Miracle-dz/UniFAR-FTUs huggingface dataset:
HPV Vaccination Coverage Among US Teens Across the Rural-Urban Continuum.

BACKGROUND In this study, we used data from the National Immunization Survey-Teen (NIS-Teen) to examine HPV vaccination uptake by rural and urban residence defined by ZIP code. METHODS We used 2012-2013 NIS-Teen data to examine associations of HPV vaccination among teens aged 13-17 years with ZIP code measures of rural/urban (Rural-Urban Commuting Area (RUCA) codes, population density). Multivariable logistic regression was used to estimate the odds of HPV vaccination initiation (≥ 1 dose) and completion (≥ 3 doses). RESULTS HPV vaccination was lower among girls from isolated small rural towns (≥1 dose 51.0%; ≥3 doses 30.0%) and small rural towns (≥1 dose 50.2%; ≥3 doses 26.8%) than among urban girls (≥1 dose 56.0%; ≥3 doses 35.9%). Girls from small rural towns had lower odds of completion (0.74, 95% CI: 0.60-0.91) than girls from urban areas. HPV vaccination was lower among boys from isolated small rural towns (≥1 dose 17.3%; ≥3 doses 5.31%) and small rural towns (≥1 dose 18.7%; ≥3 doses 5.50%) than those in urban areas (≥1 dose 28.7%; ≥3 doses 10.7%). Boys in isolated small rural towns had statistically significantly lower odds of initiation (0.68, 95% CI: 0.52-0.88) and completion (0.63, 95% CI: 0.41-0.97) than urban boys. Girls and boys from high-poverty rural areas had lower odds of initiation and completion than did their counterparts from high-poverty urban areas. CONCLUSION Rural girls had lower odds of completing the HPV vaccine than their urban counterparts. Rural boys had lower odds than urban boys for HPV vaccination initiation and completion.
A Novel Cartilage Fragments Stimulation Model Revealed that Macrophage Inflammatory Response Causes an Upregulation of Catabolic Factors of Chondrocytes In Vitro

Objective Osteoarthritis is a progressive joint disease characterized by cartilage degradation and synovial inflammation. Presence of cartilage fragments in the joint due to degradation of cartilage is thought to be associated with local inflammatory response and progressive osteoarthritic process. Understanding the mechanism by which cartilage fragments elicit this destructive process should aid in designing novel therapeutic approaches. Therefore, objective of current study is to establish an in vitro model to examine the cross-talk between chondrocytes and cartilage fragments–stimulated macrophages. Design Cartilage fragments were prepared from femoral head cartilages of mice and analyzed using a scanning electron microscope and particle size analyzer. Bone marrow–derived macrophages were co-cultured with cartilage fragments and chondrocytes using transwell co-culture system. Macrophage inflammatory mediators in supernatant of cultures were determined by ELISA and gene expression of macrophages and chondrocyte were quantified by qRT-PCR. Results Shapes of cartilage fragments were irregular with sizes ranged between 0.54 and 55 μm. Macrophages cultured with cartilage fragments released significantly higher concentrations of TNF-α, IL-6, and NO than those of mock and control. Consistently, gene expressions of TNF-α, IL-6, and MMP-9 were significantly increased in stimulated macrophages. The elevation in production of pro-inflammatory molecules in stimulated macrophages cultures were coincident with an increase in gene expression of chondrocyte MMP-13, iNOS, and IL-6. Conclusion We developed an in vitro co-culture model to study the impact of stimulation of macrophage by cartilage fragments on the expression of chondrocyte carbolic factors. Our results revealed that cartilage fragments triggered macrophages inflammatory response that enhanced the production of chondrocyte catabolic factors.
The Roberts–2: Italian Validation on a Sample of Children and Adolescents

