bluuebunny/crossref_metadata_2025 huggingface dataset:
The Gut Microbiome: A New Player in Breast Cancer Metastasis
Authors: Ingman Wendy V.
Published: July 2019

There is increasing interest in the role of the gut microbiome in health and disease, and a number of observational and in vitro studies have suggested it may play a role in breast cancer development and progression. Buchta Rosean and colleagues present the first functional evidence that a preexisting disturbance in the gut microbiome leads to increased breast cancer cell metastasis in a mouse model. This discovery places the gut microbiome as a new player in breast cancer metastasis; however, further studies are required to determine the relevance of the findings in this mouse model to human disease. A better understanding of the relationship between the bacterial ecosystem of the gut and progression of breast cancer has enormous potential for improving treatment outcomes for patients with breast cancer.

See related article by Buchta Rosean et al., p. 3662
Molecular and Clinical Activity of CDX-3379, an Anti-ErbB3 Monoclonal Antibody, in Head and Neck Squamous Cell Carcinoma Patients
Authors: Duvvuri Umamaheswar , George Jonathan , Kim Seungwon , Alvarado Diego , Neumeister Veronique M. , Chenna Ahmed , Gedrich Richard , Hawthorne Thomas , LaVallee Theresa , Grandis Jennifer R. , Bauman Julie E.
Published: July 2019

Purpose:

ErbB3 and its ligand neuregulin-1 (NRG1) are widely expressed in head and neck squamous cell carcinoma (HNSCC) and associated with tumor progression. A “window-of-opportunity” study (NCT02473731) was conducted to evaluate the pharmacodynamic effects of CDX-3379, an anti-ErbB3 mAb, in patients with HNSCC.

Patients and Methods:

Twelve patients with newly diagnosed, operable HNSCC received two infusions of CDX-3379 (1,000 mg) at a 2-week interval prior to tumor resection. The primary study objective was to achieve ≥50% reduction in tumor ErbB3 signaling (phosphorylation of ErbB3; pErbB3) in ≥30% of patients. Other potential tumor biomarkers, pharmacokinetics, safety, and tumor measurements were also assessed.

Results:

pErbB3 was detectable in all tumors prior to treatment and decreased for 10 of 12 (83%) patients following CDX-3379 dosing, with ≥50% reduction in 7 of 12 (58%; P = 0.04; 95% confidence interval, 27.7%–84.8%). Target trough CDX-3379 serum levels were achieved in all patients. CDX-3379 treatment–related toxicity was grade 1–2 and included diarrhea, fatigue, and acneiform dermatitis. Five of 12 (42%) patients had shrinkage in tumor burden, including a marked clinical response in a patient with human papillomavirus–negative oral cavity HNSCC. All patients with tumor shrinkage had tumors that expressed both NRG1 and ErbB3 and demonstrated reduced pErbB3 with CDX-3379 treatment.

Conclusions:

This study demonstrates that CDX-3379 can inhibit tumor ErbB3 phosphorylation in HNSCC. CDX-3379 was well tolerated and associated with measurable tumor regression. A phase II study (NCT03254927) has been initiated to evaluate CDX-3379 in combination with cetuximab for patients with advanced HNSCC.
Dose-Ranging and Cohort-Expansion Study of Monalizumab (IPH2201) in Patients with Advanced Gynecologic Malignancies: A Trial of the Canadian Cancer Trials Group (CCTG): IND221
Authors: Tinker Anna V. , Hirte Holger W. , Provencher Diane , Butler Marcus , Ritter Heather , Tu Dongsheng , Azim Hatem A. , Paralejas Paulo , Grenier Nathalie , Hahn Shirley-Ann , Ramsahai Janelle , Seymour Lesley
Published: July 2019

Purpose:

Monalizumab binds CD94/NKG2A, preventing HLA-E inhibition of tumor lymphocytes. A dose-ranging/cohort expansion trial of monalizumab for recurrent gynecologic malignancies was conducted to determine the recommended phase II dose (RP2D) and to explore clinical activity, pharmacokinetics, pharmacodynamics, safety, and immunogenicity.

Patients and Methods:

Participants (and part 2 expansion cohorts) included (i) platinum-sensitive ovarian, (ii) platinum-resistant ovarian, (iii) squamous cervical (CX), and (iv) epithelial endometrial (END) carcinomas. Part 1 assessed monalizumab at 1, 4, or 10 mg/kg every 2 weeks. In part 2, ≥4 patients/cohort underwent pre- and on-treatment tumor biopsies. Preset criteria determined cohort expansion.

Results:

A total of 58 participants were evaluable. The RP2D was 10 mg/kg i.v. every 2 weeks. Dose proportionality and 100% NKG2A saturation were observed. Related adverse events were mild: headache, abdominal pain, fatigue, nausea, and vomiting. Grade 3 related adverse events were nausea (1), vomiting (1), dehydration (1), fatigue (2), anorexia (1), dyspnea (1), and proctitis (1). Dose-limiting toxicities were not observed. Hematologic and biochemical changes were mild and not dose related. Best response was SD: part 1, 7 of 18 (39%) [3.4 months (1.4–5.5)], and part 2, 7 of 39 (18%) [1.7 months (CX) to 14.8 months (END)]. Neither a predictive biomarker for SD nor evidence of pharmacodynamic effects was identified. There was a trend to significance between a reduction in lymphocyte HLA-E total score and pharmacodynamics.

Conclusions:

Monalizumab 10 mg/kg i.v. every 2 week is well tolerated in patients with pretreated gynecologic cancers. Short-term disease stabilization was observed. Future studies should assess combinations with other agents, including immunotherapeutics.
Loss of Function of DOCK4 in Myelodysplastic Syndromes Stem Cells is Restored by Inhibitors of DOCK4 Signaling Networks
Authors: Sundaravel Sriram , Kuo Wen-Liang , Jeong Jong Jin , Choudhary Gaurav S. , Gordon-Mitchell Shanisha , Liu Hui , Bhagat Tushar D. , McGraw Kathy L. , Gurbuxani Sandeep , List Alan F. , Verma Amit , Wickrema Amittha
Published: July 2019

Purpose:

Myelodysplastic syndromes (MDS) with deletion of chromosome 7q/7 [-7/(del)7q MDS] is associated with worse outcomes and needs novel insights into pathogenesis. Reduced expression of signaling protein dedicator of cytokinesis 4 (DOCK4) in patients with -7/(del)7q MDS leads to a block in hematopoietic stem cell (HSC) differentiation. Identification of targetable signaling networks downstream of DOCK4 will provide means to restore hematopoietic differentiation in MDS.

