Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of Prostate-Specific Membrane Antigen in Tumor-Associated Vasculature Predicts Poor Prognosis in Hepatocellular Carcinoma

INTRODUCTION: Prostate-specific membrane antigen (PSMA) was originally found to be specifically expressed in normal prostate, and its expression was upregulated in almost all stages of prostate cancer. In recent years, PSMA was also found to be expressed in tumor-associated vasculature in many nonprostatic solid tumors. However, the expression pattern of PSMA in hepatocellular carcinoma (HCC) is not well studied. METHODS: In this study, we examined PSMA expression in 103 HCC tissues using immunohistochemical staining and analyzed the association between PSMA expression and other clinicopathological features and prognosis. RESULTS: Among the 103 cases, 27 cases (26%) showed PSMA expression in more than 50% of tumor-associated vasculature, 49 cases (48%) showed PSMA expression in less than 50% of vasculature, and 27 cases (26%) did not have detectable PSMA expression. Vascular PSMA expression was associated with several clinicopathological features, such as tumor stage, tumor differentiation, lymph node metastasis, and Ki-67 index. Furthermore, high vascular PSMA expression was also associated with poor prognosis in patients with HCC. Univariate and multivariate analyses showed that high vascular PSMA expression can be used as an independent prognostic marker for HCC. DISCUSSION: Our study provides the evidence that PSMA is specifically expressed in tumor-associated vasculature of HCC, and vascular PSMA expression may be used as a novel prognostic marker and a vascular therapeutic target for HCC.
Combining immunotherapies to treat non-small cell lung cancer

ABSTRACT Introduction: In recent years, immunotherapy has become an integral part of the treatment of many cancers, including non-small cell lung cancer (NSCLC). Precious therapeutic weapons impacting survival are monoclonal antibodies directed against the programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) immune checkpoint. Areas covered: Unfortunately, not all patients treated with checkpoint inhibitors have durable clinical responses. However, a better understanding of the complexity of interactions between the immune system and cancer, the latter capable of adopting evasion mechanisms, indicates different opportunities to enhance anti-tumor immunity. Expert opinion: In this paper, we review multiple strategies of combining immunotherapies that exploit not only additional immune checkpoint receptors and ligands but also other synergistic approaches such as vaccines or indoleamine 2,3-dioxygenase (IDO) inhibitors with the potential to extend the number of NSCLC patients achieving successful outcomes.
Characterization of Stool Virome in Children Newly Diagnosed With Moderate to Severe Ulcerative Colitis

Abstract Background Viral infections have been suggested as possible triggers for the onset of ulcerative colitis (UC). Methods We employed VirCapSeq-Vert, a high-throughput sequencing virus capture platform, to examine the stool virome of children with newly diagnosed moderate to severe UC. We surveyed fecal samples collected at presentation, after symptom remission, and from a control group diagnosed with irritable bowel syndrome. Results Seventy subjects with UC (mean age 13 years, 45 had moderate symptoms, 25 had severe, 69 of 70 had a Mayo endoscopy subscore 2/3) were studied. We detected a wide range of animal viruses that were taxonomically classified into 12 viral families. A virus was present in 50% of fecal samples collected at presentation, 41% of samples collected after remission, and 40% of samples in our control group. The most frequently identified viruses were diet-based gyroviruses. The UC cohort had a significantly higher prevalence of anelloviruses compared with the control cohort. However, we did not identify a single virus that can be implicated in the onset of UC and did not find an association between UC disease severity and viral presence. Conclusion Presence of virus in stool was not associated with the onset of pediatric UC.
Issues in the determination of ‘responders’ and ‘non‐responders’ in physiological research

What is the topic for this review? We discuss the dichotomization of continuous‐level physiological measurements into ‘responders’ and ‘non‐responders’ when interventions/treatments are examined in robust parallel‐group studies. What advances does it highlight? Sample responder counts are biased by pre‐to‐post within‐subject variability. Sample differences in counts may be explained wholly by differences in mean response, even without individual response heterogeneity and even if test–retest measurement error informs the choice of response threshold. A less biased and more informative approach uses the SD of individual responses to estimate the chance a new person from the population of interest will be a responder.
Cardiopulmonary resuscitation in poorly resourced settings: better to pre-empt than to wait until it is too late

