Miracle-dz/UniFAR-FTUs huggingface dataset:
The Price We Pay for Radical Curative Pelvic Exenterations: Prevalence and Management of Pain

BACKGROUND: Pelvic exenterations are extensive surgical procedures for locally advanced or recurrent malignancies of the pelvis. However, this is often at the cost of significant morbidity due to perioperative pain, which has been poorly studied. OBJECTIVE: This study aims to review perioperative pain management in patients undergoing pelvic exenteration. DESIGN: This is a retrospective review of patients undergoing pelvic exenteration between January 2013 and December 2014. Data were gathered from medical records and a prospectively maintained database. SETTING: This study was conducted at a single quaternary referral center for pelvic exenteration. PATIENTS: Consecutive patients underwent pelvic exenteration at a single center. INTERVENTIONS: Pelvic exenteration was performed in consecutive patients. MAIN OUTCOMES MEASURES: Primary outcomes were the prevalence of preoperative pain, preoperative opiate use (type, dosage), and postoperative pain (verbal numerical rating scale). Secondary outcomes included the number of pain consultations and correlations between preoperative opiate use, length of stay, and extent of resection (en bloc sacrectomy and nerve excision). RESULTS: Ninety-nine patients underwent pelvic exenteration. Sixty-one patients (61.6%) underwent major nerve resection and/or sacrectomy. Thirty patients (30%) required opiates preoperatively, with a mean daily morphine equivalent of 72.9 mg (SD 65.0 mg). Patients on preoperative opiates were more likely to have worse pain postoperatively and to require higher opiate doses and more pain consultations (9.3 vs 4.8; p < 0.001). Major nerve excision and sacrectomy were not associated with worse postoperative pain. By discharge, 60% still required opiate analgesia. LIMITATIONS: Retrospective study design, the subjective nature of pain assessment because of a lack of valid methods to objectively quantify pain, and the lack of long-term follow-up were limitations of this study. CONCLUSIONS: Perioperative pain is a significant issue among patients undergoing pelvic exenteration. One in three patients require high-dose opiates preoperatively that is associated with worse pain outcomes. Potential areas to improve pain outcomes in these complex patients could include increased use of regional anesthesia, antineuropathic agents, and opiate-sparing techniques. See Video Abstract at http://links.lww. com/DCR/A572.
The effect of Valerian on the severity and frequency of hot flashes: A triple-blind randomized clinical trial

ABSTRACT Valerian is one of the most widely used herbal supplements and a phytoestrogenic herb. The aim of this study was to determine the effect of Valerian on the severity and frequency of hot flashes. This triple-blind, randomized, controlled clinical trial was conducted during a three-month period in Hamadan, Iran, in 60 postmenopausal women aged 45–55 years. Participants were randomly assigned to one of two groups– either placebo or Valerian. An oral Valerian 530 mg capsule was given twice per day for two months. An oral placebo 530 mg capsule (starch) was similarly administered. The severity and frequency of hot flashes were determined by the Kupperman index, before the intervention, one month after, and two months after initiation of the intervention. The severity of hot flashes in the Valerian group was significantly lower than that in the placebo group at one (p = .048) and two months (p = .020) after initiation of the intervention. Compared with the placebo group, the mean frequency of hot flashes was significantly reduced two months after initiating the use of Valerian (p = .033). Health-care providers should consider Valerian to be effective for menopausal women with hot flashes.
The mutational spectrum of holoprosencephaly‐associated changes within the SHH gene in humans predicts loss‐of‐function through either key structural alterations of the ligand or its altered synthesis

Mutations within either the SHH gene or its related pathway components are the most common, and best understood, pathogenetic changes observed in holoprosencephaly patients; this fact is consistent with the essential functions of this gene during forebrain development and patterning. Here we summarize the nature and types of deleterious sequence alterations among over one hundred distinct mutations in the SHH gene (64 novel mutations) and compare these to over a dozen mutations in disease‐related Hedgehog family members IHH and DHH. This combined structural analysis suggests that dysfunction of Hedgehog signaling in human forebrain development can occur through truncations or major structural changes to the signaling domain, SHH‐N, as well as due to defects in the processing of the mature ligand from its pre‐pro‐precursor or defective post‐translation bi‐lipid modifications with palmitate and cholesterol Published 2009 by Wiley‐Liss, Inc.
Prognostic and biological significance of the proangiogenic factor EGFL7 in acute myeloid leukemia

