Miracle-dz/UniFAR-FTUs huggingface dataset:
Paternal transmission of fragile X syndrome

We present a family in which a fragile X mosaic male, who carries both premutation and full mutation alleles in his peripheral blood leukocytes, has a daughter with both premutation and partially methylated full mutation alleles and a significant developmental disability. To our knowledge, this is the first report of such an occurrence and it challenges current thinking about the expansion and transmission of unstable FMR1 alleles from men to their daughters. It is currently accepted that neither males with premutations nor full mutations are at risk for having daughters with full mutations and fragile X syndrome. The sperm cells of full mutation males are thought to carry only premutation alleles. These alleles, when transmitted through a male, regardless of his cognitive status, are thought to be unable to expand to full mutations in the next generation. In effect, the expansion from premutation to full mutation has only been observed through female meioses. The sperm cells in the father in this family have been shown to contain only alleles in the premutation range. Since his daughter has both premutation and full mutation alleles the expansion to full mutation in this case must have occurred postzygotically. © 2004 Wiley‐Liss, Inc.
Air1 Zinc Knuckles 4 and 5 and a Conserved IWRXY Motif Are Critical for the Function and Integrity of the Trf4/5-Air1/2-Mtr4 Polyadenylation (TRAMP) RNA Quality Control Complex*

In Saccharomyces cerevisiae, non-coding RNAs, including cryptic unstable transcripts (CUTs), are subject to degradation by the exosome. The Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) complex in S. cerevisiae is a nuclear exosome cofactor that recruits the exosome to degrade RNAs. Trf4/5 are poly(A) polymerases, Mtr4 is an RNA helicase, and Air1/2 are putative RNA-binding proteins that contain five CCHC zinc knuckles (ZnKs). One central question is how the TRAMP complex, especially the Air1/2 protein, recognizes its RNA substrates. To characterize the function of the Air1/2 protein, we used random mutagenesis of the AIR1/2 gene to identify residues critical for Air protein function. We identified air1-C178R and air2-C167R alleles encoding air1/2 mutant proteins with a substitution in the second cysteine of ZnK5. Mutagenesis of the second cysteine in AIR1/2 ZnK1–5 reveals that Air1/2 ZnK4 and -5 are critical for Air protein function in vivo. In addition, we find that the level of CUT, NEL025c, in air1 ZnK1–5 mutants is stabilized, particularly in air1 ZnK4, suggesting a role for Air1 ZnK4 in the degradation of CUTs. We also find that Air1/2 ZnK4 and -5 are critical for Trf4 interaction and that the Air1-Trf4 interaction and Air1 level are critical for TRAMP complex integrity. We identify a conserved IWRXY motif in the Air1 ZnK4-5 linker that is important for Trf4 interaction. We also find that hZCCHC7, a putative human orthologue of Air1 that contains the IWRXY motif, localizes to the nucleolus in human cells and interacts with both mammalian Trf4 orthologues, PAPD5 and PAPD7 (PAP-associated domain containing 5 and 7), suggesting that hZCCHC7 is the Air component of a human TRAMP complex.
Targeting screening mammography according to life expectancy among women undergoing dialysis.

BACKGROUND Screening guidelines recommend that mammography be targeted to women likely to live longer than 5 years. Because women undergoing dialysis have a reduced but variable life expectancy, their appropriate use of screening is controversial. Therefore, we conducted this study to describe national mammography rates among women undergoing dialysis with differing prognostic factors and to determine whether screening is targeted to healthier women who live longer. METHODS Using the US Renal Data System, we identified 17,090 women aged 50 years or older who started dialysis in 1997. We tracked women for 5 years to ascertain their use of screening mammography or death. RESULTS The 5-year survival rate was 25%. The biennial screening mammography rate was 25%, ranging from 12% for women aged 80 years or older to 69% for women who were ever on the transplant list. Women who were screened in the past year had a lower death rate than those who were not (hazards ratio, 0.55; 95% confidence interval, 0.51-0.59). Yet, 2198 women (13%) who died within 5 years underwent screening, and 2004 women (12%) who lived more than 5 years while receiving dialysis did not undergo screening. CONCLUSIONS Screening mammography rates are appropriately low among women undergoing dialysis because the 5-year survival rate is low. Screening is being targeted to women who are healthier and live longer. However, targeting could be improved by increasing screening in the few women undergoing dialysis with substantial life expectancies while decreasing screening in most women undergoing dialysis who live less than 5 years.
Coencapsulation of CpG Oligodeoxynucleotides with Recombinant Leishmania major Stress-Inducible Protein 1 in Liposome Enhances Immune Response and Protection against Leishmaniasis in Immunized BALB/c Mice

