bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss
Authors: Gao Xue , Yuan Yong-Yi , Lin Qiong-Fen , Xu Jin-Cao , Wang Wei-Qian , Qiao Yue-Hua , Kang Dong-Yang , Bai Dan , Xin Feng , Huang Sha-Sha , Qiu Shi-Wei , Guan Li-Ping , Su Yu , Wang Guo-Jian , Han Ming-Yu , Jiang Yi , Liu Han-Kui , Dai Pu
Published: February 2018

Background Hereditary sensorineural hearing loss is a genetically heterogeneous disorder.

Objectives This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL).

Methods Whole exome sequencing and linkage analysis were performed to identify pathogenic mutation. Inner ear expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1 Morpholino knockdown Zebrafish were constructed to explore the deafness mechanism.

Results We identified a cosegregating heterozygous missense mutation, c.296G>A (p.Arg99His) in the gene encoding interferon lambda receptor 1 (IFNLR1) – a protein that functions in the Jak/ STAT pathway– are associated with ADNSHL. Morpholino knockdown of ifnlr1 leads to a significant decrease in hair cells and non-inflation of the swim bladder in late-stage zebrafish, which can be reversed by injection with normal Zebrafish ifnlr1 mRNA. Knockdown of ifnlr1 in zebrafish causes significant upregulation of cytokine receptor family member b4 (interleukin-10r2), jak1, tyrosine kinase 2, stat3, and stat5b in the Jak1/STAT3 pathway at the mRNA level.

ConclusionIFNLR1 function is required in the auditory system and that IFNLR1 mutations are associated with ADNSHL. To the best of our knowledge, this is the first study implicating an interferon lambda receptor in auditory function.
Reversible cerebellar oedema secondary to profound hypomagnesaemia
Authors: Ross Russell Amy Louise , Prevett Martin , Cook Paul , Barker Charles Simon , Pinto Ashwin Arnold
Published: February 2018

Magnesium is the second most abundant intracellular cation. Deficiency can cause several neurological complications, including cerebellar syndromes, with various MRI findings. These include cerebellar oedema, presumably through a similar mechanism to that in posterior reversible encephalopathy syndrome (PRES). People particularly vulnerable to deficiency include those with high alcohol consumption, excessive loss due to gastrointestinal pathology and those taking certain medications, including proton pump inhibitors. We report three patients with cerebellar syndromes associated with hypomagnesaemia. These cases support the previously reported association between hypomagnesaemia and reversible cerebellar dysfunction and illustrate the range of potential presentations. They highlight an uncommon but treatable cause of cerebellar ataxia that may present to acute neurological liaison services.
Relative pollen productivity estimates and changes in Holocene vegetation cover in the deciduous forest of southeastern Quebec, Canada
Authors: Chaput Michelle A. , Gajewski Konrad
Published: February 2018

The Regional Estimates of VEgetation Abundance from Large Sites (REVEALS) model was used to quantify Holocene changes in vegetation cover in the deciduous forest of southeastern Quebec, Canada. The Extended R-Value (ERV) model was used to obtain relative pollen productivity estimates (PPEs) for eight tree taxa and to determine the relevant source area of pollen (RSAP) for lakes in this ecosystem. Modern vegetation was estimated using pollen data from 16 small (<0.5 km2) lakes and a species-level vegetation survey of southern Quebec. The RSAP was estimated to be within 1600 m of the lakes. Tsuga, Fagus, and Quercus were the most productive taxa, and Populus and Acer were the lowest. Reconstructed changes in absolute vegetation cover show a high abundance of Picea followed by Populus in the early Holocene. The reconstructed values for Populus suggest that it was widely distributed across the landscape. Abies and Acer were dominant on the landscape during the late to mid-Holocene, and an increase in Picea during the Neoglacial is more significant than in percentage diagrams. The REVEALS results provide estimates of land-cover change that are more realistic and informative than the use of pollen percentages alone.
Evaluation of bitumen physical properties modified with waste plastic pipes
Authors: Köfteci Sevil , Ahmedzade Perviz , Günay Taylan
Published: February 2018

The aim of this paper is to examine the effects of ground plastic pipe wastes on bitumen. For this purpose, three modified bitumen samples with modifier contents of 2%, 4%, and 6% along with pure bitumen were prepared and tested. To understand the effect of modifier on bitumen, conventional bitumen tests, rotational viscosity tests at 135 °C and 165 °C, dynamic shear rheometer tests at three different frequencies that represent three different traffic speeds, and bending beam rheometer (BBR) test were performed. The BBR test results showed that resistance of pure bitumen to low-temperature cracking increased by using additives up to 4%. Based on the results of this study, it can be said that waste plastic pipes can be used as modifier for the bitumen binder. The 4% additive showed the best performance.
Welcome to AI matters, volume 3, issue 4
Authors: Eaton Eric , McGovern Amy
Published: February 2018

Welcome to the final issue in our third year!

