Miracle-dz/UniFAR-FTUs huggingface dataset:
Outcomes of Twin Pregnancies in Women 45 Years of Age or Older.

OBJECTIVE To investigate outcomes of twin gestations in women 45 years or older at the time of delivery. METHODS This was a retrospective cohort study of 139 women with twin gestations who were at least 45 years old when they delivered. They were cared for at two referral centers between 2005 and 2016. Analysis included baseline characteristics and pregnancy outcomes including mode of delivery, gestational age at delivery, hypertensive disease in pregnancy, gestational diabetes, and fetal growth restriction. Univariate analysis of the association between patient characteristics and outcomes was performed. RESULTS The mean maternal age at delivery was 47.3±1.9 years with 99.3% undergoing in vitro fertilization and 95% using donor eggs. Patients had low baseline rates of hypertension (7.2%), obesity (9.5%), and pregestational diabetes (1.4%). The average gestational age of delivery was 35.4 weeks; 22.3% delivered before 34 weeks of gestation. There were high rates of cesarean delivery (93.5%, 95% confidence interval [CI] 87.7-96.8%), preeclampsia (44.6%, 95% CI 36.3-53.3%), and gestational diabetes (19%, 95% CI 13.0-26.8%). Preeclampsia developed in 50.5% of nulliparous women compared with 30.5% of women with a prior birth (P=.028). Preterm birth at less than 34 weeks of gestation occurred in 18.1% of women of white race compared with 30.3% of women of nonwhite race (P=.036). CONCLUSION Twin pregnancy in a predominantly healthy cohort of women who were at least 45 years old when they delivered was associated with high rates of cesarean delivery, preeclampsia, and gestational diabetes, but overall favorable outcomes.
Clinical responses with T lymphocytes targeting malignancy-associated κ light chains.

BACKGROUND Treatment of B cell malignancies with adoptive transfer of T cells with a CD19-specific chimeric antigen receptor (CAR) shows remarkable clinical efficacy. However, long-term persistence of T cells targeting CD19, a pan-B cell marker, also depletes normal B cells and causes severe hypogammaglobulinemia. Here, we developed a strategy to target B cell malignancies more selectively by taking advantage of B cell light Ig chain restriction. We generated a CAR that is specific for the κ light chain (κ.CAR) and therefore recognizes κ-restricted cells and spares the normal B cells expressing the nontargeted λ light chain, thus potentially minimizing humoral immunity impairment. METHODS We conducted a phase 1 clinical trial and treated 16 patients with relapsed or refractory κ+ non-Hodgkin lymphoma/chronic lymphocytic leukemia (NHL/CLL) or multiple myeloma (MM) with autologous T cells genetically modified to express κ. CAR (κ.CARTs). Other treatments were discontinued in 11 of the 16 patients at least 4 weeks prior to T cell infusion. Six patients without lymphopenia received 12.5 mg/kg cyclophosphamide 4 days before κ. CART infusion (0.2 × 108 to 2 × 108 κ.CARTs/m2). No other lymphodepletion was used. RESULTS κ. CART expansion peaked 1-2 weeks after infusion, and cells remained detectable for more than 6 weeks. Of 9 patients with relapsed NHL or CLL, 2 entered complete remission after 2 and 3 infusions of κ. CARTs, and 1 had a partial response. Of 7 patients with MM, 4 had stable disease lasting 2-17 months. No toxicities attributable to κ. CARTs were observed. CONCLUSION κ. CART infusion is feasible and safe and can lead to complete clinical responses. TRIAL REGISTRATION ClinicalTrials.gov NCT00881920. FUNDING National Cancer Institute (NCI) grants 3P50CA126752 and 5P30CA125123 and Leukemia and Lymphoma Society (LLS) Specialized Centers of Research (SCOR) grant 7018.
Damage propagation in complex biological systems following exposure to low doses of ionising radiation

Biological organisms present hierarchical levels of organisation capable of maintaining homeostasis at low-level perturbations through intricate signalling between cells. Ionising radiation may damage DNA and other molecular components. This primary risk rises linearly with dose over a certain dose range. A second risk describes the probability of the initial DNA and other damage to propagate in the body to cause disease, such as cancer. The homeostatic control of the second risk does not function in a linear fashion. Moreover, low-dose irradiation may adaptively up-regulate protective responses at different organisational levels genetically controlled. Such adaptive protections (APs) usually defend also against the inevitable abundant non-radiogenic perturbations. Below ≅0.1Gy, APs are potentially beneficial in outweighing the consequences of the relatively rare radiogenic damage at low doses. The balance between health risk and benefit of low-level irradiation of an individual may become predictable by gene-expression profiles also for eventually treating disease.
Dental and skeletal development in various endocrine and metabolic diseases.

