bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-alcoholic steatohepatitis associated with Netherton syndrome
Authors: Tanner Stephanie , Julai Atharina , Gorard David Angelo
Published: December 2018

A 21-year-old man with Netherton syndrome underwent investigation of a persistently elevated serum alanine transaminase, detected on routine monitoring. He drank no alcohol, was not diabetic or overweight (body mass index 23 kg/m2) and had no clinical features of liver dysfunction. AFibroScanyielded an elevated result of 9.3 kPa. An ultrasound guided liver biopsy showed histological features consistent with non-alcoholic steatohepatitis, with activity score of 4 and fibrosis stage of 3. The patient was started on vitamin E supplementation and remains under surveillance.
Primitive neuroectodermal tumour with synchronous ipsilateral clear cell carcinoma of the kidney
Authors: Taha Mohamed , Mohammed Nur M , Crowther Stephen , Manecksha Rustom P , Thomas Arun Z
Published: December 2018

We report the first case of a synchronous ipsilateral primitive neuroectodermal tumour (PNET) and clear cell renal cell carcinoma of the kidney. A 37-year-old man presented to the emergency department with a 24-hour history of colicky abdominal pain and visible haematuria. He had no relevant surgical or medical history. Physical examination was unremarkable apart from mild left flank tenderness. Triphasic CT of the abdomen and pelvis showed two solid lesions in the left kidney. Further staging CT of the chest showed no evidence of local or distal metastasis. He subsequently underwent laparoscopic radical nephrectomy. Pathological analysis of the kidney showed two synchronous renal tumours, a clear cell carcinoma and PNET of the kidney. The patient received adjuvant chemotherapy according to Ewing’s sarcoma chemotherapy protocol. Surveillance CT scans at 3, 6 and 12 months showed no evidence of disease recurrence or metastasis.
Successful outcome after spontaneous first trimester intra-amniotic haematoma and early preterm premature rupture of membranes
Authors: Bakalis Spyros , David Anna L
Published: December 2018

A spontaneous intra-amniotic haematoma is a rare cause of preterm premature rupture of the membranes (PPROM) but can have significant fetal and maternal consequences. It has previously been reported to occur in the second and third trimesters but not in an earlier gestation. We present a case that presented acutely in the first trimester of pregnancy, which leads to early PPROM at 15 weeks and spontaneous preterm delivery at 28 weeks of gestation. There were no maternal complications during the pregnancy.
Double pyramid technique of transoral laser partial laryngectomy for radiorecurrent laryngeal cancer
Authors: Misirovs Rasads , Gartner Isabel , Manickavasagam Jaiganesh
Published: December 2018

Management of recurrent head and neck cancer is challenging. Surgical treatments for residual or radiorecurrent laryngeal cancer include total laryngectomy, open partial laryngectomy and transoral laser microsurgery (TLM). TLM has been shown to achieve good oncological and functional outcomes in radiorecurrent laryngeal cancer. We describe a case of a patient with radiorecurrent T2 (rT2) with impaired vocal cord mobility laryngeal cancer who underwent transoral laser partial laryngectomy using our proposed double pyramid technique. It encompasses two steps: resection of the superior and inferior pyramids. Full resection is achieved by staying close to the thyroid and cricoid cartilages. In this technique, the dissection principle is to remove anterior commissure in two pyramid fashions without having to actually follow the tumour. This method is easy and simple to master. Two years postoperatively, the patient has no signs of recurrence and is able to use her voice and has full swallowing ability.
Acute dyskinesia in a patient with schizophrenia
Authors: Berry Alex James
Published: December 2018

A case of acute dyskinesia in a 42-year-old man with a history of cocaine use and schizophrenia is described. He had discontinued clozapine approximately 1 month before presenting to the emergency department displaying signs of psychosis, with generalised choreiform and dystonic movements. Urinary toxicology was positive for cocaine. Clozapine treatment was reinitiated, and within 2 weeks the dyskinesia had subsided. Review of his records revealed two previous episodes of similar dyskinesia, both of which were temporally associated with cocaine use. Dyskinesia occurring in the context of cocaine use, and clozapine withdrawal-associated dyskinesia were considered to be the main differential diagnoses. A range of differential diagnoses should be considered in patients presenting with an acute-onset movement disorder who have a history of long-term exposure to antipsychotic medication.
Diffuse idiopathic neuroendocrine cell hyperplasia as a rare cause of chronic cough
Authors: Pedro Paula Inês , Canário Dolores , Lopes Miguel , Oliveira Ana
Published: December 2018

A 39-year-old Caucasian woman, who has never smoked, presented a 16-year-duration chronic dry cough. She was prescribed by her general physician with corticosteroid and long-acting β-agonist inhalers assuming it was asthma, with mild symptomatic improvement. When cough got more persistent and associated with exertional dyspnoea and wheezing, a chest CT scan was performed, which showed multiple bilateral micronodular formations and diffuse mosaic lung pattern with air trapping. She was sent to our Respiratory Department and performed a bronchoalveolar lavage and cryobiopsy that were inconclusive. She underwent surgical lung biopsy with pathology revealing multiple foci of neuroendocrine cell hyperplasia and tumourlets associated with constrictive bronchiolitis, a histological pattern suggestive of diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH). DIPNECH is a rare and preinvasive disease. Presenting symptoms can be cough and breathlessness. At the time of writing, the patient is on octreotide with symptomatic improvement.
Dandy-Walker variant with precocious puberty: a rare association
Authors: Rajput Rajesh , Mishra Sanat , Ahlawat Parul , Yadav Pawan Kumar
Published: December 2018

