Miracle-dz/UniFAR-FTUs huggingface dataset:
Mycobacterium Tuberculosis PPE Family Protein Rv1808 Manipulates Cytokines Profile via Co-Activation of MAPK and NF-κB Signaling Pathways

Background/Aims: Mycobacterium tuberculosis is an extremely successful intracellular pathogen armed with multiple tactics to subvert host immunity. PPE (Pro-Pro-Glu) family exclusively distributed in mycobacteria might be responsible for the virulence and pathogenicity of M.tuberculosis. The up-regulation of Rv1808 (PPE32) in many conditions prompted us to define its role in host innate immune response. Methods: The Rv1808 encoding gene was expressed in nonpathogenic fast growing Mycobacterium smegmatis, mycobacteria- Escherichia coli shuttle plasmid pNITmyc served as control. RT-PCR and ELISA were used to detect the transcription and translation of host cytokines in culture supernatant from macrophage incubated with purified Rv1808 protein. Pharmacological inhibitors were applied to confirm the specificity of the effector interfering of host signaling. Results: Recombinant Ms_Rv1808 survived better than Ms_pNITmyc within macrophage, accompanied by slightly higher host cell death. Rv1808 protein is associated with the cell wall and exposed on the cell surface. Physical binding of Rv1808 to TLR2 resulted in increase in the secretion of anti-inflammatory cytokine interleukin-10 (IL-10) and pro-inflammatory cytokines tumor necrosis factor (TNF-a) and interleukin-6 (IL-6) possibly via co-activation of NF-κB and MAPK (p38MAPK, JNK and ERK) signalling. Conclusion: Cell wall associated Rv1808 protein manipulated the host cytokines via MAPK and NF-κB signaling pathways.
PUB1 is a major nuclear and cytoplasmic polyadenylated RNA-binding protein in Saccharomyces cerevisiae

Proteins that directly associate with nuclear polyadenylated RNAs, or heterogeneous nuclear RNA-binding proteins (hnRNPs), and those that associate with cytoplasmic mRNAs, or mRNA-binding proteins (mRNPs), play important roles in regulating gene expression at the posttranscriptional level. Previous work with a variety of eukaryotic cells has demonstrated that hnRNPs are localized predominantly within the nucleus whereas mRNPs are cytoplasmic. While studying proteins associated with polyadenylated RNAs in Saccharomyces cerevisiae, we discovered an abundant polyuridylate-binding protein, PUB1, which appears to be both an hnRNP and an mRNP. PUB1 and PAB1, the polyadenylate tail-binding protein, are the two major proteins cross-linked by UV light to polyadenylated RNAs in vivo. The deduced primary structure of PUB1 indicates that it is a member of the ribonucleoprotein consensus sequence family of RNA-binding proteins and is structurally related to the human hnRNP M proteins. Even though the PUB1 protein is a major cellular polyadenylated RNA-binding protein, it is nonessential for cell growth. Indirect cellular immunofluorescence combined with digital image processing allowed a detailed comparison of the intracellular distributions of PUB1 and PAB1. While PAB1 is predominantly, and relatively uniformly, distributed within the cytoplasm, PUB1 is localized in a nonuniform pattern throughout both the nucleus and the cytoplasm. The cytoplasmic distribution of PUB1 is considerably more discontinuous than that of PAB1. Furthermore, sucrose gradient sedimentation analysis demonstrates that PAB1 cofractionates with polyribosomes whereas PUB1 does not. These results suggest that PUB1 is both an hnRNP and an mRNP and that it may be stably bound to a translationally inactive subpopulation of mRNAs within the cytoplasm.
The Interaction between Bank Solvency and Funding Costs: A Crucial Effect in Stress Tests

