bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender Differences in Mental Health of Bereaved Parents in an Only-Child Society: Evidence From China
Authors: Wang Enjian , Hu Hongwei , Shi Zhenzhen , Liu Hongting , Zhang Chu , Jiang Haixia , Xia Lu , Li Sisi , He Yongjia
Published: June 2019

This study examined gender differences in mental health of bereaved parents related to the gender of deceased only child in China, an only-child society with traditional culture of son preference, using data drawn from the China Family Planning Survey on Vulnerable Households in 2017. The findings indicated that parents with deceased only child suffered from more negative mental health symptoms than nonbereaved parents. For only-child-death families, there were no statistically significant gender differences in mental health of parents, and the gender of the deceased only child was basically unrelated to maternal/paternal mental health. Due to the implementation of one-child policy in China, both sons and daughters are highly prized and equally relied on by aging parents owing to the irreplaceability of the only child, which might moderate the effects of traditional culture of son preference on bereaved parental mental health.
Longitudinal Adaptive Pattern Analysis of Child Abuse Victims During Childhood and Adolescence
Authors: Paik In Shil , Ahn Sungsik , Lee Sang Min
Published: June 2019

Adopting a contextual, systematic perspective, the present study aimed to understand whether an individual’s adverse circumstances in one domain have a continuous effect on his or her maladaptation in another domain. The Korean Children and Youth Panel Survey data set, comprising a stratified sample of 1,932 students recruited from 95 schools from 16 cities in Korea, was used for pattern identification, latent class analysis, and latent transition analysis. Consistent with Masten’s resilience model, latent class analysis was used to identify the following four types of patterns: resilient, maladaptive, vulnerable, and competent-unchallenged. These four patterns were clearly identified at Time 1, Time 2, and Time 3. Latent transition analysis was used to identify the continuity and change patterns in the four groups across the developmental pathology. The transition probabilities from Time 1 to Time 2 were relatively unstable, with many variations observed among the latent classes; however, the transition probabilities from Time 2 to Time 3 remained relatively stable. An in-depth discussion of the findings and their implications is provided.
Assessment of cognitive functions and psychiatric symptoms in hepatitis C patients receiving pegylated interferon alpha and ribavirin: A prospective cohort study
Authors: Hassaan Shehab H , Darwish Alaa M , Khalifa Hossam , Ramadan Haidi Karam Alla , Hassany Sahar M , Ahmed Gellan K , Moustafa Ehab F
Published: June 2019

Objective

This study aimed to prospectively evaluate cognitive functioning in hepatitis C virus patients before, during, and after interferon alpha and to assess the psychiatric side effects of interferon alpha such as depression and anxiety.

Methods

A total of 100 chronic hepatitis C virus patients eligible for interferon therapy from the hepatitis outpatient clinic of Assiut University Hospital were included. A full medical and psychiatric assessment was done using the Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Rating Scale (HAM-A). Cognitive assessment was done using The Mini-Mental State Examination (MMSE), Memory Assessment Scales (MAS), and Wechsler Adult Intelligence Scale (WAIS). Medical, cognitive, and psychiatric assessments were conducted at the start of the study and after starting the treatment at two, four, and six months.

Results

There was a significant increase in the mean scores of HAM-D (t = 7.739, p < 0.001; t = 5.707, p < 0.001; t = 5.115, p < 0.001) and HAM-A (t = 6.237, p < 0.001; t = 4.154, p < 0.001; t = 3.955, p < 0.001) scales at the two, four, and six month follow-ups, respectively, in comparison to the baseline measurements. As regards to the MAS, repeated assessments after two, four, and six months showed no statistically significant difference from the baseline apart from deterioration in the verbal memory performance after six months in comparison to the baseline (t = −2.605, p = 0.011). As regards to MMSE, the verbal intelligence quotient (IQ), performance IQ, and total IQ, there was a significant improvement in the patients’ cognitive performance, in comparison to the baseline, after two months (t = 2.144, p = 0.035), four months (t = 2.868, p = 0.002), and six months (t = 3.505, p = 0.001), respectively. There was also a significant negative correlation between HAM-D mean scores and the MAS verbal mean scores of the patients (r = −.219, p = 0.039).

Conclusion

There were increases in symptoms of depression and anxiety during interferon alpha and ribavirin treatment, which do not correlate with the patients’ cognitive performance. There was a significant improvement in cognitive performance except in verbal memory with the progress of interferon alpha treatment. Years of education, socioeconomic status, and lower quantitative polymerase chain reaction are predictors for better cognitive performance.
Universal Measures of School Functioning in Middle School Special Education Students
Authors: Mattison Richard E.
Published: June 2019

Universal measures of school functioning/impairment (i.e., grade point average, subject failures, absenteeism, disciplinary referrals/suspensions) were examined over the course of 1 school year for a cohort of 89 special education students classified as having emotional disturbance (ED) who were taught in a unique public school program. On average during the year the students achieved at a high “C” level, failed major subjects infrequently, missed 11 days of school, and rarely were tardy. They averaged one disciplinary referral per marking period, but the majority were never suspended out of school. The measures generally were consistent across marking periods, independent of each other, and significantly correlated to DSM-IV psychiatric disorders (as rated by their teachers). Teachers contributed little variance to the measures. The findings support the increased use of these universal indicators of school function in students with ED as a research tool and a meaningful way of communication with educators about such students.
Effects of MDMA on neuroplasticity, amyloid burden and phospho-tau expression in APPswe/PS1dE9 mice
Authors: Abad Sonia , Ramon-Duaso Carla , López-Arnau Raúl , Folch Jaume , Pubill David , Camarasa Jordi , Camins Antoni , Escubedo Elena
Published: June 2019

Background:

3,4-Methylenedioxymethamphetamine (MDMA) is still one of the most consumed drugs by adolescents. Its abuse is related with cognitive impairment, which seems due to maladaptive plasticity and neural stress. In turn, new hypotheses suggest that Alzheimer’s disease (AD) may be promoted by neural stressors.

