Miracle-dz/UniFAR-FTUs huggingface dataset:
Behavioral Impact of Return of Genetic Test Results for Complex Disease: Systematic Review and Meta-Analysis

Objective: Advances in genomewide association studies have made possible the return of genetic risk results for complex diseases. Two concerns about these results are (a) negative psychological consequences and (b) viewing probabilistic results as deterministic, leading to misinterpretation and inappropriate decisions. The present study evaluates these concerns through a meta-analytic review of existing literature. Method: Seventeen genetic testing studies of complex disease, including 1,171 participants and reporting 195 effects, 104 of which were unadjusted for covariates, were meta-analyzed under a random effects model. Diseases included Alzheimer’s, cardiovascular and coronary heart disease, lung cancer, melanoma, thrombophilia, and type II diabetes. Six domains of behavioral–psychological reactions were examined. Results: Carriers showed significantly increased self-reported behavior change compared to noncarriers when assessed 6 months or later after results return (Hedges’s g = .36, p = .019). Conclusions: Return of genetic testing results for complex disease does not strongly impact self-reported negative behavior or psychological function of at-risk individuals. Return of results does appear to moderately increase self-reported healthy behavior in carriers, although research on objectively observed behavior change is needed. This is a growing area of research, with preliminary results suggesting potential positive implications of genetic testing for complex disease on behavior change.
Clinical outcomes of implants placed in ridge‐preserved versus nonpreserved sites: A 4‐year randomized clinical trial

BACKGROUND Consistent bone changes occur after tooth removal, often compromising the success of implants placed within the socket left to natural healing The long-term effect of ridge preservation on implant outcomes is still unclear. PURPOSE The aim of the study was to assess success and survival rates of implants placed in extraction sockets, with spontaneous healing, or grafted with cortical porcine bone, or collagenated corticocancellous porcine bone. MATERIALS AND METHODS Ninety patients in need for a single premolar/molar tooth extraction and an implant treatment were selected for the present study. Patients were randomly distributed among 3 groups: sites that healed naturally (ctrl), or sites that received ridge preservation with either cortical (cort) or collagenated corticocancellous porcine bone (coll). Three months after, all the experimental sites were reentered to insert implants. Marginal bone levels were recorded; soft tissues were analyzed and summarized with the Pink Esthetic Score (PES). Forty-two patients out of 90 (initial cohort study) completed the entire follow-up of 4 years. RESULTS Cumulative survival and success rates for all implants were 100% at a 4-year evaluation. Mean marginal bone loss (MBL) was 1.14 ± 0.23 mm in the cort group, 1.13 ± 0.29 mm in the coll group, and 1.92 ± 0.07 mm in the ctrl group. There were no significant differences between the 2 grafting materials but MBL was significantly greater in the nongrafted sites (P value < .001). The PES resulted significantly better (9.42 ± 0.75) for the cort group than for the coll group (8.53 ± 1.18) and ctrl group (6.07 ± 1.89) at 4-year evaluation. CONCLUSIONS Ridge preservation was more effective than natural healing in preserving marginal bone and in achieving better esthetic outcomes around implants 4 years after placement. The cortical porcine bone showed better clinical outcomes than collagenated corticocancellous porcine bone.
Impaired myogenic development, differentiation and function in hESC-derived SMA myoblasts and myotubes

Spinal muscular atrophy (SMA) is a severe genetic disorder that manifests in progressive neuromuscular degeneration. SMA originates from loss-of-function mutations of the SMN1 (Survival of Motor Neuron 1) gene. Recent evidence has implicated peripheral deficits, especially in skeletal muscle, as key contributors to disease progression in SMA. In this study we generated myogenic cells from two SMA-affected human embryonic stem cell (hESC) lines with deletion of SMN1 bearing two copies of the SMN2 gene and recapitulating the molecular phenotype of Type 1 SMA. We characterized myoblasts and myotubes by comparing them to two unaffected, control hESC lines and demonstrate that SMA myoblasts and myotubes showed altered expression of various myogenic markers, which translated into an impaired in vitro myogenic maturation and development process. Additionally, we provide evidence that these SMN1 deficient cells display functional deficits in cholinergic calcium signaling response, glycolysis and oxidative phosphorylation. Our data describe a novel human myogenic SMA model that might be used for interrogating the effect of SMN depletion during skeletal muscle development, and as model to investigate biological mechanisms targeting myogenic differentiation, mitochondrial respiration and calcium signaling processes in SMA muscle cells.
Comparison of Speed, accuracy, and User Friendliness between SSVEP-based BCI and Eyetracker

