Miracle-dz/UniFAR-FTUs huggingface dataset:
Bone morphogenic protein signaling regulates development and activation of CD4 + T cells

Bone morphogenetic proteins (BMPs) are growth factors belonging to the TGF- β (Transforming Growth Factor β ) superfamily. BMPs were found to regulate multiple cell processes such as proliferation, survival, differentiation and apoptosis. They were originally described to play a pivotal role in inducing bone, cartilage, ligament, and tendon formation at both heterotopic and orthotopic sites, but were found to play significant role in embryogenesis, and development of multiple tissues and organs. Activities of BMPs are regulated by a number of secreted proteins, which modulate their availability to bind cellular receptors. The functions of individual BMPs are highly redundant due to binding the same receptors and inducing overlapping signal transduction pathways. Recently, BMPs were found to regulate cells of the innate and adaptive immune system. BMPs are involved in thymic development of T cells at the early, double negative, as well as later, double positive, stages of thymopoesis. They specifically modulate thymic development of regulatory T cells (T reg ). In the periphery, BMPs affect T cell activation, promoting generation of Treg cells. We found that mice deficient for one of the receptors activated by BMPs demonstrated slower growth of transplantable melanoma tumors. NK-Natural B-B MF-Macrophage, DC-Dendritic Cell
APOBEC3H Haplotypes and HIV-1 Pro-Viral vif DNA Sequence Diversity in Early Untreated HIV-1 Infection

We examined single nucleotide polymorphisms (SNP) in the APOBEC3 locus on chromosome 22, paired to population sequences of pro-viral HIV-1 vif of peripheral blood mononuclear cells (PBMC), from 96 recently HIV-1 infected treatment naïve adults. We found evidence for the existence of an APOBEC3H linkage disequilibrium (LD) block associated with variation in GA->AA, or APOBEC3F signature, sequence changes in pro-viral HIV-1 vif sequence (top significant 10 SNPs with a top-significant p=4.8×10 − 3 ). We identified a common 5 position risk haplotype distal to APOBEC3H (A3Hrh). These markers were in high LD (D ′ = 1; r 2 =0.98) to a previously described A3H ‘RED’ haplotype containing a variant (E121) with enhanced susceptibility to HIV-1 Vif (Zhen et al 2009 [1]). This association is confirmed by a haplotype analysis: Homozygote carriers of the A3Hrh had lower GA->AA (A3F) sequence editing on pro-viral HIV-1 vif sequence (p = 0.01), and lower HIV-1 RNA levels over time during early, untreated HIV-1 infection, (p = 0.015 mixed effects model). This effect may be due to enhanced susceptibility of A3H forms to HIV-1 Vif mediated viral suppression of sequence editing activity, slowing viral diversification and escape from immune responses.
Localizing Circuits of Atrial Macro-Reentry Using ECG Planes of Coherent Atrial Activation

Background— The complexity of ablation for atrial macro-reentry (AFL) varies significantly depending upon the circuit location. Presently, surface ECG analysis poorly separates left from right atypical AFL and from some cases of typical AFL, delaying diagnosis until invasive study. Objective— To differentiate and localize the intra-atrial circuits of left atypical AFL, right atypical, and typical AFL using quantitative ECG analysis. Methods— We studied 66 patients (54 M, age 59±14 years) with typical (n=35), reverse typical (n=4) and atypical (n=27) AFL. For each, we generated filtered atrial waveforms from ECG leads V5 (X-axis), aVF (Y) and V1 (Z) by correlating a 120 ms F-wave sample to successive ECG regions. Atrial spatial loops were plotted for 3 orthogonal planes (frontal, XY=V5/aVF; sagittal, YZ=aVF/ V1; axial, XZ=V5/V1), then cross-correlated to measure spatial regularity (‘coherence’: range − 1 to 1). Results— Mean coherence was greatest in the XY plane (p<10 − 3 vs XZ or YZ). Atypical AFL showed lower coherence than typical AFL in XY (p<10 − 3 ), YZ (p<10 − 6 ) and XZ (p<10 − 5 ) planes. Atypical left AFL could be separated from atypical right AFL by lower XY coherence (p=0.02); for this plane coherence < 0.69 detected atypical left AFL with 84% specificity and 75% sensitivity. F-wave amplitude did not separate typical, atypical right or atypical left AFL (p=NS). Conclusions— Atypical AFL shows lower spatial coherence than typical AFL, particularly in sagittal and axial planes. Coherence in the Cartesian frontal plane separated left and right atypical AFL. Such analyses may be used to plan ablation strategy from the bedside.
Ethnic Disparities in Imaging Utilization at Diagnosis of Non-Small Cell Lung Cancer

