Miracle-dz/UniFAR-FTUs huggingface dataset:
Intracardiac flow analysis in cardiac resynchronization therapy: A new challenge?

In the past years, assessment of cardiac function has become possible through the analysis of intracardiac flow dynamics, performed noninvasively using phase‐contrast cardiac magnetic resonance and contrast and noncontrast ultrasound techniques. From 2013 to 2019, 9 echocardiographic investigations have considered 215 patients with cardiac resynchronization therapy (CRT) as a model for assessing flow dynamics within the left ventricle. Preliminary results have been reported about the acute hemodynamic effects of CRT and programming of the CRT device, showing the potential of an approach based on analysis of intracardiac flows. At present, there are only scarce data on the capability of intracardiac flow dynamics to predict LV remodeling after CRT and no information on clinical outcome prediction. Future investigations should be aimed at clarifying the mechanisms and impact of maladaptive intracardiac vortex dynamics on progressive LV remodeling as well as the prognostic meaning of implanted CRT device based on cardiac flow analysis.
Tissue rheology in embryonic organization

Tissue morphogenesis in multicellular organisms is brought about by spatiotemporal coordination of mechanical and chemical signals. Extensive work on how mechanical forces together with the well‐established morphogen signalling pathways can actively shape living tissues has revealed evolutionary conserved mechanochemical features of embryonic development. More recently, attention has been drawn to the description of tissue material properties and how they can influence certain morphogenetic processes. Interestingly, besides the role of tissue material properties in determining how much tissues deform in response to force application, there is increasing theoretical and experimental evidence, suggesting that tissue material properties can abruptly and drastically change in development. These changes resemble phase transitions, pointing at the intriguing possibility that important morphogenetic processes in development, such as symmetry breaking and self‐organization, might be mediated by tissue phase transitions. In this review, we summarize recent findings on the regulation and role of tissue material properties in the context of the developing embryo. We posit that abrupt changes of tissue rheological properties may have important implications in maintaining the balance between robustness and adaptability during embryonic development.
Cytogenetic landscape in 1012 newly diagnosed chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) stratification mainly relies on FISH markers according to Döhner's hierarchical model which includes high‐risk FISH markers, intermediate FISH, or low‐risk FISH. Recently, complex karyotype (CK) has been demonstrated as an independent negative prognostic factor in CLL.
Mechanisms underlying TNFα‐induced enhancement of force generation in airway smooth muscle

Airway diseases such as asthma are triggered by inflammation and mediated by proinflammatory cytokines such as tumor necrosis factor alpha (TNFα). Our goal was to systematically examine the potential mechanisms underlying the effect of TNFα on airway smooth muscle (ASM) contractility. Porcine ASM strips were incubated for 24 h with and without TNFα. Exposure to TNFα increased maximum ASM force in response to acetylcholine (Ach), with an increase in ACh sensitivity (hyperreactivity), as reflected by a leftward shift in the dose–response curve (EC50). At the EC50, the [Ca2+]cyt response to ACh was similar between TNFα and control ASM, while force increased; thus, Ca2+ sensitivity appeared to increase. Exposure to TNFα increased the basal level of regulatory myosin light chain (rMLC) phosphorylation in ASM; however, the ACh‐dependent increase in rMLC phosphorylation was blunted by TNFα with no difference in the extent of rMLC phosphorylation at the EC50 ACh concentration. In TNFα‐treated ASM, total actin and myosin heavy chain concentrations increased. TNFα exposure also enhanced the ACh‐dependent polymerization of G‐ to F‐actin. The results of this study confirm TNFα‐induced hyperreactivity to ACh in porcine ASM. We conclude that the TNFα‐induced increase in ASM force, cannot be attributed to an enhanced [Ca2+]cyt response or to an increase in rMLC phosphorylation. Instead, TNFα increases Ca2+ sensitivity of ASM force generation due to increased contractile protein content (greater number of contractile units) and enhanced cytoskeletal remodeling (actin polymerization) resulting in increased tethering of contractile elements to the cortical cytoskeleton and force translation to the extracellular matrix.
Current status of simulation and training models in microsurgery: A systematic review