Precocious puberty is characterised by premature appearance of secondary sexual characteristics before the age of 7 years in girls and 9 years in boys. Dandy-Walker malformation comprises a spectrum of intracranial malformations of the posterior fossa. We present a case of a 7-year-old male child who has presented with features of central precocious puberty and on further evaluation has been found to have Dandy-Walker variant and secondary hypothyroidism. The following case report describes this association which is extremely rare and has never been described in literature.
Thyroid storm: a case of haemodynamic failure promptly reversed by aggressive medical therapy with antithyroid agents and steroid pulse
Authors: Andrade Luz Ivan , Pereira Tiago , Catorze Nuno
Published: December 2018

Hyperthyroidism is a common metabolic disorder, although its presentation as an endocrine emergency called thyroid storm is rare. Here we review a case of a thyroid storm as the initial presentation of thyrotoxicosis, with multiple organ failure and haemodynamic collapse due to low-output cardiac dysfunction. Quick intervention with aggressive antithyroid therapy, including steroid pulse, and supportive intensive care measures led to an outstanding improvement and full recovery. The present case clearly shows the beneficial impact of initial clinical suspicion resulting in an early diagnosis and intensive therapy. Moreover, it supports the additional role of steroids to aggressive antithyroid strategy in order to control associated deleterious systemic inflammatory reactions.
Special form of osteoporosis in a 53-year-old man
Authors: Lampart Simon , Azzarello-Burri Silvia , Henzen Christoph , Fischli Stefan
Published: December 2018

Male osteoporosis often remains unrecognised. Osteoporotic fractures occur approximately 10 years later in men than in women due to higher peak bone mass. However, 30% of all hip fractures occur in men. Risk factors of osteoporotic fractures can be grouped into primary and secondary causes. We present the case of a 53-year-old man, who suffered a compression fracture of a lumbar vertebra after a generalised seizure and an atraumatic rib fracture 5 months later. We could exclude secondary causes of bone mineral loss such as primary hyperparathyroidism, glucocorticoid use and hypogonadism. However, a heterozygous missense mutation of theCOL1A1gene in exon 48 in further search of a secondary cause was found. Therapy was changed from bisphosphonate treatment to teriparatide. Considering the lack of other osteogenesis imperfecta (OI) symptoms and signs, the patient’s illness can be classified as mild. OI should be considered as differential diagnosis in unexplained cases with osteoporosis.
Unusual presentation of a life-threatening intraperitoneal haemorrhage after elective inguinal hernia repair
Authors: Chan Kenrick Kai Chi , Khan Shahab , Lewis Christopher
Published: December 2018

A 57-year-old man who was hypotensive at induction of anaesthesia was having intermittent episodes of hypotension after an uncomplicated and relatively bloodless open inguinal hernia repair of a large left-sided hernia . His hypotension was responsive to small fluid boluses. He did not show any tachycardia, had no abdominal pain, no signs of bruising or bleeding in his abdomen, flanks, or scrotum. Remained clinically well and alert throughout until being transferred to a tertiary centre. Eventually became haemodynamically unstable approximately 6 hours postoperatively. CT angiogram showed a large haemoperitoneum with active bleeding. Diagnostic laparoscopy revealed an actively bleeding inferior epigastric artery which was stopped. The patient received 2 units of red blood cells and made a full recovery.
Methylprednisolone-induced hepatotoxicity in a 16-year-old girl with multiple sclerosis
Authors: Rotondo Eleonora , Graziosi Alessandro , Di Stefano Vincenzo , Mohn Angelika Anna
Published: December 2018

Multiple sclerosis (MS) is a chronic inflammatory disease with demyelination of the central nervous system. High-dosage corticosteroids are the first-line therapy in the acute relapsing of MS. We report a case of severe high-dose methylprednisolone-induced acute hepatitis in a patient with a new diagnosis of MS. A 16-year-old girl was admitted for urticaria, angioedema, nausea and vomiting a month later she had been diagnosed with MS and treated with high-dosage methylprednisolone. Laboratory investigations showed hepatic insufficiency with grossly elevated liver enzymes. A liver biopsy showed focal centrilobular hepatocyte necrosis with interface hepatitis. Methylprednisolone-induced hepatotoxicity can confuse the clinical picture of patients with MS and complicate the differential diagnosis. We believe that each specialist should know it and monitor patients with MS taking high doses of methylprednisolone. As there is no screening model that predicts idiosyncratic hepatotoxicity, we promote screening for potential liver injury following pulse steroid therapy.
Unexpected source ofProteus mirabilisbacteraemia
Authors: Nagiah Sureshkumar , Badbess Rassam
Published: December 2018

Mycotic (infected) aneurysm involving the thoracic aorta is an exceedingly rare and life-threatening condition that is associated with high morbidity and mortality. We report an unusual source ofProteus mirabilisbacteraemia thought to be due to an infected aneurysm in the thoracic aortic arch in an elderly woman. Source of gram-negative bacteraemia is usually isolated to an intra-abdominal or a pelvic source.Proteusbacteraemia from an intrathoracic pathology is very uncommon, and in this case led to a delay in diagnosis. Although an infected aneurysm is a rare source of gram-negative bacteraemia, it must always be considered when common causes of bacteraemia have been ruled out especially in patients with vascular risk factors.
Early detection of vertebral artery dissection
Authors: MacArthur Alice Morag , Mehdi Syed
Published: December 2018

