Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of pharmacological therapies for the treatment of opioid-induced constipation: systematic review and network meta-analysis

Objective Opioids are increasingly prescribed in the West and have deleterious GI consequences. Pharmacological therapies to treat opioid-induced constipation (OIC) are available, but their relative efficacy is unclear. We performed a systematic review and network meta-analysis to address this deficit in current knowledge. Design We searched MEDLINE, EMBASE, EMBASE Classic and the Cochrane central register of controlled trials through to December 2017 to identify randomised controlled trials (RCTs) of pharmacological therapies in the treatment of adults with OIC. Trials had to report a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Efficacy and safety of pharmacological therapies was reported as a pooled relative risk (RR) with 95% CIs to summarise the effect of each comparison tested and ranked treatments according to their P-score. Results Twenty-seven eligible RCTs of pharmacological therapies, containing 9149 patients, were identified. In our primary analysis, using failure to achieve an average of ≥3 bowel movements (BMs) per week with an increase of ≥1 BM per week over baseline or an average of ≥3 BMs per week, to define non-response, the network meta-analysis ranked naloxone first in terms of efficacy (RR=0.65; 95% CI 0.52 to 0.80, P-score=0.84), and it was also the safest drug. When non-response to therapy was defined using failure to achieve an average of ≥3 BMs per week, with an increase of ≥1 BM per week over baseline, naldemedinewas ranked first (RR=0.66; 95% CI 0.56 to 0.77, P score=0.91) and alvimopan second (RR=0.74; 95% CI 0.57 to 0.94, P-score=0.71). Conclusion In network meta-analysis, naloxone and naldemedine appear to be the most efficacious treatments for OIC. Naloxone was the safest of these agents.
Self-determined motivation for practice in university music students

This study adopted self-determination theory as means to understanding the motivation of university music students. The self-determination theory framework contends that three psychological needs of competence, relatedness, and autonomy must be fulfilled in order to maintain psychological wellbeing. In turn, needs fulfilment results in autonomous motivation, in which activities are perceived to be aligned with the self and are consequently experienced as personally important, interesting, and enjoyable. We surveyed students (N = 392) from schools of music in nine universities in Australia and New Zealand to examine whether needs fulfilment and autonomous motivation within the university music learning context would explain context-specific affect and behaviour. Hypothesised relationships were tested using structural equation modelling. Psychological needs fulfilment and autonomous motivation explained more frequent practice, more frequent quality practice, and a higher preference for challenging tasks. This study is among the first self-determination theory studies in the domain of music learning at the university level, and thus the results are described in terms of the potential of this theory to more fully explain interesting and under-researched aspects of this environment, including student wellbeing, anxiety, preparations for a long-term career in music, and pedagogical implications.
Interinstrument Variability in Hertel-Type Exophthalmometers

Purpose To investigate variability in measurements of axial globe position taken with different exophthalmometers of the same style and manufacturer by the same observer. Methods In this small clinical study, 10 Hertel-type mirror exophthalmometers were used to measure the degree of exophthalmos of a plastic head. The deepest points on the lateral orbital margins were marked to ensure accurate placement of the instrument. A single observer, masked to previous measurements, recorded multiple measurements with each instrument over several days. Results Variation was seen between instruments from different manufacturers and more interestingly, between the same design of instruments from the same company. The measurement of axial globe position varied by up to 2.9 mm between instruments of the same make. There was also variation in the measurement of the relative axial globe position of the model. This measurement varied from 0.6 to 2.4 mm. The mean variation of readings taken with the same instrument was 0.5 mm. Conclusions It is already considered good practice to minimize interobserver error by recording the make of exophthalmometer used. This small study also suggests that the same instrument should be used for each examination to minimize error caused by variation between instruments of the same make. Variation of 1.5 to 2.0 mm could affect patient treatment when a difference in measurement of 2 mm is regarded as significant during serial or relative exophthalmometry.
Soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors required during Trypanosoma cruzi parasitophorous vacuole development