: This article intends to compare two rivaling technology tools that could reestablish communication for people with severe disabilities. One of the tested technologies, steady state visual evoked potentials (SSVEPs)- based Brain-Computer Interface (BCI), detects patterns in brain activity. Eye-tracking devices, on the other hand, measure the eye position, blinks, saccades, ﬁxation paths, and other eye-speciﬁc parameters. Both methods can be used to interpret the users intent allowing control of spelling applications. Accuracy and speed of these two control methods are compared. A graphical user interface (GUI) with 30 targets (letters of the alphabet and special characters) was developed implementing each of the two technologies. Nine participants (two female) completed the phrase “RHINE WAAL UNIVERSITY” with both technologies. As expected, the achieved ITR with the eye-tracking device was signiﬁcantly higher (91.8 bpm compared to 38.2 bpm for the SSVEP-based BCI). However, the eye tracking did not work for all of the participants, in this case the SSVEP-based interface can offer an alternative. The optimal interface needs to be customized individually.
Contralesional macrostructural plasticity of the insular cortex in patients with glioma

Objective To assess the homotopic structural plasticity in case of unilateral damage of the insula. Methods To detect changes in gray matter volumes of the contralesional insula from structural MRIs, we used voxel-based morphometry (VBM) in a sample of 84 patients with a diffuse low-grade glioma invading the left insula (insL group; n = 47) or the right insula (insR group; n = 37). Results The region of interest–based VBM analysis highlighted a large cluster of voxels with gray matter volume increase in the contralesional insula in both patient groups (k = 2,214 voxels for insL and k = 879 voxels for insR, p < 0.05, family-wise error corrected) compared with 24 age-matched healthy controls. Gray matter volume was increased for the entire insula (t69 = 3.63, p = 0.0016 for insL; t59 = 3.54, p = 0.0024 for insR, Bonferroni corrected), whereas no significant changes were found in 2 control regions for both patient groups. Furthermore, an increase of 24.6% and 31.6% in the gray matter volume was observed in the insula-related VBM cluster for insL and insR patients, respectively, compared with healthy controls (t69 = 7.39, p = 2.59 × 10−10 and t59 = 7.51, p = 3.61 × 10−10). Conclusions The reported results demonstrate that slow-growing but massive lesion infiltration of the insula induces marked increase of gray matter volume in the contralateral one. Our findings give support for a homotopic reorganization that might be a physiologic basis for the high level of functional compensation observed in patients with glioma.
Trends in the Incidence and Recurrence of Inpatient-Treated Spontaneous Pneumothorax, 1968-2016