Background: Prior research demonstrated statistically signiﬁcant racial disparities related to lung cancer treatment and outcomes. We examined differences in initial imaging and survival between blacks, Hispanics, and non-Hispanic whites. Methods: The linked Surveillance, Epidemiology, and End Results-Medicare database between 2007 and 2015 was used to compare initial imaging modality for patients with lung cancer. Participants included 28881 non-Hispanic whites, 3123 black, and 1907 Hispanics, patients age 66 years and older who were enrolled in Medicare fee-for-service and diagnosed with lung cancer. The primary outcome was comparison of positron emission tomography (PET) imaging with computerized tomography (CT) imaging use between groups. A secondary outcome was 12-month cancer-speciﬁc survival. Information on stage, treatment, and treatment facility was included in the analysis. Chi-square test and logistic regression were used to evaluate factors associated with imaging use. Kaplan-Meier method and Cox proportional hazards regression were used to calculate adjusted hazard ratios and survival. All statistical tests were two-sided. Results: After adjusting for demographic, community, and facility characteristics, blacks were less likely to undergo PET or CT imaging at diagnosis compared with non-Hispanic whites odds ratio (OR) ¼ 0.54 (95% conﬁdence interval [CI] ¼ 0.50 to 0.59; P < .001). Hispanics were also less likely to receive PET with CT imaging (OR ¼ 0.72, 95% CI ¼ 0.65 to 0.81;
Healthcare-Associated Pneumonia in the ICU: Guideline-Concordant Antibiotics and Outcomes

Purpose— Recent data have not demonstrated improved outcomes when guideline-concordant (GC) antibiotics are given to patients with healthcare-associated pneumonia (HCAP). This study was designed to evaluate the relationship between health outcomes and GC therapy in patients admitted to an ICU with HCAP. Materials and Methods— We performed a population-based cohort study of patients admitted to >150 hospitals in the U.S. Veterans Health Administration system to compare baseline characteristics, bacterial pathogens, and health outcomes in ICU patients with HCAP receiving either GC-HCAP therapy, GC community-acquired pneumonia (GC-CAP) therapy, or non-GC therapy. The primary outcome was 30-day patient mortality. Risk factors for the primary outcome were assessed in a multivariable logistic regression model. Results— A total of 3,593 patients met inclusion criteria and received GC-HCAP therapy (26%), GC-CAP therapy (23%), or non-GC therapy (51%). GC-HCAP patients had higher 30-day patient mortality compared to GC-CAP patients (34% vs. 22%, p<0.0001). After controlling for confounders, risk factors for 30-day patient mortality were vasopressor use (OR, 95% CI; 1.67, 1.30–2.13), recent hospital admission (1.53, 1.15–2.02), and receipt of GC-HCAP therapy (1.51, 1.20–1.90). Conclusions— Our data do not demonstrate improved outcomes among ICU patients with HCAP who received GC-HCAP therapy.
Fever of Unknown Origin: 18F-Fluorodeoxyglucose Positron Emission Tomography–Computed Tomography Showing Renal Cyst Infection in Autosomal Dominant Polycystic Kidney Disease

Fever of unknown origin (FUO) is a convoluted clinical dilemma. It can be caused by infective, inflammatory, malignant, and other pathologies. The identification of etiopathogenesis is essential for instituting definitive management. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) is now an integral part of FUO management. We present the case of a 60-year-old female with autosomal dominant polycystic kidney disease (ADPKD), where the infected renal cyst was detected as the cause of FUO on18F-FDG PET-CT.
The Association Between BMI and the Risk of Severe Hypoglycemia in Type 2 Diabetes