This paper presents new evidence on the empirical relationship between bank solvency and funding costs. Building on a newly constructed data set drawing on the supervisory data of 54 large banks from six advanced countries over 2004&#8211;2013, we use a simultaneous equation approach with panel data to estimate the contemporaneous interaction between solvency and funding costs. Our results and test&#160;statistics show that these two are (a) determined simultaneously and (b) more pronounced than suggested by the existing empirical literature. A 100&#8208;bps increase in regulatory capital ratios is associated with a decrease of bank funding costs of about 113 bps. A 100&#8208;bps increase in funding costs reduces regulatory capital buffers by 48 bps. Applying our estimation results to the 2014 EU&#8208;wide stress test reveals that neglecting the solvency&#8208;funding cost nexus leads to the systematical&#160;and significant underestimation of the impact of shocks on bank capital ratios.
Lacrimal gland innervation is not altered with the onset and progression of disease in a murine model of Sjögren's syndrome.

The lacrimal glands of patients with Sjögren's syndrome develop extensive lymphocytic infiltration, but also contain a large number of seemingly healthy looking acinar and ductal cells. Despite this, the secretory function of this tissue is impaired, leading to aqueous tear-deficient dry eye. This raises the possibility that there is a defect in the neural innervation of the remaining portion of the lacrimal gland. To test for this possibility, we used antibodies specific to various markers of the parasympathetic, sympathetic, and sensory nerves and performed immunohistochemical analyses of lacrimal glands from a murine model of Sjögren's syndrome, the MRL/Mp-Fas-lpr/lpr (MRL/lpr) and the control mice MRL/Mp-+/+ (MRL/+). Our results show that the MRL/lpr, but not the MRL/+, lacrimal glands become infiltrated with lymphocytes starting at 8 weeks of age which worsens by 12 and 18 weeks. The density and the pattern of parasympathetic, sympathetic, and sensory innervation of the noninflamed acinar tissue of MRL/lpr lacrimal glands, at 4, 8, 12, and 18 weeks, is indistinguishable from that of age-matched control MRL/+ lacrimal glands. We conclude that the loss of the secretory function in Sjögren's syndrome lacrimal glands is not due to a loss or decrease of its innervation.
Long-Term Follow-Up of Renal Transplantation in Children: A Dutch Cohort Study

Background. Few data exist on long-term morbidity, overall survival, and graft survival of pediatric renal transplantation. Methods. The authors performed a long-term cohort study in all Dutch patients, born before 1979, with onset of end-stage renal disease (ESRD) between 1972 and 1992 at age 0 to 15 years. Data on graft survival and determinants of outcome were obtained by reviewing all medical charts. The health status was assessed by cross-sectional examination of surviving patients. Results. Three hundred ninety-seven transplantations were performed in 231 of all 249 patients, of whom 25 died with a functioning graft. Cardiovascular disease was the most prominent cause of death. Graft survival estimates for all transplantations were 59.2%, 45.3%, 35.4%, and 30.3% at 5, 10, 15, and 20 years, respectively. In comparison with azathioprine, cyclosporine as the immunosuppressant was associated with increased graft survival in retransplantations but not in first transplantations. Cross-sectional examination was performed on 110 patients. In 44 patients, the most recent graft survival exceeded 15 years. Co-morbidity was found in 40% of all patients; motor, hearing, or visual disabilities were found in 19%. Bone disease, headaches, itching, and tremors were the most reported disabling problems. Cyclosporine use was associated with hypertension and a history of epilepsy. Compared with all age-matched Dutch inhabitants, the educational attainment was low, and unemployment and parental dependency were high. Conclusions. The authors’ results emphasize the need for reducing cardiovascular disease and metabolic bone disease in pediatric ESRD, a policy toward less toxic antirejection therapy, a more strict treatment of hypertension, and more attention for schooling and social development toward independence.
An empirical analysis of the effect of key policy rate changes on the unbiasedness hypothesis

