Takshan/R1 huggingface dataset:
Prevalence of multimorbidity in general practice: a cross-sectional study within the Swiss Sentinel Surveillance System (Sentinella).

OBJECTIVES: To estimate the prevalence of multimorbidity using a list of 75 chronic conditions derived from the International Classification for Primary Care, Second edition and developed specifically to assess multimorbidity in primary care. Our aim was also to provide prevalence data for multimorbidity in primary care in a country in which general practitioners (GPs) do not play a gatekeeping role in the health system. SETTING: A representative sample of GPs within the Swiss Sentinel Surveillance Network. PARTICIPANTS: 118 GPs completed a paper-based questionnaire about 25 consecutive patients of all ages between September and November 2015. There were no patient exclusion criteria. Recorded data included date of birth, gender and the patients' chronic conditions. PRIMARY AND SECONDARY OUTCOME MEASURES: We estimated the prevalence of multimorbidity, defined as ≥2, and ≥3 chronic conditions stratified by gender and age group, and adjusted for clustering by GPs. We also computed the prevalence of each chronic condition individually and grouped by system. RESULTS: Data from 2904 patients were included (mean age (SD)=56.5 (20.5) years; male=43.7%). Prevalence was 52.1% (95% CI 48.6% to 55.5%) for ≥2 and 35.0% (95% CI 31.6% to 38.5%) for ≥3 chronic conditions, with no significant gender differences. Prevalence of two or more chronic conditions was low (6.2%, 95% CI 2.8% to 13.0%) in those below 20 but affected more than 85% (85.8%, 95% CI 79.6% to 90.3%) of those above the age of 80. The most prevalent conditions were cardiovascular (42.7%, 95% CI 39.7% to 45.7%), psychological (28.5%, 95% CI 26.1% to 31.1%) and metabolic or endocrine disorders (24.1%, 95% CI 21.6% to 26.7%). Elevated blood pressure was the most prevalent cardiovascular condition and depression the most common psychological disorder. CONCLUSION: In a country in which GPs do not play a gatekeeping role within the health system, the prevalence of multimorbidity, as assessed using a list of chronic conditions specifically relevant to primary care, is high and increases with age.
Insulin-like growth factor type 1 deficiency in a Moroccan patient with de novo inverted duplication 9p24p12 and developmental delay: a case report.

BACKGROUND: 9p duplication is a structural chromosome abnormality, described in more than 150 patients to date. In most cases the duplicated segment was derived from a parent being a reciprocal translocation carrier. However, about 15 cases with de novo 9p duplication have been reported previously. Clinically, this condition is characterized by mental retardation, short stature, developmental delay, facial dysmorphism, hand and toe anomalies, heart defects and/or ocular manifestations. CASE PRESENTATION: We report here the case of a 2-year-old Moroccan girl with a de novo duplication of 9p24 to p12. Clinical manifestations included failure to thrive, psychomotor delay, microcephaly, dysmorphic features, equinus feet, and umbilical hernia. Further clinical investigations showed an insulin-like growth factor type 1 deficiency. Banding cytogenetics identified a derivative chromosome 9, with an abnormally elongated short arm. Molecular cytogenetics based on multicolor banding probes characterized an inverted duplication 9p24 to p12 involving several genes especially an insulin-like growth factor binding protein named insulin-like growth factor binding protein-like 1, which seemed to be overexpressed, leading to the insulin-like growth factor deficiency in our patient. CONCLUSIONS: This study showed that insulin-like growth factor type 1 deficiency can be another feature of 9p duplication, suggesting a likely involvement of insulin-like growth factor binding protein-like 1 overexpression in growth delay. However, further studies of the gene expressions are needed to better understand the phenotype-karyotype correlations.
Thioredoxin interacting protein (TXNIP) is a novel tumor suppressor in thyroid cancer.

