bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term effect of cytotoxic treatments on sperm DNA fragmentation in patients affected by testicular germ cell tumor
Authors: Farnetani Ginevra , Fino Maria Grazia , Cioppi Francesca , Riera‐Escamilla Antoni , Tamburrino Lara , Vannucci Matteo , Rosta Viktoria , Vinci Serena , Casamonti Elena , Turki Leila , Degl'Innocenti Selene , Spinelli Matilde , Marchiani Sara , Lotti Francesco , Muratori Monica , Krausz Csilla 
Published: March 2023

AbstractIntroductionTesticular germ cell tumor is the most frequent neoplasia in men of reproductive age, with a 5‐year survival rate of 95%. Antineoplastic treatments induce sperm DNA fragmentation, especially within the first year post‐therapy. Data in the literature are heterogeneous concerning longer follow‐up periods, and the large majority is limited to 2 years.ObjectiveTo define the timing for the recovery of sperm DNA damage and the proportion of patients with severe DNA damage at 2 and 3 years from the end of therapy.Materials and methodsSperm DNA fragmentation was evaluated in 115 testicular germ cell tumor patients using terminal deoxynucleotidyl transferase dUTP nick end labeling assay coupled with flow cytometry before (T0) and 2 (T2) and 3 (T3) years post‐treatment. Patients were divided based on the type of treatment: carboplatin, bleomycin–etoposide–cisplatin, and radiotherapy. For 24 patients, paired sperm DNA fragmentation data were available at all time‐points (T0–T2–T3). Seventy‐nine cancer‐free, fertile normozoospermic men served as controls. Severe DNA damage was defined as the 95th percentile in controls (sperm DNA fragmentation = 50%).ResultsComparing patients versus controls, we observed: (i) no differences at T0 and T3 and (ii) significantly higher sperm DNA fragmentation levels (p < 0.05) at T2 in all treatment groups. Comparing pre‐ and post‐therapy in the 115 patients, the median sperm DNA fragmentation values were higher in all groups at T2, reaching significance (p < 0.05) only in the carboplatin group. While the median sperm DNA fragmentation values were also higher in the strictly paired cohort at T2, about 50% of patients returned to baseline. The proportion of severe DNA damage in the entire cohort was 23.4% and 4.8% of patients at T2 and T3, respectively.DiscussionCurrently, testicular germ cell tumor patients are advised to wait 2 years post‐therapy before seeking natural pregnancy. Our results suggest that this period may not be sufficient for all patients.ConclusionThe analysis of sperm DNA fragmentation may represent a useful biomarker for pre‐conception counseling following cancer treatment.
Effectiveness and acceptability of home use of misoprostol for medical abortion up to 10 weeks of pregnancy
Authors: Podolskyi Volodymyr , Gemzell‐Danielsson Kristina , Maltzman Lena L. , Marions Lena 
Published: March 2023

AbstractIntroductionThe administration of mifepristone, followed by misoprostol, is widely used for medical abortion. Many studies have demonstrated home abortion to be safe in pregnancies up to 63 days of gestation, and recent data support its safety when extended to more advanced pregnancies. We studied the efficacy and acceptability of home use of misoprostol up to 70 days of gestation in a Swedish setting and compared the outcomes between pregnancies with a gestational age of up to 63 days and pregnancies with gestational age 64–70 days.Material and methodsThis prospective cohort study was performed between November 2014 and November 2021 at Södersjukhuset and Karolinska University Hospital, Stockholm, and some patients were also recruited from Sahlgrenska University Hospital, Göteborg and Helsingborg Hospital. The primary outcome was the rate of complete abortions and was defined as complete abortion without any need for surgical or medical intervention and assessed by clinical assessment, pregnancy test and/or vaginal ultrasound. Secondary objectives were assessed by daily self‐reporting in a diary and included pain, bleeding, side effects and women's satisfaction and perception of home use of misoprostol. A comparison of categorical variables was made with Fisher's exact test. The significance level was set to a p‐value ≤0.05. The study was registered at Clinicaltrials.gov on July 14, 2014 (NCT02191774).ResultsDuring the study period we enrolled 273 women opting for medical abortion with home use of misoprostol. In the early group, up to 63 days of gestation, 112 women were included with a mean gestational length of 45 days and in the late group, 64–70 days of gestation, 161 women with a mean gestations length of 66.3 days were included. Complete abortion occurred in 95% (95% CI 89–98) of women in the early group and in 96% (95% CI 92–99) in the late group. No differences were found regarding side effects and acceptability was similarly high in both groups.ConclusionsOur results show high efficacy and acceptability of medical abortion when misoprostol is administered at home up to 70 days of gestation. This supports previous findings about maintained safety when misoprostol is administered at home even past a very early pregnancy.
The role of positive information provision in open‐label placebo effects
Authors: Barnes Kirsten , Babbage Emily , Barker Jessica , Jain Natasha , Faasse Kate 
Published: March 2023

