bluuebunny/crossref_metadata_2025 huggingface dataset:
Szkodliwość cyberprzemocy w ocenie młodzieży
Authors: Nowakowski Krzysztof
Published: September 2018

Badania nad cyberprzemocą i różnymi formami agresji z użyciem nowoczesnych technologii komunikacyjnych stanowią znaczący obszar w analizie nowych, zagrażających zjawisk występujących wśród młodych osób. Charakteryzując specyfikę cyberprzemocy podkreśla się kluczową rolę mechanizmów takich jak anonimowość, rozproszenie odpowiedzialności czy modelowanie w genezie zachowań agresywnych w sieci internetowej. Większość danych wskazuje na negatywne skutki doświadczania cyberprzemocy przez adolescentów, jednak stosunkowo nieliczne pozostają doniesienia podejmujące problematykę postaw młodych osób wobec zjawiska cyberprzemocy. Celem podjętych badań było poznanie przekonań młodzieży na temat szkodliwości cyberprzemocy. W badaniach zastosowano ankietę do pomiaru cyberprzemocy z podwójnej perspektywy tj. sprawcy i ofiary zachowań agresywnych. W przeprowadzonej analizie uzyskanych wyników wzięto pod uwagę różnice w ocenie szkodliwości badanego zjawiska wynikające z płci ankietowanych. Wyśmiewanie, obrażanie i poniżanie innych użytkowników sieci zostało ocenione jako najbardziej dotkliwe przez badanych nastolatków. Nie zanotowano różnic międzypłciowych w tym zakresie – zarówno badani chłopcy jak i dziewczęta uznawali tę formę agresji elektronicznej za najbardziej krzywdzącą. Najczęściej podawanym uzasadnieniem szkodliwości cyberprzemocy okazały się krzywda psychiczna i odrzucenie społeczne doznawane przez ofiary agresji elektronicznej. Badania umożliwiają spojrzenie na agresję elektroniczną wśród młodych ludzi z perspektywy przejawianych przez nich postaw wobec tego typu zachowań. Eksploracyjny charakter analizy pozwala również na wskazanie kierunków i rekomendacji do dalszych badań poszerzających podjętą tematykę.
The recent expansion of Fox Sparrow (Passerella iliaca iliaca) breeding range into the northeastern United States
Authors: Lloyd John D
Published: September 2018

The breeding range of the Red Fox Sparrow (Passerella iliaca iliaca) is generally recognized as comprising the boreal forest of Canada. However, recent observations suggest that the species is present during the summer months throughout much of the northeastern U.S., unexpected for a species characterized as a passage migrant in the region. To clarify, I conducted a literature review to document the historical status of the species in the northeastern U.S. and then analyzed observations submitted to eBird to describe its recent and current status in the region. Historical accounts consistently identify Fox Sparrow as a passage migrant through the region during early spring and late fall. Beginning in the early 1980s, observers began noting regular extralimital records of Fox Sparrow in northern Maine. A single nest was discovered in the state in 1983, and another in northern New Hampshire in 1997. Despite the paucity of breeding records, observations submitted to eBird suggest that the southern limit of the breeding range of Fox Sparrow has expanded rapidly to the south and west in recent years. The proportion of complete checklists submitted to eBird that contained at least one observation of Fox Sparrow grew at an annual rate of 18% from 2003-2016 and was independent of observer effort. Fox Sparrow now occurs regularly on mountaintops and in young stands of spruce (Picea spp.) and balsam fir (Abies balsamea) during the breeding season throughout northern and western Maine and northern New Hampshire, with occasional records from the Green Mountains of Vermont and the Adirondack Mountains of New York. The cause of this rapid expansion of its breeding range is unknown, but may be related to an increase in the amount of young conifer forest in the northeastern U.S. created by commercial timber harvest.
Genome-wide identification and characterization of the MADS-box gene family in Salix suchowensis
Authors: Qu Yanshu , Bi Changwei , He Bing , Ye Ning , Yin Tongming , Xu Li-an
Published: September 2018

MADS-box genes encode transcription factors that participate in various plant growth and development processes, particularly floral organogenesis. To date, MADS-box genes have been reported in many species, the completion of the sequence of the willow genome provides us with the opportunity to conduct a comprehensive analysis of the willow MADS-box gene family. Here, we identified 60 willow MADS-box genes using bioinformatics-based methods and classified them into 22 M-type (11 Mα, 7 Mβ and 4 Mγ) and 38 MIKC-type (32 MIKCc and 6 MIKC*) genes based on a phylogenetic analysis. Fifty-six of the 60 SsMADS genes were randomly distributed on 19 putative willow chromosomes. By combining gene structure analysis with evolutionary analysis, we found that the MIKC-type genes were more conserved and played a more important role in willow growth. Further study showed that the MIKC* type was a transition between the M-type and MIKC-type. Additionally, the number of MADS-box genes in gymnosperms was notably lower than that in angiosperms. Finally, the expression profiles of these willow MADS-box genes were analysed in five different tissues (root, stem, leave, bud and bark). This study is the first genome-wide analysis of the willow MADS-box gene family, and the results establish a basis for further functional studies of willow MADS-box genes and serve as a reference for related studies of other woody plants.
What is the Real State of Financial Management in Companies in the Republic of Serbia?
Authors: Petkovic Goran , Konjikusic Snezana , Barjaktarović Lidija , Pindzo Renata
Published: September 2018