A 36-year-old female patient presented to hospital with a 1-week history of occipital headache. It was sudden onset following a fall into a swimming pool. Examination was unremarkable. CT angiogram brain scan showed right vertebral artery dissection with a 1 cm dissection flap and a 3 mm left middle cerebral artery aneurysm. She was discharged on aspirin, with outpatient neurology clinic follow-up.
Exogenous steroid-induced hypoadrenalism in a person living with HIV caused by a drug–drug interaction between cobicistat and intrabursal triamcinolone
Authors: Makaram Navnit , Russell Clark D , Roberts Simon Benedict , Stevens Jarrad , Macpherson Gavin
Published: December 2018

We report a diagnosis of exogenous steroid-induced hypoadrenalism in a person living with HIV caused by a drug–drug interaction (DDI) between intrabursal triamcinolone and the pharmacokinetic booster cobicistat. A 53-year-old woman living with HIV, managed with dolutegravir and cobicistat-boosted darunavir, presented to the orthopaedic clinic with worsening hip pain. She was diagnosed with greater trochanteric pain syndrome (GTPS) of the hip and was treated with intrabursal injection of bupivacaine and triamcinolone. Seven days following this injection, she presented with Cushingoid features, an undetectable cortisol and was diagnosed with exogenous steroid-induced hypoadrenalism. Cobicistat is a cytochrome P450 3A inhibitor and in this case inhibited clearance of intrabursal triamcinolone, leading to exogenous glucocorticoid excess and adrenal suppression. This is the first report to describe this predictable DDI with cobicistat following intrabursal glucocorticoid injection. This case highlights the complexities in managing non-HIV-related chronic morbidities in people living with HIV.
Simultaneous treatment of ischaemic bowel and ischaemic stroke with intravenous thrombolysis therapy
Authors: Chen Lucia Y , Ainscough Charlotte , Sayed Mohamed , Bhargava Maneesh
Published: December 2018

Novel treatment of simultaneous mesenteric and cerebral ischaemia with systemic thrombolysis. A 75-year-old man presented to the acute stroke team with aphasia, right-sided weakness and distressed with a pain he was unable to localise. He was treated with intravenous thrombolysis with tissue plasminogen activator for a left middle cerebral artery stroke. Decompensation on the ward during thrombolysis with worsening abdominal distension and pain, hypotension and tachycardia prompted a CT angiogram scan, which displayed proximal inferior mesenteric artery occlusion. Thrombolysis treatment resulted in excellent improvement of both his dysphasia and weakness from the left cerebral ischaemic stroke and reperfusion of the ischaemic bowel, without surgical intervention.
Ground response to tunnelling incorporating soil reinforcement system
Authors: Le Binh Thanh , Taylor R.N.
Published: December 2018

The forepole umbrella system (FUS) uses steel pipes installed from within a tunnel to provide a canopy above the tunnel heading that both increases stability and reduces tunnelling-induced ground movements. Although the system is known to be beneficial and has been used in a number of projects, there is little information on how key parameters including length and forepole stiffness combine to produce effective support. To investigate this, centrifuge tests incorporating the three-dimensional (3D) geometry of a tunnel heading in clay and the model FUS have been undertaken. The tunnel heading was supported by a pressurized rubber bag lining with excavation being simulated by a reduction in air support pressure. Image analysis was used to obtain subsurface ground movements and a newly developed 3D imaging system was used to measure the soil surface deformations accurately. The performance of the FUS and the influences of key FUS parameters were quantified via the settlement reduction factor. The results showed that the FUS, arranged in various settings, reduced the maximum surface settlement by 35%–75%. The effects of the FUS parameters on the reinforcing effectiveness are dependent on the ratio of cover depth to tunnel diameter. An optimum design arrangement of the FUS is suggested.
Endpoint Effect Suppression Based on Multipoint Extension in Bearing Fault Diagnosis
Authors: Xia Shuang , Zhou Guohui
Published: December 2018

In the rolling bearing fault detection, the Hilbert–Huang transform (HHT) has made remarkable achievements, but at present, the HHT still has the end effect problem, which will cause a lot of data distortion, spectrum confusion that will affect fault diagnosis result and error in the detection of rolling bearing faults in a serious manner. In response to this problem, this paper proposes a method of multi-point continuation at both ends of the signal to suppress the endpoint effectExtend at both ends of the signal, then perform empirical mode decomposition (EMD). The experimental comparison shows that the method has an effect on the endpoint effect.
Clinical and Complement Long-Term Follow-Up of a Pediatric Patient with C3 Mutation-Related Atypical Hemolytic Uremic Syndrome
Authors: Bjerre Anna , Bergseth Grethe , Ludviksen Judith Krey , Stokke Arne , Bosnes Vidar , Karpman Diana , Mollnes Tom Eirik
Published: December 2018

We report a pediatric patient with atypical hemolytic uremic syndrome due to a C3 gain-of-function mutation diagnosed in infancy. She was treated from the start with a constant dose of 300 mg eculizumab every second week from the onset and followed by routine complement analyses for six years. Her complement system was completely inhibited and the dose interval was prolonged from 2 to 3 weeks without alteration of the dose and the complement activity continued to be completely inhibited. Blood samples taken immediately before, immediately after, and between eculizumab doses were analyzed for eculizumab-C5 complexes and percentage of total complement activity, using the Wieslab® test, and compared to a pool of sera from 20 healthy controls. The patient exhibited complete complement inhibition at all three time-points and had no free circulating C5 suggesting there was complete binding to eculizumab. She has now been treated for six years with full complement blockade. We suggest therefore that analysis of complement activity using the Wieslab® test is useful for evaluating the effect of eculizumab when dose intervals are prolonged.
The Use of Natural Health Products Especially Papaya Leaf Extract and Dandelion Root Extract in Previously Untreated Chronic Myelomonocytic Leukemia
Authors: Rahmat Leena T. , Damon Lloyd E.
Published: December 2018