Abbreviations: APLS: advanced paediatric life support; CA: cardiac arrest; CPR: cardiopulmonary resuscitation; CPA: cardiopulmonary arrest; ETAT: emergency triage assessment and treatment; ETAT+: emergency triage assessment and treatment (includes first 48 h); ICP: intracranial pressure; LMIC: lowand middleincome countries; MET: medical emergency team; PALS: paediatric advanced life support; PEA: pulseless electrical activity; PEWS: paediatric early warning signs; PICU: paediatric intensive care unit; ROSC: return of spontaneous circulation; RRT: rapid response team; VF: ventricular fibrillation
Tumor Characteristics Associated with Benefit from Pembrolizumab in Advanced Non–Small Cell Lung Cancer

Purpose: Several biomarkers have been individually associated with response to PD-1 blockade, including PD-L1 and tumor mutational burden (TMB) in non–small cell lung cancer (NSCLC), and CD8 cells in melanoma. We sought to examine the relationship between these distinct variables with response to PD-1 blockade and long-term benefit. Experimental Design: We assessed the association between baseline tumor characteristics (TMB, PD-L1, CD4, and CD8) and clinical features and outcome in 38 patients with advanced NSCLC treated with pembrolizumab (median follow-up of 4.5 years, range 3.8–5.5 years). Results: PD-L1 expression and CD8 infiltration correlated with each other and each significantly associated with objective response rate (ORR) and progression-free survival (PFS). TMB was independent of PD-L1 and CD8 expression, and trended towards association with ORR and PFS. There was no association between CD4 infiltration and outcomes. Only PD-L1 expression was correlated with overall survival (OS). Among 5 patients with long-term survival >3 years with no additional systemic therapy, PD-L1 expression was the only discriminating feature. The increased predictive value for PFS and OS of composite biomarker inclusive of PD-L1, CD8, CD4, and TMB was limited. Conclusions: In patients with NSCLC treated with PD-1 blockade with long-term follow up, TMB, PD-L1, and CD8 were each associated with benefit from PD-1 blockade. Pretreatment PD-L1 expression was correlated with T lymphocyte infiltration and OS, whereas models incorporating TMB and infiltrating CD4 and CD8 lymphocytes did not substantially add to the predictive value of PD-L1 alone for OS.
Cardiac Resynchronization Therapy in Heart Failure: Rationale, Results, Indications, Limits and Perspectives

Heart Failure is the result of heterogeneous structural heart diseases, especially ischemic disease, and is becoming increasingly common in all Western countries. Many patients continue to be symptomatic in spite of progress in pharmacological therapy, and the risk of mortality remains high in the most advanced functional classes. Cardiac resynchronization therapy can be used as a therapeutic strategy for alleviating symptoms and reducing mortality in a considerable percentage of patients with heart failure.Cardiac resynchronization therapy provides both immediate and medium/long-term results. The immediate results are the reduced QRS duration, the synchrony restoration between the ventricles and between the lateral and septal walls of the left ventricle, the reduced mitral regurgitation and the increased stroke volume. In the medium/long term, left ventricular reverse remodeling occurs and left ventricular ejection fraction is increased. Several trials have documented both increased functional capacity and improvements in quality of life and New York Heart Association class. Moreover, cardiac resynchronization therapy has been seen to reduce HF hospitalizations and mortality and the total number of days of hospitalization. In order to reduce the percentage of non-responders to cardiac resynchronization therapy, it is necessary to optimize the prognostic stratification of candidates for implantation through multi-parameter evaluations and to ensure correct device programming with periodic updates which are widely recommended but not so often performed. Whether indications should be extended will need to be evaluated in view of the known complications mainly associated with lead implantation.
Cartilage regeneration following septal surgery in young rabbits