BACKGROUND: Thyroid cancer is the most common endocrine malignancy, and many patients with metastatic differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC), and anaplastic thyroid cancer (ATC) fail to respond to conventional therapies, resulting in morbidity and mortality. Additional therapeutic targets and treatment options are needed for these patients. We recently reported that peroxisome proliferator-activated receptor gamma (PPARγ) is highly expressed in ATC and confers an aggressive phenotype when overexpressed in DTC cells. METHODS: Microarray analysis was used to identify downstream targets of PPARγ in ATC cells. Western blot analysis and immunohistochemistry (IHC) were used to assess thioredoxin interacting protein (TXNIP) expression in thyroid cancer cell lines and primary tumor specimens. Retroviral transduction was used to generate ATC cell lines that overexpress TXNIP, and assays that assess glucose uptake, viable cell proliferation, and invasion were used to characterize the in vitro properties of these cells. An orthotopic thyroid cancer mouse model was used to assess the effect of TXNIP overexpression in ATC cell lines in vivo. RESULTS: Using microarray analysis, we show that TXNIP is highly upregulated when PPARγ is depleted from ATC cells. Using Western blot analysis and IHC, we show that DTC and ATC cells exhibit differential TXNIP expression patterns. DTC cell lines and patient tumors have high TXNIP expression in contrast to low or absent expression in ATC cell lines and tumors. Overexpression of TXNIP decreases the growth of HTh74 cells compared to vector controls and inhibits glucose uptake in the ATC cell lines HTh74 and T238. Importantly, TXNIP overexpression in T238 cells results in attenuated tumor growth and decreased metastasis in an orthotopic thyroid cancer mouse model. CONCLUSIONS: Our findings indicate that TXNIP functions as a tumor suppressor in thyroid cells, and its downregulation is likely important in the transition from differentiated to advanced thyroid cancer. These studies underscore the potential of TXNIP as a novel therapeutic target and prognostic indicator in advanced thyroid cancer.
IntEREst: intron-exon retention estimator.

BACKGROUND: In-depth study of the intron retention levels of transcripts provide insights on the mechanisms regulating pre-mRNA splicing efficiency. Additionally, detailed analysis of retained introns can link these introns to post-transcriptional regulation or identify aberrant splicing events in human diseases. RESULTS: We present IntEREst, Intron-Exon Retention Estimator, an R package that supports rigorous analysis of non-annotated intron retention events (in addition to the ones annotated by RefSeq or similar databases), and support intra-sample in addition to inter-sample comparisons. It accepts binary sequence alignment/map (.bam) files as input and determines genome-wide estimates of intron retention or exon-exon junction levels. Moreover, it includes functions for comparing subsets of user-defined introns (e.g. U12-type vs U2-type) and its plotting functions allow visualization of the distribution of the retention levels of the introns. Statistical methods are adapted from the DESeq2, edgeR and DEXSeq R packages to extract the significantly more or less retained introns. Analyses can be performed either sequentially (on single core) or in parallel (on multiple cores). We used IntEREst to investigate the U12- and U2-type intron retention in human and plant RNAseq dataset with defects in the U12-dependent spliceosome due to mutations in the ZRSR2 component of this spliceosome. Additionally, we compared the retained introns discovered by IntEREst with that of other methods and studies. CONCLUSION: IntEREst is an R package for Intron retention and exon-exon junction levels analysis of RNA-seq data. Both the human and plant analyses show that the U12-type introns are retained at higher level compared to the U2-type introns already in the control samples, but the retention is exacerbated in patient or plant samples carrying a mutated ZRSR2 gene. Intron retention events caused by ZRSR2 mutation that we discovered using IntEREst (DESeq2 based function) show considerable overlap with the retained introns discovered by other methods (e.g. IRFinder and edgeR based function of IntEREst). Our results indicate that increase in both the number of biological replicates and the depth of sequencing library promote the discovery of retained introns, but the effect of library size gradually decreases with more than 35 million reads mapped to the introns.
NK cells require antigen-specific memory CD4(+) T cells to mediate superior effector functions during HSV-2 recall responses in vitro.

