Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomics of racial and ethnic disparities in childhood acute lymphoblastic leukemia

Although the cure rates of childhood acute lymphoblastic leukemia (ALL) have improved dramatically in the past 40 years, not all children have benefited equally from this impressive progress. Racial and ethnic disparities in the incidence and treatment outcome of childhood ALL persist, with Hispanic children having an elevated risk of developing ALL and one of the lowest survival rates after ALL therapy. A critical barrier to progress is the lack of an understanding of the causes of ALL disparities, particularly racial and ethnic differences in ALL biology. In this review, the authors summarize the current knowledge on population variation in childhood ALL incidence and treatment outcome, discuss the contributing genetic and nongenetic variables, and highlight possible therapeutic interventions to mitigate disparities in ALL. Cancer 2014;120:955–962. © 2013 American Cancer Society.
A SIMPLE STUDY OF AWARENESS AND DREAMING DURING ANAESTHESIA

SUMMARY An investigation is described into the problems of recall and dreaming under light anaesthesia with nitrous oxide, muscle relaxation being provided by tubocurarine, and the anaesthetic technique being, as far as possible, standardized. Tape-recorded music of two types was used to test the patient's ability to hear and, in addition, the nature and quality of dreams was investigated. There was no evidence that patients were able to hear the tape-recordings and there was no evidence of “awareness” during the operative procedure. Dreaming occurred in 44 per cent of the patients and details of the dreams were recalled in some two-thirds of these. Hypocapnia did not protect against dreaming. Patients who showed marked movement during the operative procedure were more liable to dream than those who did not; the significance of this movement is discussed. In this (unpremedicated) group of patients nearly half described waiting for surgery as the most unpleasant feature of their surgical experience, and postoperative pain was the major complaint in a further 20 per cent. The third commonest of the major complaints was related to requests to lift the head, etc., when unable to do so in the time immediately after operation, and this finding would seem to have some minor practical significance. Unpleasant dreams were the fourth commonest major complaint.
The association of single nucleotide polymorphisms of Toll-like receptor 3, Toll-like receptor 7 and Toll-like receptor 8 genes with the susceptibility to HCV infection

ABSTRACT Background: Single nucleotide polymorphisms (SNPs) of Toll-like receptors (TLRs) are linked with functional modification of cytokine responses. In chronic hepatitis C virus (HCV) infection, studies of TLR polymorphisms have primarily targeted receptor pathways implicated in viral immune responses. We hypothesized that one or more variant(s) of TLR3, TLR7 and TLR8 are associated with different outcomes of HCV infection. Materials & methods: A total of 3368 subjects from 850 families were recruited and divided into three main groups categorized as chronic HCV CHC spontaneous viral clearance (SVC), and controls. All individuals were genotyped for three SNPs for TLR3, two SNPs for TLR7, and two SNPs for TLR8 using allelic discrimination real-time PCR. Results: Carriage of the C allele in three SNPs of TLR3 (rs3775290, rs3775291, and rs5743312), the C allele in TLR7 (rs3853839) in females only, and the C allele in TLR8 (rs3764879) in males only were significantly higher in SVC group than CHC group (P < 0.001), while carriage of the T allele in TLR7 (rs179008) in females only and the A allele in TLR8 (rs3764880) in both males and females were significantly higher in CHC infection more than SVC group (P < 0.001). Conclusion: The C allele is protective of HCV in TLR3, TLR7 (rs3853839) in females only, and TLR8 (rs3764879) in males only, while risk of infection is linked to the T allele in TLR7 (rs179008) in females only and the A allele in TLR8 (rs3764880) in both sexes.
Electrocardiograma preoperatorio: ¿rutina inútil o herramienta esencial?