Aims and methods:

To test if there is an increase in vulnerability to AD after chronic MDMA consumption, we investigated the effects of this drug on recognition memory and its neurotoxic and neuroplastic effects in a transgenic mouse model of presymptomatic familiar AD (APP/PS1 dE9, Tg).

Results:

MDMA-treated animals showed recognition memory deficits, regardless of genotype, which were accompanied by changes in plasticity markers. Tg mice showed an impaired expression of Arc compared with wild-type animals, but exposure to MDMA induced an increase in the expression of this factor of the same percentage in both genotypes. However, the expression of c-fos, BDNF and p-CREB was not significantly altered by MDMA treatment in Tg mice. Although Tg mice had higher free choline levels than wild-type mice (about 123%), MDMA did not modify these levels in any case, ruling out any specific effect of this drug on the acetylcholine pathway. MDMA treatment significantly increased the presence of cortical amyloid plaques, as well as Aβ40, Aβ42 and secreted APPβ levels in Tg mice. These plaques were accompanied by increased tau phosphorylation (S199), which does not seem to occur via the canonic pathway involving AKT, CDK5 or GSK3β.

Conclusions:

The present results support previous evidences that MDMA can contribute to the amyloid cascade.
Identification of microRNAs and genes as biomarkers of atrial fibrillation using a bioinformatics approach
Authors: Li Yingyuan , Tan Wulin , Ye Fang , Xue Faling , Gao Shaowei , Huang Wenqi , Wang Zhongxing
Published: June 2019

Objective

We aimed to explore potential microRNAs (miRNAs) and target genes related to atrial fibrillation (AF).

Methods

Data for microarrays GSE70887 and GSE68475, both of which include AF and control groups, were downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs between AF and control groups were identified within each microarray, and the intersection of these two sets was obtained. These miRNAs were mapped to target genes in the miRNet database. Functional annotation and enrichment analysis of these target genes was performed in the DAVID database. The protein-protein interaction (PPI) network from the STRING database and the miRNA-target-gene network were merged into a PPI-miRNA network using Cytoscape software. Modules of this network containing miRNAs were detected and further analyzed.

Results

Ten differentially expressed miRNAs and 1520 target genes were identified. Three PPI-miRNA modules were constructed, which contained miR-424, miR-15a, miR-542-3p, and miR-421 as well as their target genes, CDK1, CDK6, and CCND3.

Conclusion

The identified miRNAs and genes may be related to the pathogenesis of AF. Thus, they may be potential biomarkers for diagnosis and targets for treatment of AF.
Multi-View and Multi-Scale Localization for Intelligent Vehicles in Underground Parking Lots
Authors: Huang Gang , Hu Zhaozheng , Mu Mengchao , Wang Xianglong , Zhang Fan
Published: June 2019

Because of limited access to global positioning system (GPS) signals, accurate and reliable localization for intelligent vehicles in underground parking lots is still an open problem. This paper proposes a multi-view and multi-scale localization method aiming at solving this problem. The proposed method is divided into an offline mapping stage and an online localization stage. In the mapping stage, the offline map is generated by fusing 3-D information, WiFi features, visual features, and trajectory from visual odometry (VO). In the localization stage, WiFi fingerprint matching is exploited for coarse localization. Based on the result of coarse localization, multi-view localization is exploited for image-level localization. Finally, metric localization is exploited to refine the localization results. By applying this multi-scale strategy, it is possible to fuse WiFi localization and visual localization and reduce the image matching and error rate to a great extent. Because of exploiting more information, multi-view localization is more robust and accurate than single-view localization. The method is tested in a 2,000 m2 underground parking lot. The result demonstrates that this method can achieve sub-meter localization on average. The proposed localization method can be a supplement to the existing intelligent vehicle localization techniques.
Abortion travels: An international history
Authors: Reagan Leslie J
Published: June 2019

This article examines how women crossed local and national borders in order to obtain abortions despite laws and religious injunctions that forbade abortion. Investigating that travel reveals transnational networks of information and assistance among abortion providers, physicians, feminists, and others; it also makes visible how changing laws changed patterns of abortion travel. This article considers travelling for abortion from the 19th through the 21st century primarily by North Americans and Europeans who travelled across borders, oceans, and continents to many different countries around the world in order to obtain abortions.
An Efficient Synthesis of Phenanthroindolizidine Core via Hetero Diels-Alder Reaction of In Situ Generated α-Allenylchalcogenoketenes With Cyclic Imines
Authors: Shimada Kazuaki , Suzuki Mariko , Yahaba Kohei , Aoyagi Shigenobu , Takikawa Yuji , Korenaga Toshinobu
Published: June 2019

Synthesis of phenanthroindolizidine core was efficiently achieved through a pathway involving hetero Diels-Alder reaction of α-allenylchalcogenoketenes, generated in situ by thermal [3,3] sigmatropic rearrangement of alkynyl propargyl sulfides or selenides, with cyclic imines and the subsequent iodine-assisted photochemical cyclization.
Surgical Outcomes of Endoscopic Versus Open Resection for Primary Sinonasal Malignancy: A Meta-analysis
Authors: Lu Victor M. , Ravindran Krishnan , Phan Kevin , Van Gompel Jamie J. , Smith Timothy R. , Donaldson Angela M. , Quinones-Hinojosa Alfredo , Mekary Rania A. , Chaichana Kaisorn L.
Published: June 2019

Background

Endoscopic resection (ER) for uncommon sinonasal malignancies (SNMs) has been reported to confer superior surgical outcomes compared to open resection (OR) based on indirect comparisons of limited evidence.