AbstractOpen label placebos (OLPs) appear generally efficacious among clinical samples, but the empirical evidence regarding their use in non‐clinical and sub‐clinical samples, as well as when administered independent of a convincing rationale, is mixed. Healthy participants (N = 102) were randomised to either a 6‐day course of OLP pills with information provision (OLP‐plus: N = 35), without information provision (OLP‐only: N = 35), or no‐treatment control group (N = 32). OLP pills were described as enhancing physical (symptoms and sleep) and psychological (positive and negative emotional) well‐being. Well‐being was assessed at baseline and on Day 6. Expectancies and adherence were measured. OLP administration interacted with baseline well‐being. The OLP‐plus group demonstrated increased well‐being on all outcomes other than positive emotions, but only when they reported decreased baseline well‐being. OLP‐only and control groups did not differ. The OLP‐plus group demonstrated elevated expectancies, that mediated the OLP effect on physical symptoms relative to control, but only when well‐being was lower than average at baseline (i.e. moderated‐mediation). Results demonstrate the importance of information provided with OLPs. The moderating effect of baseline outcomes may reconcile inconsistent results regarding clinical and non‐clinical samples. Accounting for baseline symptoms in non‐clinical and sub‐clinical samples is likely to enhance our understanding of when OLPs are effective.
Herbivores regulate native–alien plants dynamics in sub‐Antarctic beech (Nothofagus antarctica) forests of Tierra del Fuego, Argentina
Authors: Soler Rosina , Bustamante Gimena , Cruz‐Alonso Verónica , Lenzner Bernd , Essl Franz 
Published: March 2023

AbstractQuestionsWhat is the role of native and domestic herbivores in native–alien vegetation changes in sub‐Antarctic forests? Does herbivory suppression increase native while reducing alien species diversity?LocationCentral–eastern Tierra del Fuego Island, Argentina.MethodsIn four sites, we set up three different treatments: excluded grazing by livestock (cattle), by livestock and native (guanaco) herbivores, and grazed control plots in Nothofagus antarctica forests. We then monitored the dynamics of understorey native and alien plants (species richness, abundance) of dicots, monocots, and ferns over 6 years. Generalized Linear Mixed Models were used to determine the effects of herbivore exclusion and time on species richness and abundance. In addition, we calculated the abundance rate of change to quantify temporal dynamics.ResultsOverall species richness did not change in the exclusion plots, but native and alien abundances were affected by herbivory and time since exclusion. The abundance of native monocots changed after herbivore exclusion, increasing its dominance significantly inside exclusion plots. However, the cessation of herbivory did not reduce alien species in general. Only alien dicots significantly declined in the livestock exclusion treatment. Further, we found that the two dominant alien grass species (Holcus lanatus and Poa pratensis) respond differently to grazing exclusion, and their response was modulated by forest basal area.ConclusionsOur results indicate that cattle and guanaco grazing had variable effects on native and alien plants, and that herbivore exclusion has a substantially positive effect on native grasses. However, the magnitude of temporal changes was more significant for vegetation richness and abundance than the effect of exclusion treatments. Herbivore exclusions can initiate a rapid recovery of compositional attributes of native vegetation in N. antarctica forests grazed by livestock.
Rangeland resilience to droughts: Changes across an intensification gradient
Authors: Tommasino Andrea , Lezama Felipe , Gallego Federico , Camba Sans Gonzalo , Paruelo José María 
Published: March 2023

