Miracle-dz/UniFAR-FTUs huggingface dataset:
Dopamine Modulates Homeostatic Excitatory Synaptic Plasticity of Immature Dentate Granule Cells in Entorhino-Hippocampal Slice Cultures

Homeostatic plasticity mechanisms maintain neurons in a stable state. To what extent these mechanisms are relevant during the structural and functional maturation of neural tissue is poorly understood. To reveal developmental changes of a major homeostatic plasticity mechanism, i.e., homeostatic excitatory synaptic plasticity, we analyzed 1-week- and 4-week-old entorhino-hippocampal slice cultures and investigated the ability of immature and mature dentate granule cells (GCs) to express this form of plasticity. Our experiments demonstrate that immature GCs are capable of adjusting their excitatory synaptic strength in a compensatory manner at early postnatal stages, i.e., in 1-week-old preparations, as is the case for mature GCs. This ability of immature dentate GCs is absent in 4-week-old slice cultures. Further investigations into the signaling pathways reveal an important role of dopamine (DA), which prevents homeostatic synaptic up-scaling of immature GCs in young cultures, whereas it does not affect immature and mature GCs in 4-week-old preparations. Together, these results disclose the ability of immature GCs to express homeostatic synaptic plasticity during early postnatal development. They hint toward a novel role of dopaminergic signaling, which may gate activity-dependent changes of newly born neurons by blocking homeostasis.
Cracking KD-Tree: The First Multidimensional Adaptive Indexing (Position Paper)

htmlabstractWorkload-aware physical data access structures are crucial to achieve short response time with (exploratory) data analysis tasks as commonly required for Big Data and Data Science applications. Recently proposed techniques such as automatic index advisers (for a priori known static workloads) and query-driven adaptive incremental indexing (for a priori unknown dynamic workloads) form the state-of-the-art to build single-dimensional indexes for single-attribute query predicates. However, similar techniques for more demanding multi-attribute query predicates, which are vital for any data analysis task, have not been proposed, yet. In this paper, we present our on-going work on a new set of workload-adaptive indexing techniques that focus on creating multidimensional indexes. We present our proof-of-concept, the Cracking KD-Tree, an adaptive indexing approach that generates a KD-Tree based on multidimensional range query predicates. It works by incrementally creating partial multidimensional indexes as a by-product of query processing. The indexes are produced only on those parts of the data that are accessed, and their creation cost is effectively distributed across a stream of queries. Experimental results show that the Cracking KD-Tree is three times faster than creating a full KD-Tree, one order of magnitude faster than executing full scans and two orders of magnitude faster than using uni-dimensional full or adaptive indexes on multiple columns.
Telocinobufagin, a Novel Cardiotonic Steroid, Promotes Renal Fibrosis via Na+/K+-ATPase Profibrotic Signaling Pathways

Cardiotonic steroids (CTS) are Na+/K+-ATPase (NKA) ligands that are elevated in volume-expanded states and associated with cardiac and renal dysfunction in both clinical and experimental settings. We test the hypothesis that the CTS telocinobufagin (TCB) promotes renal dysfunction in a process involving signaling through the NKA α-1 in the following studies. First, we infuse TCB (4 weeks at 0.1 µg/g/day) or a vehicle into mice expressing wild-type (WT) NKA α-1, as well as mice with a genetic reduction (~40%) of NKA α-1 (NKA α-1+/−). Continuous TCB infusion results in increased proteinuria and cystatin C in WT mice which are significantly attenuated in NKA α-1+/− mice (all p < 0.05), despite similar increases in blood pressure. In a series of in vitro experiments, 24-h treatment of HK2 renal proximal tubular cells with TCB results in significant dose-dependent increases in both Collagens 1 and 3 mRNA (2-fold increases at 10 nM, 5-fold increases at 100 nM, p < 0.05). Similar effects are seen in primary human renal mesangial cells. TCB treatment (100 nM) of SYF fibroblasts reconstituted with cSrc results in a 1.5-fold increase in Collagens 1 and 3 mRNA (p < 0.05), as well as increases in both Transforming Growth factor beta (TGFb, 1.5 fold, p < 0.05) and Connective Tissue Growth Factor (CTGF, 2 fold, p < 0.05), while these effects are absent in SYF cells without Src kinase. In a patient study of subjects with chronic kidney disease, TCB is elevated compared to healthy volunteers. These studies suggest that the pro-fibrotic effects of TCB in the kidney are mediated though the NKA-Src kinase signaling pathway and may have relevance to volume-overloaded conditions, such as chronic kidney disease where TCB is elevated.
Fractional Multiscale Fusion-based De-hazing