This issue features the second installment of
essays on the "Responsible Use of AI Technologies"
from the winners of the ACM SIGAI-sponsored student essay contest. In addition to having their essay appear in
AI Matters
, the contest winners received either monetary prizes or one-on-one Skype sessions with leading AI researchers.
An interview with Ayanna Howard
Authors: McGovern Amy , Eaton Eric
Published: February 2018

This column is the fifth in our series profiling senior AI researchers. This month focuses on Ayanna Howard.
Impact of Micronutrients on the Immune Response of Animals
Authors: Smith Allen D. , Panickar Kiran S. , Urban Joseph F. , Dawson Harry D.
Published: February 2018

Vitamins and minerals (micronutrients) play an important role in regulating and shaping an immune response. Deficiencies generally result in inadequate or dysregulated cellular activity and cytokine expression, thereby affecting the immune response. Decreased levels of natural killer, granulocyte, and phagocytic cell activity and T and B cell proliferation and trafficking are associated with inadequate levels of micronutrients, as well as increased susceptibility to various adverse health conditions, including inflammatory disorders, infection, and altered vaccine efficacy. In addition, most studies of micronutrient modulation of immune responses have been done in rodents and humans, thus limiting application to the health and well-being of livestock and companion animals. This exploratory review elucidates the role of vitamins and minerals on immune function and inflammatory responses in animals (pigs, dogs, cats, horses, goats, sheep, and cattle), with reference to rodents and humans.
Protection from vascular dysfunction in female rats with chronic stress and depressive symptoms
Authors: Brooks Steven D. , Hileman Stanley M. , Chantler Paul D. , Milde Samantha A. , Lemaster Kent A. , Frisbee Stephanie J. , Shoemaker J. Kevin , Jackson Dwayne N. , Frisbee Jefferson C.
Published: February 2018

The increasing prevalence and severity of clinical depression are strongly correlated with vascular disease risk, creating a comorbid condition with poor outcomes but demonstrating a sexual disparity whereby female subjects are at lower risk than male subjects for subsequent cardiovascular events. To determine the potential mechanisms responsible for this protection against stress/depression-induced vasculopathy in female subjects, we exposed male, intact female, and ovariectomized (OVX) female lean Zucker rats to the unpredictable chronic mild stress (UCMS) model for 8 wk and determined depressive symptom severity, vascular reactivity in ex vivo aortic rings and middle cerebral arteries (MCA), and the profile of major metabolites regulating vascular tone. While all groups exhibited severe depressive behaviors from UCMS, severity was significantly greater in female rats than male or OVX female rats. In all groups, endothelium-dependent dilation was depressed in aortic rings and MCAs, although myogenic activation and vascular (MCA) stiffness were not impacted. Higher-resolution results from pharmacological and biochemical assays suggested that vasoactive metabolite profiles were better maintained in female rats with normal gonadal sex steroids than male or OVX female rats, despite increased depressive symptom severity (i.e., higher nitric oxide and prostacyclin and lower H2O2and thromboxane A2levels). These results suggest that female rats exhibit more severe depressive behaviors with UCMS but are partially protected from the vasculopathy that afflicts male rats and female rats lacking normal sex hormone profiles. Determining how female sex hormones afford partial vascular protection from chronic stress and depression is a necessary step for addressing the burden of these conditions on cardiovascular health.

NEW & NOTEWORTHY This study used a translationally relevant model for chronic stress and elevated depressive symptoms to determine how these factors impact conduit and resistance arteriolar function in otherwise healthy rats. While chronic stress leads to an impaired vascular reactivity associated with elevated oxidant stress, inflammation, and reduced metabolite levels, we demonstrated partial protection from vascular dysfunction in female rats with normal sex hormone profiles compared with male or ovariectomized female rats.
Overexpression of heart-specific small subunit of myosin light chain phosphatase results in heart failure and conduction disturbance
Authors: Arimura Takuro , Muchir Antoine , Kuwahara Masayoshi , Morimoto Sachio , Ishikawa Taisuke , Du Cheng-Kun , Zhan Dong-Yun , Nakao Shu , Machida Noboru , Tanaka Ryo , Yamane Yoshihisa , Hayashi Takeharu , Kimura Akinori
Published: February 2018

Mutations in genes encoding components of the sarcomere cause cardiomyopathy, which is often associated with abnormal Ca2+sensitivity of muscle contraction. We have previously shown that a heart-specific myosin light chain phosphatase small subunit (hHS-M21) increases the Ca2+sensitivity of muscle contraction. The aim of the present study was to investigate the function of hHS-M21in vivo and the causative role of abnormal Ca2+sensitivity in cardiomyopathy. We generated transgenic mice with cardiac-specific overexpression of hHS-M21. We confirmed that hHS-M21increased the Ca2+sensitivity of cardiac muscle contraction in vivo, which was not followed by an increased phosphorylation of myosin light chain 2 isoforms. hHS-M21transgenic mice developed severe systolic dysfunction with myocardial fibrosis and degeneration of cardiomyocytes in association with sinus bradycardia and atrioventricular conduction defect. The contractile dysfunction and cardiac fibrosis were improved by treatment with the Rho kinase inhibitor fasudil. Our findings suggested that the overexpression of hHS-M21results in cardiac dysfunction and conduction disturbance via non-myosin light chain 2 phosphorylation-dependent regulation.

