Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic associations of T cell cancer immune response with tumor aggressiveness in localized prostate cancer patients and disease reclassification in an active surveillance cohort

ABSTRACT Determining prostate cancer (PCa) aggressiveness and reclassification are critical events during the treatment of localized disease and for patients undergoing active surveillance (AS). Since T cells play major roles in cancer surveillance and elimination, we aimed to identify genetic biomarkers related to T cell cancer immune response which are predictive of aggressiveness and reclassification risks in localized PCa. The genotypes of 3,586 single nucleotide polymorphisms (SNPs) from T cell cancer immune response pathways were analyzed in 1762 patients with localized disease and 393 who elected AS. The aggressiveness of PCa was defined according to pathological Gleason score (GS) and D’Amico criteria. PCa reclassification was defined according to changes in GS or tumor characteristics during subsequent surveillance biopsies. Functional characterization and analysis of immune phenotypes were also performed. In the localized PCa cohort, seven SNPs were significantly associated with the risk of aggressive disease. In the AS cohort, another eight SNPs were identified as predictors for aggressiveness and reclassification. Rs1687016 of PSMB8 was the most significant predictor of reclassification. Cumulative analysis showed that a genetic score based on the identified SNPs could significantly predict risk of D’Amico high risk disease (P-trend = 2.4E-09), GS4 + 3 disease (P-trend = 1.3E-04), biochemical recurrence (P-trend = 0.01) and reclassification (P-trend = 0.01). In addition, the rs34309 variant was associated with functional somatic mutations in the PI3K/PTEN/AKT/MTOR pathway and tumor lymphocyte infiltration. Our study provides plausible evidence that genetic variations in T cell cancer immune response can influence risks of aggressiveness and reclassification in localized PCa, which may lead to additional biological insight into these outcomes. Abbreviations: PCa, prostate cancer; AS, active surveillance; GS, Gleason score; PSA, prostate specific antigen; TCGA, The Cancer Genome Atlas; SNP, single nucleotide polymorphisms; UFG, unfavorable genotype.
Profile and Motivations of Registered Whole‐Body Donors in Turkey: Istanbul University Experience

Little is known regarding the profiles of whole body donors in Muslim majority countries where donation is scarce. Therefore, this study aims to profile registered donors in Turkey by means of a survey. The explored data could be used to improve ongoing campaign efforts and ethical practices such as commemoration services. Registered donors of the donation programs at the two faculties of medicine of Istanbul University were compared with the national population and a cluster analysis was performed to reveal any concealed sub‐groups. Data from 188 respondents were analyzed. The majority of registered donors were married (42%), male (65.4%), aged over 50 years (76%), held a tertiary education degree (49.7%), and were irreligious (58.5%). Cluster analysis revealed two groups with significantly different educational levels, marital statuses, and religious choices. Regarding whether their bodies could be used for education or research, the majority (64.5%) of the respondents left the decision to the anatomy department. Similarly, 73.8% approved indefinite use of their organs, body parts and/or skeletons. The respondents were also willing to share their medical history (94.2%) and personal information (81.6%) if needed. Motivational themes for body donation including usefulness, impermanence, religion, awareness, and kinship were devised after a thematic analysis. Among the respondents, 56.5% were registered organ donors and 63.3% were frequent blood donors. The results of this study provide data that may help revising informed consent forms, developing and implementing thanksgiving ceremonies, and selecting additional targets for supporting body donation campaign activities such as organ and blood donation units.
Brief resolved unexplained events: Retrospective validation of diagnostic criteria and risk stratification

This study retrospectively evaluated the AAP guidelines for diagnosis and risk stratification of Brief Resolved Unexplained Events (BRUE) in a well‐characterized cohort of infants admitted with an Apparent Life Threatening Event (ALTE). Further, using prospective follow‐up, we endeavored to determine the safety of implementing ambulatory care for the lower risk BRUE population (LR‐BRUE) and estimate the cost‐savings of this practice.
The ventilation mechanism of the Pacific hagfish Eptatretus stoutii.