AbstractAimThe intensification of livestock systems generates structural and functional changes in native grassland, which alter their capacity to respond to disturbances. Our objective was to evaluate the resilience to an extraordinary consecutive‐droughts event, across an intensification gradient of livestock systems. Our prediction was that sites with more intensive management (less diverse) will have lower resilience (as resistance and/or recovery) to drought.LocationSouth‐central region of Uruguay.MethodsWe evaluated the resilience (as resistance and recovery) to consecutive droughts, across an intensification gradient of livestock systems. We analyzed the effect of diversity on resilience at two scales: (1) regional — an observational experiment with real commercial farms, where we compared three systems with an increasing level of intensification that determine changes in diversity, (2) patch — we carried out a manipulative experiment with different grazing management intensities determined by the level of biomass removal and fertilization. In both experiments, resistance and recovery were calculated from the Normalized Difference Vegetation Index.ResultsThe most intensified and less diverse management (sown pastures) had significantly lower resistance than native and overseeded grassland. Also, it showed the lowest recovery rate, and its productivity did not reach previous values after the drought's end. The grazing intensification gradient at the plot scale did not show clear differences among treatments both for resistance and recovery. However, resistance of the individual plots showed a positive significant association not only with species richness and diversity, but also with evenness and diversity of functional groups.ConclusionOur research supports the insurance hypothesis by demonstrating that farms with greater biodiversity (less intensive management) have higher resistance to drought. We found that species richness is not enough to account for the effect of diversity on resilience. Our results emphasize the importance of preserving grassland biodiversity to maintain resilient ecosystems in the face of climate change.
Nonparametric Failure Time: Time-to-Event Machine Learning with Heteroskedastic Bayesian Additive Regression Trees and Low Information Omnibus Dirichlet Process Mixtures
Authors: Sparapani Rodney A. , Logan Brent R. , Maiers Martin J. , Laud Purushottam W. , McCulloch Robert E. 
Published: March 2023

AbstractMany popular survival models rely on restrictive parametric, or semiparametric, assumptions that could provide erroneous predictions when the effects of covariates are complex. Modern advances in computational hardware have led to an increasing interest in flexible Bayesian nonparametric methods for time-to-event data such as Bayesian additive regression trees (BART). We propose a novel approach that we call nonparametric failure time (NFT) BART in order to increase the flexibility beyond accelerated failure time (AFT) and proportional hazard models. NFT BART has three key features: (1) a BART prior for the mean function of the event time logarithm; (2) a heteroskedastic BART prior to deduce a covariate-dependent variance function; and (3) a flexible nonparametric error distribution using Dirichlet process mixtures (DPM). Our proposed approach widens the scope of hazard shapes including nonproportional hazards, can be scaled up to large sample sizes, naturally provides estimates of uncertainty via the posterior and can be seamlessly employed for variable selection. We provide convenient, user-friendly, computer software that is freely available as a reference implementation. Simulations demonstrate that NFT BART maintains excellent performance for survival prediction especially when AFT assumptions are violated by heteroskedasticity. We illustrate the proposed approach on a study examining predictors for mortality risk in patients undergoing hematopoietic stem cell transplant (HSCT) for blood-borne cancer, where heteroskedasticity and nonproportional hazards are likely present.
Evaluation of an adapted version of the International Trauma Questionnaire for use by people with intellectual disabilities
Authors: Langdon Peter E. , Bisson Jonathan I. , Rogers Gemma , Swain Sophie , Hiles Steve , Watkins Alan , Willner Paul 
Published: March 2023