Experimental Design: We utilized phosphoproteomics approaches to identify signaling proteins perturbed as a result of reduced expression of DOCK4 in human HSCs and tested their functional significance in primary model systems.

Results:

We demonstrate that reduced levels of DOCK4 lead to increased global tyrosine phosphorylation of proteins in primary human HSCs. LYN kinase and phosphatases INPP5D (SHIP1) and PTPN6 (SHP1) displayed greatest levels of tyrosine phosphorylation when DOCK4 expression levels were reduced using DOCK4-specific siRNA. Our data also found that increased phosphorylation of SHIP1 and SHP1 phosphatases were due to LYN kinase targeting these phosphatases as substrates. Increased migration and impediment of HSC differentiation were consequences of these signaling alterations. Pharmacologic inhibition of SHP1 reversed these functional aberrations in HSCs expressing low DOCK4 levels. In addition, differentiation block seen in DOCK4 haplo-insufficient [-7/(del)7q] MDS was rescued by inhibition of SHP1 phosphatase.

Conclusions:

LYN kinase and phosphatases SHP1 and SHIP1 are perturbed when DOCK4 expression levels are low. Inhibition of SHP1 promotes erythroid differentiation in healthy HSCs and in -7/(del)7q MDS samples with low DOCK4 expression. Inhibitors of LYN, SHP1 and SHIP1 also abrogated increased migratory properties in HSCs expressing reduced levels of DOCK4.
KIT-Dependent and KIT-Independent Genomic Heterogeneity of Resistance in Gastrointestinal Stromal Tumors — TORC1/2 Inhibition as Salvage Strategy
Authors: Mühlenberg Thomas , Ketzer Julia , Heinrich Michael C. , Grunewald Susanne , Marino-Enriquez Adrian , Trautmann Marcel , Hartmann Wolfgang , Wardelmann Eva , Treckmann Jürgen , Worm Karl , Bertram Stefanie , Herold Thomas , Schildhaus Hans-Ulrich , Glimm Hanno , Stenzinger Albrecht , Brors Benedikt , Horak Peter , Hohenberger Peter , Fröhling Stefan , Fletcher Jonathan A. , Bauer Sebastian
Published: July 2019

Sporadic gastrointestinal stromal tumors (GIST), characterized by activating mutations of KIT or PDGFRA, favorably respond to KIT inhibitory treatment but eventually become resistant. The development of effective salvage treatments is complicated by the heterogeneity of KIT secondary resistance mutations. Recently, additional mutations that independently activate KIT-downstream signaling have been found in pretreated patients—adding further complexity to the scope of resistance. We collected genotyping data for KIT from tumor samples of pretreated GIST, providing a representative overview on the distribution and incidence of secondary KIT mutations (n = 80). Analyzing next-generation sequencing data of 109 GIST, we found that 18% carried mutations in KIT-downstream signaling intermediates (NF1/2, PTEN, RAS, PIK3CA, TSC1/2, AKT, BRAF) potentially mediating resistance to KIT inhibitors. Notably, we found no apparent other driver mutations in refractory cases that were analyzed by whole exome/genome sequencing (13/109). Using CRISPR/Cas9 methods, we generated a panel of GIST cell lines harboring mutations in KIT, PTEN, KRAS, NF1, and TSC2. We utilized this panel to evaluate sapanisertib, a novel mTOR kinase inhibitor, as a salvage strategy. Sapanisertib had potent antiproliferative effects in all cell lines, including those with KIT-downstream mutations. Combinations with KIT or MEK inhibitors completely abrogated GIST-survival signaling and displayed synergistic effects. Our isogenic cell line panel closely approximates the genetic heterogeneity of resistance observed in heavily pretreated patients with GIST. With the clinical development of novel, broad spectrum KIT inhibitors, emergence of non-KIT–related resistance may require combination treatments with inhibitors of KIT-downstream signaling such as mTOR or MEK.
Semaphorin 4C Promotes Macrophage Recruitment and Angiogenesis in Breast Cancer
Authors: Yang Jie , Zeng Zhen , Qiao Long , Jiang Xuefeng , Ma Jingjing , Wang Junnai , Ye Shuangmei , Ma Quanfu , Wei Juncheng , Wu Mingfu , Huang Xiaoyuan , Ma Ding , Gao Qinglei
Published: July 2019

Semaphorins are a large family of evolutionarily conserved morphogenetic molecules that are associated with repelling axonal guidance. Intriguingly, recent researches indicate that semaphorins are involved in cancer progression. Semaphorin 4C (SEMA4C) has long been considered a neuronal migration gene, but we detected that it is also highly expressed in many malignant human cancers. During an investigation of subcutaneous tumor models, we found that SEMA4C expression promoted tumor growth and progression. We discovered that SEMA4C was involved in maintaining tumor cell self-renewal, likely by regulating the p53 pathway. Inhibiting the expression of endogenous SEMA4C in tumor cells impaired growth and induced senescence and cell-cycle arrest in the G2-phase. In addition, we found that SEMA4C induced the production of angiogenin and colony-stimulating factor-1 (CSF-1) in tumor cells by activating the NF-κB pathway in a plexinB2-dependent manner. In conclusion, SEMA4C expression in breast cancer cells promotes cancer cell proliferation, macrophage recruitment, and angiogenesis. Thus, inhibition of SEMA4C activity may be a novel therapeutic strategy for human breast cancer.