We made anatomical and physiological observations of the breathing mechanisms in Pacific hagfish Eptatretus stoutii, with measurements of nostril flow and pressure, mouth and pharyngo-cutaneous duct (PCD) pressure and velum and heart impedance and observations of dye flow patterns. Resting animals frequently exhibit spontaneous apnea. During normal breathing, water flow is continuous at a high rate (~125 ml kg-1 min-1 at 12°C) powered by a two-phase unidirectional pumping system with a fast suction pump (the velum, ~22 min-1 ) for inhalation through the single nostril and a much slower force pump (gill pouches and PCD ~4.4 min-1 ) for exhalation. The mouth joins the pharynx posterior to the velum and plays no role in ventilation at rest or during swimming. Increases in flow up to >400 ml kg-1 min-1 can be achieved by increases in both velum frequency and stroke volume and the ventilatory index (product of frequency x nostril pressure amplitude) provides a useful proxy for ventilatory flow rate. Two types of coughing (flow reversals) are described. During spontaneous swimming, ventilatory pressure and flow pulsatility becomes synchronised with rhythmic body undulations.
Hemodynamic abnormalities during muscle metaboreflex activation in patients with type 2 diabetes mellitus.

Metaboreflex is a reflex triggered during exercise or postexercise muscle ischemia (PEMI) by metaboreceptor stimulation. Typical features of metaboreflex are increased cardiac output (CO) and blood pressure. Patients suffering from metabolic syndrome display hemodynamic abnormalities, with an exaggerated systemic vascular resistance (SVR) and reduced CO response during PEMI-induced metaboreflex. Whether patients with type 2 diabetes mellitus (DM2) have similar hemodynamic abnormalities is unknown. Here we contrast the hemodynamic response to PEMI in 14 patients suffering from DM2 (age 62.7 ± 8.3 yr) and in 15 age-matched controls (CTLs). All participants underwent a control exercise recovery reference test and a PEMI test to obtain the metaboreflex response. Central hemodynamics were evaluated by unbiased operator-independent impedance cardiography. Although the blood pressure response to PEMI was not significantly different between the groups, we found that the SVR and CO responses were reversed in patients with DM2 as compared with the CTLs (SVR: 392.5 ± 549.6 and -14.8 ± 258.9 dyn·s-1·cm-5; CO: -0.25 ± 0.63 and 0.46 ± 0.50 l/m, respectively, in DM2 and in CTL groups, respectively; P < 0.05 for both). Of note, stroke volume (SV) increased during PEMI in the CTL group only. Failure to increase SV and CO was the consequence of reduced venous return, impaired cardiac performance, and augmented afterload in patients with DM2. We conclude that patients with DM2 have an exaggerated vasoconstriction in response to metaboreflex activation not accompanied by a concomitant increase in heart performance. Therefore, in these patients, blood pressure response to the metaboreflex relies more on SVR increases rather than on increases in SV and CO. NEW & NOTEWORTHY The main new finding of the present investigation is that subjects with type 2 diabetes mellitus have an exaggerated vasoconstriction in response to metaboreflex activation. In these patients, blood pressure response to the metaboreflex relies more on systemic vascular resistance than on cardiac output increments.
The Burden of Caring for a Child or Adolescent With Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): An Observational Longitudinal Study.