NEW & NOTEWORTHY The present study is the first to develop mice with transgenic overexpression of a heart-specific myosin light chain phosphatase small subunit (hHS-M21) and to examine the effects of hHS-M21on cardiac function. Elevation of hHS-M21induced heart failure with myocardial fibrosis and degeneration of cardiomyocytes accompanied by supraventricular arrhythmias.
Replication of Type 2 diabetes-associated variants in a Saudi Arabian population
Authors: Li-Gao Ruifang , Wakil Salma M. , Meyer Brian F. , Dzimiri Nduna , Mook-Kanamori Dennis O.
Published: February 2018

Over 120 Type 2 diabetes (T2D) loci have been identified from genome-wide association studies (GWAS), mainly from Caucasian populations. Very limited knowledge is available on the Saudi Arabian population. In this study, 122 previously reported T2D-related variants from 84 loci were examined in a Saudi Arabian cohort of 1,578 individuals (659 T2D cases and 919 controls). Eleven single nucleotide polymorphisms (SNPs) corresponding to nine independent loci had a P value <0.05. If a more stringent Bonferroni threshold of P = 4.1 × 10−4 ( = 0.05/122) were applied, none of the SNPs would have reached the significance level. Nine of the SNPs with a P value <0.05 showed similar odds ratios as previously described, but rs11605924 ( CRY2) and rs9470794 ( ZFAND3) were in the opposite direction. This study demonstrates the importance of large-scale GWAS in the Saudi Arabian population to identify ethnicity-specific disease-associated variants.
Targeted Therapies for Targeted Populations: Anti-EGFR Treatment for EGFR-Amplified Gastroesophageal Adenocarcinoma
Authors: Maron Steven B. , Alpert Lindsay , Kwak Heewon A. , Lomnicki Samantha , Chase Leah , Xu David , O'Day Emily , Nagy Rebecca J. , Lanman Richard B. , Cecchi Fabiola , Hembrough Todd , Schrock Alexa , Hart John , Xiao Shu-Yuan , Setia Namrata , Catenacci Daniel V.T.
Published: February 2018

Previous anti-EGFR trials in unselected patients with gastroesophageal adenocarcinoma (GEA) were resoundingly negative. We identified EGFR amplification in 5% (19/363) of patients at the University of Chicago, including 6% (8/140) who were prospectively screened with intention-to-treat using anti-EGFR therapy. Seven patients received ≥1 dose of treatment: three first-line FOLFOX plus ABT-806, one second-line FOLFIRI plus cetuximab, and three third/fourth-line cetuximab alone. Treatment achieved objective response in 58% (4/7) and disease control in 100% (7/7) with a median progression-free survival of 10 months. Pretreatment and posttreatment tumor next-generation sequencing (NGS), serial plasma circulating tumor DNA (ctDNA) NGS, and tumor IHC/FISH for EGFR revealed preexisting and/or acquired genomic events, including EGFR-negative clones, PTEN deletion, KRAS amplification/mutation, NRAS, MYC, and HER2 amplification, and GNAS mutations serving as mechanisms of resistance. Two evaluable patients demonstrated interval increase of CD3+ infiltrate, including one who demonstrated increased NKp46+, and PD-L1 IHC expression from baseline, suggesting an immune therapeutic mechanism of action. EGFR amplification predicted benefit from anti-EGFR therapy, albeit until various resistance mechanisms emerged.

Significance: This paper highlights the role of EGFR inhibitors in EGFR-amplified GEA—despite negative results in prior unselected phase III trials. Using serial ctDNA and tissue NGS, we identified mechanisms of primary and acquired resistance in all patients, as well as potential contribution of antibody-dependent cell-mediated cytotoxicity to their clinical benefit. Cancer Discov; 8(6); 696–713. ©2018 AACR.

See related commentary by Strickler, p. 679.

This article is highlighted in the In This Issue feature, p. 663
What We Do and Do Not Know about Women and Kidney Diseases; Questions Unanswered and Answers Unquestioned: Reflection on World Kidney Day and International Woman’s Day
Authors: Piccoli Giorgina B. , Alrukhaimi Mona , Liu Zhi-Hong , Zakharova Elena , Levin Adeera ,   on behalf of the World Kidney Day Steering Committee
Published: February 2018

Chronic kidney disease affects approximately 10% of the world’s adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women’s Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women’s health and specifically their kidney health, on the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world’s population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to have an impact on women, with profound consequences for child bearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.
Clinical Features and Response to Treatment of Prolactinomas in Children and Adolescents: A Retrospective Single-Centre Analysis and Review of the Literature
Authors: Breil Thomas , Lorz Catherine , Choukair Daniela , Mittnacht Janna , Inta Ioana , Klose Daniela , Jesser Jessica , Schulze Egbert , Bettendorf Markus
Published: February 2018

Background: Paediatric prolactinomas are rare. The aim of this study was to investigate the clinical features and outcome of paediatric patients with prolactinomas. Methods: In this single-centre retrospective analysis, clinical, biochemical, and radiological features of all paediatric patients with pituitary adenomas diagnosed between 2000 and 2016 were evaluated. Results: Among 21 patients with pituitary adenomas, 12 patients with prolactinomas (median age 14.2 years, range 11–16.6 years, 8 females, 4 males) were identified (7 macro- and 5 microprolactinomas). The most common clinical symptoms were headaches (67%) and pubertal delay (67%). All patients with macroprolactinomas with prolactin concentrations >10,000 mU/L had at least 1 pituitary hormone deficiency. Cabergoline as first-line treatment (n = 11, median follow-up of 37 months, range 12–89 months) induced normoprolactinemia (n = 8), reduced the mean tumour volume by 80%, and ameliorated headaches (p = 0.016) and pubertal delay (p = 0.031), whereas intermittent moderate side effects occurred in 55%. Conclusion: Adolescents with headaches and pubertal delay should be investigated for prolactinomas. Treatment with cabergoline is well tolerated and effective in reducing clinical symptoms and prolactin concentrations was well as inducing tumour shrinkage. Further clinical prospective studies are needed to standardize paediatric treatment modalities.
Intratympanic Injections of Dexamethasone in Delayed Endolymphatic Hydrops: A Prospective Clinical Study
Authors: Morgan Ashraf Elsayed , Ismail Elshahat Ibrahem , Ashraf Bassem
Published: February 2018