To define the rule of various intrinsic hormonal factors and their relative importance in normal dental development, a study was made of dental growth in patients with known endocrine or metabolic dysfunction. Skeletal and dental ages were determined radiographically and compared with chronologic age to learn the effect of the disease on the rate of development.
The abuse potential of propofol

Context. Propofol is a sedative-hypnotic prescription medication that is widely used in anesthesia, long-term sedation, and conscious sedation. It is short acting, effective, and, when used appropriately, safe. It is not a controlled substance by the U.S. Drug Enforcement Administration, suggesting that it has little potential for abuse. The objective of this review was to evaluate the evidence for the abuse potential of propofol. Methods. A systematic review of the medical literature was performed using the search terms: propofol, Diprivan, abuse, addiction, tolerance, misuse, and withdrawal. Six online literature citation databases and relevant bibliographies were searched for articles. Results. Seventy-two articles were identified for review and 45 were relevant to the topic. These articles described propofol's biochemical and pharmacokinetic mechanisms of action that lend themselves to its abuse, propofol's physical and psychological effects that make it alluring as a recreational drug, the current evidence supporting the possibility of tolerance to and withdrawal from propofol, the risk involved in recreational propofol use, and the evidence supporting current abuse of this medication. We found evidence to support propofol's abuse potential from a pharmacological and experiential standpoint with multiple reports describing tolerance, dependence, withdrawal phenomena, abuse, and death from recreational use. Conclusions. Propofol has alluring and addictive properties that lend itself to potential recreational abuse and dependence. We recommend that the U.S. Drug Enforcement Administration and other international agencies should consider regulating propofol as a controlled substance.
Clinical and pathophysiological consequences of on-demand treatment with PPI in endoscopy-negative reflux disease. Is rebound hypersecretion of acid a problem?

Abstract Objective. Rebound acid hypersecretion after withdrawal of proton pump inhibitor (PPI) may lead to symptom aggravation and difficulties in withdrawing anti-reflux medication. The aim was to investigate pathophysiological and clinical consequences of on-demand treatment with PPI in patients with endoscopy-negative reflux disease. Material and methods. Twenty-six patients with endoscopy-negative reflux disease were investigated for rebound effects of lansoprazole 15 mg, used on-demand, maximum 4 capsules daily during a 6-month period. P-CgA and s-gastrin were measured before, at termination and 2 weeks after stopping treatment. Symptom score was performed the week before and the second week after treatment, 24-h pH-metry after both periods. Results. Median daily consumption of lansoprazole was 15.1 mg (95% CI: 10.5; 18.8). S-gastrin before treatment was 31.2 pmol/l, 54.8 at the end (p < 0.01), 31.7 two weeks after withdrawal. P-CgA was 16.7 u/l before treatment, 37.5 at the end (p < 0.01), 17.7 two weeks after withdrawal (p = 0.35). A positive correlation was found between total consumption of lansoprazole and CgA increase during treatment (r = 0.44 p = 0.03). There was a reduction in symptom score during the treatment period from 30 (24–38) before, to 20 (15–36) the second week after treatment, p = 0.06. 32% had increase in symptoms. Conclusions. Rebound acid hypersecretion is probably an infrequent problem in on-demand treatment with PPI in patients with endoscopy-negative reflux disease. A significant increase in p-CgA and s-gastrin was found after 6 months treatment. Fourteen days after withdrawal, CgA and gastrin returned to pretreatment levels. Overall, no aggravation of symptoms was found, but 1/3 experienced increased symptoms.
Expression of ectonucleotide pyrophosphatase‐1 in end‐plate chondrocytes with transforming growth factor beta 1 siRNA interference by cyclic mechanical tension

