bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin‐like growth factor‐II and bioactive proteins containing a part of the E‐domain of pro‐insulin‐like growth factor‐II
Authors: van Doorn Jaap
Published: February 2020

Insulin‐like growth factor (IGF)‐II is considered to function as an important fetal growth factor, which is structurally and functionally related to IGF‐I and proinsulin. At least in vitro, IGF‐II actions are mediated through the IGF‐I receptor and to a lesser extent the insulin receptor. After birth, the function of IGF‐II is less clear although in adults the serum level of IGF‐II exceeds that of IGF‐I several fold. The IGF‐II gene is maternally imprinted, with exception of the liver and several parts of the brain, where it is expressed from both alleles. The regulation, organization, and translation of the IGF‐II gene is complex, with five different putative promotors leading to a range of noncoding and coding mRNAs. The 180‐amino acid pre‐pro‐IGF‐II translation product can be divided into five domains and include a N‐terminal signal peptide of 24 amino acid residues, the 67 amino acid long mature protein, and an 89 residues extension at the COOH terminus, designated as the E‐domain. After removal of the signal peptide, the processing of pro‐IGF‐II into mature IGF‐II requires various steps including glycosylation of the E‐domain followed by the action of endo‐proteases. Several of these processing intermediates can be found in the human circulation. There is increasing evidence that, besides IGF‐II, several incompletely processed precursor forms of the protein, and even a 34‐amino acid peptide (preptin) derived from the E‐domain of pro‐IGF‐II, exhibit distinct biological activities. This review will focus on the current insights regarding the specific roles of the latter proteins in cancer, glucose homeostasis, and bone physiology. To address this topic clearly in the right context, a concise overview of the biological and biochemical properties of IGF‐II and several relevant aspects of the IGF system will be provided.
A narrative review of research on clinical responses to the problem of sexual offenses in the last decade
Authors: Ly Thanh , Fedoroff J. Paul , Briken Peer
Published: February 2020

Research on the treatment and programs for people who have committed sexual offenses has greatly increased in the past decade. The aim of this review is to discuss research that has been published over that period (2010–2019) that is relevant for treatment providers. The articles included in this review were found through PsycINFO and PubMed (Medline) using the keywords “treatment or therapy” and “sex offen*”. The inclusion criteria were publications that discuss treatment of persons who have committed sexual offenses (written in the English language only). Any articles that examined only special populations were excluded, such as those that examined persons who committed sexual offenses who were female, had intellectual disabilities, deafness, juveniles, etc., because these groups will likely have needs and responsivity factors that differ from the “average” natal‐born male sex offender. Results showed that several meta‐analyses indicate that treatment is effective in reducing sexual recidivism. The most frequently used treatment for sex offenders is cognitive behavioral therapy, which is often provided in conjunction with pharmacological treatment to reduce sexual impulsivity and/or sex drive. This review is limited to the specific key search terms. The findings of this review support the use of treatment and a community reintegration approach when treating persons who have committed sexual crimes to prevent sexual recidivism.
A qualitative study of forensic patients' perceptions of quasi‐coercive offers of biological treatment
Authors: Knack Natasha , Chandler Jennifer A. , Fedoroff J. Paul
Published: February 2020

At various points in the trajectory through the criminal justice system, a person may be encouraged by the hope of legal benefit to consent to medical treatment. This benefit may consist of diversion from prosecution, a favorable sentence, or parole. This form of legal encouragement has been referred to as legal leverage, quasi‐coercive, or quasi‐compulsory treatment. In this article, we analyze interviews with 15 men convicted of sexual offenses to explore their reactions to two hypothetical scenarios involving men consenting to a range of treatments intended to reduce risk of recidivism. In particular, we explore their reactions to quasi‐coercive treatment using both real and hypothetical forms of biological therapy (e.g., drugs, brain stimulation, surgery), as opposed to psychological counselling. Here, we consider the extent to which these individuals perceive the situation to be coercive, the factors affecting these perceptions, and the ways in which physicians may mitigate perceived coercion. We found there is usually some degree of coercion identified when treatment consent is given in exchange for potential legal benefit, although this fact alone did not necessarily render the practice unacceptable. The degree of concern expressed over this potential coercion was related to the invasiveness and/or permanence of the treatment, and all participants highlighted the necessity of obtaining fully informed consent in the context of legally motivated treatment offers.
Second‐trimester prenatal diagnosis of Nager syndrome with a deletion including SF3B4 detected by chromosomal microarray
Authors: Drozniewska Malgorzata , Kilby Mark D. , Vogt Julie , Togneri Fiona , Quinlan‐Jones Elizabeth , Reali Lisa , Allen Stephanie , McMullan Dominic
Published: February 2020

Nager syndrome is a rare, complex malformation syndrome, for which there is limited information on prenatal genetic testing. Clinical diagnosis of Nager syndrome, which can be caused by deletions encompassing SF3B4 gene, is possible prenatally. Prenatal chromosomal microarray can aid genotype‐phenotype correlation in pregnancies with structural abnormalities seen on ultrasound.
Crohn's disease of the vulva: A tough diagnosis (a case report of a 47 y.o. patient)
Authors: Bondarenko Karina R. , Dobrokhotova Yulia E. , Rumyantseva Tatiana A. , Nasyrova Nailya I.
Published: February 2020