Interest rate parity is one of the most important theory in international finance which determines the relationship between the exchange rate and interest rates of two countries. However, there are many empirical findings showing that interest rate parity condition does not hold. A phenomenon called the forward premium puzzle commonly exists in the currency markets. It refers to the situation that the high-interest country’s currency tends to appreciate with respect to the low-interest country’s currency which contradicts the interest rate parity theory. Intrigued by this fascinating puzzle, we want to explore the causes of this puzzle, especially how the central bank announcements might affect the foreign exchange market. This thesis focuses on uncovering whether a country's central bank announcements of changes in the key policy rate would affect how the unbiasedness hypothesis holds. Using daily observations of spot exchange rates and 1-month and 3-month forward exchange rates enables us to remove the days of change from the dataset. This thesis distinguishes itself from the literature by its research question and methodology. Empirical literature usually find evidence against the unbiasedness hypothesis. This thesis on the other hand, finds some evidence supporting that unbiasedness hypothesis holds for the six currency pairs: CAD/USD, EUR/USD, JPY/USD, NOK/USD, CHF/USD and GBP/USD in the period 01/01/2002 to 19/10/2018. In order to solve econometric issues like serial correlation incurred by using daily observations of regression variables, necessary adjustments are made to correct for them. By comparing the regression results of different models, we can see the effect of removing days of key policy rate changes on the unbiasedness hypothesis. The main results from the empirical analysis show that removing the days surrounding changes in the key policy rate does not affect the regression results notably, except in the case of removing seven days for the CHF/USD.
Apoptosis and Autophagy After Mitochondrial or Endoplasmic Reticulum Photodamage †

Photodynamic therapy (PDT) can cause lethal photodamage by both direct and indirect mechanisms. Direct modes of cell death relate to nonspecific necrosis and the initiation of signaling pathways that elicit apoptosis, autophagy or both. In this report, effects of low‐dose and high‐dose PDT are explored, comparing sensitizers that localize in the endoplasmic reticulum (the porphycene termed CPO) or mitochondria (mesochlorin). To explore the role of autophagy, two cell lines were examined—the murine L1210 leukemia and an Atg7 knockdown derivative of L1210. The Atg7 gene is central to the process of autophagy. High‐dose PDT with either sensitizer resulted in a substantial loss of the Bcl‐2 protein. As Bcl‐2 regulates both apoptosis and autophagy, loss of this protein can lead to initiation of either or both processes. Low‐dose PDT with either sensitizer resulted in the initiation of apoptosis in the L1210/Atg7− cell line and a 20% loss of viability. In contrast, the same PDT dose led to the rapid appearance of autophagic cells in the L1210 line, less apoptosis and only a 5% loss of viability. These results are consistent with autophagy serving as a pro‐survival response via the recycling of damaged organelles. At a higher PDT dose more apoptosis was again seen in the L1210/Atg7‐ line, but both cell lines exhibited comparable cytotoxicity in colony formation assays. We conclude that autophagy offers protection from the phototoxic effects of low‐dose PDT, but can serve as an alternate death mode when the PDT dose is increased.
Best oral empirical treatment for pyelonephritis in children: Do we need to differentiate between age and gender?

Abstract Background: Pyelonephritis is a common infection in childhood and may cause renal scarring. The aim was to determine an effective oral antibiotic treatment of first time pyelonephritis in children. Methods: The study is a retrospective analysis of positive urine cultures collected at a Danish paediatric department from 2010–2013. Urine samples from 378 children aged 0–15.9 years, without renal anomalies and treated for first time pyelonephritis, were included. The urine pathogens and antimicrobial susceptibilities were analysed. Results: The most common aetiologic agents found were Escherichia coli (85%), Klebsiella species and other Enterobacteriaecea (9.7%) and Enterococcus species (5.3%). Escherichia coli was significantly more common in girls than in boys (90% vs 74%, p < 0.001) and in children older than 6 months (89% vs 77%, p < 0.001). Children younger than 6 months had a higher prevalence of other Gram-negative rods (16% vs 7%, p < 0.001). These differences may be due to boys representing 63% of patients in the youngest age group compared to 16% of older children (p < 0.001). For all urine isolates, piv-mecillinam and amoxicillin-clavulanate had the lowest resistance rates of 6.9% and 7.2%, respectively, and 6% for both antimicrobials in patients older than 6 months. Uropathogens from boys above 6 months of age were more resistant to piv-mecillinam compared to girls (25% vs 2.4%, p < 0.001). Conclusion: This study recommends piv-mecillinam or amoxicillin-clavulanate as empirical treatment of first time pyelonephritis in Danish children from 6 months of age. Age and gender of patients should be taken into consideration when initiating empirical treatment.
Validation of the RTOG recursive partitioning classification for head and neck tumors