La evaluación clínica previa a cualquier intervención quirúrgica generalmente corre a cargo de los anestesiólogos, aunque en muchos casos también se requiere de los cardiólogos, dado que el riesgo cardiovascular es el de más trascendencia clínica y pronóstica en la gran mayoría de las intervenciones. Componente inveterado de dicha evaluación cardiológica preoperatoria es la práctica de un electrocardiograma (ECG). Las directrices de práctica clínica de entidades oficiales dan por hecho que el ECG forma parte de la evaluación básica preoperatoria añadida a la estratificación del riesgo por los baremos usuales; incluso señalan que su anormalidad determina la pertinencia de consulta cardiológica. Se ha demostrado que la simple clasificación de los ECG preoperatorios en «normales» o «anormales» mejora la utilidad pronóstica de la evaluación clínica basada en el riesgo del paciente y el de la intervención. No obstante, el 51% de los ECG preoperatorios son anormales y rara vez ello modifica la actitud terapéutica o se correlaciona con los desenlaces en la población de bajo riesgo. En cambio, en los pacientes Cartas al Editor
Surface expression and distribution of voltage-gated potassium channels in neurons (Review)

The last decade has witnessed an exponential increase in interest in one of the great mysteries of nerve cell biology: Specifically, how do neurons know where to place the ion channels that control their excitability? Many of the most important insights have been gleaned from studies on the voltage-gated potassium channels (Kvs) which underlie the shape, duration and frequency of action potentials. In this review, we gather recent evidence on the expression, trafficking and maintenance mechanisms which control the surface density of Kvs in different subcellular compartments of neurons and how these may be regulated to control cell excitability.
Insights into outer membrane protein crystallization

Outer membrane proteins are structurally distinct from those that reside in the inner membrane and play important roles in bacterial pathogenicity and human metabolism. X-ray crystallography studies on >40 different outer membrane proteins have revealed that the transmembrane portion of these proteins can be constructed from either β-sheets or less commonly from α-helices. The most common architecture is the β-barrel, which can be formed from either a single anti-parallel sheet, fused at both ends to form a barrel or from multiple peptide chains. Outer membrane proteins exhibit considerable rigidity and stability, making their study through x-ray crystallography particularly tractable. As the number of structures of outer membrane proteins increases a more rational approach to their crystallization can be made. Herein we analyse the crystallization data from 53 outer membrane proteins and compare the results to those obtained for inner membrane proteins. A targeted sparse matrix screen for outer membrane protein crystallization is presented based on the present analysis.
Postoperative serum methylation levels of TAC1 and SEPT9 are independent predictors of recurrence and survival of patients with colorectal cancer

Serum carcinoembryonic antigen (CEA) is the only marker recommended for surveillance of colorectal cancer (CRC) recurrence; its sensitivity and specificity, however, are suboptimal. This study sought to evaluate the values of postoperative serum methylation levels of 7 genes for prognostication and especially for recurrence detection after curative resection.
A study of the initial fluid resuscitation and pain management of patients with fractured neck of femur

s from the Age Anaesthesia Association Annual Meeting in Grange over Sands, Cumbria, on 10 May 2002 A study of the initial fluid resuscitation and pain management of patients with fractured neck of femur N. Levy Specialist Registrar, Anaesthetic Department, Lister Hospital, Coreys Mill Lane, Stevenage, Herts. SG1 4AB, UK It is recommended that patients with fractured neck of femur should receive early and appropriate fluid resuscitation and analgesia on arrival to hospital [1]; multimodal postoperative analgesia to reduce side effects and improve efficacy [2]; and surgery within 24 h of their optimisation [1]. The aim of this study was to examine whether these recommendations were being met at the Lister Hospital, Stevenage. Methods All patients with fractured neck of femur who attended the Accident and Emergency Department between October 2000 and March 2001 were identified. However, only 33 sets of notes could be located and examined. The following were recorded: demographic details; time of admission; time and amount of fluids administered; time and type of initial analgesia; ongoing analgesia; and time of operation. From these data, the delay between arrival and administration of analgesia, and time to surgery could be calculated, as well as the amount of fluid administered over the initial 12 h after arrival in hospital. Results Mean age was 76 y; 76% were female; 54% were ASA 1–2; 48% were taking either no medication or only one form of medication; and 66% were living at home at the time of admission. Only 42% received analgesia within 1 h of admission, mostly intramuscular pethidine or oral paracetamol, while 64% had their operation within 48 h of admission. Postoperatively, 87% received a combination of analgesics for pain. Only 6% had intravenous fluids within 2 h of admission; 48% received < 900 ml in the first 12 h and 10% received < 500 ml. In-hospital mortality for patients receiving < 900 ml and < 500 ml was 31% and 66%, respectively, whilst none who received > 900 ml fluid died. Discussion This study demonstrates that initial fluid and pain management of patients attending Accident and Emergency with fractured neck of femur can be very poor. Intramuscular pethidine is a poor choice of analgesic due to its erratic absorption in trauma victims, its poor efficacy, its side effects, and accumulation of its metabolite norpethidine [1]. Oral paracetamol is probably insufficient when given alone for acute pain arising from lower limb fracture. However, multimodal analgesia was used for postoperative pain and this is encouraging, as it has the least side effects and appears to be the most effective [2]. Initial fluid resuscitation does not compensate either for blood loss into the fracture site or for periods of dehydration before or after the fracture. This may be the reason for the association between initial fluid management and outcome. This needs further investigation, as there is now evidence that guided intra-operative fluid resuscitation improves outcome [3].
TechnoWellness: A New Wellness Construct in the 21st Century