Objective: This study was designed to evaluate the effectiveness of intratympanic dexamethazone (ITD) for the treatment of ipsilateral delayed endolymphatic hydrops (DEH). Methods: Forty-one patients were diagnosed with ipsilateral DEH. Only 37 patients completed this study. Patients were randomly divided into 2 groups. Group A (n = 16) received oral medication, and group B (n = 21) received ITD once weekly for 4 consecutive weeks. Results: In group A, 6 patients showed improvement in their vertigo. Four patients (25%) showed complete vertigo control, and 2 patients (12.5%) showed substantial vertigo control. In group B, 21 patients showed improvement in their vertigo, 11 patients (52%) showed complete vertigo control, and 10 patients (47%) showed substantial vertigo control. Only 1 case did not show any improvement in their vertigo. Conclusion: ITD is proven to be a valuable and promising alternative modality for the management of ipsilateral DEH.
Clinical and Videodermoscopic Evaluation of the Efficacy, Safety, and Tolerability of a Shampoo Containing Ichthyol, Zanthalene, Mandelic Acid, and Honey in the Treatment of Scalp Psoriasis
Authors: Mariano Maria , De Padova Maria Pia , Lorenzi Sandra , Cameli Norma
Published: February 2018

Purpose of the Study: The aim of the present prospective multicenter open study was to clinically and instrumentally evaluate the efficacy, safety, and tolerability of a shampoo, Mellis Cap® shampoo, containing ichthyol, zanthalene, mandelic acid, and honeydew honey in the treatment of mild to moderate scalp psoriasis. Procedures: Thirty subjects with mild to moderate psoriasis applied the shampoo three times a week for 12 weeks. The outcome was evaluated at 30 days (T1), 60 days (T2), and 90 days (T3) of treatment, comparing it to baseline (T0) by means of clinical and patients’ evaluation, digital photographs, and videodermoscopy. Results: Clinical and patients’ evaluation showed improvement of scalp psoriasis and itching. This was confirmed by videodermoscopy analysis with a significant reduction of scalp psoriasis severity at T2 and T3 compared to baseline. No side effects were observed or reported. Conclusions: Study treatment was well tolerated and showed significant clinical and instrumental improvement of scalp psoriasis. Mellis Cap® shampoo is a good alternative to other medicated shampoos in the treatment of mild to moderate scalp psoriasis.
Obstructive Sleep Apnea and Otolaryngologic Manifestations in Children with Pseudohypoparathyroidism
Authors: Curley Kathleen L. , Kahanda Sachini , Perez Katia M. , Malow Beth A. , Shoemaker Ashley H.
Published: February 2018

Background/Aims: Pseudohypoparathyroidism (PHP) is a rare, genetic disorder. Patients with PHP may have increased prevalence of obstructive sleep apnea (OSA) but this has not been prospectively studied. Methods: We enrolled children aged 6–18 years with PHP and matched controls. Evaluation included physical examination, medical history, and polysomnography. Results: Fifteen children with PHP type 1A (PHP1A) and 15 controls completed the study. Both groups were obese (BMI 32.2 ± 8.7 vs. 31.7± 6.5). The majority of PHP1A patients required tympanostomy tubes (86.7%) and adenotonsillectomy (73.3%). The primary outcome, i.e., the obstructive disturbance index, was significantly higher in PHP1A children versus controls (1.8 ± 2.3 vs. 0.6 ± 0.5, p = 0.045). Children with PHP1A were more likely to have OSA compared with controls (60.0 vs. 13.3%, p = 0.008). Three siblings with PHP type 1B (PHP1B) were also studied (BMI 25.9 ± 9.0). None had a history of adenotonsillectomy, one had tympanostomy tubes. The obstructive disturbance index (2.0 ± 2.3) was similar to that of children with PHP1A. Two (66.7%) PHP1B participants had OSA. Conclusion: Children with PHP1A are at an increased risk for OSA compared with similarly obese peers. They also have higher rates of otitis media and adenotonsillar hypertrophy. Screening for OSA should be considered in all patients with PHP1A and possibly PHP1B though more research is needed.
Intraplatelet Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor: New Biomarkers in Carcinoembryonic Antigen-Negative Colorectal Cancer?
Authors: Chater Charbel , Bauters Anne , Beugnet Claire , M’Ba Lena , Rogosnitzky Moshe , Zerbib Philippe
Published: February 2018

Background/Aim: Colorectal cancer (CRC) is associated with high incidence and mortality rates. Carcinoembryonic antigen (CEA), a prognostic biomarker for recurrent CRC following curative resection, suffers from low sensitivity, especially in early-stage screening. Intraplatelet angiogenesis regulators (IPAR), such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), have been identified as important regulators of tumor growth in CRC. The aim of this study was to confirm the higher preoperative level of IPAR (VEGF and PDGF) in CRC patients compared to controls and to measure IPAR in CEA-negative CRC patients. Methods: The data and blood of 30 CRC patients and 30 presumably healthy controls were prospectively analyzed and compared. Results: We confirmed elevated preoperative intraplatelet VEGF and PDGF levels in CRC patients compared to controls. Importantly, IPAR were significantly elevated even in CEA-negative CRC patients. Conclusion: Elevated preoperative intraplatelet VEGF and PDGF levels in CRC patients suggest new possibilities for postoperative monitoring in CRC patients, especially when CEA is negative.
A Potential Mechanism for Immune Suppression by Beta-Adrenergic Receptor Stimulation following Traumatic Injury
Authors: Shubin Nicholas J. , Pham Tam N. , Staudenmayer Kristan Lea , Parent Brodie A. , Qiu Qian , O’Keefe Grant E.
Published: February 2018

