Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Splicing Defects Caused by Mutations in the Dysferlin Gene

Missense, iso‐semantic, and intronic mutations are challenging for interpretation, in particular for their impact in mRNA. Various tools such as the Human Splicing Finder (HSF) system could be used to predict the impact on splicing; however, no diagnosis result could rely on predictions alone, but requires functional testing. Here, we report an in vitro approach to study the impact of DYSF mutations on splicing. It was evaluated on a series of 45 DYSF mutations, both intronic and exonic. We confirmed splicing alterations for all intronic mutations localized in 5′ or 3′ splice sites. Then, we showed that DYSF missense mutations could also result in splicing defects: mutations c.463G>A and c.2641A>C abolished ESEs and led to exon skipping; mutations c.565C>G and c.1555G>A disrupted Exonic Splicing Enhancer (ESE), while concomitantly creating new 5′ or 3′ splice site leading to exonic out of frame deletions. We demonstrated that 20% of DYSF missense mutations have a strong impact on splicing. This minigene strategy is an efficient tool for the detection of splicing defects in dysferlinopathies, which could allow for a better comprehension of splicing defects due to mutations and could improve prediction tools evaluating splicing defects.
Risk factors for acquiring sporadic Campylobacter infection in France: results from a national case-control study.

BACKGROUND To better document the risk factors for sporadic Campylobacter infection in France, we conducted a national case-control study from September 2002 to June 2004. METHODS Cases with confirmed Campylobacter infection were sampled through the national surveillance laboratory network. Cases and controls who were matched for age, as well as attending physicians, were interviewed about foods consumed, food preparation practices, travel history, contact with cases and animals during the 8 days before the onset of infection, and any antibiotic use occurring during the 30 days before onset. Matched odds ratios [ORs] were calculated using conditional logistic regression and multiple imputation methods. RESULTS A total of 285 pairs of cases and matched controls were enrolled. "Ate undercooked beef" (OR, 2.86; 95% confidence interval [CI], 1.65-4.95), "ate at restaurant" (OR, 2.20; 95% CI, 1.23-3.93), and "poor utensils hygiene in the kitchen" (OR, 2.12; 95% CI, 1.33-3.37) were the main independent risk factors for infection. Cases infected with a ciprofloxacin-resistant Campylobacter jejuni strain were more likely than controls to have used antibiotics in the month before onset. CONCLUSION Good hygiene practices in the kitchen remain a strong recommendation to avoid cross-contamination. However, studies are needed to explore the mechanism of contamination throughout the food chain. The use of antibiotics in humans may favor the development of a resistant infection.
Correlation of morphometric analysis of pancreatic islets and diabetes in spontaneously diabetic BB/W rats.

Morphometric analysis of pancreatic islets was performed on BB/W rats, which were divided into moderately diabetic and severely diabetic as well as normoglycemic during four months of observation. In normoglycemic rats, total islet area occupied 1.2% of total pancreatic tissue area with a mean area of 19,000 microns2 per islet. Total pancreatic area was markedly decreased to 22% and 10% in moderately and severely diabetic rats, respectively, compared with that of normoglycemic rats. Mean islet area of moderately and severely diabetic rats decreased to 28% and 25% per islet that of normoglycemic rats, respectively, in which severely diabetic rats showed variable sizes of islets. Concomitant morphometric analysis of renal glomeruli showed decreasing sizes of glomeruli in severely diabetic rats whereas number of glomeruli in renal cortex increased in severely diabetic rats compared with normoglycemic rats. Moderately and severely diabetic states were also studied by I.V. glucose and insulin tolerance tests in regard to plasma glucose and insulin levels compared with normoglycemic rats. During months of observation severely diabetic rats had their total islet area reduced to 10% that of normoglycemic rats as a result of cell mediated immune destruction of islets. And concomitant reduction of glomeruli may be a part of diabetic glomerulopathy. Yet, diabetic rats were normotensive. The degree of water intake, urine volume, urine glucose, urine protein and albumin was also correlated with the degree of diabetes. This study further provides the feasibility of using diabetic BB/W rats for diabetic conditions and their complications.
Response selectivity for multiple dimensions of frequency sweeps in the pallid bat inferior colliculus.

