bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sperm global DNA methylation level: association with semen parameters and genome integrity
Authors: Montjean D. , Zini A. , Ravel C. , Belloc S. , Dalleac A. , Copin H. , Boyer P. , McElreavey K. , Benkhalifa M. 
Published: March 2015

SummarySperm DNA methylation abnormalities have been detected in oligozoospermic men. However, the association between sperm DNA methylation defects, sperm parameters and sperm DNA, and chromatin integrity remains poorly understood. This study was designed to clarify this issue. We recruited a cohort of 92 men (62 normozoospermic and 30 oligoasthenozoospermic) presenting for infertility evaluation during a 1‐year period. Sperm global DNA methylation was evaluated by an ELISA‐like method, DNA fragmentation was evaluated by flow cytometry‐based terminal transferase dUTP nick end‐labeling (TUNEL) assay (reported as DNA fragmentation index or DFI), and sperm denaturation was evaluated by aniline blue staining (reported as sperm denaturation index or SDI, a marker of chromatin compaction). We found a significant positive association between sperm global DNA methylation level and conventional sperm parameters (sperm concentration and motility), supported by the results of methylation analysis on H19‐DMR. We also identified significant inverse relationships between sperm global DNA methylation, and, both DFI and SDI. However, sperm global DNA methylation level was not related to sperm vitality or morphology. Our findings suggest that global sperm DNA methylation levels are related to conventional sperm parameters, as well as, sperm chromatin and DNA integrity.
Comprehensive investigation in patients affected by sperm macrocephaly and globozoospermia
Authors: Chianese C. , Fino M. G. , Riera Escamilla A. , López Rodrigo O. , Vinci S. , Guarducci E. , Daguin F. , Muratori M. , Tamburrino L. , Lo Giacco D. , Ars E. , Bassas L. , Costa M. , Pisatauro V. , Noci I. , Coccia E. , Provenzano A. , Ruiz‐Castañé E. , Giglio S. , Piomboni P. , Krausz C. 
Published: March 2015

SummaryThe aim of this study was to provide a comprehensive genetic/phenotypic characterization of subjects suffering infertility owing to sperm macrocephaly (n = 3) or globozoospermia (n = 9) and to investigate whether the patients’ genetic status was correlated with the alteration of various sperm parameters. AURKC was sequenced in case of sperm macrocephaly while the DPY19L2 status has been analyzed by multiple approaches including a novel qPCR–based copy number assay in case of globozoospermia. Globozoospermic patients were also analyzed for SPACA1, a novel candidate gene herein tested for the first time in humans. The effect of the patients’ genetic status was interrogated by implementing the molecular screening with the characterization of several sperm parameters: (i) routine sperm analysis, integrated with transmission electron microscopy; (ii) sperm fluorescent in situ hybridization (FISH) analysis; (iii) sperm DNA fragmentation (DF) analysis. Moreover, for the first time, we performed microsatellite instability analysis as a marker of genome instability in men with sperm macrocephaly and globozoospermia. Finally, artificial reproductive technology (ART) history has been reported for those patients who underwent the treatment. Macrocephalic patients had an AURKC mutation and >89% tetraploid, highly fragmented spermatozoa. DPY19L2 was mutated in all patients with >80% globozoospermia: the two homozygous deleted men and the compound heterozygous showed the severest phenotype (90–100%). The newly developed qPCR method was fully validated and has the potential of detecting also yet undiscovered deletions. DPY19L2 status is unlikely related to FISH anomalies and DF, although globozoospermic men showed a higher disomy rate and DF compared with internal reference values. No patient was mutated for SPACA1. Our data support the general agreement on the negative correlation between macro/globozoospermia and conventional intracytoplasmic sperm injection outcomes. Microsatellites were stable in all patients analyzed. The comprehensive picture provided on these severe phenotypes causing infertility is of relevance in the management of patients undergoing ART.
Angiogenic biomarkers in pregnancy: defining maternal and fetal health
Authors: Rasmussen Lene G. , Lykke Jacob A. , Staff Anne C. 
Published: March 2015