Abstract The Roberts–2 (Roberts & Gruber, 2005) is a narrative test that was specifically designed to assess developmental and clinical functioning in children and adolescents. It was developed with the intent of addressing the lack of objective scoring systems for narrative instruments to assess childhood. The Roberts–2 is characterized by a standardized administration, scoring system, and interpretation guidelines that use a performance-based approach to narrative testing. This instrument has gained wide recognition in clinical practice but is minimally supported by empirical literature. This study aims to decrease this gap between clinical application and research findings through the Italian validation of the Roberts–2. The Italian version of the Roberts–2 was validated in both nonclinical and clinical participants. Study 1 (N = 738) assessed an Italian community sample to validate the Roberts–2. Specifically, interrater reliability, factorial structure, and developmental trends were explored. In Study 2, we compared a community sample with a sample of clinically referred children (N = 86) to test the clinical significance of the Roberts–2 indexes. The test performed well in differentiating between developmental groups as well as between clinical and nonclinical samples. The test is a useful tool for assessing both developmental and clinical aspects of the psychological functioning of children and adolescents.
Predictions of Birmingham hip resurfacing implant offset - In vitro and numerical models

Abstract The number of hip resurfacing arthroplasty procedures has declined dramatically in recent years, for reasons related to the survival rate. Some studies suggest that metal particles are the main critical problem, but do not specify the effect of femoral position on the failure rate. The present study aims to analyze whether the positioning of the resurfacing head implant is important in the distribution of bone strains and in the risk of fracture of the femur. Three in vitro experimental models received the Birmingham hip resurfacing implant to replicate the total hip joint. The resurfacing head of the implanted models was placed in three different offset positions: in a positive offset, with the same femoral head center and in a negative offset. The numerical models were validated by correlating numerical and experimental results. Comparing experimental results from the implanted and intact femurs highlights a strain increase of up to 48% in the proximal medial femur region for positive offset and up to 18% in the neutral position. A reduction of 72% for negative offset (valgus position) was also measured experimentally. A significant change in strain distributions was observed with a resurfacing hip system and increased risk of neck fracture was found using the resurfacing head in positive offset. The iliac bone presents a high decrease in strains that will induce bone loss in the long term. Among the offset positions tested, results suggest that the negative offset (valgus position) and the natural position are the best equilibrated for better long-term results.
Fracture Risk in Patients With Inflammatory Bowel Disease: A Nationwide Population-Based Cohort Study From 1964 to 2014

INTRODUCTION: Most studies on fractures in inflammatory bowel disease (IBD) are based on patients from tertiary centers or patients followed up before the introduction of immunomodulators or biologics. In addition, the role of corticosteroids in fracture risk has rarely been examined. METHODS: We conducted a nationwide population-based cohort study of 83,435 patients with incident IBD (ulcerative colitis [UC]: n = 50,162, Crohn's disease [CD]: n = 26,763, and IBD unclassified: 6,510) and 825,817 reference individuals from 1964 to 2014. Using multivariable Cox regression, we estimated hazard ratios (HRs) for hip fracture and any fracture and the association with cumulative corticosteroid exposure. RESULTS: During 1,225,415 person-years of follow-up in patients with IBD, there were 2,491 first-time hip fractures (203/100,000 person-years) compared with 20,583 hip fractures during 12,405,642 person-years in reference individuals (159/100,000 person-years). This corresponded to an HR of 1.42 (95% confidence interval [CI] = 1.36–1.48). The risk for hip fracture was higher in CD compared with UC (P < 0.001). Inflammatory bowel disease was also associated with any fracture (IBD: HR = 1.18; 95% CI = 1.15–1.20). Hazard ratios for hip fracture had not changed since the introduction of immunomodulators or biologics. Increasing exposure to corticosteroids was associated with hip fracture in both IBD and non-IBD individuals (P < 0.001), but only in elderly (>60 years) patients with IBD. The association between IBD and hip fracture was nonsignificant among individuals without corticosteroids (HR = 1.11; 95% CI = 0.86–1.44). CONCLUSIONS: Inflammatory bowel disease (CD and UC) is associated with an increased risk of hip fracture and any fracture, but not in individuals without a history of corticosteroid treatment. The association between corticosteroids and hip fracture was restricted to elderly patients with IBD.
Procalcitonin for prediction of chorioamnionitis in preterm premature rupture of membranes*

