Miracle-dz/UniFAR-FTUs huggingface dataset:
IFITM1 is a tight junction protein that inhibits hepatitis C virus entry†, ‡

Type 1 interferon (IFN) continues to be the foundation for the current standard of care combination therapy for chronic hepatitis C virus (HCV) infection, yet the component interferon‐stimulated genes (ISGs) that mediate the antiviral actions of IFN are not fully defined. Interferon‐induced transmembrane protein 1 (IFITM1) is an ISG product that suppresses early stage infection by a number of viruses through an unknown mechanism of action. Moreover, the actions of IFITM1 on HCV infection are not fully elucidated. Here we identify IFITM1 as a hepatocyte tight junction protein and a potent anti‐HCV effector molecule. IFITM1 expression is induced early during IFN treatment of hepatocytes and accumulates at hepatic tight junctions in HCV‐infected human patient liver during IFN therapy. Additionally, we found that IFITM1 interacts with HCV coreceptors, including CD81 and occludin, to disrupt the process of viral entry. Thus, IFITM1 is an anti‐HCV ISG whose actions impart control of HCV infection through interruption of viral coreceptor function. Conclusion: This study defines IFITM1 as an ISG effector with action against HCV entry. Design of therapy regimens to enhance IFITM1 expression should improve the virologic response among HCV patients undergoing treatment with type I IFN. (HEPATOLOGY 2013)
Identification of Polymorphisms in the Rabbit Growth Hormone Receptor (GHR) Gene and Association with Finishing Weight in a Commercial Meat Rabbit Line

ABSTRACT A shortcut to identify DNA markers associated with economic traits is to use a candidate gene approach that is still useful in livestock species in which molecular tools and resources are not advanced or not well developed. Mutations in the growth hormone receptor (GHR) gene associated with production traits have been already described in several livestock species. For this reason GHR could be an interesting candidate gene in the rabbit. In this study we re-sequenced all exons and non-coding regions of the rabbit GHR gene in a panel of 10 different rabbits and identified 10 single nucleotide polymorphisms (SNPs). One of them (g.63453192C>G or c.106C>G), located in exon 3 was a missense mutation (p.L36V) substituting an amino acid in a highly conserved position across all mammals. This mutation was genotyped in 297 performance tested rabbits of a meat male line and association analysis showed that the investigated SNP was associated with weight at 70 days (P < 0.05). The most frequent genotype (GG) was in animals with higher weight at this age, suggesting that the high directional selection pressure toward this trait since the constitution of the genotyped line might have contributed to shape allele frequencies at this polymorphic site.
Regional differences in the effects of task difficulty and motor output on blood flow response in the human anterior cingulate cortex: a review of 107 PET activation studies

WE reviewed 107 blood flow activation studies carried out with positron emission tomography and published between January 1993 and November 1996. These studies had reported their findings as peaks of significant difference in cerebral blood-flow (CBF) between two scans/tasks and had located the peaks in standardized stereotaxic space. We coded each task along several dimensions, including the type and rate of input and output, the types of cognitive processes, and the relative difficulty of tasks within a study. Based on this coding, a difference score (A–B) was calculated for each subtraction. Subsequently, the frequency distributions of the difference scores for subtractions yielding a peak in the anterior cingulate region (cingulate peak) were compared with those distributions obtained from subtractions without a cingulate peak (no cingulate-peak). The cingulate peak subtractions (n = 158) differed from the no cingulate peak subtractions (n = 229) in terms of difficulty level (p = 0.001) and the presence of a remote memory component (p = 0.01). Regional differences in the frequency distribution of certain task parameters, such as difficulty level, recent memory and the use of the hand for responding, were also observed when peaks found in the anterior cingulate cortex (ACC) were further classified as located in the rostral vs caudal ACC, supracallosal vs subcallosal ACC, and limbic vs paralimbic parts of the supracallosal ACC. We conclude that task difficulty plays a major role in modulating blood-flow response in the ACC, possibly interacting with other parameters such as the nature of the response and memory demands.
Economic evaluation alongside a clinical trial of psycho-educational interventions to improve adjustment to survivorship among patients with breast cancer.