Nasal septal surgery in children remains a controversial subject because of its possible detrimental effect on the subsequent growth of the mid-facial skeleton and also because of the associated increase of nasal saddling. Following Hayton's (1948) careful study of 31 children who had undergone Killian's submucous resection, a third of whom developed nasal saddling and broadening, a more conservative approach was generally adopted, delaying surgery till the age of 16 years. Encouraged by clinical and experimental studies, others have challenged this concept. Jennes (1964) found no growth retardation in his series and Huizing (1979), in his review of 150 cases of septoplasty for severe septal deformity, found only one case of late arrest of mid-facial growth. Bernstein (1973), in his experimental study, found that submucous resection in young pups was followed by normal facial development and stressed the critical importance of preserving septal mucoperichondrium. In a review of 700 cases of septoplasty, Maran (1979) concluded that septoplasty was justified under the age of 10 years in cases of severe deformity. More recent experiments, however, have shown that, even with preservation, of mucoperichondrium (Nordgaard and Kvinnsland, 1979; Verwoerd et al., 1979; Rhys Evans and Brain, 1981), resections of cartilage have caused retardation of nasal growth. A histological examination of septal cartilage following septal surgery is a useful adjuvant in clarifying this controversy. Pirsig (1979) reviewed 100 septal biopsies obtained from septorhinoplasties in children and concluded that partial cartilagenous regeneration occurred mainly from the perichondrium. Animal studies are worthwhile practical investigations provided that their absolute interpretation in Man is considered cautiously. Bernstein (1973) in fact suggested that primates should be used, although his work on canine pups provided useful information. Fuchs (1969) demonstrated that some cartilagenous regeneration and limited osteogenesis occurred in young rabbits following septal surgery. Complementary to a previous paper on mid-facial development in rabbits (Rhys Evans and Brain, 1981), a histological study was carried out in order to investigate the regeneration of septal cartilage following various surgical procedures.
Perinatal and childhood risk factors for overweight in a provincial sample of Canadian Grade 5 students.

BACKGROUND The risk of obesity is determined by a complex interaction of prenatal, lifestyle, genetic, and environmental factors. OBJECTIVE To investigate the differential impact of prenatal, child, and family factors on body weight status in childhood. METHODS The current study links population-based survey data of Grade 5 students who participated in the 2003 Children's Lifestyle and School Performance Study in Nova Scotia, Canada, with a provincial perinatal registry. Multilevel logistic regression was used to investigate the association between prenatal, lifestyle, and socioeconomic factors and childhood overweight. RESULTS Of the 4 298 participating children, 3 426 (80%) could be linked with information in the perinatal registry. Small-for-gestational age infants appeared to be less likely to be overweight at age 10 or 11 years (odds ratio [OR]=0.68) whereas those born large-for-gestational age were more likely to be overweight (OR=1.23). Maternal pre-pregnancy weight was associated with childhood overweight (OR=4.42 for >80 kg vs. <60 kg) as were the child's physical activity (OR=0.65 for >7x/week vs. < or =2x/week) and screen time (OR=1.82 for >6 h/day vs. < or =1h/day). Smoking during pregnancy increased the child's odds for being overweight (OR=1.42 for >0.5 packs/day vs. none). Children living in neighborhoods with higher housing values were less likely to be overweight (OR=0.68 for highest vs. lowest tertile). CONCLUSIONS Overweight young women should be advised on the importance of healthy eating, active living and maintaining a healthy weight in the pre-pregnancy years to reduce the risk of overweight in their offspring.
Speech profiles of Spanish-Catalan children with developmental language disorder

ABSTRACT Children with developmental language disorders (DLD) are especially characterised by morphosyntactic difficulties. Nevertheless, previous studies have also shown that children with DLD have phonological difficulties. This paper aims to describe the productive and perceptive phonological speech profile of Spanish-Catalan children with DLD at the age of six in order to characterise the underlying nature of their difficulties. Fourteen Spanish-Catalan six-year-old children with DLD and 14 control children without language difficulties who attended the same class were assessed with the screening and discrimination tasks of the A-RE-HA: Análisis del Retraso del Habla (Speech Delay Analysis – Catalan and Spanish version). We analysed the production of words, syllables and phonemes, phoneme discrimination and phonological simplification processes used by these children. The results showed that children with DLD have a lower percentile in correct word structures, syllabic structures and phonemes, and have more difficulty discriminating phonemes. Detailed analyses revealed more difficulties with the most complex word and syllabic templates, and with almost all phonemes. Furthermore, children with DLD applied more phonological simplification processes than the control group. An individual analysis showed that only ten of the children with DLD also had a speech delay (percentile < 25), while four had scores in line with their age. These results show that most of the six-year-old children with DLD maintain speech difficulties, which are mainly phonological and not (or not only) articulatory. Therefore, individual differences with respect to speech delay in DLD must be taken into consideration to better detect these children.
Galectins‐1 and ‐3 in Human Intervertebral Disc Degeneration: Non‐Uniform Distribution Profiles and Activation of Disease Markers Involving NF‐κB by Galectin‐1

