Miracle-dz/UniFAR-FTUs huggingface dataset:
A review of virtual reality technologies in the field of communication disability: implications for practice and research

Abstract Background: Technology devices and applications including virtual reality (VR) are increasingly used in healthcare research and practice as tools to promote health and wellbeing. However, there is limited research examining the potential for VR to enable improved communication for people with communication disability. Aims: To review: (a) current research using VR in speech-language pathology; and (b) the ethical and safety considerations of VR research, to inform an agenda for future research applying VR in the field of speech-language pathology. Main contribution: This review reveals that there is an emergent body of literature applying VR to improve or develop physical, psychological and communication interventions. Use of non-immersive virtual environments to provide speech-language pathology assessment or intervention for people with communication disability has demonstrated positive outcomes, with emerging evidence of the transfer of functional communication skills from virtual to real-world environments. However, the use of VR technology and immersive virtual environments in communication disability practice and research introduces safety and ethical issues that must be carefully considered. Conclusions: Research employing VR is in its infancy in the field of speech-language pathology. Early evidence from other healthcare disciplines suggests that VR is an engaging means of delivering immersive and interactive training to build functional skills that can be generalized to the real world. While the introduction of new technology requires careful consideration of research ethics and patient safety, future VR communication research could proceed safely with adequate engagement of interdisciplinary teams and technology specialists. Implications for rehabilitation Immersive virtual reality may be used in rehabilitation to simulate natural environments to practice and develop communication skills. The sense of immersion that can be achieved using virtual reality may promote the generalization of skills learnt during clinical rehabilitation to real-world situations. Ethical and safety considerations, including cybersecurity and cybersickness, must be carefully monitored during all virtual reality research.
Pharmacokinetic Simulations of Intravitreal Biologicals: Aspects of Drug Delivery to the Posterior and Anterior Segments

Biologicals are important ocular drugs that are be delivered using monthly and bimonthly intravitreal injections to treat retinal diseases, such as age-related macular degeneration. Long acting delivery systems are needed for prolongation of their dosing interval. Intravitreal biologicals are eliminated from the eye via the aqueous humor outflow. Thus, the anterior and posterior segments are exposed to the drug. We utilized a kinetic simulation model to estimate protein drug concentrations in the vitreous and aqueous humor after bolus injection and controlled release administration to the vitreous. The simulations predicted accurately the experimental levels of 5 biologicals in the vitreous and aqueous humor. The good match between the simulations and experimental data demonstrated almost complete anterior segment bioavailability, and major dose sparing with ocular controlled release systems. Overall, the model is a useful tool in the design of intraocular delivery of biologicals.
Differential gene expression between in vivo and in vitro maturation: a comparative study with bovine oocytes derived from the same donor pool

Objective: In vitro maturation has been shown to influence gene expression in oocytes, but a common shortcoming in reports on the matter has been the use of different donors in each experimental group thus disregarding donor effects. This study aimed to investigate the abundance of mRNA in oocytes matured in vivo and in vitro obtained from the same group of donors. Methods: A bovine model was used to assess the relative abundance of specific transcripts in in vitro-matured (IN VITRO-OPU) and in vivo-matured (IN VIVO-OPU) oocytes collected from the same donors by transvaginal ovum pick-up (OPU). Transcript abundance in oocytes from the IN VIVO-OPU group and oocytes matured in vitro but retrieved from different cows slaughtered at a commercial abattoir (IN VITRO-Abattoir group) was also compared. Total RNA was extracted from denuded oocytes and cDNA was produced via reverse transcription using an oligo(dT) primer for relative quantification of eight target transcripts by real-time PCR. Results: Oocytes in the IN VITRO-OPU group had lower (p<0.05) abundance of peroxiredoxin 1 (Prdx1), heat shock protein 70.1 (Hsp70.1), growth and differentiation factor 9 (Gdf9), and maternal antigen that embryo requires (Mater) transcripts than the oocytes in the IN VIVO-OPU group, all obtained from the same pool of donor cows. Similar results were seen in the comparisons involving the IN VIVO-OPU and IN VITRO-Abattoir groups (p<0.05). Conclusion: In vitro maturation affected the abundance of polyadenylated transcripts in the oocyte cytoplasm when compared to in vivo maturation induced by exogenous hormones in oocytes collected from the same donor pool.
KEYNOTE‐025: Phase 1b study of pembrolizumab in Japanese patients with previously treated programmed death ligand 1–positive advanced non–small‐cell lung cancer