Abstract: Research Question: This paper focuses on the basic financial decision making practices of domestic companies and their knowledge of the operational risk management concept. Motivation: Chief Financial Officers (CFOs) play a significant role in the company’s development and achieving the company’s objectives (Van Horne & Wachowicz, 2007). Different authors carry out research based on one of the fields of finances-related decision making, like Graham & Harvey, 2001. The goal of this research is to show that difference in decision making process on companies’ finances and risk management depends on the company’s ownership structure.  Idea: The paper is aimed at the recognition of differences found in corporate decision making, relating both to capital budgeting and capital structure, dividend payout policy and risk management concept, depending on the ownership structure. Data: During the first half of 2016, a research consisting of the 392-companies sample operating in the Republic of Serbia was conducted, including all four listed fields concerning their economic operations. Nevertheless, only a total of 54 CFOs completed and handed back the distributed questionnaires. Tools: Some basic descriptive statistics techniques, one-way analysis of variance (ANOVA) and Kruskal-Wallis test were applied throughout the complete data analysis, while data processing involved the use of standard statistical package IBM SPSS 20.0. Findings: As shown by research findings, there is a notable difference in decision making, both on dividend payout and on risk management concept, depending on the types of ownership, with companies operating in our domestic market. The future research will concentrate on practice of companies merging both domestic and foreign entities, in order to determine whether a similar pattern might be found. Contribution: Furthermore, the research is intended to be complemented by the data contained in the official financial reports of those companies, with a view to ascertaining if the statements made by their CFOs are actually applied in the corporate practice.
The Possibility of Predictions in Auditor’s Opinion: The Case of the Serbian Tobacco Industry
Authors: Spahić Nataša , Vuković Bojana
Published: September 2018

Research Questions: This paper investigated whether there is a possibility for predictions of an auditor’s opinion that can be used to predict, in an extremely accurate way, future developments in one company. Motivation: The research of Dopuch, Holhausen and Leftwich (1987); Kirkos, Spathis and Manolopoulos (2007) or Kirskos (2012) and Kim and Upneja (2014) open space for new challenges for using auditing methods.The most trying task is to find a technique that will be able to timely, accurately and with the least waste of resources respond to the challenge. The fact that auditors are forced to expand the scope and purpose of the audit work, respecting new risks that are continually changing represents the primary inspiration for this paper. Idea: Our goal was to explore whether one of the possible techniques for prediction the auditor’s opinion – multivariate discriminant analysis – can precisely predict a correct future audit opinion and whether this analysis is useful for finding solutions to performing predictions. Data: The analysis was conducted using data from financial statements of 4 Serbian tobacco companies of years 2011, 2012, 2013, 2014 and 2015 published by the Serbian Business Registers Agency. Tools: The presented research, based on theoretical and mathematical support, uses statistical software tools Statistica. Findings: The application of discriminant analysis in Serbian tobacco companies showed statistically major variables of the balance sheet, manely “Intangible assets", "Supplies" and "Liabilities". Following these variables, we obtained results which we used as the predictors. The outcome of our preliminary investigation presented accurate and correct prediction which is also confirmed by historical data. The result of this investigation can be used for further more complex investigations when using some variables that will lead to discriminatory analysis for more classification groups to mark and rank the most significant variables for expressing the audit opinion. Contribution: Provided information is important for every business, because every entity that is listed on the business market aims to be as better as possible, and find out and exploit the possibility of avoiding a negative result.
Antiviral therapy effectively improves liver hemodynamics as evidenced by serum biomarker and contrast-enhanced ultrasound examinations in patients with hepatitis B cirrhosis
Authors: Xu Xiaoyong , Zhang Chaoxue , Shi Chen , Hu Naizhong , Sun Bin , Kong Derun , Xu Jianming
Published: September 2018

Background and Aims

To prospectively evaluate the effects of antiviral therapy on liver hemodynamics in patients with hepatitis B cirrhosis.

Methods

Seventy consecutive eligible HBV-related cirrhotic inpatients were enrolled in the prospective study. Fifty-two received different nucleoside analogs monotherapy and 18 denied antiviral therapy. Their liver biochemistry profiles and HBV-DNA were measured at the baseline and every 3 months. Peripheral blood vWF and sCD163, as well as liver ultrasound Doppler parameters including portal vein diameter (PVD), portal vein velocity (PVV), portal vein congestion index (PV-CI), hepatic vein damping index (HV-DI), hepatic arterial arrival time (HAAT), hepatic vein arrival time (HVAT) and intrahepatic cycle time (HV-HA), were measured at the baseline and the follow-up periods.

Results

In the antiviral group, all patients achieved complete virologic and liver biochemical responses after 3-month antiviral treatment. Furthermore, the response states were maintained till the follow-up endpoint. However, in the non-antiviral group, HBV DNA replication resulted in higher levels of ALT and AST compared to the baseline values (P < 0.05). In the antiviral group, PVD, PV-CI, HV-DI, vWF-Ag and sCD163 were all significantly reduced than the baseline values (P < 0.05), and PVV was significantly increased than the baseline value (P < 0.05).

Conclusions

Antiviral therapy could effectively suppress hepatocyte inflammation and alleviate the dysfunction of intrahepatic vascular endothelial and hepatic macrophages, which might improve hepatic hemodynamic function in HBV-related cirrhosis.
Molecular typing and profiling of topoisomerase mutations causing resistance to ciprofloxacin and levofloxacin inElizabethkingiaspecies
Authors: Jian Ming-Jr , Cheng Yun-Hsiang , Perng Cherng-Lih , Shang Hung-Sheng
Published: September 2018

Objectives

SeveralElizabethkingiaspecies often exhibit extensive antibiotic resistance, causing infections associated with severe morbidity and high mortality rates worldwide. In this study, we determined fluoroquinolone susceptibility profiles of clinicalElizabethkingiaspp. isolates and investigated the resistance mechanisms.