ABSTRACT CpG oligodeoxynucleotides (CpG ODN) have been shown to have potent adjuvant activity for a wide range of antigens. The purpose of this study was to determine the potential benefit of using liposomes as a delivery vehicle to enhance the adjuvant activity of CpG ODN with Leishmania major stress-inducible protein 1 (LmSTI1) antigen in induction of the Th1 response in a murine model of leishmaniasis. BALB/c mice were immunized subcutaneously three times in 3-week intervals with liposomal recombinant LmSTI1 (Lip-rLmSTI1), rLmSTI1 coencapsulated with CpG ODN in a liposome (Lip-rLmSTI1-CpG ODN), rLmSTI1 plus CpG ODN in phosphate-buffered saline (PBS), rLmSTI1 plus non-CpG ODN in PBS, rLmSTI1 in PBS, empty liposome, or PBS. The intensity of infection induced by L. major promastigote challenge was measured by footpad swelling. A significant (P < 0.001) inhibition of infection in mice immunized with Lip-rLmSTI1-CpG ODN was shown compared to the other groups, and no parasite was detected in the spleens of this group 14 weeks after challenge. The highest immunoglobulin G2a (IgG2a) titer and the highest IgG2a/IgG1 ratio were also shown in the sera of mice immunized with Lip-rLmSTI1-CpG ODN before and 14 weeks after challenge. The results indicated the superiority of CpG ODN in its liposomal form over its soluble form to induce the Th1 response when used in association with rLmSTI1 antigen. It seems that using a liposome delivery system carrying CpG ODN as an adjuvant coencapsulated with Leishmania antigen plays an important role in vaccine development strategies against leishmaniasis.
Phytochelatins in Cadmium-Sensitive and Cadmium-Tolerant Silene vulgaris (Chain Length Distribution and Sulfide Incorporation)

In response to a range of Cd concentrations, the root tips of Cd-tolerant plants of Silene vulgaris exhibit a lower rate of PC production accompanied by a lower rate of longer chain PC synthesis than those of Cd-sensitive plants. At the same Cd exposure level, stable PC-Cd complexes are more rapidly formed in the roots of Cd-sensitive plants than in those of tolerant plants. At an equal PC concentration in the roots, the PC composition and the amount of sulfide incorporated per unit of PC-thiol is the same in both populations. Although these compounds might play some role in mechanisms that contribute to Cd detoxification, the ability to produce these compounds in greater amounts is not, itself, the mechanism that produces increased Cd tolerance in tolerant S. vulgaris plants.
A Metabolomic Approach to Study Major Metabolite Changes during Acclimation to Limiting CO2 in Chlamydomonas reinhardtii1[W]

Using a gas chromatography-mass spectrometry-time of flight technique, we determined major metabolite changes during induction of the carbon-concentrating mechanism in the unicellular green alga Chlamydomonas reinhardtii. In total, 128 metabolites with significant differences between high- and low-CO2-grown cells were detected, of which 82 were wholly or partially identified, including amino acids, lipids, and carbohydrates. In a 24-h time course experiment, we show that the amino acids serine and phenylalanine increase transiently while aspartate and glutamate decrease after transfer to low CO2. The biggest differences were typically observed 3 h after transfer to low-CO2 conditions. Therefore, we made a careful metabolomic examination at the 3-h time point, comparing low-CO2 treatment to high-CO2 control. Five metabolites involved in photorespiration, 11 amino acids, and one lipid were increased, while six amino acids and, interestingly, 21 lipids were significantly lower. Our conclusion is that the metabolic pattern during early induction of the carbon-concentrating mechanism fit a model where photorespiration is increasing.
Internal and External Determinants of Economic Growth: A closer look at Pakistan’s Economy