Natural killer (NK) cells have an important role in mounting protective innate responses against genital herpes simplex virus type 2 (HSV-2) infections. However their role as effectors in adaptive immune responses against HSV-2 is unclear. Here, we demonstrate that NK cells from C57BL/6 mice in an ex vivo splenocyte culture produce significantly more interferon γ (IFN-γ) upon re-exposure to HSV-2 antigens in a mouse model of genital HSV-2 immunization. We find that naïve NK cells do not require any prior stimulation or priming to be activated to produce IFN-γ. Our results demonstrate that HSV-2-experienced CD4(+) T cells have a crucial role in coordinating NK cell activation and that their presence during HSV-2 antigen presentation is required to activate NK cells in this model of secondary immune response. We also examined the requirement of cell-to-cell contacts for both CD4(+) T cells and NK cells. NK cells are dependent on direct interactions with other HSV-2-experienced splenocytes, and CD4(+) T cells need to be in close proximity to NK cells to activate them. This study revealed that NK cells do not exhibit any memory toward HSV-2 antigens and, in fact, require specific interactions with HSV-2-experienced CD4(+) T cells to produce IFN-γ.
An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease trajectory. The aim of this study was to assess potential biomarkers to predict outcomes for people with IPF. METHODS: PROFILE is a large prospective longitudinal cohort of treatment-naive patients with IPF. We adopted a two-stage discovery and validation design using patients from the PROFILE cohort. For the discovery analysis, we examined 106 patients and 50 age and sex matched healthy controls from Nottingham University Hospitals NHS Trust and the Royal Brompton Hospital. We did an unbiased, multiplex immunoassay assessment of 123 biomarkers. We further investigated promising novel markers by immunohistochemical assessment of IPF lung tissue. In the validation analysis, we examined samples from 206 people with IPF from among the remaining 212 patients recruited to PROFILE Central England. We used the samples to attempt to replicate the biomarkers identified from the discovery analysis by use of independent immunoassays for each biomarker. We investigated the predictive power of the selected biomarkers to identify individuals with IPF who were at risk of progression or death. The PROFILE studies are registered on ClinicalTrials.gov, numbers NCT01134822 (PROFILE Central England) and NCT01110694 (PROFILE Royal Brompton Hospital). FINDINGS: In the discovery analysis, we identified four serum biomarkers (surfactant protein D, matrix metalloproteinase 7, CA19-9, and CA-125) that were suitable for replication. Histological assessment of CA19-9 and CA-125 suggested that these proteins were markers of epithelial damage. Replication analysis showed that baseline values of surfactant protein D (46·6 ng/mL vs 34·6 ng/mL, p=0·0018) and CA19-9 (53·7 U/mL vs 22·2 U/mL; p<0·0001) were significantly higher in patients with progressive disease than in patients with stable disease, and rising concentrations of CA-125 over 3 months were associated with increased risk of mortality (HR 2·542, 95% CI 1·493-4·328, p=0·00059). INTERPRETATION: We have identified serum proteins secreted from metaplastic epithelium that can be used to predict disease progression and death in IPF. FUNDING: GlaxoSmithKline R&D and the UK Medical Research Council.
Radiosurgery alone versus radiosurgery plus whole-brain irradiation for very few cerebral metastases from lung cancer.

BACKGROUND: It is unclear whether patients with few cerebral metastases benefit from whole-brain irradiation added to radiosurgery. Since primary tumors disseminating to the brain show different behavior, this question should be answered separately for each tumor type. This study compared both treatments in patients with 1-3 cerebral metastases from lung cancer. METHODS: Ninety-eight patients receiving radiosurgery alone were retrospectively compared to 50 patients receiving radiosurgery plus whole-brain irradiation for local control, distant cerebral control and overall survival. Ten other characteristics were additionally considered including radiosurgery dose, age, gender, Eastern Cooperative Oncology Group (ECOG) performance score, histology, number of cerebral metastases, maximum diameter of all cerebral metastases, site of cerebral metastases, extra-cerebral metastases, and interval from lung cancer diagnosis to irradiation. RESULTS: The treatment approach had no significant impact on local control (p = 0.61). On multivariate analysis of local control, ECOG performance score was significant (risk ratio [RR]: 2.10; p < 0.001). The multivariate analysis of distant brain control revealed significant positive associations with radiosurgery plus whole-brain irradiation (RR: 4.67; p < 0.001) and one cerebral metastasis (RR: 2.62; p < 0.001). Treatment approach was not significantly associated with overall survival (p = 0.32). On multivariate analysis, significant associations with overall survival were found for maximum diameter of all cerebral metastases (RR: 1.81; p = 0.008), extra-cerebral metastases (RR: 2.98; p < 0.001), and interval from lung cancer diagnosis to irradiation (RR: 1.19; p < 0.001). CONCLUSION: Addition of whole-brain irradiation to radiosurgery significantly improved distant brain control in patients with few cerebral metastases from lung cancer. This improvement did not translate into better overall survival.
Initial Assessments of E-Learning Modules in Cytotechnology Education.