Methods

In 2017–2018, 131Elizabethkingiaspp. isolates were recovered from specimens collected at tertiary care centers in northern Taiwan. Initial species identification using the Vitek MS system and subsequent verification by 16S rRNA sequencing confirmed the presence ofElizabethkingia anophelis(n= 111),E. miricola(n= 11), andE. meningoseptica(n= 9). Fluoroquinolone susceptibility was determined using the microbroth dilution method, and fluoroquinolone resistance genes were analyzed by sequencing.

Results

AmongElizabethkingiaspp. isolates, 91% and 77% were resistant to ciprofloxacin and levofloxacin, respectively. The most prevalent alterations were two single mutations in GyrA, Ser83Ile, and Ser83Arg, detected in 76% of the isolates exhibiting fluoroquinolone MIC between 8 and 128 μg/ml. Another GyrA single mutation, Asp87Asn, was identified in two quinolone-resistantE. miricolastrains. None of the isolates had alterations in GyrB, ParC, or ParE. We developed a high-resolution melting assay for rapid identification of the prevalentgyrAgene mutations. The genetic relationship between the isolates was evaluated by random amplified polymorphic DNA PCR that yielded diverse pulsotypes, indicating the absence of any temporal or spatial overlap among the patients during hospitalization.

Conclusion

Our analysis of fluoroquinolone-resistantElizabethkingiaspp. isolates provides information for further research on the variations of the resistance mechanism and potential clinical guidance for infection management.
Distraction of cyclists: how does it influence their risky behaviors and traffic crashes?
Authors: Useche Sergio A. , Alonso Francisco , Montoro Luis , Esteban Cristina
Published: September 2018

Background

Undisputedly, traffic crashes constitute a public health concern whose impact and importance have been increasing during the past few decades. Specifically, road safety data have systematically shown how cyclists are highly vulnerable to suffering traffic crashes and severe injuries derived from them. Furthermore, although the empirical evidence is still very limited in this regard, in addition to other human factors involved in cycling crashes, distractions while cycling appear to be a major contributor to the road risk of cyclists.

Objectives

The main objectives of this study were, first, to explore the prevalence and trends of cycling distractions within an international sample of bike users, and second, to determine the influence of such distractions on road crashes suffered by cyclists, simultaneously considering the explanatory role of risky behaviors (errors and traffic violations) as potentially mediating variables between cycling distractions and traffic crashes.

Methods

For this cross-sectional study, we analyzed the data obtained from 1,064 cyclists—61.2% male and 38.8% female—from 20 different countries, who answered an on-line questionnaire on cycling-related features, habits, behaviors and accidents.

Results

The prevalence of different cycling distractions oscillated between 34.7% and 83.6%. The most common distractions were those related to the behavior of other users, physical elements of the road, weather conditions and phone calls. Age trends and differences were also found, thus establishing a positive association between age and distractibility during cycling. Furthermore, the effect of distractions on traffic crashes of cyclists was significant when tested together with age, risk perception and risky behaviors on the road.

Conclusion

The results of this study support the hypotheses that distractions have a major prevalence among bike users, and that they play a significant role in the prediction of the traffic crash rates of cyclists, through the mediation of risky behaviors.
Recognition of modified cytosine variants by the DNA‐binding domain of methyl‐directed endonuclease McrBC
Authors: Zagorskaitė Evelina , Manakova Elena , Sasnauskas Giedrius
Published: September 2018

Cytosine modifications expand the information content of genomic DNA in both eukaryotes and prokaryotes, providing means for epigenetic regulation and self versus nonself discrimination. For example, the methyl‐directed restriction endonuclease, McrBC, recognizes and cuts invading bacteriophage DNA containing 5‐methylcytosine (5mC), 5‐hydroxymethylcytosine (5hmC), and N4‐methylcytosine (4mC), leaving the unmodified host DNA intact. Here, we present cocrystal structures of McrB‐N bound to DNA oligoduplexes containing 5hmC, 5‐formylcytosine (5fC), and 4mC, and characterize the relative affinity of McrB‐N to various cytosine variants. We find that McrB‐N flips out modified bases into a protein pocket and binds cytosine derivatives in the order of descending affinity: 4mC > 5mC > 5hmC ≫ 5fC. We also show that pocket mutations alter the relative preference of McrB‐N to 5mC, 5hmC, and 4mC.
Tripeptide binding in a proton‐dependent oligopeptide transporter
Authors: Martinez Molledo Maria , Quistgaard Esben M. , Löw Christian
Published: September 2018

Proton‐dependent oligopeptide transporters (POTs) are important for the uptake of di‐/tripeptides in many organisms and for drug transport in humans. The binding mode of dipeptides has been well described. However, it is still debated how tripeptides are recognized. Here, we show that tripeptides of the sequence Phe‐Ala‐Xxx bind with similar affinities as dipeptides to the POT transporter from Streptococcus thermophilus (PepTSt). We furthermore determined a 2.3‐Å structure of PepTSt in complex with Phe‐Ala‐Gln. The phenylalanine and alanine residues of the peptide adopt the same positions as previously observed for the Phe‐Ala dipeptide, while the glutamine side chain extends into a hitherto uncharacterized pocket. This pocket is adaptable in size and can likely accommodate a wide variety of peptide side chains.
Changes in quaternary structure cause a kinetic asymmetry of glutamate racemase‐catalyzed homocysteic acid racemization
Authors: Mackie Joanna , Kumar Himank , Bearne Stephen L.
Published: September 2018