This study aims to investigate the impact of internal and external determinants of economic growth on the economic growth of Pakistan. Major internal determinants include stock of physical capital and developmental expenditures, while external determinants include trade openness and real effective exchange rate. In doing so, study utilizes the annual time series data from 1972 to 2011. Advanced Autoregressive Distributed Lag model (ARDL) approach has been employed for co-integration and error correction model (ECM) for short-run results. Empirical investigations indicate that developmental expenditures, physical capital and trade openness are positively correlated with economic growth in long run, while real effective exchange rate negatively and significantly affect economic growth in long run in case of Pakistan.
Effect of dietary protein content and tryptophan supplementation on dominance aggression, territorial aggression, and hyperactivity in dogs.

OBJECTIVE To evaluate the effect of high- and low-protein diets with or without tryptophan supplementation on behavior of dogs with dominance aggression, territorial aggression, and hyperactivity. DESIGN Prospective crossover study. ANIMALS 11 dogs with dominance aggression, 11 dogs with territorial aggression, and 11 dogs with hyperactivity. PROCEDURE In each group, 4 diets were fed for 1 weeks each in random order with a transition period of not < 3 days between each diet. Two diets had low protein content (approximately 18%), and 2 diets had high protein content (approximately 30%). Two of the diets (1 low-protein and 1 high-protein) were supplemented with tryptophan. Owners scored their dog's behavior daily by use of customized behavioral score sheets. Mean weekly values of 5 behavioral measures and serum concentrations of serotonin and tryptophan were determined at the end of each dietary period. RESULTS For dominance aggression, behavioral scores were highest in dogs fed unsupplemented high-protein rations. For territorial aggression, [corrected] tryptophan-supplemented low-protein diets were associated with significantly lower behavioral scores than low-protein diets without tryptophan supplements. CONCLUSIONS AND CLINICAL RELEVANCE For dogs with dominance aggression, the addition of tryptophan to high-protein diets or change to a low-protein diet may reduce aggression. For dogs with territorial aggression, tryptophan supplementation of a low-protein diet may be helpful in reducing aggression.
Chemotherapy and Targeted Therapy in Advanced Biliary Tract Carcinoma: A Pooled Analysis of Clinical Trials

Background: In biliary tract cancer, gemcitabine platinum (GP) doublet palliative chemotherapy is the current standard treatment. The aim of this study was to analyze recent trials, even those small and nonrandomized, and identify superior new regimens. Methods: Trials published in English between January 2000 and January 2014 were analyzed, as well as ASCO abstracts from 2010 to 2013. Results: In total, 161 trials comprising 6,337 patients were analyzed. The pooled results of standard therapy GP (no fluoropyrimidine, F, or other drug) were as follows: the median response rate (RR), tumor control rate (TCR), time to tumor progression (TTP) and overall survival (OS) were 25.9 and 63.5%, and 5.3 and 9.5 months, respectively. GFP triplets as well as G-based chemotherapy plus targeted therapy were significantly superior to GP concerning tumor control (TCR, TTP) and OS, with no difference in RR. Conclusion: Triplet combinations of GFP as well as G-based chemotherapy with (predominantly EGFR) targeted therapy are most effective concerning tumor control and survival.
Inherited Thrombophilias Could Influence the Reproductive Outcome in Women with Systemic Lupus Erythematosus

Abstract Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with different reproductive complications in the affected women. Inherited thrombophilias are genetic factors increasing the risk for thromboembolism and recurrent pregnancy loss, but their influence on other reproductive disturbances in SLE patients has not been completely clarified. Two hundred and twenty-three Caucasian women (112 with SLE and 111 controls) were included in the study. Complete reproductive history of all SLE patients was carefully obtained. Genotyping for the FVLeiden, FIIG20210A, and MTHFRC677T polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. No significant differences in the prevalence of the FVLeiden, FIIG20210A, and MTHFRC677T polymorphisms between patients and controls were established. Patients with FVLeiden had fewer pregnancies (0.57 ± 0.98 vs. 2.18 ± 1.58; p = 0.007) than the others, while no significant differences in the reproductive history of FIIG20210A carriers and non-carriers were observed (p >0.05). In the SLE group, 41.67% of women with the MTHFRC677T TT genotype had at least one miscarriage in comparison to only 14.00% of the other female patients (p = 0.030). While the prevalence of the investigated thrombophilias was similar in patients with SLE and healthy women, a substantial influence of the inherited prothrombotic factors on the reproductive history of patients was revealed. The investigations of the FVLeiden and MTHFRC677T polymorphisms in SLE patients could help to identify women at highest risk for reproductive failure and thus, further studies in other ethnic groups would be of strong clinical importance.
Intestinal nematode infections in Romania: an epidemiological study and brief review of literature.