Objective

The aim of this study was to pool all direct comparative studies in the literature to validate this potential superior association.

Methods

Systematic searches of 7 electronic databases from their inception to April 2019 were conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. There were 1001 articles identified for screening. Outcomes of interest were pooled as risk ratios (RRs) and mean difference (MD) and analyzed using a random-effects model.

Results

There were 10 studies included in this meta-analysis, with 900 SNM patients in total where ER and OR were utilized in 399 (44%) and 501 (56%) cases, respectively. Compared to OR, random-effects (RE) modeling indicated ER resulted in statistically comparable complications (RR = 0.68; P-effect = .12) and recurrence (RR = 0.84; P-effect = .35). ER was associated with significantly shorter length of stay (LOS) compared to OR (MD = −2.9 days; P-effect <.01).

Conclusions

The use of ER to manage SNM was associated with significantly favorable reduction in LOS compared to OR. However, with respect to other surgical outcomes and recurrence, the current literature does not indicate either ER or OR as statistically superior. Therefore, until greater validation of these associations can be proven, expectations that ER for SNMs confers superior surgical outcomes compared to OR should be tempered.
Mineralogical and crystal-chemical characterization of the talc ore deposit of Minzanzala, Gabon
Authors: Poirier Mathilde , Boulingui Jean-Eudes , Martin François , Mbina Mounguengui Michel , Nkoumbou Charles , Thomas Fabien , Cathelineau Michel , Yvon Jacques
Published: June 2019

This research aims to characterize the mineralogical and crystal-chemical purity of two samples of natural talc (BTT6, BTT7) from the occurrence ‘Ecole1’ in the deposit of Minzanzala, southwest Gabon. X-ray diffraction and modal-composition calculations demonstrated the presence of quartz and Al–Fe-bearing phases (kaolinite and/or chlorite and/or Al–Fe oxyhydroxides) as accessory minerals in both ores. In contrast, the chemical and spectroscopic characterization of the talc component revealed remarkable chemical purity expressed by very low Fe contents. According to these results, the talc of Minzanzala might be used as a filler in a wide range of industrial applications, such as in cosmetics, paints, polymers or ceramics.
External validation and comparison of multiple prognostic scores in allogeneic hematopoietic stem cell transplantation
Authors: Shouval Roni , Fein Joshua A. , Shouval Aniela , Danylesko Ivetta , Shem-Tov Noga , Zlotnik Maya , Yerushalmi Ronit , Shimoni Avichai , Nagler Arnon
Published: June 2019

Clinical decisions in allogeneic hematopoietic stem cell transplantation (allo-HSCT) are supported by the use of prognostic scores for outcome prediction. Scores vary in their features and in the composition of development cohorts. We sought to externally validate and compare the performance of 8 commonly applied scoring systems on a cohort of allo-HSCT recipients. Among 528 patients studied, acute myeloid leukemia was the leading transplant indication (44%) and 46% of patients had a matched sibling donor. Most models successfully grouped patients into higher and lower risk strata, supporting their use for risk classification. However, discrimination varied (2-year overall survival area under the receiver operating characteristic curve [AUC]: revised Pretransplantation Assessment of Mortality [rPAM], 0.64; PAM, 0.63; revised Disease Risk Index [rDRI], 0.62; Endothelial Activation and Stress Index [EASIx], 0.60; combined European Society for Blood and Marrow Transplantation [EBMT]/Hematopoietic Cell Transplantation-specific Comorbidity Index [HCT-CI], 0.58; EBMT, 0.58; Comorbidity-Age, 0.58; HCT-CI, 0.55); AUC ranges from 0.5 (random) to 1.0 (perfect prediction). rPAM and PAM, which had the greatest predictive capacity across all outcomes, are comprehensive models including patient, disease, and transplantation information. Interestingly, EASIx, a biomarker-driven model, had comparable performance for nonrelapse mortality (NRM; 2-year AUC, 0.65) but no predictive value for relapse (2-year AUC, 0.53). Overall, allo-HSCT prognostic systems may be useful for risk stratification, but individual prediction remains a challenge, as reflected by the scores’ limited discriminative capacity.
Plasma Cell-Free DNA Testing of Patients With EGFR Mutant Non–Small-Cell Lung Cancer: Droplet Digital PCR Versus Next-Generation Sequencing Compared With Tissue-Based Results
Authors: Steendam Christi M.J. , Atmodimedjo Peggy , de Jonge Evert , Paats Marthe S. , van der Leest Cor , Oomen-de Hoop Esther , Jansen Maurice P.H.M. , Del Re Marzia , von der Thüsen Jan H. , Dinjens Winand N.M. , van Schaik Ron H.N. , Aerts Joachim G.J.V. , Dubbink Hendrikus Jan ,   on behalf of Erasmus MC Cancer Institute
Published: June 2019

PURPOSE

To compare the results of plasma cell-free DNA (cfDNA) droplet digital PCR (ddPCR) and next-generation sequencing (NGS) on detection of epidermal growth factor receptor ( EGFR) primary activating mutations and p.T790M with results of tissue analysis in patients with EGFR mutated non–small-cell lung cancer.