Implications:

In breast cancer, therapeutic targeting of the SEMA4C pathway may prevent tumor growth, angiogenesis, metastasis, and progression.
HILPDA Regulates Lipid Metabolism, Lipid Droplet Abundance, and Response to Microenvironmental Stress in Solid Tumors
Authors: VandeKopple Matthew J. , Wu Jinghai , Auer Erich N. , Giaccia Amato J. , Denko Nicholas C. , Papandreou Ioanna
Published: July 2019

Accumulation of lipid droplets has been observed in an increasing range of tumors. However, the molecular determinants of this phenotype and the impact of the tumor microenvironment on lipid droplet dynamics are not well defined. The hypoxia-inducible and lipid droplet associated protein HILPDA is known to regulate lipid storage and physiologic responses to feeding conditions in mice, and was recently shown to promote hypoxic lipid droplet formation through inhibition of the rate-limiting lipase adipose triglyceride lipase (ATGL). Here, we identify fatty acid loading and nutrient deprivation–induced autophagy as stimuli of HILPDA-dependent lipid droplet growth. Using mouse embryonic fibroblasts and human tumor cells, we found that genetic ablation of HILPDA compromised hypoxia–fatty acid– and starvation-induced lipid droplet formation and triglyceride storage. Nutrient deprivation upregulated HILPDA protein posttranscriptionally by a mechanism requiring autophagic flux and lipid droplet turnover, independent of HIF1 transactivation. Mechanistically, loss of HILPDA led to elevated lipolysis, which could be corrected by inhibition of ATGL. Lipidomic analysis revealed not only quantitative but also qualitative differences in the glycerolipid and phospholipid profile of HILPDA wild-type and knockout cells, indicating additional HILPDA functions affecting lipid metabolism. Deletion studies of HILPDA mutants identified the N-terminal hydrophobic domain as sufficient for targeting to lipid droplets and restoration of triglyceride storage. In vivo, HILPDA-ablated cells showed decreased intratumoral triglyceride levels and impaired xenograft tumor growth associated with elevated levels of apoptosis.

Implications:

Tumor microenvironmental stresses induce changes in lipid droplet dynamics via HILPDA. Regulation of triglyceride hydrolysis is crucial for cell homeostasis and tumor growth.
Angiotensin II Receptor Type 1 Antagonists Modulate Vascular Smooth Muscle Cell Proliferation and Migration via AMPK/mTOR
Authors: Zhao Yingshuai , Shang Fenqing , Shi Weili , Zhang Jiao , Zhang Junjian , Liu Xiaoyu , Li Bing , Hu Xingang , Wang Liuyi
Published: July 2019

The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) in the vascular wall are crucial pathological events involved in cardiovascular impairments including hypertension, heart failure, and atherosclerosis. At the molecular level, the mammalian target of rapamycin (mTOR)-ribosomal protein S6 kinase beta-1 (p70S6K) signaling pathway is essential to potentiate VSMC proliferation and migration. Although angiotensin II receptor type 1 ­(AT1-R) antagonists such as valsartan and telmisartan have a significant cardiovascular protective effect, the molecular basis of this class of drugs in VSMC proliferation and migration remains elusive. By using cultured VSMCs, adenosine monophosphate-activated protein kinase (AMPK) α2 knockout mice, and hypertensive rat models, this study investigated whether AT1-R antagonists can inhibit the mTOR-p70S6K signaling pathway in VSMCs and the vascular wall. Valsartan activated AMPK, which in turn suppressed reactive oxygen species production and consequently attenuated VSMC proliferation and migration. In vivo, a clinical dose of telmisartan significantly inhibited the mTOR-p70S6K signaling pathway in the vascular wall of wild-type but not AMPKα2–/– mice. Furthermore, spontaneously hypertensive rats had significantly elevated phosphorylation of mTOR and p70S6K in the aorta compared to Wistar-Kyoto rats, which were reduced by telmisartan administration. These data suggest that AT1-R antagonists inhibit VSMC proliferation and migration via their regulation of AMPK, mTOR, and p70S6K, which contribute to the cardioprotective effects of these drugs.
The Clinical Risk Index for Babies II for Prediction of Time-Dependent Mortality and Short-Term Morbidities in Very Low Birth Weight Infants
Authors: Lee Soon Min , Lee Myung Hee , Chang Yun Sil ,   and the Korean Neonatal Network
Published: July 2019

Background: A simple predictive indicator of mortality and morbidities is essential to assess neonatal illness severity and plan proper management. Objective: This study aimed to test the time-dependent performance of the Clinical Risk Index for Babies (CRIB) II in predicting mortality and major short-term morbidities among very low birth weight infants (VLBWIs). Methods: This population-based prospective study from 67 Korean Neonatal Network centers performed between 2013 and 2016 included 5,296 VLBWIs with CRIB II calculation and 6,398 infants with CRIB II calculation but without the base excess (CRIB II-BE). A regression model predicting time-dependent mortality and morbidities using the CRIB II score was designed. The discriminate ability of the CRIB II and CRIB II-BE scores in predicting mortality and morbidities was explored using receiver-operating characteristic analysis. Results: CRIB II performed significantly better in predicting mortality than did gestational age or birth weight alone. The time-dependent performance of CRIB II was good in the first 30 days (area under the curve [AUC], 0.8435) and at 31–90 days (AUC, 0.8458). However, it was poor after 90 days (AUC, 0.6576). Specific CRIB II cutoffs were associated with severe intraventricular hemorrhage (AUC, 0.81), bronchopulmonary dysplasia (AUC, 0.77), and mortality or major morbidities (AUC, 0.80), respectively. The model using CRIB II-BE showed similar performance in predicting mortality and morbidities to that of the CRIB II model. Conclusion: Certain CRIB II cutoffs were significantly associated with time-dependent mortality, particularly within the first 90 days after birth as well as with short-term morbidities.
Sustained Improvement of Left Ventricular Strain following Transcatheter Aortic Valve Replacement
Authors: Lozano Granero Vanesa Cristina , Fernández Santos Sara , Fernández-Golfín Covadonga , González Gómez Ariana , Plaza Martín María , de la Hera Galarza Jesús María , Faletra Francesco Fulvio , Swaans Martin J. , López-Fernández Teresa , Mesa Dolores , La Canna Giovanni , Echeverría García Tomás , Habib Gilbert , Martínez Monzonís Amparo , Zamorano Gómez José Luis ,   SITAR (Strain Imaging in Transcatheter Aortic-Valve Replacement) group
Published: July 2019