This report presents the results of a proposed multi-scale fusion-based single image de-hazing algorithm, which can also be used for underwater image enhancement. Furthermore, the algorithm was designed for very fast operation and minimal run-time. The proposed scheme is the faster than existing algorithms for both de-hazing and underwater image enhancement and amenable to digital hardware implementation. Results indicate mostly consistent and good results for both categories of images when compared with other algorithms from the literature.
Midazolam and Dexmedetomidine Affect Neuroglioma and Lung Carcinoma Cell Biology In Vitro and In Vivo

What We Already Know about This Topic Dexmedetomidine reduces cellular apoptosis, and it has been demonstrated previously that this antiapoptotic effect can not only increase cancer cell proliferation and migration but also reduce survival in experimental models of cancer growth. Midazolam has proapoptotic effects and can reduce cancer cell survival. The mechanisms by which midazolam suppresses cancer cell progression remain to be defined. What This Article Tells Us That Is New As expected, dexmedetomidine enhanced cancer cell proliferation and migration, primarily by the upregulation of antiapoptotic proteins. By contrast, midazolam suppressed cancer cell proliferation and migration, induced mitochondria mediated apoptosis, and enhanced free radical production. These anticancer effects of midazolam, mediated by its activity at the peripheral benzodiazepine receptor, were achieved at high concentrations only. The data suggest that commonly used agents in the perioperative period may impact tumor cell growth; these effects have been demonstrated in preclinical studies, and therefore their relevance to clinical management of patients undergoing cancer surgery remains to be determined. Background: Several factors within the perioperative period may influence postoperative metastatic spread. Dexmedetomidine and midazolam are widely used general anesthetics during surgery. The authors assessed their effects on human lung carcinoma (A549) and neuroglioma (H4) cell lines in vitro and in vivo. Methods: Cell proliferation and migration were measured after dexmedetomidine (0.001 to 10 nM) or midazolam (0.01 to 400 &mgr;M) treatment. Expression of cell cycle and apoptosis markers were assessed by immunofluorescence. Mitochondrial membrane potential and reactive oxygen species were measured by JC-1 staining and flow cytometry. Antagonists atipamezole and flumazenil were used to study anesthetic mechanisms of action. Tumor burden after anesthetic treatment was investigated with a mouse xenograft model of lung carcinoma. Results: Dexmedetomidine (1 nM) promoted cell proliferation (2.9-fold in A549 and 2-fold in H4 cells vs. vehicle, P < 0.0001; n = 6), migration (2.2-fold in A549 and 1.9-fold in H4 cells vs. vehicle, P < 0.0001; n = 6), and upregulated antiapoptotic proteins in vitro. In contrast, midazolam (400 &mgr;M) suppressed cancer cell migration (2.6-fold in A549 cells, P < 0.0001; n = 4), induced apoptosis via the intrinsic mitochondrial pathway, decreased mitochondrial membrane potential, and increased reactive oxygen species expression in vitro—effects partly attributable to peripheral benzodiazepine receptor activation. Furthermore, midazolam significantly reduced tumor burden in mice (1.7-fold vs. control; P < 0.05; n = 6 per group). Conclusions: Midazolam possesses antitumorigenic properties partly mediated by the peripheral benzodiazepine receptor, whereas dexmedetomidine promotes cancer cell survival through signaling via the &agr;2-adrenoceptor in lung carcinoma and neuroglioma cells.
A comparative study of the effects of palm olein, cocoa butter and extra virgin olive oil on lipid profile, including low-density lipoprotein subfractions in young healthy Chinese people