Abstract Objective: To assess serum procalcitonin (PCT), a marker of monocyte activity, in predicting chorioamnionitis in preterm premature rupture of membranes (PPROM). Methods: Prospective cohort study in singleton gestation patients with PPROM between 2 2 + 0 to 3 3 + 6 weeks gestation. Two blood samples were taken – admission and delivery or diagnosis of clinical chorioamnionitis. Maternal serum PCT > 0.1 ng/mL was considered positive. Patients were divided into four groups: clinical evidence of chorioamnionitis confirmed by placental pathology (group C + P); pathological evidence of chorioamnionitis without clinical signs (group P); clinical signs only (group C); and patients without clinical or pathological findings (group N). Groups were compared to gestational age matched controls. Results: Forty eight patients recruited, with 28 eligible for analysis: 10 in C + P group, 10 P group, 3 C group, and 5 N group. None of the control or PPROM patients had positive PCT on admission. At delivery, 3 of 10 group C + P and 4 of 10 group P had positive PCT. Maternal serum PCT sensitivity was 50% and specificity 55.6% for diagnosis of pathological chorioamnionitis. Conclusions: Maternal serum PCT is not detectable in PPROM patients at admission or in uncomplicated pregnant controls and is a poor predictor for clinical or pathological chorioamnionitis.
Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazilian centers to compare the type and prevalence of RET mutations with those from other countries. The most frequent mutations, classified by the number of families affected, occur in codon 634, exon 11 (76 families), followed by codon 918, exon 16 (34 families: 26 with M918T and 8 with M918V) and codon 804, exon 14 (22 families: 15 with V804M and 7 with V804L). When compared with other major published series from Europe, there are several similarities and some differences. While the mutations in codons C618, C620, C630, E768 and S891 present a similar prevalence, some mutations have a lower prevalence in Brazil, and others are found mainly in Brazil (G533C and M918V). These results reflect the singular proportion of European, Amerindian and African ancestries in the Brazilian mosaic genome.
Potential involvement of S1PR1/STAT3 signaling pathway in cardiac valve damage due to rheumatic heart disease

ABSTRACT Rheumatic heart disease (RHD) is a public health burden in developing countries. Th17 cell-associated cytokines might play a role in the pathogenesis and development of RHD, but the specific molecular mechanism is not completely understood. We investigated the potential role of sphingosine-1-phosphate receptor 1 (S1PR1)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in cardiac valve damage in a rat model of RHD. We used 20 Lewis rats divided randomly into control and RHD groups. The RHD model was constructed by injecting inactivated group A Streptococci and complete Freund’s adjuvant (CFA). The rats in the control group were injected with normal saline and CFA. Th17 cell-related cytokines were measured by ELISA. Fibrosis was assessed by histological examination. RT-qPCR and western blot were used to detect the expression of S1PR1 and STAT3/phosphorylated STAT3 (p-STAT3). The S1PR1/STAT3 signaling pathway was activated in the RHD model. Compared to the control group, serum levels of IL-17 and IL-21 cytokines associated with Th17 cells were increased significantly in the RHD group; the collagen volume fraction also was substantially increased. The S1PR1/STAT3 signaling pathway might be involved in RHD induced cardiac valve damage by regulating Th17 cells.
Kinematics of the diffuse intragroup and intracluster light in groups and clusters of galaxies in the local universe within 100 Mpc distance