PURPOSE There is little economic research on psychosocial interventions. We aimed to collect data alongside a randomized trial to compare the costs and benefits of three psycho-educational strategies to improve transition to cancer survivorship. METHODS We evaluated the incremental delivery costs per unit increase in energy (using the Medical Outcomes Study vitality scale) or decrease in distress (from the Revised Impact of Events Scale) in the 6 months postintervention. We also evaluated 1-year post-treatment health care costs. RESULTS The costs of the control, video, and video plus counseling arms were $11.30, $25.85, and $134.47 per person, respectively. The video costs were $2.22 per unit increase in energy compared with control; among women who were the least prepared for transition, the video was more effective, resulting in even lower costs. The video cost $7,275 per unit change in distress versus control, but costs were lower in the subgroup least prepared for transition ($355). The counseling arm was more expensive and less effective than the video for virtually all end points. However, in one group, women more prepared for transition, counseling cost $1,066 per unit decrease in distress compared with the video. Health care costs tended to increase as intervention intensity increased. CONCLUSION There are no standards for evaluating cost-effectiveness of trials with psychosocial end points. In this trial, the educational video was the most cost-effective way to improve transition to survivorship. It will be important to confirm whether there is an increased use of services after such interventions and if this represents appropriate use of rehabilitative and supportive care or over-use.
Adherence to and Acceptance of Once-Daily Tacrolimus After Kidney and Liver Transplant: Results From OSIRIS, a French Observational Study

Background Adherence to immunosuppressive treatments is a major concern in transplanted patients. Methods This 6-month French observational, longitudinal, prospective study aimed to assess patient adherence to and acceptance of once-daily tacrolimus (Advagraf) initiation in kidney and liver transplant recipients. Data from 1106 patients initiating once-daily tacrolimus during posttransplant follow-up were analyzed. Adherence and acceptance were assessed using self-administered questionnaires at inclusion and at 3 and 6 months. Results Mean age was 52.4 ± 13.2 years, 61.5% were men. For 94.9% of patients, once-daily tacrolimus was prescribed after switching from twice-daily tacrolimus. At inclusion, 20.9% of patients reported good treatment adherence, 72.0% minor nonadherence, and 7.1% were nonadherent. Mean general acceptance score (range, 0-100) was 77.7 (±24.7). At 3 months, adherence was improved in 21.1%, unchanged in 69.2%, and worsened in 9.7% of patients. Mean general acceptance score was 75.4 (±26.5). General acceptance score was improved in 28.0%, unchanged in 39.4%, and worsened in 32.7% of patients. At 6 months, similar changes in adherence and acceptance were observed. Higher general acceptance score at month 3 was significantly associated with better adherence at month 6. Conclusions Conversion to once-daily tacrolimus led to an improved rate of adherence at month 3 in more than 20% of patients and a worsened rate of adherence in less than 10% of patients.
Reconstructing the Evolution of Brachypodium Genomes Using Comparative Chromosome Painting

Brachypodium distachyon is a model for the temperate cereals and grasses and has a biology, genomics infrastructure and cytogenetic platform fit for purpose. It is a member of a genus with fewer than 20 species, which have different genome sizes, basic chromosome numbers and ploidy levels. The phylogeny and interspecific relationships of this group have not to date been resolved by sequence comparisons and karyotypical studies. The aims of this study are not only to reconstruct the evolution of Brachypodium karyotypes to resolve the phylogeny, but also to highlight the mechanisms that shape the evolution of grass genomes. This was achieved through the use of comparative chromosome painting (CCP) which hybridises fluorescent, chromosome-specific probes derived from B. distachyon to homoeologous meiotic chromosomes of its close relatives. The study included five diploids (B. distachyon 2n = 10, B. sylvaticum 2n = 18, B. pinnatum 2n = 16; 2n = 18, B. arbuscula 2n = 18 and B. stacei 2n = 20) three allotetraploids (B. pinnatum 2n = 28, B. phoenicoides 2n = 28 and B. hybridum 2n = 30), and two species of unknown ploidy (B. retusum 2n = 38 and B. mexicanum 2n = 40). On the basis of the patterns of hybridisation and incorporating published data, we propose two alternative, but similar, models of karyotype evolution in the genus Brachypodium. According to the first model, the extant genome of B. distachyon derives from B. mexicanum or B. stacei by several rounds of descending dysploidy, and the other diploids evolve from B. distachyon via ascending dysploidy. The allotetraploids arise by interspecific hybridisation and chromosome doubling between B. distachyon and other diploids. The second model differs from the first insofar as it incorporates an intermediate 2n = 18 species between the B. mexicanum or B. stacei progenitors and the dysploidic B. distachyon.
Transformation of two‐pyroxene hornblende granulite to garnet granulite involving simultaneous melting and fracturing of the lower crust, Fiordland, New Zealand