Extraintestinal symptoms of Crohn's disease may occur in the eye, the urinary system, on the skin, or subcutaneous fat. We report the case of a 7‐year diagnostic search of isolated vulvar Crohn's disease in a 47‐year‐old woman. The disease is characterized by gradual formation of pronounced bilateral asymmetric labial hypertrophy.
Controlled preparation of silicon and magnesium silicide on silica glass substrate through magnesiothermic reduction
Authors: Henmi Takashi , Shiono Takeshi , Matsubara Keisuke , Kiyomura Tsutomu , Kurata Hiroki , Wakasugi Takashi , Okada Arifumi , Kadono Kohei
Published: February 2020

Magnesiothermic reduction has received attention as a method to produce silicon retaining the morphology of the silicon dioxides that serve as the starting materials of the reduction. We performed the reduction of silica glass substrates with magnesium deposited on them under various conditions, including changing the reaction temperature from 500 to 700°C, changing the reaction time from 15 to 420 minutes, and changing the thickness of the deposited magnesium film from 6.6 to 12.1 μm. Crystalline products and their amounts were investigated using X‐ray diffraction. In these reactions, the silica glass substrates were reduced to silicon and/or magnesium silicide depending on the conditions. Under the conditions where the reaction temperature is higher, the reaction time is longer, and the thickness of the magnesium is thinner, silicon was generated more predominantly than magnesium silicide, and vice versa. Under the intermediate conditions, both crystalline silicon and magnesium silicide were generated. Furthermore, it was revealed that the magnesium silicide was rapidly generated within 15 minutes at temperatures higher than 600°C. Then, as the reaction continued, the amount of magnesium silicide gradually decreased, and that of silicon increased. From these results, a two‐step reaction model was proposed: At first, silicon dioxide is reduced to magnesium silicide with the complete consumption of the deposited magnesium; and subsequently, the magnesium silicide reacts with unreacted silicon dioxide and silicon in the intermediate oxidation states to produce silicon. Based on this model, silicon and magnesium silicide were selectively prepared under well‐controlled conditions.
Defect Engineering for Photocatalysis: From Ternary to Perovskite Oxynitrides
Authors: Brown Joshua J. , Ke Zhuofeng , Ma Tianyi , Page Alister J.
Published: February 2020

Exploiting defects and specific anion non‐stoichiometry in mixed‐anion semiconductors is a challenge that remains at the forefront of photocatalytic and photoelectrochemical water splitting research. The interplay between of oxygen and nitrogen defects in perovskite oxynitrides specifically creates exciting, yet complex, opportunities for optimizing phase stability, ionic conduction and anion order in these materials. In this Minireview we highlight the recent advances in defect engineering in oxynitride semiconductors, such as anion content/non‐stoichiometry, surface modification, cation doping and formation of anisotropic layered structures, on photocatalytic and photoelectrochemical water splitting. Avenues warranting further investigation are discussed.
Reciprocal transplantation of the heterotrophic coral Tubastraea coccinea (Scleractinia: Dendrophylliidae) between distinct habitats did not alter its venom toxin composition
Authors: Kitahara Marcelo V. , Jaimes‐Becerra Adrian , Gamero‐Mora Edgar , Padilla Gabriel , Doonan Liam B. , Ward Malcolm , Marques Antonio C. , Morandini André C. , Long Paul F.
Published: February 2020

Tubastraea coccinea is an azooxanthellate coral species recorded in the Indian and Atlantic oceans and is presently widespread in the southwestern Atlantic with an alien status for Brazil. T. coccinea outcompete other native coral species by using a varied repertoire of biological traits. For example, T. coccinea has evolved potent venom capable of immobilizing and digesting zooplankton prey. Diversification and modification of venom toxins can provide potential adaptive benefits to individual fitness, yet acquired alteration of venom composition in cnidarians is poorly understood as the adaptive flexibility affecting toxin composition in these ancient lineages has been largely ignored. We used quantitative high‐throughput proteomics to detect changes in toxin expression in clonal fragments of specimens collected and interchanged from two environmentally distinct and geographically separate study sites. Unexpectedly, despite global changes in protein expression, there were no changes in the composition and abundance of toxins from coral fragments recovered from either site, and following clonal transplantation between sites. There were also no apparent changes to the cnidome (cnidae) and gross skeletal or soft tissue morphologies of the specimens. These results suggest that the conserved toxin complexity of T. coccinea co‐evolved with innovation of the venom delivery system, and its morphological development and phenotypic expression are not modulated by habitat pressures over short periods of time. The adaptive response of the venom trait to specific predatory regimes, however, necessitates further consideration.
Small fish, large river: Surprisingly minimal genetic structure in a dispersal‐limited, habitat specialist fish
Authors: Washburn Brooke A. , Cashner Mollie F. , Blanton Rebecca E.
Published: February 2020

