a stable MARC-145 cell line constitutively expressing nsp11 using a lentivirus system. Notably, we further demonstrated that the endoribonuclease activity rather than the deubiquitinating activity of nsp11 is essential for p21 degradation via mutagenic analysis. Finally, we demonstrated that nsp11 mediates p21 degradation via a ubiquitin-independent proteasomal degradation manner. Altogether, our study not only uncovers a new pathogenesis of PRRSV, but also provides new insights into development of novel antiviral strategies.
Adsorption of Hg2+ and Ni2+ from Aqueous Solutions Using Unmodified and Carboxymethylated Granular Activated Carbon (GAC)

The use of unmodified and carboxymethylated granular activated carbon (GAC) for adsorption of Hg 2+ and Ni 2+ from aqueous solutions was assessed in this work. The effect of concentration and modification by carboxymethyl group on the adsorption of these metal ions was studied in batch process. The adsorption data were correlated with Langmuir, Freundlich, Dubinin-Radushkevich and Temkin isotherm models. Results show that Freundlich model gave the best description for the adsorption process followed by the Langmuir model. Langmuir adsorption capacity corresponding to sites saturation was found to be 20.83 mg g -1 and 19.05 mg g -1 for adsorption of the Hg 2+ and Ni 2+ respectively onto the unmodified adsorbent and 19.72 mg g -1 and 17.01 mg g -1 for adsorption onto the carboxymethylated substrate. The apparent energy values obtained from the Dubinin-Radushvich model further indicates that the forces of the adsorption follow physical mode. Modification by carboxymethyl group generally caused a decline in the adsorption capacity by the adsorbent. Results obtained generally showed that Hg (II) ions were better adsorbed onto both adsorbents as compared to Nickel (II).
Equilibrium moisture characteristics of dried eggplant and okra

Equilibrium moisture characteristics of dried eggplant and dried okra were studied at 20 °C and 27 °C Moisture sorption isotherms of these dried vegetables were derived using the static method. Sorption data were treated according to some well-known isotherm equations. The parameters of these equations were obtained and goodness of fit of data to these equations were tested. The trends in monolayer moisture contents at different temperatures were examined. Finally, the heat of sorption data were derived with the use of Clausius Clapeyron type equation and presented in graphical form. Feuchtigkeitseigenschaften getrockneter Auberginen und Okra im Gleichgewicht Im Rahmen dieser Arbeit wurden die Feuchtigkeitseigenschaften der getrockneten Aubergine und Okra im Gleichgewicht bei 20 °C und 27 °C untersucht. Die Feuchtigkeitssorptionsisothermen dieser getrockneten Gemusearten wurden durch Verwendung statischer Methoden erhalten. Die Sorptionsdaten wurden mit einigen gut bekannten Isothermgleichungen bearbeitet. Die Parameter dieser Gleichungen wurden ermittelt und die Ubereinstimmung der Daten mit diesen Gleichungen uberpruft. Die Trends der Feuchtigkeitsinhalte der einzelnen Schichten bei verschiedenen Temperaturen wurden untersucht. Zum Schlus wurden die Warmedaten der Sorption unter Verwendung einer Gleichung, ahnlich der Clausius-Clapeyron-Gleichung, ermittelt und graphisch dargestellt.