Miracle-dz/UniFAR-FTUs huggingface dataset:
Commitment to Aerobic Glycolysis Sustains Immunosuppression of Human Mesenchymal Stem Cells

Human mesenchymal stem cells (hMSCs) promote endogenous tissue repair in part by coordinating multiple components of the host immune system in response to environmental stimuli. Recent studies have shown that hMSCs are metabolically heterogeneous and actively reconfigure metabolism to support the biochemical demands of tissue repair. However, how hMSCs regulate their energy metabolism to support their immunomodulatory properties is largely unknown. This study investigates hMSC metabolic reconfiguration during immune activation and provides evidence that the hMSC metabolic state significantly influences their immunomodulatory properties. Specifically, hMSC immune polarization by interferon‐gamma (IFN‐γ) treatment leads to remodeling of hMSC metabolic pathways toward glycolysis, which is required to sustain the secretion of immunosuppressive factors. IFN‐γ exposure also inhibited mitochondrial electron transport activity, and the accumulation of mitochondrial reactive oxygen species plays an important signaling role in this metabolic reconfiguration. The results also show that activation of the Akt/mTOR signaling pathway is required for metabolic reconfiguration during immune polarization and that interruption of these metabolic changes alters the immune response in IFN‐γ licensed hMSCs. The results demonstrate the potential of altering hMSC metabolism to enhance their immunomodulatory properties and therapeutic efficacy in various diseases. Stem Cells Translational Medicine 2019;8:93–106
Effect of hyperbaric oxygen therapy on chronic neurocognitive deficits of post-traumatic brain injury patients: retrospective analysis

Objectives The aim of the study is to evaluate the effect of hyperbaric oxygen therapy (HBOT) in participants suffering from chronic neurological deficits due to traumatic brain injury (TBI) of all severities in the largest cohort evaluated so far with objective cognitive function tests and metabolic brain imaging. Methods A retrospective analysis was conducted of 154 patients suffering from chronic neurocognitive damage due to TBI, who had undergone computerised cognitive evaluations pre-HBOT and post-HBOT treatment. Results The average age was 42.7±14.6 years, and 58.4% were men. All patients had documented TBI 0.3–33 years (mean 4.6±5.8, median 2.75 years) prior to HBOT. HBOT was associated with significant improvement in all of the cognitive domains, with a mean change in global cognitive scores of 4.6±8.5 (p<0.00001). The most prominent improvements were in memory index and attention, with mean changes of 8.1±16.9 (p<0.00001) and 6.8±16.5 (p<0.0001), respectively. The most striking changes observed in brain single photon emission computed tomography images were in the anterior cingulate and the postcentral cortex, in the prefrontal areas and in the temporal areas. Conclusions In the largest published cohort of patients suffering from chronic deficits post-TBI of all severities, HBOT was associated with significant cognitive improvements. The clinical improvements were well correlated with increased activity in the relevant brain areas.
Dynamic functional connectivity analysis reveals decreased variability of the default‐mode network in developing autistic brain

Accumulating neuroimaging evidence suggests that abnormal functional connectivity of the default mode network (DMN) contributes to the social‐cognitive deficits of autism spectrum disorder (ASD). Although most previous studies relied on conventional functional connectivity methods, which assume that connectivity patterns remain constant over time, understanding the temporal dynamics of functional connectivity during rest may provide new insights into the dysfunction of the DMN in ASD. In this work, dynamic functional connectivity analysis based on sliding time window correlation was applied to the resting‐state functional magnetic resonance imaging data of 28 young children with ASD (age range: 3–7 years) and 29 matched typically developing controls (TD group). In addition, k‐means cluster analysis was performed to identify distinct temporal states based on the spatial similarity of each functional connectivity pattern. Compared with the TD group, young children with ASD showed decreased dynamic functional connectivity variance between the posterior cingulate cortex (PCC) and the right precentral gyrus, which is negatively correlated with social motivation and social relating. Cluster analysis revealed significant differences in functional connectivity patterns between the ASD and TD groups in discrete temporal states. Our findings reveal that atypical dynamic interactions between the PCC and sensorimotor cortex are associated with social deficits in ASD. Results also highlight the critical role of PCC in the social‐cognitive deficits of ASD and support the concept that understanding the dynamic neural interactions among brain regions can provide insights into functional abnormalities in ASD. Autism Research 2018, 11: 1479–1493. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.
Internal, External, and Ecological Validity in Research Design, Conduct, and Evaluation