AbstractWe review diagnostic and predictive roles of the angiogenic proteins placental growth factor, soluble fms‐like tyrosine kinase 1, and soluble endoglin in preeclampsia, and their association with future cardiovascular disease, diabetes, and breast cancer. Specific patterns of these proteins represent preeclamptic prediction markers and combined with maternal and clinical characteristics, the predictive values increase. Women experiencing preeclampsia have increased risks of developing cardiovascular diseases and diabetes, and a decreased risk of breast cancer. High placental growth factor concentrations have, in elderly patients, been shown to predict cardiovascular events. Diabetes is also a risk factor for future cardiovascular disease. Diabetic vascular complications are associated with increased soluble endoglin concentrations, and vascular endothelial growth factor concentrations are correlated to HbA1c and fasting glucose. Hence dysregulation in angiogenic proteins may link preeclampsia and cardiovascular diseases, targeting women who could in future benefit from prophylactic programs to possibly prevent, delay or reduce cardiovascular disease.
Review article: the safety of therapeutic drugs in male inflammatory bowel disease patients wishing to conceive
Authors: Sands K. , Jansen R. , Zaslau S. , Greenwald D. 
Published: March 2015

SummaryBackgroundMany therapeutic drugs are used by patients with inflammatory bowel disease, often around the time of conception. The pregnancy outcomes of males and females exposed to these therapeutics needs to be examined and this information is necessary to counsel patients appropriately.AimTo review the literature describing male infertility and inflammatory bowel disease to educate practitioners of the impact of inflammatory bowel disease on male reproduction and the impact of therapeutics on pregnancy outcomes.MethodsWe performed a PubMed search using the search terms ‘male infertility,’ ‘Crohn's disease,’ ‘inflammatory bowel disease,’ ‘ulcerative colitis,’ ‘ciprofloxacin AND infertility,’ ‘metronidazole AND infertility,’ ‘sulfasalazine AND infertility,’ ‘azathioprine AND infertility,’ ‘methotrexate AND infertility,’ ‘ciclosporin AND infertility,’ ‘corticosteroids AND infertility,’ ‘infliximab AND male fertility,’ ‘infliximab AND infertility,’ ‘infliximab AND foetus,’ ‘infliximab AND paternal exposure’ and ‘infliximab AND sperm.’ References from selected papers were reviewed and used if relevant.ResultsOver half of male patients with IBD have some degree of infertility, compared to 8–17% of the general population. Semen parameters including total count, motility and morphology may be adversely affected by therapeutics. IBD medications in males do not increase foetal risk with the possible exception of azathioprine and mercaptopurine; however, increased foetal risk is seen in other drugs if taken by female patients.ConclusionsIt is recognised that male infertility is often impacted with therapeutic drugs used to treat inflammatory bowel disease; however, the effects of the paternal drug exposure at the time of conception and exposure in utero should be considered to counsel patients appropriately.
Reduced risk of relapse after long‐term nucleos(t)ide analogue consolidation therapy for chronic hepatitis B
Authors: Chi H. , Hansen B. E. , Yim C. , Arends P. , Abu‐Amara M. , van der Eijk A. A. , Feld J. J. , de Knegt R. J. , Wong D. K. H. , Janssen H. L. A. 
Published: March 2015

SummaryBackgroundBefore stopping nucleos(t)ide analogue (NA) treatment in chronic hepatitis B (CHB), 6–12 months of consolidation therapy is recommended.AimTo investigate the effect of consolidation therapy on off‐treatment outcomes in CHB patients.MethodsWe included 94 patients who stopped NA after at least 1 year of therapy. Patients could be HBeAg‐positive or HBeAg‐negative at start‐of‐treatment, but were HBeAg‐negative and had undetectable HBV DNA at time of discontinuation. Consolidation therapy was defined as treatment after the first undetectable HBV DNA (and HBeAg loss for HBeAg‐positive patients) until NA cessation.ResultsAt 3 years, 74% of the start‐of‐treatment HBeAg‐positive and 75% of the start‐of‐treatment HBeAg‐negative patients developed HBV DNA >2000 IU/mL at a single time point, whereas a persistent virological relapse (≥2 tests of HBV DNA >2000 IU/mL 6 months apart within 1 year) developed in 49% of the start‐of‐treatment HBeAg‐positive and 53% of the start‐of‐treatment HBeAg‐negative patients. For both HBeAg‐positive and HBeAg‐negative patients, consolidation therapy of ≥3 years was associated with lower persistent virological relapse rates compared to <1 year (1‐year relapse rate: 25% vs. 54%; P = 0.063 and 24% vs. 57%; P = 0.036, respectively). At 3 years, 9% of the HBeAg‐positive and 14% of the HBeAg‐negative patients became HBsAg‐negative. Prolonged consolidation therapy increased the likelihood of HBsAg loss. Two cirrhotic patients developed hepatic decompensation but both recovered.ConclusionsAfter nucleos(t)ide analogue discontinuation, relapse was common in patients with chronic hepatitis B. Prolongation of consolidation therapy beyond 3 years decreased the risk of persistent virological relapse and increased the likelihood of HBsAg loss.
Low muscle mass and sarcopenia: common and predictive of osteopenia in inflammatory bowel disease
Authors: Bryant R. V. , Ooi S. , Schultz C. G. , Goess C. , Grafton R. , Hughes J. , Lim A. , Bartholomeusz F. D. , Andrews J. M. 
Published: March 2015