Pembrolizumab, a humanized monoclonal antibody against programmed death 1 (PD‐1), has been shown to improve overall survival (OS) in patients with previously treated advanced non–small‐cell lung cancer (NSCLC) with programmed death ligand 1 (PD‐L1) tumor proportion score (TPS) ≥1%. We report safety and efficacy results from the phase 1b KEYNOTE‐025 study, which evaluated pembrolizumab in Japanese patients with previously treated NSCLC. Eligible patients had histologically/cytologically confirmed advanced NSCLC with PD‐L1 TPS ≥1% and had received ≥1 platinum‐doublet chemotherapy. Patients received pembrolizumab 10 mg/kg once every 3 weeks for 2 years or until disease progression/unacceptable toxicity. Primary objectives were to evaluate the safety of pembrolizumab in patients with PD‐L1 TPS ≥1% and the objective response rate (ORR) per RECIST version 1.1 in patients with PD‐L1 TPS ≥50%. Thirty‐eight patients were enrolled and received ≥1 pembrolizumab dose. The median (range) age was 66.0 (41‐78) years, and 61% had received ≥2 prior systemic therapies. Eleven patients (29%) experienced grade 3‐5 treatment‐related adverse events (AE); 9 patients (24%) experienced immune‐mediated AE and infusion reactions, with pneumonitis (11%; any grade) being most common. Among evaluable patients with PD‐L1 TPS ≥50% (n = 11), ORR was 27% (95% CI, 6‐61). Among evaluable patients with PD‐L1 TPS ≥1% (n = 37), ORR was 22% (95% CI, 10‐38). Median (95% CI) progression‐free survival and OS were 3.9 (2.0‐6.2) months and 19.2 (8.0‐26.7) months, respectively. In summary, pembrolizumab was generally well tolerated and showed promising antitumor activity in Japanese patients with previously treated PD‐L1–expressing NSCLC. Outcomes were consistent with those from the phase 3 KEYNOTE‐010 study. (Trial registration number: ClinicalTrials.gov, NCT02007070.)
How the cell cycle clock ticks

Eukaryotic cell division has been studied thoroughly and is understood in great mechanistic detail. Paradoxically, however, we lack an understanding of its core control process, in which the master regulator of the cell cycle, cyclin-dependent kinase (CDK), temporally coordinates an array of complex molecular events. The core elements of the CDK control system are conserved in eukaryotic cells, which contain multiple cyclin–CDK forms that have poorly defined and partially overlapping responsibilities in the cell cycle. However, a single CDK can drive all events of cell division in both mammalian and yeast cells, and in fission yeast a single mitotic cyclin can drive the cell cycle without major problems. But how can the same CDK induce different events when activated at different times during the cell cycle? This question, which has bewildered cell cycle researchers for decades, now has a sufficiently clear mechanistic answer. This Perspective aims to provide a synthesis of recent data to facilitate a better understanding of this central cellular control system.
Multiplex assay for multiomics advances in personalized-precision medicine

ABSTRACT Building the future of precision medicine is the main focus in cancer domain. Clinical trials are moving toward an array of studies that are more adapted to precision medicine. In this domain, there is an enhanced need for biomarkers, monitoring devices, and data-analysis methods. Omics profiling using whole genome, epigenome, transcriptome, proteome, and metabolome can offer detailed information of the human body in an integrative manner. Omes profiles reflect more accurately real-time physiological status. Personalized omics analyses both disease as a whole and the main disease processes, for a better understanding of the individualized health. Through this, multi-omic approaches for health monitoring, preventative medicine, and personalized treatment can be targeted simultaneously and can lead clinicians to have a comprehensive view on the diseasome.
Tackling the complexity of nonalcoholic steatohepatitis treatment: challenges and opportunities based on systems biology and machine learning approaches.

