Miracle-dz/UniFAR-FTUs huggingface dataset:
Spontaneous low‐frequency voltage oscillations in frog saccular hair cells

Spontaneous membrane voltage oscillations were found in 27 of 130 isolated frog saccular hair cells. Voltage oscillations had a mean peak‐to‐peak amplitude of 23 mV and a mean oscillatory frequency of 4.6 Hz. When compared with non‐oscillatory cells, oscillatory cells had significantly greater hyperpolarization‐activated and lower depolarization‐activated current densities. Two components, the hyperpolarization‐activated cation current, Ih, and the K+‐selective inward‐rectifier current, IK1, contributed to the hyperpolarization‐activated current, as assessed by the use of the IK1‐selective inhibitor Ba2+ and the Ih‐selective inhibitor ZD‐7288. Five depolarization‐activated currents were present in these cells (transient IBK, sustained IBK, IDRK, IA, and ICa), and all were found to have significantly lower densities in oscillatory cells than in non‐oscillatory cells (revealed by using TEA to block IBK, 4‐AP to block IDRK, and prepulses at different voltages to isolate IA). Bath application of either Ba2+ or ZD‐7288 suppressed spontaneous voltage oscillations, indicating that Ih and IK1 are required for generating this activity. On the contrary, TEA or Cd2+ did not inhibit this activity, suggesting that IBK and ICa do not contribute. A mathematical model has been developed to test the interpretation derived from the pharmacological and biophysical data. This model indicates that spontaneous voltage oscillations can be generated when the electrophysiological features of oscillatory cells are used. The oscillatory behaviour is principally driven by the activity of IK1 and Ih, with IA playing a modulatory role. In addition, the model indicates that the high densities of depolarization‐activated currents expressed by non‐oscillatory cells help to stabilize the resting membrane potential, thus preventing the spontaneous oscillations.
Gene Expression Signatures in Circulating Tumor Cells Correlate with Response to Therapy in Metastatic Breast Cancer.

BACKGROUND Circulating tumor cells (CTCs) are thought to be an ideal surrogate marker to monitor disease progression in metastatic breast cancer (MBC). We investigated the prediction of treatment response in CTCs of MBC patients on the basis of the expression of 46 genes. METHODS From 45 MBC patients and 20 healthy donors (HD), 2 × 5 mL of blood was collected at the time of disease progression (TP0) and at 2 consecutive clinical staging time points (TP1 and TP2) to proceed with the AdnaTest EMT-2/StemCellSelectTM (QIAGEN). Patients were grouped into (a) responder (R) and non-responder (NR) at TP1 and (b) overall responder (OR) and overall non-responder (ONR) at TP2. A 46-gene PCR assay was used for preamplification and high-throughput gene expression profiling. Data were analyzed by use of GenEx (MultiD) and SAS. RESULTS The CTC positivity was defined by the four-gene signature (EPCAM, KRT19, MUC1, ERBB2 positivity). Fourteen genes were identified as significantly differentially expressed between CTC+ and CTC- patients (KRT19, FLT1, EGFR, EPCAM, GZMM, PGR, CD24, KIT, PLAU, ALDH1A1, CTSD, MKI67, TWIST1, and ERBB2). KRT19 was highly expressed in CTC+ patients and ADAM17 in the NR at TP1. A significant differential expression of 4 genes (KRT19, EPCAM, CDH1, and SCGB2A2) was observed between OR and ONR when stratifying the samples into CTC+ or CTC-. CONCLUSIONS ADAM17 could be a key marker in distinguishing R from NR, and KRT19 was powerful in identifying CTCs.
A retrospective study comparing the outcome of horses undergoing small intestinal resection and anastomosis with a single layer (Lembert) or double layer (simple continuous and Cushing) technique.