Importance Spontaneous pneumothorax is a common disease known to have an unusual epidemiological profile, but there are limited contemporary population-based data. Objective To estimate the incidence of hospital admissions for spontaneous pneumothorax, its recurrence and trends over time using large, longstanding hospitalization data sets in England. Design, Setting, and Participants A population-based epidemiological study was conducted using an English national data set and an English regional data set, each spanning 1968 to 2016, and including 170 929 hospital admission records of patients 15 years and older. Final date of the study period was December 31, 2016. Exposures Calendar year (for incidence) and readmission to hospital for spontaneous pneumothorax (for recurrence). Main Outcomes and Measures Primary outcomes were rates of hospital admissions for spontaneous pneumothorax and recurrence, defined as a subsequent hospital readmission with spontaneous pneumothorax. Record-linkage was used to identify multiple admissions per person and comorbidity. Risk factors for recurrence over 5 years of follow-up were assessed using cumulative time-to-failure analysis and Cox proportional hazards regression. Results From 1968 to 2016, there were 170 929 hospital admissions for spontaneous pneumothorax (median age, 44 years [IQR, 26-88]; 73.0% male). In 2016, there were 14.1 spontaneous pneumothorax admissions per 100 000 population 15 years and older (95% CI, 13.7-14.4), a significant increase compared with earlier years, up from 9.1 (95% CI, 8.1-10.1) in 1968. The population-based rate per 100 000 population 15 years and older was higher for males (20.8 [95% CI, 20.2-21.4]) than for females (7.6 [95% CI, 7.2-7.9]). Of patients with spontaneous pneumothorax, 60.8% (95% CI, 59.5%-62.0%) had chronic lung disease. Record-linkage analysis demonstrated that the overall increase in admissions over time could be due in part to an increase in repeat admissions, but there were also significant increases in the annual rate of first-known spontaneous pneumothorax admissions in some population subgroups, for example in women 65 years and older (annual percentage change from 1968 to 2016, 4.08 [95% CI, 3.33-4.82], P < .001). The probability of recurrence within 5 years was similar by sex (25.5% [95% CI, 25.1%-25.9%] for males vs 26.0% [95% CI, 25.3%-26.7%] for females), but there was variation by age group and presence of chronic lung disease. For example, the probability of readmission within 5 years among males aged 15 to 34 years with chronic lung disease was 39.2% (95% CI, 37.7%-40.7%) compared with 19.6% (95% CI, 18.2%-21.1%) in men 65 years and older without chronic lung disease. Conclusions and Relevance This study provides contemporary information regarding the trends in incidence and recurrence of inpatient-treated spontaneous pneumothorax.
Thinking about your running movement makes you less efficient: attentional focus effects on running economy and kinematics

ABSTRACT A number of studies have shown that attentional focus instructions can effect running economy. This study assessed spiroergometry, as well as running kinematics as a possible mechanism to explain these effects. Twelve runners had to focus their attention on either their running movement, their breathing or on a video while running on a treadmill at a set, submaximum speed. Spiroergometry and running kinematics were measured. Results revealed worse running economy in both internal focus conditions (breathing and movement) compared to the external focus condition (video), replicating previous findings. In addition, vertical oscillation during the running movement was elevated in the movement compared to the video condition, indicating a less efficient running style. No changes in kinematics were found for the breathing compared to the video condition. Therefore, consciously focusing on the running movement moves runners away from their optimised running pattern and leads to detriments in economy. The decreases in running economy in the breathing condition can be better explained by changes in breathing patterns.
An integrative review on family caregivers’ involvement in care of home‐dwelling elderly

Often family members provide care-giving, which allows older adults to remain in their homes. With declining health and increasing frailty, care-giving of elderly people becomes a task of family caregivers (FC) in conjunction with home care nurses. It has been shown in both acute care settings and long-term care facilities that family members prefer to be involved in decision-making and care planning for their next of kin. Therefore, an integrative review was conducted to explore the body of knowledge of FCs' involvement in home-care settings from the FCs' perspective. CINAHL, PubMed, and Cochrane databases was searched with the terms family caregiver, involvement, home care, and community dwelling. Studies written in German or English between 1996 and 2017 focusing on FCs' caring for home-dwelling older adults together with home care nurses were included and critically appraised. The extracted findings were analysed with concept analysis method. Twenty-six studies were included and five themes were identified. Four themes formed the basis of assistance towards family caregivers by nurses and included "relationship building with professionals," "negotiating with professional care," "being professionally supported," and "managing role expectations and knowledge sharing". The fifth theme, "working together" described the mutual care for the care recipient. Although the first four themes were consistent with a pre-existing conceptual model by Sims-Gould and Marin-Matthews (2010), the fifth required an expansion of the model with an additional contribution "collaborative practice". The findings illustrate that involvement in care is an interactional process, which provides the basis for collaborative practices with the home care nurses for family caregivers. Family members often want to be part of the healthcare team, and nurses need contextual factors that allow providing their full range of skills and knowledge to involve family caregivers accordingly.
Comprehensive analysis of microRNA‐messenger RNA regulatory network in gemcitabine‐resistant bladder cancer cells