Trypanosoma cruzi, the etiologic agent of Chagas disease, is an obligate intracellular parasite that exploits different host vesicular pathways to invade the target cells. Vesicular and target soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors (SNAREs) are key proteins of the intracellular membrane fusion machinery. During the early times of T. cruzi infection, several vesicles are attracted to the parasite contact sites in the plasma membrane. Fusion of these vesicles promotes the formation of the parasitic vacuole and parasite entry. In this work, we study the requirement and the nature of SNAREs involved in the fusion events that take place during T. cruzi infection. Our results show that inhibition of N‐ethylmaleimide‐sensitive factor protein, a protein required for SNARE complex disassembly, impairs T. cruzi infection. Both TI‐VAMP/VAMP7 and cellubrevin/VAMP3, two v‐SNAREs of the endocytic and exocytic pathways, are specifically recruited to the parasitophorous vacuole membrane in a synchronized manner but, although VAMP3 is acquired earlier than VAMP7, impairment of VAMP3 by tetanus neurotoxin fails to reduce T. cruzi infection. In contrast, reduction of VAMP7 activity by expression of VAMP7's longin domain, depletion by small interfering RNA or knockout, significantly decreases T. cruzi infection susceptibility as a result of a minor acquisition of lysosomal components to the parasitic vacuole. In addition, overexpression of the VAMP7 partner Vti1b increases the infection, whereas expression of a KIF5 kinesin mutant reduces VAMP7 recruitment to vacuole and, concomitantly, T. cruzi infection. Altogether, these data support a key role of TI‐VAMP/VAMP7 in the fusion events that culminate in the T. cruzi parasitophorous vacuole development.
Towards a Dynamic Visualization of Online Collaborative Learning

Socio-constructivism and connectivism theories pinpoint the importance of collaboration for learning. Nevertheless , the online social interactions underlying the collaboration processes are still not well understood. As a result, learning designers have difficulties creating effective collaborative activities in Massive Open On-line Courses (MOOCs). As for online learners, they are often isolated and require a lot of self-regulation to succeed. The research effort presented in this paper covers a review of visualization techniques supporting the online collaborative learning process. Our findings show that some visualizations have the potential to develop the learners' reflexivity. Therefore, we give an overview of collaboration importance and how it could be enhanced with such visualizations. Our goal is to identify a new approach to visualize learners' activities in MOOCs, while supporting collaboration and self-regulation.
Interactions between Measles, Mumps and Rubella(Mmr) Vaccines and Atopic Diseases in Children

Background: Epidemiologic data on atopic diseases are scared. Different studies have shown that the burden of atopic diseases is varying in space and time. Several factors are impacting on epidemiology of atopic in children. Among them, MMR vaccination has been a topic of divergences. Objective: To establish whether the MMR vaccination may influence the risk of atopic diseases in children. Methods: We conducted electronic search terms included MESH or key words with “Atopic diseases” and “MMR vaccination” and “Children”. Databases for peer-reviewed articles included Pub Med, CENTRAL, Scopus and CINAHL Plus. Additionally, Grey literature was obtained from Google and WHO database. Main results: Among 304 potentially relevant articles identified, 8 peer-reviewed articles met the inclusion criteria. Due to the lack of standardized reporting of different outcomes and different study designs, we reported the results narratively based on P-value and 95% CI. We found three studies that demonstrated that MMR vaccination increased the fold of asthma in children (P<0.05). In contrast, two studies have approved that MMR vaccination is benefit in preventing asthma in children. MMR vaccination decreases asthma respectively by OR 0.36 95%CI (0.14-0.91) and OR 0.96 95% CI (0.76-1.21). Two studies reported MMR vaccination increase the eczema OR in two studies with respectively OR: 1.77 95% CI (1.20-2.61) and OR 1.86 95%CI (1.25-2.79). On the other hand, three studies revealed that MMR vaccination did not have any effect on atopic eczema with respectively P=0.830, OR 0.94 95% CI (0.77-1.15) and P=0.90. Conclusion: Based on the variability between studies, we hypothesize that judging the association between MMR vaccination and atopic diseases could not be fruitful in understanding different mechanisms. In this context, we suggested the interactions between Gene-environment MMR vaccination and atopic diseases that could clarify divergences between the results.
Practical Report on Long-term Disaster Mental Health Services Following the Great East Japan Earthquake: Psychological and Social Background of Evacuees in Sendai City in the Mid- to Long-term Post-disaster Period