Glutamate racemases (GR) catalyze the racemization ofd‐ andl‐glutamate and are targets for the development of antibiotics. We demonstrate thatGRfrom the periodontal pathogenFusobacterium nucleatum(FnGR) catalyzes the racemization ofd‐homocysteic acid (d‐HCA), whilel‐HCAis a poor substrate. This enantioselectivity arises becausel‐HCAperturbsFnGR's monomer–dimer equilibrium toward inactive monomer. The inhibitory effect ofl‐HCAmay be overcome by increasing the totalFnGRconcentration or by adding glutamate, but not by blocking access to the active site through site‐directed mutagenesis, suggesting thatl‐HCAbinds at an allosteric site. This phenomenon is also exhibited byGRfromBacillus subtilis, suggesting that enantiospecific, “substrate”‐induceddissociationof oligomers to form inactive monomers may furnish a new inhibition strategy.
The effect of divalent cations on the thermostability of type II polyketide synthase acyl carrier proteins
Authors: Rivas Marco A. , Courouble Valentine C. , Baker Miranda C. , Cookmeyer David L. , Fiore Kristen E. , Frost Alexander J. , Godbe Kerilyn N. , Jordan Michael R. , Krasnow Emily N. , Mollo Aurelio , Ridings Stephen T. , Sawada Keisuke , Shroff Kavita D. , Studnitzer Bradley , Thiele Grace A. R. , Sisto Ashley C. , Nawal Saadia , Huff Adam R. , Fairman Robert , Johnson Karl A. , Beld Joris , Kokona Bashkim , Charkoudian Louise K.
Published: September 2018

The successful engineering of biosynthetic pathways hinges on understanding the factors that influence acyl carrier protein (ACP) stability and function. The stability and structure of ACPs can be influenced by the presence of divalent cations, but how this relates to primary sequence remains poorly understood. As part of a course‐based undergraduate research experience, we investigated the thermostability of type II polyketide synthase (PKS) ACPs. We observed an approximate 40 °C range in the thermostability among the 14 ACPs studied, as well as an increase in stability (5–26 °C) of the ACPs in the presence of divalent cations. Distribution of charges in the helix II‐loop–helix III region was found to impact the enthalpy of denaturation. Taken together, our results reveal clues as to how the sequence of type II PKS ACPs relates to their structural stability, information that can be used to study how ACP sequence relates to function. © 2018 American Institute of Chemical Engineers AIChE J, 64: 4308–4318, 2018
Utility and prognostic value of 18F‐FDG positron emission tomography‐computed tomography scans in patients with newly diagnosed multiple myeloma
Authors: Aljama Mohammed A. , Sidiqi M. Hasib , Buadi Francis K. , Lacy Martha Q. , Gertz Morie A. , Dispenzieri Angela , Dingli David , Muchtar Eli , Fonder Amie L. , Hayman Suzanne R. , Hobbs Miriam A. , Gonsalves Wilson I. , Warsame Rahma M. , Kourelis Taxiarchis , Hwa Yi Lisa , Kapoor Prashant , Kyle Robert A. , Leung Nelson , Go Ronald S. , Rajkumar S. Vincent , Kumar Shaji K.
Published: September 2018

Positron emission tomography‐computed tomography (PET‐CT) can identify bony lesions, assess disease burden, and detect extramedullary disease (EMD) in patients with multiple myeloma. We retrospectively reviewed records of patients who underwent PET‐CT within 60 days of a new diagnosis (before therapy commenced) to identify the nature and prognostic impact of PET‐CT abnormalities. Patients (N = 313) were seen from April 2005 through June 2017. Of the 234 patients (75%) with focal lesions (FLs), 182 (58%) had at least 3 FLs, 38 (12%) had EMD, and 204 (65%) had documented myelomatous lytic lesions. The median maximum standardized uptake value (SUVmax) for the entire cohort was 5.9 (range 1.5‐48.3). Presence of at least 3 FLs and EMD predicted inferior overall survival (OS); median OS was 57.8 months for patients with 3 or more FLs and 103.6 months for patients with fewer than 3 FLs (P = .003). The median OS was 45.5 and 71.8 months for patients with and without EMD, respectively (P = .004). No clear SUVmax cutoff was predictive of progression‐free survival or OS. PET‐CT is a valuable tool for assessing disease burden and could provide prognostic information about a contemporary cohort of patients with newly diagnosed myeloma who received treatment with novel agents.
Sequential HLA‐haploidentical transplantation utilizing post‐transplantation cyclophosphamide for GvHD prophylaxis in high‐risk and relapsed/refractory AML/MDS
Authors: Fraccaroli Alessia , Prevalsek Dusan , Fritsch Susanne , Haebe Sarah , Bücklein Veit , Schulz Christoph , Hubmann Max , Stemmler Hans‐Joachim , Ledderose Georg , Hausmann Andreas , Schmid Christoph , Tischer Johanna
Published: September 2018

This study evaluates the role of sequential therapy in HLA‐haploidentical transplantation (haplo‐HSCT) of high‐risk, relapsed/refractory AML/MDS. We analyzed the course of 33 adults with active disease at time of transplantation (AML n = 30; MDS n = 3; median age 58 years, range: 32‐71). Sequential therapy consisted of cytoreductive chemotherapy (FLAMSA n = 21; clofarabine n = 12) applied shortly prior to reduced intensity conditioning for T‐cell‐replete haplo‐HSCT using post‐transplantation cyclophosphamide as GvHD prophylaxis. No graft rejection was observed. Complete remission at day +30 was achieved in 97% of patients. CI of acute GvHD grade II‐IV and chronic GvHD was 24% (no grade IV) and 23%, respectively. NRM at 1 and 3 years was 15%, each. Severe regimen‐related toxicities (grade III‐IV) were observed in 58%, predominantly involving the gastrointestinal tract (diarrhea 48%, mucositis 15%, transient elevation of transaminases 18%). Probability of relapse at 1 and 3 years was 28% and 35%. At a median follow‐up of 36 months, the estimated 1‐ and 3‐year overall survival was 56% and 48%. Disease‐free survival was 49% and 40%, respectively. At 3 years, GvHD and relapse‐free survival (GRFS) was 24% while chronic GvHD and relapse‐free survival (CRFS) was 29%. Thus, our results indicate that sequential haplo‐HSCT is an effective salvage treatment providing high anti‐leukemic activity, favorable tolerance, and acceptable toxicity in patients suffering from advanced AML/MDS.
Influence of nutritional status on basal metabolic rates among rural agriculturalists of Ngilo‐Ilo, East Java
Authors: Miller Aaron A. , Indriati Etty , Leonard William R.
Published: September 2018