Reliability and validity describe desirable psychometric characteristics of research instruments. The concept of validity is also applied to research studies and their findings. Internal validity examines whether the study design, conduct, and analysis answer the research questions without bias. External validity examines whether the study findings can be generalized to other contexts. Ecological validity examines, specifically, whether the study findings can be generalized to real-life settings; thus ecological validity is a subtype of external validity. These concepts are explained using examples so that readers may understand why the consideration of internal, external, and ecological validity is important for designing and conducting studies, and for understanding the merits of published research.
Persistently Transmitted Viruses Restrict the Transmission of Other Viruses by Affecting Their Vectors

Diverse pathogens, plant hosts, insect vectors, and non-vector herbivores coexist and interact in natural systems. An example is the cooccurrence of insects Bemisia tabaci Q and Frankliniella occidentalis and the pathogens tomato yellow leaf curl virus (TYLCV) and tomato spotted wilt virus (TSWV) on the same plant. In addition, both TYLCV and TSWV are persistently transmitted in these insect species. However, TSWV reduces the fitness of B. tabaci Q; therefore, we investigated whether TSWV affects the transmission of TYLCV to tomato. Both TYLCV and TSWV are persistently transmitted. Although B. tabaci Q cannot transmit TSWV, we found that this insect species is able to acquire and retain this virus serotype, indicating that the effects of TSWV on TYLCV transmission in the current study result from effects on the vector. The acquisition, retention, and transmission of TYLCV by B. tabaci Q were reduced when the insect vector contained TSWV. Additionally, the TYLCV acquisition and transmission by B. tabaci Q were reduced when the host plant was inoculated with TSWV before TYLCV or simultaneously with TYLCV. We also found that F. occidentalis fecundity and transmission of TSWV were reduced when F. occidentalis contained TYLCV. Our findings are consistent with the hypothesis that persistently transmitted viruses can restrict the transmission of other viruses by affecting their insect vectors.
The circadian clock regulates the diurnal levels of microbial short‐chain fatty acids and their rhythmic effects on colon contractility in mice

The microbiota shows diurnal oscillations that are synchronized by the host's circadian clock and feeding rhythms. Short‐chain fatty acids (SCFAs) produced by the microbiota are possible synchronizers of peripheral circadian clocks. We aimed to investigate whether faecal SCFAs show a diurnal rhythm that regulates the rhythm of SCFA receptor expression (FFAR2/3, OLFR78, HCAR2) and SCFA‐induced colonic contractility. The role of the circadian clock was studied in mice lacking the core clock gene Bmal1.
Multi-Phase Obfuscation of Fault Secured DSP Designs With Enhanced Security Feature

Digital signal processing (DSP) cores are an integral part of consumer electronics devices. This paper presents a novel methodology for obfuscation of transient fault secured circuits. The approach presented obfuscates fault secured DSP circuits such that the functions of the resulting hardware become non-obvious to an adversary (hindering reverse engineer process). The proposed methodology employs hybrid transformations in succession such as redundant operation removal, resource transformation, and connectivity change using tree height transformation, logic transformation, etc. These are achieved without affecting the functionality of the underlying DSP circuits or requiring significant increase in silicon footprint. The proposed methodology integrates an enhanced fault security feature using multi-cuts that ensures maximum detection capability against transient faults in the DSP circuit. Results of proposed approach indicate stronger obfuscation and enhanced fault security at lower design cost (avg. reduction ~14%), compared to prior art.
Unprecedented pace and partnerships: the story of and lessons learned from one Ebola vaccine program