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic disorder which shares clinical and morphological features of myelodysplastic syndrome and myeloproliferative neoplasms. Conventional therapeutic options include hydroxyurea, hypomethylating agents, and systemic chemotherapy, which are all palliative measures and are associated with potential side effects. Allogeneic hematopoietic cell transplantation is the only curative option. Natural health products such as papaya leaf extract and dandelion root extract have been shown to demonstrate anticancer activity in preclinical and clinical studies, respectively. We present a case study of a 76-year-old male with previously untreated CMML, whose hematological parameters remained stable and whose bone marrow blast counts vastly improved while taking papaya leaf extract and dandelion root extract.
Dietary Variations in a Multiethnic Parkinson’s Disease Cohort and Possible Influences on Nonmotor Aspects: A Cross-Sectional Multicentre Study
Authors: Sauerbier Anna , Schrag Anette , Martinez-Martin Pablo , Hall Lynsey J. , Parry Miriam , Mischley Laurie K. , Zis Panagiotis , Chaudhuri K. Ray
Published: December 2018

Dietary habits may differ between Parkinson’s disease (PD) patients of different ethnicities. The primary aim of this cross-sectional analysis was to compare dietary habits in a multiethnic PD population and investigate potential nonmotor differences. All patients completed a dietary habits questionnaire. Besides basic demographics, patients’ motor involvement (Hoehn and Yahr (HY)) and nonmotor symptoms (Nonmotor Symptoms Scale; Hospital Anxiety and Depression Scale) were assessed. 139 PD patients were included (mean age 66.8 ± 11.6 years; 61.2% male; mean disease duration 6.2 ± 5.2 years; median HY 3): 47.5% were White, 24.5% Asian, and 28.0% Black African and Caribbean (BAC). We found dietary differences between the groups, including a greater frequency of vegetarians and greater consumption of cumin, turmeric, and cinnamon as well as lower consumption of beef in Asian patients than in White and BAC and greater consumption of chili than in White patients and higher consumption of pork in White than Asian and BAC patients. There were no significant differences in dietary supplement consumption after correction for multiple comparisons. None of the dietary factors examined were associated with differences in nonmotor symptoms. Diet and supplement use vary in PD patients across ethnicities, this is both a problem and opportunity for nutritional medicine research. These data support the importance of considering ethnic diversity as part of recruitment strategy in nutrition and clinical studies.
A Randomized Clinical Trial of a Functional Electrical Stimulation Mimic to Gait Promotes Motor Recovery and Brain Remodeling in Acute Stroke
Authors: Zheng Xiuyuan , Chen Danfeng , Yan Tiebin , Jin Dongmei , Zhuang Zhiqiang , Tan Zhimei , Wu Wei
Published: December 2018

Functional electrical stimulation can improve motor function after stroke. The mechanism may involve activity-dependent plasticity and brain remodeling. The aim of our study was to investigate the effectiveness of a patterned electrical stimulation FES mimic to gait in motor recovery among stroke survivors and to investigate possible mechanisms through brain fMRI. Forty-eight subjects were recruited and randomly assigned to a four-channel FES group (n=18), a placebo group (n=15), or a dual-channel FES group (n=15). Stimulation lasted for 30 minutes in each session for 3 weeks. All of the subjects were assessed at baseline and after weeks 1, 2, and 3. The assessments included the Fugl-Meyer Assessment, the Postural Assessment Scale for Stroke Patients, Brunel’s Balance Assessment, the Berg Balance Scale, and the modified Barthel Index. Brain fMRI were acquired before and after the intervention. All of the motor assessment scores significantly increased week by week in all the three groups. The four-channel group showed significantly better improvement than the dual-channel group and placebo groups. fMRI showed that fractional anisotropy was significantly increased in both the four-channel and dual-channel groups compared with the placebo group and fiber bundles had increased significantly on the ipsilateral side, but not on the contralateral side in the group given four-channel stimulation. In conclusion, when four-channel FES induces cycling movement of the lower extremities based on a gait pattern, it may be more effective in promoting motor recovery and induce more plastic changes and brain remodeling than two-channel stimulation. This trial is registered with clinical trial registration unique identifier ChiCTR-TRC-11001615.
Nutrient Stress–Dysregulated Antisense lncRNA GLS-AS Impairs GLS-Mediated Metabolism and Represses Pancreatic Cancer Progression
Authors: Deng Shi-Jiang , Chen Heng-Yu , Zeng Zhu , Deng Shichang , Zhu Shuai , Ye Zeng , He Chi , Liu Ming-Liang , Huang Kang , Zhong Jian-Xin , Xu Feng-Yu , Li Qiang , Liu Yang , Wang Chunyou , Zhao Gang
Published: December 2018

