Miracle-dz/UniFAR-FTUs huggingface dataset:
Remediation of perceptual organisation in schizophrenia

ABSTRACT Introduction Impaired perceptual organisation in schizophrenia has been repeatedly described in clinical and research literatures. It has also been associated with problems in more complex aspects of visual function, including visuospatial and visual cognitive test performance. Two therapeutic interventions were developed here that target perceptual organisation: (1) Computer-based training, which emphasized stimulus-driven processing (bottom-up approach), and (2) Instrumental Enrichment therapy, which is a therapist-guided interactive learning method (top-down approach). Methods Twenty-eight patients diagnosed with schizophrenia or schizoaffective disorder participated in a 12-week programme. For both forms of interventions, task difficulty increased progressively, based upon successful performance. The third group of patients, which served as controls, received a similar therapeutic intervention that did not include a perceptual organisation component. Before and after intervention, participants received tests of perceptual organisation, as well as a battery of neuropsychological tests. Results Results indicate that both forms of intervention improved perceptual organisation ability relative to the control condition. In addition, the improvement was found for select neuropsychological tests, although the pattern of improvement did not favour capacities more closely associated with visual organisational or visuospatial function. Conclusions Together, results demonstrate the effectiveness of new remediation protocols that target mid-level visual processing, which generalized to select visual cognitive functions.
Staged Thoracoscopic Repair of Long-Gap Esophageal Atresia Without Temporary Gastrostomy.

INTRODUCTION Primary repair of long-gap esophageal atresia (LGEA) continues to present a surgical challenge. The number of treatment options, including the use of native esophagus or esophageal replacement, shows the difficulty in the treatment and lack of one superior option. Until recently all children with LGEA required temporary gastrostomy before esophageal reconstruction. OBJECTIVE The aim of the study is to present new therapeutic management in patients with LGEA, involving staged thoracoscopic procedure with internal traction without gastrostomy. MATERIALS AND METHODS Four neonates with LGEA were treated in two academic Departments of Pediatric Surgery in Poland from 2015 to 2018. The intervention was staged thoracoscopic approach, consisting in internal traction, followed by delayed esophageal anastomosis in neonatal period. The outcome measures were successful anastomosis, short time anastomosis complications, and timing of gastric/oral feeding. RESULTS Internal traction was placed between 2 and 6 days of life. A successful repair of native esophagus by the second approach in neonatal period without gastrostomy was achieved in 3 out of 4 neonates, 5-8 days after internal traction placement. No anastomotic leakage was observed, two anastomoses developed stricture managed with three and four sessions of repeated dilatation. Nasogastric tube feeding started between 5 and 7 days with full oral feeding achieved between 10 and 35 days after anastomosis. Follow-up was after 1-34 months. CONCLUSIONS Our technique should be considered an alternative first-line strategy for the repair of LGEA without the use of a gastrostomy.
Effectiveness and safety of rivaroxaban vs. warfarin in non-valvular atrial fibrillation patients with a non-sex-related CHA2DS2-VASc score of 1

AIMS To compare the effectiveness and safety of standard-dose rivaroxaban (20 mg o.d.) and warfarin in non-valvular atrial fibrillation (NVAF) patients with a non-sex-related CHA2DS2-VASc score of 1. METHODS AND RESULTS Analysis of United States Truven MarketScan claims from November 2011 to December 2016 for anticoagulant-naïve NVAF patients with a single non-sex-related stroke risk factor assigned 1-point in the CHA2DS2-VASc score and ≥12-months of continuous medical/prescription insurance coverage prior to the qualifying oral anticoagulant dispensing. Standard-dose rivaroxaban users were 1:1 propensity score-matched to warfarin users. Patients were followed until outcome occurrence, insurance disenrollment, or end of data availability. Primary outcomes included stroke or systemic embolism and major bleeding and were compared using Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). In all, 3319 rivaroxaban users were 1:1 propensity score-matched to 3319 warfarin users. Median (interquartile range) duration of follow-up was 1.6 (0.7, 2) years and the most common qualifying stroke risk factor was hypertension (n = 4532, 68.3%). Rivaroxaban was associated with a significant reduction in the 1-year stroke or systemic embolism vs. warfarin (HR 0.41, 95% CI 0.17-0.98), with no significant difference in overall major bleeding (HR 0.74, 95% CI 0.44-1.26) or major bleeding subtypes (HR ranging from 0.33 to 0.78, P > 0.05 for all). Similar results were seen after extending follow-up to 2 years. CONCLUSIONS Rivaroxaban may lower the rate of stroke or systemic embolism vs. warfarin in NVAF patients with a non-sex-related CHA2DS2-VASc score of 1 without impacting major bleeding.
In vitro model to assess the adsorption of oral veterinary drugs to mycotoxin binders in a feed- and aflatoxin B1-containing buffered matrix