Objectives

Previous research has shown that tropical island populations have reduced basal metabolic rates (BMR) associated with the joint influences of heat stress and undernutrition. This study examines variation in BMR among an indigenous population of Indonesia, and compares these data with those collected from earlier studies in Indonesia.

Methods

Anthropometric dimensions and BMR were measured on a sample of 35 Indonesian adults (28 men, 7 women) from the rural village of Ngilo‐Ilo, East Java.

Results

Mean measured BMRs (±SD) were 1433 ± 344 kcal/d in men and 1256 ±257 kcal/d in women, and were not significantly different from estimates using the FAO/WHO/UNU predictive questions. Underweight individuals (BMIs <18.5 kg/m2) had BMRs that were 7.6% below predicted levels, while those with BMIs ≥18.5 kg/m2 had BMRs that were 8.0% above predicted levels (P < .01). Underweight individuals also had significantly higher respiratory quotients (RQ = .94 vs. .89; P < .05), suggesting lower levels of fat oxidation. Compared to data from previous studies (1929–1979), men of the Ngilo‐Ilo sample had similar BMIs (19.8 vs. 19.2 kg/m2), but higher BMRs, after adjusting for age and body weight (+2.1% vs. −5.6%; P < .05).

Conclusions

Among the agriculturalists of Ngilo‐Ilo, measured BMRs were low, but not significantly different from those predicted by the FAO/WHO/UNU equations. Among subjects of this sample and from earlier studies, poorer physical nutritional status was associated with reduced BMRs. These results suggest that chronic energy stress has consistently shaped metabolic function among Indonesian rural populations.
A novel mutation in CDH11, encoding cadherin‐11, cause Branchioskeletogenital (Elsahy‐Waters) syndrome
Authors: Castori Marco , Ott Claus‐Eric , Bisceglia Luigi , Leone Maria Pia , Mazza Tommaso , Castellana Stefano , Tomassi Jurgen , Lanciotti Silvia , Mundlos Stefan , Hennekam Raoul C. , Kornak Uwe , Brancati Francesco
Published: September 2018

Cadherins are cell‐adhesion molecules that control morphogenesis, cell migration, and cell shape changes during multiple developmental processes. Until now four distinct cadherins have been implicated in human Mendelian disorders, mainly featuring skin, retinal and hearing manifestations. Branchio‐skeleto‐genital (or Elsahy‐Waters) syndrome (BSGS) is an ultra‐rare condition featuring a characteristic face, premature loss of teeth, vertebral and genital anomalies, and intellectual disability. We have studied two sibs with BSGS originally described by Castori et al. in 2010. Exome sequencing led to the identification of a novel homozygous nonsense variant in the first exon of the cadherin‐11 gene (CDH11), which results in a prematurely truncated form of the protein. Recessive variants in CDH11 have been recently demonstrated in two other sporadic patients and a pair of sisters affected by BSGS. Although the function of this cadherin (also termed Osteoblast‐Cadherin) is not completely understood, its prevalent expression in osteoblastic cell lines and up‐regulation during differentiation suggest a specific function in bone formation and development.

This study identifies a novel loss‐of‐function variant in CDH11 as a cause of BSGS and supports the role of cadherin‐11 as a key player in axial and craniofacial malformations.
Understanding the pediatric psychiatric phenotype of 22q11.2 deletion syndrome
Authors: Fiksinski Ania M. , Schneider Maude , Murphy Clodagh M. , Armando Marco , Vicari Stefano , Canyelles Jaume M. , Gothelf Doron , Eliez Stephan , Breetvelt Elemi J. , Arango Celso , Vorstman Jacob A. S.
Published: September 2018