Background: Nine E-learning modules (ELMs) were developed in our program using Articulate software. This study assessed our cytotechnology (CT) students' perceptions on the content of the ELMs, and the perceived influence of the ELMs on students' performance during clinical rotations. Subjects and Methods: All CT students watched nine ELMs before the related classroom lecture and group discussion. Following that, students completed nine preclinical rotation surveys. After their clinical rotations, students completed nine postclinical rotation surveys. Results: Statements on the content of the ELMs regarding the quality of the video and audio, duration, navigation, and the materials presented, received positive responses from the majority of the students. While there were a few disagreements and neutral responses, most of the students responded positively saying that the ELMs better prepared them for their role, as well as helped them to better perform their roles during the clinical rotation. The majority of the students recommended developing more EMLs for cytology courses in the future. Conclusions: This study has given hope that the ELMs have potential to enhance our online curriculum and benefit students, within the United States and internationally, who have no easy access to cytology clinical laboratories for hands-on training.
Role of Gut Inflammation in Altering the Monocyte Compartment and Its Osteoclastogenic Potential in HLA-B27-Transgenic Rats.

OBJECTIVE: To investigate the relationship between intestinal inflammation and the central and peripheral innate immune system in the pathogenesis of HLA-B27-associated spondyloarthritis using an HLA-B27-transgenic (B27-Tg) rat model. METHODS: The myeloid compartment of the blood and bone marrow (BM) of B27-Tg rats, as well as HLA-B7-Tg and non-Tg rats as controls, was evaluated by flow cytometry. Plasma from rats was assessed by enzyme-linked immunosorbent assay for levels of CCL2 and interleukin-1α (IL-1α). Rats were treated with antibiotics for 4 weeks, and the myeloid compartment of the blood and BM was evaluated by flow cytometry. The osteoclastogenic potential of BM-derived cells from antibiotic-treated rats, in the presence or absence of tumor necrosis factor (TNF), was evaluated in vitro. RESULTS: B27-Tg rats had substantially higher numbers of circulating Lin-CD172a+CD43(low) monocytes as compared to control animals, and this was significantly correlated with higher levels of plasma CCL2. Antibiotic treatment of B27-Tg rats markedly reduced the severity of ileitis, plasma levels of CCL2 and IL-1α, and number of BM and blood Lin-CD172a+CD43(low) monocytes, a cell subset shown in the present study to have the greatest in vitro osteoclastogenic potential. Antibiotic treatment also prevented the TNF-dependent enhancement of osteoclastogenesis in B27-Tg rats. CONCLUSION: Microbiota-dependent intestinal inflammation in B27-Tg rats directly drives the systemic inflammatory and bone-erosive potential of the monocyte compartment.
Molecular cytogenetic characterization of a prenatally detected supernumerary minute marker chromosome 8.

The characterization of a prenatally detected very small (approximately half of 18p-(karyotype: 47,XX,+mar[16]/46,XX[7]) supernumerary marker chromosome (SMC) identified by GTG-banding analysis is described. The marker has been identified as derived from chromosome 8 centromeric material using a combination of different cytogenetic (GTG-, NOR-, CBG banding), molecular cytogenetic (24 colour-fluorescent in situ hybridization [FISH], three-colour FISH using centromeric probes for all human chromosomes) and molecular genetic techniques (microsatellite analysis). This is the first case described with such a minute SMC derived from chromosome 8 diagnosed prenatally, the 15th case reporting on a SMC originating from chromosome 8 and the third such case without any severe clinical features.
Deletion of a CD2-like gene, 8-DR, from African swine fever virus affects viral infection in domestic swine.