ABSTRACT Mycotoxin binders are feed additives which are mixed in the feed to adsorb mycotoxins and thereby reducing their toxic effects on animals. Interactions with orally administered veterinary medicinal products, such as antimicrobials or coccidiostats, have been reported previously. This paper describes an in vitro model to screen the interaction between mycotoxin binders and veterinary drugs with respect to the non-specific binding of drugs. It is designed as a static setup using a single concentration of drug and binder in a feed-containing or a feed-plus-mycotoxin-containing matrix, buffered at different pH values. The model was applied to two frequently used antimicrobials in veterinary medicine, doxycycline (DOX) and tylosin (TYL), one major mycotoxin, aflatoxin B1 (AFB1), and four mycotoxin binders. Proportions of feed, DOX or TYL, AFB1, and binder are equivalent to the in vivo situation for broiler chickens, while pH and volume of the buffer are representative of the gastrointestinal tract of chickens. A substantial binding of DOX (~ 88%) and TYL (~ 66%) to the feed-matrix was observed. For the mycotoxin binders, similar results were obtained for DOX and TYL; more specifically up to an inclusion rate of 20 g binder/kg feed, no significant binding was demonstrated, determined as the free concentration of DOX and TYL. A single exception was noticed for TYL and one specific bentonite-based mycotoxin binder, for which no significant interaction could be demonstrated up to 10 g binder/kg but there was an effect at 20 g/kg. In all cases, there was no competition between the tested drugs DOX or TYL and the mycotoxin AFB1 for binding to the bentonite-based mycotoxin binder.
Comparative effectiveness of management options for patients with small renal masses: a prospective cohort study

To explore the comparative effectiveness of partial nephrectomy (PN), radical nephrectomy (RN), ablative therapies (ablation) and active surveillance (AS) for small renal masses (SRMs; tumour diameter ≤4.0 cm) in the domains of survival, renal function and quality of life (QoL) using the prospectively maintained Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) Registry.
Dietary Patterns Prior to Pregnancy and Associations with Pregnancy Complications

Few studies have explored pre-pregnancy diet and its relationship with pregnancy outcomes. The objectives of this study were to: (1) derive pre-pregnancy dietary patterns for women enrolled in a prospective cohort in the province of Alberta, Canada; (2) describe associations between dietary patterns and socio-demographic characteristics; and (3) describe associations between dietary patterns and pregnancy complications. Upon enrolment into the Alberta Pregnancy Outcomes and Nutrition (APrON) study (median age of gestation, 17 weeks), women (n = 1545) completed a validated 142-item food frequency questionnaire recording food and beverages consumed “in the 12 months prior to pregnancy”. Other assessments included pre-pregnancy body mass index (BMI), gestational weight gain, gestational hypertension, gestational diabetes, and socio-demographic characteristics. Dietary patterns were derived using principal components analysis. Scores were calculated to represent adherence with each dietary pattern retained. Four dietary patterns were retained, accounting for 22.9% of the variation in the overall diet. Dietary patterns were named the “healthy”, “meat and refined carbohydrate”, “beans, cheese and salad” or “tea and coffee” patterns. Higher “healthy” pattern scores prior to pregnancy were associated with lower odds of developing gestational hypertension during pregnancy (adjusted Odds Ratio (OR): 0.6, 95% Confidence Intervals (CI): 0.4, 0.9). Diet prior to pregnancy is an important target for interventions and may reduce the likelihood of developing complications such as gestational hypertension during pregnancy.
Team Red, White & Blue: a community-based model for harnessing positive social networks to enhance enrichment outcomes in military veterans reintegrating to civilian life

Abstract Military service assimilates individuals into a socially cohesive force to address dangerous and traumatic situations that have no counterpart in civilian life. Upon leaving active duty, many veterans experience a “reverse culture shock” when trying to reintegrate into civilian institutions and cultivate supportive social networks. Poor social reintegration is associated with greater morbidity and premature mortality in part due to adoption of risky health behaviors, social isolation, and inadequate engagement in health care services. Although institutions like the Veterans Health Administration (VA) do much to address the complex psychosocial and health care needs of veterans and their families with evidence-based care, only 61% of Operations Enduring and Iraqi Freedom (OEF/OIF) Veterans are enrolled in VA care and there are numerous perceived barriers to care for enrollees. To address this gap, a community-based nonprofit organization, Team Red, White & Blue (RWB), was created to help veterans establish health-enriching social connections with communities through the consistent provision of inclusive and locally tailored physical, social, and service activities. This article provides an overview of the development and refinement of a theory-based framework for veteran health called the Enrichment Equation, comprised of three core constructs: health, people, and purpose. By operationalizing programming activities and roles, we describe how theoretical components were translated into a social networking implementation package that enabled rapid national spread of Team RWB. We conclude with future opportunities to partner with researchers and other organizations to understand program impact, and to identify effective intervention components that could be adapted for similar vulnerable groups.
Crystal structure of plasma kallikrein reveals the unusual flexibility of the S1 pocket triggered by Glu217