Significance In this work we report on the previously uncharacterized clinical and biological role for EGFL7 in acute myeloid leukemia (AML). Patients with increased EGFL7 mRNA expression had lower complete remission rates and shorter overall and event-free survival, demonstrating the clinical relevance of EGFL7 expression in cytogenetically normal AML. Our results show that AML blasts are able to synthesize and secrete EGFL7 protein, promoting autocrine blast cell growth. Inhibition of EGFL7 results in decreased proliferation and induces apoptosis of AML cells. Taken together, our data provide the rationale for targeting EGFL7 using blocking antibodies as a therapy for patients with AML. Epithelial growth factor-like 7 (EGFL7) is a protein that is secreted by endothelial cells and plays an important role in angiogenesis. Although EGFL7 is aberrantly overexpressed in solid tumors, its role in leukemia has not been evaluated. Here, we report that levels of both EGFL7 mRNA and EGFL7 protein are increased in blasts of patients with acute myeloid leukemia (AML) compared with normal bone marrow cells. High EGFL7 mRNA expression associates with lower complete remission rates, and shorter event-free and overall survival in older (age ≥60 y) and younger (age <60 y) patients with cytogenetically normal AML. We further show that AML blasts secrete EGFL7 protein and that higher levels of EGFL7 protein are found in the sera from AML patients than in sera from healthy controls. Treatment of patient AML blasts with recombinant EGFL7 in vitro leads to increases in leukemic blast cell growth and levels of phosphorylated AKT. EGFL7 blockade with an anti-EGFL7 antibody reduced the growth potential and viability of AML cells. Our findings demonstrate that increased EGFL7 expression and secretion is an autocrine mechanism supporting growth of leukemic blasts in patients with AML.
Menopausal characteristics and physical functioning in older adulthood in the National Health and Nutrition Examination Survey III

ObjectiveWe hypothesized that natural menopause would be related to better physical functioning compared with surgical menopause and that later age at menopause would be related to better physical functioning. MethodsOur sample comprised 1,765 women 60 years or older who participated in the National Health and Nutrition Examination Survey III, a cross-sectional study representative of the US population. Women recalled age at final menstrual period and age at removal of the uterus and ovaries and reported age, race and ethnicity, height, weight, educational attainment, smoking status, number of children, and use of estrogen therapy. Respondents completed a walk trial and chair rises and reported functional limitations. ResultsWomen with surgical menopause had chair rise times that were an average of 4.4% slower than did those of women with natural menopause (95% CI, 0.56-8.27). Women with natural menopause at age 55 years or more had an average walking speed of 0.05 meters/second (95% CI, 0.01-0.10) faster than did women with natural menopause at age less than 45 years. Later ages at natural and surgical menopause were also related to lower self-reported functional limitation. Women with surgical menopause at age 55 years or more had odds of functional limitation 0.52 times (95% CI, 0.29-0.95) that of women with surgical menopause at age less than 40 years, with similar patterns for natural menopause. ConclusionsWomen with surgical menopause and earlier age at menopause had worse physical function in older adulthood. These groups of women may benefit from interventions to prevent functional decline.
Effect of distal ulnar ostectomy on carpal joint stability during weight bearing in the dog

OBJECTIVE To assess the influence of a 50% distal ulnectomy on mediolateral carpal stability in the dog. STUDY DESIGN Canine cadaveric study. SAMPLE POPULATION Seven canine thoracic limbs METHODS: Thoracic limbs were placed in a jig to mimic weight bearing with a load representing 30% of body weight. Carpal extension angle was standardized at 190° ± 5°. Frontal plane carpal angles were measured with the limb loaded on craniocaudal radiographs before and after ulnectomy. Valgus and varus stress radiographs with the limb loaded were acquired before and after ulnectomy. The limbs were palpated and were subjectively graded for valgus or varus instability by 2 investigators before and after ulnectomy. RESULTS Mean (±SD) valgus angulation increased after ulnectomy (2.1° ± 1.7°; P = .017; CI95 = 0.5°-3.7°) when the limb was loaded without valgus or varus stress applied. Mean valgus angulation increased after ulnectomy (2.7° ± 2.8°; P = .032; CI95 = -0.2°-5.5°) when valgus stress was applied to the loaded limb. Varus angulation was unchanged after ulnectomy (0.6° ± 4.6°; P = .383; CI95 = -4.2°-5.3°) when varus stress was applied to the loaded limb. Palpation detected increased valgus score after ulnectomy. CONCLUSION Distal ulnectomy with excision of the lateral styloid process induces a slight increase in valgus in canine cadaver carpi. The clinical consequences of that valgus on carpal function and health should be assessed in clinical patients.
Similar but not consistent: Revisiting the pitfalls of measuring IgG subclasses with different assays