OBJECTIVES To (1) compare postoperative complications and survival in horses after small intestinal resection and anastomosis using 2 anastomosis techniques (single layer Lembert; double layer simple continuous oversewn with Cushing), and (2) to compare outcome by anastomosis type (jejunoileostomy; jejunojejunostomy). STUDY DESIGN Retrospective case series. ANIMALS Horses (n = 53). METHODS Medical records (July 2006-July 2010) of all horses that had small intestinal resection and anastomosis. Horses were divided into groups based on technique and type of anastomosis. Comparisons of pre- and intraoperative findings (disease severity), postoperative complications, and survival rates were made between groups. RESULTS There were no differences in disease severity, postoperative complications, or survival between single layer (n = 23) or double layer (n = 31) anastomoses. There were no differences in disease severity or survival between jejunoileostomy (n = 16) or jejunojejunostomy (n = 38). There was a higher incidence of postoperative colic in hospital after jejunoileostomy (13/16) compared with jejunojejunostomy (18/38) (P = .0127). CONCLUSIONS Postoperative complications and survival are comparable between horses undergoing single layer and double layer small intestinal end-to-end anastomoses. With the exception of increased postoperative colic in the hospital, postoperative complications and survival after jejunoileostomy and jejunojejunostomy are also comparable.
Two-Step Disentanglement for Financial Data

In this work, we address the problem of disentanglement of factors that generate a given data into those that are correlated with the labeling and those that are not. Our solution is simpler than previous solutions and employs adversarial training in a straightforward manner. We demonstrate the new method on visual datasets as well as on financial data. In order to evaluate the latter, we developed a hypothetical trading strategy whose performance is affected by the performance of the disentanglement, namely, it trades better when the factors are better separated.
Can we prevent the next epidemic? The elimination of childhood diseases by mass vaccination

Recently in New Zealand there have been outbreaks of measles and pertussis every six and five years respectively. A model has been used to compare the dynamics of these diseases, and to determine the optimum ages at which children should be vaccinated against them. Whereas measles could be eliminated by giving the second vaccination at five years instead of eleven, it is difficult to devise a practical scheme that would eliminate pertussis. It is then necessary to consider vaccination schemes in the light of the age-structure of future epidemics as well as their timing.
Birthweight is associated with DNA promoter methylation of the glucocorticoid receptor in human placenta

Birthweight has been associated with a number of health outcomes throughout life. Crucial to proper infant growth and development is the placenta, and alterations to placental gene function may reflect differences in the intrauterine environment which functionally contribute to infant growth and may ultimately affect the child’s health. To examine if epigenetic alteration to the glucocorticoid receptor (GR) gene was linked to infant growth, we analyzed 480 human placentas for differential methylation of the GR gene exon 1F and examined how this variation in methylation extent was associated with fetal growth. Multivariable linear regression revealed a significant association (p < 0.0001) between differential methylation of the GR gene and large for gestational age (LGA) status. Our work is one of the first to link infant growth as a measure of the intrauterine environment and epigenetic alterations to the GR and suggests that DNA methylation may be a critical determinant of placental function.
Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection.

Human immunodeficiency virus type 1 (HIV-1)–associated nephropathy is the chief cause of chronic renal disease in patients with HIV-1 infection and is now the third leading cause of end-stage renal disease in blacks 20 to 64 years of age.1,2 These patients typically have proteinuria followed by a reduction in the glomerular filtration rate that progresses to end-stage renal disease in a few weeks or months. HIV-1–associated nephropathy is characterized morphologically by focal segmental glomerulosclerosis, tubular microcysts, interstitial fibrosis, and inflammation.2–5 The pathogenesis of HIV-1–associated nephropathy is poorly understood, but increasing evidence suggests it is due to HIV-1 infection .
A Comparison of Exposure Between the Classic and Modified Judet Approaches to the Scapula

Objectives: A debate exists over the optimal approach for addressing fractures of the scapula and glenoid. The purpose of this study is to (1) quantify and compare osseous exposure using modified Judet (MJ) and classic Judet (CJ) approaches and (2) assess the change in scapular exposure after triceps release from the inferior glenoid. Methods: Ten arms on 5 fresh-frozen torsos underwent MJ and CJ approaches. A triceps release was performed following the CJ approach in all specimens. Visual and/or palpable access to relevant surgical landmarks was recorded. Calibrated digital photographs were taken of each approach and analyzed using Image J (NIH, Bethesda, MD) to calculate the surface area of exposed bone. Results: The MJ and CJ approaches exposed 16.8 (±7.58) cm2 and 98.6 (±25.39) cm2 of bone, respectively (P < 0.001). The full medial and lateral borders of the scapula were visualized in all approaches with mobilization of the teres minor. Palpable access to the full scapular spine was possible in all cadavers. Although the MJ and CJ approaches only allowed the inferior gleniod neck to be visualized in 1 and 2 specimens, respectively, performing a triceps release provided access to this structure. It also increased the CJ exposure by 12.6 cm2 (P < 0.001) and allowed palpation of the anterior glenoid margin in 100% of specimens. Conclusions: In conclusion, the MJ approach allows similar access to landmarks important for reduction and fixation while exposing only 20% of the surface area typically visualized with the CJ approach.
Marrow adipose tissue spectrum in obesity and type 2 diabetes mellitus.