Background: β-Adrenergic agents suppress inflammation and may play an important role in posttraumatic infections. Mechanisms may include inhibition of MAP kinase signaling. We sought to determine whether MKP-1 contributed to catecholamine suppression of innate immunity and also wanted to know whether early catecholamine treatment after traumatic injury increases the risk of later nosocomial infection. Methods: We performed experiments using THP-1 cells and peripheral blood mononuclear cells from healthy individuals. We exposed cells to epinephrine and/or LPS and measured inflammatory gene transcription and MAP kinase activation. We inhibited MKP-1 activity to determine its role in catecholamine-induced immune suppression. Finally, we studied injured subjects to determine whether early catecholamine treatment was associated with nosocomial infection. Results: Epinephrine increases MKP-1 transcripts and protein and decreases LPS-induced p38 and JNK phosphorylation and TNF-α gene transcription. RNAi inhibition of MKP-1 at least partially restores LPS-induced TNF-α gene expression (p = 0.024). In the clinical cohort, subjects treated with β-adrenergic agents had an increased risk of ventilator-associated pneumonia (aOR = 1.9; 95% CI = 1.3–2.6) and bacteremia (aOR = 1.5; 95% CI = 1.1–2.3). Conclusions: MKP-1 may have a role in catecholamine-induced suppression of innate immunity, and exogenous catecholamines might contribute to nosocomial infection risk.
Use of Array Comparative Genomic Hybridization for the Diagnosis of DiGeorge Syndrome in Saudi Arabian Population
Authors: Bahamat Abeer A. , Assidi Mourad , Lary Sahira A. , Almughamsi Muna M. , Peer Zada Abdul A. , Chaudhary Adeel , Abuzenadah Adel , Abu-Elmagd Muhammad , Al-Qahtani Mohammed
Published: February 2018

DiGeorge syndrome (DGS) is a genetic disorder known as a clinically variable syndrome with over 180 associated phenotypic features. It is caused by a common human deletion in the 22q11.2 chromosomal region and currently is affecting approximately 1 in 4,000 individuals. Despite the prevalence of inherited diseases mainly due to consanguineous marriages, the current diagnosis of DGS in Saudi Arabia is mainly based on conventional high-resolution chromosome banding (karyotyping) and FISH techniques. However, advanced genome-wide studies for detecting microdeletions or duplications across the whole genome are needed. The aim of this study is to implement and use aCGH technology in clinical diagnosis of the 22q11.2 deletion in Saudi Arabian DGS patients and to confirm its effectiveness compared to conventional FISH and chromosome banding techniques. Thirty suspected DGS patients were assessed for chromosome 22q11.2 deletion using high-resolution G-banding, FISH, and aCGH. The aCGH results were compared with those obtained by the other 2 cytogenetic techniques. G-banding detected the 22q11.2 deletion in only 1 patient in the cohort. Moreover, it detected additional chromosomal aberrations in 3 other patients. Using FISH, allowed for detection of the 22q11.2 deletion in 2 out of 30 patients. Interestingly, the use of aCGH technique showed deletions in the chromosome 22q11.2 region in 8 patients, indicating a 4-fold increase in diagnostic detection capacity compared to FISH. Our results show the effectiveness of aCGH to overcome the limitations of FISH and G-banding in terms of diagnostic yield and allow whole genome screening and detection of a larger number of deletions and/or duplications in Saudi Arabian DGS patients. Except for balanced translocations and inversions, our data demonstrate the suitability of aCGH in the diagnostics of submicroscopic deletion syndromes such as DGS and most chromosomal aberrations or complex abnormalities scattered throughout the human genome. Our results recommend the implementation of aCGH in clinical genomic testing in Saudi Arabia to improve the diagnostic capabilities of health services while maintaining the use of conventional cytogenetic techniques for subsequent validation or for specific and known aberrations whenever required.
Sessão de Tai Chi Chuan promove hipotensão pós-exercício e redução da sobrecarga cardiovascular em idosos hipertensos
Authors: Carvalho Raphael Santos Teodoro de , Joaquim Anderson Gregorio , Xavier Joab Jefferson da Silva , Suen Vivian Marques Miguel , Ancheschi Leila Maria Marchi Alves
Published: February 2018

Design: Interventional study, prospective and quantitative study. Objective: To determine blood pressure and double product values of elderly hypertensive patients, after a single Tai Chi Chuan (TCC) session. Methods: Twenty elderly hypertensive patients participated in the study, in which the hemodynamic variables were measured pre-TCC session and control session (without exercise), and monitored for 60 minutes after the end of both sessions. Each session had an interval of 7 days. Results: The results showed that at the end of the TCC, the heart rate remained elevated for 30 minutes, returning to pre-exercise values from the 40th minute. Significant reduction in mean blood pressure (MBP) from the 10th minute, and significant reduction in systolic (SBP) and diastolic (DBP) blood pressure from the 20th minute to the 60th minute after TCC session (p<0.001) were observed. A magnitude reduction compared to pre-exercise was around -22 / -18 mmHg for SBP and DBP respectively (p<0.001). Significant reduction of the DP was observed from the 30th minute, and reduced until the 60th minute after TCC (p<0.001). The magnitude of DP reduction compared to pre-exercise was around -1675 (p<0.01). Conclusions: These findings show that single TCC session promotes post-exercise hypotension (PEH) and reduces cardiac overload in elderly hypertensive patients.
Primary synchronic melanomas: dermoscopic aspects
Authors: D’Assumpção Daniela Gomes Cunha , Chagas Gabriella Campos do Carmo das , Guedes Juliana Chaves Ruiz , Verardino Gustavo Costa
Published: February 2018