Laboratory quantification of IgG subclasses (IgGSc) is a well‐established second‐line tool for differential diagnosis of immune deficiencies. However, so far there is still no internationally approved standard available for IgGSc, and different assays are prone to produce divergent results. In this study, we evaluated the comparability and equivalence of two commercially available IgGSc assays, one being the Siemens IgGSc assay on a BN ProSpec analyzer and the other being The Binding Site (TBS) IgGSc assay on a Roche cobas c502 analyzer.
A Reliability-Aware Network Service Chain Provisioning With Delay Guarantees in NFV-Enabled Enterprise Datacenter Networks

Traditionally, service-specific network functions (NFs) (e.g., Firewall, intrusion detection system, etc.) are executed by installation-and maintenance-costly hardware middleboxes that are deployed within a datacenter network following a strictly ordered chain. NF virtualization (NFV) virtualizes these NFs and transforms them into instances of plain software referred to as virtual NFs (VNFs) and executed by virtual machines, which, in turn, are hosted over one or multiple industry-standard physical machines. The failure (e.g., hardware or software) of any one of a service chain’s VNFs leads to breaking down the entire chain and causing significant data losses, delays, and resource wastage. This paper establishes a reliability-aware and delay-constrained (READ) routing optimization framework for NFV-enabled datacenter networks. READ encloses the formulation of a complex mixed integer linear program (MILP) whose resolution yields an optimal network service VNF placement and traffic routing policy that jointly maximizes the achieved respective reliabilities of supported network services and minimizes these services’ respective end-to-end delays. A heuristic algorithm dubbed Greedy- ${k}$ -shortest paths (GSP) is proposed for the purpose of overcoming the MILP’s complexity and develop an efficient routing scheme whose results are comparable to those of READ’s optimal counterparts. Thorough numerical analyses are conducted to evaluate the network’s performance under GSP, and hence, gauge its merit; particularly, when compared to existing schemes, GSP exhibits an improvement of 18.5% in terms of the average end-to-end delay as well as 7.4% to 14.8% in terms of reliability.
A Preliminary Evaluation of the SMAP Radiometer Soil Moisture Product Over United States and Europe Using Ground-Based Measurements

The Soil Moisture Active Passive (SMAP) mission, which is the newest L-band satellite that is specifically designed for soil moisture monitoring, was launched on January 31, 2015. A beta quality version of the SMAP radiometer soil moisture product was recently released to the public. It is crucial to evaluate the reliability of this product before it can be routinely used in hydrometeorological studies at a global scale. In this paper, we carried out a preliminary evaluation of the SMAP radiometer soil moisture product against in situ measurements collected from three networks that cover different climatic and land surface conditions, including two dense networks established in the U.S. and Finland, and one sparse network set up in Romania. Results show that the SMAP soil moisture product is in good agreement with the in situ measurements, although it exhibits dry or wet bias at different network regions. It well reproduces the temporal evolution and anomalies of the observed soil moisture with a favorable correlation greater than 0.7. The overall ubRMSE (unbiased root mean square error) of SMAP product is 0.036 m3 · m-3, well within the mission requirement of 0.04 m3 · m-3. The error sources of SMAP soil moisture product may be associated with the parameterization of vegetation and surface roughness but still needs to be tested and confirmed in more extent. Considering that the algorithms are still under refinement, it can be reasonably expected that hydrometeorological applications will benefit from the SMAP radiometer soil moisture product.
Bone microarchitecture is impaired in adolescent amenorrheic athletes compared with eumenorrheic athletes and nonathletic controls.