Purpose: Left ventricular (LV) mechanics are impaired in patients with severe aortic stenosis (AS). Transcatheter aortic valve replacement (TAVR) has become a widespread technique for patients with severe AS considered inoperable or high risk for open surgery. This procedure could have a positive impact in LV mechanics. The aim of the study was to evaluate the effect of TAVR on LV function recovery, as assessed by myocardial deformation parameters, both immediately and in the long term. Methods: One-hundred nineteen consecutive patients (81.2 ± 6.9 years, 50.4% female) from 10 centres in Europe with severe AS who successfully underwent TAVR with either a self-expanding CoreValve (Medtronic, Minneapolis, MN, USA) or a mechanically expanded Lotus valve (Boston Scientific, Natick, MA, USA) were enrolled in a prospective observational study. A complete echocardiographic examination was performed prior to device implantation, before discharge and 1 year after the procedure, including the assessment of LV strain using standard 2D images. Results: Between baseline and discharge, only a modest but statistically significant improvement in GLS (global longitudinal strain) could be seen (GLS% –14.6 ± 5.0 at baseline; –15.7 ± 5.1 at discharge, p = 0.0116), although restricted to patients in the CoreValve group; 1 year after the procedure, a greater improvement in GLS was observed (GLS% –17.1 ± 4.9, p < 0.001), both in the CoreValve and the Lotus groups. Conclusions: Immediate and sustained improvement in GLS was appreciated after the TAVR procedure. Whether this finding continues to be noted in a more prolonged follow-up and its clinical implications need to be assessed in further studies.
No Effect of Genome-Wide Significant Schizophrenia Risk Variation at the DRD2 Locus on the Allelic Expression of DRD2 in Postmortem Striatum
Authors: Toste Carolina C. , Duarte Rodrigo R.R. , Jeffries Aaron R. , Selvackadunco Sashika , Troakes Claire , O’Donovan Michael C. , Hill Matthew J. , Bray Nicholas J.
Published: July 2019

A genome-wide significant association has been reported between non-coding variants at the dopamine D2 receptor (DRD2) gene locus and schizophrenia. However, effects of identified schizophrenia risk alleles on DRD2 function are yet to be demonstrated. Using highly sensitive measures of allele-specific expression, we have assessed cis-regulatory effects associated with genotype at lead SNP rs2514218 on DRD2expression in the adult human striatum. No significant differences were observed in the extent of allelic expression imbalance between samples that were genomic heterozygotes for rs2514218 (where cis-regulatory effects of the risk allele are compared with those of the non-risk allele within individual subjects) and samples that were homozygous for rs2514218 (where cis-regulatory effects of this SNP on each expressed DRD2 allele will be equal). We therefore conclude that rs2514218 genotype is not associated with large effects on overall DRD2 RNA expression, at least in postmortem adult striatum. Alternative explanations for the genetic association between this variant and schizophrenia include effects on DRD2 that are transcript specific, restricted to minor DRD2-expressing cell populations or elicited only under certain physiological circumstances, or mediation through effects on another gene (or genes) at the locus.
Elevated TNIP3 mRNA Expression in TNF-α-Secreting Cells from Patients with Major Depressive Disorder
Authors: Huang Kai-Wei , Wu Ming-Kung , Hung Yi-Yung
Published: July 2019

Objective: Elevated levels of pro-inflammatory cytokines, in particular tumor necrotic factor alpha (TNF-α), and abnormalities in negative regulation in Toll-like receptor (TLR) signaling pathways are associated with major depressive disorder (MDD). Previous research by our group disclosed lower expression of TNF-α-induced protein 3 (TNFAIP3), one of the negative regulators of the TLR4 signaling pathway, in depressive patients than in healthy controls. Methods: In this study, we assessed the mRNA levels of TNFAIP3, TNFAIP3-interacting proteins (TNIP), including TNIP1, TNIP2, and TNIP3, and TNFAIP3-like proteins, such as cezanne1, cezanne2, trabid, and VCIP135, in TNF-α-secreting cells and examined their association with severity of depression using the 17-item Hamilton Depression Rating Scale (HAMD-17) scores from 30 MDD patients and 30 healthy controls. Twenty-six patients received a second assessment after treatment with antidepressants for 4 weeks. Results: TNF-α-secreting cells displayed higher TNIP3 mRNA expression in MDD patients than in healthy controls before treatment, which was marginally decreased after antidepressant treatment. In addition, the TNIP2 level could be effectively applied to predict changes in HAMD scores after linear regression analysis. Conclusion: Our collective findings suggest that molecules associated with negative regulation of innate immunity are aberrantly expressed in patients with MDD and present potential therapeutic targets.
Smaller Head Circumference Combined with Lower Education Predicts High Risk of Incident Dementia: The Shanghai Aging Study
Authors: Wang Fei , Mortimer James A. , Ding Ding , Luo Jianfeng , Zhao Qianhua , Liang Xiaoniu , Wu Wanqing , Zheng Li , Guo Qihao , Borenstein Amy R. , Hong Zhen
Published: July 2019

Introduction: An important index of brain reserve is the maximal attained brain size, which can be estimated by measuring the head circumference (HC). We investigated the association of HC and education with incident dementia in a population-based study of Chinese older adults. Methods: We conducted a prospective follow-up study of 1,659 non-demented participants with a mean age of 71.5 years. Characteristics and anthropometry of the participants were collected at baseline. Consensus diagnoses for dementia were made using DSM-IV criteria based on functional, neurological, and neuropsychological assessments. Results: We identified 168 new-onset dementia cases after a mean of 5.2 years of follow-up. Participants with smaller HC combined with low educational attainment had a significantly higher risk of incident dementia than those with larger HC who had completed more than 12 years of education (adjusted hazard ratio 4.48, 95% CI 2.47–8.12). Discussion/Conclusion: Our results suggest that smaller HC in combination with low education leads to a markedly increased risk of dementia.
Dreamy State, Delusions, Audiovisual Hallucinations, and Metamorphopsia in a Lesional Lateral Temporal Lobe Epilepsy Followed by Ipsilateral Hippocampal Sclerosis
Authors: Hatano Keiko , Shimizu Takahiro , Matsumoto Hideyuki , Suzuki Ichiro , Hashida Hideji
Published: July 2019