SummaryBackgroundBody composition is poorly studied in inflammatory bowel disease (IBD). Sarcopenia describes a loss of muscle mass and strength.AimTo assess the prevalence of low lean mass (LM), sarcopenia and associated morbidity in an adultIBDcohort.MethodsCross‐sectional data were gathered on pre‐menopausal 18‐ to 50‐year‐old patients withIBD. Whole‐body dual‐energyX‐ray absorptiometry, anthropometric assessment and grip strength were performed. LowLMwas defined as ≥1 s.d. below the population mean for appendicular skeletal muscle index [ASMI(kg)/height (m)²], and sarcopenia as bothASMIand grip strength ≥1 s.d. below population mean. Multivariate regression analyses were performed.ResultsOf 137 participants (median age 31 years, BMI 24.8 kg/m2), 56% were male and 69% had Crohn's disease (CD). LowLMand sarcopenia were observed in 21% and 12% of patients, respectively, and osteopenia/osteoporosis in 38% of patients (mean lumbar spinet‐score −0.3 ± s.d. 1.1). Grip strength predicted lowLMand sarcopenia better than did body mass index (BMI) (OR4.8 vs.OR0.7 for low‐LM,P < 0.05 both). NormalBMIwas falsely reassuring in 72% and 76% of patients with lowASMIand sarcopenia, respectively. LowLMand sarcopenia (OR = 3.6,P = 0.03;OR = 6.3,P = 0.02; respectively), but notBMInor fat mass, predicted osteopenia/osteoporosis.ConclusionsLow lean mass and sarcopenia are common in patients with IBD, and important to recognise as they predict osteopenia/osteoporosis. Grip strength testing should be incorporated into routine clinical practice to detect low lean mass deficits, which may go unrecognised using BMI alone.
CD19 chimeric antigen receptor T cell therapy for haematological malignancies
Authors: Ghorashian Sara , Pule Martin , Amrolia Persis 
Published: March 2015

SummaryT cells can be redirected to recognize tumour antigens by genetic modification to express a chimeric antigen receptor (CAR). These consist of antibody‐derived antigen‐binding regions linked to T cell signalling elements. CD19 is an ideal target because it is expressed on most B cell malignancies as well as normal B cells but not on other cell types, restricting any ‘on target, off tumour’ toxicity to B cell depletion. Recent clinical studies involving CD19 CAR‐directed T cells have shown unprecedented responses in a range of B cell malignancies, even in patients with chemorefractory relapse. Durable responses have been achieved, although the persistence of modified T cells may be limited. This therapy is not without toxicity, however. Cytokine release syndrome and neurotoxicity appear to be frequent but are treatable and reversible. CAR T cell therapy holds the promise of a tailored cellular therapy, which can form memory and be adapted to the tumour microenvironment. This review will provide a perspective on the currently available data, as well as on future developments in the field.
Ikaros and leukaemia
Authors: Olsson Linda , Johansson Bertil 
Published: March 2015