1. While hunting, the pallid bat uses passive sound localization at low frequencies to find terrestrial prey, and echolocation for general orientation. It must therefore process two different types of acoustic input at the same time. The pallid bat's echolocation pulse is a downward frequency-modulated (FM) sweep from 60 to 30 kHz. This study examined the response selectivity of single neurons in the pallid bat's central nucleus of the inferior colliculus (ICC) for FM sweeps, comparing the response properties of the high-frequency population, tuned to the biosonar pulse, with the low-frequency population, tuned below the pulse. The working hypothesis was that the high-frequency population would exhibit a response selectivity for downward FM sweeps that was not present in the low-frequency population. 2. Neurons were tested for their selectivity for FM sweep direction, duration, frequency range and bandwidth, and rate of frequency change. The extent to which they responded exclusively to tones, noise, and FM sweeps was also examined. Significant differences in the response properties of neurons in the two populations were found. In the low-frequency population, all neurons responded to tones, but only 50% responded to FM sweeps. Only 23% were selective for sweep direction. In the high-frequency population, all neurons responded to FM sweeps, but 31% did not respond to tones. Over one-half of this population was selective for sweep direction, and of those that were selective, all preferred the downward sweep direction of the biosonar pulse. A large percentage (31%) responded exclusively to downward sweeps, and not to tones or upward sweeps. None of the cells in either population responded to noise, or did so only at very high relative thresholds. 3. Both populations contained neurons that were selective for short stimulus durations that approximated the duration of the biosonar pulse, although the percentage was greater in the high-frequency population (58% vs. 20%). In the high-frequency population, 31% of the neurons tested for duration responded exclusively to both the sweep direction and duration of the biosonar pulse. 4. Downward FM-selective neurons, with one exception, were generally insensitive to the rate of frequency change of the FM sweep, as well as the frequency range and bandwidth of the sweep. They responded similarly to both the full 60- to 30-kHz sweep and to 5-kHz bandwidth portions of the full sweep. (ABSTRACT TRUNCATED AT 400 WORDS)
Flotillin-Dependent Clustering of the Amyloid Precursor Protein Regulates Its Endocytosis and Amyloidogenic Processing in Neurons

The flotillins/reggie proteins are associated with noncaveolar membrane microdomains and have been implicated in the regulation of a clathrin- and caveolin-independent endocytosis pathway. Endocytosis is required for the amyloidogenic processing of the amyloid precursor protein (APP) and thus to initiate the release of the neurotoxic β-amyloid peptide (Aβ), the major component of extracellular plaques found in the brains of Alzheimer's disease patients. Here, we report that small interference RNA-mediated downregulation of flotillin-2 impairs the endocytosis of APP, in both neuroblastoma cells and primary cultures of hippocampal neurons, and reduces the production of Aβ. Similar to tetanus neurotoxin endocytosis, but unlike the internalization of transferrin, clathrin-dependent endocytosis of APP requires cholesterol and adaptor protein-2 but is independent of epsin1 function. Moreover, on a nanoscale resolution using stimulated emission depletion microscopy and by Förster resonance energy transfer with fluorescence lifetime imaging microscopy, we provide evidence that flotillin-2 promotes the clustering of APP at the cell surface. We show that the interaction of flotillin-2 with APP is dependent on cholesterol and that clustering of APP enhances its endocytosis rate. Together, our data suggest that cholesterol/flotillin-dependent clustering of APP may stimulate the internalization into a specialized clathrin-dependent endocytosis pathway to promote amyloidogenic processing.
Impact of Safta on Capital Market Integration of South Asia: Evidence from Cointegration Analysis

Abstract Regional Trade agreements (RTAs) are increasing worldwide because of associated economic benefits such as increased cross border investment and trade, development and integration markets. This paper investigates how South Asian Free Trade Agreement (SAFTA) impact on the integration of South Asian capital markets. Weekly data of capital market indices of three countries (India, Pakistan and Sri Lanka) have been analyzed for overall (1998-2017) and two sub periods, 1998-2006 (Pre SAFTA) and 2009-2017 (Post SAFTA). Correlation coefficients, Unit root tests and Johansen and Juselius (JJ) Cointegration technique has been applied to access the integration between the markets. The main findings suggest that integration between the South Asian capital markets has been increased in Post-SAFTA period. The evidence that SAFTA pact results in increased integration of regional capital markets has important implications for investors and policymakers.
On the recursive implementation of adaptive control for robot manipulators