Genetic connectivity is expected to be lower in species with limited dispersal ability and a high degree of habitat specialization (intrinsic factors). Also, gene flow is predicted to be limited by habitat conditions such as physical barriers and geographic distance (extrinsic factors). We investigated the effects of distance, intervening pools, and rapids on gene flow in a species, the Tuxedo Darter (Etheostoma lemniscatum), a habitat specialist that is presumed to be dispersal‐limited. We predicted that the interplay between these intrinsic and extrinsic factors would limit dispersal and lead to genetic structure even at the small spatial scale of the species range (a 38.6 km river reach). The simple linear distribution of E. lemniscatum allowed for an ideal test of how these factors acted on gene flow and allowed us to test expectations (e.g., isolation‐by‐distance) of linearly distributed species. Using 20 microsatellites from 163 individuals collected from 18 habitat patches, we observed low levels of genetic structure that were related to geographic distance and rapids, though these factors were not barriers to gene flow. Pools separating habitat patches did not contribute to any observed genetic structure. Overall, E. lemniscatum maintains gene flow across its range and is comprised of a single population. Due to the linear distribution of the species, a stepping‐stone model of dispersal best explains the maintenance of gene flow across its small range. In general, our observation of higher‐than‐expected connectivity likely stems from an adaptation to disperse due to temporally unstable and patchy habitat.
Management of heart failure with reduced ejection fraction in Europe: design of the ARIADNE registry
Authors: Zeymer Uwe , Clark Andrew L. , Barrios Vivencio , Damy Thibaud , Drożdż Jaroslaw , Fonseca Candida , Lund Lars H. , Di Comite Gabriele , Hupfer Stephan , Maggioni Aldo P.
Published: February 2020

Aims

The introduction of sacubitril/valsartan (an angiotensin receptor–neprilysin inhibitor) is likely to change the approach to the management of patients with chronic heart failure with reduced ejection fraction (HFrEF). The Assessment of Real Life Care–Describing European Heart Failure Management (ARIADNE) registry will evaluate patient characteristics, practice patterns, outcomes, and healthcare resource utilization in the outpatient setting across Europe, with the main focus on factors that guide physicians' decisions to start and continue sacubitril/valsartan in patients with HFrEF.

Methods and results

ARIADNE, a prospective, observational registry will enrol 9000 ambulatory patients with HFrEF in 23 European countries . The study will describe 4500 patients treated with conventional treatment (including an angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker), and 4500 patients started on sacubitril/valsartan. In each country, patients will be enrolled consecutively over an expected period of 12 months, and followed‐up for 12 months. The primary objective is to describe the baseline clinical and demographic characteristics of patients with chronic HFrEF, which guide the decision of the treating physician to initiate sacubitril/valsartan or to continue conventional treatment. A co‐primary objective is to identify the baseline characteristics that are associated with the likelihood of reaching the target dose of sacubitril/valsartan 97/103 mg twice daily during follow‐up.

Conclusions

The ARIADNE registry will provide a comprehensive profile of patients with chronic HFrEF in Europe, will elucidate how management varies between countries, and will help clarify the usage and outcomes associated with use of sacubitril/valsartan in real life.
Construction of 4‐(Methylthio)isochromenones Skeleton through Regioselective Intramolecular Cyclization of 2‐Alkynylbenzoate Mediated by DMSO/[D6]DMSO and SOCl2
Authors: An Xuechan , Zhang Beibei , Li Xiaoxian , Du Tianshu , Ai Zhenkang , Zhang Chenglin , Xu Jun , Sun Fengxia , Zhang Yilin , Du Yunfei
Published: February 2020

DMSO/SOCl2 was found to be an effective system for the intramolecular cyclization of 2‐alkynylbenzoates or 2‐alkynylbenzoic acids, which can afford biologically interesting 4‐(methylthio)isochromenones through regioselective electrophilic 6‐endo‐dig cyclization. DMSO plays the roles of both solvent and sulfur source and can also be replaced with its deuterated counterpart [D6]DMSO, enabling the incorporation of the SCD3 moiety into the isochromenone skeleton.
Aliphatic α‐Boryl‐α‐bromoketones: Synthesis and Reactivity
Authors: Ivon Yevhen M. , Kuchkovska Yuliya O. , Voitenko Zoya V. , Grygorenko Oleksandr O.
Published: February 2020

A protocol for the preparation of α‐boryl‐α‐bromoketones from alkenyl MIDA boronates was developed and applied to functionalized aliphatic derivatives. The reaction sequence included regioselective hydroxybromination of olefin moiety, followed by oxidation of alcohol group with Dess–Martin periodinane. The target trifunctional boronate‐containing derivatives were obtained in up to 94 % yield over two steps starting from alkenyl MIDA boronates. In some cases, functional groups present in the substrate participated in the bromohydroxylation step via intramolecular nucleophilic attack at the bromonium cation leading to cyclic products. Additionally, the reactivity of aliphatic α‐boryl‐α‐bromoketones was illustrated by nucleophilic substitution at the α‐C atom and heterocyclization reactions.
Gochujang prepared using rice and wheat koji partially alleviates high‐fat diet‐induced obesity in rats
Authors: Son Hee‐Kyoung , Shin Hye‐Won , Jang Eun‐Seok , Moon Byoung‐Seok , Lee Choong Hwan , Lee Jae‐Joon
Published: February 2020

