bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxicologic Pathology Forum*: Opinion on Sexual Maturity and Fertility Assessment in Long-tailed Macaques (Macaca fascicularis) in Nonclinical Safety Studies
Authors: Mecklenburg Lars , Luetjens C. Marc , Weinbauer Gerhard F. 
Published: March 2019

If nonhuman primates represent the only relevant species for nonclinical safety evaluation of biotechnology-derived products, male and female fertility effects can be assessed in repeat dose toxicity studies given that sexually mature monkeys are used. This opinion piece provides recommendations for determining sexual maturity and when/how fertility assessments should be conducted in the cynomolgus monkey. Male sexual maturity should be proven by presence of sperm in a semen sample, female sexual maturity by at least two consecutive menstrual bleedings. As per regulatory guidance, default parameters for an indirect assessment of fertility in both sexes are reproductive organ weight and histopathology. Beyond default parameters, daily vaginal swabs are recommended for females, and for males, it is recommended to include blood collections (for potential analysis of reproductive hormones), testis volume sonography, and collection of frozen testis samples at necropsy. Only if there is a cause for concern, blood collection for potential reproductive hormone analysis should be conducted in females and semen analysis in males. In principle, adverse reproductive effects can be detected within 4 weeks of test article administration, depending on study design and reproductive end point chosen. Therefore, there are options for addressing reproductive toxicity aspects with studies of less than 3 months dosing duration. [Box: see text]
Comparison of invasive micropapillary and invasive ductal carcinoma of the breast: a matched cohort study
Authors: Yoon Ga Young , Cha Joo Hee , Kim Hak Hee , Shin Hee Jung , Chae Eun Young , Choi Woo Jung 
Published: March 2019

Background Invasive micropapillary carcinoma (IMPC) is a rare subtype of breast cancer and is presumed to have a poorer survival outcome than invasive ductal carcinoma (IDC). However, studies for clinical outcomes including imaging features are still scarce. Purpose To investigate differences in clinical outcomes between IMPC and IDC and to determine prognostic factors indicating survival, including imaging features. Material and Methods This retrospective study was approved by the institutional review board. Between 2007 and 2012, 308 women diagnosed with IMPC were matched with patients from a group of 6816 women diagnosed with IDC. Patients were matched with 17 clinicopathologic covariates using propensity score matching. Recurrence-free survival (RFS) and overall survival (OS) were compared between the IMPC and IDC groups using Kaplan–Meier estimates. Log-rank tests were performed to compare the survival curves. A Cox proportional hazard model was used to analyze the association of imaging features with survival. Results In total, 308 matched patient pairs were available for survival analysis. The IMPC group showed worse total RFS (hazard ratio [HR] = 1.63, P = 0.016), local RFS (HR = 2.86, P = 0.042), and distant RFS (HR = 1.85 P = 0.018), but there was no significant difference in OS (HR = 1.30, P = 0.335). A mass with calcification on mammography was an independent factor for worse RFS in the IMPC group and combined IMPC and IDC groups. IMPC subtype was a significant independent factor for worse RFS in the combined groups. Conclusion The IMPC group showed poorer recurrence-free survival outcomes than the IDC group. A mass with calcification on mammography were associated with poor RFS.
Bi-exponential versus mono-exponential diffusion-weighted imaging for evaluating prostate cancer aggressiveness after radical prostatectomy: a whole-tumor histogram analysis
Authors: Zhang Peipei , Min Xiangde , Wang Liang , Feng Zhaoyan , Ke Zan , You Huijuan , Fan Chanyuan , Li Qiubai 
Published: March 2019