ABSTRACT Introduction: The Ebola epidemic in West Africa from 2014 to 2016 was unique in its size, location, and duration; this article reviews the experiences and lessons learned for one vaccine candidate developed during the outbreak and discusses critical gaps that still exist today which will need to be addressed for successful end to end emerging infectious disease vaccine product development in the future. Areas Covered: Through the formation of numerous international partnerships, the rVSVΔG-ZEBOV-GP vaccine advanced through Phase I/II/III clinical trials which resulted in favorable Phase III efficacy results. Key lessons learned that could be used to facilitate future vaccine development efforts include sufficient preclinical work in relevant animal models, innovative partnerships created to pool resources and expertise, and ‘hyper’ coordination and communication among partners to build trust and ensure an adequate regulatory package needed to license a vaccine. Expert Commentary: As evidenced by the 2014–2016 outbreak in West Africa as well as the two other most recent outbreaks in the Democratic Republic of the Congo in 2018, there is an urgent need to develop new models for emerging infection vaccine development where trusted partners come together and where the development of vaccines is a shared responsibility conducted in advance of the next crisis.
Justice Involvement and Treatment Use Among Rural Veterans

Veterans in rural areas and veterans involved in the criminal justice system have experienced less access to, and use of, health care. However, there is limited information on the treatment needs and health care access of justice-involved veterans who live in rural areas. This study used national Veterans Health Administration data from Fiscal Year 2014 to examine the interactive effect of rural/urban residence and justice involvement on mental health and substance use disorder treatment entry among veterans diagnosed with mental health or substance use disorders. Of veterans residing in rural areas, 15,328 (2.5%) were justice-involved and 607,819 (97.5%) veterans had no known justice involvement. Among veterans in urban areas, 54,525 (4.3%) were justice-involved and 1,213,766 (95.7%) had no known justice involvement. Rural residence was associated with lower access to mental health or substance use disorder treatment in the non-justice-involved sample but not the justice-involved sample. Justice-involvement was associated with higher odds of entering mental health or substance use disorder treatment for veterans in rural and in urban areas. Substance use disorder treatment entry could be improved for all veterans, particularly rural veterans who are not justice-involved. Telehealth, outreach services, and integrated treatment may help address challenges to treatment entry experienced by rural veterans and justice-involved veterans.
The influence of diet and behaviour on metabolic syndrome and the prevalence of metabolic syndrome according to different definitions in west China.

BACKGROUND AND OBJECTIVES This study investigated the updated prevalence of metabolic syndrome among adults in West China and the influence of diet and behaviour on metabolic syndrome. METHODS AND STUDY DESIGN A cross-sectional survey was conducted from 2013-2014, and multi-stage stratified clustering sampling was applied in 12 counties of Sichuan province. Data regarding metabolic syndrome and style risk factors were collected through interviewer-administered questionnaires, and physical measurements were recorded following a standardized protocol. Logistic regression models were used to explore the association between metabolic syndrome and its risk factors. RESULTS A total of 7,131 adults participated. The prevalence of metabolic syndrome was 16.9% and 23.8% according to the International Diabetes Federation criteria and the consensus definition, respectively. The International Diabetes Federation criteria failed to identify 28.8% of the participants identified by the consensus definition. The odds ratios (ORs) of suffering from Metabolic syndrome in people eating pork every week compared with at lower frequencies, people eating more than 100 g of red meat/day, people with more sedentary behaviour per day, and people consuming at least 20 cigarettes/day were 1.76 (1.09-2.84), 1.28 (1.01- 1.62), 1.03 (0.99-1.07), and 1.46 (1.12-1.92), respectively, according to the consensus definition, and 1.51 (1.09- 2.10), 1.4 (1.14-1.72), 1.07 (1.02-1.13), and 1.5 (1.16-1.94), respectively, based on the International Diabetes Federation criteria. CONCLUSIONS The International Diabetes Federation criteria were less sensitive in identifying metabolic syndrome than the consensus definition. More sedentary behaviour, smoking >=20 cigarettes per day, and a higher frequency of pork intake increased the risk of metabolic syndrome in this study.
How Working Memory Provides Representational Change During Insight Problem Solving