We previously demonstrated that a mathematical technique called recursive partitioning analysis (RPA), when applied to the Radiation Therapy Oncology Group Head and Neck Cancer database, created rules that formed subgroups (“classes”) having unique outcomes. We sought to learn if the application of RPA‐derived rules to a new head and neck database would create classes that were similarly associated with outcome and thereby validate this technique.
Sudden hearing loss associated with tacrolimus after pediatric renal transplant.

OBJECTIVES Hearing impairment is a frequent problem that can easily influence the quality of life for the individual. It may affect one's social and academic life. Knowledge regarding hearing impairment after renal transplant is sparse. It has been suggested that renal transplant improves hearing function. Potential ototoxic side effects may be related to immunosuppression with calcineurin inhibitors. In pediatric renal transplanted patients, we do not have enough information about this subject. We report 2 cases that developed sudden hearing loss after a renal transplant that was associated with high serum levels of tacrolimus. CASE REPORTS Two renal transplanted children (a 15-year-old boy and a 17-year-old girl), in the fourth year of their follow-up after transplant, developed symptomatic bilateral sudden hearing loss. There was a marked hearing impairment for the higher frequencies between 4000 and 8000 Hz in pure-tone audiometry evaluation. Also, a decrease of speech understanding was found, but the patients were not conscious of this problem. Hearing loss in these patients was not associated with any known risk factors such as chronic renal disease, ototoxic drugs, or acoustic trauma. Sudden hearing loss occurred under high serum levels of tacrolimus, and after dosage correction of tacrolimus pure-tone audiometry ruled out hearing loss progression for each patient. CONCLUSIONS Awareness of this potential complication of tacrolimus may be helpful for early recognition and treatment.
The relation between genotype and phenotype in cystic fibrosis--analysis of the most common mutation (delta F508).

BACKGROUND AND METHODS Both the clinical manifestations of cystic fibrosis and the genotypes of patients are heterogeneous, but the associations between the two are not known. We therefore studied blood samples from 293 patients with cystic fibrosis for the presence of the most common disease-causing mutation (delta F508) on chromosome 7 and compared the results with the clinical manifestations of the disease. RESULTS The prevalence of the delta F508 allele in the cohort was 71 percent; 52 percent of the patients were homozygous for the mutation, 40 percent were heterozygous, and 8 percent had other, undefined mutations. The patients who were homozygous for the mutation had received a diagnosis of cystic fibrosis at an earlier age and had a greater frequency of pancreatic insufficiency; pancreatic insufficiency was present in 99 percent of the homozygous patients, but in 72 percent of the heterozygous patients and only 36 percent of the patients with other genotypes. The patients with pancreatic insufficiency in all three genotype groups had similar clinical characteristics, reflected by an early age at diagnosis, similar sweat chloride values at diagnosis, similar severity of pulmonary disease, and similar percentiles for weight. In contrast, the patients in the heterozygous-genotype and other-genotype groups who did not have pancreatic insufficiency were older and had milder disease. They had lower sweat chloride values at diagnosis, normal nutritional status, and better pulmonary function after adjustment for age. CONCLUSIONS The variable clinical course in patients with cystic fibrosis can be attributed at least in part to specific genotypes at the locus of the cystic fibrosis gene.
Exploring the Relationship Between Housing Downturns and Partisan Elections: Neighborhood-Level Evidence from Maricopa County, Arizona