OBJECTIVE To describe the longitudinal association between disease severity, time established in clinical treatment, and caregiver burden in a community-based patient population diagnosed with pediatric acute-onset neuropsychiatric syndrome (PANS). METHODS The study included an observational longitudinal cohort design, with Caregiver Burden Inventories (CBIs) collected between April 2013 and November 2016 at the Stanford PANS multidisciplinary clinic. Inclusion criteria for this study were as follows: pediatric patients meeting strict PANS/pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) diagnostic criteria (n = 187), having a caregiver fill out at least 1 complete CBI during a disease flare (n = 114); and having family who lives locally (n = 97). For longitudinal analyses, only patients whose caregiver had filled out 2 or more CBIs (n = 94 with 892 CBIs) were included. In the study sample, most primary caregivers were mothers (69 [71.1%] of 97), the majority of PANS patients were male (58 [59.8%] of 97), and mean age at PANS onset was 8.8 years. RESULTS In a patient's first flare tracked by the clinic, 50% of caregivers exceeded the caregiver burden score threshold used to determine respite need in care receiver adult populations. Longitudinally, flares, compared with quiescence, predicted increases in mean CBI score (6.6 points; 95% CI, 5.1 to 8.0). Each year established in clinic predicted decreased CBI score (-3.5 points per year; 95% CI, -2.3 to -4.6). Also, shorter time between PANS onset and entry into the multidisciplinary clinic predicted greater improvement in mean CBI score over time (0.7 points per year squared; 95% CI, 0.1 to 1.3). Time between PANS onset and treatment with antibiotics or immunomodulation did not moderate the relationship between CBI score and time in clinic. CONCLUSIONS PANS caregivers suffer high caregiver burden. Neuropsychiatric disease severity predicts increased caregiver burden. Caregiver burden tends to decrease over time in a group of patients undergoing clinical treatment at a specialty PANS clinic. This decrease could be independent of clinical treatment.
The demographics of vaccine hesitancy in Shanghai, China

Background Vaccine hesitancy has been little studied in low- and middle-income countries but is a potential concern because vaccine refusal may increase the burden of infectious diseases and impede control efforts. The aim of this study was to compare vaccine hesitancy between locals, long-time city residents, and non-locals, who have more recently moved to the city from either other urban or rural areas, in Shanghai, China. Methods Parents of infants ≤3 months of age were surveyed at immunization clinics in Shanghai, China. Participants completed a paper questionnaire utilizing the 10-item Vaccine Hesitancy Scale, which was developed by the World Health Organization Strategic Advisory Group of Experts on Immunization. Items were grouped based on internal consistency, and regressed onto demographic variables using a negative binomial model. Results In total, 1,188 (92.5%) individuals participated. For most items on the scale, parents expressed positive beliefs about vaccines. However, about half of parents somewhat or strongly agreed that new vaccines carried more risks than older vaccines, and 71.6% somewhat or strongly agreed that they were concerned about serious adverse effects. Seven items from the Vaccine Hesitancy Scale were highly correlated and mapped onto “lack of confidence”; the other three items were analysed separately. Compared to mothers, fathers had less lack of confidence (β: -0.06, 95% CI: -0.12, -0.01), and individuals living in the outer suburbs (β: 0.13, 95% CI: 0.01, 0.25) and rural non-locals (β: 0.10, 95% CI: 0.02, 0.18) had greater lack of confidence in vaccines compared to their urban or local counterparts, respectively. Discussion Shanghai parents professed confidence in certain vaccine benefits, but vaccine messaging could focus on addressing misconceptions about vaccines for diseases no longer common, newer vaccines, and adverse effects associated with vaccination. These messages may need to be separately tailored to locals and non-locals, who have differing concerns.
Immunotherapeutic effects of recombinant adenovirus encoding interleukin 12 in experimental pulmonary tuberculosis

High dose of Mycobacterium tuberculosis (Mtb) strain H37Rv administered by intratracheal injection in BALB/c mice induce progressive tuberculosis (TB). In this model, during the first month there is a temporal control of bacillary growth, in coexistence with macrophage activation, granuloma formation and Th‐1 response. Then, bacterial proliferation recommences, accompanied by progressive pneumonia and decreasing expression of protective cytokines (IFN‐γ and TNF‐α). In this model, we studied the IL‐12 gene expression kinetics and cellular source. There is a rapid and progressive IL‐12 expression peaking at day 14, when granulomas start their formation and numerous macrophages show strong IL‐12 immunostaining, while during progressive TB there is a significant decrease of IL‐12 expression and occasional macrophages showed IL‐12 immunolabeling. In the second part of this study, we determined the immunotherapeutic effect of recombinant adenoviruses that codify IL‐12 (AdIL‐12). Intratracheal administration of only one dose of AdIL‐12 one day before Mtb infection produced significant decrease of bacterial loads, lesser pneumonia and higher expression of TNF‐α, IFN‐γ and iNOS. When only one dose of AdIL‐12 was given in healthy mice cohoused with infected mice with highly virulent and transmissible Mtb, total prevention of infection was conferred. Moreover, when AdIL‐12 was administered by intranasal route in animals suffering late active TB after 2 months of infection, a very low pulmonary bacilli burdens was detected. These experimental data confirm that IL‐12 is a significant cytokine in the immune protection against Mtb, and gene therapy based in adenoviruses coding this cytokine increased protective immunity and prevent Mtb transmission.
MRI phenotypes of the brain are related to future stroke and mortality in patients with manifest arterial disease: The SMART-MR study