Background The diagnostic efficacy of mono- and bi-exponential diffusion models are controversial in prostate cancer (PCa) aggressiveness evaluation. Whole-tumor histogram analysis may have the potential to improve their efficacy. Purpose To compare the efficacy of mono- and bi-exponential diffusion models for evaluating PCa aggressiveness using whole-tumor histogram analysis. Material and Methods In this retrospective study, 72 patients with PCa confirmed by radical prostatectomy were included. All patients underwent multi-b-value diffusion-weighted imaging (DWI). The mono-exponential model parameter (apparent diffusion coefficient [ADC]) and bi-exponential model parameters ( D, D*, and f ) were calculated and whole-tumor histogram analysis was performed. Tumor lesions were classified into low-grade (LG) and high-grade (HG) Gleason grade groups. Spearman analysis was used to evaluate the correlations between the histogram metrics and Gleason score (GS). The area under the receiver operating characteristic curve (AUC) was used to assess the discriminatory capacity of each parameter in distinguishing LG from HG PCa. Results Most histogram metrics of ADC and D showed significant correlations with the GS. None of the histogram metrics of D* and only the maximum value and skewness of f showed significant correlations with GS. The 90th percentile ADC and 90th and 75th percentile D showed relatively higher efficacies than other histogram metrics. However, their AUCs were not significantly higher than that of mean ADC. Conclusion The bi-exponential model was not superior to the mono-exponential diffusion model for evaluating PCa aggressiveness. The histogram metrics did not outperform the conventional mean value.
Effect of large follicle puncture on IVF-ET outcome in patients with unsynchronized follicle maturationcan
Authors: Wang Xinrong , Wang Wenjuan , Qu Qinglan , Zhang Ning , Hao Cuifang , Ma Ding 
Published: March 2019

Objective This retrospective study was conducted to explore causes of unsynchronized follicular maturation (UFM) and analyze the effects of large follicle puncture on embryo quality and pregnancy outcome. Methods Clinical features and controlled ovulation hyperstimulation (COH) were compared between the puncture group (n = 48) and the control group (n = 2545). We analyzed the COH process with in vitro fertilization during fresh cycle embryo transfer with different clinical pregnancy outcomes. We compared clinical characteristics and COH process of patients in the clinical pregnancy (n = 774) and non-clinical pregnancy (n = 527) groups. Finally, factors related to pregnancy outcomes were analyzed using multivariate logistic regression analysis. Results Age, level of estradiol on down-regulation day, and initial gonadotropin dose were significantly higher in the puncture group than in the control group. We detected significant differences in age, infertility, and body mass index (BMI) between the clinical and non-clinical pregnancy groups. Age, BMI, and endometrial thickness on the day of human chorionic gonadotropin administration were the independent factors influencing pregnancy outcome. Conclusions Patient’s age and level of anti-Müllerian hormone were the main factors causing UFM in patients undergoing COH. Large follicle puncture had no significant effect on pregnancy outcome.
Discover, Instrumentalize, Monopolize: Fidesz’s Three-Step Blueprint for a Populist Take-over of Referendums
Authors: van Eeden Pepijn 
Published: March 2019

This article assesses the referendums in Hungary in 2004, 2008, and 2016 diachronically. The review is framed by two competing liberal parliamentary approaches to direct democracy: A useful democratic corrective to the distortions of particracy, or a risky option leading to tyranny of the majority? Rather than choosing sides, this article shows how the conundrum conceals another, more interesting question: Which are the constraints under which the liberal parliamentary viewpoint shifts from the one to the other? Theorizing on post-democracy and populism provides a provisional answer: A consensualized, “post-political” parliament is key, as this, in combination with widening social-economic disparities, incentivizes illiberal populist parties to harness referendums, which prompts liberal parliamentarianists to change their minds. The referendums in 2004, 2008, and 2016 in Hungary substantiate this suspicion. Taken together, they offer a step-by-step blueprint for how, in a thoroughly postpolitical situation, a referendum evolves into a perfect catalyst for populists on their road to power, enabling them with (a) agenda-setting; (b) an explosive emphasis on popular legitimacy; (c) arousing voluntarism, while luring opponents into campaigning for boycott and political apathy; (d) combining social equalitarianism with identarian protectionism, and most importantly; (e) bypassing parliament itself. This article is part of the special cluster titled Political Parties and Direct Democracy in Eastern Europe, guest-edited by Sergiu Gherghina.
Developing and employing a ‘responsive manualization’ in the ‘Acupuncture Approaches to Decrease Disparities in Outcomes of Pain Treatment’ comparative effectiveness study
Authors: Nielsen Arya , Anderson Belinda , Citkovitz Claudia , Botet Patricia , Correia Susana , Duque Valentina , Greene Selina , Mah Donna , Moore Dana , Pagliarini Amy , McKee M Diane , Kligler Benjamin 
Published: March 2019