Numerous studies of insight problem solving are focused on both the control and storage systems of working memory. We obtained contradictory data about how working memory systems are involved in insight problem solving process. We argue that measuring the dynamics of the control system and storage systems through the course of problem solving can provide a more refined view on the processes involved, as a whole, and explain the existing controversies. We theorize that specific insight mechanisms require varying working memory capacities at different stages of the problem solving process. Our study employed a dual task paradigm to track the dynamics of working memory systems load during problem solving by measuring the reaction time in a secondary probe-task during different stages of problem solving. We varied the modality (verbal, visual) and the complexity of the probe-task during insight and non-insight problem solving. The results indicated that the dynamics of working memory load in insight problems differs from those in non-insight problems. Our first experiment shows that the complexity of the probe-task affects overall probe-task reaction times in both insight and non-insight problem solving. Our second experiment demonstrates that the solution of a non-insight problem is primarily associated with the working memory control system, while insight problems rely on relevant storage systems. Our results confirm that insight process requires access to various systems of working memory throughout the solution. We found that working memory load in non-insight problems increases from stage to stage due to allocation of the attentional control resources to interim calculations. The nature of the dynamics of working memory load in insight problems remains debatable. We claim that insight problem solving demands working memory storage during the entire problem solving process and that control system plays an important role just prior to the solution.
Adaptive Input Representations for Neural Language Modeling

We introduce adaptive input representations for neural language modeling which extend the adaptive softmax of Grave et al. (2017) to input representations of variable capacity. There are several choices on how to factorize the input and output layers, and whether to model words, characters or sub-word units. We perform a systematic comparison of popular choices for a self-attentional architecture. Our experiments show that models equipped with adaptive embeddings are more than twice as fast to train than the popular character input CNN while having a lower number of parameters. On the WikiText-103 benchmark we achieve 18.7 perplexity, an improvement of 10.5 perplexity compared to the previously best published result and on the Billion Word benchmark, we achieve 23.02 perplexity.
The national burden of periprosthetic hip fractures in the US: costs and risk factors for hospital readmission

Introduction: Periprosthetic hip fractures (PPFX) are serious complications that result in increased morbidity, mortality and healthcare costs. Decreasing hospital readmissions has been a recent healthcare focus, but little is known about the overall costs associated with PPFX or the risk factors associated with readmissions. We investigated patient demographics, treatment types, 30- and 90-day readmission rates, direct costs, and patient risk factors associated with PPFX readmission. Methods: We used the 2013 Nationwide Readmissions Database to select patients who underwent total hip arthroplasty (THA), revision THA, and PPFX treated with open reduction internal fixation (ORIF) or revision THA. Survival analysis was used to evaluate the 90-day all-cause hospital readmission rate, and risk factors were identified using a Cox proportional hazards model, adjusting for patient and hospital characteristics. Results: We identified 1269 patients with PPFX treated with ORIF and 3254 treated with revision THA. 90-day readmissions were 20.9% and 27.3%, respectively. Patients with PPFX were older, female, and had multiple medical comorbidities. Patient factors associated with increased risk of readmission include: age; comorbidities; and discharge to skilled nursing facility; Medicare or Medicaid insurance. Hospital factors associated with increased risk of readmission include: large hospitals; nonprofits; metropolitan and teaching hospitals. The cost of readmission for PPFX treated with ORIF was $17,206 and revision THA was $16,504. Discussion: Periprosthetic hip fractures have high rates of hospital readmission, implying a significant burden to the healthcare system. Identifying risk factors is an important step towards identifying treatment pathways that can improve outcomes.
Vitamin D Deficiency Is Highly Prevalent in Critically Ill Patients and a Risk Factor for Mortality: A Prospective Observational Study Comparing Noncirrhotic Patients and Patients With Cirrhosis