OBJECTIVE To assess the association of bone mass and marrow adipose tissue (MAT) with other fat depots, insulin resistance, bone remodeling markers, adipokines and glucose control in type 2 diabetes and obesity. DESIGN AND METHODS The study groups comprised 24 controls (C), 26 obese (O) and 28 type 2 diabetes. Dual-energy X-ray absorptiometry was used to determine bone mineral density (BMD). Blood samples were collected for biochemical measurements. 1H Magnetic resonance spectroscopy was used to assess MAT in the L3 vertebra, and abdominal magnetic resonance imaging was used to assess intrahepatic lipids in visceral (VAT) and subcutaneous adipose tissue. Regression analysis models were used to test the association between parameters. RESULTS At all sites tested, BMD was higher in type 2 diabetes than in O and C subjects. The C group showed lower VAT values than the type 2 diabetes group and lower IHL than the O and type 2 diabetes groups. However, MAT was similar in the 3 groups. Osteocalcin and C-terminal telopeptide of type 1 collagen were lower in type 2 diabetes than those in C and O subjects. Moreover, at all sites, BMD was negatively associated with osteocalcin. No association was observed between MAT and VAT. No relationship was observed among MAT and HOMA-IR, leptin, adiponectin or Pref-1, but MAT was positively associated with glycated hemoglobin. CONCLUSIONS MAT is not a niche for fat accumulation under conditions of energy surplus and type 2 diabetes, also is not associated with VAT or insulin resistance. MAT is associated with glycated hemoglobin.
Immunophenotypic Analysis of Mononuclear Phagocyte Antigens in the Arthritic Synovium of the Hip Joint

The antigenic phenotype of lining and subintimal mononuclear phagocytes (MPs) of the synovium in osteoarthritis (OA) and rheumatoid arthritis (RA) was characterised, using monoclonal antibodies directed against a range of monocyte/macroph-ageassociated antigens, in order to determine the role of MPs in the pathobiology of OA and RA of the hip. A major proportion of synovial lining cells (SLCs) and subintimal cells in RA and OA consisted of CD68 positive MPs which expressed a wide range of macrophage-associated antigens. The monocyte marker, CD14, was downregulated on SLCs in RA while OA and early markers of MP activation predominated in the OA synovium which was independent of the level of inflammation. In contrast, synovial MPs in RA showed increased expression of activation, maturation and functional antigens such as CD11a, CD11b, CD11c, CD16, CD32, CD54, CD64. Moreover, MP recruitment did not correlate with the degree of lymphocytic infiltration in RA. Thus, synovial MPs in RA are rapidly and fully activated with upregulation of activation, differentiation, and functional antigens occurring in situ. There was also no difference in antigenic phenotype of synovial MPs in inflammatory and non-inflammatory OA.
Alcohol involvement and developmental task completion during young adulthood.

OBJECTIVE Relations among young adult alcohol use disorders (AUDs), preadulthood variables (gender, family history of alcoholism, childhood stressors, high-school class rank, religious involvement, neuroticism, extraversion, psychoticism) and young adult developmental tasks (baccalaureate degree completion, full-time employment, marriage) were evaluated. METHOD Participants were 424 first-time college students (228 women) who were 18-20 years old; approximately half had a history of paternal alcoholism. Participants were assessed on five occasions over 7 years (Years 1, 2, 3, 4 and 7). RESULTS Structural equation modeling results suggest preadulthood variables were more salient predictors of developmental tasks than AUD diagnoses, with the majority of effects due to apparent selection processes. In addition, marriage protected against later AUD diagnosis at Year 7. CONCLUSIONS Findings highlight the importance of prospective multivariate models that specify potential selection, causation, socialization and reciprocal effects in order to fully examine complex relations among variables, including alcohol involvement, during major life-transition periods.
Inhibition of Glycosaminoglycan Synthesis Using Rhodamine B in a Mouse Model of Mucopolysaccharidosis Type IIIA