Researchers in various disciplines have investigated how interaction with technology affects health and well-being, but evidence-based wellness models in counseling do not currently address the implications of technology use. The new concept of TechnoWellness encourages recognition that individuals’ interactions with technology can have powerful impacts on holistic wellness over the life span. TechnoWellness interventions, guided by empirically supported wellness models, can support professional counselors in their efforts to help clients attain optimal wellness.
Physiology and pathophysiology of thoracic sympathetic blockade

Abstract Sympathetic innervation of the heart and lung is mediated by fibres originating from the thoracic segments T1–4. Sympathetic stimulation in healthy subjects causes coronary vasodilation, whereas stenotic coronary arteries show vasoconstriction in response to sympathetic stimulation. Thus, in patients at risk of ischaemia, high thoracic epidural anaesthesia (TEA) should dilate constricted coronary vessels, decrease heart rate and myocardial metabolism, and improve cardiac function by reducing pre- and afterload and optimizing oxygen availability. The pulmonary effects include an improved postoperative diaphragmatic function in lambs and humans and enhanced respiratory function parameters. Hypoxic pulmonary vasoconstriction, an important mechanism for the maintenance of adequate oxygenation after induction of general anaesthesia, is not affected by TEA in dogs. Beneficial effects of epidural sympathetic blockade on myocardial perfusion and function, and on pulmonary parameters, can only be achieved by a thoracic blockade, whereas lumbar epidural anaesthesia may exert adverse effects due to a compensatory increase of thoracic sympathetic activity.
The Future of B2C E-Commerce

Condensing the understanding of Business‐to‐Consumer (B2C) e‐commerce and its causal relations with the environment in a set of future meaningful, specific and exhaustive variables is a prerequisite for long‐term forecasting. There is no consensus regarding even present quantitative estimates of e‐commerce, nor does current research pinpoint immediate cause or effect. In around 50 semi‐structured interviews with cross‐functional e‐commerce practitioners, academics, users and non‐users, 14 variables describing the future structure of e‐commerce and 35 environment variables have been identified. The understanding of e‐commerce is focusing on the terms ‘automation’ and ‘spatial separated delivery’, leading to a differentiation between distance selling e‐commerce and automated transactions at retail outlets. The environments investigated include Society, Distribution, Technology, Retail Outlets, Socio‐Politics and Market environments, providing a holistic view on the long‐term outlook of e‐commerce.
A low renal threshold for glucose in diabetic patients with a mutation in the hepatocyte nuclear factor‐1α (HNF‐1α) gene

One form of maturity‐onset diabetes of the young, Type 3 (MODY3), results from mutations in the gene coding for hepatocyte nuclear factor‐1α (HNF‐1α), a transcription factor first described in the liver. MODY3 is characterized by a defective glucose‐stimulated insulin secretion. Earlier observations of glycosuria with normal blood glucose levels in some MODY families suggest an additional renal manifestation of the respective genetic defect.
Basic fibroblast growth factor induces down‐regulation of α‐smooth muscle actin and reduction of myofibroblast areas in open skin wounds