Abstract The aim of this study is to investigate the effects of palm olein (POL), cocoa butter (CB) and extra virgin olive oil (EVOO) on the lipid profile and low-density lipoprotein subfractions in a young, healthy Chinese population. After screening, 72 subjects were randomly assigned to three groups, and an 18-week randomized crossover trial was conducted. The first phase was a 2-week run-in period, followed by three phases of the 4-week experimental periods with a 2-week washout period between experimental periods. Three groups of subjects alternately consumed a Chinese diet enriched with the different test oils. The various indices of subjects were collected before and after each experimental period. Sixty-seven subjects completed the study, and there were no significant differences in conventional indices amongst the three groups at the beginning of the three experimental periods (p > .05). Each test oil accounted for approximately 40% of total fat intake and approximately 11.3% of the total energy supply. After controlling for dietary interventions, only the serum triglyceride level of the POL-Diet was significantly lower than that of the EVOO-Diet (p = .034), and most indices did not significantly differ amongst the three test oil diets (p > .05). POL, CB and EVOO have almost identical effects on serum lipids.
Dual targeting of HER2-positive breast cancer with trastuzumab emtansine and pertuzumab: understanding clinical trial results

Targeting of HER2-positive tumors with trastuzumab has shown to improve survival in early stage and advanced breast cancer. The addition of pertuzumab, another anti-HER2 antibody, to trastuzumab-containing regimens has demonstrated a modest increase in disease-free survival in the adjuvant setting. Unexpectedly, when pertuzumab was explored in combination with the antibody-drug conjugate TDM1 in the metastatic setting, no additional benefit was observed compared with dual targeting of HER2 with pertuzumab and trastuzumab, together with chemotherapy. Similar results were observed when exploring pathologic complete response in the neoadjuvant setting. In this article, we discuss basic science and translational data that may explain the limited efficacy observed with the combination of TDM1 and pertuzumab, including tumor heterogeneity, clonal selection, bystander effect or downregulation of the receptor by competitive binding. In addition, we review ongoing studies that could help to understand these findings.
Weight Loss Medications in Young Adults after Bariatric Surgery for Weight Regain or Inadequate Weight Loss: A Multi-Center Study

This paper presents a retrospective cohort study of weight loss medications in young adults aged 21 to 30 following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) between November 2000 and June 2014. Data were collected from patients who used topiramate, phentermine, and/or metformin postoperatively. Percentage of patients achieving ≥5%, ≥10%, or ≥15% weight loss on medications was determined and percent weight change on each medication was compared to percent weight change of the rest of the cohort. Our results showed that 54.1% of study patients lost ≥5% of their postsurgical weight; 34.3% and 22.9% lost ≥10% and ≥15%, respectively. RYGB had higher median percent weight loss (−8.1%) than SG (−3.3%) (p = 0.0515). No difference was found in median percent weight loss with medications started at weight plateau (−6.0%) versus after weight regain (−5.4%) (p = 0.5304). Patients taking medications at weight loss plateau lost 41.2% of total body weight from before surgery versus 27.1% after weight regain (p = 0.076). Median percent weight change on metformin was −2.9% compared to the rest of the cohort at −7.7% (p = 0.0241). No difference from the rest of the cohort was found for phentermine (p = 0.2018) or topiramate (p = 0.3187). Topiramate, phentermine, and metformin are promising weight loss medications for 21 to 30 year olds. RYGB patients achieve more weight loss on medications but both RYGB and SG benefit. Median total body weight loss from pre-surgical weight may be higher in patients that start medication at postsurgical nadir weight. Participants on metformin lost significantly smaller percentages of weight on medications, which could be the result of underlying medical conditions.
Ontogeny and variability of trabecular bone in the chimpanzee humerus, femur and tibia.