METHODS

All patients with EGFR mutated non–small cell lung cancer for which a pathology and a plasma specimen were available upon progression between November 2016 and July 2018 were selected. Concordance, Cohen’s κ, and intraclass correlation coefficients were calculated.

RESULTS

Plasma cfDNA and pathology specimens of 36 patients were analyzed. Agreement between ddPCR and NGS was 86% (κ = 0.63) for the primary activating mutation and 94% (κ = 0.89) for the p.T790M detection. Allele ratios were comparable, with an intraclass correlation coefficient of 0.992 and 0.997, respectively. Discrepancies of some degree were found in 15 patients (41.7%). In six patients (16.7%), no mutations were detected in cfDNA. In three patients (8.3%), p.T790M was detected in plasma but not in the pathology specimen, whereas in three other patients (8.3%), p.T790M was demonstrated in the pathology specimen but not in plasma. Concordance of cfDNA and pathology for the primary activating mutation was 69% for ddPCR and 83% for NGS. For the detection of p.T790M, this was 75% (κ = 0.49) for ddPCR as well as for NGS.

CONCLUSION

Mutual agreement is high between NGS and ddPCR in cfDNA on the level of a specific mutation, with comparable ratio results. Plasma testing of EGFR primary activating mutations and p.T790M shows high concordance with pathology results, for NGS as well as for ddPCR, depending on the extent of the panel used. In NGS, more genetic aberrations can be investigated at once.
Clinical Utility of Real-Time Targeted Molecular Profiling in the Clinical Management of Ovarian Cancer: The ALLOCATE Study
Authors: Kondrashova Olga , Ho Gwo-Yaw , Au-Yeung George , Leas Leakhena , Boughtwood Tiffany , Alsop Kathryn , Zapparoli Giada , Dobrovic Alexander , Ko Yi-An , Hsu Arthur L. , Love Clare J. , Lunke Sebastian , Wakefield Matthew J. , McNally Orla , Quinn Michael , Ananda Sumitra , Neesham Deborah , Hamilton Anne , Grossi Marisa , Freimund Alison , Kanjanapan Yada , Rischin Danny , Traficante Nadia , Bowtell David , Scott Clare L. , Christie Michael , Taylor Graham R. , Mileshkin Linda , Waring Paul M. ,   on behalf of the Australian Ovarian Cancer Study Group
Published: June 2019

PURPOSE

The ALLOCATE study was designed as a pilot to demonstrate the feasibility and clinical utility of real-time targeted molecular profiling of patients with recurrent or advanced ovarian cancer for identification of potential targeted therapies.

PATIENTS AND METHODS

A total of 113 patients with ovarian cancer of varying histologies were recruited from two tertiary hospitals, with 99 patient cases suitable for prospective analysis. Targeted molecular and methylation profiling of fresh biopsy and archived tumor samples were performed by screening for mutations or copy-number variations in 44 genes and for promoter methylation of BRCA1 and RAD51C.

RESULTS

Somatic genomic or methylation events were identified in 85% of all patient cases, with potentially actionable events with defined targeted therapies (including four resistance events) detected in 60% of all patient cases. On the basis of these findings, six patients received molecularly guided therapy, three patients had unsuspected germline cancer–associated BRCA1/ 2 mutations and were referred for genetic counseling, and two intermediate differentiated (grade 2) serous ovarian carcinomas were reclassified as low grade, leading to changes in clinical management. Additionally, secondary reversion mutations in BRCA1/ 2 were identified in fresh biopsy samples of two patients, consistent with clinical platinum/poly (ADP-ribose) polymerase inhibitor resistance. Timely reporting of results if molecular testing is done at disease recurrence, as well as early referral for patients with platinum-resistant cancers, were identified as factors that could improve the clinical utility of molecular profiling.

CONCLUSION

ALLOCATE molecular profiling identified known genomic and methylation alterations of the different ovarian cancer subtypes and was deemed feasible and useful in routine clinical practice. Better patient selection and access to a wider range of targeted therapies or clinical trials will further enhance the clinical utility of molecular profiling.
Evaluating the Low-Dose ACTH Stimulation Test in Children: Ideal Times for Cortisol Measurement
Authors: Gill Harpreet , Barrowman Nick , Webster Richard , Ahmet Alexandra
Published: June 2019

Context

Central adrenal insufficiency (AI) can be diagnosed with the low-dose ACTH stimulation test (LDST). Protocols determining timing of cortisol sampling vary, with 30 minutes after stimulation being most common.

Objectives

To determine optimal times to draw cortisol levels and factors predicting timing of peak cortisol levels in children undergoing LDST.

Design

Retrospective chart review of LDSTs between February 2014 and September 2017.

Setting

The Children’s Hospital of Eastern Ontario.

Patients

Patients 3 months to 20 years who underwent LDSTs.

Intervention

LDSTs were performed with cortisol levels at 0, 15, 30, and 60 minutes after 1 μg cosyntropin. Cortisol values <18 μg/dL (500 nmol/L) determined AI.