To examine the effects of basic fibroblast growth factor (bFGF) on the inhibition of α‐smooth muscle actin (α‐SMA) expression in dermal fibroblasts, we have established two dermal myofibroblastic cell lines positive for α‐SMA (rat myofibroblasts [RMF] and rat myofibroblast‐like [RMFL] cells) and one fibroblastic cell line negative for α‐SMA (rat fibroblasts cells) as a model of fibroblast differentiation. In contrast to the increased expression of α‐SMA in RMF and RMFL cells, irrespective of transforming growth factor‐β1 treatment, bFGF induced a decrease in α‐SMA expression in the myofibroblastic cells and the reduced expression patterns of α‐SMA differed between cells, as demonstrated by Western blot and reverse transcription polymerase chain reaction analyses. Along with the inhibition of α‐SMA expression by bFGF, the RMF and RMFL cells also showed different activated expression of extracellular signal‐regulated kinase 1/2, suggesting the involvement of extracellular signal‐regulated kinase 1/2 activation in the down‐regulation of α‐SMA expression in myofibroblasts. Furthermore, an in vivo study demonstrated that bFGF administration markedly decreases the area that is positive for α‐SMA expression in the treated wounds after day 18. In contrast, bFGF administration significantly increased the number of terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP nick‐end labeling (TUNEL) staining and α‐SMA‐positive cells at days 10 and 14, and reduced the double‐positive cells rapidly after day 18. Collectively, the current investigation identified bFGF as a potent stimulator for the reduction of the myofibroblastic area in vivo, presumably because of its effects on the down‐regulation of α‐SMA expression as well as rapid induction of apoptosis in myofibroblasts.
Screening and early detection efforts in lung cancer

Lung cancer is the leading cause of cancer‐related death in the United States. Since publication of results from the National Lung Screening Trial, several professional organizations, including the US Preventive Services Task Force, have published guidelines recommending low‐dose computed tomography for screening in asymptomatic, high‐risk individuals. The benefits of screening include detection of cancer at an early stage when a definitive cure is possible, but the risks include overdiagnosis, false‐positive results, psychological distress, and radiation exposure. The current review covers the scope of low‐dose computed tomography screening, potential risks, costs, and future directions in the efforts for early detection of lung cancer. Cancer 2015;121:1347–1356. © 2015 American Cancer Society.
Downstage migration after neoadjuvant chemoradiotherapy for rectal cancer: The reverse of the Will Rogers phenomenon?

Downstaging after neoadjuvant treatment is increasingly used as a prognostic factor and surrogate endpoint in clinical trials. However, in recent trials of neoadjuvant 5‐fluorouracil–based chemoradiotherapy for rectal cancer, downstaging did not translate into a benefit with regard to either disease‐free survival (DFS) or overall survival. By analyzing the 10‐year outcome data of the German CAO/ARO/AIO‐94 phase 3 trial, the authors demonstrated that significantly fewer patients had poor prognostic features (eg, ypT3‐4, ypN1‐2) after preoperative 5‐fluorouracil–based chemoradiotherapy. Nevertheless, these patients with International Union for Cancer Control stage II disease were found to be at a higher risk of developing distant metastases and had poorer DFS compared with patients with corresponding TNM tumor (sub)groups in the postoperative treatment arm, whereas patients with International Union for Cancer Control stage III disease demonstrated a nonsignificant trend toward a worse outcome after preoperative treatment. Overall, DFS remained identical in both treatment arms. Thus, “downstage migration” after neoadjuvant treatment resembles the reverse of the Will Rogers phenomenon and therefore may not be a reliable endpoint for long‐term outcomes. Cancer 2015;121:1724–1727. © 2015 American Cancer Society.
Motivation for behavior change in patients with chest pain

Purpose – To assess the effect of diagnostic testing for coronary artery disease (CAD) on motivation for change, and on lifestyle change for patients with chest pain.Design/methodology/approach – This observational study followed patients with chest pain suggestive of CAD for three years. Constructs of autonomous and controlled motivation for lifestyle change, autonomous orientation, and autonomy support from self‐determination theory were assessed. Self‐reported tobacco use, physical activity, and diet were assessed at baseline and three years later. Physician rating of pre‐ and post‐test probability of CAD were also assessed. CAD diagnosis was established after three years.Findings – Physicians' autonomy‐supportive style and patients' autonomous orientations both predicted greater patient autonomous motivation, which in turn predicted improved diet, more exercise, and marginally less smoking. High probability of CAD also led patients to become more autonomously motivated for lifestyle change.Research li.
Ocular perfusion pressure and glaucoma: clinical trial and epidemiologic findings