OBJECTIVES Trabecular bone structure is known to be influenced by joint loading during life. However, many additional variables have the potential to contribute to trabecular bone structure of an adult individual, including age, sex, body size, genetics, and overall activity level. There is little research into intraspecific variability in trabecular bone and ontogeny of trabecular bone structure, especially in nonhuman primates. MATERIALS AND METHODS This study investigates trabecular structure in adult and immature chimpanzees from a single population using high-resolution microcomputed tomographic scans of the proximal humerus, proximal femur, and distal tibia. Trabecular bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular spacing (Tb.Sp), and degree of anisotropy (DA) were quantified in specific regions of adult and immature chimpanzees, and color maps were generated to visualize the distribution of BV/TV throughout the joint in the metaphysis of immature specimens. RESULTS The results demonstrate that variability in adult trabecular structure cannot be explained by sex or body size. During ontogeny, there is a general increase in trabecular BV/TV and Tb.Th with age, and ratios of trabecular parameters between the fore- and hindlimb may be consistent with locomotor transitions during ontogeny. DISCUSSION Variation in trabecular morphology among adult individuals is not related to sex or body size, and the factors contributing to intraspecific variability, such as overall activity levels and genetic differences, require further investigation. Trabecular ontogeny in chimpanzees differs from humans in some respects, most notably the absence of a high BV/TV at birth.
Prognostic value of the heart rate profile during exercise in patients with atrial fibrillation

Aims This study aimed to investigate the correlation of heart rate profile during exercise with exercise capacity and heart failure occurrence in patients with atrial fibrillation compared with patients with sinus rhythm. Methods We analyzed 2231 patients (atrial fibrillation: n = 321, sinus rhythm: n = 1910) who underwent a symptom-limited maximal cardiopulmonary exercise test at our institute. Their heart rate profile during exercise was assessed using peak heart rate and chronotropic response; (peak heart rate−resting heart rate)/(220−age−resting heart rate). The endpoint was the occurrence of heart failure events, defined as hospitalization for heart failure or heart failure-related death. Results There were significant positive correlations of peak heart rate and chronotropic response to peak oxygen consumption, both in atrial fibrillation and sinus rhythm. During a median follow-up period of 1262 (interquartile range 974–2921) days, 117 (5.2%) heart failure events were observed. Multivariate analyses showed that peak heart rate and chronotropic response were statistically significant predictors of heart failure events both in atrial fibrillation (peak heart rate: heart rate 0.975, p = 0.002, chronotropic response: heart rate 0.196, p = 0.003) and in sinus rhythm (peak heart rate: heart rate 0.988, p = 0.036, chronotropic response: heart rate 0.347, p = 0.020). Bivariate models showed that compared with chronotropic response, peak heart rate was a stronger predictor of heart failure in atrial fibrillation, whereas the finding was reversed in sinus rhythm. Conclusion The exercise- heart rate profile was significantly related to exercise capacity and future heart failure events, regardless of rhythm. However, the impacts of peak heart rate and chronotropic response on the endpoint varied according to the cardiac rhythm.
Educational Video Followed by Retelling Bowel Preparation Process to Improve Colonoscopy Bowel Preparation Quality: A Prospective Nursing Intervention Study

Background This study investigated the effect of a patient education video followed by retelling the process of bowel preparation on colonoscopy bowel preparation quality. Material/Methods This was a prospective, randomized, controlled clinical trial of outpatients undergoing colonoscopy. Patients were randomized (1: 1) to the video + retelling group or the control group. The primary endpoint was to assess the bowel preparation quality using the Ottawa Bowel Preparation Quality scale (Ottawa score). Risk factors associated with poor bowel preparation were also evaluated. Result The video + retelling group had a higher percentage of patients with adequate colonoscopy bowel preparation (Ottawa score <6) than the control group (P<0.001). Mean Ottawa total scores significantly differed between the control group and the video + retelling group (4.18±1.4 vs. 3.05±1.3, P<0.001). The video + retelling group showed superior cleanliness in the right, middle, and recto-sigmoid colon segments (all Ps <0.001). Logistic regression analysis revealed that male gender (OR=2.10, 95%CI: 1.098–4.018, P=0.025), diabetes mellitus (OR=2.830, 95%CI: 1.257–6.372, P=0.012), and no educational video followed by retelling bowel preparation process (OR=3.02, 95%CI: 1.731–5.270, P<0.001) were independently associated with poor bowel preparation. Conclusions Use of an educational video followed by asking patients to retell the process of bowel preparation after receiving regular instructions is a convenient and risk-free practice that enhances the compliance with bowel preparation guidance and improves bowel preparation quality.
Screening for Middle East respiratory syndrome coronavirus among febrile Indonesian Hajj pilgrims: A study on 28,197 returning pilgrims

