Miracle-dz/UniFAR-FTUs huggingface dataset:
Fluoxetine treatment of depressed patients with comorbid anxiety disorders

Major depression with comorbid anxiety disorder is associated with poor antidepressant outcome compared to major depression without comorbid anxiety disorder. The purpose of our study was to assess changes in severity of both depressive and anxiety symptoms in outpatients with major depression with comorbid anxiety disorder following fluoxetine treatment. We enrolled 123 outpatients (mean age 38.9 ± 10.8 years; 49% women) with major depressive disorder accompanied by one or more current comorbid anxiety disorders in our study. Patients were treated openly with fluoxetine 20 mg/day for 8 weeks. Efficacy assessments included the 17-item Hamilton Rating Scale for Depression (HAM-D) and the patient-rated Symptom Questionnaire (SQ) Scales for Depression and Anxiety. The mood and anxiety disorder modules of the Structured Clinical Interview for DSM-III-R were administered at screen and endpoint. We used ‘intent to-treat’ analysis in examining all patients assigned to treatment and completing the baseline visit. The mean number of comorbid anxiety disorders per patient was 1.5 ± 0.68. The mean HAM-D-17 score and mean Clinical Global Impressions-Severity scores decreased significantly from baseline to endpoint (week 8) following fluoxetine treatment (p < 0.0001). There were significant decreases in all four SQ scale scores, from baseline to endpoint: depression, anxiety, somatic symptoms and anger-hostility (p < 0.0001). Fifty-three percent of patients (n = 65) were depression responders (i.e. ≥ 50% decrease in HAM-D-17 score at endpoint) and 46% (n = 57) were remitters (HAM-D-17 ≤ 7 at endpoint). Patients with panic disorder had significantly higher baseline HAM-D-17 scores compared to those without panic disorder (p< 0.01). Patients with comorbid obsessive–compulsive disorder (OCD) were significantly less likely to be responders to fluoxetine at endpoint (≥ 50% decrease in HAM-D-17) and to be remitters (HAM-D-17 score of ≤ 7 at endpoint) compared to patients without comorbid OCD (p < 0.01). Of the 41 patients on whom endpoint Structured Clinical Interview for DSM-III-R modules for anxiety disorders were available, 49% (n = 20) no longer met criteria for one or more of their anxiety disorder diagnoses at endpoint. Our preliminary findings suggest that fluoxetine is effective in treating outpatients with major depression with comorbid anxiety disorders, with a significant effect on both depression and anxiety symptoms. Further double-blind, placebo-controlled trials are required in larger samples to confirm our findings.
Total hip replacement with dorsal acetabular rim augmentation using the SOP(TM) implant and polymethylmethacrylate cement in seven dogs with dorsal acetabular rim deficiency.

OBJECTIVE To describe a surgical technique for reinforced augmentation of the dorsal acetabular rim (DAR) using a string-of-pearls (SOP™) locking plate and polymethylmethacrylate (PMMA) bone cement, and to report clinical outcome in 7 dogs. STUDY DESIGN Case series. ANIMALS Dogs (n=7). METHODS Medical records (November 2009-April 2010) of 7 dogs with large DAR deficits, that had total hip replacement (THR) with reinforced augmentation of the DAR using a SOP™ plate and PMMA were evaluated retrospectively. Reinforced augmentation of the DAR involved anchorage of a precontoured 2.0 or 2.7 mm SOP™ plate dorsal to the acetabulum followed by application of PMMA cement to cover the reamed acetabulum and plate. Cemented acetabular components were used. Implant associated complications were recorded and ≥6-month follow-up obtained. RESULTS In all dogs, lameness improved at medium-term reassessment (median, 8 months; range, 6-11 months). Complications included transient sciatic neurapraxia in 2 dogs, which resolved by 3 months. CONCLUSIONS Reinforced augmentation of the DAR using a SOP™ plate and PMMA cement may facilitate placement of acetabular THR component implantation in dogs with severe DAR insufficiency.
Multivariate Quantitative Multifactor Dimensionality Reduction for Detecting Gene-Gene Interactions