OBJECTIVES The main aim of this report was to present the epidemiological, clinical, laboratory, and therapeutic aspects of a series of patients admitted to a reference hospital from Romania and found to be infected with intestinal nematodes. Additionally, we attempted to overview, for the first time in the international literature, the most relevant data regarding diseases caused by these helminthes in Romania. PATIENTS AND METHODS We have retrospectively investigated the medical records of patients admitted at Victor Babes Hospital of Infectious Diseases in Timisoara (Timis County) who presented infections with intestinal nematode helminthes between 1971 and 2007. RESULTS Forty-two patients were found to be infected with intestinal nematode worms, with the predominance of Enterobius vermicularis (42.8%). The mean age of patients in this series was 23.5 ± 16.4 years. Women were affected in 66.7% of cases and inhabitants of urban regions in 71.4% of cases. Of this series, 57.2% of patients were adults and most of them were people with limited formal education belonging to the low social class. Overall, abdominal pain was most frequently detected (59.5%) and the mean eosinophil count was 8.2% ± 10.9% (range 1%-56%). Piperazine was administered in most of the cases (33.3%). CONCLUSIONS Infections with intestinal nematodes are less frequently diagnosed in hospitalized patients despite that they are quite common in the Romanian population. To further limit their occurrence, public health measures and informative campaigns for the whole population should be implemented.
Tranfusion risk: is “two-step” vaginal delivery a risk for postpartum hemorrhage?

Abstract Objective: In the active management strategy of third stage of labor, the optimal timing for clamping the umbilical cord after birth has been a subject of controversy. We want to evaluate if “two-step” delivery is a risk factor for postpartum hemorrhage (PPH), defined as need of transfusion, comparing to operative delivery, elective caesarean delivery and emergency caesarean delivery. Methods: This is a retrospective cohort study conducted in division of Perinatal Medicine, Policlinico Abano Terme. We evaluated the need of transfusion in all cases of PPH verified in all single deliveries between January 2011 and December 2012. The main outcome measure was blood loss and red blood cell transfusion. Results: We found 17 cases of PPH (0.88%). The distribution of PPH in relation to mode of delivery was 0.71%, 2.46% and 1.98% respectively for two-step vaginal delivery (RR = 0.81 (0.56–1.22)), emergency cesarean section (RR = 2.88 (1.27–7.77)) and operative vaginal delivery (RR = 2.88 (0.59–5.66)). In labor induction there is a stronger relative risk association between PPH and as emergency cesarean delivery (p < 0.05) as operative vaginal delivery (p < 0.05). Conclusion: “Two-step” delivery approach did not increase the risk of PPH with respect to operative delivery, elective caesarean section and emergency caesarean section.
Prevention of type 2 diabetes mellitus with angiotensin-converting-enzyme inhibitors.