Chemotherapy is still a standard treatment of unresectable bladder cancer or distant metastases. The chemotherapy resistance always occurs after a period of treatment indicating poor prognosis. The current study aimed to explore the molecular mechanism of chemoresistance in bladder cancer cells. The gene expression profiles of GSE77883, including three untreated T24 cells samples and three gemcitabine‐resistant T24 cells samples, was downloaded from Gene Expression Omnibus database. The screening of differentially expressed genes (DEGs), gene function analysis, and interaction prediction between microRNAs (miRNAs) and DEGs were performed by R software. The protein‐protein interaction (PPI) and miRNA‐DEGs networks were constructed and visualized by Cytoscape software. Then, the small molecules, with potential synergistic or antagonistic effects to gemcitabine resistance, were identified using the Connectivity Map database. Finally, gemcitabine‐resistant T24 cell line was established and key genes were validated by quantitative real‐time polymerase chain reaction (qRT‐PCR). In total, 536 upregulated and 513 downregulated genes were screened and mainly enriched in oxidative stress response and signaling pathways related to extracellular matrix–receptor interaction and focal adhesion. PPI network showed interleukin 6, tumor necrosis factor, kinesin family member 11, and BUB1 mitotic checkpoint serine/threonine kinase B were key genes. The miRNA‐DEGs regulatory networks included 18 miRNAs and 185 DEGs, including miR‐182‐5p, miR‐590‐3p, miR‐320a and serum‐ and glucocorticoid‐regulated kinase 1 (SGK1). Then, the related key genes and miRNAs were confirmed by qRT‐PCR. Furthermore, 81 small molecules with antagonistic or synergistic effect to GEM were screened. We have investigated the molecular mechanisms driving GEM‐resistance in bladder cancer cells that would contribute to the development of chemotherapy for advanced bladder cancer.
Effects of pitch spatial references on players’ positioning and physical performances during football small-sided games

ABSTRACT The aim of this study was to identify the effects of adding spatial references during football small-sided games in youth players’ tactical and physical performance. Twelve under-15 players performed a Gk+ 6v6+ Gk game under two playing conditions: (i) without spatial references (CONTROL condition); (ii) with spatial references, by dividing equally the pitch into three corridors and three sectors (experimental situation, LINES). Players’ positional data was used to compute time-motion and tactical-related variables. The results revealed that performance under LINES situation increased the regularity in the zones occupied (~14%, Cohen’s d: 0.5; ±0.3; p = 0.003) and in the distance between teammates’ dyads (~19%, 0.9; ±0.2; p < 0.001). Oppositely, LINES condition decreased the longitudinal synchronization of players’ displacements (0.4; ±0.2; p = 0.002), players’ average speed (0.5; ±0.3; p = 0.002) and distance covered at lower (0.9; ±0.3; p < 0.001) and moderate speed (0.5; ±0.3; p < 0.001). Adding spatial references seems to promote a more structured pattern of play and increase positional regularity. However, coaches should be aware that this constraint may decrease the synchronization between players. Overall, these findings may be generalized to most invasion team sports.
Structure-Based Classification Defines the Discrete Conformational Classes Adopted by the Arenaviral GP1