Objectives: To determine gene-gene interactions and missing heritability of complex diseases is a challenging topic in genome-wide association studies. The multifactor dimensionality reduction (MDR) method is one of the most commonly used methods for identifying gene-gene interactions with dichotomous phenotypes. For quantitative phenotypes, the generalized MDR or quantitative MDR (QMDR) methods have been proposed. These methods are known as univariate methods because they consider only one phenotype. To date, there are few methods for analyzing multiple phenotypes. Methods: To address this problem, we propose a multivariate QMDR method (Multi-QMDR) for multivariate correlated phenotypes. We summarize the multivariate phenotypes into a univariate score by dimensional reduction analysis, and then classify the samples accordingly into high-risk and low-risk groups. We use different ways of summarizing mainly based on the principal components. Multi-QMDR is model-free and easy to implement. Results: Multi-QMDR is applied to lipid-related traits. The properties of Multi- QMDR were investigated through simulation studies. Empirical studies show that Multi-QMDR outperforms existing univariate and multivariate methods at identifying causal interactions. Conclusions: The Multi-QMDR approach improves the performance of QMDR when multiple quantitative phenotypes are available.
The importance of thinking beyond the water-supply in cholera epidemics: A historical urban case-study

Background Planning interventions to respond to cholera epidemics requires an understanding of the major transmission routes. Interrupting short-cycle (household, foodborne) transmission may require different approaches as compared long-cycle (environmentally-mediated/waterborne) transmission. However, differentiating the relative contribution of short- and long-cycle routes has remained difficult, and most cholera outbreak control efforts focus on interrupting long-cycle transmission. Here we use high-resolution epidemiological and municipal infrastructure data from a cholera outbreak in 1853 Copenhagen to explore the relative contribution of short- and long-cycle transmission routes during a major urban epidemic. Methodology/Principal findings We fit a spatially explicit time-series meta-population model to 6,552 physician-reported cholera cases from Copenhagen in 1853. We estimated the contribution of long-cycle waterborne transmission between neighborhoods using historical municipal water infrastructure data, fitting the force of infection from hydraulic flow, then comparing model performance. We found the epidemic was characterized by considerable transmission heterogeneity. Some neighborhoods acted as localized transmission hotspots, while other neighborhoods were less affected or important in driving the epidemic. We found little evidence to support long-cycle transmission between hydrologically-connected neighborhoods. Collectively, these findings suggest short-cycle transmission was significant. Conclusions/Significance Spatially targeted cholera interventions, such as reactive vaccination or sanitation/hygiene campaigns in hotspot neighborhoods, would likely have been more effective in this epidemic than control measures aimed at interrupting long-cycle transmission, such as improving municipal water quality. We recommend public health planners consider programs aimed at interrupting short-cycle transmission as essential tools in the cholera control arsenal.
BILATERAL INTERNAL CAROTID ARTERY THROMBOSIS Prognosis and Risk Factors

Fourteen patients with bilateral internal carotid artery thrombosis were analysed with respect to long‐term prognosis and the prevalence of risk factors of cerebrovascular disease. The patients comprised seven per cent of all patients with internal carotid thrombosis treated in 1966–73 at the Department of Neurology, University of Helsinki. During the follow‐up period of 3 to 86 months (median 50 months) five patients died, three during the first, and two during the second year of follow‐up. Of the surviving patients: two needed institutionalization; three were able to take care of themselves; and four who were virtually symptom‐free, were able to work. The risk factors of cerebrovascular disease were analysed: 91 per cent were cigarette smokers; 70 per cent had serum triglycerides of 140 mg/100 ml or higher; and 62 per cent had cholesterol values of 280 mg/100 ml or higher. Fasting glucose values higher than 95 mg/100 ml, and ECG abnormalities were encountered in every third, and obesity and hypertension in every fourth patient. Cigarette smoking and high triglycerides were more prevalent than in the general population. No association between the number of risk factors in the individual patients and the prognosis could be found.
Estimating the effects of regional political climate on Russian tourists to Spain

Regional political climate has become an increasingly significant force influencing travel behaviour in many tourist destinations. This paper attempts to address impacts of regional political stability on Russian inbound tourism into Spain within a demand model framework and using a cointegration approach. The results show that visa openness as well as political instability and civil unrest in substitute destinations attract more Russian tourists, boosting economic growth and reducing unemployment rates in Spain. On the contrary, international political confrontation results in disadvantage to Russian tourism demand to Spain.
Methylation profiles of hereditary and sporadic ovarian cancer

