Miracle-dz/UniFAR-FTUs huggingface dataset:
Water stress limits transpiration and growth of European larch up to the lower subalpine belt in an inner‐alpine dry valley

Summary Climate change will further constrain water availability in dry inner‐alpine environments and affect water relations and growth conditions in mountain forests, including the widespread larch forests. To estimate the effects of climate conditions on water balance and growth, variation in sap flow and stem radius of European larch was measured for 3 yr along an elevation transect from 1070 to 2250 m above sea level (asl) in an inner‐alpine dry valley in South Tyrol/Italy. Additionally, long‐term climate–growth relations were derived from tree cores. Sap flow and radial growth were reduced in dry periods up to an elevation of 1715 m, leading to maximum annual growth at 2000 m. In a wet year no growth difference between elevations was observed. Long‐term tree ring data showed a positive growth response to precipitation up to 1715 m and to temperature only above 2000 m. Our results demonstrate that reduced water availability and higher atmospheric water demand limit larch at low elevation within dry Alpine regions. This indicates a general upward shift of this species’ elevational amplitude upon climate change, and respective negative effects on future silvicultural use and ecosystem services at lower elevations in the European Alps.
Current Status of Prostaglandins for Cervical Ripening.

OBJECTIVE: To review the safety and efficacy of administering various prostaglandin formulations to achieve cervical ripening and spontaneous vaginal delivery in women near or at term. STUDY DESIGN: Peer-reviewed clinical research articles in English and searchable on PubMed.com. A thorough literature search was conducted on PubMed.com using the following terms: [misoprostol], [dinoprostone], [prostaglandin E1], [prostaglandin E2], [PGE1], [PGE2], [cervical ripening], [induction of labor]. RESULTS: The review shows conflicting opinions concerning the safety and efficacy of current standard-of-care formulations for cervical ripening. A gold standard option for optimal treatment has not been confirmed. CONCLUSION: While the clinical evidence suggests that prostaglandin E1 (PGE1) and E2 (PGE2) both could be used for cervical ripening when no contraindications are present, PGE2 formulations remain the only commercially available prostaglandin products for cervical ripening approved by the U.S. Food and Drug Administration. We conclude that more research is warranted on the risks of treatment-emergent adverse events and serious complications during induction of labor.
A quality-by-design study to develop Nifedipine nanosuspension: examining the relative impact of formulation variables, wet media milling process parameters and excipient variability on drug product quality attributes

Abstract Wet milling is a multifunctional and the most common method to prepare a drug nanosuspension for improving the bioavailability of poorly water soluble drugs. A suitable way of preparing a high drug-loaded nifedipine nanosuspension using wet stirred media milling was investigated in the present study. Nifedipine, a poorly water soluble drug, was selected as a model drug to enhance its dissolution rate and oral bioavailability by preparing an appropriate crystalline nanosuspension. Process parameters, such as milling media volume, milling speed and milling time, were optimized using the one variable at a time (OVAT) approach. A similar method was used to select an appropriate polymeric stabilizer and a surfactant from different categories of polymeric stabilizers (HPC SL, HPC SSL Soluplus®, Kollidon® VA 64 and HPMC E 15) and surfactants (Poloxamer 407, Kolliphor TPGS and Docusate sodium). A systematic optimization of critical formulation parameters (such as drug concentration, polymer concentration and surfactant concentration) was performed with the aid of the Box-Behnken design. Mean particle size, polydispersity index and zeta potential as critical quality attributes (CQAs) were selected in the design for the evaluation and optimization of the formulation and validation of the improved product. The nifedipine nanosuspension that was prepared using HPC and poloxamer 407 was found to be most stable with the lowest mean particle size as compared with the formulations prepared using other polymeric stabilizers and surfactants. The optimized formulation was further spray-dried and characterized using the Fourier Transform Infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), polarized light microscopy (PLM) and in-vitro dissolution study. Results have shown no interaction between the drug particles and stabilizers, nor a reduction in the crystallinity of drug, nor an increase in the saturation solubility and rapid in vitro dissolution as compared with pure nifedipine crystals. Thus, the current study supports the suitability of the wet stirred media milling method and a combination of HPC SSL and poloxamer 407 as stabilizers for the preparation of nifedipine nanosuspension.
Does the Presence of a Cantilever Influence the Survival and Success of Partial Implant-Supported Dental Prostheses? Systematic Review and Meta-Analysis.