We report a 65-year-old man who was diagnosed with focal status epilepticus generating a dreamy state, delusions with anxiety, complex audiovisual hallucinations, elementary auditory hallucinations, and metamorphopsia with a growing large lateral temporal lobe lesion. After administrating anti-seizure drugs, all the symptoms disappeared, and brain magnetic resonance imaging revealed ipsilateral hippocampal sclerosis. To the best of our knowledge, this is the first report to present all the symptoms in one epilepsy case. On the basis of semiology, electroencephalography, and brain magnetic resonance imaging, we speculated that epileptic activities that have originated from the lateral lesion might have propagated to the ipsilateral mesial temporal lobe, causing hippocampal sclerosis.
Periacetabular Osteotomy Performed with Imageless Computer-Assisted Navigation: Case Report
Authors: Kamath Atul F. , Mays Rachel R.
Published: July 2019

Periacetabular osteotomy (PAO) is an effective surgical treatment for developmental hip dysplasia. The goal of PAO is to reorient the acetabulum to increase acetabular coverage of the femoral head, as well as to reduce contact pressures within the hip joint. The primary challenge of PAO is to accurately achieve the desired acetabular fragment orientation, while maximizing containment and congruency. As key parts of the procedure are performed out of direct field of view of the surgeon, combined with this challenge of precise spatial orientation, there is a potential role for technologies such as surgical navigation. Adjunctive technology may provide information on the orientation of repositioned acetabulum and may offer a useful assist in performing PAO. Here, we present a case of developmental dysplasia of the hip treated via PAO with the addition of an imageless computer navigation device. Surgery was successful, and, at 3 months after procedure, the patient was progressing well. To our best knowledge, this is the first case using imageless computer-assisted navigation in PAO surgery.
A implantação do Núcleo Interno de Regulação em Hospital Público Terciário
Authors: Ferreira Alex Junior , Laurindo Mariana Candida , Moraes Aline de Araújo , Cerantola Rodrigo , Barbosa Luciane Brito , Pereira Julie Giacomini da Cruz , Volpe Gustavo Jardim , Pazin-Filho Antonio
Published: July 2019

Introdução: O Núcleo Interno de Regulação (NIR) é uma das estratégias de gestão criadas pela Política Nacional de Atenção Hospitalar do Ministério da Saúde em 2013. Visa a organização do acesso à consultas, serviços diagnósticos e terapêuticos e aos leitos de internação, sendo fundamental o conhecimento do perfil epidemiológico e ajuste de seus processos de trabalho de modo a garantir o fluxo no sistema de saúde. Como as normas para implantação só foram realizadas em 2018, vários serviços implantaram o NIR sem diretrizes e há necessidade de se avaliar o grau de implantação.

Objetivo: Avaliar o nível de implantação do NIR em duas unidades de um complexo hospitalar público terciário.

Metodologia: Estudo de avaliação, exploratório, descritivo e longitudinal, realizado em duas unidades de internação hospitalar público terciário implantadas no primeiro semestre de 2016 (Unidade de Emergência) e no primeiro semestre de 2017 (Unidade Campus).

Resultados: Devido à natureza de sua vocação (eletivo ou urgência), observou-se perfil epidemiológico distinto nas unidades, embora tenha sido possível a construção de processo e análise de SWOT integrada para efeitos de tomada de decisão e planejamento. De acordo com os pilares propostos pelo Manual, ambas em maior ou menor grau apresentam iniciativas recomendadas. Mas, por outro lado, os entrevistados reforçam a necessidade de maior investimento para aprimorar o processo.

Conclusão: É necessário o estabelecimento de uma política de implantação dos NIR’s com referenciais objetivos que possam ser pontuados e permitam o acompanhamento temporal do seu desenvolvimento.
Síndrome de Rosai-Dormfan associada a Lúpus eritematoso sistêmico
Authors: Roballo Carla Adriane , Bastos Stéphany Oliveira , Sales Guilherme Moura , Soares Renata Fernandes Mendes
Published: July 2019

Objetivo: Relatar um caso de associação de Síndrome de Rosai-Dorfman e Lúpus Eritematoso Sistêmico acompanhado no ambulatório de Clínica Médica de nosso Hospital Universitário. Metodologia: O estudo é em formato de relato de caso, realizado a partir de revisão de prontuário e exames complementares. O termo de consentimento livre e esclarecido foi assinado pela paciente. Resultados: Paciente do sexo feminino, 37 anos, com quadro de pneumonia associada a derrame pleural recorrente e linfonodomegalia generalizada. Na investigação clínica, foi realizado diagnóstico de Lúpus Eritematoso Sistêmico. Os exames anatomopatológico e imuno-histoquímico da biópsia linfonodal foi compatível com Síndrome de Rosai-Dorfman. Conclusões: A Síndrome de Rosai-Dorfman é uma doença benigna que pode mimetizar neoplasias. A progressão da doença é variável e não há tratamento efetivo estabelecido atualmente, sendo o seguimento regular importante para avaliar compressão de estruturas vitais. Lúpus eritematoso sistêmico é uma doença inflamatória crônica com acometimento multissistêmico. Seu tratamento adequado costuma resultar em sobrevida longa e com qualidade. Importância do problema e comentários: De acordo com nosso levantamento bibliográfico, este é o quarto artigo relatando a ocorrência concomitante de Síndrome de Rosai-Dorfman e Lúpus Eritematoso Sistêmico em um paciente.
Relationship Between Pregnancy Complications and Subsequent Coronary Artery Disease Assessed by Coronary Computed Tomographic Angiography in Black Women
Authors: Wichmann Julian L. , Takx Richard A.P. , Nunez Johanna H. , Vliegenthart Rozemarijn , Otani Katharina , Litwin Sheldon E. , Morris Pamela B. , De Cecco Carlo N. , Rosenberg Russell D. , Bayer Richard R. , Baumann Stefan , Renker Matthias , Vogl Thomas J. , Wenger Nanette K. , Schoepf U. Joseph
Published: July 2019

Background:

Maternal pregnancy complications, particularly preeclampsia and gestational diabetes mellitus, are described to increase the risk for subsequent coronary artery disease (CAD). In addition, black women are at higher risk for CAD. The objective of this study was to compare the prevalence and extent of CAD as detected by coronary computed tomographic angiography (CCTA) in black women with and without a history of prior pregnancy complications.