Bol G M, Suijkerbuijk K P M, Bart J, Vooijs M, van der Wall E & van Diest P J (2010) Histopathology 57, 363–370 Methylation profiles of hereditary and sporadic ovarian cancer
Diabetic neuropathy, foot ulceration, peripheral vascular disease and potential risk factors among patients with diabetes in bahrain: a nationwide primary care diabetes clinic-based study

BACKGROUND Although epidemiological studies have persistently shown a high prevalence of diabetes in Arabs, the control of diabetes is still poor and complications of diabetes are common. We examined the prevalence of diabetic peripheral neuropathy (DN), neuropathic foot ulceration (FU) and peripheral vascular disease (PVD), and potential risk factors for these complications among patients attending primary care diabetes clinics in Bahrain. PATIENTS AND METHODS We studied 1477 diabetic patients (Type 2 diabetes 93%); to, including 635 men and 842 women, with ages ranging from 18–75 years in a cross-sectional study. The main predictor variables were demographic and clinical data, including assessment of foot and blood parameters. RESULTS Mean age of the patients and duration of diabetes were 57.3±6.32 and 9.5±8.4 years, respectively. DN was present in 36.6% of the population, FU in 5.9%, and PVD in 11.8%. Diabetic patients with neuropathy were older than patients without neuropathy (P=0.001) and had had diabetes longer (P=0.002). Diabetic patients with foot ulcers had more severe neuropathy and higher vibration perception thresholds values than patients without foot ulcers (P<0.05). Older age, poor glycemic control, longer duration of diabetes, elevated cholesterol levels, current smoking, obesity defined by body mass index, large waist circumference, elevated triglycerides levels and hypertension but not gender, were significant risk factors for DN in both the univariate and the multivariate analyses (P< 0.05). DN and PVD also remained significant risk factors for foot ulceration in the multiple logistic regression analysis. CONCLUSION Rates of DN and PVD are high among diabetic patients in Bahrain. Implementation of strategies for prevention, early detection, and appropriate treatment at the primary health care level are urgently needed.
Mechanism of HIV-1 Neutralization by Antibodies Targeting a Membrane-Proximal Region of gp41

ABSTRACT Induction of broadly neutralizing antibodies (bNAbs) is an important goal for HIV-1 vaccine development. Two autoreactive bNAbs, 2F5 and 4E10, recognize a conserved region on the HIV-1 envelope glycoprotein gp41 adjacent to the viral membrane known as the membrane-proximal external region (MPER). They block viral infection by targeting a fusion-intermediate conformation of gp41, assisted by an additional interaction with the viral membrane. Another MPER-specific antibody, 10E8, has recently been reported to neutralize HIV-1 with potency and breadth much greater than those of 2F5 or 4E10, but it appeared not to bind phospholipids and might target the untriggered envelope spikes, raising the hope that the MPER could be harnessed for vaccine design without major immunological concerns. Here, we show by three independent approaches that 10E8 indeed binds lipid bilayers through two hydrophobic residues in its CDR H3 (third heavy-chain complementarity-determining region). Its weak affinity for membranes in general and preference for cholesterol-rich membranes may account for its great neutralization potency, as it is less likely than other MPER-specific antibodies to bind cellular membranes nonspecifically. 10E8 binds with high affinity to a construct mimicking the fusion intermediate of gp41 but fails to recognize the envelope trimers representing the untriggered conformation. Moreover, we can improve the potency of 4E10 without affecting its binding to gp41 by a modification of its lipid-interacting CDR H3. These results reveal a general mechanism of HIV-1 neutralization by MPER-specific antibodies that involves interactions with viral lipids.
Contrasting ecophysiological strategies related to drought: the case of a mixed stand of Scots pine (Pinus sylvestris) and a submediterranean oak (Quercus subpyrenaica)