PURPOSE To investigate if the presence of a cantilever influences the survival and success of partial fixed implant-supported prostheses, through a systematic review and meta-analysis, with additional analysis of the survival and marginal bone loss rates and prosthesis complications. MATERIALS AND METHODS The register protocol of the review in the PROSPERO database is CRD42016052008. The MEDLINE and Scopus databases were used for an electronic search of relevant studies up to November 2016, by means of two independent reviewers. The keywords included the combinations "fixed partial denture" with "dental implants", and with "extension" or "cantilever"; and "implant-supported dental prosthesis" with "extension" or "cantilever". The inclusion criteria were randomized clinical trials and prospective and retrospective clinical studies in English that addressed the comparison of success and survival of the use of implant-supported fixed prostheses, with and without cantilevers. Data from the selected studies were used to perform the statistical analysis. RESULTS Among the 408 articles identified, 4 articles met the eligibility criteria. The presence of a cantilever did not compromise marginal bone loss or the survival of the prostheses. However, minor complications were encountered for the group of partial fixed prostheses without cantilevers, with a statistical difference (P = .008). CONCLUSION Cantilevers can be used in fixed prostheses and do not interfere negatively in the survival or success of the prosthesis or the marginal bone loss. However, there are minor complications when prostheses without cantilevers, or short cantilevers, are used.
Efficacy of Trabodenoson in a Mouse Keratoconjunctivitis Sicca (KCS) Model for Dry-Eye Syndrome.

Purpose To determine the efficacy of trabodenoson, an adenosine mimetic with highly selective adenosine A1 receptor binding properties, in a preclinical mouse model for dry-eye disease. Methods Dry-eye disease was induced in adult male C57BL/6 mice using a combination of desiccating environment and transdermal administration of scopolamine. Mice were treated concurrently and twice daily with either vehicle, 6% trabodenoson, or 0.05% cyclosporine (Restasis). Efficacy (P < 0.05 versus vehicle) was determined by clinical assessment of dry-eye symptoms using corneal fluorescein staining and tear volumes and histopathologically by quantifying lacrimal gland pathology and conjunctival goblet cells. Results Twice-daily topical (ocular) administration of trabodenoson increased tear levels and reduced corneal fluorescein staining (P < 0.05) as compared with vehicle-treated eyes in a mouse model of dry-eye disease. Furthermore, significant infiltration of immune cells in the lacrimal gland and reduced number of mucin-producing conjunctival goblet cells were noted in both untreated and vehicle-treated eyes. Comparatively, trabodenoson treatment significantly reduced lacrimal gland infiltration and increased the number of goblet cells (P < 0.05 for both versus vehicle). These trabodenoson-related effects on lacrimal gland pathology and goblet cells were similar to or better than the effects observed with cyclosporine treatment. Conclusions Topical ocular delivery of trabodenoson significantly improves the clinical and histopathological signs associated with dry-eye disease in mice. This improvement appears to be related to anti-inflammatory effects from targeting adenosine signaling and represents a novel therapeutic approach to develop for the management of dry-eye disease.
Achievement Anxiety with Respect to Reference Groups in School.

AbstractReference group theory predicts that students of low ability in good classes feel worse than students of high ability in poor classes. With this in mind a field study was conducted in West Germany where a traditional school system provides three types of schools at different academic levels. Achievement anxiety was measured on 1,479 fifth- and eight-graders attending these three tracks. An interaction between type of school and grade level confirmed the expectation that after some years in a selective system students display a paradox pattern of well-being. Theoretically, reference group theory and test anxiety theory were tied together by focussing on self-evaluations in a social context.
Comparison of the Survival Outcomes of Pancreatic Cancer and Intraductal Papillary Mucinous Neoplasms