The aim of this study was to compare whether gochujang products prepared using giant embryo rice koji (rice gochujang, RG) and wheat koji (wheat gochujang, WG) have anti‐obesity effects on rats fed a high‐fat diet (HFD), who served as a model for obesity. The nutritional composition of RG and WG including proximate constituents, amino acid and fatty acid compositions were investigated. Consequently, the secondary fermented metabolites were analyzed in RG and WG by ultrahigh‐performance liquid chromatography and mass spectrometry. Rats were fed a HFD containing 10% RG powder (HFD‐RG) or 10% WG powder (HFD‐WG) for 8 weeks. Body weight gain, weights of liver, epididymal, retroperitoneal, perirenal, and total white fat pads, and levels of serum triglyceride (TG), total cholesterol, low‐density lipoprotein cholesterol, and leptin were lower in all gochujang groups than in the HFD group. Furthermore, RG and WG treatment decreased the hepatic TG content and lipid accumulation and significantly reduced the size of epididymal adipocytes. These effects are probably mediated through inhibition of hepatic fatty acid synthase, acetyl CoA carboxylase, malic enzyme, and adipose tissue lipoprotein lipase activities. The anti‐obesity effect was slightly greater in the HFD‐RG group than in the HFD‐WG group. This effect may be attributed to secondary metabolites, such as capsaicin, genistein, daidzein, soyasaponin, and lysophosphatidylcholines, contained in gochujang prepared using giant embryo rice or wheat koji.
Schwann cells: Rescuers of central demyelination
Authors: Garcia‐Diaz Beatriz , Baron‐Van Evercooren Anne
Published: February 2020

The presence of peripheral myelinating cells in the central nervous system (CNS) has gained the neurobiologist attention over the years. Despite the confirmed presence of Schwann cells in the CNS in pathological conditions, and the long list of their beneficial effects on central remyelination, the cues that impede or allow Schwann cells to successfully conquer and remyelinate central axons remain partially undiscovered. A better knowledge of these factors stands out as crucial to foresee a rational therapeutic approach for the use of Schwann cells in CNS repair. Here, we review the diverse origins of Schwann cells into the CNS, both peripheral and central, as well as the CNS components that inhibit Schwann survival and migration into the central parenchyma. Namely, we analyze the astrocyte‐ and the myelin‐derived components that restrict Schwann cells into the CNS. Finally, we highlight the unveiled mode of invasion of these peripheral cells through the central environment, using blood vessels as scaffolds to pave their ways toward demyelinated lesions. In short, this review presents the so far uncovered knowledge of this complex CNS‐peripheral nervous system (PNS) relationship.
The properties of human Schwann cells: Lessons from in vitro culture and transplantation studies
Authors: Monje Paula V.
Published: February 2020

Human Schwann cells (hSCs) can be isolated directly from peripheral nerve and cultured using methods similar to those used for SCs from other species. Yet, important interspecies differences are revealed when the primary or expanded hSCs are compared to their nonhuman counterparts. This review addresses the special properties of nerve‐derived hSCs that have resulted to date from both in vitro studies and in vivo research on cell transplantation in animal models and human subjects. A consensus has yet to emerge about the essential attributes of cultured normal hSCs. Thus, an emphasis is placed on the importance of validating hSC cultures by means of purity, identity, and biological activity to reliably use them as in vitro models of the SC phenotype and cell therapy products for injury repair. Combining traditional immunological methods, high‐resolution omics approaches, and assorted cell‐based assays is so far the best approach to unequivocally identify hSC populations obtained by direct isolation or derivation from stem cells. Special considerations are required to understand and manage the variability and heterogeneity proper of donor batches, as well as to evaluate risk factors. This is particularly important if the intended use of the hSCs is implantation in the human body, diagnosis of disease, or drug testing aimed at targeting any aspect of SC function in human patients. To conclude, in view of their unique properties, new concepts and methods are needed to better understand the biology of hSCs and exploit their full potential in basic science and regenerative medicine.
Fe‐porphyrin on Co(001) and Cu(001): A Comparative Dispersion‐augmented Density Functional Theory Study
Authors: Azuri Ido , Ali Md. Ehesan , Tarafder Kartick , Oppeneer Peter M. , Kronik Leeor
Published: February 2020

We present a comparative density functional theory (DFT) investigation of the interaction of the iron porphyrin (FeP) molecule with the metallic Co(001) and Cu(001) surfaces, with the aim of elucidating the effect of different choices for the treatment of dispersion. We compare a GGA+U approach, several flavors of dispersion‐augmented terms, and two variants of the vdW‐DF approach, which treats long‐range correlation explicitly. For the Co surface, we find that all approaches predict chemisorption and a high‐spin state, although vdW‐DF functionals generally predict weaker bonds and weaker chemisorption. For the Cu surface, we find that the functionals augmented by pair‐wise dispersion once again predict chemisorption and a preferred HS state, but the vdW‐DF functionals predict physisorption and a LS state. These results demonstrate the importance of careful assessment of the level of theory at which dispersion is treated, as this may have significant quantitative and even qualitative effects on the predictions made. The results also call for additional experimental data for these systems.
Enabling an intrinsically safe and high‐energy‐density 4.5 V‐class Li‐ion battery with nonflammable electrolyte
Authors: Zeng Ziqi , Liu Xingwei , Jiang Xiaoyu , Liu Zhenjie , Peng Zhangquan , Feng Xiangming , Chen Weihua , Xia Dingguo , Ai Xinping , Yang Hanxi , Cao Yuliang
Published: February 2020