Methods:

We retrospectively evaluated patient characteristics and CCTA findings in groups of black women with a prior history of preterm delivery (n=154), preeclampsia (n=137), or gestational diabetes mellitus (n=148), and a matched control group of black women who gave birth without such complications (n=445). Univariate and multivariate analyses were performed to assess risk factors of CAD.

Results:

All groups with prior pregnancy complications showed higher rates of any (≥20% luminal narrowing) and obstructive (≥50% luminal narrowing) CAD (preterm delivery: 29.2% and 9.1%; preeclampsia: 29.2% and 7.3%; and gestational diabetes mellitus: 47.3% and 15.5%) compared with control women (23.8% and 5.4%). After accounting for confounding factors at multivariate analysis, gestational diabetes mellitus remained a strong risk factor of any (odds ratio, 3.26; 95% CI, 2.03–5.22;
P
<0.001) and obstructive CAD (odds ratio, 3.00; 95% CI, 1.55–5.80;
P
<0.001) on CCTA.

Conclusions:

Black women with a history of pregnancy complications, particularly gestational diabetes mellitus, have a higher prevalence of CAD on CCTA while only a history of gestational diabetes mellitus was independently associated with any and obstructive CAD on CCTA.
Hospital Variation in 30‐Day Mortality for Patients With Stroke; The Impact of Individual and Municipal Socio‐Demographic Status
Authors: Skyrud Katrine Damgaard , Vikum Eirik , Hansen Tonya Moen , Kristoffersen Doris Tove , Helgeland Jon
Published: July 2019

Background

Thirty‐day mortality after hospitalization for stroke is commonly reported as a quality indicator. However, the impact of adjustment for individual and/or neighborhood sociodemographic status (
SDS
) has not been well documented. This study aims to evaluate the role of individual and contextual sociodemographic determinants in explaining the variation across hospitals in Norway and determine the impact when testing for hospitals with low or high mortality.

Methods and Results

Patient Administrative System data on all 45 448 patients admitted to hospitals in Norway with an incident stroke diagnosis from 2005 to 2009 were included. The data were merged with data from several databases to obtain information on vital status (dead/alive) and individual
SDS
variables. Logistic regression models were compared to estimate the predictive effect of individual and neighborhood
SDS
on 30‐day mortality and to determine outlier hospitals. All individual
SDS
factors, except travel time, were statistically significant predictors of 30‐day mortality. Of the municipal variables, only the municipal variable proportion of low income was statistically significant as a predictor of 30‐day mortality. Including sociodemographic characteristics of the individual and other characteristics of the municipality improved the model fit. However, performance classification was only changed for 1 (out of 56) hospital, from “significantly high mortality” to “nonoutlier.”

Conclusions

Our study showed that those stroke patients with a lower
SDS
have higher odds of dying after 30 days compared with those with a higher
SDS
, although this did not have a substantial impact when classifying providers as performing as expected, better than expected, or worse than expected.
Classical Cardiovascular Risk Factors and HIV are Associated With Carotid Intima‐Media Thickness in Adults From Sub‐Saharan Africa: Findings From H3Africa AWI‐Gen Study
Authors: Nonterah Engelbert A. , Boua Palwende R. , Klipstein‐Grobusch Kerstin , Asiki Gershim , Micklesfield Lisa K. , Agongo Godfred , Ali Stuart A. , Mashinya Felistas , Sorgho Herman , Nakanabo‐Diallo Seydou , Debpuur Cornelius , Kyobutungi Catherine , Alberts Marianne , Norris Shane , Tollman Stephen , Tinto Halidou , Soo Cassandra C. , Mukomana Freedom , Hazelhurst Scott , Wade Alisha N. , Kahn Kathleen , Oduro Abraham R. , Grobbee Diederick E. , Sankoh Osman , Ramsay Michèle , Bots Michiel L. , Crowther Nigel J. ,   as members and collaborators of AWI‐Gen and the H3Africa Consortium, Lombard Zane , Gómez‐Olivé Casas Frances Xavier , Wagner Ryan , Cook Ian , Ntuli Sam , Khayeka‐Wandabwa Christopher , Haregu Tilahun Nigatu , Mohammed Shukri F. , Muthuri Stella , Rouamba Toussaint , Fato Eric , Anati Immaculate , Amega‐Etego Lucas , Baloyi Nomses , Kagura Juliana , Munthali Richard , Guman Yusuf , Choudhury Ananyo
Published: July 2019

Background

Studies on the determinants of carotid intima‐media thickness (
CIMT
), a marker of sub‐clinical atherosclerosis, mostly come from white, Asian, and diasporan black populations. We present
CIMT
data from sub‐Saharan Africa, which is experiencing a rising burden of cardiovascular diseases and infectious diseases.

Methods and Results

The H3 (Human Hereditary and Health) in Africa’s AWI‐Gen (African‐Wits‐INDEPTH partnership for Genomic) study is a cross‐sectional study conducted in adults aged 40 to 60 years from Burkina Faso, Kenya, Ghana, and South Africa. Cardiovascular disease risk and ultrasonography of the CIMT of right and left common carotids were measured. Multivariable linear and mixed‐effect multilevel regression modeling was applied to determine factors related to CIMT. Data included 8872 adults (50.8% men), mean age of 50±6 years with age‐ and sex‐adjusted mean (±SE) CIMT of 640±123μm. Participants from Ghana and Burkina Faso had higher CIMT compared with other sites. Age (β = 6.77, 95%CI [6.34–7.19]), body mass index (17.6[12.5–22.8]), systolic blood pressure (7.52[6.21–8.83]), low‐density lipoprotein cholesterol (5.08[2.10–8.06]) and men (10.3[4.75– 15.9]) were associated with higher CIMT. Smoking was associated with higher CIMT in men. High‐density lipoprotein cholesterol (−12.2 [−17.9– −6.41]), alcohol consumption (–13.5 [−19.1–−7.91]) and HIV (−8.86 [−15.7–−2.03]) were inversely associated with CIMT.