This paper investigates the recursive implementation of adaptive control for robot manipulators. Using the spatial vector tool and exploiting some physical properties of multi-body systems, we propose a general framework on the seeking of the Coriolis and centripetal matrix which satisfies the so-called skew-symmetric requirement. Then two existing choices are analyzed and a new kind of Coriolis and centripetal matrix is proposed. Comparisons between these choices show that the simplest-form Coriolis and centripetal matrix comes from the original recursive Newton-Euler dynamics based on spatial vectors, which implies that skew-symmetric property is an inherent property possessed by spatial-vector based recursive Newton-Euler dynamics formulation. Under the proposed general framework regarding establishment of the Coriolis and centripetal matrix, a class of recursive passivity based adaptive algorithms have been proposed. In the next, we present an algorithm on how to derive the filtered manipulator torque recursively. With this filtered torque, the prediction error of the filtered torque is obtained and injected to the direct adaptation, forming the well-known composite adaptation law. Composite adaptation driven by both the tracking errors and the prediction errors gives more smooth tracking error response and estimated parameter response, and also better tracking accuracy. A six-DOF manipulator is employed as a simulation example to show the performance of the proposed recursive algorithms.
Comparison of the semen analysis results obtained from two branded computer‐aided sperm analysis systems

The study evaluated the comparability of two branded computer‐aided sperm analysis (CASA) systems commonly used in andrology laboratories in China. The same semen sample was analysed using two branded CASA systems (WLJY‐9000 and CFT‐9200) by one well‐trained technician. Results of semen analysis obtained from two branded CASA systems were then compared. The accuracy of counting results of CASA systems was evaluated using latex bead solutions with known concentrations of (35 ± 5) × 106 ml−1 and (18 ± 2.5) × 106 ml−1. There were significant differences in all parameters (P < 0.01) except for LIN and WOB. The counting results of CFT‐9200 were close to the standard solutions [(38.86 ± 3.79) × 106 ml−1 and (19.03 ± 1.99) × 106 ml−1], while those of WLJY‐9000 were underestimated [(28.53 ± 2.06) × 106 ml−1 and (14.62 ± 0.95) × 106 ml−1]. But the coefficient of variation of WLJY‐9000 was lower than that of CFT‐9200 (7.22%, 6.50% vs. 9.82%, 10.46%). It is concluded that factors such as parameter settings and evaluation algorithms could significantly affect the results obtained from these two branded CASA systems. Great attention should also be paid to the quality control in semen analysis with CASA.
Functional Aspects of Recollective Experience in Face Recognition

This article describes two experiments on awareness in recognition memory for novel faces. Two kinds of awareness, recollective experience and feelings of familiarity in the absence of recollective experience, were measured by "remember" and "know" responses. Experiment 1 showed that "remember" but not "know" responses were reduced by divided attention at study. Experiment 2 showed that massed versus spaced repetition of faces in the study list had opposite effects on "remember" and "know" responses. Massed repetition increased "know" responses and reduced "remember" responses. Spaced repetition increased "remember" responses and reduced "know" responses. The results of both experiments replicate previous findings from the verbal domain in the domain of face recognition, and hence they increase the ecological validity of this experimental approach to memory and awareness and the generality of its database. These findings are discussed from a rehearsal perspective on factors influencing the two states of awareness and in relation to the alternative "process dissociation" procedure.
Renal lesions associated with autoimmune pancreatitis: CT findings