AbstractAimsThe International Trauma Questionnaire (ITQ) is a novel assessment instrument that is aligned to the ICD‐11 diagnoses of post‐traumatic stress disorder (PTSD) and complex PTSD (CPTSD). The purpose of this study was to develop and evaluate an adapted version of the ITQ suitable for use by people with intellectual disabilities.MethodsThe ITQ‐ID follows the original ITQ, using wording developed in collaboration with a focus group of people with intellectual disabilities The ITQ‐ID was administered to 40 people with intellectual disabilities recruited from learning disability forensic and community settings, alongside a Trauma Information Form and the Impact of Event Scale‐Intellectual Disabilities (IES‐IDs).ResultsMost participants reported multiple traumatizing events. Around half of the participants met strict criteria for a diagnosis of PTSD, and around three quarters met looser criteria. Depending on definitions, between 66% and 93% of those who met criteria for PTSD also met criteria for a diagnosis of CPTSD. The ITQ‐ID showed a single‐component structure, with very good‐to‐excellent internal consistency, excellent test–retest reliability, and evidence of concurrent, discriminant, and content validity.SignificanceThe results support the potential of the ITQ‐ID for assessment of PTSD and CPTSD in people with intellectual disabilities in both clinical and research contexts and highlight the need for further validation work.
Job satisfaction and employer‐sponsored training
Authors: Kosteas Vasilios D. 
Published: March 2023

AbstractThis article examines whether participation in employer‐sponsored training has a causal impact on job satisfaction by accounting for individual fixed effects, individual‐by‐employer fixed effects and controlling for promotions in a sub‐sample of the data to address the endogeneity of participation arising from within employer job changes. The estimates show a consistent, positive effect of participation in employer‐sponsored training on job satisfaction. Conversely, participation in other types of training does not have a significant impact upon job satisfaction. Additionally, participation in employer‐sponsored training has a strong, negative correlation with turnover even while controlling for job satisfaction. Training does not exhibit a lasting effect of either job satisfaction or turnover.
Risks and benefits of partial nephrectomy performed with limited or with zero ischaemia time
Authors: Cignoli Daniele , Basile Giuseppe , Fallara Giuseppe , Rosiello Giuseppe , Belladelli Federico , Cei Francesco , Musso Giacomo , Re Chiara , Bertini Roberto , Karakiewicz Pierre , Mottrie Alexandre , Dehò Federico , Gallina Andrea , Montorsi Francesco , Salonia Andrea , Capitanio Umberto , Larcher Alessandro 
Published: March 2023

ObjectiveTo test the hypothesis that longer warm ischaemia time (WIT) might have a marginal impact on renal functional outcomes and might, in fact, reduce haemorrhagic risk intra‐operatively.Patients and MethodsData from 1140 patients treated with elective partial nephrectomy (PN) for a cT1‐2 cN0 cM0 renal mass were prospectively collected. WIT was defined as the duration of clamping of the main renal artery with no refrigeration and was tested as a continuous variable. The primary outcome of the study was evaluation of the effect of WIT on renal function (estimated glomerular filtration rate [eGFR]) postoperatively, at 6 months and in the long term (measured between 1 and 5 years after surgery). The secondary outcome of the study was haemorrhagic risk, defined as estimated blood loss (EBL) or peri‐operative transfusions. Multivariable linear, logistic and Cox regression analyses, accounting for age, Charlson comorbidity index, clinical size, preoperative eGFR and year of surgery, were used and the potential nonlinear relationship between WIT and the study outcomes was modelled using restricted cubic splines.ResultsA total of 863 patients (76%) underwent PN with WIT and 277 (24%) without. The baseline median eGFR was 87.3 (68.8–99.2) mL/min/1.73m2 for the on‐clamp population and 80.6 (63.2–95.2) mL/min/1.73m2 for the off‐clamp population. The median duration of WIT was 17 (13–21) min. At multivariable analyses predicting renal function, longer WIT was associated with decreased postoperative eGFR (estimate: −0.21, 95% confidence interval [CI] −0.31; −0.11 [P < 0.001]). Conversely, no association between WIT and eGFR was recorded at 6‐month or long‐term follow‐up (all P > 0.8). At multivariable analyses predicting haemorrhagic risk, clampless resection with no ischaemia time and PN with short WIT was associated with an increased EBL (estimate: −21.56, 95% CI −28.33; −14.79 [P < 0.001]) and peri‐operative transfusion rate (estimate: −0.009, 95% CI −0.01; −0.003 [P = 0.002]). No association between WIT and positive surgical margin status was recorded (all P = 0.1).ConclusionPatients and clinicians should be aware that performing PN with very limited or even with zero WIT might increase bleeding and the need for peri‐operative transfusion while not improving long‐term renal function outcomes.
Comparison between preoperative chemoradiotherapy and lateral pelvic lymph node dissection in clinical T3 low rectal cancer without enlarged lateral lymph nodes
Authors: Tsukada Yuichiro , Rullier Eric , Shiraishi Takuya , Capdepont Maylis , Sasaki Takeshi , Celerier Bertrand , Denost Quentin , Ito Masaaki 
Published: March 2023