The purpose of this article is to provide an overview of current insights into the neurodevelopmental and psychiatric manifestations of 22q11.2 deletion syndrome (22q11DS) in children and adolescents. The pediatric neuropsychiatric expression of 22q11DS is characterized by high variability, both interindividual and intraindividual (different expressions over the lifespan). Besides varying levels of intellectual disability, the prevalence of autism spectrum disorders, attention deficit disorders, anxiety disorders, and psychotic disorders in young individuals with 22q11DS is significantly higher than in the general population, or in individuals with idiopathic intellectual disability. Possible explanations for this observed phenotypic variability will be discussed, including genetic pleiotropy, gene‐environment interactions, the age‐dependency of phenotypes, but also the impact of assessment and ascertainment bias as well as the limitations of our current diagnostic classification system. The implications inferred by these observations aforementioned bear direct relevance to both scientists and clinicians. Observations regarding the neuropsychiatric manifestations in individuals with 22q11DS exemplify the need for a dimensional approach to neuropsychiatric assessment, in addition to our current categorical diagnostic classification system. The potential usefulness of 22q11DS as a genetic model to study the early phases of schizophrenia as well as the phenomenon of neuropsychiatric pleiotropy observed in many CNV's will be delineated. From a clinical perspective, the importance of regular neuropsychiatric evaluations with attention to symptoms not always captured in diagnostic categories and of maintaining equilibrium between individual difficulties and competencies and environmental demands will be discussed.
Refining the phenotype associated with GNB1 mutations: Clinical data on 18 newly identified patients and review of the literature
Authors: Hemati Parisa , Revah‐Politi Anya , Bassan Haim , Petrovski Slavé , Bilancia Colleen G. , Ramsey Keri , Griffin Nicole G. , Bier Louise , Cho Megan T. , Rosello Monica , Lynch Sally Ann , Colombo Sophie , Weber Astrid , Haug Marte , Heinzen Erin L. , Sands Tristan T. , Narayanan Vinodh , Primiano Michelle , Aggarwal Vimla S. , Millan Francisca , Sattler‐Holtrop Shannon G. , Caro‐Llopis Alfonso , Pillar Nir , Baker Janice , Freedman Rebecca , Kroes Hester Y. , Sacharow Stephanie , Stong Nick , Lapunzina Pablo , Schneider Michael C. , Mendelsohn Nancy J. , Singleton Amanda , Loik Ramey Valerie , Wou Karen , Kuzminsky Alla , Monfort Sandra , Weisz Hubshman Monika , Doyle Samantha , Iglesias Alejandro , Martinez Francisco , Mckenzie Fiona , Orellana Carmen , van Gassen Koen L.I. , Palomares Maria , Bazak Lily , Lee Andy , Bircher Ana , Basel‐Vanagaite Lina , Hafström Maria , Houge Gunnar ,   C4RCD Research Group,   DDD study, Goldstein David B. , Anyane‐Yeboa Kwame
Published: September 2018

De novo germline mutations in GNB1 have been associated with a neurodevelopmental phenotype. To date, 28 patients with variants classified as pathogenic have been reported. We add 18 patients with de novo mutations to this cohort, including a patient with mosaicism for a GNB1 mutation who presented with a milder phenotype. Consistent with previous reports, developmental delay in these patients was moderate to severe, and more than half of the patients were non‐ambulatory and nonverbal. The most observed substitution affects the p.Ile80 residue encoded in exon 6, with 28% of patients carrying a variant at this residue. Dystonia and growth delay were observed more frequently in patients carrying variants in this residue, suggesting a potential genotype–phenotype correlation. In the new cohort of 18 patients, 50% of males had genitourinary anomalies and 61% of patients had gastrointestinal anomalies, suggesting a possible association of these findings with variants in GNB1. In addition, cutaneous mastocytosis, reported once before in a patient with a GNB1 variant, was observed in three additional patients, providing further evidence for an association to GNB1. We will review clinical and molecular data of these new cases and all previously reported cases to further define the phenotype and establish possible genotype–phenotype correlations.
Spinal manifestations in 12 patients with musculocontractural Ehlers‐Danlos syndrome caused by CHST14/D4ST1 deficiency (mcEDS‐CHST14)
Authors: Uehara Masashi , Kosho Tomoki , Yamamoto Noriaki , Takahashi Hideaki E. , Shimakura Taketoshi , Nakayama Jun , Kato Hiroyuki , Takahashi Jun
Published: September 2018

Musculocontractural Ehlers‐Danlos syndrome caused by mutations in CHST14 (mcEDS‐CHST14) is a recently delineated disorder, characterized by craniofacial, skeletal, visceral, and ocular malformations; and progressive cutaneous, skeletal, vascular, and visceral fragility‐related manifestations. Spinal lesions, though one of the most serious complications, have not been investigated systematically. In this study, we report detailed and comprehensive information about spinal lesions of 12 patients with a mean age at the first visit of 13.4 years. Eight patients (66.7%) had scoliosis with a Cobb angle ≥10°, including one with severe scoliosis with a Cobb angle ≥45°. Five patients (41.7%) had kyphosis at the thoracolumbar junction with a kyphotic angle ≥20°. Three patients (25%) developed severe thoracolumbar kyphosis with a kyphotic angle ≥50° accompanied by thoracic lordosis with a wedge‐like vertebral deformity and anterior vertebral osteophyte at the thoracolumbar junction, and two of them underwent surgical correction: complicated by fistula formation in one and performed safely and effectively through two‐staged operation in the other. Six patients (50.0%) had cervical kyphosis, all of whom except one had kyphosis ≥20° at the thoracolumbar level. Two patients (16.7%) had atlantoaxial subluxation, and 10 patients (83.3%) had cervical vertebral malformations. Patients with mcEDS‐CHST14 are susceptible to develop scoliosis, thoracolumbar kyphosis, and cervical kyphosis; and are recommended to have regular surveillance including total spine radiology. The present findings also suggest the critical role of dermatan sulfate in the development and maintenance of the spine.
Heterometallic Cluster‐Capped Tetrahedral Assemblies with Postsynthetic Modification of the Metal Cores
Authors: Shakirova Julia R. , Grachova Elena V. , Gurzhiy Vladislav V. , Thangaraj Senthil Kumar , Jänis Janne , Melnikov Alexey S. , Karttunen Antti J. , Tunik Sergey P. , Koshevoy Igor O.
Published: September 2018

Combining the star‐shaped alkynyl ligands with low‐nuclearity gold–copper triphosphane clusters produces 3D metallocage aggregates, which demonstrate room temperature phosphorescence in solution (max Φem=0.6). Their luminescence mainly originates from cluster‐localized metal‐to‐ligand charge transfer excited state. These supramolecular assemblies can be easily converted into the isostructural gold‐silver congeners by the direct exchange of the metal ions. Such modification of the terminal metal cores switches the emission to the intraligand (alkyne) electronic transitions of the triplet manifold, that represents an unusual optical functionality among the metallocycle/metallocage complexes.
A P−P Bond as a Redox Reservoir and an Active Reaction Site
Authors: Kim Yeong‐Eun , Lee Yunho
Published: September 2018