CONTEXT Bone mineral density (BMD) is lower in young amenorrheic athletes (AA) compared to eumenorrheic athletes (EA) and nonathletic controls and may contribute to fracture risk during a critical time of bone accrual. Abnormal bone microarchitecture is an independent determinant of fracture risk and has not been assessed in young athletes and nonathletes. OBJECTIVE We hypothesized that bone microarchitecture is impaired in AA compared to EA and nonathletes despite weight-bearing exercise. DESIGN AND SETTING We conducted this cross-sectional study at the Clinical Research Center of Massachusetts General Hospital. SUBJECTS AND OUTCOME MEASURES We assessed BMD and bone microarchitecture in 50 subjects [16 AA, 18 EA, and 16 nonathletes (15-21 yr old)] using dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography. RESULTS Groups did not differ for chronological age, bone age, body mass index, or vitamin D levels. Lumbar BMD Z-scores were lower in AA vs. EA and nonathletes; hip and femoral neck BMD Z-scores were highest in EA. At the weight-bearing tibia, athletes had greater total area, trabecular area, and cortical perimeter than nonathletes, whereas cortical area and thickness trended lower in AA. Trabecular number was lower and trabecular separation higher in AA vs. EA and nonathletes. At the non-weight-bearing radius, trabecular density was lower in AA vs. EA and nonathletes. Later menarchal age was an important determinant of impaired microarchitecture. After controlling for covariates, subject grouping accounted for 18-24% of the variability in tibial trabecular number and separation. CONCLUSION In addition to low BMD, AA have impaired bone microarchitecture compared with EA and nonathletes. These are the first data to show abnormal bone microarchitecture in AA.
Implementation and evaluation of a Danish test battery for auditory processing disorder in children

Abstract Objective: This study presents a Danish test battery for auditory processing disorder (APD). The tests were evaluated as to normative cut-off values (pass-fail criteria) and their test–retest reliability. Design: The battery consists of four behavioural tests: the filtered words (FW) test, the dichotic digits (DD) test, the gap detection (GD) test and the binaural masking level difference (BMLD) test. The tests were evaluated through listening experiments on children with no known history of auditory problems. Study sample: The normative cut-off values were obtained from 158 children (75 boys and 83 girls, aged 6–16 years), whereas the test–retest reliability was obtained from 20 children (10 boys and 10 girls, aged 6–11 years). Results: For each of the four tests one to four different cut-off values were determined depending on whether the scores from the two ears and the different age groups could be pooled. For each of the four tests the test–retest reliability was found to be satisfactory. The test–retest reliability was highest for the FW and the DD test. Conclusions: A Danish APD test battery is now available for clinical use with normative data.
Filarial Infection Modulates the Immune Response to Mycobacterium tuberculosis through Expansion of CD4+ IL-4 Memory T Cells

Exaggerated CD4+ T helper 2–specific cytokine producing memory T cell responses developing concomitantly with a T helper 1 response might have a detrimental role in immunity to infection caused by Mycobacterium tuberculosis. To assess the dynamics of Ag-specific memory T cell compartments in the context of filarial infection, we used multiparameter flow cytometry on PBMCs from 25 microfilaremic filarial-infected (Inf) and 14 filarial-uninfected (Uninf) subjects following stimulation with filarial Ag (BmA) or with the M. tuberculosis–specific Ag culture filtrate protein-10 (CFP-10). Our data demonstrated that the Inf group had a marked increase in BmA-specific CD4+IL-4+ cells (median net frequency compared with baseline [Fo] = 0.09% versus 0.01%; p = 0.038) but also to CFP-10 (Fo = 0.16% versus 0.007%; p = 0.04) and staphylococcal enterotoxin B (Fo = 0.49% versus 0.26%; p = 0.04). The Inf subjects showed a BmA-specific expansion of CD4+CD45RO+IL-4+ producing central memory (TCM, CD45RO+CCR7+CD27+; Fo = 1.1% versus 0.5%; p = 0.04) as well as effector memory (TEM, CD45RO+CCR7−CD27−; Fo = 1.5% versus 0.2%; p = 0.03) with a similar but nonsignificant response to CFP-10. In addition, there was expansion of CD4+IL-4+CD45RA+CCR7+CD27+ (naive-like) in Inf individuals compared with Uninf subjects. Among Inf subjects with definitive latent tuberculosis, there were no differences in frequencies of IL-4–producing cells within any of the memory compartments compared with the Uninf group. Our data suggest that filarial infection induces Ag-specific, exaggerated IL-4 responses in distinct T cell memory compartments to M. tuberculosis–specific Ags, which are attenuated in subjects who are able to mount a delayed type hypersensitivity reaction to M. tuberculosis.
Molecular analysis of HIV‐1 gp120 antibody response using isotype IgM and IgG phage display libraries from a long‐term non‐progressor HIV‐1‐infected individual