Main Outcome Measures

The incremental value of testing cortisol at 15 or 60 minutes, in addition to the standard 30-minute sample, was estimated.

Results

A total of 221 patients met inclusion criteria. The mean age was 9.7 years, and 32% were female. Peak cortisol levels were 19%, 67%, and 14% at 15, 30, and 60 minutes, respectively. One false positive LDST result would be prevented for every 24 (95% CI, 13 to 46) or 55 (95% CI, 22 to 141) patients tested at 15 or 60 minutes in addition to the standard 30-minute test. Of the 122 patients who passed the LDST, discontinuing the 15- and 60-minute samples would have misdiagnosed 12 patients (9.8%). Glucocorticoid exposure, age, and body mass index z scores were independent predictors of peak cortisol timing.

Conclusion

Although the majority of patients peak 30 minutes after cosyntropin administration, testing cortisol levels at 15 and 60 minutes reduces the risk of false positive LDSTs.
Haptoglobin Phenotype Modulates Lipoprotein-Associated Risk for Preeclampsia in Women With Type 1 Diabetes
Authors: Kelly Clare B , Yu Jeremy Y , Jenkins Alicia J , Nankervis Alison J , Hanssen Kristian F , Garg Satish K , Scardo James A , Basu Arpita , Hammad Samar M , Aston Christopher E , Lyons Timothy J
Published: June 2019

Context

The incidence of preeclampsia (PE) is increased in women with diabetes (∼20% vs ∼5% in the general population), and first trimester lipoprotein profiles are predictive. Haptoglobin (Hp), a protein with functional genetic polymorphisms, has antioxidant, anti-inflammatory, and angiogenic effects. Among people with diabetes, the Hp 2-2 phenotype is associated with cardiorenal disease.

Objective

To investigate whether Hp phenotype is associated with PE in type 1 diabetes mellitus (T1DM) and/or modulates lipoprotein-associated risks.

Design and Setting

Multicenter prospective study of T1DM pregnancy.

Patients

Pregnant women with T1DM (normal albuminuria, normotensive at enrolment, n = 47) studied at three visits, all preceding PE onset: 12.3 ± 1.9, 21.8 ± 1.5, and 31.5 ± 1.6 weeks’ gestation (mean ± SD).

Main Outcome Measures

Hp phenotype and lipoprotein profiles in women with (n = 23) vs without (n = 24) subsequent PE.

Results

Hp phenotype did not predict PE, but lipoprotein associations with subsequent PE were confined to women with Hp 2-2, in whom the following associations with PE were observed: increased low-density lipoprotein (LDL) cholesterol, LDL particle concentration, apolipoprotein B (APOB), triacylglycerol/high-density lipoprotein (HDL) cholesterol ratio, and APOB/apolipoprotein AI (APOA1) ratio; decreased HDL cholesterol, APOA1, large HDL particle concentration, and peripheral lipoprotein lipolysis (all P < 0.05). In women with one or two Hp-1 alleles, no such associations were observed.

Conclusions

In women with T1DM, although Hp phenotype did not predict PE risk, lipoprotein-related risks for PE were limited to those with the Hp 2-2 phenotype. Hp phenotype may modulate PE risk in diabetes.
Pasireotide and Pegvisomant Combination Treatment in Acromegaly Resistant to Second-Line Therapies: A Longitudinal Study
Authors: Chiloiro Sabrina , Bima Chiara , Tartaglione Tommaso , Giampietro Antonella , Gessi Marco , Lauretti Liverana , Anile Carmelo , Colosimo Cesare , Rindi Guido , Pontecorvi Alfredo , De Marinis Laura , Bianchi Antonio
Published: June 2019

Context

The treatment of acromegaly resistant to first- and second-line therapies can be extremely challenging.

Design

We have described six patients who were successfully treated with a combination therapy of pasireotide and pegvisomant and compared them with a control group of patients resistant to conventional somatostatin analogs (SSAs), whose disease was controlled with other treatment, such as pasireotide (as monotherapy) or pegvisomant (as monotherapy or combined with conventional SSAs).

Results

In these six patients, acromegaly was controlled with combined pasireotide and pegvisomant treatment after failure of all other treatments. Compared with the 49 patients in the control group, these six patients had giant and invasive pituitary adenomas (at both the cavernous sinus and other structures). Although not statistically significant, higher growth hormone levels, more elevated Ki-67 expression, greater somatostatin receptor (SSTR) subtype 5 expression, and lower SSTR subtype 2 expression at the diagnosis of acromegaly were detected in patients receiving combination treatment with pasireotide and pegvisomant compared with the control group.

Conclusion

Our data have reinforced the importance of personalized treatment of patients with acromegaly according to the clinical, biochemical, molecular, and morphological disease markers and suggest that combined treatment with pasireotide and pegvisomant can induce disease control in tumors with low SSTR2 expression, resistant to conventional SSAs (alone or combined with pegvisomant) and to new-generation SSAs alone (pasireotide).
Differences in Trabecular Plate and Rod Structure in Premenopausal Women Across the Weight Spectrum
Authors: Schorr Melanie , Fazeli Pouneh K , Bachmann Katherine N , Faje Alexander T , Meenaghan Erinne , Kimball Allison , Singhal Vibha , Ebrahimi Seda , Gleysteen Suzanne , Mickley Diane , Eddy Kamryn T , Misra Madhusmita , Klibanski Anne , Miller Karen K
Published: June 2019

Context

Premenopausal women with anorexia nervosa (AN) and obesity (OB) have elevated fracture risk. More plate-like and axially aligned trabecular bone, assessed by individual trabeculae segmentation (ITS), is associated with higher estimated bone strength. Trabecular plate and rod structure has not been reported across the weight spectrum.