Reduction of an enzyme activity required for the lysosomal degradation of glycosaminoglycan (gag) chains will result in a mucopolysaccharidosis (MPS) disorder. Substrate deprivation therapy (SDT), a potential therapy option for MPS with residual enzyme activity, aims to reduce the synthesis of gag chains, the natural substrate for the deficient enzyme. Reduced substrate levels would balance the reduced level of enzyme in patient cells, resulting in normalized gag turnover. Rhodamine B, a nonspecific inhibitor, reduced gag synthesis in a range of normal and MPS cells and also decreased lysosomal storage of gag in MPS VI (72%) and MPS IIIA (60%) cells. Body weight gain of male MPS IIIA mice treated with 1 mg/kg rhodamine B was reduced compared with untreated MPS IIIA mice and was indistinguishable from that of normal mice. Liver size, total gag content, and lysosomal gag was reduced in treated MPS IIIA animals as was urinary gag excretion. Lysosomal gag content in the brain was also reduced by treatment. The alteration in MPS IIIA clinical pathology by rhodamine B, combined with the observation that treatment had no effect on the health of normal animals, demonstrates the potential for SDT in general as a therapy for MPS disorders.
Small RNA profiling in Chlamydomonas: insights into chloroplast RNA metabolism

Abstract In Chlamydomonas reinhardtii, regulation of chloroplast gene expression is mainly post-transcriptional. It requires nucleus-encoded trans-acting protein factors for maturation/stabilization (M factors) or translation (T factors) of specific target mRNAs. We used long- and small-RNA sequencing to generate a detailed map of the transcriptome. Clusters of sRNAs marked the 5′ end of all mature mRNAs. Their absence in M-factor mutants reflects the protection of transcript 5′ end by the cognate factor. Enzymatic removal of 5′-triphosphates allowed identifying those cosRNA that mark a transcription start site. We detected another class of sRNAs derived from low abundance transcripts, antisense to mRNAs. The formation of antisense sRNAs required the presence of the complementary mRNA and was stimulated when translation was inhibited by chloramphenicol or lincomycin. We propose that they derive from degradation of double-stranded RNAs generated by pairing of antisense and sense transcripts, a process normally hindered by the traveling of the ribosomes. In addition, chloramphenicol treatment, by freezing ribosomes on the mRNA, caused the accumulation of 32–34 nt ribosome-protected fragments. Using this ‘in vivo ribosome footprinting’, we identified the function and molecular target of two candidate trans-acting factors.
Cancer mortality among workers in the German rubber industry: 1981-91.

OBJECTIVES: To determine the cancer specific mortality of active and retired workers of the German rubber industry with emphasis on cancer sites which have been associated with the rubber industry in previous studies. METHODS: A cohort of 11,663 German men was followed up for mortality from 1 January 1981 to 31 December 1991. Cohort members were active (n = 7536) or retired (n = 4127) at the beginning of the study, and had been employed for at least one year in one of five study plants producing types or general rubber goods. Vital status was ascertained for 99.7% of the cohort members, and cause of death found for 96.8% of the 2719 decedents. Age and calendar year adjusted standardised mortality ratios (SMR) and 95% confidence intervals (95% CI) were calculated overall from national reference rates and stratified by year of hire and by years since hire. RESULTS: Mortalities from all causes (SMR 108; 95% CI 104-112) and all cancers (SMR 111; 95% CI 103-119) were significantly increased in the study cohort. Significant excesses in the mortalities from lung cancer (SMR 130; 95% CI 115-147) and pleural cancer (SMR 401; 95% CI 234-642) were identified. SMRs higher than 100 were found for cancers of the pharynx (SMR 144; 95% CI 76-246), oesophagus (SMR 120; 95% CI 74-183), stomach (SMR 110; 95% CI 86-139), rectum (SMR 123; 95% CI 86-170), larynx (SMR 129; 95% CI 69-221), prostate (SMR 108; 95% CI 84-136), and bladder (SMR 124; 95% CI 86-172), as well as for leukaemia (SMR 148; 95% CI 99-213). Mortalities from liver cancer, brain cancer, and lymphoma were lower than expected. CONCLUSIONS: Mortalities from cancer of several sites previously associated with the rubber industry were also increased among workers of the German rubber industry. Results of the stratified analyses are consistent with a role of occupational exposure in the aetiology of some of these cancers.
Integrated Machine Learning and Optimization Frameworks with Applications in Operations Management