AIM: This study aimed to assess the association between body mass index and the development of severe hypoglycemia in patients with type 2 diabetes using the nationwide data of the entire Korean population. METHODS: The association between body mass index and severe hypoglycemia was retrospectively examined from the claims and national health examination data from 2002 to 2015. A total of 1,366,692 subjects with assigned clinic codes on type 2 diabetes and who were prescribed with anti-hypoglycemic agents were included. The primary outcome was a new development of severe hypoglycemia after the baseline health examination. RESULTS: A total of 37,682 subjects (2.7%) developed a severe hypoglycemic event during the follow-up period (mean of 8.6 years). An inverse J-shaped association was observed between body mass index and severe hypoglycemic events. The association between low body mass index and high-risk of severe hypoglycemia was similar among subjects who had never smoked, did not consume alcohol, did not use insulin, and had no major comorbidities, after adjusting multiple confounders. The association between low body mass index and severe hypoglycemia was found to be intensified in men, young people aged 30–49 years, people with major comorbidities, and insulin users. CONCLUSIONS: Body mass index and severe hypoglycemia were found to be inversely associated. Those individuals who fall into
Cardiac Autonomic Balance vs. Cardiac Regulatory Capacity

The concept of autonomic balance views autonomic states along a bipolar continuum from sympathetic (S) to parasympathetic (P) dominance, whereas regulatory capacity models emphasize overall autonomic flexibility as a marker of the capacity for regulation. These two concepts were evaluated for their utility in characterizing patterns of autonomic control. Measures of P (high frequency heart rate variability, HF) and S (pre-ejection period, PEP) cardiac control were obtained. A measure of cardiac autonomic balance (CAB) was derived as the difference in the normalized P index minus the S index, and a measure of cardiac autonomic regulation (CAR) was derived as the normalized P index plus the S index. Results reveal that CAR, but not CAB, was a significant predictor of the prior occurrence of a myocardial infarction, net of demographic and other variables, whereas CAB, but not CAR, was a significant predictor of concurrent diabetes.
Sepsis Deﬁnitions in Burns

Background: Sepsis is the leading cause of death in burns. Despite its importance, sepsis lacks a proper deﬁnition. An established deﬁnition will lead to early and accurate diagnosis, prompt treatment, and a reduced mortality rate. The aim of this work is to discuss current deﬁnitions and to look ahead at novel deﬁnitions with clinical implications. Method: A review of the current understanding of sepsis deﬁnitions in burns. Results: Adaptation of sepsis deﬁnitions in the general population and speciﬁc burn deﬁnitions have gotten better but still need improvements and, potentially, incorporation of molecular, laboratory, patient-speciﬁc, and clinical factors. This work includes the history, evolution, and predictive value of current deﬁnitions of sepsis in burns. A review of current and future markers of sepsis and potentially useful deﬁnitions are presented. Conclusions: Sepsis deﬁnitions have evolved over the last decades and will continue to do so. We believe the best deﬁnition in burn patients is the Sepsis-3 that was developed originally for critically ill patients. However, there are several studies investigating more speciﬁc deﬁnitions with better sensitivity and speciﬁcity. the history of sepsis and sepsis indicators, as well as to give a perspective of current and potentially future sepsis indicators and deﬁnitions.
Longer Forms of Amyloid (cid:1) Protein: Implications for the Mechanism of Intramembrane Cleavage by (cid:2) -Secretase

(cid:2) -Cleavage of (cid:1) -amyloid precursor protein (APP) in the middle of the cell membrane generates amyloid (cid:1) protein (A (cid:1) ), and (cid:3) -cleavage, (cid:1) 10 residues downstream of the (cid:2) -cleavage site, releases the APP intracellular domain (AICD). A significant link between generation of A (cid:1) and AICD and failure to detect AICD41–99 led us to hypothesize that (cid:3) -cleavage generates longer A (cid:1) s, which are then processed to A (cid:1) 40/42. Using newly developed gel systems and an N-end-specific monoclonal antibody, we have identified the longerA (cid:1) s(A (cid:1) 1–43,A (cid:1) 1–45,A (cid:1) 1–46,andA (cid:1) 1–48)withinthecellsandinbraintissues.TheproductionoftheselongerA (cid:1) saswellas A (cid:1) 40/42 is presenilin dependent and is suppressed by {1 S -benzyl-4 R -[1 S -carbamoyl-2-phenylethylcarbamoyl-1 S -3-methylbutylcar-bamoyl]-2 R -hydroxy-5-phenylpentyl}carbamicacidtert-butylester,atransitionstateanaloginhibitorforaspartylprotease.Incontrast, N -[ N -(3,5-difluorophenacetyl)- L -alanyl]- S -phenylglycine t-butyl ester, a potent dipeptide (cid:2) -secretase inhibitor, builds up A (cid:1) 1–43 and A (cid:1) 1–46 intracellularly, which was also confirmed by mass spectrometry. Notably, suppression of A (cid:1) 40 appeared to lead to an increase inA (cid:1) 43,whichinturnbringsanincreaseinA (cid:1) 46,inadose-dependentmanner.Wethereforeproposean (cid:4) -helicalmodelinwhichlonger A (cid:1) species generated by (cid:3) -cleavage is cleaved at every three residues in its carboxyl portion.
Activation and Deactivation Rates of Recombinant GABAA Receptor