With the prolific uptake of simulation‐based training courses, this systematic review aims to identify the available microsurgical simulation and training models, their status of validation, associated studies, and levels of evidence (LoE) for each training model, thereby establishing a level of recommendation (LoR). MEDLINE, Embase, and the Cochrane Library databases were searched for English language articles, describing microsurgery simulators and/or validation studies. All studies were assessed for LoE, and each model was subsequently awarded a LoR using a modified Oxford Centre for Evidence‐Based Medicine classification, adapted for education, with 1 being the highest and 4 the lowest score. A total of 86 studies were identified describing 64 models and simulators ranging from bench models, cadaveric animal tissue, cadaveric human tissue, live animal models, virtual reality simulators, and training curricula. Of these, 49 simulators had at least one validation study. Models were assessed for face (n = 42), content (n = 31), construct (n = 25), transfer (n = 10), and concurrent validity (n = 1) by these studies. The most commonly identified modality was bench models (n = 28) followed by cadaveric animal tissue (n = 24). The cryopreserved rat aorta model received the highest LoR followed by chicken wing, chicken thigh and practice cardboard models. Microsurgery simulation is a growing field and increasing numbers of models are being produced. However, there are still only a few validation studies with a high LoE. It is therefore imperative that training models and/or programs are evaluated for validity and efficacy in order to allow utilization in microsurgical skills acquisition.
Semantic and lexical features of words dissimilarly affected by non-fluent, logopenic, and semantic primary progressive aphasia

Abstract Objective: To determine the effect of three psycholinguistic variables—lexical frequency, age of acquisition (AoA), and neighborhood density (ND)—on lexical-semantic processing in individuals with non-fluent (nfvPPA), logopenic (lvPPA), and semantic primary progressive aphasia (svPPA). Identifying the scope and independence of these features can provide valuable information about the organization of words in our mind and brain. Method: We administered a lexical decision task—with words carefully selected to permit distinguishing lexical frequency, AoA, and orthographic ND effects—to 41 individuals with PPA (13 nfvPPA, 14 lvPPA, 14 svPPA) and 25 controls. Results: Of the psycholinguistic variables studied, lexical frequency had the largest influence on lexical-semantic processing, but AoA and ND also played an independent role. The results reflect a brain-language relationship with different proportional effects of frequency, AoA, and ND in the PPA variants, in a pattern that is consistent with the organization of the mental lexicon. Individuals with nfvPPA and lvPPA experienced an ND effect consistent with the role of inferior frontal and temporoparietal regions in lexical analysis and word form processing. By contrast, individuals with svPPA experienced an AoA effect consistent with the role of the anterior temporal lobe in semantic processing. Conclusions: The findings are in line with a hierarchical mental lexicon structure with a conceptual (semantic) and a lexeme (word-form) level, such that a selective deficit at one of these levels of the mental lexicon manifests differently in lexical-semantic processing performance, consistent with the affected language-specific brain region in each PPA variant.
Inhibition of spindle extension through the yeast S phase checkpoint is coupled to replication fork stability and the integrity of centromeric DNA

Budding yeast treated with hydroxyurea (HU) activate the S phase checkpoint kinase Rad53, which prevents DNA replication forks from undergoing aberrant structural transitions and nuclease processing. Rad53 is also required to prevent premature extension of the mitotic spindle that assembles during a HU-extended S phase. Here we present evidence that checkpoint restraint of spindle extension is directly coupled to Rad53 control of replication fork stability. In budding yeast, centromeres are flanked by replication origins that fire in early S phase. Mutations affecting the Zn2+-finger of Dbf4, an origin activator, preferentially reduce centromere-proximal origin firing in HU, corresponding with suppression of rad53 spindle extension. Inactivating Exo1 nuclease or displacing centromeres from origins provides a similar suppression. Conversely, short-circuiting Rad53 targeting of Dbf4, Sld3, and Dun1, substrates contributing to fork stability, induces spindle extension. These results reveal spindle extension in HU-treated rad53 mutants is a consequence of replication fork catastrophes at centromeres. When such catastrophes occur, centromeres become susceptible to nucleases, disrupting kinetochore function and spindle force balancing mechanisms. At the same time, our data indicate centromere duplication is not required to stabilize S phase spindle structure, leading us to propose a model for how monopolar kinetochore-spindle attachments may contribute to spindle force balance in HU.
Health‐Related Quality of Life and Cognitive Functioning in Pediatric Liver Transplant Recipients