SummaryThe IKZF1 gene at 7p12.2 codes for IKAROS (also termed IKZF1), an essential transcription factor in haematopoiesis involved primarily in lymphoid differentiation. Its importance is underlined by the fact that deregulation of IKAROS results in leukaemia in both mice and men. During recent years, constitutional as well as acquired genetic changes of IKZF1 have been associated with human disease. For example, certain germline single nucleotide polymorphisms in IKZF1 have been shown to increase the risk of some disorders and abnormal expression and somatic rearrangements, mutations and deletions of IKZF1 (ΔIKZF1) have been detected in a wide variety of human malignancies. Of immediate clinical importance is the fact that ΔIKZF1 occurs in 15% of paediatric B‐cell precursor acute lymphoblastic leukaemia (BCP ALL) and that the presence of ΔIKZF1 is associated with an increased risk of relapse and a poor outcome; in some studies such deletions have been shown to be an independent risk factor also when minimal residual disease data are taken into account. However, cooperative genetic changes, such as ERG deletions and CRLF2 rearrangements, may modify the prognostic impact of ΔIKZF1, for better or worse. This review summarizes our current knowledge of IKZF1 abnormalities in human disease, with an emphasis on BCP ALL.
Dynamic contrast‐enhanced ultrasound parametric imaging for the detection of prostate cancer
Authors: Postema Arnoud W. , Frinking Peter J.A. , Smeenge Martijn , De Reijke Theo M. , De la Rosette Jean J.M.C.H. , Tranquart Francois , Wijkstra Hessel 
Published: March 2015

ObjectiveTo investigate the value of dynamic contrast‐enhanced (DCE)‐ultrasonography (US) and software‐generated parametric maps in predicting biopsy outcome and their potential to reduce the amount of negative biopsy cores.Materials and MethodsFor 651 prostate biopsy locations (82 consecutive patients) we correlated the interpretation of DCE‐US recordings with and without parametric maps with biopsy results. The parametric maps were generated by software which extracts perfusion parameters that differentiate benign from malignant tissue from DCE‐US recordings. We performed a stringent analysis (all tumours) and a clinical analysis (clinically significant tumours). We calculated the potential reduction in biopsies (benign on imaging) and the resultant missed positive biopsies (false‐negatives). Additionally, we evaluated the performance in terms of sensitivity, specificity negative predictive value (NPV) and positive predictive value (PPV) on a per‐prostate level.ResultsBased on DCE‐US, 470/651 (72.2%) of biopsy locations appeared benign, resulting in 40 false‐negatives (8.5%), considering clinically significant tumours only. Including parametric maps, 411/651 (63.1%) of the biopsy locations appeared benign, resulting in 23 false‐negatives (5.6%). In the per‐prostate clinical analysis, DCE‐US classified 38/82 prostates as benign, missing eight diagnoses. Including parametric maps, 31/82 prostates appeared benign, missing three diagnoses. Sensitivity, specificity, PPV and NPV were 73, 58, 50 and 79%, respectively, for DCE‐US alone and 91, 56, 57 and 90%, respectively, with parametric maps.ConclusionThe interpretation of DCE‐US with parametric maps allows good prediction of biopsy outcome. A two‐thirds reduction in biopsy cores seems feasible with only a modest decrease in cancer diagnosis.
Feeding practices in infancy associated with caries incidence in early childhood
Authors: Chaffee Benjamin W. , Feldens Carlos Alberto , Rodrigues Priscila Humbert , Vítolo Márcia Regina 
Published: March 2015

AbstractBackgroundEarly‐life feeding behaviors foretell later dietary habits and health outcomes. Few studies have examined infant dietary patterns and caries occurrence prospectively.ObjectiveAssess whether patterns in food and drink consumption before age 12 months are associated with caries incidence by preschool age.MethodsWe collected early‐life feeding data within a birth cohort from low‐income families in Porto Alegre, Brazil. Three dietary indexes were defined, based on refined sugar content and/or previously reported caries associations: a count of sweet foods or drinks introduced <6‐months (e.g., candy, cookies, soft drinks), a count of other, nonsweet items introduced <6‐months (e.g., beans, meat), and a count of sweet items consumed at 12 months. Incidence of severe early childhood caries (S‐ECC) at age 38 months (N = 458) was compared by score tertile on each index, adjusted for family, maternal, and child characteristics using regression modeling.ResultsIntroduction to a greater number of presumably cariogenic items in infancy was positively associated with future caries. S‐ECC incidence was highest in the uppermost tertile of the ‘6‐month sweet index’ (adjusted cumulative incidence ratio, RR, versus lowest tertile: 1.46; 95% CI: 0.97, 2.04) and the uppermost tertile of the ‘12‐month sweet index’ (RR: 1.55; 95% CI: 1.17, 2.23). The association was specific for sweet items: caries incidence did not differ by tertile of the ‘6‐month nonsweet index’ (RR: 1.00; 95% CI: 0.70, 1.40). Additionally, each one‐unit increase on the 6‐month and the 12‐month sweet indexes, but not the 6‐month nonsweet index, was statistically significantly associated with greater S‐ECC incidence and associated with more decayed, missing, or restored teeth. Results were robust to minor changes in the items constituting each index and persisted if liquid items were excluded.ConclusionsDietary factors observed before age 12‐months were associated with S‐ECC at preschool age, highlighting a need for timely, multilevel intervention.
Predictive value of the Groningen Frailty Indicator for treatment outcomes in elderly patients after head and neck, or skin cancer surgery in a retrospective cohort
Authors: Bras L. , Peters T.T.A. , Wedman J. , Plaat B.E.C. , Witjes M.J.H. , van Leeuwen B.L. , van der Laan B.F.A.M. , Halmos G.B. 
Published: March 2015