Objective: The aim of this article is to describe the process used to develop an acupuncture therapy manual for a large effectiveness trial comparing individual care against group care for chronic pain in an underserved population. The design needed to not only ensure research consistency and replicability but also be ‘responsive’ to real world heterogeneous and evolving presentations in challenging physical settings. Background: Chronic pain is prevalent in the United States. While acupuncture is effective for chronic pain, minority, ethnically diverse and lower socioeconomic populations have limited access. Group acupuncture is proposed as a lower cost option to facilitate access in safety net settings, but research on the effectiveness of group versus individual acupuncture is lacking. Methods: We engaged a modified Delphi process with expert practitioners from diverse backgrounds who were experienced in individual and group practice. All contributions were recorded and collated for second- and third-round consensus discussions that included contributions by the trial’s research acupuncturists. Results: A ‘responsive manual’ flow chart was created with suggested sequencing that included interviews concurrent with palpation, Tui na, Gua sha, acupuncture needling, ear treatment, basic recommendations and options for departure with rationale. The manual was implemented by six research acupuncturists in five primary care settings in the Bronx, New York, with weekly team meetings to discuss manual use. There were no serious adverse events (AE) and few minor AE reported in this trial. Conclusion: A ‘responsive manual’ can be structured and implemented that is not only consistent and replicable but also flexible to accommodate the real-world clinical needs of practitioners and patients in challenging physical settings.
Preliminary investigation on feline coronavirus presence in the reproductive tract of the tom cat as a potential route of viral transmission
Authors: Stranieri Angelica , Probo Monica , Pisu Maria C , Fioletti Alberto , Meazzi Sara , Gelain Maria E , Bonsembiante Federico , Lauzi Stefania , Paltrinieri Saverio 
Published: March 2019

Objectives Feline infectious peritonitis (FIP) is an immune-mediated disease initiated by feline coronavirus (FCoV) infection. To date, the only proven route of transmission is the faecal–oral route, but a possible localisation of FCoV in the reproductive tract of tom cats is of concern, owing to the involvement of the male reproductive tract during FIP and to the presence of reproduction disorders in FCoV-endemic feline catteries. The aim of the study was to investigate the presence and localisation of FCoV in semen and/or in the reproductive tract of tom cats, and its possible association with seroconversion and viraemic phase. Methods Blood, serum, semen and/or testicle samples were obtained from 46 tom cats. Serology was performed on 38 serum samples, nested reverse transcriptase PCR (nRT-PCR) and reverse transcriptase quantitative PCR (RT-qPCR) were performed on 39 blood samples and on 17 semen samples, and histology, immunohistochemistry and nRT-PCR were performed on 39 testicles. Results Twenty-four of 38 serum samples were positive on serology. Semen samples were negative on RT-PCR and RT-qPCR for FCoV, while all blood samples were negative at both molecular methods, except for one sample positive at RT-qPCR with a very low viral load. All testicles were negative at immunohistochemistry, while six were positive at nRT-PCR for FCoV. Serology and blood PCR results suggest that the virus was present in the environment, stimulating transient seroconversion. FCoV seems not to localise in the semen of tom cats, making the venereal route as a way of transmission unlikely. Although viral RNA was found in some testicles, it could not be correlated with the viraemic phase. Conclusions and relevance In the light of these preliminary results, artificial insemination appears safer than natural mating as it eliminates the direct contact between animals, thus diminishing the probability of faecal–oral FCoV transmission.
Inter- and intra-observer reliability of quantitative sensory testing performed with the SMall animal ALGOmeter (SMALGO) to evaluate pain associated with feline gingivostomatitis
Authors: Machin Hanna , Pevere Serena , Adami Chiara 
Published: March 2019