Abstract Objective The Great East Japan Earthquake, which occurred on March 11, 2011, caused unprecedented damage. To address evacuees’ psychosocial issues, our disaster mental health team provided psychosocial support in the form of careful listening and providing information for reconstruction. Methods To summarize evacuees’ psychosocial issues, we reviewed records of our daily activities and analyzed factors related to continuation or termination of support. Terminated support was defined as the resolution or improvement of psychological issues relative to the time of initial support. Results Based on logistic regression analysis, living in prefabricated temporary housing (odds ratio [OR]: 0.37; 95% confidence interval [CI]: 0.19-0.72), a high number of improved stress symptoms (0.81; 95% CI: 0.67-0.99), and higher support frequency (0.84; 95% CI: 0.78-0.90) were significantly associated with a lower likelihood of continuing support. Conversely, economic and resettlement issues (2.75; 95% CI: 1.63-4.64) and high numbers of stress symptoms (1.24; 95% CI: 1.06-1.45) were strongly and significantly associated with continuing support, particularly in the mid- to long-term phase following the earthquake (ie, after August 1, 2011). No significant association was found between support status and alcohol problems or disaster-related experiences (eg, loss of family or housing). Conclusion Our findings highlight the need to be aware of evacuees’ social issues such as resettlement in the mid- to long-term post-disaster phase. (Disaster Med Public Health Preparedness. 2017;11:439–450)
The Clinical Activity of PD-1/PD-L1 Inhibitors in Metastatic Non–Clear Cell Renal Cell Carcinoma

A multicenter pooled analysis revealed modest antitumor activity of PD-1/PD-L1 inhibitors in patients with rare kidney cancer subtypes. Programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors have shown activity in metastatic clear cell renal cell carcinoma (ccRCC). Data on the activity of these agents in patients with non–clear cell RCC (nccRCC) or patients with sarcomatoid/rhabdoid differentiation are limited. In this multicenter analysis, we explored the efficacy of PD-1/PD-L1 inhibitors in patients with nccRCC or sarcomatoid/rhabdoid differentiation. Baseline and follow-up demographic, clinical, treatment, and radiographic data were collected. The primary endpoint was objective response rate. Secondary endpoints include time-to-treatment failure (TTF), overall survival (OS), and biomarker correlates. Forty-three patients were included: papillary (n = 14; 33%), chromophobe (n = 10; 23%), unclassified (n = 9; 21%), translocation (n = 3; 7%), and ccRCC with sarcomatoid differentiation (n = 7, 16%). Of those 43 patients, 11 patients (26%) had sarcomatoid and/or rhabdoid differentiation (n = 7 with ccRCC; n = 4 nccRCC). Overall, 8 patients (19%) objectively responded, including 4 patients (13%) who received PD-1/PD-L1 monotherapy. Responses were observed in patients with ccRCC with sarcomatoid and/or rhabdoid differentiation (n = 3/7, 43%), translocation RCC (n = 1/3, 33%), and papillary RCC (n = 4/14, 29%). The median TTF was 4.0 months [95% confidence interval (CI), 2.8–5.5] and median OS was 12.9 months (95% CI, 7.4–not reached). No specific genomic alteration was associated with clinical benefit. Modest antitumor activity for PD-1/PD-L1–blocking agents was observed in some patients with nccRCC. Further prospective studies are warranted to investigate the efficacy of PD-1/PD-L1 blockade in this heterogeneous patient population. Cancer Immunol Res; 6(7); 758–65. ©2018 AACR.
Predicting the Surgical Margin of Resection in Periocular Cutaneous Neoplasms and the Significance of Reconstruction Following Mohs Micrographic Surgery