Granulite facies gabbroic and dioritic gneisses in the Pembroke Valley, Milford Sound, New Zealand, are cut by vertical and planar garnet reaction zones in rectilinear patterns. In gabbroic gneiss, narrow dykes of anorthositic leucosome are surrounded by fine‐grained garnet granulite that replaced the host two‐pyroxene hornblende granulite at conditions of 750 °C and 14 kbar. Major and trace element whole‐rock geochemical data indicate that recrystallization was mostly isochemical. The anorthositic veins cut contacts between gabbroic gneiss and dioritic gneiss, but change in morphology at the contacts, from the anorthositic vein surrounded by a garnet granulite reaction zone in the gabbroic gneiss, to zones with a septum of coarse‐grained garnet surrounded by anorthositic leucosome in the dioritic gneiss. The dioritic gneiss also contains isolated garnet grains enclosed by leucosome, and short planar trains of garnet grains linked by leucosome. Partial melting of the dioritic gneiss, mostly controlled by hornblende breakdown at water‐undersaturated conditions, is inferred to have generated the leucosomes. The form of the leucosomes is consistent with melt segregation and transport aided by fracture propagation; limited retrogression suggests considerable melt escape. Dyking and melt escape from the dioritic gneiss are inferred to have propagated fractures into the gabbroic gneiss. The migrating melt scavenged water from the surrounding gabbroic gneiss and induced the limited replacement by garnet granulite.
Diurnal changes in maize leaf photosynthesis : I. Carbon exchange rate, assimilate export rate, and enzyme activities.

Diurnal changes in photosynthetic parameters and enzyme activities were characterized in greenhouse grown maize plants (Zea mays L. cv Pioneer 3184). Rates of net photosynthesis and assimilate export were highest at midday, coincident with maximum irradiance. During the day, assimilate export accounted for about 80% of net carbon fixation, and the maximum export rate (35 milligrams CH(2)O per square decimeter per hour) was substantially higher than the relatively constant rate maintained through the night (5 milligrams CH(2)O per square decimeter per hour). Activities of sucrose phosphate synthase and NADP-malate dehydrogenase showed pronounced diurnal fluctuations; maximum enzyme activities were generally coincident with highest light intensity. Reciprocal light/dark transfers of plants throughout the diurnal cycle revealed that both enzymes were deactivated by 30 minutes of darkness during the day, and they could both be substantially activated by 30 minutes of illumination at night. During 24 hours of extended darkness, sucrose phosphate synthase activity declined progressively to an almost undetectable level, but was activated after 1.5 hours of illumination. Thus, the diurnal fluctuation in maize sucrose phosphate synthase can be explained by some form of light modulation of enzyme activity and is not due to an endogenous rhythm in activity. No diurnal fluctuations were observed in the activities of NADP-malic enzyme or fructose 6-phosphate-2-kinase. Phosphoenolpyruvate carboxylase was activated by light to some extent (about 50%) when activity was measured under suboptimal conditions in vitro. The results suggested that the rates of sucrose formation and assimilate export were closely aligned with the rate of carbon fixation and the activation state of sucrose phosphate synthase.
Computer-aided diagnosis in two-phase 201Tl-SPECT of thoracic lesions