Conclusions

Given the rising prevalence of cardiovascular diseases risk factors in sub‐Saharan Africa, atherosclerotic diseases may become a major pan‐African epidemic unless preventive measures are taken particularly for prevention of hypertension, obesity, and smoking.
HIV
‐specific studies are needed to fully understand the association between
HIV
and
CIMT
in sub‐Saharan Africa.
ELAZIĞ ORGANİZE SANAYİ BÖLGESİNDEKİ FİRMALARIN ENDÜSTRİ 4.0 ALGISI
Authors: METİN Serkan , TÜRKOĞLU İbrahim
Published: July 2019

Bu çalışmanın amacı Elazığ’da Organize Sanayi Bölgesi
içerisinde üretim yapan firmaların, Endüstri 4.0 olarak adlandırılan ve
ülkemizde Sanayide Dijitalleşme olarak benimsenen bu yeni üretim modeli
hakkındaki bilgi seviyelerini ölçmek ve mevcut alt yapılarının bu yeni teknolojik
dönüşüme ne kadar uygun olduğunu belirlemektir. Elazığ Organize Sanayi
Bölgesi’nde faaliyet gösteren 10 farklı sektörden, 49 farklı firmanın
yetkililerine hazırlanan anket uygulanmıştır. Araştırmada kullanılan ölçeklerin
normal dağılıma uymaması ve araştırmanın küçük örneklem özelliklerinden dolayı
parametrik olmayan test istatistiklerinin kullanılması uygun görülmüştür.
Sürekli değişkenler arasında ilişkiler korelasyon analizi ile incelenmiştir.
Kategorik değişkenler ile sürekli değişkenler arasındaki ilişkiler ise Mann
Whitney U testi ve Kruskall Wallis H Testi ile değerlendirilmiştir.
ENERJİ SEKTÖRÜNDE WASPAS YÖNTEMİYLE PERFORMANS ANALİZİ
Authors: ORÇUN Çağatay
Published: July 2019

Bu çalışmada, Borsa İstanbul A. Ş. Elektrik
endeksinde (XELKT) yer alan şirketlerin finansal performanslarının WASPAS
yöntemi ile değerlendirilmesi amaçlanmaktadır. Buna ek olarak, firmaların
finansal performans ve borsa getiri sıralamaları kendi içerisinde analiz
edilerek, iki değişken arasında bir ilişkinin var olup olmadığının bulgulanması
da amaçlanmaktadır. Çalışmada ilk olarak firmalara ilişkin cari rasyo, hazine
rasyosu, dönen ve duran varlık devir hızı rasyoları, borçlanma rasyosu, aktif,
özsermaye ve satış karlılığı rasyoları veri olarak belirlenmiş ve 5 firma için
ayrı ayrı hesaplanmıştır. Gerçekleştirilen analiz sonucunda 2016 ve 2017
yılları için en başarılı firma Ayen Enerji (AYEN) olarak bulgulanmıştır.
Ayrıca, firmaların borsa getirileri ile finansal performans sıralamaları
arasındaki ilişki Spearman sıra korelasyonu ile incelenmiş ve istatistiksel
açıdan anlamlı bir ilişki bulunamamıştır. Firmaların finansal performanslarının
değerlendirilmesinde WASPAS yönteminin yeni bir metot olarak enerji sektöründe
uygulanması, çalışmayı diğer çalışmalardan farklılaştırmaktadır.
Ancyrocephalidae (Monogenea) of Lake Tanganyika: Does the Cichlidogyrus parasite fauna of Interochromis loocki (Teleostei, Cichlidae) reflect its host’s phylogenetic affinities?
Authors: Pariselle Antoine , Van Steenberge Maarten , Snoeks Jos , Volckaert Filip A.M. , Huyse Tine , Vanhove Maarten P.M.
Published: July 2019

The faunal diversity of Lake Tanganyika, with its fish species flocks and its importance as a cradle and reservoir of ancient fish lineages seeding other radiations, has generated a considerable scientific interest in the fields of evolution and biodiversity. The Tropheini, an endemic Tanganyikan cichlid tribe, fills a peculiar phylogenetic position, being closely related to the haplochromine radiations of Lakes Malawi and Victoria. Several problems remain regarding their genus-level classification. For example, the monotypic genus Interochromis is phylogenetically nested within Petrochromis; its only representative, I. loocki, has often been reclassified. As monogenean flatworms are useful markers for fish phylogeny and taxonomy, the monogenean fauna of Interochromis loocki was examined and compared to that of other tropheine cichlids. Three new monogenean species belonging to Cichlidogyrus are described from Interochromis loocki: Cichlidogyrus buescheri Pariselle and Vanhove, sp. nov., Cichlidogyrus schreyenbrichardorum Pariselle and Vanhove, sp. nov. and Cichlidogyrus vealli Pariselle and Vanhove, sp. nov. Their haptoral anchors remind more of congeners infecting species of Petrochromis than of all Cichlidogyrus spp. hitherto described from other tropheine cichlids. Attachment organ morphology has been proven to mirror the phylogenetic affinities of Cichlidogyrus lineages. Therefore the monogenean parasite fauna of I. loocki reflects this host’s position within Petrochromis. Moreover, I. loocki differs in habitat choice from Petrochromis spp. This study hence confirms that host range and host-specificity in Cichlidogyrus spp. parasitizing tropheines is determined by the host’s phylogenetic position, rather than by a shared ecological niche.
Regionalism or Clientelism?
Authors: Black Clayton
Published: July 2019

This article examines the Leningrad Opposition of 1925 not so much as a regionally based schism in the party opposed to Stalin’s increasing monopoly of power, but rather as a cohesive expression of the city’s frustration with NEP and the economic hardships it imposed on the most industrialized city in the Soviet Union in the first seven years of Soviet power. Contrary to Western historiography on the Opposition, Zinoviev did not so much lead as align with the city’s leaders.
The Genus Hemicypris (Crustacea, Ostracoda) in the West Indies
Authors: Broodbakker Nico W.
Published: July 2019