Objectives The aims of the study were to compare survival outcomes between patients with pancreatic ductal adenocarcinoma (PDAC) and invasive intraductal papillary mucinous neoplasms (IPMN) and to determine candidates for adjuvant chemotherapy. Methods A total of 579 consecutive patients, including 375 PDAC and 204 IPMN patients, were reviewed. Stage-matched comparisons of survival data were conducted using the Cox proportional hazards model and propensity analysis. To evaluate prognostic factors, univariate and multivariate Cox regression analyses were performed. Results The overall survival for invasive IPMN was significantly longer than that for PDAC (hazard ratio, 2.34; P = 0.0001). When the analysis was limited to stage I patients, the 5-year overall survival rate of invasive IPMN patients was significantly better than that of PDAC patients (100% vs 74.1%, P = 0.0092); however, no difference was observed between stage II patients with invasive IPMN and PDAC (hazard ratio, 1.49; P = 0.09). The Cox proportional hazards model and propensity analysis demonstrated no difference in stage-matched survival. Multivariate analysis revealed that only T (≥3) was an independent prognostic factor for invasive IPMN. Conclusions Stage-matched analysis did not show a significant survival difference between invasive IPMN and PDAC patients, and T3 or higher was an independent prognostic factor for invasive IPMN.
Mutations in voltage-gated L-type calcium channel: implications in cardiac arrhythmia

ABSTRACT The voltage-gated L-type calcium channel (LTCC) is essential for multiple cellular processes. In the heart, calcium influx through LTCC plays an important role in cardiac electrical excitation. Mutations in LTCC genes, including CACNA1C, CACNA1D, CACNB2 and CACNA2D, will induce the dysfunctions of calcium channels, which result in the abnormal excitations of cardiomyocytes, and finally lead to cardiac arrhythmias. Nevertheless, the newly found mutations in LTCC and their functions are continuously being elucidated. This review summarizes recent findings on the mutations of LTCC, which are associated with long QT syndromes, Timothy syndromes, Brugada syndromes, short QT syndromes, and some other cardiac arrhythmias. Indeed, we describe the gain/loss-of-functions of these mutations in LTCC, which can give an explanation for the phenotypes of cardiac arrhythmias. Moreover, we present several challenges in the field at present, and propose some diagnostic or therapeutic approaches to these mutation-associated cardiac diseases in the future.
Visual Performance as a Function of Luminance in Glaucoma: The De Vries-Rose, Weber's, and Ferry-Porter's Law.

Purpose To determine whether the De Vries-Rose, Weber's, and Ferry-Porter's law, which describe visual performance as a function of luminance, also hold in patients with glaucoma. Methods A case-control study with 19 glaucoma patients and 45 controls, all with normal visual acuity. We measured foveal and peripheral contrast sensitivity (CS) using static perimetry and foveal and peripheral critical fusion frequency (CFF; stimulus diameter 1°) as a function of luminance (0.02 to 200 cd/m2). ANOVA was used to analyze the effect of glaucoma and luminance on CS and CFF; analyses were adjusted for age and sex. Results Foveally, logCS was proportional to log luminance at lower luminances (de Vries-Rose) and saturated at higher luminances (Weber); glaucoma patients had a 0.4 log unit lower logCS than controls (P < 0.001), independent of luminance. Peripherally, the difference was more pronounced at lower luminances (P = 0.007). CFF was linearly related to log luminance (Ferry-Porter). Glaucoma patients had a lower CFF compared with controls (P < 0.001), with a smaller slope of the CFF versus log luminance curve, for both the fovea (6.8 vs. 8.7 Hz/log unit; P < 0.001) and the periphery (2.5 vs. 3.4 Hz/log unit; P = 0.012). Conclusions Even in apparently intact areas of the visual field, visual performance is worse in glaucoma patients than in healthy subjects for a wide range of luminances, without a clear luminance dependency that is consistent across the various experiments. This indicates impaired signal processing downstream in the retina and beyond, rather than an impaired light adaptation in the strictest sense.
Surgical Removal of Internal Limiting Membrane and Layering of AAV Vector on the Retina Under Air Enhances Gene Transfection in a Nonhuman Primate.