Purpose of review A possible connection between ocular perfusion pressure and open-angle glaucoma (OAG) has been hypothesized. This review summarizes the scientific rationale for the proposed relationship, presents recent data, and outlines potential implications. Recent findings Population-based epidemiologic studies found strong relationships between low ocular perfusion pressure and OAG prevalence, as well as OAG incidence. Clinical studies report similar associations between low perfusion pressure and OAG progression. These consistent findings suggest that altered blood flow in the optic disc increases both the risk of OAG development and the progression of established OAG. An underlying factor would be impaired vascular autoregulation, which may lead to poor perfusion in OAG. In contrast, there is conflicting evidence on the possible link of glaucoma to blood pressure/hypertension. Summary Current evidence supports the role of vascular factors as part of the multifactorial cause of OAG. As ocular perfusion pressure reflects the vascular status at the optic disc, it may be more relevant than systemic blood pressure alone. Although the associations of OAG to perfusion pressure are strong, consistent, and biologically plausible, they require careful interpretation. The evidence implicating a vascular cause in OAG is mounting, but the clinical implications for patient management are still uncertain.
Splenic marginal zone lymphoma: excellent outcomes in 64 patients treated in the rituximab era

ABSTRACT Objectives and methods: Splenic marginal zone lymphoma (SMZL) is a rare non-Hodgkin lymphoma. We sought to identify prognostic factors and define outcomes in a cohort of 64 patients with SMZL who were treated at two large academic medical centers in North America in the rituximab era. Results: Over a median follow-up of 37.8 (range 6–167.1) months, Kaplan–Meier estimate of median OS was 156.3 months and median PFS was 52.9 months. On univariate analysis, baseline hemoglobin <12 g/dl was associated with inferior OS (p = 0.045). High-risk FLIPI score was associated with inferior PFS when compared with intermediate/low risk (p = 0.05) and marginally significant with regard to OS (p = 0.056). Splenectomy was not predictive of OS or PFS (p = 0.563 and 0.937, respectively). Transformation to diffuse large B-cell lymphoma occurred in four (6.3%) patients during the observation period. OS was comparable to contemporaneous cohorts of patients with extranodal and nodal marginal lymphomas and FLIPI score was highly predictive for inferior PFS and OS when all three cohorts were analyzed together. Conclusion: Outcomes of SMZL, in our series, were excellent, with a median OS of >13 years. Low hemoglobin and high-risk FLIPI were associated with inferior outcomes.
Interaction between Hb E and Hb Yala (HBB:c.129delT); a novel frameshift beta globin gene mutation, resulting in Hemoglobin E/β0 thalassemia

ABSTRACT Objectives: There are more than 200 known mutations found in patients with β-thalassemia, a possibility to identify an unknown or novel mutation becomes less possible. Here, we report a novel mutation in a patient from Thailand who presented with chronic hemolytic anemia. Methods: A comprehensive hematology and DNA analysis was applied in the index patient and her mother. Results: Hematological and hemoglobin analyses were consistent with the clinical diagnosis of Hb E/β0-thalassemia. However, we could find only Hb E heterozygous mutation using our common polymerase chain reaction-based mutation detection of the β-globin genes. Furthermore, the molecular analysis demonstrated a novel T-deletion at codon 42 of the second exon of the β-globin gene which we named ‘Hb Yala’ according to the origin of this index family. Discussion: This mutation was assumed to generate a truncated β-globin chain terminating at codon 60 with possible unstable variant leading to a ‘null’ or β0-thalassemia. However, the clinical phenotype was surprisingly mild and no other ameliorating genetic factors, including co-inheritance of α-thalassemia and high propensity of Hb F by Xmn I polymorphism, were found. Conclusion: This report has provided evidence that genotype–phenotype correlation in thalassemia syndromes is highly complex and a correct clinical severity classification of thalassemia should be mainly based on clinical evaluation.