A worldwide list of species that have to be assigned to the genus Hemicypris is given. H. exigua n. sp. and H. barbadensis n. sp. are described. A redescription is given of H. reticulata (Klie, 1930), a species from Paraguay, which was also encountered in the Antillean islands. Descriptions of chaetotaxy are made according to the system of Broodbakker & Danielopol (1982). The morphology of the limbs of the three species is similar to that of the species of the genus Heterocypris encountered in the West Indies.
An inventory of the names of native, non-endemic vascular plants described from Italy, their loci classici and types
Authors: PERUZZI LORENZO , GALASSO GABRIELE , DOMINA GIANNIANTONIO , BARTOLUCCI FABRIZIO , SANTANGELO ANNALISA , ALESSANDRINI ALESSANDRO , ASTUTI GIOVANNI , D’ANTRACCOLI MARCO , ROMA-MARZIO FRANCESCO , ARDENGHI NICOLA M.G. , BARBERIS GIUSEPPINA , CONTI FABIO , BERNARDO LILIANA , PECCENINI SIMONETTA , STINCA ADRIANO , WAGENSOMMER ROBERT P. , BONARI GIANMARIA , IAMONICO DUILIO , IBERITE MAURO , VICIANI DANIELE , DEL GUACCHIO EMANUELE , GIUSSO DEL GALDO GIANPIETRO , LASTRUCCI LORENZO , VILLANI MARIACRISTINA , BRUNU ANTONELLO , MAGRINI SARA , PISTARINO ANNALAURA , BRULLO SALVATORE , SALMERI CRISTINA , BRUNDU GIUSEPPE , CLEMENTI MORENO , CARLI EMANUELA , VACCA GABRIELLA , MARCUCCI ROSSELLA , BANFI ENRICO , LONGO DANIELA , DI PIETRO ROMEO , PASSALACQUA NICODEMO G.
Published: July 2019

The census of the loci classici of 1,227 native, non-endemic vascular plants described from Italy is here presented and described. The effective place of publication of accepted names, basionyms and homotypic synonyms were identified and critically verified. The geographic information on the loci classici was excerpted from the protologues, as well as information on typification for the taxa described before 1 January 1958. The names without a holotype are 1,165. For 591 names a lecto- or neo-typification is available in literature, while 572 currently accepted taxa still need a type designation. For ten of these names showing previous ineffective typification, nomenclatural types are designated here (Allium savii, A. tenuiflorum, Anemone millefoliata, Catapodium tuberculosum, Cynosurus siculus, Filago congesta, Saponaria bellidifolia, Sclerochloa patens, S. zwierleinii, and Vicia leucantha). A new combination (Trisetaria aurea comb. nov.) is proposed. The general picture of the currently accepted taxa of vascular plants described from Italy, including endemics, amounts to 2,631, i.e. about 32% of the native flora currently recorded for the country.
Discovery of Eubasilissa signata Wiggins, 1998 (Trichoptera, Phryganeidae) from Taiwan

Authors: KURANISHI RYOICHI B. , HSU LI-PENG
Published: July 2019

The phryganeid caddisfly Eubasilissa signata Wiggins, 1998 was originally described based on a single female specimen from Korea, and no other information on the species was available. Here we record an additional five male and five female specimens of E. signata from Taiwan and describe the male morphology for the first time. Based on morphological differences with other Eubasilissa species, E. signata should be regarded as a separate species and also not a member of the “tibetana” species group. A 658-bp fragment of the mitochondrial cytochrome c oxidase subunit I (COI) gene of the new specimens of E. signata is provided as a DNA barcode.
Proceedings of the 15th International Symposium on Trichoptera (Table of Content)
Authors: MENDEZ PATINA K. , SPAGNA JOSEPH C. , HOLZENTHAL RALPH W. , HOUGHTON DAVID C.
Published: July 2019

TOC
The larva of the Neotropical caddisfly genus Centromacronema Ulmer, 1905 (Trichoptera: Hydropsychidae)

Authors: BARCELOS-SILVA PATRIK , PES ANA MARIA , ANDRADE-SOUZA VANDERLY , DESIDÉRIO GLEISON ROBSON
Published: July 2019

The Neotropical caddisfly genus Centromacronema (Hydropsychidae: Macronematinae) contains 17 species. Many of the species are taxonomically poorly known and their biology and immature stages are also very incompletely known. Here, we provide the first complete description of the larval stages of the genus, based on those of Centromacronema obscurum (Ulmer, 1905) collected from a stream flowing through a small fragment of the Atlantic Forest biomes of southeastern Brazil.
A new species of genus Lepidostoma Rambur (Trichoptera: Lepidostomatidae) from India

Authors: PAREY SAJAD H. , PANDHER MANPREET S.
Published: July 2019

A new species of Lepidostoma Rambur is described and illustrated from the Indian Himalayas, namely Lepidostoma kjeri sp. nov under Lepidostoma ferox branch. Lepidostoma meghalayense Saini and Parey, 2011 is synonymized with Lepidostoma brueckmanni (Malicky & Chantramongkol 1994). With these changes, the genus Lepidostoma Rambur is now represented by 50 species from India.
PREFACE: Proceedings of the 15th International Symposium on Trichoptera
Authors: MENDEZ PATINA K. , SPAGNA JOSEPH C. , HOLZENTHAL RALPH W. , HOUGHTON DAVID C.
Published: July 2019

The 15th International Symposium on Trichoptera found the world caddisfly community once again in the United States of America, 4-8 June 2015. This second US-based symposium was hosted at Rutgers University, New Brunswick in the Garden State of New Jersey. The 8th International Symposium, the last meeting in the United States, occurred 20 years before at the University of Minnesota in Minneapolis and at Lake Itasca, headwaters of the Mississippi River.
New species of Allomyia Banks from the Western United States (Trichoptera: Apataniidae)

Authors: RUITER DAVID E. , NISHIMOTO HIROYUKI
Published: July 2019

Six new Allomyia species from the western United States are described: Allomyia kondratieffi sp. nov., Allomyia leei sp. nov., Allomyia meachamensis sp. nov., Allomyia sarahae sp. nov., Allomyia sheldoni sp. nov., Allomyia whatcomensis sp. nov. The majority of these species were collected from small headwater, high altitude streams on relatively isolated mountain ranges. These species bring the number of known North American Allomyia to 18. Additional notes on state/county distribution records, taxonomic problems, species diagnostics and adult emergence periods for the 18 North American species are provided.