Developing nonflammable electrolyte with a wide electrochemical window has become an urgent demand for high‐energy‐density and high‐safe lithium‐ion batteries (LIBs). Herein, a fluorinated nonflammable phosphate electrolyte is developed to construct a safe 4.5 V‐class LIB (Si‐SiC‐C/0.35Li2MnO3·0.65LiNi0.5Mn0.5O2). The proposed fluorinated phosphate electrolyte, 0.8 M LiPF6/tris(2,2,2‐trifluoroethyl) phosphate (TFEP) + 5 vol% fluoroethylene carbonate (FEC) + 5 vol% vinylene carbonate (VC), is not only completely nonflammable but also exhibits excellent oxidative/reductive stability on 0.35Li2MnO3·0.65LiNi0.5Mn0.5O2 cathode and Si‐SiC‐C anode. The in situ differential electrochemical mass spectrometry and X‐ray photoelectron spectroscopy proved that TFEP‐based electrolyte does not decompose into gases but forms a high‐quality electrode‐electrolyte interface on cathode surface at high working potential. The 4.5 V‐class LIBs using 0.8 M LiPF6 TFEP‐based nonflammable electrolyte shed some light on potential application for high‐safe and low‐cost larger‐scale energy storage.

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Quercetin radiosensitizes non‐small cell lung cancer cells through the regulation of miR‐16‐5p/WEE1 axis
Authors: Wang Qi , Chen Yaokun , Lu Haijun , Wang Haiji , Feng Hui , Xu Jinpeng , Zhang Biyuan
Published: February 2020

Background

Quercetin, a widely distributed bioflavonoid, plays a role in combating diverse human cancers including non‐small cell lung cancer (NSCLC). However, the role of quercetin in reversing the radioresistance of NSCLC cells and its underlying mechanism are far from being elucidated.

Method

Radiation‐resistant NSCLC cell lines were established. Quantitative real‐time PCR (qRT‐PCR) was used to detect the expression of miR‐16‐5p and WEE1 G2 checkpoint kinase (WEE1) mRNA in radiation‐resistant cells. After being treated with different concentrations of quercetin and different doses of X‐ray, cell proliferation and apoptosis were monitored by CCK‐8 assay, colony formation assay, and flow cytometry, respectively. Ultimately, the targeting relationship between miR‐16‐5p and WEE1 was verified via a dual fluorescent reporter gene assay.

Results

The expression of miR‐16‐5p was down‐regulated in radiation‐resistant cells, while the expression of WEE1 was up‐regulated. Quercetin enhanced the radiosensitivity of NSCLC cells in a dose‐ and time‐dependent manner. Furthermore, quercetin treatment increased the expression of miR‐16‐5p and decreased the expression of WEE1. The function of quercetin was reversed by miR‐16‐5p inhibitors or the transfection of WEE1 overexpressing plasmids.

Conclusion

In conclusion, quercetin enhanced the radiosensitivity of NSCLC cells via modulating the expression of miR‐16‐5p and WEE1.
Continuous Production of l‐Alanine Using Pseudomonas dacunhae Immobilized with Carrageenan
Authors: Yamamoto Kozo , Tosa Tetsuya , Chibata Ichiro
Published: February 2020

Continuous production of l‐alanine from l‐aspartic acid using immobilized Pseudomonas dacunhae was investigated. Pseudomonas dacunhae cells were immobilized with carrageenan gel. The l‐aspartate β‐decarboxylase activity of immobilized cells was enhanced by incubating the immobilized cells with a solution of 1M ammonium l‐aspartate (pH 5.5) containing 0.1mM pyridoxal‐5′‐phosphate (PLP) at 37°C over 20 hr. The enzyme activity of immobilized cells was 59% that of intact cells. The pH profile of the enzyme reaction was broader in the immobilized cells than in the free cells. The enzyme activity of immobilized cells was maintained through repeated uses when a substrate solution containing 0.1mM PLP was used. Complete conversion of l‐aspartate to l‐alanine was attained when a solution of 2M ammonium l‐aspartate (pH 6.2) containing 0.1mM PLP was passed upward through the immobilized cell column at a retention time of 8 hr at 37°C. Glutaraldehyde treatment of the immobilized cells resulted in a slight decrease of the enzyme activity but a marked increase of the operational stability. The half‐life of enzyme activity was 46 days in glutaraldehyde‐treated immobilized cells.
Systematic microsolvation approach with a cluster‐continuum scheme and conformational sampling
Authors: Simm Gregor N. , Türtscher Paul L. , Reiher Markus
Published: February 2020

Solvation is a notoriously difficult and nagging problem for the rigorous theoretical description of chemistry in the liquid phase. Successes and failures of various approaches ranging from implicit solvation modeling through dielectric continuum embedding and microsolvated quantum chemical modeling to explicit molecular dynamics highlight this situation. Here, we focus on quantum chemical microsolvation and discuss an explicit conformational sampling ansatz to make this approach systematic. For this purpose, we introduce an algorithm for rolling and automated microsolvation of solutes. Our protocol takes conformational sampling and rearrangements in the solvent shell into account. Its reliability is assessed by monitoring the evolution of the spread and average of the observables of interest.
Intergroup fears and concerns among minority and majority groups: Implications for contact and attitudes
Authors: Stathi Sofia , Pavetich Melissa , Di Bernardo Gian Antonio , Cadamuro Alessia , Cocco Veronica Margherita , Vezzali Loris
Published: February 2020

Aims

Driven by the literature on pluralistic ignorance, our research investigates fear of appearing racist, being rejected, discriminated, and disinterest in intergroup contact as antecedents of contact and outgroup attitudes, focusing on attributional differences between the majority and minority group perspectives.