Background Ectonucleotide pyrophosphatase/phosphodiesterase (ENPP)‐1 is a membrane‐bound protein that catalyzes the hydrolysis of extracellular nucleoside triphosphates to monophosphate and extracellular inorganic pyrophosphate (ePPi). Mechanical stimulation regulates ENPP‐1 expression. This study sought to investigate the changes in ENPP‐1 expression after stimulation using cyclic mechanical tension (CMT). Methods Rat end‐plate chondrocytes were cultured and subjected to CMT (at 3%, 6%, and 9% elongation) for 20, 40, and 60 minutes to observe changes in the expression of ENPP‐1. To investigate the pathway, end‐plate chondrocytes were exposed to 10 ng/ml of transforming growth factor beta 1 (TGF‐&bgr;1), TGF‐&bgr;1 siRNA, or a specific extracellular signal‐regulated kinase (ERK)1/2 inhibitor, U0126, in addition to CMT. Changes in ENPP‐1 expression were measured by reverse transcription PCR (RT‐PCR) and Western blotting. Results We observed the largest increase in ENPP‐1 expression following 3% elongation CMT stimulation. ENPP‐1 expression was also increased when end‐plate chondrocytes were exposed to 10 ng/ml of TGF‐&bgr;1, but decreased after TGF‐&bgr;1 knockdown with siRNA. ERK1/2 phosphorylation was activated after 3% elongation for 40 minutes, and the stimulatory effect of TGF‐&bgr;1 on ENPP‐1 mRNA and protein expression was inhibited by the suppression of the ERK1/2 pathway using U0126. Conclusion CMT increases the expression of ENPP‐1 in end‐plate chondrocytes in a manner likely dependent on TGF‐&bgr;1 induction by the ERK1/2 signaling pathway.
Audit quality and cost of equity capital

The purpose of this research is to examine the relationship between audit quality and cost of equity capital. This research argues that the higher the levels of audit quality, the lower the rate of return required by the investor. The cost of equity capital is measured by the price-earnings growth (PEG) model. Audit quality is measured by proxies, including audit fees, non-audit fees, industry specialist auditors and earnings management. Based on 226 largest companies listed on the London Stock Exchange (FTSE 350) during 2005-2008, findings report a significant relationship between earnings management and the cost of equity capital. The research does not find a relationship between the other three audit quality proxies. The results suggest that among larger firms, earnings management is a major issue. Auditors are mainly expected to deal with earnings management. It is more likely that investors perceive auditing as an important mechanism to detect earnings management in large firms, enhancing the value of financial information.
From meiosis to mitosis – the sperm centrosome defines the kinetics of spindle assembly after fertilization in Xenopus

ABSTRACT Bipolar spindle assembly in the vertebrate oocyte relies on a self-organization chromosome-dependent pathway. Upon fertilization, the male gamete provides a centrosome, and the first and subsequent embryonic divisions occur in the presence of duplicated centrosomes that act as dominant microtubule organizing centres (MTOCs). The transition from meiosis to embryonic mitosis involves a necessary adaptation to integrate the dominant chromosome-dependent pathway with the centrosomes to form the bipolar spindle. Here, we took advantage of the Xenopus laevis egg extract system to mimic in vitro the assembly of the first embryonic spindle and investigate the respective contributions of the centrosome and the chromosome-dependent pathway to the kinetics of the spindle bipolarization. We found that centrosomes control the transition from the meiotic to the mitotic spindle assembly mechanism. By defining the kinetics of spindle bipolarization, the centrosomes ensure their own positioning to each spindle pole and thereby their essential correct inheritance to the two first daughter cells of the embryo for the development of a healthy organism. Highlighted Article: During the first embryonic division, the duplicated sperm centrosomes define the kinetics of spindle bipolarization, ensuring their own inheritance to the daughter cells.
A Common Polymorphism in the Interleukin 8 Gene Promoter Is Associated with Clostridium difficile Diarrhea