Serine proteases play important roles in numerous physiological and pathophysiological processes. Moreover, serine proteases are classical subjects for studies of catalytic and inhibitory mechanisms of enzymes. Here, we determined the crystal structures of a serine protease, murine plasma kallikrein (mPK), and its complex with a peptidic inhibitor. Although mPK in the complex adopts a canonical protease structure, the apo‐mPK exhibits a previously unobserved structural feature: the entrance of the intact S1 pocket is blocked by Glu217. In addition, molecular dynamics simulations and functional assays support the flexibility of Glu217 and suggest that this flexibility plays a role in regulating the activity of serine proteases.
Phyllanthusmin Derivatives Induce Apoptosis and Reduce Tumor Burden in High-Grade Serous Ovarian Cancer by Late-Stage Autophagy Inhibition

High-grade serous ovarian cancer (HGSOC) is a lethal gynecological malignancy with a need for new therapeutics. Many of the most widely used chemotherapeutic drugs are derived from natural products or their semi-synthetic derivatives. We have developed potent synthetic analogues of a class of compounds known as phyllanthusmins, inspired by natural products isolated from Phyllanthus poilanei Beille. The most potent analogue, PHY34, had the highest potency in HGSOC cell lines in vitro and displayed cytotoxic activity through activation of apoptosis. PHY34 exerts its cytotoxic effects by inhibiting autophagy at a late stage in the pathway, involving the disruption of lysosomal function. The autophagy activator, rapamycin, combined with PHY34 eliminated apoptosis, suggesting that autophagy inhibition may be required for apoptosis. PHY34 was readily bioavailable through intraperitoneal administration in vivo where it significantly inhibited the growth of cancer cell lines in hollow fibers, as well as reduced tumor burden in a xenograft model. We demonstrate that PHY34 acts as a late-stage autophagy inhibitor with nanomolar potency and significant antitumor efficacy as a single agent against HGSOC in vivo. This class of compounds holds promise as a potential, novel chemotherapeutic and demonstrates the effectiveness of targeting the autophagic pathway as a viable strategy for combating ovarian cancer. Mol Cancer Ther; 17(10); 2123–35. ©2018 AACR.
Health professionals’ dealing with hope in palliative patients with cancer, an explorative qualitative research

Hope is important for individuals with cancer in palliative care. Health professionals' perspective on hope affects the communication with palliative patients. The aim of this study was to explore how Dutch health professionals deal with palliative patients with cancer who hope for prolongation of life. Focus group discussions (FGD) were conducted. An interpretive description approach was used to understand the interpretation of and reaction to hopefulness in palliative patients with cancer by health professionals. Three FGDs were held, each consisting of five to ten health professionals working with palliative patients recruited in a general Dutch hospital and homecare organisation. The ways in which the participating health professionals interpret hope in palliative individuals with cancer and their behaviour towards these hopeful palliative patients are shaped by their reliance on their own normative ideas. Patients' hopefulness generally violates these norms and is, therefore, considered a problem that requires intervention. Hope that does not correspond with the medical facts is experienced as problematic by Dutch health professionals who therefore believe they should intervene and do something about it. Health professionals are challenged to face and address patients' and families' perceptions of hope, especially when those perceptions might differ from their own as professionals.
Independent validation of machine performance check for the Halcyon and TrueBeam linacs for daily quality assurance

Abstract Purpose To evaluate the ability of the machine performance check (MPC) on the Halcyon to detect errors, with comparison with the TrueBeam. Methods MPC is an automated set of quality assurance (QA) tests that use a phantom placed on the couch and the linac's imaging system(s) to verify the beam constancy and mechanical performance of the Halcyon and TrueBeam linacs. In order to evaluate the beam constancy tests, we inserted solid water slabs between the beam source and the megavoltage imager to simulate changes in beam output, flatness, and symmetry. The MPC results were compared with measurements, using two‐dimensional array under the same conditions. We then studied the accuracy of MPC geometric tests. The accuracies of the relative gantry offset and couch shift tests were evaluated by intentionally inserting phantom shifts, using a rotating or linear motion stage. The MLC offset and absolute gantry offset tests were assessed by miscalibrating these motions on a Halcyon linac. Results For the Halcyon system, the average difference in the measured beam output between the IC Profiler and MPC, after intentional changes, was 1.3 ± 0.5% (for changes ≤5%). For Halcyon, the MPC test failed (i.e., prevented treatment) when the beam symmetry change was over 1.9%. The accuracy of the MLC offset test was within 0.05 mm. The absolute gantry offset test was able to detect an offset as small as 0.02°. The accuracy of the absolute couch shift test was 0.03 mm. The accuracy of relative couch shift test of Halcyon was measured as 0.16 mm. Conclusion We intentionally inserted errors to evaluate the ability of the MPC to identify errors in dosimetric and geometric parameters. These results showed that the MPC is sufficiently accurate to be effectively used for daily QA of the Halcyon and TrueBeam treatment devices.
Competitive organelle-specific adaptors recruit Vps13 to membrane contact sites