ObjectivesCareful selection of patients eligible for extensive head and neck cancer surgery is extremely important. A reliable predictor for postoperative outcomes in the vulnerable elderly population is not yet available. The concept of frailty describes a clinical state of increased vulnerability and can be assessed using frailty tests, such as the Groningen Frailty Indicator. In the current study, the influence of Groningen Frailty Indicator‐measured frailty on clinical outcome was investigated in elderly patients surgically treated for head and neck cancer.DesignRetrospective, explorative cohort study.SettingTertiary referral centre.ParticipantsA total of 90 patients of 65 years and older receiving surgical treatment for head and neck cancer with different primary sites.Main outcome measuresThe influence of frailty (Groningen Frailty Indicator) on postoperative complications (Clavien–Dindo classification), subjective postoperative experience of both patient and surgeon and survival were analysed.ResultsA total of 36 patients were considered as frail (40%). Postoperative complications could not be predicted by frailty status. However, the Groningen Frailty Indicator dimension ‘health problems’ was a significant predictor for postoperative complications (P = 0.020). Unlike age and comorbidity, frailty was associated with a poor subjective patients’ experience of the postoperative recovery (P < 0.01). Although not statistically significant, survival analysis showed a worse 5‐year overall survival in the frail group (33%) versus the non‐frail group (74%).ConclusionsAnalysis of frailty could identify elderly patients who might suffer more than expected during the postoperative period after head and neck cancer surgery. In this study, frailty was not identified as a new predictor of complications after head and neck cancer surgery.
Prevalence and correlates of adult overweight in the Muslim world: analysis of 46 countries
Authors: Kahan D. 
Published: March 2015

SummaryThe primary objectives of the study were to calculate overweight prevalence (body mass index ≥ 25.0) and simple correlations between 10 demographic, social welfare and behavioural variables and overweight prevalence for Muslim countries (populations >50% Muslim; N = 46). Overweight data for a country's total, male and female populations were extracted from the World Health Organization's (WHO) STEPwise country reports and relevant publications. Country‐level data for potential correlates were extracted from multiple sources: Central Intelligence Agency (literacy), Gallup Poll (religiosity), United Nations (agricultural employment, food supply, gender inequality, human development), World Bank (automobile ownership, Internet, labour force) and WHO (physical inactivity). The overall, male and female overweight prevalence was 37.4, 33.0 and 42.1%, respectively. Prevalence estimates significantly differed by economic classification, gender and ethnicity. Middle‐ and upper income countries were 1.54–7.76 (95% confidence interval [CI]: 1.49–8.07) times more likely overweight than low‐income countries, females were 1.48 (CI: 1.45–1.50) times more likely overweight than males and Arab countries were 2.92 (CI: 2.86–2.97) times more likely overweight than non‐Arab countries. All 10 of the potential correlates were significantly associated with overweight for at least one permutation (total, economic classification, gender, ethnicity). The greater percentage of poorer countries among non‐Arab Muslim countries, which compared with Arab countries have not as rapidly been transformed by globalization, nutrition transition and urbanization, may partially explain prevalence differences. Evaluation of correlational data generally followed associations seen in non‐Muslim countries but more complex analysis of subnational data is needed. Arab women are a particularly vulnerable subgroup and governments should act within religious and cultural parameters to provide environments that are conducive to negative energy balance.