Objective

To investigate trabecular plate and rod structure in premenopausal women.

Design

Cross-sectional study.

Setting

Clinical research center.

Participants

A total of 105 women age 21 to 46 years: (i) women with AN (n = 46), (ii) eumenorrheic lean healthy controls (HCs) (n = 29), and (iii) eumenorrheic women with OB (n = 30).

Measures

Trabecular microarchitecture by ITS.

Results

Mean age (±SD) was similar (28.9 ± 6.3 years) and body mass index differed (16.7 ± 1.8 vs 22.6 ± 1.4 vs 35.1 ± 3.3 kg/m2; P < 0.0001) across groups. Bone was less plate-like and axially aligned in AN (P ≤ 0.01) and did not differ between OB and HC. After controlling for weight, plate and axial bone volume fraction and plate number density were lower in OB vs HC; some were lower in OB than AN (P < 0.05). The relationship between weight and plate variables was quadratic (R = 0.39 to 0.70; P ≤ 0.0006) (i.e., positive associations were attenuated at high weight). Appendicular lean mass and IGF-1 levels were positively associated with plate variables (R = 0.27 to 0.67; P < 0.05). Amenorrhea was associated with lower radial plate variables than eumenorrhea in AN (P < 0.05).

Conclusions

In women with AN, trabecular bone is less plate-like. In women with OB, trabecular plates do not adapt to high weight. This is relevant because trabecular plates are associated with greater estimated bone strength. Higher muscle mass and IGF-1 levels may mitigate some of the adverse effects of low weight or excess adiposity on bone.
Overcoming Language Barriers Using an Information Video on Spinal Anesthesia for Cesarean Delivery: Implementation and Impact on Maternal Anxiety
Authors: Purcell-Jones Jessica M. A. , Haasbroek Marlis , Van der Westhuizen Justine L. , Dyer Robert A. , Lombard Carl J. , Duys Rowan A.
Published: June 2019

BACKGROUND:

It is unknown whether the implementation of an information video on spinal anesthesia for cesarean delivery, narrated in a patient’s first language, reduces anxiety, increases satisfaction, and improves doctor–patient communication if there is a language barrier. In South Africa, most doctors speak English, and patients speak Xhosa, with educational and cultural disparities existing in many doctor–patient interactions.

METHODS:

One hundred seventy-five Xhosa patients scheduled for elective cesarean delivery were enrolled in the study. The first 92 patients received “usual care” verbal explanations of the spinal anesthesia procedure (control group); the next 83 patients watched a spinal anesthesia information video (intervention group), narrated in Xhosa. Videos were displayed using smartphones. Maternal anxiety was assessed before and after spinal explanation, using a Numerical Visual Analog Anxiety Scale (NVAAS). A difference in postexplanation NVAAS score of 1.5 points between intervention and control groups was regarded as clinically significant. Patient satisfaction was assessed using the Maternal Satisfaction Scale for Cesarean Section (MSSCS).

RESULTS:

The mean (standard deviation [SD]) age (31.5 years [5.2 years] and 32.1 years [5.4 years]) and preexplanation NVAAS score (4.2 [3.2] and 4.0 [3.0]) of the intervention and control groups, respectively, showed no difference at baseline. The mean (SD) postexplanation decrease in NVAAS score was greater in the intervention than in the control group (1.6 [3.5] vs 0.7 [2.3]; P = .046; unadjusted mean difference, 0.9 points [95% confidence interval {CI}, 0.02–1.8]). A linear regression model for the postexplanation NVAAS score showed that the intervention effect was significantly associated with the preexplanation score (P = .002), adjusted for age and English fluency. Patients with preexplanation NVAAS scores ≥5 showed a statistically significant intervention effect. There was no significant difference in patient satisfaction between the intervention and control groups. The smartphone was an accessible and convenient display medium for the video. Ninety-nine percent of patients exposed to the intervention would recommend watching the video before the procedure.

CONCLUSIONS:

In this pilot study, lower NVAAS scores were observed in anxious patients, when a Xhosa information video was used to ameliorate challenges posed by a doctor–patient language barrier. It is easily implemented and demonstrates a novel use of mobile health technology. The study provides baseline data to inform sample size calculations for future studies. A high level of patient recommendation for the video suggests that this is an agreeable practice.
Anesthesia Type Is Not Associated With Postoperative Complications in the Care of Patients With Lower Extremity Traumatic Fractures
Authors: Brovman Ethan Y. , Wallace Frances C. , Weaver Michael J. , Beutler Sasha S. , Urman Richard D.
Published: June 2019

BACKGROUND:

Lower extremity fracture fixation is commonplace and represents the majority of orthopedic trauma surgical volume. Despite this, few studies have examined the use of regional anesthesia or neuraxial anesthesia (RA/NA) versus general anesthesia (GA) in this surgical population. We aimed to determine the overall rates of RA/NA use and whether RA/NA was associated with lower mortality and morbidity versus GA for patients with lower extremity orthopedic trauma.