Objectives The aim of this study was to evaluate the inter- and intra-observer reliability of quantitative sensory testing performed with the SMall animal ALGOmeter (SMALGO) in healthy cats and in cats with chronic gingivostomatitis (CGS), and to evaluate the SMALGO as a tool to detect and quantify pain in cats with CGS. Methods Thirty cats from a private shelter were included and assigned to one of two groups: group C (healthy cats; n = 15) or group CGS (cats with CGS; n = 15). In all cats the mechanical thresholds were measured with the SMALGO, with the sensor tip applied to the superior lip above the canine root, by two independent investigators (A, experienced; B, unexperienced), on two different occasions (day 1 and day 2) with a 24 h interval. A CGS scale was used in the diseased cats to assess the severity of the condition. For the reliability analysis, intra-class correlation coefficients (ICCs) were calculated. Other statistical tests used were Pearson correlation coefficient and a paired t-test. Results The inter- and intra-observer levels of agreement were fair (ICC = 0.50) and good, respectively (ICC = 0.73 for investigator A; ICC = 0.60 for investigator B). However, the thresholds measured in healthy cats (169 ± 59 g) did not differ from those obtained from diseased cats (156 ± 82 g; P = 0.35). There was no correlation between the scores of the CGS scale and the thresholds measured in diseased cats (Pearson correlation coefficient = 0.047; P = 0.87). Conclusions and relevance Quantitative sensory testing performed with the SMALGO in cats is repeatable and reliable, regardless of the expertise of the investigator. However, the findings of this study suggest that the mechanical thresholds measured with the SMALGO may not be a valuable indicator of pain in cats with CGS.
Validation of a Hidradenitis Suppurativa Self-Assessment Tool
Authors: Senthilnathan Aditi , Kolli Sree S. , Cardwell Leah A. , Richardson Irma , Feldman Steven R. , Pichardo Rita O. 
Published: March 2019

Background: Hidradenitis suppurativa (HS) is a debilitating dermatologic condition presenting with recurrent abscesses. While there are multiple scales to determine HS severity, none are designed for self-administration. A validated severity self-assessment tool may facilitate survey research and improve communication by allowing patients to objectively report their HS severity between clinic visits. Objectives: The purpose of this study was to assess a self-administered HS measure. Methods: An HS self-assessment tool (HSSA) with 10 photographs of different Hurley stages was developed. The tool was administered to patients diagnosed with HS who visited the Wake Forest Baptist Health dermatology clinic over a span of 2 months. Physician-administered Hurley stage was recorded to determine criterion validity. To assess test-retest reliability of the measure, patients completed the HSSA again at least 30 minutes after the first completion. Results: Twenty-four patients completed the measure, and 20 of these patients completed it twice. Agreement between physician-determined Hurley stage and self-determined Hurley stage was 66.7% with a weighted kappa of 0.57 (95% confidence interval [CI]: 0.30-0.84). The weighted kappa for agreement between patients’ initial and second completion of the HSSA was 0.81 (95% CI: 0.64-0.99). Conclusions: The self-administered measure provides moderate agreement with physician-determined Hurley stage and good test-retest reliability.
Neurovascular disorders in pregnancy: A review
Authors: Roth Julie , Deck Gina 
Published: March 2019

While rare, neurovascular disorders that occur in pregnant or postpartum women are associated with high morbidity and mortality, thus necessitating prompt identification and treatment. The most common symptoms include headache, focal neurological features, and seizures. Factors such as pregnancy-related hypercoagulability and hemodynamic changes put women at risk for neurovascular disorders in the third trimester and early postpartum period. The biggest risk factors for stroke in pregnancy are hypertension and the preeclampsia/eclampsia spectrum. This review outlines the diagnosis and treatment of pregnant and postpartum women with ischemic and hemorrhagic stroke, cerebral venous sinus thrombosis, posterior reversible encephalopathy syndrome, and reversible cerebral vasoconstriction syndrome. Trial registration: Not applicable.
Intermittent Parathyroid Hormone [1-34] Augments Chondrogenesis of the Mandibular Condylar Cartilage of the Temporomandibular Joint
Authors: Dutra Eliane H. , O’Brien Mara H. , Chen Po-Jung , Wei Mei , Yadav Sumit 
Published: March 2019