Cancer cells are known to undergo metabolic reprogramming, such as glycolysis and glutamine addiction, to sustain rapid proliferation and metastasis. It remains undefined whether long noncoding RNAs (lncRNA) coordinate the metabolic switch in pancreatic cancer. Here we identify a nuclear-enriched antisense lncRNA of glutaminase (GLS-AS) as a critical regulator involved in pancreatic cancer metabolism. GLS-AS was downregulated in pancreatic cancer tissues compared with noncancerous peritumor tissues. Depletion of GLS-AS promoted proliferation and invasion of pancreatic cancer cells both in vitro and in xenograft tumors of nude mice. GLS-AS inhibited GLS expression at the posttranscriptional level via formation of double stranded RNA with GLS pre-mRNA through ADAR/Dicer-dependent RNA interference. GLS-AS expression was transcriptionally downregulated by nutrient stress–induced Myc. Conversely, GLS-AS decreased Myc expression by impairing the GLS-mediated stability of Myc protein. These results imply a reciprocal feedback loop wherein Myc and GLS-AS regulate GLS overexpression during nutrient stress. Ectopic overexpression of GLS-AS inhibited proliferation and invasion of pancreatic cancer cells by repressing the Myc/GLS pathway. Moreover, expression of GLS-AS and GLS was inversely correlated in clinical samples of pancreatic cancer, while low expression of GLS-AS was associated with poor clinical outcomes. Collectively, our study implicates a novel lncRNA-mediated Myc/GLS pathway, which may serve as a metabolic target for pancreatic cancer therapy, and advances our understanding of the coupling role of lncRNA in nutrition stress and tumorigenesis.

Significance: These findings show that lncRNA GLS-AS mediates a feedback loop of Myc and GLS, providing a potential therapeutic target for metabolic reprogramming in pancreatic cancer.

See related commentary by Mafra and Dias, p. 1302
Smoking and Urinary Cotinine Levels Are Predictors of Increased Risk for Gastric Intestinal Metaplasia
Authors: Kim Kyungeun , Chang Yoosoo , Ahn Jiin , Yang Hyo-Joon , Jung Ju Young , Kim Seokkyun , Sohn Chong Il , Ryu Seungho
Published: December 2018

Studies on a longitudinal relationship between smoking status and intestinal metaplasia (IM), a premalignant lesion of stomach cancer, are limited. Here we examined the association of smoking status and urinary cotinine levels, an objective measure of smoking, with the development of endoscopic IM. This cohort study included 199,235 Korean adults free of endoscopic IM who underwent upper endoscopy at baseline and subsequent visits and who were followed for up to 6.8 years (median, 3.7 years). Former and current smoking status and pack-years based on self-reports were associated with an increased risk of new-onset IM in men but not in women. However, urinary cotinine levels were positively associated with incident IM in a dose–response manner in both men and women. For men, the multivariable-adjusted HR [95% confidence interval (CI)] for incident IM comparing the urinary cotinine levels of 50 to 99 ng/mL, 100 to 499 ng/mL, and ≥500 ng/mL with <50 ng/mL were 1.20 (0.94–1.55), 1.26 (1.14–1.40), and 1.54 (1.44–1.64), respectively, whereas for women, corresponding HR (95% CI) were 0.75 (0.19–2.99), 1.86 (1.20–2.88), and 1.57 (1.07–2.30), respectively. These associations were observed when changes in smoking status and other confounders were updated during follow-up as time-varying covariates. In this large cohort of young and middle-aged men and women, urinary cotinine levels were independently associated with an increased incidence of endoscopic IM in a dose–response manner. Collectively, these data confirm smoking as an independent risk factor for the development of gastric IM, a precursor lesion of stomach cancer.

Significance:

A large-scale cohort study of nearly 200,000 adults associates smoking with increased risk for gastric intestinal metaplasia, a precursor lesion of stomach cancer.
Arylsulfonamide 64B Inhibits Hypoxia/HIF-Induced Expression of c-Met and CXCR4 and Reduces Primary Tumor Growth and Metastasis of Uveal Melanoma
Authors: Dong Lei , You Shuo , Zhang Qing , Osuka Satoru , Devi Narra S. , Kaluz Stefan , Ferguson Jalisa H. , Yang Hua , Chen Guoliang , Wang Binghe , Grossniklaus Hans E. , Van Meir Erwin G.
Published: December 2018

Purpose:

Uveal melanoma (UM) is the most prevalent and lethal intraocular malignancy in adults. Here, we examined the importance of hypoxia in UM growth and tested the antitumor effects of arylsulfonamide 64B, an inhibitor of the hypoxia-induced factor (HIF) pathway in animal models of UM and investigated the related mechanisms.

Experimental Design:

UM cells were implanted in the uvea of mice eyes and mice systemically treated with 64B. Drug effect on primary eye tumor growth, circulating tumor cells, metastasis formation in liver, and survival were examined. 64B effects on UM cell growth, invasion and hypoxia-induced expression of C-X-C chemokine receptor type 4 (CXCR4) and mesenchymal–epithelial transition factor (c-Met) were measured. Luciferase reporter assays, chromatin immunoprecipitation, co-immunoprecipitation, and cellular thermal shift assays were used to determine how 64B interferes with the HIF transcriptional complex.

Results:

Systemic administration of 64B had potent antitumor effects against UM in several orthotopic mouse models, suppressing UM growth in the eye (∼70% reduction) and spontaneous liver metastasis (∼50% reduction), and extending mice survival (P < 0.001) while being well tolerated. 64B inhibited hypoxia-induced expression of CXCR4 and c-Met, 2 key drivers of tumor invasion and metastasis. 64B disrupted the HIF-1 complex by interfering with HIF-1α binding to p300/CBP co-factors, thus reducing p300 recruitment to the MET and CXCR4 gene promoters. 64B could thermostabilize p300, supporting direct 64B binding to p300.