OBJECTIVE:Mucosal interleukin 8 (IL-8) and neutrophil recruitment are central to the pathogenesis of Clostridium difficile (CD) toxin-induced diarrhea (CDD). We hypothesized that like other inflammatory mucosal infections, susceptibility to CDD would relate to genetically determined variations in the production of IL-8.METHODS:Fecal IL-8 production and single nucleotide polymorphism (SNP) frequency in the −251 region of the IL-8 gene were determined in hospitalized patients: 42 with CDD, 42 with CD-negative diarrhea, and 41 without diarrhea. Cases and controls were matched by age, length of hospital stay, comorbidity, and receipt of antibiotics.RESULTS:An association was found between the IL-8 −251 A/A allele and occurrence of CDD, 39%versus 16% (OR = 3.26, 95% CI 1.09–9.17) and 17% (OR = 5.50, 95% CI 1.22–24.8) for the two control groups. Comparing results by IL-8 genotype for the CDD cases, median and mean fecal IL-8 levels were significantly higher for the −251 A/A genotype (p= 0.03 for median and 0.001 for mean). CONCLUSIONS:These studies indicate a common SNP in the IL-8 gene is associated with increased susceptibility to CDD and with increased fecal IL-8 in diarrheal stools.
Correlation of Cervical Smear and Pathohistological Findings

ABSTRACT Introduction: In endeavor to suppress the cervical carcinoma there are several possible approaches including measures of primary and secondary prevention. So far effects of these measures on the number of cases and mortality rate of cervical carcinoma were modest. Only exception is organized testing based on cytological exam of the cervical smear – Pap test, which has proven to be highly effective in reducing the number of cases and mortality of cervical carcinoma in countries with this program. Goal: of this research is analysis of correlation between abnormal cytological test results and pathohistological diagnosis of all patients in the analyzed period. ] Material and methods: Research is descriptive, analytical, comparative, and partly epidemiological. Results of cytological and pathohistological diagnostic in the period between January 1, 2009 and December 31, 2011 were used for analysis. All analyzed patients had colposcopy exam and Pap test, and patients with abnormal results of this test underwent cervical biopsy for pathohistological diagnostics. Results: We came to following results and conclusions: total number of L-SIL and H-SIL (PAPA III) results was 395 (6.20%) in comparison to total sample of 5894 (92.44%) patients. There is a statistically significant difference in relation to PHD result of cervical biopsy after L-SIL and H-SIL (PAPA II and IV), and highest statistical margin is in relation of CIN II changes to cytological findings, issued at Clinic of Obstetrics and Gynecology and other health institutions. We come to conclusion that the highest percentage of patients with L-SIL and H-SIL findings is in age group between 0-29 years old. Statistical analysis has shown a positive trend in number of younger patients with L-SIL and H-SIL (PAPA III and IV), with average age of patients in 2011 being 31.12±9.12 years old.
Myelodysplastic syndromes: Analysis of 131 cases according to the FAB classification

The clinical and haematological findings in 131 patients with myelodysplastic syndromes (MDS), none of which had previously received chemotherapy or radiotherapy, classified according to the FAB criteria, were analysed. The distribution among the 5 subgroups was: RA 31 patients, RAS 19, RAEB 23, CMML 29 and RAEBT 29 patients. There were difficulties in the classification of 24 patients. These included, first, 8 cases with myeloid hyperplasia of the bone marrow (BM) but without mono‐cytosis or excess of blasts of the BM. They were classified as RA. Second, 8 cases with sideroblastosis but with monocytosis or excess of blasts of the BM were classified 3 as RAEB, 2 as CMML and 3 as RAEBT. Finally, 8 cases with absolute monocytosis and BM blasts 15–30% were classified as CMML. 37 of 82 dead patients (45.1%) had transformed to acute non‐lymphoblastic leukaemia (ANLL). The incidence of evolution to ANLL was low for RA and RAS (6.30% and 12.5% respectively), while it was 37.5% for RAEB, 57.1% for CMML and 77.2% for RAEBT. The median survival for each subgroup was: RA 18 months; RAS 25; RAEB 13; CMML 14 and RAEBT 10 months. It is concluded that the FAB classification with some modifications recognises group of MDS with different prognosis.
Serious Money: Fundraising and Contributing in Presidential Nomination Campaigns

Figures and tables Acknowledgments 1. Introduction 2. Regulatory environment 3. The contributor pool 4. Mobilizing the pool: methods of soliciting campaign funds 5. Candidate resources 6. Recruiting contributors and solicitors: candidate and individual decisions 7. Conclusion Appendices Works cited Index.
Digital Opportunities and the Missing Link for Developing Countries