The regulated expansion of membrane contact sites, which mediate the nonvesicular exchange of lipids between organelles, requires the recruitment of additional contact site proteins. Yeast Vps13 dynamically localizes to membrane contacts that connect the ER, mitochondria, endosomes, and vacuoles and is recruited to the prospore membrane in meiosis, but its targeting mechanism is unclear. In this study, we identify the sorting nexin Ypt35 as a novel adaptor that recruits Vps13 to endosomal and vacuolar membranes. We characterize an interaction motif in the Ypt35 N terminus and identify related motifs in the prospore membrane adaptor Spo71 and the mitochondrial membrane protein Mcp1. We find that Mcp1 is a mitochondrial adaptor for Vps13, and the Vps13–Mcp1 interaction, but not Ypt35, is required when ER-mitochondria contacts are lost. All three adaptors compete for binding to a conserved six-repeat region of Vps13 implicated in human disease. Our results support a competition-based model for regulating Vps13 localization at cellular membranes.
Propofol inhibits the voltage-gated sodium channel NaChBac at multiple sites

Voltage-gated sodium (NaV) channels are important targets of general anesthetics, including the intravenous anesthetic propofol. Electrophysiology studies on the prokaryotic NaV channel NaChBac have demonstrated that propofol promotes channel activation and accelerates activation-coupled inactivation, but the molecular mechanisms of these effects are unclear. Here, guided by computational docking and molecular dynamics simulations, we predict several propofol-binding sites in NaChBac. We then strategically place small fluorinated probes at these putative binding sites and experimentally quantify the interaction strengths with a fluorinated propofol analogue, 4-fluoropropofol. In vitro and in vivo measurements show that 4-fluoropropofol and propofol have similar effects on NaChBac function and nearly identical anesthetizing effects on tadpole mobility. Using quantitative analysis by 19F-NMR saturation transfer difference spectroscopy, we reveal strong intermolecular cross-relaxation rate constants between 4-fluoropropofol and four different regions of NaChBac, including the activation gate and selectivity filter in the pore, the voltage sensing domain, and the S4–S5 linker. Unlike volatile anesthetics, 4-fluoropropofol does not bind to the extracellular interface of the pore domain. Collectively, our results show that propofol inhibits NaChBac at multiple sites, likely with distinct modes of action. This study provides a molecular basis for understanding the net inhibitory action of propofol on NaV channels.
Radiographic and Anatomic Landmarks of the Major Knee Ligaments.

Proper knee function relies on multiple ligaments that provide stability during force transmission across the joint. Although there are various secondary stabilizers, ligaments are the primary restraints against anterior, posterior, varus, and valgus forces. The anterior cruciate ligament (ACL); posterior cruciate ligament (PCL); medial, or tibial, collateral ligament (MCL); lateral, or fibular, collateral ligament (LCL); medial patellofemoral ligament (MPFL); and (controversial) anterolateral ligament (ALL) are the most frequently discussed knee ligaments. When these ligaments are repaired or reconstructed, biomechanical data support recreating the patient’s normal anatomy by locating the native insertion sites. For example, Stephen et al. demonstrated that an incorrect MPFL femoral location during reconstruction results in significant increases in articular contact pressures and medial patellar tilt. Okoroafor et al. showed that a nonanatomic proximal tibial PCL tunnel led to an increase in posterior tibial translation after cyclic loading. Araujo et al. found that anatomic ACL reconstructions more accurately recreated the in situ native ACL forces compared with nonanatomic femoral tunnel locations. These nonanatomic constructs may be predisposed to premature failure because of abnormal strain and loading patterns, as evidenced by a study that showed that 19% (8) of 42 ACL reconstruction failures were associated with a nonanatomic femoral ACL tunnel. The osseous insertions of these ligaments have been described in the literature using anatomic and radiographic landmarks. However, such publications are often focused on a particular insertion of a ligament andmaydescribe the anatomic, but not the radiographic, insertion or the converse. A thorough understanding of the anatomic and radiographic landmarks is imperative