Synchronic melanomas are rare and poorly described in the literature. They are classified in this way when a second melanoma is observed on the first examination or up to three months after the first diagnosis. An unusual case and the dermoscopic examination of a patient with two primary synchronic melanomas is described. The dermatoscopy is a very useful tool in the early diagnosis of melanomas. Some dermatoscopy patterns suggestive of melanomas on the face are asymmetric pigmented anexiais openings, rhomboidal structures and blue-gray globules and dots. The dermatoscopy characteristic pattern of melanoma in the region of plant is the default in parallel ridges that has high sensitivity and specificity in detecting acrais melanomas.
Organ donation and transplantation: a binomial to be optimized
Authors: Graf Catarina Piolla , Silva Orlando de Castro e
Published: February 2018

Over the years, organ transplantation has become a viable alternative for the treatment of end-stage diseases that, in the recent past, had high mortality rates. In this way, the number of people in the waiting list for organ transplantation has grown disproportionately to the number of organ donations, creating a gap that remains until now. In this article, we intend to discuss the issues that limit donation, especially family refusal, addressing the issue through the psychological bias of relatives at the time of death. In addition, we show updated numbers of donations and organ transplants in Brazil. Thus, it is concluded that an alternative to increase the donation rate is the instruction of the medical team that conducts the conversation with the relatives of the donor, as well as the awareness of the society, aiming at greater knowledge and understanding of the binomial donation and transplantation. Finally, it is discussed the project of the Academic League of Surgery and Transplantation of the FMRP- USP that, when promoting lectures in high schools, can induce discussions and solve possible doubts, in order to inform the young people about the reality of donations of organs and improve long-term donation rates.
Hemodynamic Characteristics in Significant Symptomatic and Asymptomatic Primary Mitral Valve Regurgitation at Rest and During Exercise
Authors: Bakkestrøm Rine , Banke Ann , Christensen Nicolaj L. , Pecini Redi , Irmukhamedov Akhmadjon , Andersen Mads , Borlaug Barry A. , Møller Jacob E.
Published: February 2018

Background—

In severe asymptomatic primary mitral valve regurgitation without risk factors, surgery strategy is controversial. We sought to clarify whether being symptomatic corresponds to the hemodynamic burden and reduced exercise capacity. A better understanding of this may contribute to optimize timing of surgery.

Methods and Results—

Subjects with asymptomatic (New York Heart Association functional class I, n=29) or symptomatic (New York Heart Association functional class II and III, n=28) significant primary mitral valve regurgitation (effective regurgitant orifice, ≥0.30 cm
2
; left ventricular ejection fraction, >60%) were included. Right heart catheterization during rest and exercise, echocardiography, magnetic resonance imaging, and peak oxygen consumption test was performed. Symptomatic subjects had significantly higher pulmonary capillary wedge pressure at rest (14±4 versus 11±3 mm Hg;
P
=0.003) and at maximal exercise (30±6 versus 25±7 mm Hg;
P
=0.02) and higher mean pulmonary artery pressure (PAP) at rest (22±7 versus 18±4 mm Hg;
P
=0.005) and maximal exercise (46±8 versus 39±7 mm Hg;
P
=0.005) than asymptomatic subjects. Among asymptomatic subjects with normal resting value, exercise testing revealed a systolic PAP >60 mm Hg in 34%. Also the reverse response with minimal increase in pulmonary capillary wedge pressure and mean PAP during exercise was seen, especially in asymptomatic subjects. Among symptomatic subjects, we found a significant inverse correlation between resting mean PAP and left ventricular ejection fraction (
r
=−0.52;
P
=0.02) and right ventricular ejection fraction (
r
=−0.67;
P
<0.01). Peak oxygen consumption was equal and normal in both groups and correlated with left ventricular stroke volume but not with pulmonary capillary wedge pressure.

Conclusions—

Symptoms in patients with severe mitral valve regurgitation relate to congestion (pulmonary capillary wedge pressure and PAP), but not to peak oxygen consumption, which is determined by forward left ventricular stroke volume. Exercise testing reveals a higher mitral valve regurgitation burden in apparently asymptomatic patients.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02961647.
Clinical Relevance of Functionally Insignificant Moderate Coronary Artery Stenosis Assessed by 3‐Vessel Fractional Flow Reserve Measurement
Authors: Park Jonghanne , Lee Joo Myung , Koo Bon‐Kwon , Shin Eun‐Seok , Nam Chang‐Wook , Doh Joon‐Hyung , Hwang Doyeon , Zhang Jinlong , Hu Xinyang , Wang JianAn , Ye Fei , Chen Shaoliang , Yang Junqing , Chen Jiyan , Tanaka Nobuhiro , Yokoi Hiroyoshi , Matsuo Hitoshi , Takashima Hiroaki , Shiono Yasutsugu , Akasaka Takashi
Published: February 2018

Background

Understanding of the risk conferred by functionally insignificant lesions in multiple coronary vessels is limited. We investigated the prognostic implications of coronary artery disease (
CAD
) based on 3‐vessel fractional flow reserve (
FFR
).