METHODS:

We conducted a propensity-matched, retrospective cohort study of hospitalized patients. We used the American College of Surgeons National Surgical Quality Improvement Project (ACS-NSQIP) dataset to identify patients undergoing surgical correction of low velocity orthopedic lower extremity traumas between 2011 and 2016. Patients were separated into 2 groups based on anesthesia type (RA/NA versus GA). The primary outcome was 30-day mortality. Secondary outcomes included return to the operating room, failure to wean from the ventilator, intubation, pneumonia, acute kidney injury, myocardial infarction, transfusion, venous thromboembolism (VTE), urinary tract infection, sepsis, length of stay, days from operation to discharge, number of complications, and unplanned readmission.

RESULTS:

We identified 18,467 patients undergoing surgical repair of lower extremity fractures. Approximately 9.58% had RA/NA and 89.9% had GA as their primary anesthetic. After 1:1 propensity matching, the final cohort had 3254 patients. Our analysis did not find a difference in 30-day mortality between the 2 groups. There were also no significant differences in secondary outcomes.

CONCLUSIONS:

Despite the potential advantages of RA/NA, utilization for lower extremity trauma was low in our analysis; only 9.58% of patients were in the RA/NA group, with the majority receiving spinal anesthesia. This may be due to surgeon preference to allow for postoperative monitoring for neurologic injury and compartment syndrome or logistical factors given the urgent nature of these trauma cases. No significant differences in 30-day mortality and postoperative complications were found between RA/NA and GA for patients with lower extremity orthopedic fractures. The choice of anesthesia is multifactorial and may be driven by patient and provider preferences in these operations.
Development of mouse models of angiosarcoma driven by p53
Authors: Salter Donald M. , Griffin Meredyth , Muir Morwenna , Teo Katy , Culley Jayne , Smith James R. , Gomez-Cuadrado Laura , Matchett Kylie , Sims Andrew H. , Hayward Larry , Henderson Neil C. , Brunton Valerie G.
Published: June 2019

Angiosarcomas are a rare group of tumours which have poor prognosis and limited treatment options. The development of new therapies has been hampered by a lack of good preclinical models. Here, we describe the development of an autochthonous mouse model of angiosarcoma driven by loss of p53 in VE-cadherin-expressing endothelial cells. Using Cdh5-Cre to drive recombination in adult endothelial cells, mice developed angiosarcomas with 100% penetrance upon homozygous deletion of Trp53 with a median lifespan of 325 days. In contrast, expression of the R172H mutant p53 resulted in formation of thymic lymphomas with a more rapid onset (median lifespan 151 days). We also used Pdgfrb-Cre-expressing mice, allowing us to target predominantly pericytes, as these have been reported as the cell of origin for a number of soft tissue sarcomas. Pdgfrb-Cre also results in low levels of recombination in venous blood endothelial cells in multiple tissues during development. Upon deletion of Trp53 in Pdgfrb-Cre-expressing mice (Pdgfrb-Cre, Trp53fl/fl mice), 65% developed lymphomas and 21% developed pleomorphic undifferentiated soft tissue sarcomas. None developed angiosarcomas. In contrast, 75% of Pdgfrb-Cre, Trp53R172H/R172H mice developed angiosarcomas, with 60% of these mice also developing lymphomas. The median lifespan of the Pdgfrb-Cre, Trp53R172H/R172H mice was 151 days. Re-implantation of angiosarcoma tumour fragments from Cdh5-Cre, Trp53fl/fl mice provided a more consistent and rapid model of angiosarcoma than the two spontaneous models. The ability to passage tumour fragments through the mouse provides a novel model which is amenable to preclinical studies and will help the development of potential new therapies for angiosarcoma.
The exocyst complex and Rab5 are required for abscission by localizing ESCRT III subunits to the cytokinetic bridge
Authors: Kumar Harsh , Pushpa Kumari , Kumari Amrita , Verma Kuldeep , Pergu Rajaiah , Mylavarapu Sivaram V. S.
Published: June 2019

Cytokinesis is the final step of cell division following chromosome segregation that generates two daughter cells. The conserved exocyst complex is required for scission of the intercellular cytokinetic bridge, although the molecular mechanisms it employs in this process are unclear. We identify and validate the early endocytic GTPase Rab5 as interacting with the exocyst complex in mammalian cells. Rab5 localizes in the cytokinetic bridge and on the midbody ring in a manner similar to the exocyst complex. Depletion of Rab5 led to delayed abscission. Caenorhabditis elegans orthologs of both exocyst complex subunits and Rab5 localize along the cleavage furrow and are required for cytokinesis in early embryos. Cytokinetic cells depleted of either Rab5 or the exocyst subunits Exoc3 and Exoc4 showed impaired deposition of the endosomal sorting complexes required for transport (ESCRT) III subunits CHMP2B and/or CHMP4B near the midbody ring. The study reveals an evolutionarily conserved role for the early endocytic marker Rab5 in cytokinetic abscission. In addition, it uncovers a key requirement of the exocyst and Rab5 for the delivery of components of the membrane-severing ESCRT III machinery to complete cytokinesis.
MRB10130 is a RESC assembly factor that promotes kinetoplastid RNA editing initiation and progression
Authors: McAdams Natalie M. , Harrison Gregory L. , Tylec Brianna L. , Ammerman Michelle L. , Chen Runpu , Sun Yijun , Read Laurie K.
Published: June 2019