Conclusions:

Our preclinical efficacy studies support the further optimization of the 64B chemical scaffold toward a clinical candidate for the treatment of UM.
Early Predictors of Trajectories of Tobacco Use Level from Adolescence to Young Adulthood: A 16-Year Follow-Up of the TEMPO Cohort Study (1999–2015)
Authors: Clergue-Duval Virgile , Mary-Krause Murielle , Bolze Camille , Fombonne Eric , Melchior Maria
Published: December 2018

Purpose: Individual and family characteristics early on in life are associated with adolescent smoking; however, their role with regard to long-term tobacco smoking trajectories into young adulthood is not well-known, which is what we set out to study using data from a longitudinal community-based cohort. Methods: We used data from 2,025 youths in France (12–26 years at baseline, 16 years of follow-up), participating in the longitudinal TEMPO cohort study. First, we modeled smoking trajectories from adolescence onwards using Group-Based Trajectory Modeling, by using the declared consumption of cigarettes at different ages. Second, among trajectories of smokers, associations with individual and family characteristics in childhood and adolescence were studied using multinomial logistic regression. Results: We observed 5 smoking trajectories: non-smokers (62.3%), 3 groups of persistent smokers with different levels of tobacco use (low, intermediate, high), and a group characterized by high-level smoking followed by cessation. Among participants who were lifetime smokers (n = 763), the trajectory of tobacco use was associated with early substance use initiation, academic attainment, grade retention, and parental smoking. Early tobacco and cannabis use initiation predicted high-level tobacco use, whether it persisted (OR 2.29, 95% CI 1.23–4.28) or not (OR 2.99, 95% CI 1.59–5.63). Grade retention and parental smoking predicted persistent smoking of intermediate (respectively OR 1.53, 95% CI 1.03–1.92; OR 1.74, 95% CI 1.03–2.92) or high level use (respectively OR 1.74, 95% CI 1.07–2.85; OR 1.70, 95% CI 0.91–3.18). Poor academic attainment predicted all 3 smoking trajectories, especially persistent high-level smoking (no high school degree: OR 5.29, 95% CI 1.65–16.97, vocational degree: OR 1.94, 95% CI 0.99–3.80). Conclusions: Tobacco smoking trajectories from adolescence to adulthood are associated with early substance use initiation, parental smoking, and academic difficulties.
Expression of PRDX6 Correlates with Migration and Invasiveness of Colorectal Cancer Cells
Authors: Huang Wen-Shih , Huang Cheng-Yi , Hsieh Meng-Chiao , Kuo Yi-Hung , Tung Shui-Yi , Shen Chien-Heng , Hsieh Yung-Yu , Teng Chih-Chuan , Lee Ko-Chao , Lee Kam-Fai , Kuo Hsing-Chun
Published: December 2018

Background/Aims: Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related deaths worldwide. PRDXs are antioxidant enzymes that play an important role in cell differentiation, proliferation and apoptosis and have diverse functions in malignancy development. However, the mechanism of aberrant overexpression of PRDX6 in CRC remains unclear. Methods: Boyden chamber assay, flow cytometry and a lentiviral shRNA targeting PRDX6 and transient transfection with pCMV-6-PRDX6 plasmid were used to examine the role of PRDX6 in the proliferation capacity and invasiveness of CRC cells. Immunohistochemistry (IHC) with tissue array containing 40 paraffin- embedded CRC tissue specimens and Western blot assays were used to detect target proteins. Results: PRDX6 was significantly up-expressed in different comparisons of metastasis of colorectal adenomas in node-positive CRC (P = 0.03). In in vitro HCT-116, PRDX6 silencing markedly suppressed CRC cell migration and invasiveness while also inducing cell cycle arrest as well as the generation of reactive oxygen species (ROS); specific overexpression of PRDX6 had the opposite effect. Mechanistically, the PRDX6 inactivation displayed decreased levels of PRDX6, N-cadherin, β-catenin, Vimentin, Slug, Snail and Twist-1 through the activation of the PI3K/ AKT/p38/p50 pathways, but they were also significantly inhibited by PRDX6 transfectants. There was also increased transcriptional activation of dimethylation of histone H3 lysine 4 (H3K4me3) of PRDX6 promoter via the activation of the PI3K/Akt/NFkB pathways. Conclusion: Our findings demonstrated that PRDX6 expression plays a characteristic growth-promoting role in CRC metastasis. This study suggests that PRDX6 may serve as a biomarker of node-positive status and may have a role as an important endogenous regulator of cancer cell tumorigenicity in CRC. PRDX6 may also be an effective therapeutic target.
Decreased Spontaneous Brain Activity and Functional Connectivity in Type 1 Diabetic Patients Without Microvascular Complications
Authors: Xia Wenqing , Chen Yu-Chen , Luo Yong , Zhang Dan-Feng , Chen Huiyou , Ma Jianhua , Yin Xindao
Published: December 2018