Nonalcoholic fatty liver disease (NAFLD) is regarded as the most frequent cause of chronic liver damage (1,2). The natural history of the disease presents a complex scenario of potential progression into severe clinical outcomes, including nonalcoholic steatohepatitis (NASH), NASH-fibrosis, cirrhosis, and hepatocellular carcinoma (1,2). In addition, NAFLD is closely associated with comorbidities of the metabolic syndrome (MetS), including type 2 diabetes, obesity, arterial hypertension, and dyslipidemia, which together aggravate the morbidity and mortality associated with the disease.
Subjective Executive Function Weaknesses Are Linked to Elevated Internalizing Symptoms Among Community Adolescents

Adolescence is a period of high risk for the emergence of problems with anxiety and depression. Theory and research suggest that executive function deficits accompany internalizing and externalizing problems, although more evidence is required to understand these relationships. This study employed a commonly used rating scale of executive function, the Brief Rating Inventory of Executive Function, and examined relationships with self- and parent-reported internalizing and externalizing problems among a community sample of 299 adolescents. The sample was 56.2% female, with a mean age of 16.22 years (SD = 2.36 years). Analyses revealed strong associations between poorer self- and parent-reported executive function skills and the severity of anxiety and depression symptoms. Problems with executive function were also associated with externalizing symptoms. These results indicate that subjective ratings of executive function capture important aspects of cognitive problems that are highly relevant to adolescent psychopathology in a transdiagnostic fashion.
Mesocarnivore community structure under predator control: Unintended patterns in a conservation context

Across the Mediterranean, conservation programmes often operate concomitantly with hunting interests within game-lands. Carnivore guilds lie at the interface between contrasting management goals, being simultaneously fundamental components of ecosystems and targets of predator control to reduce predation on game species. Here, we evaluate the composition and spatial structure of a mesocarnivore community in a protected area of Southeast Portugal, with high economic investment in conservation and significant hunting activity. Between June and August 2015, we deployed 77 camera-traps across a ~80 km2 area. We report on interspecific disparities in mesocarnivore occupancy and associated environmental determinants. Contrasting occupancy states suggest an unbalanced community, biased towards the widespread occurrence of the red fox Vulpes vulpes (ψ^=0.92±0.04) compared to other species (stone marten Martes foina, European badger Meles meles, Egyptian mongoose Herpestes ichneumon, common genet Genetta genetta, and Eurasian otter Lutra lutra) exhibiting spatially-restricted occupancy patterns (ψ^/naïveoccupancy<0.35). The feral cat Felis silvestris catus was the exception (ψ^=0.48±0.11) and, together with the stone marten, exhibited a positive association with human settlements. These findings are consistent with theoretical predictions on how mesocarnivore communities are shaped by the effects of non-selective predator control, paradoxically favouring species with higher population growth rates and dispersal abilities, such as the red fox. Our results reinforce the need to understand the role of predator control as a community structuring agent with potential unintended effects, while exposing issues hindering such attempts, namely non-selective illegal killing or biased/concealed information on legal control measures.
TCR Retrogenic Mice as a Model To Map Self-Tolerance Mechanisms to the Cancer Mucosa Antigen GUCY2C