To characterize the variable heavy chain (VH)3 antibody response to HIV‐1 gp120, we analyzed a panel of IgM and IgG1 Fab fragments from phage display isotype libraries from a long‐term, non‐progressor HIV‐1‐infected individual. The IgM Fab antibodies isolated had low affinity for gp120, were not restricted to a particular VH3 germ‐line gene, and consisted mainly of unmutated VH genes. In contrast, IgG Fab fragments were gp120 specific, with high affinity and extensive somatic mutation; all were clonally related and were derived from a single VH3 germ‐line gene (DP50). One IgG Fab (S8) has DP50 VH region nucleotide substitutions identical to those of IgM Fab M025 and uses similar DH and JH segments, suggesting that S8 arose from M025 by isotype switching. In addition, somatic mutation in the IgG heavy chain third complementarity‐determining region results in a 100‐fold affinity increase for gp120, which correlates with a similar increase in neutralization capacity. These results imply that in vivo IgM to IgG isotype switch and affinity maturation may be important for protection and long‐term survival in certain HIV‐1‐infected individuals.
Materials and Methods Long-term Exposure to Airborne Particles and Arterial Stiffness: the Multi-ethnic Study of Atherosclerosis (mesa)

Research Chronic exposure to elevated levels of particulate matter (PM) air pollution has been associated with cardiovascular mortality in several studies (Dockery et al. 1993; Hoek et al. 2002; Pope et al. 2002). However, mechanisms underlying these associations have yet to be fully elucidated, and understanding how long-term exposure to air pollution may affect cardiovascular health is an important public health goal. The primary candidate mechanisms (Pope et al. 2004) for which some preliminary evidence exists include air pollution influencing the development of atherosclerotic disease (Künzli et al. 2005), increasing vascular stiffness and impairing autonomic function (Brook et al. 2002; Gold et al. 2000), and enhancing pulmonary and systemic inflammation (Ghio et al. 2000; Peters et al. 2001). Arterial stiffness with increased blood pressure may be in the mechanistic pathway linking air pollution to cardiovascular risk. Arterial stiffness refers to the artery's capacity to expand and contract in response to cardiac flow (Arnett et al. 1994). The under lying physiological mechanisms for stiffening of arteries are both functional and structural (Glasser et al. 1997). Functional determinants include " neurohumoral influences, such as the renin-angiotensin system, the adrener-gic nervous system, and endothelium-derived factors " (Glasser et al. 1997). Structurally, elastin in the vessel wall may thin and fracture because of aging and such conditions as hypertension and increased collagen deposi-tion can reduce compliance of the vessel wall (Glasser et al. 1997). Other structural influences include smooth muscle tone or smooth muscle cell hypertrophy and cell–cell and cell–matrix attachments (Glasser et al. 1997). Stiffer arteries are linked with higher pulse pressure and adverse ventricular remodeling (Arnett et al. 1994; O'Rourke and Mancia 1999; Rowe 1987), which along with hyper-tension are major risk factors for cardio-vascular outcomes (Malhotra et al. 2003; Meaume et al. 2001). Therefore, various measures of arterial stiffness predict risk of future cardiovascular events (Arnett et al. 1994; Liao et al. 1999; Pannier et al. 2005) and are correlated with other known cardiovascular risk factors (Salomaa et al. 1995). Arterial stiffness has been related to exposure to tobacco smoke (Tanaka and Safar 2005), but previous findings have not been uniformly consistent (Din-Dzietham et al. results differed according to which measure of arterial stiffness was examined (Li et al. 2005). Although changes in blood pressure and vasoconstriction have been associated with short-term exposure to outdoor air pollution (Auchincloss et al. 2008; Brook et al. 2002; Zanobetti et al. 2004), the relationship …
Dorsolateral Prefrontal-Aminobutyric Acid in Men Predicts Individual Differences in Rash Impulsivity

Background: Impulsivity is a multifaceted personality construct associated with numerous psychiatric disorders. Recent research has characterized four facets of impulsivity: “urgency” (the tendency to act rashly especially in the context of distress or cravings); “lack of premeditation” (not envisaging the consequences of actions); “lack of perseverance” (not staying focused on a task); and “sensation seeking” (engaging in exciting activities). Urgency is particularly associated with clinical populations and problematic disinhibited behavior.