The role of subunit composition in determining intrinsic maximum activation and deactivation kinetics of GABAA receptor channels is unknown. We used rapid ligand application (1 00-,us solution exchange) to examine the effects of a-subunit composition on GABA-evoked activation and deactivation rates. HEK 293 cells were transfected with human cDNAs encoding a1, ly2or a2f1y2-subunits. Channel kinetics were similar across different transfections of the same subunits and reproducible across several GABA applications in the same patch. Current rise to peak was at least twice as fast for a2/13y2 receptors than for alI31 y2 receptors (reflected in 10-90% rise times of 0.5 versus 1.0 ms, respectively), and deactivation was six to seven times slower (long time constants of 208 ms versus 31 ms) after saturating GABA applications. Thus a-subunit composition determined activation and deactivation kinetics of GABAA receptor channels and is therefore likely to influence the kinetics and efficacy of inhibitory postsynaptic currents.
The Neural Signature of Impaired Inhibitory Control in Individuals with Heroin Use Disorder

Heroin addiction imposes a devastating toll on society, with little known about its neurobiology. Excessive salience attribution to drug over nondrug cues/reinforcers, with concomitant inhibitory control decreases, are common mechanisms underlying drug addiction. Although inhibitory control alterations generally culminate in prefrontal cortex (PFC) hypoactivations across drugs of abuse, patterns in individuals with heroin addiction (iHUDs) remain unknown. We used a stop-signal fMRI task designed to meet recent consensus guidelines in mapping inhibitory control in 41 iHUDs and 24 age- and sex-matched healthy controls (HCs). Despite group similarities in the stop-signal response time (SSRT; the classic inhibitory control measure), compared with HCs, iHUDs exhibited impaired target detection sensitivity (proportion of hits in go vs false alarms in stop trials; p = 0.003). Additionally, iHUDs exhibited lower right anterior PFC (aPFC) and dorsolateral PFC (dlPFC) activity during successful versus failed stops (the hallmark inhibitory control contrast). Lower left dlPFC/supplementary motor area (SMA) activity was associated with slower SSRT specifically in iHUDs and lower left aPFC activity with worse target sensitivity across all participants (p < 0.05 corrected). Importantly, in iHUDs, lower left SMA and aPFC activity during inhibitory control was associated with shorter time since last use and higher severity of dependence, respectively (p < 0.05 corrected). Together, results revealed lower perceptual sensitivity and hypoactivations during inhibitory control in cognitive control regions (e.g., aPFC, dlPFC, SMA) as associated with task performance and heroin use severity measures in iHUDs. Such neurobehavioral inhibitory control deficits may contribute to self-control lapses in heroin addiction, constituting targets for prevention and intervention efforts to enhance recovery. SIGNIFICANCE STATEMENT Heroin addiction continues its deadly impact, with little known about the neurobiology of this disorder. Although behavioral and prefrontal cortical impairments in inhibitory control characterize addiction across drugs of abuse, these patterns remain underexplored in heroin addiction. Here, we illustrate a significant behavioral impairment in target discrimination in individuals with heroin addiction compared with matched healthy controls. We further show lower engagement during inhibitory control in the anterior and dorsolateral prefrontal cortex (key regions that regulate cognitive control) as associated with slower stopping, worse discrimination, and heroin use measures. Mapping the neurobiology of inhibitory control in heroin addiction for the first time, we identify potential treatment targets inclusive of prefrontal cortex-mediated cognitive control amenable for neuromodulation en route to recovery.
A novel MRI‐based three‐dimensional model of stomach volume, surface area, and geometry in response to gastric filling and emptying