The genetically and geographically diverse group of viruses within the family Arenaviridae includes a number of zoonotic pathogens capable of causing fatal hemorrhagic fever. The multisubunit GPC glycoprotein spike complex displayed on the arenavirus envelope is a key determinant of species tropism and a primary target of the host humoral immune response. Here, we show that the receptor-binding GP1 subcomponent of the GPC spike from Old World but not New World arenaviruses adopts a distinct, pH-independent conformation in the absence of the cognate GP2. Our analysis provides a structure-based approach to understanding the discrete conformational classes sampled by these therapeutically important targets, informing strategies to develop arenaviral glycoprotein immunogens that resemble GPC as presented on the mature virion surface. ABSTRACT The emergence of Old and New World arenaviruses from rodent reservoirs persistently threatens human health. The GP1 subunit of the envelope-displayed arenaviral glycoprotein spike complex (GPC) mediates host cell recognition and is an important determinant of cross-species transmission. Previous structural analyses of Old World arenaviral GP1 glycoproteins, alone and in complex with a cognate GP2 subunit, have revealed that GP1 adopts two distinct conformational states distinguished by differences in the orientations of helical regions of the molecule. Here, through comparative study of the GP1 glycoprotein architectures of Old World Loei River virus and New World Whitewater Arroyo virus, we show that these rearrangements are restricted to Old World arenaviruses and are not induced solely by the pH change that is associated with virus endosomal trafficking. Our structure-based phylogenetic analysis of arenaviral GP1s provides a blueprint for understanding the discrete structural classes adopted by these therapeutically important targets. IMPORTANCE The genetically and geographically diverse group of viruses within the family Arenaviridae includes a number of zoonotic pathogens capable of causing fatal hemorrhagic fever. The multisubunit GPC glycoprotein spike complex displayed on the arenavirus envelope is a key determinant of species tropism and a primary target of the host humoral immune response. Here, we show that the receptor-binding GP1 subcomponent of the GPC spike from Old World but not New World arenaviruses adopts a distinct, pH-independent conformation in the absence of the cognate GP2. Our analysis provides a structure-based approach to understanding the discrete conformational classes sampled by these therapeutically important targets, informing strategies to develop arenaviral glycoprotein immunogens that resemble GPC as presented on the mature virion surface.
Endothelial Cell Lineage Analysis Does Not Provide Evidence for EMT in Adult Valve Homeostasis and Disease

Epithelial‐to‐mesenchymal transition (EMT) enables stationary epithelial cells to exhibit migratory behavior and is the key step that initiates heart valve development. Recent studies suggest that EMT is reactivated in the pathogenesis of myxomatous valve disease (MVD), a condition that involves the progressive degeneration and thickening of valve leaflets. These studies have been limited to in vitro experimentation and reliance on histologic costaining of epithelial and mesenchymal markers as evidence of EMT in mouse and sheep models of valve disease. However, longitudinal analysis of cell lineage origins and potential pathogenic or reparative contributions of newly generated mesenchymal cells have not been reported previously. In this study, a genetic lineage tracing strategy was pursued by irreversibly labeling valve endothelial cells in the Osteogenesis imperfecta and Marfan syndrome mouse models to determine whether they undergo EMT during valve disease. Tie2‐CreER T2 and Cdh5(PAC)‐CreER T2 mouse lines were used in combination with colorimetric and fluorescent reporters for longitudinal assessment of endothelial cells. These lineage tracing experiments showed no evidence of EMT during adult valve homeostasis or valve pathogenesis. Additionally, CD31 and smooth muscle α‐actin (αSMA) double‐positive cells, used as an indicator of EMT, were not detected, and levels of EMT transcription factors were not altered. Interestingly, contrary to the endothelial cell‐specific Cdh5(PAC)‐CreER T2 driver line, Tie2‐CreER T2 lineage‐derived cells in diseased heart valves also included CD45+ leukocytes. Altogether, our data indicate that EMT is not a feature of valve homeostasis and disease but that increased immune cells may contribute to MVD. Anat Rec, 302:125–135, 2019. © 2018 Wiley Periodicals, Inc.
5G: performance and evaluation of FS-FBMC against OFDM for high data rate applications at 60 GHz

This study presents a frequency spreading filter bank multi-carrier (FS-FBMC) waveform as a potential candidate for the fifth generation (5G) network applications at millimetre-waves (mmWaves). The proposed model is developed based on the orthogonal frequency division multiplexing (OFDM) waveform standardised by IEEE 802.15. 3c for 60 GHz high data-rate applications. The effects of non-linearities of power amplifiers (PAs) at 60 GHz for both OFDM and FS-FBMC are presented and compared using a realistic PA model. In particular, the sensitivity of both transmission schemes to the non-linear effects is investigated and its impact on the performance degradation in terms of output-power-backoff, is characterised over typical indoor line-of-sight, kiosk and residential, 60 GHz IEEE channel models. The assessment metrics considered are bit error rate and out-of-band emissions. This study concludes radio access schemes for future communication generations, i.e. 5G may employ OFDM for up-link and FS-FBMC for down-link due to the sensitivity to PA non-linearities of both waveforms.