Methods

Questionnaires were distributed in schools in Northern Italy. Participants were 400 Italian and 141 immigrant high‐school students.

Results

The results showed that the lack of interest in contact was the strongest predictor of contact for the majority group. For the minority group, fear of rejection emerged as the strongest predictor. The majority group attributed the minority to avoid contact most strongly due to the fear that they would be rejected, and the minority group perceived it was due to the majority not being interested in contact.

Conclusion

Our research contributes to understanding the divergent concerns the majority and minority groups have in relation to intergroup contact and discusses the importance of tackling these concerns.
Population Pharmacokinetics and Exposure‐Response Modeling Analyses of Ustekinumab in Adults With Moderately to Severely Active Ulcerative Colitis
Authors: Xu Yan , Hu Chuanpu , Chen Yang , Miao Xin , Adedokun Omoniyi J. , Xu Zhenhua , Sharma Amarnath , Zhou Honghui
Published: February 2020

To characterize the pharmacokinetics (PK) and exposure‐response (E‐R) relationship of ustekinumab, an anti‐interleukin‐12/interleukin‐23 (IL‐12/IL‐23) human monoclonal antibody, in the treatment of moderately to severely active ulcerative colitis (UC), population PK and E‐R modeling analyses were conducted based on the data from the pivotal phase 3 induction and maintenance studies in UC patients. The observed serum concentration‐time data of ustekinumab were adequately described by a 2‐compartment linear PK model with first‐order absorption and first‐order elimination. Body weight, baseline serum albumin, sex, and antibodies to ustekinumab were the covariates to influence ustekinumab PK, but the magnitudes of the effects of these covariates were not considered clinically relevant, and dose adjustment was not warranted. Positive E‐R relationships were demonstrated between ustekinumab exposure metrics and clinical endpoints (including clinical response, clinical remission, and endoscopic healing based on Mayo score) at induction week 8 and maintenance week 44, consistent with the effectiveness of ustekinumab in the induction and maintenance treatment of patients with UC. E‐R modeling results suggest that ustekinumab ∼6 mg/kg intravenous induction and 90‐mg subcutaneous every‐8‐week maintenance dose would produce greater efficacy than the 130 mg intravenous induction and the 90‐mg subcutaneous every‐12‐week maintenance regimen, respectively. Our work provides a comprehensive evaluation of ustekinumab PK and E‐R in a modeling framework to support ustekinumab dose recommendations in patients with UC.
Micromorphology, pharmacognosy, and bio‐elemental analysis of an important medicinal herb: Verbascum thapsus L.
Authors: Khan Shafqat Ali , Dastagir Ghulam , Uza Noor Ul , Muhammad Akhtar , Ullah Rahim
Published: February 2020

The present study was conducted on characterization of morpho‐anatomical, phytochemical, and bio‐elemental analysis of root, stem, and leaf of Verbascum thapsus. Morphologically Verbascum is a biennial plant that flowers for a month and a half in mid‐ to late summer. Various organoleptic features of root, leaf, and stem were recorded. Anatomically the T. S of the root, stem, and leaf showed a typical dicot histological differentiation. Leaf possessed anomocytic stomata, crescent shape vascular bundles, and covered with long and stellate type trichomes while, stem contained collateral type of vascular bundles and a well‐developed pith to store phytochemicals responsible for various pharmacological activities. The powder drug study through scanning electron microscopy revealed the presence of various types of tissues. Branched, tree like and stellate trichomes in root and leaf help in absorption and reduce loss of water. These anatomical features are responsible for the survival of the plant as biennial. Four macro elements (Na, K, Ca, and Mg) and seven microelements (Cr, Cu, Fe, Mn, Ni, Zn, and Cd) and their concentrations in ppm were also studied using Atomic Absorption Spectroscopy. Phytochemical screening of methanolic extract showed existence of various secondary metabolites, while mucilage and anthraquinones was not detected. The present study helps to understand the taxonomic identification of the plant based on morpho‐anatomical features and throws the attention of the researchers to carry out the work for developing its various formulations, which can ultimately be beneficial for the human beings as well as animals.
Impact of hereditary pancreatitis on patients and their families
Authors: Shelton Celeste A. , Grubs Robin E. , Umapathy Chandraprakash , Yadav Dhiraj , Whitcomb David C.
Published: February 2020