The goal of this work was to examine the change in health‐related quality of life (HRQOL) and cognitive functioning from early childhood to adolescence in pediatric liver transplantation (LT) recipients. Patients were recruited from 8 North American centers through the Studies of Pediatric Liver Transplantation consortium. A total of 79 participants, ages 11‐18 years, previously tested at age 5‐6 years in the Functional Outcomes Group study were identified as surviving most recent LT by 2 years and in stable medical follow‐up. The Pediatric Quality of Life 4.0 Generic Core Scale, Pediatric Quality of Life Cognitive Function Scale, and PROMIS Pediatric Cognitive Function tool were distributed to families electronically. Data were analyzed using repeated measures and paired t tests. Predictive variables were analyzed using univariate regression analysis. Of the 69 families contacted, 65 (94.2%) parents and 61 (88.4%) children completed surveys. Median age of participants was 16.1 years (range, 12.9‐18.0 years), 55.4% were female, 33.8% were nonwhite, and 84.0% of primary caregivers had received at least some college education. Median age at LT was 1.1 years (range, 0.1‐4.8 years). The majority of participants (86.2%) were not hospitalized in the last year. According to parents, adolescents had worse HRQOL and cognitive functioning compared with healthy children in all domains. Adolescents reported HRQOL similar to healthy children in all domains except psychosocial, school, and cognitive functioning (P = 0.02; P < 0.001; P = 0.04). Participants showed no improvement in HRQOL or cognitive functioning over time. For cognitive and school functioning, 60.0% and 50.8% of parents reported “poor” functioning, respectively (>1 standard deviation below the healthy mean). Deficits in HRQOL seem to persist in adolescence. Over half of adolescent LT recipients appear to be at risk for poor school and cognitive functioning, likely reflecting attention and executive function deficits.
The Clinical dietitian's essential pocket guide

Part I: NUTRITION ASSESSMENT AND SUPPORT Chapter 1: Nutrition Assessment Chapter 2: Assessing Pregnant Patients Chapter 3: Assessing Pediatric Patients Chapter 4: Assessing Elderly Patients Chapter 5: Nutrition Support Part II: NUTRITION CONSIDERATIONS FOR SPECIFIC DISEASES Chapter 6: Cancer Chapter 7: Cardiovascular Disease Chapter 8: Diabetes Chapter 9: Gastrointestinal Diseases Chapter 10: Liver and Pancreatic Diseases Chapter 11: Renal Diseases Chapter 12: Pulmonary Diseases Appendix A: Laboratory Assessment Appendix B: Food-Drug Interactions Appendix C: Miscellaneous Appendix D: Notes
Treatments and Mortality Trends in Cases With and Without Dialysis Who Have an Acute Myocardial Infarction: An 18-Year Nationwide Experience.