Neurodegenerative and neurovascular diseases lead to heterogeneous brain abnormalities. A combined analysis of these abnormalities by phenotypes of the brain might give a more accurate representation of the underlying aetiology. We aimed to identify different MRI phenotypes of the brain and assessed the risk of future stroke and mortality within these subgroups. In 1003 patients (59 ± 10 years) from the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study, different quantitative 1.5T brain MRI markers were used in a hierarchical clustering analysis to identify 11 distinct subgroups with a different distribution in brain MRI markers and cardiovascular risk factors, and a different risk of stroke (Cox regression: from no increased risk compared to the reference group with relatively few brain abnormalities to HR = 10.34; 95% CI 3.80↔28.12 for the multi-burden subgroup) and mortality (from no increased risk compared to the reference group to HR = 4.00; 95% CI 2.50↔6.40 for the multi-burden subgroup). In conclusion, within a group of patients with manifest arterial disease, we showed that different MRI phenotypes of the brain can be identified and that these were associated with different risks of future stroke and mortality. These MRI phenotypes can possibly classify individual patients and assess their risk of future stroke and mortality.
Early Diagnosis of Spastic Cerebral Palsy in Infants with Periventricular White Matter Injury Using Diffusion Tensor Imaging

BACKGROUND AND PURPOSE: Periventricular white matter injury is the common cause of spastic cerebral palsy. However, the early diagnosis of spastic cerebral palsy still remains a challenge. Our aim was to investigate whether infants with periventricular white matter injury with bilateral spastic cerebral palsy have unique lesions different from those in infants without cerebral palsy and to evaluate the efficiency of DTI in the early diagnosis of spastic cerebral palsy. MATERIALS AND METHODS: Infants with periventricular white matter injury and controls underwent MR imaging at 6–18 months of age. Fractional anisotropy was calculated from DTI. Cerebral palsy was diagnosed by 24–30 months of age. Subjects were divided into 3 groups: infants with periventricular white matter injury with bilateral spastic cerebral palsy, infants with periventricular white matter injury without cerebral palsy, and controls. Tract-Based Spatial Statistics and Automated Fiber Quantification were used to investigate intergroup differences. Receiver operating characteristic curves were used to assess the diagnostic accuracy of spastic cerebral palsy. Correlations between motor function scores and fractional anisotropy were evaluated along white matter tracts. RESULTS: There were 20, 19, and 33 subjects in periventricular white matter injury with spastic cerebral palsy, periventricular white matter injury without cerebral palsy, and control groups, respectively. Decreased fractional anisotropy in the corticospinal tract was only observed in infants with periventricular white matter injury with spastic cerebral palsy, whereas decreased fractional anisotropy in the posterior thalamic radiation and genu and splenium of the corpus callosum was seen in both periventricular white matter injury subgroups. Fractional anisotropy in the corticospinal tract at the internal capsule level was effective in differentiating infants with periventricular white matter injury with spastic cerebral palsy from those without cerebral palsy by a threshold of 0.53, and it had strong correlations with motor function scores. CONCLUSIONS: Corticospinal tract lesions play a crucial role in motor impairment related to spastic cerebral palsy in infants with periventricular white matter injury. Fractional anisotropy in the corticospinal tract at the internal capsule level could aid in the early diagnosis of spastic cerebral palsy with high diagnostic accuracy.
The ability of three nickel–titanium mechanized systems to negotiate and shape MB2 canals in extracted maxillary first molars: a micro‐computed tomographic study