Nearly all intragroup (IGL) and intracluster light (ICL) comes from stars that are not bound to any single galaxy but were formed in galaxies and later unbound from them. In this review we focus on the physical properties–phase space properties, metallicity and age distribution–of the ICL and IGL components of the groups and clusters in the local universe, within 100 Mpc distance. Kinematic–information on these very low surface brightness structures mostly comes from discrete tracers such as planetary nebulae and globular clusters, showing highly unrelaxed velocity distributions. Cosmological hydrodynamical simulations provide key predictions for the dynamical state of IGL and ICL and find that most IC stars are dissolved from galaxies that subsequently merge with the central galaxy. The increase of the measured velocity dispersion with radius in the outer halos of bright galaxies is a physical feature that makes it possible to identify IGL and ICL components. In the local groups and clusters, IGL and ICL are located in the dense regions of these structures. Their light fractions relative to the total luminosity of the satellite galaxies in a given group or cluster are between a few to ten percent, significantly lower than the average values in more evolved, more distant clusters. IGL and ICL in the Leo I and M49 groups, and the Virgo cluster core around M87, has been found to arise from mostly old (≥10 Gyr) metal-poor ([Fe/H] <-1.0) stars of low-mass progenitor galaxies. New imaging facilities such as LSST, Euclid, and the “big eyes’’ on the sky–ELT and JWST with their advanced instrumentation–promise to greatly increase our knowledge of the progenitors of the IGL and ICL stars, their ages, metal content, masses and evolution, there by increasing our understanding of this enigmatic component.
How Well Do Results From Randomized Clinical Trials and/or Recommendations for Implantable Cardioverter‐Defibrillator Programming Diffuse Into Clinical Practice?

Background Inappropriate implantable cardioverter‐defibrillator programming can be detrimental. Whether trials/recommendations informing best implantable cardioverter‐defibrillator programming (high‐rate cutoff and/or extended duration of detection) influence practice is unknown. Methods and Results We measured reaction to publication of MADIT‐RIT (Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy; 2012) and the Consensus Statement (2015) providing generic programming parameters, in a national cohort of implantable cardioverter‐defibrillator recipients, using the ALTITUDE database (Boston Scientific). Yearly changes in programmed parameters to either trial‐specified or class 1 recommended parameters (≥185 beats per minute or delay ≥6 seconds) were assessed in parallel. From 2008 to 2017, 232 982 patients (aged 67±13 years; 28% women) were analyzed. Prevalence of MADIT‐RIT–specific settings before publication was <1%, increasing to 13.6% in the year following. Thereafter, this increased by <6% over 5 years. Among preexisting implants (91 171), most patients (58 739 [64.4%]) underwent at least 1 in‐person device reprogramming after trial publication, but <2% were reprogrammed to MADIT‐RIT settings. Notably, prevalence of programming to ≥185 beats per minute or delay ≥6 seconds was increased by MADIT‐RIT (57.4% in 2013 versus 40.2% at baseline), but the following publication of recommendations had minor incremental effect (73.2% in 2016 versus 70.8% in 2015). High‐rate cutoff programming was favored almost 2‐fold compared with extended duration throughout the test period. Practice changes demonstrated large interhospital and interstate variations. Conclusions Trial publication had an immediate effect during 1 year postpublication, but absolute penetration was low, and amplified little with time. Consensus recommendations had a negligible effect. However, generic programming was exercised more widely, and increased after trial publication, but not following recommendations.
[Left Atrial Strain Independently and Incrementally Predicts High Risk Thromboembolic Findings Over CHA2DS2-VASc Score and BNP].

BACKGROUND Left atrial longitudinal strain(LAs) is a novel and useful parameter of LA function and reflecting thromboembolic risk. CHA₂DS₂-VASc score and brain natriuretic protein (BNP) are also used for risk stratifica- tion. However, little is known about the impact of LAs on stroke risk stratification over these parameters. In this study, we aimed to examine whether LAs has independent and incremental risk stratification over them. METHODS We studied 97 consecutive patients (age: 66 ± 12, 70 males) who underwent transesophageal echocardi- ography for evaluation of left atrial appendage (LAA) thrombus with persistent or paroxysmal atrial fibrillation. We assessed whether patients had spontaneous echo contrast (SEC) or not. Patients with LAA thrombus or sponta- neous echo contrast (SEC) were defined as high risk. LAs was assessed by averaging the segments measured in the 4- and 2-chamber views by transthoracic echocardiography. RESULTS Among the 97 patients, 51(53%) patients had sinus rhythm and 36 were with SEC. Although LAs (21.0 ? 9.0%), CHA₂DS₂-VASc score (2.7± 1.7) and BNP were mutually associated, only LAs and CHA₂DS₂-VASc score were independent predictors of high thromboembolic risk but BNP not. In nested logistic regression model anal- yses, predictive ability of a model with CHA₂DS₂-VASc score was improved by the addition of BNP (p =0.004) and further by adding LAs (p =0.027). CONCLUSION LAs predicts independently and incrementally LAA thrombus or SEC over CHA₂DS₂-VASc score and BNP, suggesting that LAs serves as a functional predictor for future thromboembolism. [Original].
SPR-Measured Dissociation Kinetics of PROTAC Ternary Complexes Influence Target Degradation Rate