BACKGROUND Patients on dialysis who have an acute myocardial infarction (AMI) have an exceedingly poor prognosis, but it is unknown to what extent guideline-recommended interventions and treatments are used and to which benefit. We aimed to assess temporal changes in the use of treatments and survival rates in dialysis patients with an AMI. METHODS AND RESULTS All consecutive AMI cases from 1996 to 2013 enrolled in the SWEDEHEART registry (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) were included. The Swedish Renal Registry identified all chronic dialysis cases. Multivariable adjusted standardized 1-year mortality was estimated. An age-sex-calendar year-matched dialysis background population from the Swedish Renal Registry was used to obtain a standardized incidence ratio. All analyses were performed in 2-year blocks, where each individual could be included several times but in different time blocks; hence the term AMI cases and not patients is used. Of 289 699 cases with AMI, 1398 (0.5%) were on dialysis (73.6% hemodialysis; 26.4% peritoneal dialysis). Among dialysis cases, 29.4% were women, and 21.0% had ST-segment-elevation myocardial infarction. Through 1996 to 2013, dialysis cases had similar age (median, 70 years [interquartile range, 62-77]; P for trend, 0.14), but the proportion with diabetes mellitus increased (36.0%-55.3%; P for trend, 0.005). Dialysis cases admitted with AMI were treated more invasively and received more discharge medications in the later years. From 1995 to 2013, in-hospital and 1-year mortality decreased from 25.4% to 9.4% and from 59.6% to 41.2%, respectively. The standardized in-hospital and 1-year mortality decreased from 25.7% to 9.4% and from 54.6% to 41.2%. Yet, compared with the matched dialysis population, the odds of death remained as high in 2012/2013 as in 1996/1997 (odds ratio, 2.04; 95% CI, 1.62-2.58 and odds ratio, 1.99; 95% CI, 1.52-2.60, respectively; P for trend, 0.34). CONCLUSIONS Over the last 18 years, more patients on dialysis with AMI have been treated with evidence-based therapies. Overall, dialysis cases with AMI have an improved in-hospital and 1-year survival in the more recent years compared with earlier years. However, this appears largely to be because of improved survival in the general dialysis population.
On-Site 4-in-1 Alignment: Visualization and Interactive CAD Model Retrofitting Using UAV, LiDAR’s Point Cloud Data, and Video

Acquisition of 3D point cloud data (PCD) using a laser scanner and aligning it with a video frame is a new approach that is efficient for retrofitting comprehensive objects in heavy pipeline industrial facilities. This work contributes a generic framework for interactive retrofitting in a virtual environment and an unmanned aerial vehicle (UAV)-based sensory setup design to acquire PCD. The framework adopts a 4-in-1 alignment using a point cloud registration algorithm for a pre-processed PCD alignment with the partial PCD, and frame-by-frame registration method for video alignment. This work also proposes a virtual interactive retrofitting framework that uses pre-defined 3D computer-aided design models (CAD) with a customized graphical user interface (GUI) and visualization of a 4-in-1 aligned video scene from a UAV camera in a desktop environment. Trials were carried out using the proposed framework in a real environment at a water treatment facility. A qualitative and quantitative study was conducted to evaluate the performance of the proposed generic framework from participants by adopting the appropriate questionnaire and retrofitting task-oriented experiment. Overall, it was found that the proposed framework could be a solution for interactive 3D CAD model retrofitting on a combination of UAV sensory setup-acquired PCD and real-time video from the camera in heavy industrial facilities.
Functional connectivity between white matter and gray matter based on fMRI for Alzheimer's disease classification

Alzheimer's disease (AD) is a chronic neurodegenerative disease that generally starts slowly and leads to deterioration over time. Finding biomarkers more effective to predict AD transition is important for clinical medicine. And current research indicated that the lesion regions occur in both gray matter (GM) and white matter (WM).
Exosome DNA: Critical regulator of tumor immunity and a diagnostic biomarker

Nanosized cellular vesicles “exosome” contains a variety of biological cargo including DNA fragments from cell‐of‐origin. Despite its biological stability and clinical utility in tumor diagnosis, exosome DNA (ExoDNA) is very little studied as compare with exosome RNA. Cytoplasmic accumulation of damaged DNA from nucleus and mitochondria often leads to its packaging in exosomes by yet unknown pathways. ExoDNA modulates tumor immunity via paracrine interactions and activation of cytosolic DNA sensor pathways, for example, STING, cGAS, and so forth in specific immune cell subsets. In addition to priming tumor immunity, ExoDNA is also emerging as a critical regulator of check‐point immunotherapy. As a useful diagnostic biomaterial, ExoDNA contains a variety of clinically relevant tumor‐specific mutations representing multiple genes (e.g., EGFR, BRAF, RAS, IDH, and HER2), thus making it a promising “liquid biopsy” material for therapy recommendations. Hence, ExoDNA in addition to tumor immunity modulation, is also emerging as a suitable diagnostic material for personalized therapy in cancer. Here, we review the current status of ExoDNA research and its potential uses in tumor biology.
Ethanol Induction of Innate Immune Signals Across BV2 Microglia and SH-SY5Y Neuroblastoma Involves Induction of IL-4 and IL-13