Objective To characterize the long-term effects of intermittent parathyroid hormone (I-PTH) on the mandibular condylar cartilage (MCC) and subchondral bone of the temporomandibular joint, in vivo and in vitro. Materials and Methods For the in vivo experiments, sixteen 10-week-old mice were divided into 2 groups: (1) I-PTH ( n = 8)—subcutaneous daily injection of PTH; (2) control group ( n = 8)—subcutaneous daily injection of saline solution. Experiments were carried out for 4 weeks. Mice were injected with calcein, alizarin complexone, and cell proliferation marker before euthanasia. For the in vitro experiments, primary chondrocyte cultures from the MCC of eight 10-week-old mice were treated with I-PTH for 14 days. Results There was a significant increase in bone volume, tissue density, mineral deposition, osteoclastic activity, cell proliferation in the cartilage, and cartilage thickness in the I-PTH-treated mice when compared with the control group. In addition, immunohistochemistry in cartilage revealed that I-PTH administration led to an increase in expression of vascular endothelial growth factor and to a decreased expression of sclerostin, matrix metallopeptidase 13, and aggreganase-1 (ADAM-TS4). Quantitative polymerase chain reaction analysis of the I-PTH-treated chondrocytes revealed significantly decreased relative expression of collagen type X ( Col10a1), alkaline phosphatase ( Alp), and Indian Hedgehog ( Ihh) and remarkable increased expression of Sox9, fibroblast growth factor 2 ( Fgf2), and proteoglycan 4 ( Prg4). Conclusion I-PTH administration causes anabolic effects at the subchondral region of the mandibular condyle while triggers anabolic and protective effects at the MCC.
Sexual Dysfunction in Aging Males: A Review
Authors: Priyadarshi Shivam 
Published: March 2019

Assaults on sexuality in aging males result from changes in sexual physiology, psychosocial changes, irregular sexual activity, androgen deficiency, cardiovascular disease and risk factors, and lower urinary tract symptoms. Chronic illness, side effects of medications, and different kinds of surgery which the male may undergo during the aging process may all have its deleterious effects on sexual functions. A healthy sexual attitude combined with lifestyle changes and addressing the physical problems provide a greater potential for enjoying a more fulfilled sexual life as one ages.
NPM1 mutations define a specific subgroup of MDS and MDS/MPN patients with favorable outcomes with intensive chemotherapy
Authors: Montalban-Bravo Guillermo , Kanagal-Shamanna Rashmi , Sasaki Koji , Patel Keyur , Ganan-Gomez Irene , Jabbour Elias , Kadia Tapan , Ravandi Farhad , DiNardo Courtney , Borthakur Gautham , Takahashi Koichi , Konopleva Marina , Komrokji Rami S. , DeZern Amy , Kuzmanovic Teodora , Maciejewski Jaroslaw , Pierce Sherry , Colla Simona , Sekeres Mikkael A. , Kantarjian Hagop , Bueso-Ramos Carlos , Garcia-Manero Guillermo 
Published: March 2019

Abstract
Nucleophosmin (NPM1) mutations are common in acute myeloid leukemia and are associated with high remission rates and prolonged survival with intensive chemotherapy. NPM1 mutations are rare in myelodysplastic syndromes (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN), and the clinical outcomes of these patients, when treated with intensive chemotherapy, are unknown. We retrospectively evaluated the clinicopathologic characteristics and the impact of therapy in 31 patients with MDS or MDS/MPN and NPM1 mutations. Next-generation sequencing was performed at diagnosis in 22 patients. Median age was 62 years (range, 19-86). Twenty-four patients (77%) had normal karyotype, and all had multilineage dysplasia. Most patients could be classified as MDS with excess blasts (19/31, 61%). NPM1 mutations were detected at a median allele frequency of 0.38 (range, 0.09-0.49). Mutation burden did not correlate with bone marrow blast frequency, and its clearance seemed to be associated with decreased morphologic dysplasia. Ten of the 31 patients (32%) received cytotoxic chemotherapy, 20 (65%) hypomethylating agents, and 1 (4%) lenalidomide. Sequential sequencing was available in 16 (52%) patients, and mutation burden correlated with disease status and response to therapy. Patients treated with chemotherapy had higher complete response rates (90% vs 28%, P = .004), longer median progression-free survival (not reached vs 7.5 months, P = .023), and overall survival (not reached vs 16 months, P = .047). Intensive chemotherapy and allogeneic stem cell transplantation (SCT) may be associated with improved clinical outcomes in patients with NPM1-mutated MDS or MDS/MPN who are candidates for this form of therapy.