PURPOSE The physiological and clinical data for using angiotensin-converting- enzyme (ACE) inhibitors to prevent new-onset type 2 diabetes mellitus are reviewed. SUMMARY ACE inhibitors have established their role in hypertension, primary and secondary prevention of cardiovascular events, and prevention of progression to and worsening of renal function. However, their ability to preserve pancreatic function and prevent new-onset diabetes is also coming to the forefront. Secondary analyses of large-scale clinical trials, such as the Captopril Prevention Project, the Heart Outcomes Prevention Evaluation, and the Studies of Left Ventricular Dysfunction trial, are revealing the potential benefits of these agents in diabetes prevention. However, the results of such studies have limited application because they are secondary analyses and, in some cases, were conducted 10 or more years after the original study. Enrollees were evaluated using different diagnostic guidelines for diabetes or not formally evaluated at all. Even in the most recent of the trials, the validity of the results is questionable because researchers coadministered a disease-modifying drug with the ACE inhibitor, potentially blunting the results. While intense lifestyle modifications are still superior in the prevention of new-onset diabetes, patients and providers will continue to investigate new options for preventing the progression of impaired fasting glucose to diabetes, though this delay does not correlate with a decrease in morbidity and mortality. CONCLUSION ACE inhibitors may preserve pancreatic function and prevent new-onset diabetes, especially for patients who are hypertensive with impaired glucose tolerance. Large studies investigating the effect of ACE inhibitors on the prevention of diabetes as a primary outcome are needed to determine the use for this indication.
Late coronary stent thrombosis: Early vs. late stent thrombosis in the stent era

The incidence of coronary stent thrombosis is < 1%–2% in recent studies, with the highest‐risk period considered to be the first 30 days following stent implantation. Recently, stent thrombosis after 30 days has been reported in patients undergoing brachytherapy with stenting. We reviewed the incidence of stent thrombosis causing myocardial infarction in nonbrachytherapy patients at our institution between 1 January 1996 and 30 November 1999. A case control methodology was employed with a 1:3 ratio of stent thrombosis to control patients. Of 1,191 patients undergoing coronary stenting, acute (< 24 hr) plus subacute (1–30 days) stent thrombosis occurred in 0.92% (11 of 1,191 patients). A further 0.76% (9 of 1,191 patients) developed late stent thrombosis after 30 days. There were no clinical or angiographic features at the time of the initial procedure that were associated with stent thrombosis as an entire group compared with control group, but early (acute and subacute) stent thrombosis patients had a smaller final stent minimal lumen diameter and longer stent length compared with patients who had late stent thrombosis or controls. Late stent thrombosis occurs in nonbrachytherapy patients and is almost as frequent as early stent thrombosis. Further studies are required to determine whether longer‐term poststent pharmacological treatment may decrease or prevent this complication. Cathet Cardiovasc Intervent 2002;55:142–147. © 2002 Wiley‐Liss, Inc.
Prevention of pure red cell aplasia after major or bidirectional ABO blood group incompatible hematopoietic stem cell transplantation by pretransplant reduction of host anti-donor isoagglutinins

In this study of a large group of patients who underwent major ABO incompatible hematopoietic stem cell transplantation, it was found that pre-transplant reduction of anti-donor isoagglutinins prevented post-transplant pure red cell aplasia. Background Persistent anti-donor isoagglutinins after major ABO blood group incompatible hematopoietic stem cell transplantation may cause delayed red blood cell engraftment and post-transplant pure red cell aplasia. Design and Methods We investigated the effect of pretransplant anti-donor isoagglutinin reduction by in vivo absorption and/or plasmapheresis on the incidence of pure red cell aplasia and the time to red blood cell engraftment in 153 hematopoietic stem cell transplant recipients with major ABO incompatibility. Results Twelve patients (8%) developed pure red cell aplasia, 3/98 (3%) with, and 9/55 (16%) without prior isoagglutinin reduction (p=0.009). Red blood cell engraftment was faster in patients with isoagglutinin reduction; in addition, peripheral blood hematopoietic stem cell transplantation, acute graft-versus-host disease, and younger age were associated with faster red blood cell engraftment in Cox regression analysis. In patients with pure red cell aplasia the mean red blood cell engraftment occurred after 225 days (p<0.001) and was associated with a simultaneous decrease of anti-donor isoagglutinins. Patients with pure red cell aplasia had higher pretransplant anti-donor isoagglutinin titers (p=0.001) and received more post-transplant red blood cell transfusions (p<0.001). Conclusions Following major ABO incompatible hematopoietic stem cell transplantation, pure red cell aplasia and delayed red blood cell engraftment depend on the levels of anti-donor isoagglutinins and are efficiently prevented by the pretransplant removal of these isoagglutinins. The benefits of reducing the time of transfusion-dependency and transfusion-associated risks must be carefully balanced against the potential side effects of isoagglutinin reduction.