An understudied outcome of foreclosure crises is how their aftershocks affect partisan elections. Two hypotheses are that partisan shifts may occur in neighborhoods with concentrated foreclosures because of (1) declines in turnout among liberal leaning voters or (2) swells of anti-incumbency among all voters. This research explores these hypotheses in Maricopa County, Arizona, by using econometric modeling to uncover associations among neighborhood foreclosures, voter turnout, and changes in the Republican vote share between the 2006 and the 2010 Arizona gubernatorial and U.S. Senate elections. Our results show evidence of (1) anti-incumbent voting behavior and more liberal shifts among neighborhoods harder hit by foreclosures and (2) conservative shifts in neighborhoods experiencing African-American and Latinx population growth. These findings are suggestive of a link between neighborhood housing market distress and neighborhood partisan shifts, which in aggregate may shape state and national policymaking and future neighborhood conditions.
Qualitative analysis of how patients decide that they want risk-reducing mastectomy, and the implications for surgeons in responding to emotionally-motivated patient requests

Objective Contemporary approaches to medical decision-making advise that clinicians should respect patients’ decisions. However, patients’ decisions are often shaped by heuristics, such as being guided by emotion, rather than by objective risk and benefit. Risk-reducing mastectomy (RRM) decisions focus this dilemma sharply. RRM reduces breast cancer (BC) risk, but is invasive and can have iatrogenic consequences. Previous evidence suggests that emotion guides patients’ decision-making about RRM. We interviewed patients to better understand how they made decisions about RRM, using findings to consider how clinicians could ethically respond to their decisions. Methods Qualitative face-to-face interviews with 34 patients listed for RRM surgery and two who had decided against RRM. Results Patients generally did not use objective risk estimates or, indeed, consider risks and benefits of RRM. Instead emotions guided their decisions: they chose RRM because they feared BC and wanted to do ‘all they could’ to prevent it. Most therefore perceived RRM to be the ‘obvious’ option and made the decision easily. However, many recounted extensive post-decisional deliberation, generally directed towards justifying the original decision. A few patients deliberated before the decision because fears of surgery counterbalanced those of BC. Conclusion Patients seeking RRM were motivated by fear of BC, and the need to avoid potential regret for not doing all they could to prevent it. We suggest that choices such as that for RRM, which are made emotionally, can be respected as autonomous decisions, provided patients have considered risks and benefits. Drawing on psychological theory about how people do make decisions, as well as normative views of how they should, we propose that practitioners can guide consideration of risks and benefits even, where necessary, after patients have opted for surgery. This model of practice could be extended to other medical decisions that are influenced by patients’ emotions.
Influence of the period between onset of IgA nephropathy and medical intervention on renal prognosis

Background. The clinical course of IgA nephropathy (IgAN) is highly variable. In order to verify the necessity of early medical intervention in IgAN patients, the present study investigated the clinical impact of the duration between disease onset and first medical intervention on renal prognosis. Methods. We enrolled 57 patients diagnosed with IgAN on the basis of biopsy performed at our hospital. The medical records of these patients were traceable to the last 10 years, during which they had not undergone dialysis or treatment at any other hospital. On the basis of histological assessment of prognosis, these patients were classified according to the Japanese guidelines into the following groups: groups I, good prognosis; group II, relatively good prognosis; group III, relatively poor prognosis; and group IV, poor prognosis. We investigated the correlation between the duration of disease onset and the first consultation with a nephrologist and the rate of increase in serum creatinine over a 10 year period. In addition to the abovementioned patients, 6 patients with IgAN who underwent dialysis within the 10 years were separately evaluated. These patients came under the poor prognosis category; i.e., they belonged to group IV. Results. The duration between disease onset and medical consultation was significantly longer in younger patients or in those with asymptomatic proteinuria at onset when compared to that in older patients or in those with other urinary abnormalities. There was a significant correla tion between this duration and renal prognosis, particularly in group III patients. Although the duration between onset and consultation was not correlated to the serum creatinine level at the time of first medical intervention, urinary protein level among group IV patients at the time of first consultation was significantly higher in patients with dialysis than that in those without dialysis. Conclusions. Early medical intervention may lead to a better renal prognosis, particularly in group III patients, who form a major portion of the IgAN population. It therefore appears that early diagnostic screening and subsequent intervention are important for a good prognosis in IgAN patients.