Hereditary pancreatitis (HP), a highly penetrant (~80%) autosomal dominant disease associated with PRSS1 variants, causes acute pancreatitis in childhood and chronic pancreatitis by early adulthood. Other clinical features include pain, diabetes, and risk of pancreatic cancer. HP kindreds were prospectively recruited from 1995 to 2015. At enrollment, study participants completed medical and family history questionnaires, and provided samples for genotyping. Participants were recontacted between 2015 and 2017 and asked to complete a survey on concerns and experiences related to HP, PRSS1 testing, and genetic counseling. Data were analyzed with descriptive and thematic methods. Thirty‐nine affected participants with HP and 21 unaffected family members completed the survey. Among unaffected family members, ‘worry’ and ‘helplessness’ were frequently described as the most difficult problem in their family because of HP, particularly with regard to pain. Three participants described the impact of drug addiction on their family. ‘School or work limitations’ was the leading financial concern, with 65.5% (36/55) rating it as ‘moderately’ or ‘extremely important.’ Unexpectedly, only 62% (21/34) of affected PRSS1 carriers believed the chance for a parent to pass HP to his or her children was 50%, whereas 18% (6/34) believed the chance was 100%. The impact of HP on individuals and families varied, which may reflect the highly unpredictable nature of HP severity and outcomes. Based on current and previously reported findings, an overview of important issues for genetic counselors to consider for counseling HP families is included.
Wilson disease in Costa Rica: Pediatric phenotype and genotype characterization
Authors: Penon‐Portmann Monica , Lotz‐Esquivel Stephanie , Chavez Carrera Alejandra , Jiménez‐Hernández Mildred , Alvarado‐Romero Danny , Segura‐Cordero Sharon , Rimolo‐Donadio Fiorella , Hevia‐Urrutia Francisco , Mora‐Guevara Alfredo , Saborío‐Rocafort Manuel , Jiménez‐Arguedas Gabriela , Badilla‐Porras Ramsés
Published: February 2020

Introduction

The prevalence of Wilson disease (WD) in Costa Rica is among the highest reported in the world, 4.9:100 000. Previous investigators have also described a burden of autosomal recessive conditions in this country. Genetic testing for WD began in 2010 as a strategy for earlier detection due to the country's high prevalence. Here we describe what we have learned about the genotype and phenotype of the Costa Rican pediatric population with WD.

Methods

We completed a retrospective review of medical records from pediatric individuals (<18 years of age) with molecular testing for ATP7B between 2010 and 2015. We documented phenotype and genotype for cases with WD as defined by the international scoring system.

Results

Thirty‐four WD cases from 28 families were included, 15 female and 19 male patients. The most frequent pathogenic variant in ATP7B was NM_000053:c.3809A>G, p.Asn1270Ser, with 58.8% of affected individuals homozygous for this variant. Age of diagnosis ranged from 1 to 17 years, with an average of 8.8 ± 3.6 years. All individuals who presented with acute liver failure (n = 6) were homozygous for the p.Asn1270Ser variant (Chi‐squared, P < .05).

Discussion

Molecular testing has facilitated the detection of presymptomatic patients with WD in Costa Rica. We hope that ongoing efforts in the delivery of clinical services lead to optimized molecular screening for WD and other genetic conditions in Costa Rica.
Understanding hormone and hormone therapies' impact on the auditory system
Authors: Williamson Tanika T. , Zhu Xiaoxia , Pineros Jennifer , Ding Bo , Frisina Robert D.
Published: February 2020

Hormones such as estrogen, progesterone, and aldosterone all demonstrate vital roles in sustaining auditory function through either the maintenance of cochlear neurons, up/down regulation of critical molecules (i.e., IGF‐1, BDNF, etc.), or generation of the endocochlear potential. With disease and/or age, hormone expression begins to decline drastically, which ultimately affects cochlear structures and the integrity of cochlear cells. The following review explores the latest findings as well as realistic outcomes for hormone therapy treatment in the auditory system. This information could serve as a potential guide for patients considering hormone therapy as a medicinal choice to alleviate the signs of onset of presbycusis—age‐related hearing loss. Additional scientific investigations could also be carried out to further enhance recent findings.
GLIM Criteria at Hospital Admission Predict 8‐Year All‐Cause Mortality in Elderly Patients With Type 2 Diabetes Mellitus: Results From VIDA Study
Authors: Sanz‐París Alejandro , Martín‐Palmero Angela , Gomez‐Candela Carmen , García‐Almeida Jose M. , Burgos‐Pelaez Rosa , Sanz‐Arque Alejandro , Espina Silvia , Arbones‐Mainar Jose M. ,   Study VIDA group
Published: February 2020

Background

Diabetes and older age are associated with an increased risk of malnutrition and mortality. Recently, the Global Leadership Initiative on Malnutrition (GLIM) provided a 2‐step approach for the malnutrition diagnosis. In this study, we aimed to determine whether GLIM nutrition status at admission was associated with long‐term survival in elderly patients with type 2 diabetes mellitus (T2DM). Additionally, we aimed to identify which GLIM criteria were more able to become prognostic indicators of early or late death.

Methods

Our study included a convenience sample of 159 patients with T2DM older than 65 years and admitted to the internal medicine wards of different Spanish hospitals: the VIDA‐survival cohort. Nutrition status was retrospectively assessed with the new GLIM criteria. The main outcome was long‐term mortality in the cohort during an 8‐year follow‐up. Bivariate tables summarized the variables of interest. Kaplan‐Meier survival curves and adjusted Cox regressions were also performed.

Results

According to the GLIM criteria, we observed that the 35.8% and 16.3% of the VIDA‐survival cohort were categorized as having moderate and severe malnutrition, respectively. Severe malnutrition was associated with increased mortality (hazard ratio [HR] = 2.09; 95% CI, 1.29–3.38), compared with nonmalnourished participants. Moderate malnutrition had a neutral effect on all‐cause mortality (HR = 1.30; 95% CI, 0.88–1.92). Low plasma albumin levels, a surrogate marker of inflammation, were strongly associated with early mortality.