Uridine insertion deletion editing in kinetoplastid protozoa requires a complex machinery, a primary component of which is the RNA editing substrate binding complex (RESC). RESC contains two modules termed GRBC (guide RNA binding complex) and REMC (RNA editing mediator complex), although how interactions between these modules and their mRNA and gRNA binding partners are controlled is not well understood. Here, we demonstrate that the ARM/HEAT repeat containing RESC protein, MRB10130, controls REMC association with mRNA- and gRNA-loaded GRBC. High-throughput sequencing analyses show that MRB10130 functions in both initiation and 3′ to 5′ progression of editing through gRNA-defined domains. Editing intermediates that accumulate upon MRB10130 depletion significantly intersect those in cells depleted of another RESC organizer, MRB7260, but are distinct from those in cells depleted of specific REMC proteins. We present a model in which MRB10130 coordinates numerous protein–protein and protein–RNA interactions during editing progression.
Identification and phylogenetic analysis of oral Veillonella species isolated from the saliva of Japanese children
Authors: Djais Ariadna A. , Theodorea Citra Fragrantia , Mashima Izumi , Otomo Maiko , Saitoh Masato , Nakazawa Futoshi
Published: June 2019

Background:As the most frequent infectious disease among children worldwide, dental caries have a strong relationship with oral hygiene status, specifically in the development of infection. OralVeillonellaspecies have a main role as early colonizers in the oral biofilm formation. Previously, oralVeillonellastrains were detected at the species level in the saliva of Thai children with different oral hygiene statuses. Here, we studied the oral hygiene status by examining the composition and proportion of oralVeillonellaspecies in saliva of Japanese children to compare with the previous results found in Thai children.

Methods:Microbial samples collected from 15 Japanese children divided into three oral hygiene groups were cultured under anaerobic conditions after homogenization and dilution, and inoculated onto brain heart infusion and selective mediumVeillonellaagar. Genomic DNA was extracted from each isolate.Veillonellaspecies were detected by one-step PCR usingrpoBspecies-specific primers. To analyse the phylogenetic properties of the unknownVeillonellastrains, PCR amplification and sequence analysis ofrpoBwere conducted for 10 representative strains.

Results:AlthoughV. rogosaewas found as the predominant species among all groups, its prevalence was significantly lower in the children with poor oral hygiene than in those with good oral hygiene.V. parvulawas the prevalent species in the poor oral hygiene group. Approximately 10% of the isolatedVeillonellastrains were not classified to any established species; the phylogenetic analysis showed that they were most closely related toV.infantium

Conclusions:This study demonstrates that the composition and proportion of oralVeillonellaspecies in the saliva of Japanese children is correlated with different oral hygiene status. Changes in detection ratios ofV. parvulaandV. rogosaecan be useful indicators of oral hygiene status. Furthermore, new strains closely related toV.infantiumwere isolated from the saliva of Japanese children.
Longitudinal data on parental religious behaviour and beliefs from the Avon Longitudinal Study of Parents and Children (ALSPAC)
Authors: Iles-Caven Yasmin , Gregory Steven , Northstone Kate , Golding Jean
Published: June 2019

There is evidence that, in general, the West is becoming more secular. Religious belief has been shown in some studies to have positive associations with outcomes such as coping with serious illness and other life events and general well-being. In this paper, we describe the data from parents enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) on their religious behaviour and beliefs collected on three occasions during the 1990s and early 2000s, that are available for researchers to use in association with other longitudinally collected data on social, biological, genetic and epigenetic features of this culturally largely protestant Christian population. Data were collected antenatally and then subsequently at 5 and 9 years post-delivery from self-completion questionnaires completed by each parent independently.  Strong sex differences (all P<0.001) were noted regarding religious beliefs and behaviour: for example, 49.9% of women stated that they believed in God or some divine being compared with 37% of men. Almost twice as many men (28.6%) than women (14.9%) declared they were atheists. Men were less likely to have stated that they had been helped by a divine presence; to appeal to God if they were in trouble, to attend religious services or obtain help from members of religious groups. Among the 6256 women and 2355 men who answered the questions at all three time points, there was evidence of a slight reduction in professed belief and a slight increase in the proportion stating that they were atheists. Information is available from this resource, which is rich in data on the environment, traumatic incidents, health and genetic background. It can be used for research into various aspects of the antecedents and consequences of religious belief and behaviour.
A Matter of Principle: Accounting Reports Convey Both Cash-Flow News and Discount-Rate News
Authors: Penman Stephen H. , Yehuda Nir
Published: June 2019

This paper modifies the standard returns-earnings regression in accounting research to show that financial reports convey both cash-flow news and discount-rate (expected-return) news. The paper points to the realization principle, associated as it is with the resolution of risk, as the accounting feature that conveys expected-return news. The modified returns-earnings regressions indicate that the information so conveyed pertains to priced risk. In corroboration, the paper also shows that the identified expected-return news forecasts changes in both stock return betas and earnings betas, and expected-return news predicts future returns, whereas cash-flow news does not. The analysis yields a number of additional insights: financial statements distinguish expected-return news associated with operations from that associated with financing activities; given accounting information, there is not much news in dividends; and, in comparing the information content of earnings versus cash flows, cash flows largely convey expected-return news rather than cash-flow news. In sum, the paper shows that the objective of the Financial Accounting Standards Board and International Accounting Standards Board to provide information about the amount and uncertainty of future cash flows is (as least, partially) satisfied by accounting principles underlying current financial reporting.

This paper was accepted by Suraj Srinivasan, accounting.