Introduction: A 25-hydroxyvitamin D, 25(OH)D, deficiency is common among critically ill patients and correlated with increased mortality. Furthermore, deficiency is associated with advanced liver disease. However, there are no studies available comparing the dimensions and consequences of a 25(OH)D deficiency between patients with and without liver cirrhosis in the setting of intensive care units (ICUs). This study focuses on differences in 25(OH)D status between critically ill noncirrhosis patients and patients with cirrhosis (primary end point), hypothesizing that deficiency and its impact on mortality risk are even more pronounced in patients with cirrhosis. Methods: We performed a prospective observational study of 176 patients (noncirrhosis patients, N = 114; patients with cirrhosis, N = 62) with a laboratory assessment of 25(OH)D on ICU admission and survival analyses after 180 days. Results: On admission, 55% of patients showed a severe deficiency, 25(OH)D <10 ng/mL, and a further 23% moderate deficiency (10-19 ng/mL). The overall median level of 25(OH)D was 8.0 (5.0-18.0) ng/mL (10.5 [6.0-21.3] in noncirrhosis patients vs 7.0 [4.8-10.0] in patients with cirrhosis; P < .001). We found extremely low levels particularly in patients without prior vitamin D supplementation (6.0 [4.0-7.5] in patients with cirrhosis vs 8.0 [5.0-12.0] ng/mL in noncirrhosis patients; P = .004). Vitamin D status correlated inversely with the sequential organ failure assessment, acute and physiology chronic health evaluation, model of end-stage liver disease, and Child-Pugh scores. Survival analyses categorized 25(OH)D levels <10 ng/mL as a high-risk factor for mortality 180 days after admission (hazard ratio [HR]: 2.45, 95% confidence interval [CI] = 1.60-3.70; P < .001). In patients with cirrhosis, a severe deficiency (<10 ng/mL) involved a significantly higher mortality risk than in noncirrhosis patients (HR: 2.30, 95% CI = 1.39-3.82; P = .001). In cases of admission levels ≥10 ng/mL, however, mortality risk was similar between patients with cirrhosis and noncirrhosis patients (HR: 1.08, 95% CI = 0.43-2.73; P = .873). Conclusions: Hypovitaminosis D is a highly frequent disorder in critically ill patients admitted to ICU. A severe deficiency with levels <10 ng/mL is a high risk factor for increased mortality, especially in patients with cirrhosis.
Exploring the Experiences, Challenges, and Approaches of Parish Nurses in Their Community Practice

Purpose: To explore the personal experiences, challenges, and practices of parish nurses in their communities. Method/Design: The overall study used a mixed methods concurrent embedded design to describe parish nurses’ experiences with diabetes education and preconception counseling in their practice. Also included were descriptions of generalized practices. Therefore, this current report will focus on these broader experiences. Focus group data were collected using face-to-face, teleconference, and video conferencing formats with 48 nurses who consider themselves to be parish nurses and analyzed with content analysis. Findings: Four qualitative themes were identified in the data: (1) Gaining Entry Through Trust, (2) Enhanced Focus on Spiritual Caring, (3) Accomplishing Much Despite Challenges, and (4) Practice Making a Difference. Parish nurses are uniquely situated to provide holistic care for the mind, body, and spirit of their patients. Despite the many positive aspects, parish nurses experience unique challenges, such as funding their practice and working independently. Conclusions: The parish nurses can play a vital role in providing holistic care to patients in a faith-based community. Future work is needed to address the challenges of parish nurses such as access to continuing education programs related to health topics of concern to their community members.