Purpose To determine if the surgical removal of the internal limiting membrane (ILM) in nonhuman primates (NHPs) will result in safe and effective transfection of adeno-associated viral (AAV2) vectors using green fluorescent protein (GFP) as a reporter. Methods Six Macaca fascicularis NHP eyes underwent vitrectomy, ILM peel with layering of 1.7 × 1013 genome copies per milliliter of AAV2-GFP under air. Four control eyes underwent only vitrectomy and pooling under air. The intensity and area transfected was quantified in vivo with fundus autofluorescence (FAF) imaging. NHPs were euthanized 16 weeks postsurgery and immunohistochemical analysis assessed GFP expression at the cellular level. Results There was a larger area of fluorescence in ILM peeled eyes then in non-ILM peeled eyes (50.7 [33.1-58.4] pixel2 versus 5.1 [0.6-7.6] pixel2, P < 0.01). The intensity of fluorescence was also higher in ILM peeled eyes (10.3 [2.2-18.5] vs. 1.9 [0.6-4.4], P = 0.05). Non-ILM peeled eyes displayed fluorescence confined to the foveal center. Histological sections showed colocalization in the Müller cell layer, ganglion cell layer, and photoreceptor cell layer in the ILM peeled eyes. In non-ILM peeled eyes GFP expression was only in the ganglion cell layer in three eyes and was confined to the immediate vicinity of the fovea. Conclusions ILM appears to be the predominate barrier to AAV transfection. An efficacious and safe method of AAV2 gene delivery, taking into account the potential need for repeat treatments, appears to be the surgical removal of ILM and layering of AAV under air.v.
Who’s Distressed by Sexual Difficulties? Exploring Associations Between Personal, Perceived Partner, and Relational Distress and Sexual Difficulties in Heterosexual Men and Women

While not all sexual difficulties cause distress, research and clinical experience suggest that, apart from personal distress, partner and relational sexual distress are also often an important reason to seek professional help. The current study explored the associations between personal, perceived partner, and relational distress that men and women experience as a result of sexual difficulties. Data from heterosexual Flemish individuals ages 16 to 74 who were in a relationship (13,800 men and 13,242 women, mean age of 43.69, SD = 14.94) were collected via an online survey. Presence and severity of sexual difficulties and associated personal, perceived partner, and relational sexual distress were assessed. Among men and women with desire difficulties, either the three types of sexual distress were almost equally common or partner distress was most common. Arousal, orgasm, and sexual pain difficulties were most often associated with personal distress, particularly in men. Both men and women, however, most commonly reported that they experienced all three types of distress. These results are discussed in relation to Western gender-specific sexual scripts. Clinical implications and the importance of couples therapy and suggestions for clinically useful diagnostic criteria are presented.
Leveraging Self-Affirmation to Improve Behavior Change: A Mobile Health App Experiment

Background mHealth interventions can help to improve the physical well-being of participants. Unfortunately, mHealth interventions often have low adherence and high attrition. One possible way to increase adherence is instructing participants to complete self-affirmation exercises. Self-affirmation exercises have been effective in increasing many types of positive behaviors. However, self-affirmation exercises often involve extensive essay writing, a task that is not easy to complete on mobile platforms. Objective This study aimed to adapt a self-affirmation exercise to a form better suited for delivery through a mobile app targeting healthy eating behaviors, and to test the effect of differing self-affirmation doses on adherence to behavior change goals over time. Methods We examined how varied self-affirmation doses affected behavior change in an mHealth app targeting healthy eating that participants used for 28 days. We divided participants into the 4 total conditions using a 2×2 factorial design. The first independent variable was whether the participant received an initial self-affirmation exercise. The second independent variable was whether the participant received ongoing booster self-affirmations throughout the 28-day study. To examine possible mechanisms through which self-affirmation may cause positive behavior change, we analyzed three aspects of self-affirmation effects in our research. First, we analyzed how adherence was affected by self-affirmation exercises. Second, we analyzed whether self-affirmation exercises reduced attrition rates from the app. Third, we examined a model for self-affirmation behavior change. Results Analysis of 3556 observations from 127 participants indicated that higher doses of self-affirmation resulted in improved adherence to mHealth intervention goals (coefficient 1.42, SE 0.71, P=.04). This increased adherence did not seem to translate to a decrease in participant attrition (P value range .61-.96), although our definition of attrition was conservative. Finally, we examined the mechanisms by which self-affirmation may have affected intentions of behavior change; we built a model of intention (R2=.39, P<.001), but self-affirmation did not directly affect final intentions (P value range .09-.93). Conclusions Self-affirmations can successfully increase adherence to recommended diet and health goals in the context of an mHealth app. However, this increase in adherence does not seem to reduce overall attrition. The self-affirmation exercises we developed were simple to implement and had a low cost for both users and developers. While this study focused on an mHealth app for healthy eating, we recommend that other mHealth apps integrate similar self-affirmation exercises to examine effectiveness in other behaviors and contexts.
Is transesophageal echocardiography needed for evaluating tissue-based transient ischemic attack?