Background: Autoimmune pancreatitis (AIP) is a chronic inflammatory condition characterized by IgG4-positive plasma cells. Recent evidence suggests that it is a systemic disease affecting various organs. Tubulointerstitial nephritis has been reported in association with AIP. Purpose: To investigate the incidence and types of renal involvement in patients with AIP. Material and Methods: Eighteen patients with no history of renal disease and a diagnosis of AIP (on the basis of histopathologic findings or a combination of characteristic imaging features, increased serum IgG4 levels, and response to steroid treatment) were included. All patients underwent computed tomography (CT) imaging and follow-up ranged from 6 months to 2 years. CT images were reviewed for the presence of renal lesions. Results: Seven patients had renal involvement (38.8%). None of the lesions was visible on non-contrast-enhanced CT scan. Parenchymal lesions appeared as multiple nodules showing decreased enhancement (four cases). Pyelonephritis, lymphoma, and metastases were considered in the differential diagnosis. An ill-defined low-attenuation mass-like lesion was found in one patient, while diffuse thickening of the renal pelvis wall was evident in the last two cases. Renal lesions regressed in all patients after steroid treatment, the larger one leaving a fibrous cortical scar. Conclusion: Different types of renal lesions in patients with AIP are relatively common, appearing as multiple nodules with decreased enhancement. These findings support the proposed concept of an IgG4-related systemic disease. Autoimmune disease should be suspected in cases of renal involvement in association with pancreatic focal or diffuse enlargement.
Effect of quercetin on the toxicokinetics of ochratoxin A in rats

Previous studies indicate that the intestinal absorption of the nephrotoxic mycotoxin ochratoxin A (OTA) occurs mainly through passive diffusion of the undissociated form. However, several in vitro studies have shown that OTA is partly re-secreted into the intestinal lumen by the multi-drug resistance associated protein (MRP2) and breast cancer resistance protein (BRCP). In vitro studies using Caco-2 cells have shown that some polyphenols (quercetin, genistein, resveratrol) may impair OTA efflux through competitive inhibition of MRP2, possibly resulting in an increased systemic availability of OTA. Among the tested polyphenols, quercetin showed the highest potential as efflux pump inhibitor; therefore, the aim of the present in vivo study was to investigate possible effects of quercetin on the toxicokinetics of OTA in rats. Eighteen growing male F344 Fisher rats (body weight: 200 g) were allocated to two dietary treatments consisting of (1) a commercial, flavonoid-free balanced diet containing 10 mg OTA/kg derived from inoculated wheat and (2) the same diet supplemented with 100 mg quercetin/kg. The animals were fed restrictively (~0.7 of ad libitum intake, 13 g/d) to avoid differences in OTA intake. Animals were kept in metabolism cages to facilitate total urine and faeces collection. After 6 days on trial, rats were euthanised and blood, liver, kidney, muscle and brain samples were taken from each animal. Faeces, urine and tissue samples were analysed for OTA and its main metabolite ochratoxin α by high-performance liquid chromatography using fluorescence detection. Quercetin supplementation had no effect (P > 0.05) on feed consumption, OTA-intake, water intake and body weight gain. Faecal and urinary excretion of OTA and ochratoxin α and concentrations of OTA in all tissues were not affected by quercetin supplementation. Based on the total excretion and tissue concentrations of OTA, it is concluded that the polyphenol quercetin has no impact on the toxicokinetics of OTA in vivo.
On the Sum-Rate of Multiuser MIMO Uplink Channels with Jointly-Correlated Rician Fading

In this paper, we study the capacity-achieving input covariance matrices for the multiuser multiple-input multiple-output (MIMO) uplink channel under jointly-correlated Rician fading when perfect channel state information (CSI) is known at the receiver, or CSIR while only statistical CSI at the transmitter, or CSIT, is available. The jointly-correlated MIMO channel (or the Weichselberger model) accounts for the correlation at two link ends and is shown to be highly accurate to model real channels. Classically, numerical techniques together with Monte-Carlo methods (named stochastic programming) are used to resolve the problem concerned but at a high computational cost. To tackle this, we derive the asymptotic sum-rate of the multiuser (MU) MIMO uplink channel in the large-system regime where the numbers of antennas at the transmitters and the receiver go to infinity with constant ratios. Several insights are gained from the analytic asymptotic sum-rate expression, based on which an efficient optimization algorithm is further proposed to obtain the capacity-achieving input covariance matrices. Simulation results demonstrate that even for a moderate number of antennas at each link, the new approach provides indistinguishable results as those obtained by the complex stochastic programming approach.
Lectin binding sites on human sperm and spermatogenic cells