The carbonylation of a nickel(II) anilido species 2 led to the formation of a dinickel(0)–CO complex (P2P‐PP2){Ni(CO)}2 3 with a P−P bond along with isocyanate generation. In this reaction, the central phosphide moiety of an anionic PPP ligand (PPP−=−P[2‐PiPr2C6H4]2) acts as a single‐electron donor to form a P radical. Alternatively, 3 can be synthesized from the reduction of (PPP)NiCl (1) in the presence of CO; thus, the reaction proceeds by radical coupling of a .P−Ni0−CO species. The reverse reaction occurred to generate 1 when 3 was treated with AgCl. Since the P−P bond is light‐sensitive, its homolysis is possible and was explored by EPR spectroscopy and DFT analysis. Finally, various bond‐activation reactions of 3 occurred under visible‐light conditions, thus indicating that a P−P bond can act as an active reaction site.
Genome Editing Reveals Novel Thiotemplated Assembly of Polythioamide Antibiotics in Anaerobic Bacteria
Authors: Dunbar Kyle L. , Büttner Hannah , Molloy Evelyn M. , Dell Maria , Kumpfmüller Jana , Hertweck Christian
Published: September 2018

Closthioamide (CTA) is a unique symmetric nonribosomal peptide with six thioamide moieties that is produced by the Gram‐positive obligate anaerobe Ruminiclostridium cellulolyticum. CTA displays potent inhibitory activity against important clinical pathogens, making it a promising drug candidate. Yet, the biosynthesis of this DNA gyrase‐targeting antibiotic has remained enigmatic. Using a combination of genome mining, genome editing (targeted group II intron, CRISPR/Cas9), and heterologous expression, we show that CTA biosynthesis involves specialized enzymes for starter unit biosynthesis, amide bond formation, thionation, and dimerization. Surprisingly, CTA biosynthesis involves a novel thiotemplated peptide assembly line that markedly differs from known nonribosomal peptide synthetases. These findings provide the first insights into the biosynthesis of thioamide‐containing nonribosomal peptides and offer a starting point for the discovery of related natural products.
Coupling of Methane and Carbon Dioxide Mediated by Diatomic Copper Boride Cations
Authors: Chen Qiang , Zhao Yan‐Xia , Jiang Li‐Xue , Chen Jiao‐Jiao , He Sheng‐Gui
Published: September 2018

The use of CH4 and CO2 to produce value‐added chemicals via direct C−C coupling is a challenging chemistry problem because of the inertness of these two molecules. Herein, mass spectrometric experiments and high‐level quantum‐chemical calculations have identified the first diatomic species (CuB+) that can couple CH4 with CO2 under thermal collision conditions to produce ketene (H2C=C=O), an important intermediate in synthetic chemistry. The order to feed the reactants (CH4 and CO2) is important and CH4 should be firstly fed to produce the C2 product. Molecular‐level mechanisms including control of product selectivity have been revealed for coupling of CH4 with CO2 under mild conditions.
Longitudinal assessment of stability of sensory features in children with autism spectrum disorder or other developmental disabilities
Authors: Baranek Grace T. , Carlson Mike , Sideris John , Kirby Anne V. , Watson Linda R. , Williams Kathryn L. , Bulluck John
Published: September 2018

Prior research on the stability of sensory processing problems in children with autism spectrum disorder (ASD) or other developmental disabilities (DD) has produced inconsistent results. We employed a longitudinal study design to assess the stability of three clinical sensory response patterns: hyporesponsiveness; hyperresponsiveness; and sensory interests, repetitions, and seeking behaviors (SIRS). Parents of children with ASD (n = 55) or DD (n = 35) responded to sensory questionnaires at two time points (T1 and T2) separated by 3.3 years on average, with the children aged 2–12 years (M = 5.69 ± 2.46) at the first assessment. For each sensory response pattern, regression analysis revealed that, for both ASD and DD groups, scores at T1 were strong predictors of scores at T2. Over the longitudinal assessment interval, there was a significant mean decline in severity for SIRS in both groups and for hyporesponsiveness in the ASD group. Parental estimates of the amount of therapy services received were positively associated with the severity of sensory features at T2, an outcome that may result from increased intervention dosages being administered to children who fail to improve over time. The results are discussed in terms of person‐centered and environmental considerations, which, in combination, have the capacity to affect stability outcomes for sensory features. Autism Research 2019, 12: 100–111. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

Children with autism spectrum disorder (ASD) and other developmental disabilities (DD) may process sensory information differently from those who do not have ASD. For example, some children may be over‐responsive or under‐responsive to sound or touch. In this study, we showed that sensory features in preschool/school‐aged children with ASD and DD tend to decrease on average over a several year period. However, individual children tend to retain their ranking (low or high in sensory features) in comparison to other children over time.
Engineering molecular imaging strategies for regenerative medicine
Authors: Willadsen Matthew , Chaise Marc , Yarovoy Iven , Zhang An Qi , Parashurama Natesh
Published: September 2018