Submediterranean forests are considered an ecotone between Mediterranean and Eurosiberian ecosystems, and are very sensitive to global change. A decline of Scots pine (Pinus sylvestris L.) and a related expansion of oak species (Quercus spp.) have been reported in the Spanish Pre-Pyrenees. Although this has been associated with increasing drought stress, the underlying mechanisms are not fully understood, and suitable monitoring protocols are lacking. The aim of this study is to bring insight into the physiological mechanisms anticipating selective decline of the pines, with particular focus on carbon and water relations. For this purpose, we performed a sampling campaign covering two growing seasons in a mixed stand of P. sylvestris and Quercus subpyrenaica E.H del Villar. We sampled seasonally twig xylem and soil for water isotope composition (δ18O and δ2H), leaves for carbon isotope composition (δ13C) and stems to quantify non-structural carbohydrates (NSC) concentration, and measured water potential and leaf gas exchange. The first summer drought was severe for both species, reaching low predawn water potential (-2.2 MPa), very low stomatal conductance (12 ± 1.0 mmol m-2 s-1) and near-zero or even negative net photosynthesis, particularly in P. sylvestris (-0.6 ± 0.34 μmol m-2 s-1 in oaks, -1.3 ± 0.16 μmol m-2 s-1 in pines). Hence, the tighter stomatal control and more isohydric strategy of P. sylvestris resulted in larger limitations on carbon assimilation, and this was also reflected in carbon storage, showing twofold larger total NSC concentration in oaks than in pines (7.8 ± 2.4% and 4.0 ± 1.3%, respectively). We observed a faster recovery of predawn water potential after summer drought in Q. subpyrenaica than in P. sylvestris (-0.8 MPa and -1.1 MPa, respectively). As supported by the isotopic data, this was probably associated with a deeper and more reliable water supply in Q. subpyrenaica. In line with these short-term observations, we found a more pronounced negative effect of steadily increasing drought stress on long-term growth in pines compared with oaks. All these observations confer evidence of early warning of P. sylvestris decline and indicate the adaptive advantage of Q. subpyrenaica in the area.
Piagetian Liquid Conservation in Grey Parrots (Psittacus erithacus)

An understanding of Piagetian liquid conservation was investigated in four Grey parrots (Psittacus erithacus), their ages ranging from initially less than 1 year old to 18 years old. They were tested in several conditions: on the ability to choose between (a) identical containers filled with a greater or lesser quantity of a desirable liquid to see if they would reliably take the larger amount and (b) equal quantities of liquid that were visibly or invisibly transferred from identical to different-sized containers to examine their abilities with respect to conservation. Invisible transfers examined the extent to which birds chose based on perceptual evaluations of quantity and the effects of task order on their decisions. Adult birds succeeded on all or most aspects of the tests. As a chick (∼6 months), 1 bird was unable or unwilling to choose between the smaller and larger quantities in the first stage of testing, but upon reaching juvenile status succeeded in all aspects of the tests. Grey parrots thus demonstrate some understanding of liquid conservation.
Molecular response to cetuximab and efficacy of preoperative cetuximab-based chemoradiation in rectal cancer.

PURPOSE To characterize the molecular pathways activated or inhibited by cetuximab when combined with chemoradiotherapy (CRT) in rectal cancer and to identify molecular profiles and biomarkers that might improve patient selection for such treatments. PATIENTS AND METHODS Forty-one patients with rectal cancer (T3-4 and/or N+) received preoperative radiotherapy (1.8 Gy, 5 days/wk, 45 Gy) in combination with capecitabine and cetuximab (400 mg/m2 as initial dose 1 week before CRT followed by 250 mg/m2 /wk for 5 weeks). Biopsies and plasma samples were taken before treatment, after cetuximab but before CRT, and at the time of surgery. Proteomics and microarrays were used to monitor the molecular response to cetuximab and to identify profiles and biomarkers to predict treatment efficacy. RESULTS Cetuximab on its own downregulated genes involved in proliferation and invasion and upregulated inflammatory gene expression, with 16 genes being significantly influenced in microarray analysis. The decrease in proliferation was confirmed by immunohistochemistry for Ki67 (P = .01) and was accompanied by an increase in transforming growth factor-alpha in plasma samples (P < .001). Disease-free survival (DFS) was better in patients if epidermal growth factor receptor expression was upregulated in the tumor after the initial cetuximab dose (P = .02) and when fibro-inflammatory changes were present in the surgical specimen (P = .03). Microarray and proteomic profiles were predictive of DFS. CONCLUSION Our study showed that a single dose of cetuximab has a significant impact on the expression of genes involved in tumor proliferation and inflammation. We identified potential biomarkers that might predict response to cetuximab-based CRT.
Aid, Growth, Remittances and Carbon Emissions in Nepal