Characterizing self-tolerance mechanisms and their failure is critical to understand immune homeostasis, cancer immunity, and autoimmunity. However, examination of self-tolerance mechanisms has relied primarily on transgenic mice expressing TCRs targeting well-characterized, but nonphysiologic, model Ags, such as OVA and hemagglutinin. Identifying TCRs directed against bona fide self-antigens is made difficult by the extraordinary diversity of TCRs and the low prevalence of Ag-specific clones (<10–100 naive cells per organism), limiting dissection of tolerance mechanisms restricting immunity to self-proteins. In this study, we isolated and characterized TCRs recognizing the intestinal epithelial cell receptor and colorectal cancer Ag GUCY2C to establish a model to study self-antigen–specific tolerance mechanisms. GUCY2C-specific CD4+ effector T cells were isolated from immunized, nontolerant Gucy2c−/− mice. Next-generation sequencing identified GUCY2C-specific TCRs, which were engineered into CD4+ T cells in vitro to confirm TCR recognition of GUCY2C. Further, the generation of “retrogenic” mice by reconstitution with TCR-transduced hematopoietic stem cells resulted in normal CD4+ T cell development, responsiveness to immunization, and GUCY2C-induced tolerance in recipient mice, recapitulating observations in conventional models. This retrogenic model can be employed to define self-tolerance mechanisms restricting T and B cell responses to GUCY2C to optimize colorectal cancer immunotherapy without autoimmunity.
Scope and extent of healthcare-associated Middle East respiratory syndrome coronavirus transmission during two contemporaneous outbreaks in Riyadh, Saudi Arabia, 2017

Abstract Objective To investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications. Design Outbreak investigation. Setting Cases presented in 4 healthcare facilities in Riyadh, Saudi Arabia: a tertiary-care hospital, a specialty pulmonary hospital, an outpatient clinic, and an outpatient dialysis unit. Methods Contact tracing and testing were performed following reports of cases at 2 hospitals. Laboratory results were confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) and/or genome sequencing. We assessed exposures and determined seropositivity among available healthcare personnel (HCP) cases and HCP contacts of cases. Results In total, 48 cases were identified, involving patients, HCP, and family members across 2 hospitals, an outpatient clinic, and a dialysis clinic. At each hospital, transmission was linked to a unique index case. Moreover, 4 cases were associated with superspreading events (any interaction where a case patient transmitted to ≥5 subsequent case patients). All 4 of these patients were severely ill, were initially not recognized as MERS-CoV cases, and subsequently died. Genomic sequences clustered separately, suggesting 2 distinct outbreaks. Overall, 4 (24%) of 17 HCP cases and 3 (3%) of 114 HCP contacts of cases were seropositive. Conclusions We describe 2 distinct healthcare-associated outbreaks, each initiated by a unique index case and characterized by multiple superspreading events. Delays in recognition and in subsequent implementation of control measures contributed to secondary transmission. Prompt contact tracing, repeated testing, HCP furloughing, and implementation of recommended transmission-based precautions for suspected cases ultimately halted transmission.
Flat Panel Computed Tomography in the Diagnosis of Superior Semicircular Canal Dehiscence Syndrome.

HYPOTHESIS Flat panel computed tomography (FPCT) provides more accurate measurements of dimensions for superior semicircular canal dehiscence (SCD) than multislice CT (MSCT). BACKGROUND SCD syndrome occurs when a bony defect of the superior semicircular canal causes vestibular and auditory symptoms. MSCT can overestimate the size of the canal defect, with possible over-diagnosis of SCD and suboptimal selection of surgical approach. The higher resolution of FPCT should afford more accurate measurements of these defects. METHODS Radiographic and surgical measurements were compared in 22 patients (mean age 49.4) with clinical SCD syndrome and canal defects confirmed at surgery. Twenty second FPCT scans were acquired before surgery with parameters: 109Kv, small focus, 200 degrees rotation angle, and 0.4 degree per frame angulation step. Dehiscence dimensions were measured from orthogonal multiplanar reconstructions on a high-resolution liquid crystal display monitor and compared with actual measurements recorded during microsurgery. RESULTS SCD dimensions by FPCT (x) were 2.8 ± 1.6 mm for length and 0.72 ± 0.28 mm for width. The surgical measurements (y) were 2.8 ± 1.7 mm for length and 0.72 ± 0.34 mm for width. Linear fits between x and y yielded R values of 0.93 (length) and 0.66 (width). Our previous study using MSCT had R values of 0.28 (length) and 0.48 (width). The average difference between each FPCT and corresponding surgical measurement was not significantly different from zero, whereas the results for MSCT were significantly different. CONCLUSION FPCT can provide more accurate measurements of SCD than MSCT. Clinicians should consider using FPCT for imaging suspected SCD.
Analysis of Adjuvant Endocrine Therapy in Practice From Electronic Health Record Data of Patients With Breast Cancer.