AIM To evaluate the influence of three engine-driven NiTi file systems manufactured from different NiTi alloys for the preparation of second mesiobuccal (MB2) canals in extracted maxillary first molars using a micro-computed tomographic (micro-CT) scanner. METHODOLOGY Thirty maxillary molars with two canals in the mesiobuccal root were selected and randomly divided into three groups (n = 10): Reciproc [REC; size 25, . 08 taper; VDW, Munich, Germany], ProDesign R [PDR; size 25, . 06 taper; Easy, Belo Horizonte, Brazil] and Mtwo [MO; size 25, . 06 taper; VDW, Munich, Germany]. Before and after root canal preparation of the MB2 canal, the teeth were scanned using a micro-CT to evaluate canal transportation, centring ability, dentine thickness and volume change. The working time to achieve working length was also evaluated. All parameters were compared statistically using the Kruskal-Wallis and Dunn test for multiple comparisons, with a significance level of 5%. RESULTS There was no significant difference amongst the groups regarding canal transportation and centring ability (P > 0.05). However, the PDR size 25, . 06 taper group had significantly lower canal volume and volume of dentine removal compared with a MO size 25, . 06 taper and REC size 25, . 08 taper (P < 0.05). A root perforation was detected in MO size 25, . 06 taper and REC size 25, . 08 taper groups, respectively. Regarding the working time, the PDR size 25, . 06 taper required a significantly longer time to achieve working length than MO size 25, . 06 taper and REC size 25, . 08 taper (P < 0.05). CONCLUSIONS All NiTi systems had similar canal transportation, centring ability and increase in apical volume after preparation of MB2 canals. However, the PDR size 25, . 06 taper had less volume of dentine removal, absence of root canal perforation and required a longer time to accomplish the root canal preparation.
A Three-Dimensional Dense Collagen Hydrogel to Model Cancer Cell/Osteoblast Interactions

No curative treatment options exist once breast cancer metastasizes to bone. This is due, in part, to an incomplete understanding of how osteolytic cancers interact with bone. Presented here is a novel approach to study the interactions between triple negative breast cancer cells and osteoblasts within a 3D collagenous environment. More specifically, a dense collagen hydrogel was employed to model interactions between MDA-MB-231 breast cancer cells and MC3T3-E1 pre-osteoblasts. Co-cultures with these two cell types, or MDA-MB-231-derived conditioned medium applied to MC3T3-E1 cells, were established in the context of plastically compressed dense collagen gel matrices. Importantly, breast cancer-derived conditioned medium or the establishment of breast cancer/osteoblast co-cultures did not negatively influence MC3T3-E1 cell viability. The inclusion of either conditioned medium or the presence of MDA-MB-231 cells resulted in impaired MC3T3-E1 differentiation into osteoblasts, which coincided with reduced osteoblast-mediated mineralization. The results presented here demonstrate that dense collagen gels provide a model environment to examine the effect of osteolytic breast cancer cells on osteoblast differentiation and subsequent mineralization of the collagen scaffold.
Thermal Conductivity during Phase Transitions

Thermal conductivity is a very basic property that determines how fast a material conducts heat, which plays an important and sometimes a dominant role in many fields. However, because materials with phase transitions have been widely used recently, understanding and measuring temperature‐dependent thermal conductivity during phase transitions are important and sometimes even questionable. Here, the thermal transport equation is corrected by including heat absorption due to phase transitions to reveal how a phase transition affects the measured thermal conductivity. In addition to the enhanced heat capacity that is well known, it is found that thermal diffusivity can be abnormally lowered from the true value, which is also dependent on the speed of phase transitions. The extraction of the true thermal conductivity requires removing the contributions from both altered heat capacity and thermal diffusivity during phase transitions, which is well demonstrated in four selected kinds of phase transition materials (Cu2Se, Cu2S, Ag2S, and Ag2Se) in experiment. This study also explains the lowered abnormal thermal diffusivity during phase transitions in other materials and thus provides a novel strategy to engineer thermal conductivity for various applications.