Summary Aim: The retention index, a traditionally quantitative analysis of two-phase 201Tl single photon emission computed tomography (SPECT) of the chest, is manually calculated by experienced physicians from comparable 2-D ROI. However, a 3-D ROI would provide more information than a 2-D ROI extracted from a single frame of SPECT. We propose a new diagnostic system, computer-aided diagnosis (CAD), to automatically detect suspicious lesions as 3-D objects on chest 201Tl-SPECT, and assist the physician in interpreting these images. Patients, methods: Seventy patients with thoracic lesions and confirmed diagnoses were enrolled to test this automatic CAD system. The reliability of the CAD system in detecting lesions as 3-D objects was compared to the 2-D ROI of 201Tl-SPECT found by the manually visualized method. Furthermore, we also proposed a novel index, the retention index using the heart (RIH), to differentiate high retention (slow clearance, increasing target to heart ratio) as a criterion for a malignant lesion, from low retention (faster clearance, small or no increase of the target to heart ratio) for benign lesions. Results: The CAD system can achieve a detection rate of 100% in automatically searching for thoracic lesions in 201Tl-SPECT. In diagnostic performance, the CAD system with the RIH of comparable 3-D objects has an area under the ROC curve of 0.86, higher than the 0.78 of the traditional RI method (p = 0.198). Conclusion: The CAD system of two-phase 201Tl-SPECT is a promising tool for detecting and diagnosing thoracic lesions with a diagnostic accuracy of 0.81.
NIDDM is the Major Cause of Diabetic End-Stage Renal Disease: More Evidence From a Tri-Ethnic Community

Diabetes is the single largest cause of end-stage renal disease (ESRD) in adults in the U.S. Insulin-dependent diabetes mellitus (IDDM) has been recognized for some time as an important cause of ESRD, but non-insulin-dependent diabetes mellitus (NIDDM) has been assumed, until recently, to rarely cause ESRD. The objective of this study is to determine the incidence of treatment of diabetic ESRD by diabetic type for three ethnic/racial groups: non-Hispanic whites, African-Americans, and Mexican-Americans. A population-based incidence cohort was assembled from all dialysis centers in Bexar (San Antonio) and Dallas counties in Texas. All patients with diabetic ESRD beginning dialysis between 1 December 1987 (Bexar) or 1 December 1988 (Dallas) and 31 July 1991 were identified. All non-hispanic whites and African-Americans and a 1/2 random sample of Mexican-Americans were approached for enrollment. Individuals were confirmed to have diabetes using the World Health Organization criteria. Diabetes typing was done using a computerized historical algorithm. Age-specific and age-adjusted incidence rates were obtained by diabetic type and ethnic/racial group. NIDDM causes the majority of diabetic ESRD: 59.5% for non-Hispanic whites, 92.8% for Mexican-Americans, and 84.3% for African-Americans. Mexican-Americans and African-Americans, respectively, have 6.1 and 6.5 times higher incidence of treatment for diabetic ESRD than non-Hispanic whites. NIDDM results in more ESRD than does IDDM. Minorities (African-Americans and Mexican-Americans) are at increased risk, and programs aimed at prevention of NIDDM-related ESRD must focus on them.
Archaea and bacteria with surprising microdiversity show shifts in dominance over 1,000-year time scales in hydrothermal chimneys

The Lost City Hydrothermal Field, an ultramafic-hosted system located 15 km west of the Mid-Atlantic Ridge, has experienced at least 30,000 years of hydrothermal activity. Previous studies have shown that its carbonate chimneys form by mixing of ∼90 °C, pH 9–11 hydrothermal fluids and cold seawater. Flow of methane and hydrogen-rich hydrothermal fluids in the porous interior chimney walls supports archaeal biofilm communities dominated by a single phylotype of Methanosarcinales. In this study, we have extensively sampled the carbonate-hosted archaeal and bacterial communities by obtaining sequences of >200,000 amplicons of the 16S rRNA V6 region and correlated the results with isotopic (230Th) ages of the chimneys over a 1,200-year period. Rare sequences in young chimneys were commonly more abundant in older chimneys, indicating that members of the rare biosphere can become dominant members of the ecosystem when environmental conditions change. These results suggest that a long history of selection over many cycles of chimney growth has resulted in numerous closely related species at Lost City, each of which is preadapted to a particular set of reoccurring environmental conditions. Because of the unique characteristics of the Lost City Hydrothermal Field, these data offer an unprecedented opportunity to study the dynamics of a microbial ecosystem’s rare biosphere over a thousand-year time scale.
The Social Context of Infant Intention Understanding