Innate immune signaling molecules, such as Toll-like receptors (TLRs), cytokines and transcription factor NFκB, are increased in post-mortem human alcoholic brain and may play roles in alcohol dependence and neurodegeneration. Innate immune signaling involves microglia -neuronal signaling which while poorly understood, may impact learning and memory. To investigate mechanisms of ethanol induction of innate immune signaling within and between brain cells, we studied immortalized BV2 microglia and SH-SY5Y human neuroblastoma to model microglial and neuronal signaling. Cells were treated alone or in co-culture using a Transwell system, which allows transfer of soluble mediators. We determined immune signaling mRNA using real-time polymerase chain reaction. Ethanol induced innate immune genes in both BV2 and SH-SY5Y cultured alone, with co-culture altering gene expression at baseline and following ethanol exposure. Co-culture blunted ethanol-induced high mobility group box protein 1 (HMGB1)-TLR responses, corresponding with reduced ethanol induction of several proinflammatory NFκB target genes. In contrast, co-culture resulted in ethanol upregulation of cytokines IL-4 and IL-13 in BV2 and corresponding receptors, that is, IL-4 and IL-13 receptors, in SH-SY5Y, suggesting induction of a novel signaling pathway. Co-culture reduction in HMGB1-TLR levels occurs in parallel with reduced proinflammatory gene induction and increased IL-4 and IL-13 ligands and receptors. Findings from these immortalized and tumor-derived cell lines could provide insight into microglial-neuronal interactions via release of soluble mediators in vivo.
Standardized Measurement of Quality of Upper Limb Movement After Stroke: Consensus-Based Core Recommendations From the Second Stroke Recovery and Rehabilitation Roundtable

The second Stroke Recovery and Rehabilitation Roundtable “metrics” task force developed consensus around the recognized need to add kinematic and kinetic movement quantification to its core recommendations for standardized measurements of sensorimotor recovery in stroke trials. Specifically, we focused on measurement of the quality of upper limb movement. We agreed that the recommended protocols for measurement should be conceptually rigorous, reliable, valid and responsive to change. The recommended measurement protocols include four performance assays (i.e. 2D planar reaching, finger individuation, grip strength, and precision grip at body function level) and one functional task (3D drinking task at activity level) that address body function and activity respectively. This document describes the criteria for assessment and makes recommendations about the type of technology that should be used for reliable and valid movement capture. Standardization of kinematic measurement protocols will allow pooling of participant data across sites, thereby increasing sample size aiding meta-analyses of published trials, more detailed exploration of recovery profiles, the generation of new research questions with testable hypotheses, and development of new treatment approaches focused on impairment. We urge the clinical and research community to consider adopting these recommendations.
Outpatient rituximab, ifosfamide, etoposide (R-IE) in patients older than 60 years with relapsed or refractory diffuse large B-cell lymphoma who are not candidates for stem cell transplantation

Abstract Patients with relapsed-refractory diffuse large B-cell lymphoma (RR-DLBCL) ineligible for autologous stem cell transplantation (autoSCT) have poor survival. Thirty transplant-ineligible patients older than 60 years were administered rituximab 375 mg/m2 day 1, ifosfamide 1333 mg/m2 days 1 to 3, and etoposide 80 mg/m2 days 1 to 3 (R-IE) every 21 days for 6 cycles plus 2 doses of rituximab. Revised international prognostic index 3–4 was seen in 53% and prior rituximab exposure in 60%. The complete and overall response rates were 55% and 76%, respectively. Median progression free survival (PFS) and overall survival were 23 and 24 months, respectively. Patients relapsing within 12 months of prior treatment had a median PFS of 2.5 months compared to 23 months for those relapsing beyond 12 months. Grade 3–4 thrombocytopenia and neutropenia occurred in one and eight patients, respectively. R-IE is an effective, well tolerated regimen in RR-DLBCL patients not fit for autoSCT.