There were 211,000 Indonesian Hajj pilgrims going to Mecca through 11 main airports in 2015 who were at risk of contracting the Middle East respiratory syndrome coronavirus (MERS-CoV). We aimed to find out whether there was any occurrence of MERS-CoV by performing screening on 28,197 returning pilgrims. Those with a body temperature of > 38 °C and respiratory symptoms were sent to the airport clinic to have an oropharyngeal swab and a bacterial culture. Fifteen pilgrims had fever (> 38 °C) accompanied by respiratory symptoms; of these, 12 patients were diagnosed with upper and lower respiratory tract infections and three patients with pneumonia. However, none of them were found to be infected with MERS-CoV. The bacterial cultures showed evidence of normal flora growth.
Evaluation of Microleakage under Orthodontic Brackets Bonded with Nanocomposites

Background: The aim of this study was to evaluate the microleakage value under orthodontic brackets bonded with a nano-filled composite and to compare the results with a conventional adhesive using two different bonding systems. Materials and Methods: Forty human premolars were used in this cross-sectional study. The samples were randomly divided into four equal groups of ten: Group I: Acid etch plus Transbond XT primer and Transbond XT adhesive, Group II: Acid etch plus Transbond XT primer and nanocomposite (Filtek Z350), Group III: Scotchbond™ Universal primer plus Transbond XT, and Group IV: Scotchbond™ and nanocomposite. Sections were prepared for microleakage evaluation at the occlusal and gingival margins. Statistical analysis was performed to compare the microleakage values among the groups using analysis of variance (ANOVA). Statistical Analysis: Microleakage values were analyzed with two-way ANOVA test. Intraexaminer error was evaluated by the Kappa statistic. The level of significance was considered at P < 0.05. Results: Gingival side displayed statistically higher microleakage (P < 0.001). The nanocomposite Filtek Z350 generally represented higher microleakage when compared with the Transbond XT at both occlusal and gingival sides of the brackets (P < 0.001). More microleakage values were observed in brackets bonded using acid etch compared with Scotchbond. Comparison of microleakage among all the four groups revealed that Group II and Group III had the most and the least microleakage values, respectively, at the enamel–adhesive interface. Microleakage values for groups bonded with nanocomposite were significantly higher. Conclusion: This investigation clearly reveals the outstanding superiority and efficiency of a Transbond XT adhesive combined with a Scotchbond primer over that obtained using a Filtek Z350 nanocomposite in any combination with the used primers to limit microleakage under bonded brackets.
Occurrence of major complications after cochlear implant surgery in Ireland

Objectives: Cochlear implantation (CI) is considered an effective and relatively safe procedure for patients with severe-profound hearing loss. However, severe complications are reported in several studies. The purpose of this study was to report the frequency and management of major complications following CI surgery at the National CI Programme (NCIP) in Ireland. Methods: Major complications were defined according to the classification of Hansen et al. 2010. The medical records of 1017 patients undergoing CI between 1995 and 2016 were analyzed retrospectively for major complications. In addition, radiological and intraoperative findings as well as therapeutic management of all patients with a major complication were reviewed. Results: Altogether, 1017 patients underwent 1266 CI surgeries. The median follow-up of all CI surgeries was 44 months. The total number of major complications identified was 21 which corresponds to an overall rate of 1.7%. The majority of major complication (71%) occurred at least one week after surgery. The most common major complications were internal receiver/stimulator protrusion and migration (6/21), followed by migration of the electrode array (4/21) and recurrent otitis media requiring re-implantation (4/21). All patients with major complications required additional surgery, with reimplantation necessary in 19 patients (90%). Discussion: CI surgery is a safe surgical procedure for hearing rehabilitation associated with a low rate of severe complications. However, major complications can occur many years after surgery, making revision surgery necessary. Conclusion: Long-term follow-up is necessary for the early identification of complications to facilitate appropriate care.