Background/Aims: Type 1 diabetes mellitus (T1DM) has been proven to be associated with an increased risk of cognitive dysfunction. In this study, we aimed to investigate whether disrupted spontaneous activity and functional connectivity (FC) exist in T1DM patients using resting-state functional magnetic resonance imaging (rs-fMRI) and to detect the relationships of these parameters with cognitive impairment. Methods: T1DM patients (n=35) were compared with age-, sex-, and education level-matched healthy controls (n=50) through rs-fMRI. Using rs-fMRI professional software, we calculated the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and seed-based FC in the posterior cingulate cortex (PCC) to measure the spontaneous neural activity in the groups. The relationship between rs-fMRI data and cognitive performance was further investigated. Results: Compared with the healthy controls, T1DM patients showed significantly decreased ALFF values in the PCC and right inferior frontal gyrus (IFG), decreased ReHo values in the right middle frontal gyrus (MFG) and reduced FC between the PCC and the right MFG. Furthermore, a positive correlation was found between decreased ALFF values in the PCC and Rey-Osterrieth Complex Figure Test (CFT)-delay scores in T1DM patients (r=0.394, p=0.026). Moreover, the Trail Making Test-B (TMT-B) scores showed negative correlations with decreased ReHo values in the right MFG (r=-0.468, p=0.007) and reduced FC between the PCC and right MFG (r=-0.425, p=0.015). Conclusion: Our combined analyses revealed decreased spontaneous activity and FC mainly within the default mode network, which was correlated with specific impaired cognitive functioning in T1DM. This study thus elucidates the neurophysiological mechanisms underlying T1DM-related cognitive impairment and may serve as a reference for future clinical diagnosis.
Proteomic Analysis of the Myocardium in Hypertrophic Obstructive Cardiomyopathy
Authors: Coats Caroline J. , Heywood Wendy E. , Virasami Alex , Ashrafi Nadia , Syrris Petros , dos Remedios Cris , Treibel Thomas A. , Moon James C. , Lopes Luis R. , McGregor Christopher G.A. , Ashworth Michael , Sebire Neil J. , McKenna William J. , Mills Kevin , Elliott Perry M.
Published: December 2018

Background:

Hypertrophic cardiomyopathy (HCM) is characterized by a complex phenotype that is only partly explained by the biological effects of individual genetic variants. The aim of this study was to use proteomic analysis of myocardial tissue to explore the postgenomic phenotype.

Methods:

Label-free proteomic analysis was used initially to compare protein profiles in myocardial samples from 11 patients with HCM undergoing surgical myectomy with control samples from 6 healthy unused donor hearts. Differentially expressed proteins of interest were validated in myocardial samples from 65 unrelated individuals (HCM [n=51], controls [n=7], and aortic stenosis [n=7]) by the development and use of targeted multiple reaction monitoring-based triple quadrupole mass spectrometry.

Results:

In this exploratory study, 1586 proteins were identified with 151 proteins differentially expressed in HCM samples compared with controls (
P
<0.05). Protein expression profiling showed that many proteins identified in the initial discovery study were associated with metabolism, muscle contraction, calcium regulation, and oxidative stress. Proteins downregulated in HCM versus controls included creatine kinase M-type, fructose-bisphosphate aldolase A, and phosphoglycerate mutase (
P
<0.001). Proteins upregulated in HCM included lumican, carbonic anhydrase 3, desmin, α-actin skeletal, and FHL1 (four and a half LIM domain protein 1;
P
<0.01). Myocardial lumican concentration correlated with the left atrial area (ρ=0.34,
P
=0.015), late gadolinium enhancement on cardiac magnetic resonance imaging (
P
=0.03) and the presence of a pathogenic sarcomere mutation (
P
=0.04).

Conclusions:

The myocardial proteome of HCM provides supporting evidence for dysregulation of metabolic and structural proteins. The finding that lumican is raised in HCM hearts provides insight into the myocardial fibrosis that characterizes this disease.
Living on the rocks: a new species of Stenanona (Annonaceae) from karst limestone forests of southern Mexico
Authors: ORTIZ-RODRIGUEZ ANDRES ERNESTO , GÓMEZ-DOMÍNGUEZ HÉCTOR , ESPINOSA-JIMÉNEZ JOSEFA ANAHÍ , RUIZ-SANCHEZ EDUARDO , ORNELAS JUAN FRANCISCO , BREWER STEVEN
Published: December 2018

Based on morphological and phylogenetic evidence, a new species of Stenanona endemic to the karst limestone forests from southern Mexico is described and illustrated. The new species is placed in the Desmopsis-Stenanona clade and appears to be closely related to Stenanona migueliana and S. stenopetala, from which it differs in flower colour, petal margins, petal venation, sepal length and ovule arrangement. Phylogenetic relationships, evolution and conservation status of the new species are discussed.
Micropterigidae (Lepidoptera) of the Southwestern Pacific: a revision with the establishment of five new genera from Australia, New Caledonia and New Zealand
Authors: GIBBS GEORGE W.
Published: December 2018

With the discovery of new taxa and developments in biogeography and molecular phylogenetics, it has become clear that the diversity of Micropterigidae in the SW Pacific region is inadequately represented by the current taxonomy. The existing taxonomy implies a single lineage in this region, while an unpublished molecular analysis reveals the presence of three distinct lineages in Australia, New Caledonia and New Zealand, hence the need for revision. Currently only three named species are described from eastern Australia, all placed within the genus Sabatinca Walker. This revision isolates porphyrodes Turner 1932, from northern Queensland, as a new monotypic genus Austromartyria, here recognised as a member of a diverse ‘southern sabatincoid lineage’ distributed around the Southern Hemisphere. The bulk of the fauna covered in this revision includes: S. calliplaca Meyrick 1902, together with 6 new taxa in a new Australian genus Tasmantrix; S. sterops Turner 1921 plus a new species from New Caledonia, in another new genus Aureopterix. The New Zealand species Sabatinca zonodoxa Meyrick 1888, is synonymised with S. rosicoma Meyrick 1914 and placed in a new monotypic genus Zealandopterix. Finally, a new genus Nannopterix is erected for a new species from New Caledonia. The assemblage of four new genera (excluding Austromartyria) together comprise the basal lineage of Micropterigidae, previously referred to as the ‘Australian-group.’ All five new genera are distinguished from Sabatinca s.str., the focus of diversity in the region (confined to New Caledonia and New Zealand), but not revised here.
A new, remarkable genus and two new species of Ectrichodiinae (Hemiptera: Heteroptera: Reduviidae) from Madagascar
Authors: CHŁOND DOMINIK
Published: December 2018