Using historical data from Nepal—one of the largest recipients of aid among South Asian countries—this paper investigates the link between foreign aid, growth, remittances and carbon dioxide (CO2) emissions. The investigation of this issue is particularly important, as policy makers in the least developed countries are increasingly concerned about growing reliance on energy imports, particularly fossil fuels, and increasing CO2 emissions. Mounting energy consumption has not only made their economies vulnerable to environmental disasters and increased health costs, but also to external shocks due to frequent fluctuations in international market prices for petroleum products. Since available studies are largely based on cross-sectional data—which lump together countries with different characteristics— empirical evidence is contradictory. In-depth case studies of countries with different backgrounds would certainly provide better insights into the link between aid, growth, remittances and CO2 emissions, and contribute to ongoing policy dialogue. Our empirical results, based on an in-depth case study of Nepal, suggest that more foreign aid and remittances reduce CO2 emissions, whereas financial development and higher income increase CO2 emissions. These findings point to the importance of market mechanisms for regulating financial development and higher income to control CO2 emissions, without undermining competitiveness.
A biometrical analysis of perceptions of family environment: a study of twin and singleton sibling kinships.

Biometrical genetic analysis was applied to sibling and twin kinship data on 2 dimensions of perceived home environment. Correlations on 1 dimension, Restrictiveness-Permissiveness, were equal and significant for all kinships: MZ twins, DZ twins, same-sex siblings, and opposite-sex siblings significant for all 4 kinships: MZ twins, DZ twins, same-sex siblings, and opposite-sex siblings (r greater than .40). An E2-E1 biometrical model fitted Restrictiveness-Permissiveness, implying that treatments common to siblings create agreement about perceived environment. As intrapair differences were the same for all 4 kinships under this model, the equal environments assumption of the twin method was supported. In contrast, the Acceptance-Rejection dimension fitted a G-E1 model that makes the assumption that sibling similarity is the result of genetic factors and postulates an absence of shared environmental influences. This finding suggests that this aspect of home environment may depend as much on the child's inherited traits as on actual treatments and is in accord with the genetic analysis of individual traits in that developmentally effective environmental factors do not appear to be common to siblings.
Characterization of the Murine Hyaluronidase Gene Region Reveals Complex Organization and Cotranscription ofHyal1 with Downstream Genes, Fus2 andHyal3 *

Hyaluronidases are required for the breakdown of hyaluronan (HA), an abundant component of the extracellular matrix of vertebrate tissues. Multiple hyaluronidase genes have been identified, but the only clue to the function of their products has come from the identification of hyaluronidase 1 deficiency in a single patient with a mild clinical phenotype. As a first step in the generation of mice with hyaluronidase deficiency, we have used experimental and bioinformatic approaches to examine the organization of the mouse chromosome 9 region containing, in order,Hyal2, Hyal1, and Hyal3. This region was found to be complex, with Fus2 partially embedded in Hyal3, and Ifrd2 immediately downstream from Hyal3. The Hyal genes were all found to have four exons, and exons 2–4 exhibited the highest sequence conservation. Northern blot analysis demonstrated that the tissue expression profile for Hyal1 was similar in mice and humans, but a greater number of transcripts was detected in mouse tissues. Hyal3 was expressed more broadly in mice compared with humans and again exhibited additional transcripts. Reverse transcription-PCR demonstrated that some of the largerHyal1 transcripts, seen on the Northern blot, were the result of cotranscription of Hyal1 with downstream genes,Fus2 or Hyal3. In vitrotranscription/translation of one of the high abundance bicistronic transcripts produced Hyal 1, suggesting that Hyal 1 could be produced from all of the bicistronic transcripts. Characterization of the region including mouse Hyal1 and Hyal3 revealed complex organization and transcription that must be considered in the development and interpretation of mouse models involving genes in this region.