Methods and Results

A total of 1,136 patients underwent
FFR
measurement in the 3 major epicardial arteries. We defined vessels with “Moderate
CAD
” as vessels with
FFR
, 0.81 to 0.87. Patients were classified into Group 1: No apparent
CAD
(
FFR
>0.87 in all 3‐vessels); Group 2: Single‐vessel moderate
CAD
; Group 3: Multivessel moderate
CAD
; and Group 4: Functionally significant
CAD
(
FFR
≤0.80) in any vessel. The primary end point was 2‐year major adverse cardiac events, a composite of cardiac death, myocardial infarction, and ischemia‐driven revascularization. Forty‐three percent of patients had moderate
CAD
(Group 2: 403/1136, 35.5%; Group 3: 84/1136, 7.4%). The 2‐year risk of major adverse cardiac events was not significantly different between patients with single‐vessel moderate
CAD
and no apparent
CAD
(2.6 versus 2.6%;
HR
, 1.1; 95% confidence interval, 0.4%–2.8%;
P
=0.89). However, patients with multivessel moderate
CAD
were at significantly higher risk than Group 1 (7.4 versus 2.6%; hazard ratio, 3.3; 95% confidence interval, 1.1%–9.8%;
P
=0.03). The risk of major adverse cardiac events in patients with multivessel moderate
CAD
was comparable to that of patients with functionally significant
CAD
(hazard ratio, 1.2; 95% confidence interval, 0.5%–3.0%;
P
=0.67). In a multivariable regression model, multivessel moderate
CAD
was an independent predictor of greater risk of 2‐year major adverse cardiac events.

Conclusions

Global physiologic assessment with
FFR
measurement of 3 vessels can identify multivessel moderate
CAD
. The prognostic implication of multivessel moderate
CAD
appears comparable to that of functionally significant
CAD
.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier: NCT01621438.
The study of larval tail morphology reveals differentiation between two Triturus species and their hybrids
Authors: Vučić Tijana , Vukov Tanja D. , Tomašević Kolarov Nataša , Cvijanović Milena , Ivanović Ana
Published: February 2018

In amphibians, morphological differentiation and disparity at the larval and post-metamorphic ontogenetic stages can diverge, owing to various contrasting environments and different selective pressures. In the monophyletic clade of nine Triturus newt species, five different morphotypes can be recognized, but information on larval morphology is limited. Here we explore divergence of larval morphology in Triturus ivanbureschi, T. macedonicus, and their F1 hybrids. These two genetically and morphologically distinct crested newt species hybridize in nature and form a relatively wide hybrid zone in the central part of the Balkan Peninsula. Using a geometric morphometric approach and multivariate statistics, we evaluated differences of tail size and shape, colouration pattern, and the presence of a tail filament at the mid-larval stage in larvae reared under controlled laboratory conditions. We chose the tail as the main propulsive organ crucial for locomotion, feeding, and escaping predators. We found that Triturus ivanbureschi and T. macedonicus larvae differ in tail shape, but not in tail size. Two groups of F1 hybrid larvae (obtained from reciprocal crossing) were similar to each other, but differed from the parental species in size and shape of the tail, colouration pattern, and the presence of a tail filament. Our results indicate that, like adults, larvae diverge morphologically and hybrid larvae do not exhibit intermediate morphology of the parental species.
Public Interest Environmental Litigation in China
Authors: Zhang Richard , Mayer Benoit
Published: February 2018

Since January 2015, China’s Environmental Protection Law has allowed Chinese Non- Government Organisations to initiate public interest litigation in relation to activities that harm the environment. This article assesses the implementation of this reform. Based on a variety of primary and secondary sources, it documents almost every case filed in the first two-and-a-half years of the implementation of public interest environmental litigation in China. It demonstrates a rapid development of this new field of litigation which, so far, has almost systematically led to Court decisions favourable to the plaintiffs. Yet, we also recognize some limitations and room for improvement, in particular regarding barriers to access to courts and questions of enforcement of judgments. Therefore, while public interest environmental litigation is a promising opportunity for the protection of the environment in China, some possible refinements of the relevant statutory framework can be identified.
Dominikia litorea, a new species in the Glomeromycotina, and biogeographic distribution of Dominikia
Authors: BŁASZKOWSKI JANUSZ , RYSZKA PRZEMYSŁAW , KOZŁOWSKA ANNA
Published: February 2018

An arbuscular mycorrhizal fungus (AMF) producing clusters with colourless, small (11‒35 µm diam when globose) spores of unique morphological characters of two spore wall layers was grown in a trap culture and in single-species cultures. Both the spore wall layers are permanent and have the same thickness. The features of the spores prompted that the fungus most probably belongs to one of the genera, Dominikia or Kamienskia. Phylogenetic analyses of sequences of the SSU‒ITS‒LSU nrDNA and the RPB1 gene showed that the discussed AMF is an undescribed Dominikia sp. highly diverged molecularly from the 12 so far described species of the genus. Consequently, the fungus is described here as D. litorea sp. nov. The sporulation of D. litorea in the trap culture indicated that in the field the new species lived in mycorrhizal symbiosis with Xanthium spinosum that had colonized sand dunes of the Mediterranean Sea located near Verico, Greece. However, comparisons of the SSU‒ITS‒LSU sequences of D. litorea with those obtained from molecular environmental studies, which are deposited in public databases, indicated that the new species probably is also associated with roots of an unnamed plant species growing in China. In addition, based on available literature, sequence data and personal observations, the so far known geographical distribution, habitats, and plant-hosts of the described Dominikia spp. were presented and discussed. Finally, the potential participation of Dominikia spp. in influencing plants and plant communities with which they are associated and ecosystems in which they exist were discussed.
Two novel species of Lactarius subgenus Plinthogalus from Uttarakhand Himalaya
Authors: UNIYAL PRIYANKA , DAS KANAD , BHATT R.P.
Published: February 2018