Purpose: To evaluate the features of periocular cutaneous malignancies that may contribute to larger surgical defects or require more complex reconstructive procedures. Methods: A retrospective review of 181 patients with biopsy proven periocular cutaneous malignancies seen between April 2005 and September 2010, and undergoing Mohs micrographic surgery was performed. The longest horizontal and vertical diameters of the tumor and the post-Mohs surgical defect were measured in each patient. These measurements were used to calculate the relative margin of resection (MOR) required for tumor eradication as well as the size of the surgical defect. The date of surgery, histologic diagnosis and location of the tumor, type of reconstruction, and the presence of recurrence were also recorded. Results: The average MOR for all tumor subtypes taken together was 3.4 mm horizontally and 2.6 mm vertically for basal cell carcinomas (BCCA). The post-Mohs defect area was 3.2 times greater than the preoperative tumor area for all BCCA subtypes, and 3.9 times greater for morphea type (p = 0.8083). The average MOR for squamous cell carcinomas (SCCA) was 5.1 mm horizontally and 3.7 mm vertically. The post-Mohs defect area was 3.8 times greater than the preoperative tumor area for SCCAs. When comparing the preoperative horizontal tumor diameter to the horizontal MOR of BCCAs and SCCAs, the correlation was 0.23 (p < 0.0001) and 0.31 (p < 0.0001), respectively. While the average MOR was within standard limits, a significant number of tumors required a greater MOR. On review of the data, 30.6% of patients with BCCA required a MOR greater than 3 mm, 17.3% of patients with BCCA required a MOR greater than 4 mm, and 29.1% of patients with SCCA required a MOR of greater than 5 mm. Tumors located at the lateral canthus required the largest MOR (p < 0.01), while those on the lower eyelid were associated with the smallest MOR in BCCAs. As expected from anatomical considerations, tumors at the medial canthus required significantly more complex reconstruction procedures (p < 0.01). An ordered logistic regression model demonstrated that BCCA preoperative clinical tumor surface area was a significant indicator for the degree of reconstruction required (p < 0.01). Conclusions: Standard 3 mm to 4 mm MOR for BCCAs, and 5 mm MOR for SCCAs could result in an unacceptable risk of tumor recurrence if the surgical margins are not examined histologically. With increasing preoperative tumor size, there is an increase in the MOR required for BCCA and SCCA, supporting that large tumors require a greater MOR.
Modeling bacteria fate and transport in watersheds to support TMDLs

Fecal contamination of surface waters is a critical water-quality issue, leading to human illnesses and deaths. Total Maximum Daily Loads (TMDLs), which set pollutant limits, are being developed to address fecal bacteria impairments. Watershed models are widely used to support TMDLs, although their use for simulating in-stream fecal bacteria concentrations is somewhat rudimentary. This article provides an overview of fecal microorganism fate and transport within watersheds, describes current watershed models used to simulate microbial transport, and presents case studies demonstrating model use. Bacterial modeling capabilities and limitations for setting TMDL limits are described for two widely used watershed models (HSPF and SWAT) and for the load-duration method. Both HSPF and SWAT permit the user to discretize a watershed spatially and bacteria loads temporally. However, the options and flexibilities are limited. The models are also limited in their ability to describe bacterial life cycles and in their ability to adequately simulate bacteria concentrations during extreme climatic conditions. The load-duration method for developing TMDLs provides a good representation of overall water quality and needed water quality improvement, but intra-watershed contributions must be determined through supplemental sampling or through subsequent modeling that relates land use and hydrologic response to bacterial concentrations. Identified research needs include improved bacteria source characterization procedures, data to support such procedures, and modeling advances including better representation of bacteria life cycles, inclusion of more appropriate fate and transport processes, improved simulation of catastrophic conditions, and creation of a decision support tool to aid users in selecting an appropriate model or method for TMDL development.
Alleviation of Neuropathic Pain Hypersensitivity by Inhibiting Neuronal Pentraxin 1 in the Rostral Ventromedial Medulla