Incorporation of contextual inference in the optimality analysis of operational problems is a canonical characteristic of data-informed decision making that requires interdisciplinary research. In an attempt to achieve individualization in operations management, we design rigorous and yet practical mechanisms that boost efficiency, restrain uncertainty and elevate real-time decision making through integration of ideas from machine learning and operations research literature. In our first study, we investigate the decision of whether to admit a patient to a critical care unit which is a crucial operational problem that has significant influence on both hospital performance and patient outcomes. Hospitals currently lack a methodology to selectively admit patients to these units in a way that patients individual health metrics can be incorporated while considering the hospitals operational constraints. We model the problem as a complex loss queueing network with a stochastic model of how long risk-stratified patients spend time in particular units and how they transition between units. A data-driven optimization methodology then approximates an optimal admission control policy for the network of units. While enforcing low levels of patient blocking, we optimize a monotonic dual-threshold admission policy. Our methodology captures utilization and accessibility in a network model of care pathways while supporting the personalized allocation of scarce care resources to the neediest patients. The interesting benefits of admission thresholds that vary by day of week are also examined. In the second study, we analyze the efficiency of surgical unit operations in the era of big data. The accuracy of surgical case duration predictions is a crucial element in hospital operational performance. We propose a comprehensive methodology that incorporates both structured and unstructured data to generate individualized predictions regarding the overall distribution of surgery durations. Consequently, we investigate methods to incorporate such individualized predictions into operational decision-making. We introduce novel prescriptive models to address optimization under uncertainty in the fundamental surgery
Model checking embedded software of an industrial knitting machine

Model checking is a promising approach for the verification of embedded systems software. The [mc]square approach for verification of binary code provides several improvements compared to other existing methods: the system model is automatically derived from the binary code using dedicated microcontroller simulators and state spaces are reduced by applying automatic abstraction techniques. In this paper, we survey the involved mechanisms and assess the overall approach by conducting an industrial case study – the verification of the embedded software of a monitoring device of a knitting machine.
Lipid Profile and Prevalence of Dyslipidemia in Pre- and Postmenopausal Women in Yaounde, Cameroon

Aims: Lipids serve several important physiologic functions like energy homeostasis or biosynthesis of hormone within the human body. The deterioration of lipid metabolism which is favoured by menopause is the source of cardiovascular diseases. This study aimed to determine the plasma lipid profile and dyslipidemia prevalence of some Cameroonian women. Study Design: This was a cross-sectional study. Place and Duration of Study: The enrollment took place at the Yaounde Military Hospital from November 2016 to July 2017. Methodology: To achieve this goal, two sets of 105 postmenopausal and 127 premenopausal participants were enrolled in this study. 5ml of blood were collected on EDTA coated tubes from each participant. Enzymatic methods were used to evaluate total cholesterol, HDL cholesterol and triglyceride, while LDL cholesterol was determined using the Friedewald equation. These biological parameters were used to determine dyslipidemia. Thereafter, they were compared within age and year since menopause subgroups. Results: There was no significant difference in the mean values of total cholesterol, HDL-C, LDL-C as well as triglyceride between premenopausal and postmenopausal women. The mean HDL-C concentration was stable in the age subgroups while the mean total cholesterol and LDL-C were slightly increasing as postmenopausal participants got older. LDL-C level was significantly higher in women who had been in menopause for more than 15 years. The overall dyslipidemia prevalence was 53%. Dyslipidemia was significantly higher in the subgroup of women who had freshly entered menopause. Conclusion: Even though there was no change in the mean concentration of the plasma lipid parameters, of pre- and postmenopausal participants there was a general need to improve their lifestyle in order to reduce dyslipidemia prevalence.
Dynamic role of hyaluronan (HYA) in connective tissue activation and inflammation

Gerdin B, Hällgren R (University Hospital, Uppsala, Sweden). Dynamic role of hyaluronan (HYA) in connective tissue activation and inflammation (Minisymposium: Hyaluronan). J Intern Med 1997; 242: 49–55.