Degeneration of the human intervertebral disc (IVD) is assumed to underlie severe clinical symptoms, in particular chronic back pain. Since adhesion/growth‐regulatory galectins are linked to arthritis/osteoarthritis pathogenesis by activating a pro‐degradative/‐inflammatory gene expression signature, we hypothesized a similar functional involvement of galectins in IVD degeneration. Immunohistochemical evidence for the presence of galectins‐1 and ‐3 in IVD is provided comparatively for specimens of spondylochondrosis, spondylolisthesis, and spinal deformity. Immunopositivity was detected in sections of fixed IVD specimens in each cellular compartment with age‐, disease‐, and galectin‐type‐related differences. Of note, presence of both galectins correlated with IVD degeneration, whereas correlation with age was seen only for galectin‐3. In addition, staining profiles for these two galectins showed different distribution patterns in serial sections, an indication for non‐redundant functionalities. In vitro, both galectins bound to IVD cells in a glycan‐dependent manner. However, exclusively galectin‐1 binding triggered a significant induction of functional disease markers (i.e., IL6, CXCL8, and MMP1/3/13) with involvement of the nuclear factor‐kB pathway. This study thus gives direction to further network analyses and functional studies on galectins in IVD degeneration. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2204–2216, 2019
Processing of auditory deviants with changes in one versus two stimulus dimensions.

Auditory event-related potentials (ERPs) in response to 50-ms tones were recorded from the human scalp. A standard stimulus (p = .88) and three different deviants were randomly presented via earphones. There were two one-dimensional deviants (one frequency and one location deviant) and one two-dimensional deviant, with changes in both frequency and location. In one condition, subjects read a book and ignored the auditory stimuli, whereas in another condition they tried to discriminate deviants from standards. In the ignore condition, the two-dimensional deviant elicited an enhanced mismatch negativity (MMN) as compared with the MMNs elicited by the one-dimensional deviants. The temporal and the topographic distributions of the two-dimensional MMNs could be modeled by adding the one-dimensional MMNs. This activity of the MMNs probably results from the independent activity of separate neural populations generating the frequency and the location MMN. In the attend condition, the deviance-related ERP effects were not additive in the N2b and P3 range, implicating that the neural processes involved in the conscious detection of changes in location and frequency were not independent.
Five-year results from a randomised controlled trial comparing prostheses supported by 5-mm long implants or by longer implants in augmented bone in posterior atrophic edentulous jaws.