Traditional looking-time paradigms are often used to assess infants' attention to sociocognitive phenomena, but the link between these laboratory scenarios and real-world interactions is unclear. The current study investigated hypothesized relations between traditional social-cognitive looking-time paradigms and their real-world counterparts in caregiver–infant social interaction. Seventy-five 10- to 12-month-old infants participated in a structured play session with their caregiver, as well as a traditional looking-time paradigm targeting intentional action. Infants' ability to quickly parse intentional displays correlated with several key qualities of their everyday interactions. In particular, caregiver and infant interaction quality, maternal supportiveness, caregiver and infant joint engagement skill, and social attentiveness in infants correlated with faster habituation to looking-time displays. These results support a linkage between social-cognitive looking-time laboratory paradigms and more naturalistic partner interaction, at this key age. The data provide external validation for the large body of social-cognitive findings emerging from laboratory looking-time paradigms and contribute to a growing literature tracking the developmental trajectory of infants' understanding of people during the first 2 years.
Immunologic Memory Induced by a Glycoconjugate Vaccine in a Murine Adoptive Lymphocyte Transfer Model

ABSTRACT We have developed an adoptive cell transfer model in mice to study the ability of a glycoprotein conjugate vaccine to induce immunologic memory for the polysaccharide moiety. We used type III capsular polysaccharide from the clinically relevant pathogen group B streptococci conjugated to tetanus toxoid (GBSIII-TT) as our model vaccine. GBS are a major cause of neonatal infections in humans, and type-specific antibodies to the capsular polysaccharide protect against invasive disease. Adoptive transfer of splenocytes from mice immunized with the GBSIII-TT conjugate vaccine conferred anti-polysaccharide immunologic memory to naive recipient mice. The transfer of memory occurred in a dose-dependent manner. The observed anamnestic immune response was characterized by (i) more rapid kinetics, (ii) isotype switching from immunoglobulin M (IgM) to IgG, and (iii) 10-fold-higher levels of type III-specific IgG antibody than for the primary response in animals with cells transferred from placebo-immunized mice. The adoptive cell transfer model described in this paper can be used for at least two purposes: (i) to evaluate conjugate vaccines with different physicochemical properties for their ability to induce immunologic memory and (ii) to study the cellular interactions required for an immune response to these molecules.
Predictive Factors For Ipsilateral or Contralateral Central Lymph Node Metastasis in Unilateral Papillary Thyroid Carcinoma

Objectives:To investigate the incidence and the risk factors for occult ipsilateral or contralateral central neck lymph node (LN)metastasis in patients with unilateral papillary thyroid carcinoma (PTC) and a clinically negative neck. Summary Background Data:Elective central lymph node dissection (CLND) in patients with PTC remains controversial. There have been few prospective studies assessing accurate histopathologic information and predictive factors for the presence of metastasis to the ipsilateral or contralateral central compartment of the neck in patients with PTC and clinically negative neck nodes. Methods:We reviewed a prospective protocol of 111 unilateral PTC patients with clinically node-negative necks who have received total thyroidectomy and elective bilateral CLND from 2005 to 2007. The relationships between LN metastasis to the ipsilateral or contralateral central neck compartment and clinico-pathologic factors such as age, sex, size of primary tumor, perithyroidal invasion, lymphovascular invasion, and capsular invasion were analyzed. Results:Occult central neck LN metastasis was present in 54.1% (60/111). Of these patients, bilateral central LN metastases were present in 50% (30/60), unilateral ipsilateral central LN metastasis in 43.3% (26/60), and unilateral contralateral central LN metastasis in 6.7% (4/60). In the univariate analysis, the rate of ipsilateral central LN metastasis was significantly higher in male patients, high risk MACIS score, carcinoma with a maximal diameter of greater than 1 cm, and carcinoma with lymphovascular invasion (P < 0.05). The rate of contralateral central LN metastasis was significantly higher in cases of carcinoma with a maximal diameter of greater than 1 cm, lymphovascular invasion or histologically proven metastasis to the ipsilateral central LN (P < 0.05). Multivariate analysis showed that the tumor size was an independent risk factor for the presence of ipsilateral central LN metastasis, and the presence of ipsilateral central LN metastasis was the only independent predictor for the presence of contralateral central LN metastasis. Conclusions:Unilateral PTC with a maximal diameter of greater than 1 cm is associated with a high rate of ipsilateral central neck LN metastasis. Moreover, ipsilateral central LN metastasis is a potential independent predictor of synchronous contralateral central LN metastasis. These findings suggest that contralateral as well as ipsilateral elective CLND, performed during the initial thyroid operation, may be effective in the management of patients with unilateral PTC having a maximal diameter of greater than 1 cm and ipsilateral central LN metastasis.