Bifunctional degrader molecules, known as proteolysis-targeting chimeras (PROTACs), function by recruiting a target to an E3 ligase, forming a target/PROTAC/ligase ternary complex. Despite the importance of this key intermediate species, no detailed validation of a method to directly determine binding parameters for ternary complex kinetics has been reported, and it remains to be addressed whether tuning the kinetics of PROTAC ternary complexes may be an effective strategy to improve the efficiency of targeted protein degradation. Here, we develop an SPR-based assay to quantify the stability of PROTAC-induced ternary complexes by measuring for the first time the kinetics of their formation and dissociation in vitro using purified proteins. We benchmark our assay using four PROTACs that target the bromodomains (BDs) of bromodomain and extraterminal domain proteins Brd2, Brd3, and Brd4 to the von Hippel–Lindau E3 ligase (VHL). We reveal marked differences in ternary complex off-rates for different PROTACs that exhibit either positive or negative cooperativity for ternary complex formation relative to binary binding. The positively cooperative degrader MZ1 forms comparatively stable and long-lived ternary complexes with either Brd4BD2 or Brd2BD2 and VHL. Equivalent complexes with Brd3BD2 are destabilized due to a single amino acid difference (Glu/Gly swap) present in the bromodomain. We observe that this difference in ternary complex dissociative half-life correlates to a greater initial rate of intracellular degradation of Brd2 and Brd4 relative to Brd3. These findings establish a novel assay to measure the kinetics of PROTAC ternary complexes and elucidate the important kinetic parameters that drive effective target degradation.
Magnetic resonance imaging after external beam radiotherapy and concurrent chemotherapy for locally advanced cervical cancer helps to identify patients at risk of recurrence

Objective Tumor volume and regression after external beam radiotherapy have been shown to be accurate parameters to assess treatment response via magnetic resonance imaging (MRI). The aim of the study was to evaluate the prognostic value of tumor size reduction rate after external beam radiotherapy and chemotherapy prior to brachytherapy. Methods Patients with locally advanced cervical cancer treated at two French comprehensive cancer centers between 1998 and 2010 were included. Treatment was pelvic external beam radiotherapy with platinum based chemotherapy followed by brachytherapy. Records were reviewed for demographic, clinical, imaging, treatment, and follow-up data. Anonymized linked data were used to ascertain the association between pre-external and post-external beam radiotherapy MRI results, and survival data. Results 185 patients were included in the study. Median age at diagnosis was 45 years (range 26–72). 77 patients (41.6%) were International Federation of Gynecology and Obstetrics stage IB2-IIA disease and 108 patients (58.4%) were stage IIB-IVA. Median tumor size after external beam radiotherapy and chemotherapy was 2.0 cm (range 0.0–8.0) and median tumor size reduction rate was 62.4% (range 0.0–100.0%). Tumor size and tumor reduction rate at 45 Gy external beam radiotherapy MRI were significantly associated with local recurrence free survival (P<0.001), disease free survival, and overall survival (P<0.05). Tumor reduction rate ≥60% was significantly associated with a decreased risk of relapse and death (HR (95% CI) 0.21 (0.09 to 0.50), P=0.001 for local recurrence free survival; 0.48 (0.30 to 0.77) P=0.002 for disease free survival; and 0.51 (0.29 to 0.88), P=0.014 for overall survival). Conclusions Tumor size reduction rate >60% between pre-therapeutic and post-therapeutic 45 Gy external beam radiotherapy with concurrent chemotherapy was associated with improved survival. Future studies may help to identify patients who may ultimately benefit from completion surgery, adjuvant chemotherapy, and closer follow-up.