An African swine fever virus (ASFV) gene with similarity to the T-lymphocyte surface antigen CD2 has been found in the pathogenic African isolate Malawi Lil-20/1 (open reading frame [ORF] 8-DR) and a cell culture-adapted European virus, BA71V (ORF EP402R) and has been shown to be responsible for the hemadsorption phenomenon observed for ASFV-infected cells. The structural and functional similarities of the ASFV gene product to CD2, a cellular protein involved in cell-cell adhesion and T-cell-mediated immune responses, suggested a possible role for this gene in tissue tropism and/or immune evasion in the swine host. In this study, we constructed an ASFV 8-DR gene deletion mutant (delta8-DR) and its revertant (8-DR.R) from the Malawi Lil-20/1 isolate to examine gene function in vivo. In vitro, delta8-DR, 8-DR.R, and the parental virus exhibited indistinguishable growth characteristics on primary porcine macrophage cell cultures. In vivo, 8-DR had no obvious effect on viral virulence in domestic pigs; disease onset, disease course, and mortality were similar for the mutant delta8-DR, its revertant 8-DR.R, and the parental virus. Altered viral infection was, however, observed for pigs infected with delta8-DR. A delay in spread to and/or replication of delta8-DR in the draining lymph node, a delay in generalization of infection, and a 100- to 1,000-fold reduction in virus titers in lymphoid tissue and bone marrow were observed. Onset of viremia for delta8-DR-infected animals was significantly delayed (by 2 to 5 days), and mean viremia titers were reduced approximately 10,000-fold at 5 days postinfection and 30- to 100-fold at later times; moreover, unlike in 8-DR.R-infected animals, the viremia was no longer predominantly erythrocyte associated but rather was equally distributed among erythrocyte, leukocyte, and plasma fractions. Mitogen-dependent lymphocyte proliferation of swine peripheral blood mononuclear cells in vitro was reduced by 90 to 95% following infection with 8-DR.R but remained unaltered following infection with delta8-DR, suggesting that 8-DR has immunosuppressive activity in vitro. Together, these results suggest an immunosuppressive role for 8-DR in the swine host which facilitates early events in viral infection. This may be of most significance for ASFV infection of its highly adapted natural host, the warthog.
A sustainable use of Ricotta Cheese Whey for microbial biodiesel production.

The increasing demand of plant oils for biodiesel production has highlighted the need for alternative strategies based either on non-food crops or agro-industrial wastes that do not compete with food and feed production. In this context, the combined use of wastewater and oleaginous microorganisms could be a valuable production option. Ricotta cheese whey (RCW), one of the major byproducts of the dairy industry, is produced in very high and steadily increasing amounts and, due to its high organic load, its disposal is cost-prohibitive. In the present study, in order to assess the adequacy of RCW as a growth medium for lipid production, 18 strains of oleaginous yeasts were investigated in shaken flask for their growth and lipid-producing capabilities on this substrate. Among them, Cryptococcus curvatus NRRL Y-1511 and Cryptococcus laurentii UCD 68-201 adequately grew therein producing substantial amounts of lipids (6.8 and 5.1gL(-1), respectively). A high similarity between the percent fatty acid methyl esters (FAME) composition of lipids from the former and the latter strain was found with a predominance of oleic acid (52.8 vs. 48.7%) and of total saturated fatty acids (37.9 vs. 40.8%). The subsequent scale transfer of the C. laurentii UCD 68-201 lipid production process on RCW to a 3-L STR led to significantly improved biomass and total lipid productions (14.4 and 9.9gL(-1), respectively) with the biodiesel yield amounting to 32.6%. Although the C. laurentii FAME profile was modified upon process transfer, it resembled that of the Jatropha oil, a well established feedstock for biodiesel production. In conclusion, C. laurentii UCD 68-201, for which there is very limited amount of available information, turned out to be a very promising candidate for biodiesel production and wide margins of process improvement might be envisaged.