Transient ischemic attack (TIA) is a warning signal for stroke. A comprehensive evaluation of TIA may reduce the risk for subsequent stroke. Data on the findings of cardiac evaluation with transesophageal echocardiography (TEE) in patients with TIA are sparse. Our aims were to determine the frequency of TEE performance and to investigate the findings of TEE in patients with TIA based on the new definition of TIA (i.e., transient neurological symptoms without evidence of infarction). During a 4-year period (2011–2014), 1071 patients (mean age, 70 ± 13 years; female, 49.7%) with TIA were included in a prospective study and evaluated. Of 1071 consecutive patients suffering from TIA, 288 patients (27%) underwent TEE. The median time between admission and TEE was 6 days. Patients with TIA who were evaluated by TEE were younger (67 vs. 71 years, P < 0.001) than those who were not evaluated by TEE. They had a higher rate of sensibility disturbance as a TIA symptom (39% vs. 31%, P = 0.012) but a lower rate of previous stroke (15% vs. 25%, P = 0.001) and atrial fibrillation (2% vs. 21%, P < 0.001) than those who did not. Foramen ovale was detected in 71 patients (25.7%), atrial septal aneurysm in 13 patients (4.6%), and severe atherosclerotic plaques (grade 4 and 5) in the aortic arch in 25 patients (8.7%). One patient (0.3%) had a fibroma detected by TEE. In 17 of the 288 patients (6%) who underwent TEE, the indication for anticoagulation therapy was based on the TEE results, and 1 patient with fibroma underwent heart surgery. During hospitalization, 7 patients experienced a subsequent stroke, and 27 patients had a recurrent TIA. At 3 months following discharge, the rates of readmission, stroke, recurrent TIA, and death were 19%, 2.7%, 4.2%, and 1.6%, respectively. The rates of mortality (0.9% vs. 1.8%, P = 0.7), stroke risk (1.9% vs. 3.0%, P = 0.8), and recurrent TIA (5.0% vs. 3.9%, P = 0.8) were similar in patients who underwent TEE and in those who did not. Performing TEE in patients with tissue-based TIA is helpful in detecting cardiac sources for embolism and may indicate for anticoagulation.
LncRNA HOTAIR/miR‐613/c‐met axis modulated epithelial‐mesenchymal transition of retinoblastoma cells

Since lncRNAs could modulate neoplastic development by modulating downstream miRNAs and genes, this study was carried out to figure out the synthetic contribution of HOTAIR, miR‐613 and c‐met to viability, apoptosis and proliferation of retinoblastoma cells. Totally 276 retinoblastoma tissues and tumour‐adjacent tissues were collected, and human retinoblastoma cell lines (ie, Y79, HXO‐Rb44, SO‐Rb50 and WERI‐RB1) were also gathered. Moreover, transfections of pcDNA3.1‐HOTAIR, si‐HOTAIR, miR‐613 mimic, miR‐613 inhibitor, pcDNA3.1/c‐met were performed to evaluate the influence of HOTAIR, miR‐613 and c‐met on viability, apoptosis and epithelial‐mesenchymal transition (EMT) of retinoblastoma cells. Dual‐luciferase reporter gene assay was also arranged to confirm the targeted relationship between HOTAIR and miR‐613, as well as between miR‐613 and c‐met. Consequently, up‐regulated HOTAIR and down‐regulated miR‐613 expressions displayed associations with poor survival status of retinoblastoma patients (P < 0.05). Besides, inhibited HOTAIR and promoted miR‐613 elevated E‐cadherin expression, yet decreased Snail and Vimentin expressions (P < 0.05). Simultaneously, cell proliferation and cell viability were also less‐motivated (P < 0.05). Nonetheless, c‐met prohibited the functioning of miR‐613, resulting in promoted cell proliferation and viability, along with inhibited cell apoptosis (P < 0.05). Finally, HOTAIR was verified to directly target miR‐613, and c‐met was the direct target gene of miR‐613 (P < 0.05). In conclusion, the role of lncRNA HOTAIR/miR‐613/c‐met signalling axis in modulating retinoblastoma cells’ viability, apoptosis and expressions of EMT‐specific proteins might provide evidences for developing appropriate diagnostic and treatment strategies for retinoblastoma.