The reshaping of the world's aging population has created an urgent need for therapies for chronic diseases. Regenerative medicine offers a ray of hope, and its complex solutions include material, cellular, or tissue systems. We review basics of regenerative medicine/stem cells and describe how the field of molecular imaging, which is based on quantitative, noninvasive, imaging of biological events in living subjects, can be applied to regenerative medicine in order to interrogate tissues in innovative, informative, and personalized ways. We consider aspects of regenerative medicine for which molecular imaging will benefit. Next, genetic and nanoparticle‐based cell imaging strategies are discussed in detail, with modalities like magnetic resonance imaging, optical imaging (near infra‐red, bioluminescence), raman microscopy, and photoacoustic microscopy), ultrasound, computed tomography, single‐photon computed tomography, and positron emission tomography. We conclude with a discussion of “next generation” molecular imaging strategies, including imaging host tissues prior to cell/tissue transplantation.
Use of a noninfectious surrogate to predict minute virus of mice removal during nanofiltration
Authors: Cetlin David , Pallansch Melanie , Fulton Coral , Vyas Esha , Shah Aesha , Sohka Taka , Dhar Arun , Pallansch Luke , Strauss Daniel
Published: September 2018

Viruses can arise during the manufacture of biopharmaceuticals through contamination or endogenous expression of viral sequences. Regulatory agencies require “viral clearance” validation studies for each biopharmaceutical prior to approval. These studies aim to demonstrate the ability of the manufacturing process at removing or inactivating virus and are conducted by challenging scaled‐down manufacturing steps with a “spike” of live virus. Due to the infectious nature of these live viruses, “spiking studies” are typically conducted in specialized biological safety level‐2 facilities. The costs and logistics associated with these studies limit viral clearance analysis during process development and characterization. In this study, a noninfectious Minute Virus of Mice‐Mock Virus Particle (MVM‐MVP) was generated for use as an economical small virus spiking surrogate. An immunoglobin G containing solution was spiked with live MVM or MVM‐MVP and processed through Planova nanofiltration units. Flux decay data was collected and particle reduction values were calculated from TCID50 and Immuno‐qPCR analysis. The data indicated comparable filtration performance and particle reduction between infectious MVM and noninfectious surrogate, MVM‐MVP. This proof of concept study suggests the feasibility of utilizing MVPs for predictive size‐based viral clearance assessments during process development and characterization as an alternative to homologous infectious virus.
Adventitial cysts of the radial artery are joint connected
Authors: Lewallen Laura W. , Spinner Robert J. , Amrami Kimberly K. , Kakar Sanjeev
Published: September 2018

Volar radial wrist masses are common. Adventitial cysts of the radial artery are rarely reported and poorly understood. We describe a case series of adventitial cysts in association with the radial artery and detail their pathophysiology and treatment. We conducted an Institutional Review Board‐approved retrospective review of patients treated at our institution from 1997 to 2018. Twelve patients were identified. Presenting symptoms typically included pain and swelling over the volar radial wrist. High‐resolution magnetic resonance imaging (MRI) demonstrated tubular, cystic lesions within the adventitia of the radial artery with connections to the wrist joint confirmed on multiplanar imaging: (radiocarpal joint = 10; scaphotrapeziotrapezoidal joint = 1; and intercarpal joint = 1). Seven patients underwent operation, at which time the cyst was resected and the articular branch disconnected. These patients reported resolution of their symptoms without clinical recurrence. The consistent finding of a joint connection in these cases of adventitial cysts associated with the radial artery has important clinical implications. The joint connection needs to be disconnected. Level of evidence: Level IV, case series. Clin. Anat. 32:201–205, 2019. © 2018 Wiley Periodicals, Inc.
5‐Phenylcoumarin Derivatives: Design, Synthesis, and Vasodilatory Activity
Authors: Wang Cheng , Li Youjia , Zhang Ting , Wei Di , Hou Yajing , He Huaizhen
Published: September 2018

In continuation of our previous efforts towards the development of coumarin derivatives with potential vasodilatory activity, 5‐phenylcoumarin derivatives were designed and synthesized. Target compounds and their precursors exhibited moderately vasodilatory ability with EC50 at 2.5–49.0 μm. Docking studies also revealed the good binding mode of 7‐methoxy‐8‐[2‐(pyrrolidin‐1‐yl)ethoxy]‐5‐[2‐(trifluoromethyl)phenyl]‐2H‐chromen‐2‐one (8c) with the target protein. Moreover, intermediates and the final products exhibited different fluorescent properties due to their substituent effect. These results may provide new ideas for the synthesis and application of 5‐substituted coumarins.
Inhibition of Pro‐Inflammatory Functions of Human Neutrophils by Constituents of Melodorum fruticosum Leaves
Authors: Engels Nora S. , Waltenberger Birgit , Michalak Barbara , Huynh Loi , Tran Hung , Kiss Anna K. , Stuppner Hermann
Published: September 2018

In an initial screening, the dichloromethane extract from the leaves of Melodorum fruticosum showed distinct inhibitory effects on the release of interleukin‐8 (IL‐8) in human neutrophils. Therefore, the aim of the present study was the phytochemical and pharmacological investigation of this extract, to better understand which compounds might be responsible for the anti‐inflammatory effect. Phytochemical analysis led to the isolation of 12 known compounds and two new natural products, 5‐hydroxy‐6‐(2‐hydroxybenzyl)‐4′,7‐dimethoxyflavanone (13) and 2′,4′‐dihydroxy‐3′‐(2‐hydroxybenzyl)‐4,6′‐dimethoxychalcone (14). The influence of the isolated compounds on the production and release of the pro‐inflammatory factors IL‐8, tumor necrosis factor alpha (TNF‐α), reactive oxygen species (ROS), and adhesion molecules (CD62L and CD11b) in human neutrophils was evaluated. Three constituents, melodamide A, 2′,4′‐dihydroxy‐4,6′‐dimethoxychalcone, and 2′,6′‐dihydroxy‐4′‐methoxychalcone, showed significant inhibition of IL‐8 release (IC50=6.6, 8.6, and 11.6 μm, respectively) and TNF‐α production (IC50=4.5, 13.3, and 6.2 μm, respectively).