PURPOSE To evaluate whether 5-mm short dental implants could be an alternative to augmentation with anorganic bovine bone and placement of at least 10-mm long implants in posterior atrophic jaws. MATERIALS AND METHODS Fifteen patients with bilateral atrophic mandibles (5 to 7 mm bone height above the mandibular canal) and 15 patients with bilateral atrophic maxillae (4 to 6 mm bone height below the maxillary sinus), and bone thickness of at least 8 mm, were randomised according to a split-mouth design to receive one to three 5-mm short implants or at least 10-mm long implants in augmented bone. Mandibles were vertically augmented with interpositional bone blocks and maxillary sinuses with particulated bone via a lateral window. Implants were placed after 4 months, submerged and loaded, after another 4 months, with provisional prostheses. Four months later, definitive provisionally cemented prostheses were delivered. Outcome measures were: prosthesis and implant failures, any complication and peri-implant marginal bone level changes. RESULTS In five augmented mandibles the planned 10-mm long implants could not be placed and shorter implants (7.0 and 8.5 mm) had to be used instead. Five years after loading, six patients, five treated in the mandible and one in the maxilla, dropped out. Three prostheses (one mandibular and two maxillary) failed in the short-implant group versus none in the long-implant group. In mandibles one long implant failed versus two short implants in one patient. In maxillae one long implant failed versus three short implants in two patients. There were no statistically significant differences in implant (n = 26; P = 1.00, difference = 3.85%, 95% CI: -12.95% to 20.64%) and prosthetic (n = 26; P = 0.250, difference = 11.54%, 95% CI: -0.74% to 23.82%) failures. Eleven patients had 16 complications at short implants (one patient accounted for six complications) and 12 patients had 14 complications at long implants. There were no statistically significant differences in complications (n = 28; P = 1.00, difference = -3.57%, 95% CI: -30.65% to 23.51%). Five years after loading, patients with mandibular implants lost on average 1.72 mm at short implants and 2.10 mm at long implants of peri-implant marginal bone. This difference was statistically significant (difference = 0.37 ± 0.43 mm; 95% CI: 0.07 to 0.68 mm; P = 0.022). In maxillae, patients lost on average 1.31 mm at short implants and 1.79 mm at long implants. This difference was statistically significant (difference = 0.48 ± 0.43 mm; 95% CI: 0.22 to 0.74 mm; P = 0.002). CONCLUSIONS Five years after loading, 5-mm short implants achieved similar results to longer implants in augmented bone. The choice of short implants might be preferable to vertical bone augmentation, especially in mandibles, since the treatment is faster and cheaper.
Physician Versus Nonphysician Instruction: Evaluating an Expert Curriculum-Competent Facilitator Model for Simulation-Based Central Venous Catheter Training.

INTRODUCTION Healthcare simulation supports educational opportunities while maintaining patient safety. To reduce costs and increase the availability of training, a randomized controlled study evaluated central venous catheter (CVC) insertion training in the simulation laboratory with nonphysician competent facilitators (NPCFs) as instructors. METHOD A group of learners naive to central line placement participated in a blended curriculum consisting of interactive online materials and simulation-based training. Learners were randomized to training with NPCFs or attending physician faculty. The primary outcome was simulated CVC insertion task performance, graded with a validated checklist by blinded physician reviewers. Learner knowledge and satisfaction were also evaluated. Analysis was conducted using noninferiority testing. RESULTS Eighty-five students, 11 attending physicians, and 7 NPCFs voluntarily participated. Noninferiority testing of the difference in CVC insertion performance between NPCF-trained learners versus physician-trained learners found no significant difference [rejecting the null hypothesis of inferiority using an 8% noninferiority margin (P < 0.01)]. In addition, there was no difference found between the 2 groups on pre/post knowledge scores, self-reported learner comfort, course satisfaction, or instructor satisfaction. CONCLUSIONS An introductory CVC curriculum can be taught to novice learners by carefully trained and supported NPCFs and achieve skill and knowledge outcomes similar to learners taught by physicians.
Obesity as a Risk Factor for Alzheimer’s Disease: Implication of Leptin and Glutamate

Obesity is known to induce leptin and insulin resistance. Leptin is a peptide hormone synthesized in adipose tissue that mainly regulates food intake. It has been shown that insulin stimulates the production of leptin when adipocytes are exposed to glucose to encourage satiety; while leptin, via a negative feedback, decreases the insulin release and enhances tissue sensitivity to it, leading to glucose uptake for energy utilization or storage. Therefore, resistance to insulin is closely related to leptin resistance. Obesity in middle age has also been related to Alzheimer’s disease (AD). In recent years, the relation between impaired leptin signaling pathway and the onset of AD has been studied. In all this context the role of the blood brain barrier (BBB) is crucial. Slow excitotoxicity happens in AD due to an excess of the neurotransmitter glutamate. Since leptin has been shown to regulate N-methyl-D-aspartate (NMDA) receptors, we want to review the link between these pathological pathways, and how they are affected by other AD triggering factors and its role in the onset of AD.