The spread of digital information and communication technologies is enabling firms to implement electronic commerce. Many expect that the implementation of new means of trading internationally, especially using the Internet to support electronic commerce, will facilitate the entry of firms in developing countries into international markets. This paper assesses this claim. The analysis shows that the capacity to gain from the availability of the new technologies involves more than a reduction of the technological divide between (and within) countries. The institutional foundations for building capabilities that enable firms to absorb the new technological systems must also be in place. It is imperative that measures to develop electronic commerce and to devise broader technological leap-frogging strategies are embedded within the framework of appropriate institutions and development goals. Failure to do so is likely to produce enclaves of development that will persist. Copyright 2001, Oxford University Press.
Saccadic reaction times in patients with frontal and parietal lesions.

The effect of unilateral circumscribed lesions in different areas of the frontal and parietal cortex on the distributions of saccadic reaction times (SRTs) was investigated in 32 patients under four stimulus conditions: (i) gap-random: a target light appeared 200 ms after extinction of a central fixation light randomly at 8 degrees either left or right; (ii) overlap-random: like (i), but the fixation light remained on ('overlap'); (iii) gap-simultaneous: two peripheral lights appeared simultaneously left and right 200 ms after the extinction of the fixation light, one predesignated by instruction as saccadic target; (iv) overlap-simultaneous: like (iii), but the fixation light remained on. Depending on SRT and condition and based on the data of control subjects, we evaluated the percentages of anticipatory (SRT: 0-90 ms), express (91-157 ms) and regular (158-400 ms) saccades, of time (> 400 ms) and direction errors as well as the mean latencies and the standard deviations. These data were compared across control subjects, frontal lobe patients with a lesion in the region of the frontal eye field (FEF), and frontal patients with a lesion outside the FEF, as well as across control subjects, parietal lobe patients with a lesion in the dorsolateral region, and parietal patients with a lesion outside the dorsolateral region. (i) Frontal patients with a lesion in the FEF region showed an increased percentage of express saccades (gap-random condition), especially with saccades directed towards the side of the lesion (ipsilateral). If fixation was not interrupted prior to target appearance (overlap-random), express saccades were largely suppressed, similar to normals. All patients with a frontal lesion, whether in the region of the FEF or not, showed a decreased percentage of contralateral anticipatory saccades (gap-simultaneous), whereas the percentages of direction and time errors were in the normal range, even if more than one stimulus was presented (e.g. overlap-simultaneous condition). (ii) Patients with dorsolateral parietal lesions showed decomposed SRT patterns (high SRT variability, increased percentages of time and direction errors, decreased percentages of express and anticipatory saccades). The decomposition had a contralateral preponderance and increased if more than one stimulus was visible beside the saccadic target. Our results suggest that FEF lesions impair mainly the volitional control over visually triggered express or reflex-like saccades if fixation is disrupted, whereas dorsolateral parietal lesions impair mainly the selection of the visual targets.
Percutaneous Permeation of Basic Compounds Through Shed Snake Skin as a Model Membrane

Abstract— Relationships between the in‐vitro permeability of basic compounds through shed snake skin as a suitable model membrane for human stratum corneum and their physicochemical properties were investigated. Compounds with low pKa values were selected to compare the permeabilities of non‐ionized forms of the compounds. Steady‐state penetration was achieved immediately without a lag time for all compounds. Flux rate and permeability coefficient were calculated from the steady‐state penetration data and relationships between these parameters and the physicochemical properties were investigated. The results showed that permeability may be controlled by the lipophilicity and the molecular size of the compounds. Equations were developed to predict the permeability from the molecular weights and the partition coefficients of basic compounds.
Framing comparisons: gendering perspectives on cross-national comparative research on work and welfare

This article critically reviews a range of analytical frameworks used in cross-national comparative employment and welfare state research. The approaches examined include the societal effect, varieties of capitalism, welfare state regimes and benchmarking approaches, and their feminist critiques.The article concludes by assessing the critical merits and implicit assumptions of using such frameworks to examine the differential impact of work and welfare for men and women in different societies.