Peripheral nerve injury causes spontaneous and long-lasting pain, hyperalgesia, and allodynia. Excitatory amino acid receptor-dependent increases in descending facilitatory drive from the brainstem rostral ventromedial medulla (RVM) contribute to injury-evoked hypersensitivity. Although increased excitability likely reflects changes in synaptic efficacy, the cellular mechanisms underlying injury-induced synaptic plasticity are poorly understood. Neuronal pentraxin 1 (NP1), a protein with exclusive CNS expression, is implicated in synaptogenesis and AMPA receptor recruitment to immature synapses. Its role in the adult brain and in descending pain facilitation is unknown. Here, we use the spared nerve injury (SNI) model in rodents to examine this issue. We show that SNI increases RVM NP1 expression and constitutive deletion or silencing NP1 in the RVM, before or after SNI, attenuates allodynia and hyperalgesia in rats. Selective rescue of RVM NP1 expression restores behavioral hypersensitivity of knock-out mice, demonstrating a key role of RVM NP1 in the pathogenesis of neuropathic pain.
Soccer Players and Their Media-Related Behavior

Using the concept of mediatization, in this article, we analyze the relationship between sport and media from a sport-centered perspective. Examining the autobiographies of 14 German and English soccer players, we investigate how athletes use media outlets, what they perceive as the media’s influence and its logic, and—crucially—how this usage and these perceptions affect their own media-related behavior. Our findings demonstrate the important role of the media for the sports systems from the athlete’s point of view and demonstrate the research potential of mediatization as a fruitful concept in studies on sport communication. On the one hand, the sport stars reflect in their autobiographies that their status and income depend on media coverage; and on the other hand, they complain about the omnipresence of the media, especially offside the pitch and feel unfairly treated by the tabloid press, both in England and in Germany.
Radiation with or without Antiandrogen Therapy in Recurrent Prostate Cancer

Background Salvage radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate‐cancer recurrence signaled by a persistently or recurrently elevated prostate‐specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown. Methods In a double‐blind, placebo‐controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal involvement, and a detectable PSA level of 0.2 to 4.0 ng per milliliter to undergo radiation therapy and receive either antiandrogen therapy (24 months of bicalutamide at a dose of 150 mg daily) or daily placebo tablets during and after radiation therapy. The primary end point was the rate of overall survival. Results The median follow‐up among the surviving patients was 13 years. The actuarial rate of overall survival at 12 years was 76.3% in the bicalutamide group, as compared with 71.3% in the placebo group (hazard ratio for death, 0.77; 95% confidence interval, 0.59 to 0.99; P=0.04). The 12‐year incidence of death from prostate cancer, as assessed by means of central review, was 5.8% in the bicalutamide group, as compared with 13.4% in the placebo group (P<0.001). The cumulative incidence of metastatic prostate cancer at 12 years was 14.5% in the bicalutamide group, as compared with 23.0% in the placebo group (P=0.005). The incidence of late adverse events associated with radiation therapy was similar in the two groups. Gynecomastia was recorded in 69.7% of the patients in the bicalutamide group, as compared with 10.9% of those in the placebo group (P<0.001). Conclusions The addition of 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy resulted in significantly higher rates of long‐term overall survival and lower incidences of metastatic prostate cancer and death from prostate cancer than radiation therapy plus placebo. (Funded by the National Cancer Institute and AstraZeneca; RTOG 9601 ClinicalTrials.gov number, NCT00002874.)
Acute effect of 3 stretching techniques on sideward movements in tennis

Stretching exercises are widely used as a part of the warm-up in sports, although stretching benefits are still questioned. The aim of this study was to analyze the acute effect of three stretching techniques performed during the warm-up, on typical tennis sideward movements. 20 tennis players (6 women and 14 men, aged 17.75 ± 1.7 years, weight 67.05 ± 10.07 Kg, height 173, 4 ± 10.12 cm) participated. The effect of three of the most popular stretching techniques (PNF, Static and Ballistic) as well as the absence of stretching during the warm-up was analyzed using a sideward movement test (Brown, Piorkowski, Roetert & Woods, 1995). Results showed the best performance time (p 0.05) on performance time between the three conditions in which stretching was included during the warm-up. It can be concluded that to stretch (PNF, Static or Ballistic) during warm up reduces performance in sideward movements in tennis.