Gastric motility and accommodation have a critical role in maintaining normal gastrointestinal homeostasis. Different modalities can be adopted to quantify those processes, that is, scintigraphy to measure emptying time and intragastric Barostat for accommodation assessment. However, magnetic resonance imaging (MRI) can assess the same parameters noninvasively without ionizing radiation. Our study aimed to develop a detailed three‐dimensional (3D) MRI model of the stomach to describe gastric volumes, surface areas, wall tension distribution, and interobserver agreement.
Pre-Omicron vaccine breakthrough infection induces superior cross-neutralization against SARS-CoV-2 Omicron BA.1 than primo infection

SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here we compared the ability of sera from 70 unvaccinated COVID-19 patients infected before the emergence of variants of concern (VOCs) and from 16 vaccine breakthrough infection (BTI) cases infected with Gamma or Delta to neutralize the ancestral B.1 strain, and the Gamma, Delta and Omicron BA.1 variants using live virus. We further determined antibody levels against the Spike protein, the Receptor Binding Domain (RBD) and the N-terminal domain (NTD) of Spike. Convalescent sera featured considerable variability in neutralization of B.1 and in cross-neutralization of different strains, and neutralizing capacity moderately correlated with antibody levels against Spike and the RBD. All but one convalescent serum failed to neutralize Omicron BA.1. Overall, convalescent sera from patients with moderate disease had higher antibody levels and displayed higher neutralizing ability against all strains than patients with mild or severe forms of disease. Sera from BTI cases fell into one of two categories: half the sera had high neutralizing activity against the ancestral B.1 strain as well as against the infecting strain, while the other half had no or very low neutralizing activity against all strains. Although antibody levels against Spike and the RBD were lower in BTI cases than in unvaccinated convalescent sera, most neutralizing sera also retained partial neutralizing activity against Omicron BA.1, indicative of cross-neutralization between B.1, Delta and Omicron and suggestive of higher affinity, as confirmed by the IC50:Ab level ratios. Neutralizing activity of BTI sera was strongly correlated with antibodies against Spike and the RBD. Together, these findings highlight qualitative differences in antibody responses elicited by infection in vaccinated and unvaccinated individuals. They further suggest that breakthrough infection with a pre-Omicron variant boosts immunity and induces cross neutralizing antibodies against different strains, including Omicron BA.1.
Adoption of BIM in architectural design firms

ABSTRACT BIM is the trend of the future. User acceptance models of new technology have been empirically investigated in the construction industry only in a small group of studies. Three models are proposed that investigate whether the fit between BIM technology and (1) design tasks, (2) the organizational competence of the design firm, and (3) designer competence affect the performance of the design firm. The data used in the study were collected by conducting a survey of architectural design professionals employed by large design firms in the U.S. The results suggest that the fit between BIM technology and (1) design tasks, and (2) organizational competence is likely to affect project cost, time, and quality positively. The outcome of the research is expected to benefit the architectural design community by advancing their understanding of the factors that affect the acceptance of BIM technology, and their impact on a design firm's performance.
A Summary and Commentary on D. and S. Premack’s Original Intelligence *

Some evolutionary cognitive and developmental psychologists propose that the human mind consists of domain-specific modules. These are characterized as self-contained “mini-computers” that process information of a certain kind. Although, according to my reading, much of the extant human brain research does not necessarily support the module view (Greenwald, 1997), still module theories continue to occupy center stage in cognitive developmental and comparative psychology. One would think that neuroscience, as a study of the behavior beneath the skin, would simply replace cognitive psychology. But, perhaps I missed the value of the psychological construct. In their book, the Premacks set out to provide a synthesis of evidence from various fields in order to identify what they characterize as “original intelligence. ” Their synthesis is derived from their reading of findings in comparative psychology, developmental psychology, neuroscience, anthropology and other “life sciences. ” All of the evidence and theory from psychology from which they draw their evidence comes from the cognitive perspective including their own contributions to that research. For them, original intelligence includes certain phylogenetic and ontogenetic contributions that they identify as expectancies, capabilities that are present or not present in certain species including humans. These capabilities include inherited expectancies, derived from natural selection; and expectancies derived from experience and its interaction with inherited expectancies.