Gibbosella, a new remarkable genus, and two new species G. mirabilis and G. elongata are described based on specimens from Madagascar. The dorsal habitus as well as diagnostic characters of the females’ genitalia are illustrated with 13 figures. A key to the species is also provided.
The lanternfly genus Penthicodes: key to the species and review of the “Ereosoma group” with two new species and one new subspecies (Hemiptera: Fulgoromorpha: Fulgoridae)
Authors: CONSTANT JEROME
Published: December 2018

Penthicodes celebica n. sp., is described from Sulawesi, P. warleti n. sp. from India (Assam) and P. caja malayana n. ssp. from peninsular Malaysia. They are compared with the allied species of the subgenus Ereosoma Kirkaldy, 1906, as treated by Nagai & Porion (1996): P. astraea (Stål, 1864), P. atomaria (Weber, 1801) P. bimaculata (Schmidt, 1905), P. caja (Walker, 1851), P. pulchella (Guérin-Méneville, 1838), P. quadrimaculata Lallemand, 1963, P. rugulosa (Stål, 1870) and P. variegata (Guérin-Méneville, 1829). Penthicodes quadrimaculata is removed from synonymy with P. bimaculata. Male genitalia of all treated species are illustrated and described. New geographical records, distribution maps, behaviour data and photographs of habitus are given. An illustrated identification key to all 12 species of the genus, including P. farinosa and P. nicobarica, is proposed. Penthicodes basigera (Walker, 1870) is transferred to the genus Scamandra Stål, 1863 and the new combination Scamandra basigera (Walker, 1870) n. comb. is proposed. The subgenus Ereosoma is regarded as heterogenous and the species are separated in 2 new species-groups on the base of the male genitalia and colour pattern: group astraea+ (astraea, bimaculata, caja, celebica, quadrimaculata, rugulosa and variegata) and group atomaria+ (atomaria, pulchella, warleti).
Review of the Nearctic, Mexican and West Indian (Greater Antilles) species of Colliuris Degeer (Coleoptera: Carabidae: Odacanthini)
Authors: BOUSQUET YVES
Published: December 2018

The 18 species of the genus Colliuris occurring in Canada, United States of America, Mexico, and the Greater Antilles are redescribed and information on their distribution and habitat requirements is provided. A key for the separation of these species as well as other ones recorded from Central America is included. The following new synonymies are proposed: Casnonia picta Chaudoir, 1843, Casnonia limbata Waterhouse, 1878, Colliuris picta var. extrema Liebke, 1930, Colliuris picta var. concluda Liebke, 1930 and Colliuris yucatana Liebke, 1930 with Colliuris pensylvanica (Linné, 1767) and Apiodera transparens Motschulsky, 1864 and Colliuris subdistincta var. maculata Liebke, 1930 with Colliuris subdistincta (Chaudoir, 1863). Colliuris caymanensis Darlington, previously considered a subspecies of C. tetrastigma (Chaudoir), is treated as a species, new status.
Annotated catalogue of the click-beetle tribe Senodoniini (Coleoptera: Elateridae: Dendrometrinae)
Authors: KUNDRATA ROBIN , MUSALKOVA MARKETA , PROSVIROV ALEXANDER S.
Published: December 2018

An annotated catalogue of the tribe Senodoniini (Coleoptera: Elateridae: Dendrometrinae) is presented. Altogether, 21 extant species are classified in genera Senodonia Laporte, 1838 (20 species) and Sossor Candèze, 1883 (one species). Genus Parallotrius Candèze, 1878 is placed into Dendrometrinae incertae sedis, and Allotriopsis Champion, 1896 is tentatively transferred to Elaterinae: Dicrepidiini. Senodonia bicoloris Vats & Chauhan, 1993 is transferred to Arhaphes Candèze, 1860 (Elateridae: Negastriinae) as A. bicoloris (Vats & Chauhan, 1993) comb. nov. Senodoniini are distributed in the Himalayas, China and South East Asia. For each taxon we provide synonyms, information on types, type localities, distribution, and bibliography. Additionally, a list of genera earlier classified in Senodoniini but currently placed outside the group is given.
To Bargain or Not to Bargain: The Role of Fixed Costs in Price Negotiations
Authors: Jindal Pranav , Newberry Peter
Published: December 2018

Retailers routinely allow consumers to negotiate a discount off the posted price for big-ticket items such as home appliances and automobiles, and on online platforms such as Amazon and eBay. The profitability of such a strategy, relative to selling only at posted prices, depends on consumers’ willingness to initiate a negotiation and ability to negotiate a discount. In this article, the authors incorporate consumers’ decision of whether to negotiate into a demand model. The decision to negotiate hinges on how the expected discount from negotiation compares with the magnitude of a nonpecuniary cost that the consumer incurs by initiating the negotiation. The current study shows how this cost can be nonparametrically identified, separately from consumers’ ability to get a discount and marginal utility of income. The application of this model to individual-level data on refrigerator transactions reveals that, conditional on negotiating, consumers get, on average, 41% of the available surplus and incur an average cost of $28 to initiate a negotiation. The magnitude of these nonpecuniary costs’ not only affects retailer profits but also has implications for pricing strategy and consumer surplus. Ignoring these costs results in biased estimates of consumers’ willingness to pay, translating to annual losses of $1.6 million in the current study setting.