PURPOSE Adjuvant endocrine therapy is a long-term drug therapy prescribed to prevent recurrence of hormone receptor-positive breast cancer. Data on adjuvant endocrine therapy are reported though clinical trials, which may differ from treatment practice and outcomes in the general population of patients with breast cancer. With secondary use of electronic health record (EHR) data, we summarize adjuvant endocrine treatment practice and outcomes in real-world settings. METHODS We analyzed treatment data derived from EHR data on 1,587 patients with stage I to III breast cancer at a National Cancer Institute-designated comprehensive cancer center to learn the frequencies of real-world adjuvant endocrine drug switches and discontinuation and to explore the potential cause for drug switches and discontinuation from medical records. We measured rates of drug use, drug switches, early drug discontinuation, adverse events, recurrence, and death. We also measured adverse events and change in menopause status as potential causes for drug switch and discontinuation. RESULTS Within the study population, approximately 49% of patients were lost to follow-up or did not complete adjuvant treatment through 5 years. Fifty-two percent of patients switched to a different endocrine therapy drug during their treatment. We found that age is correlated with drug switches and that adverse events are correlated with drug switches and discontinuation. We also found that patients who switched to an alternative endocrine therapy during treatment were more likely to complete 5 years of treatment. CONCLUSION This study describes long-term adjuvant endocrine treatment in real-world settings and demonstrates the ability to leverage longitudinal EHR data to characterize oral medication treatment patterns in patients with cancer.
Depletion of dAKAP1–protein kinase A signaling islands from the outer mitochondrial membrane alters breast cancer cell metabolism and motility

Breast cancer screening and new precision therapies have led to improved patient outcomes. Yet, a positive prognosis is less certain when primary tumors metastasize. Metastasis requires a coordinated program of cellular changes that promote increased survival, migration, and energy consumption. These pathways converge on mitochondrial function, where distinct signaling networks of kinases, phosphatases, and metabolic enzymes regulate these processes. The protein kinase A–anchoring protein dAKAP1 compartmentalizes protein kinase A (PKA) and other signaling enzymes at the outer mitochondrial membrane and thereby controls mitochondrial function and dynamics. Modulation of these processes occurs in part through regulation of dynamin-related protein 1 (Drp1). Here, we report an inverse relationship between the expression of dAKAP1 and mesenchymal markers in breast cancer. Molecular, cellular, and in silico analyses of breast cancer cell lines confirmed that dAKAP1 depletion is associated with impaired mitochondrial function and dynamics, as well as with increased glycolytic potential and invasiveness. Furthermore, disruption of dAKAP1–PKA complexes affected cell motility and mitochondrial movement toward the leading edge in invasive breast cancer cells. We therefore propose that depletion of dAKAP1–PKA “signaling islands” from the outer mitochondrial membrane augments progression toward metastatic breast cancer.
Intensive care nurses' perceptions of various ethics concerns affecting clinical research.

BACKGROUND Intensive-care unit (ICU) nurses have an important role in the recruitment of patients for scientific research and in the performance of clinical research. AIM A study was conducted to examine ICU nurses' perceptions of ethics-related aspects of ICU-based research. The study focused on nurse attitudes and knowledge related to clinical research, with special emphasis on perceptions of the informed-consent process in ICU research. METHOD The study applied a descriptive qualitative approach, involving semi-structured group interviews and theme-based inductive content analysis. Subjects were ICU nurses (n = 28) at a university hospital ICU who had experience with research protocols applied in that unit. FINDINGS The nurses had mainly positive perceptions of clinical studies. They found research beneficial for future patients and for society. The nurses considered the information given to them about the studies inadequate. They were concerned about the fact that the consent for research is almost always obtained at the beginning of the ICU care, when patients and relatives are still in the crisis period. This limits the possibility of understanding and assimilating the information provided on the study. CONCLUSIONS The role of ICU nurses in clinical studies should be more prominent and taken into account in the planning of ICU studies.