AbstractAimThe standard strategy for clinical T3 rectal cancer without enlarged lateral lymph nodes is preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) in Western countries and TME with bilateral lateral pelvic lymph node dissection (LPLND) in Japan. This study compared surgical, pathological and oncological results of these two strategies.MethodPatients who underwent preoperative CRT followed by TME in France (CRT + TME group) and those who underwent TME with LPLND in Japan (TME + LPLND group) for clinical T3 rectal adenocarcinoma without enlarged lateral lymph nodes from 2010 to 2016 were retrospectively analysed.ResultsIn total, 439 patients were included in this study. The estimated local recurrence rate (LRR), disease‐free survival and overall survival at 5 years post‐surgery was 4.9%, 71% and 82% in the CRT + TME group, and 8.6%, 75% and 90% in the TME + LPLND group, respectively. Lateral LRR versus non‐lateral LRR was 0.5% versus 4.2% in the CRT + TME group and 1.8% versus 6.2% in the TME + LPLND group. Obturator nerve injury and isolated pelvic abscess were shown only in the TME + LPLND group. Urinary complications were more frequent in the TME + LPLND group than in the CRT + TME group.ConclusionDisease‐free survival was not significantly different after TME with LPLND and after CRT followed by TME. LRR was not significantly different after both strategies; however, there was a trend for higher LRR after TME with LPLND than after CRT followed by TME. Obturator nerve injury, isolated lateral pelvic abscess and urinary complications should be noted when TME with LPLND is applied.
Pharmacokinetics of intranasal amiloride in healthy volunteers
Authors: Yellepeddi Venkata K. , Battaglia Marco , Davies Simon J. C. , Alt Jeremiah , Ashby Shaelene , Shipman Paige , Anderson David J. , Rower Joseph E. , Reilly Christopher , Voight Michael , Mim Sabiha Rahman 
Published: March 2023

AbstractAnxiety and panic disorders are the most common mental illnesses in the United States and lack effective treatment options. Acid‐sending ion channels (ASICs) in the brain were shown to be associated with fear conditioning and anxiety responses and therefore are potential targets for treating panic disorder. Amiloride is an inhibitor of the ASICs in the brain and was shown to reduce panic symptoms in preclinical animal models. An intranasal formulation of amiloride will be highly beneficial to treat acute panic attacks due to advantages such as the rapid onset of action and patient compliance. The aim of this single‐center, open‐label trial was to evaluate the basic pharmacokinetics (PKs) and safety of amiloride after intranasal administration in healthy human volunteers at three doses (0.2, 0.4, and 0.6 mg). Amiloride was detected in plasma within 10 min of intranasal administration and showed a biphasic PK profile with an initial peak within 10 min of administration followed by a second peak between 4 and 8 h of administration. The biphasic PKs indicate an initial rapid absorption via the nasal pathway and later slower absorption by non‐nasal pathways. Intranasal amiloride exhibited a dose‐proportional increase in the area under the curve and did not exhibit any systemic toxicity. These data indicate that intranasal amiloride is rapidly absorbed and safe at the doses evaluated and can be further considered for clinical development as a portable, rapid, noninvasive, and nonaddictive anxiolytic agent to treat acute panic attacks.