Lactarius is a prevalent ectomycorrhizal genus in the forests of Uttarakhand Himalaya. During a macrofungal exploration in the high altitude forests of this region two interesting taxa belonging to Lactarius subg. Plinthogalus were collected. Based on detailed macro- and micromorphological observations along with nrITS-based phylogenetic analysis these taxa are proposed here as new species, Lactarius nodulisporus and Lactarius singeri.
Morphological and phylogenetic evidence reveal Fissuroma taiwanense sp. nov. (Aigialaceae, Pleosporales) from Hedychium coronarium
Authors: TENNAKOON DANUSHKA S. , PHOOKAMSAK RUNGTIWA , KUO CHANG-HSIN , GOH TEIK K. , JEEWON RAJESH , HYDE KEVIN D.
Published: February 2018

Fissuroma taiwanense sp. nov. was collected from Shihnong Forest Area in Chiayi, Taiwan (Elevation 350m) and is the first report of a Fissuroma species from Hedychium (Zingiberaceae). The species is markedly different from extant species of Fissuroma in having broad cylindric-clavate asci with long, club-shaped apical and basal appendages and distinct thick mucilaginous sheath in ascospores. Combined analyses of LSU, SSU and tef1-α sequence data indicate a close relationship with F. maculans, the type species, but isolates of the new taxon are phylogenetically distinct. The new species is compared with other Fissuroma species and a comprehensive description and micrographs are provided.
Euro-Atlantic Atmospheric Circulation during the Late Maunder Minimum
Authors: Mellado-Cano Javier , Barriopedro David , García-Herrera Ricardo , Trigo Ricardo M. , Álvarez-Castro Mari Carmen
Published: February 2018

This paper presents observational evidence of the atmospheric circulation during the Late Maunder Minimum (LMM, 1685–1715) based on daily wind direction observations from ships in the English Channel. Four wind directional indices and 8-point wind roses are derived at monthly scales to characterize the LMM. The results indicate that the LMM was characterized by a pronounced meridional circulation and a marked reduction in the frequency of westerly days all year round, as compared to the present (1981–2010). The winter circulation contributed the most to the cold conditions. Nevertheless, findings indicate that the LMM in Europe was more heterogeneous than previously thought, displaying contrasting spatial patterns in both circulation and temperature, as well as large decadal variability. In particular, there was an increase of northerly winds favoring colder winters in the first half of the LMM, but enhanced southerlies contributing to milder conditions in the second half of the LMM. The analysis of the atmospheric circulation yields a new and complete classification of LMM winters. The temperature inferred from the atmospheric circulation confirms the majority of extremely cold winters well documented in the literature, while uncovering other less documented cold and mild winters. The results also suggest a nonstationarity of the North Atlantic Oscillation (NAO) pattern within the LMM, with extremely cold winters being driven by negative phases of a “high zonal” NAO pattern and “low zonal” NAO patterns dominating during moderately cold winters.
Creating the World’s Deadliest Catch: The Process of Enrolling Stakeholders in an Uncertain Endeavor
Authors: Alvarez Sharon A. , Young Susan L. , Woolley Jennifer L.
Published: February 2018

There is growing interest in the processes by which entrepreneurial opportunities are cocreated between entrepreneurs and their stakeholders. The longitudinal case study of de novo firm Wakefield Seafoods seeks to understand the underlying dynamics of phenomena that play out over time as stakeholders emerge and their contributions become essential to the opportunity formation process. The king crab data show that under conditions of uncertainty, characterized by incomplete or missing knowledge, entrepreneurial processes of experimentation, failure, and learning were effective in forming and exploiting an opportunity. Moreover, contrary to existing literature that either emphasizes heroic entrepreneurs or downplays their value, this article shows that both the vision of the entrepreneur and the stakeholder contributions are critical. This detailed examination of process data shows that the cumulative actions made by entrepreneurs in concert with their stakeholders formed an opportunity that coalesced into a new market.
Comparing Metacognition Assessments of Mathematics in Academically Talented Students
Authors: Young Adena E. , Worrell Frank C.
Published: February 2018

Two studies were conducted to examine and compare the construct validity of scores on the Junior Metacognition Awareness Inventory (JMAI) and problem-solving interview protocols. Participants consisted of 183 middle and high school students attending a university summer program for academically talented youth. Study 1 results indicated that JMAI scores were internally consistent and yielded an interpretable two-factor structure after the elimination of several items; however, the scores were not significantly or meaningfully related to GPA or current and future mathematics achievement. In Study 2 ( n = 30), JMAI scores did not predict students’ metacognitive behaviors during mathematics problem-solving tasks. In contrast, students’ metacognitive behaviors observed during problem solving were meaningfully related to mathematics achievement with medium to high effect sizes. Findings support the predictive validity of metacognition with regard to academic achievement when operationalized with problem-solving interviews, but call into question the criterion-related validity of JMAI scores.