Testes of sexually mature men were studied histochemically with 20 fluorescein isothiocyanate‐labeled lectins. Based on their pattern of reactivity with intratesticular spermatogenic cells, lectins were divided into five groups: (1) lectins reacting with all spermatogenic cells (Suc. ConA, WGA, LCA, PHA‐E, PHAL, STA, MPA, and RCA‐II); (2) lectin reacting with spermatocytes, spermatids, and spermatozoa, but not with spermatogonia (RCA‐I); (3) lectins reacting with spermatids and spermatozoa only (BPA, PNA, SBA, and VVA); (4) lectins reacting only with spermatozoa (HPA, GSA‐I, UEA‐II, and GSA‐II); and (5) lectins with no distinct staining of spermatogenic cells (DBA, LBA, and UEA‐I). All lectins from groups 1–4 were reactive with ejaculated spermatozoa. On the basis of the staining patterns of the head region of ejaculated spermatozoa, four lectin reactivity groups were defined: (1) lectins reacting with the plasma membrane of the whole head (BPA, WGA, LCA, STA, RCA‐II, PHA‐E, PHA‐L, RCA‐I, UEA‐II, and GSA‐II); (2) lectin reacting with the acrosomal cap and postacrosomal region of the plasma membrane (Suc. ConA); (3) lectin reacting with the acrosomal cap region of the plasma membrane (PNA); and (4) lectins reacting with the midregion of the sperm head in a bandlike manner (HPA, VVA, SBA, GSA‐I, and MPA). These data provide a map of lectin binding sites on human testicular spermatogenic cells and ejaculated spermatozoa and show that the distribution of glycoconjugate domains of spermatogenic cell changes during differentiation and maturation.
Novel investigational drugs active as single agents in multiple myeloma

ABSTRACT Introduction: Multiple myeloma (MM) is a hematologic malignancy characterized by proliferation of malignant plasma cells. patient outcome has improved markedly over the last decades due to the introduction of novel therapeutic agents such as bortezomib, thalidomide and lenalidomide. However, MM still remains largely incurable and patients eventually become refractory to available treatments. To address this unmet medical need, a variety of new molecules are currently being developed in preclinical models and/or are being investigated in clinical studies. Areas covered: We summarized available data on new investigational drugs showing anti-myeloma single-agent activity and that might have a role in the future therapeutic armamentarium against MM. Besides their single-agent activity, the synergic potential of these new agents with the currently approved drugs will be pivotal in their integration into consolidated MM backbone therapies. The drugs discussed include alkylators, new proteasome inhibitors, novel anti-CD38 monoclonal antibodies, Bcl-2 inhibitors, Cyclin-Dependent-Kinase inhibitor, Kinesin-spindle protein inhibitors, MEK1/2 inhibitors, AKT inhibitors and PIM-Kinase inhibitors. Expert opinion: Isatuximab, oprozomib, melflufen, venetoclax and filanesib seem to be the most promising agents with single agent activity. Nevertheless, lack of clinical activity as single agent does not imply clinical inefficacy in combination treatments.
Serum vitamins in adult patients with short bowel syndrome receiving intermittent parenteral nutrition.

BACKGROUND Short bowel syndrome (SBS) occurs after massive intestinal resection, and parenteral nutrition (PN) therapy may be necessary even after a period of adaptation. The purpose of this study was to determine the vitamin status in adults with SBS receiving intermittent PN. METHODS The study was conducted on hospitalized adults with SBS who were receiving intermittent PN therapy (n = 8). Nine healthy volunteers, paired by age and sex, served as controls. Food ingestion, anthropometry, plasma folic acid, and vitamins B(12), C, A, D, E, and K were evaluated. RESULTS The levels of vitamins A, D, and B(12) in both groups were similar. SBS patients presented higher values of folic acid (21.3 ± 4.4 vs 14.4 ± 5.2, P = .01) and lower values of vitamin C (0.9 ± 0.4 vs 1.2 ± 0.3 mg/dL, P = .03), α-tocopherol (16.3 ± 3.4 vs 24.1 ± 2.7 µmol/L, P < .001), and phylloquinone (0.6 ± 0.2 vs 1.0 ± 0.5 nmol/L, P < .03). Eight-seven percent of patients had vitamin D deficiency, and all patients presented with serum vitamin E levels below reference values. CONCLUSIONS Despite all efforts to offer all the nutrients mentioned above, SBS patients had lower serum levels of vitamins C, E, and K, similar to those observed in patients on home PN. These findings suggest that the administered vitamins were not sufficient for the intermittent PN scheme and that individual adjustments are needed depending on the patient's vitamin status.