Conclusion

Our study provides evidence that severe malnutrition according to GLIM criteria is associated with increased long‐term all‐cause mortality among elderly individuals with T2DM.
Association Between AND‐ASPEN Malnutrition Criteria and Hospital Mortality in Critically Ill Trauma Patients: A Prospective Cohort Study
Authors: Ceniccola Guilherme Duprat , Okamura Aline Bassetto , Sepúlveda Neta Jeane da Silva , Lima Fernanda Cintra , Santos de Deus Andressa Cristina , de Oliveira Jessica Amarante , dos Santos Sabrina Souza Martins , de Sousa Rildo Batista , de Brito‐Ashurst Ione
Published: February 2020

Background

Malnutrition is prevalent in trauma victims because of intense muscle wasting triggered by traumatic events and is a mortality risk. The Academy of Nutrition and Dietetics–American Society for Parenteral and Enteral Nutrition (AND‐ASPEN) tool has the potential to diagnose malnutrition in this population. This study aims to evaluate this criterion as a malnutrition diagnostic tool and as a hospital mortality predictor in critically ill trauma patients.

Methods

We performed an observational prospective cohort study from April 2015 to February 2017 in a Brazilian hospital. Patients were >18 years old, remained in the intensive care unit (ICU) >48 hours, and had completed data regarding the recommended clinical characteristics (RCCs) for malnutrition. The main exposure of interest was malnutrition assessed by a specialist dietitian using AND‐ASPEN. The primary outcome was all causes of mortality during hospital stay. Secondary outcome was the RCCs assessment, to predict malnutrition and hospital mortality.

Results

Included were 414 trauma patients. Malnutrition prevalence was 26.8% at ICU admission. The main analysis showed that malnutrition increases mortality chances 1.96 times (95% CI, 1.13–3.30; P = .015). Secondary analysis showed that all 5 RCCs were significantly associated with malnutrition. The only RCC associated with mortality was energy intake (odds ratio 1.5; 95% CI, 1.1–2.0; P = .008).

Conclusions

AND‐ASPEN criterion is a feasible and accurate method to recognize malnutrition and predict hospital mortality when applied by trained dietitians for the critical care trauma population. Further studies are needed considering patient subgroups such as obese and elderly.
UV surface‐enhanced Raman scattering properties of SnSe2 nanoflakes
Authors: Liu Mei , Shi Ying , Wu Meimei , Tian Yuan , Wei Haonan , Sun Qianqian , Shafi Muhammad , Man Baoyuan
Published: February 2020

Two‐dimensional (2D)‐layered semiconductor materials have attracted considerable attention in surface‐enhanced Raman scattering spectroscopy (SERS) technology owing to their high uniformity, excellent reproducibility, and ultra‐flat surfaces without dangling bonds. However, they are rarely used in the UV laser‐excited surface‐enhanced Raman scattering spectroscopy (UV–SERS) field. In this article, 2D‐layered tin diselenide (SnSe2) nanoflakes were investigated as a UV–SERS substrate for the first time. The strong absorption in the UV region of SnSe2 induces a pre‐resonance Raman (pre‐RR) effect and charge transfer (CT) between the substrate and the probe molecules. The UV–SERS signal of crystal violet (CV) molecules adsorbed on SnSe2 nanoflakes was obtained even though the concentration was low at 10−7 mol/L. The indirect band gap structure of the SnSe2 nanoflake plays a significant role in promoting the electrons excited by incident photons and the CT process. This is a new phenomenon for 2D semiconductor materials in the UV–SERS field. The results will be helpful to develop UV–SERS technology based on 2D‐layered materials and to provide a promising method to understand the chemical enhancement mechanism of UV–SERS.
Conversion of PATP to DMAB based on Ag+‐induced catalytic oxidation
Authors: Yu Long , Ma Liping , Liu Yu , Song Peng , Xia Lixin
Published: February 2020

In this paper, the Ag+ is first adopted to oxidize PATP to DMAB, and the intermediate elementary Ag of the reaction is used to enhance the Raman signal, which acts as a surface‐enhanced Raman scattering substrate and overcomes the drawbacks of the traditional metal sol. The experimental repetition rate reached 100%; the Raman peak of the product dimercaptoazobenzene was clear and obvious. Compared with the traditional silver sol system, the intensity of the Raman peak is increased by 10 times. It is believed that the results will make a great contribution to the future research of the surface plasmon‐assisted coupling reaction.
Olfactory Cleft Width and Volume: Possible Risk Factors for Postinfectious Olfactory Dysfunction
Authors: Altundag Aytug , Temirbekov Dastan , Haci Cemal , Yildirim Duzgun , Cayonu Melih
Published: February 2020

Objectives/Hypothesis

Upper respiratory tract infections are a common cause of temporary and permanent olfactory dysfunction in the general population. Postviral or postinfectious olfactory loss (PIOL) develops only in rare cases. The aim of this study was to investigate the anatomical features of olfactory cleft (OC) in patients with PIOL to shed light on possible predisposing factors for PIOL.

Study Design

Retrospective study.

Methods

We retrospectively evaluated paranasal sinus computed tomography (CT) scan results of patients diagnosed with PIOL. A control group consisted of normosmic individuals who underwent paranasal sinus CT scans before septoplasty surgery. We compared the olfactory fossa depth, OC width, and volume on the CT scans of the PIOL and control groups.

Results

In total, 71 individuals fulfilled the study criteria (PIOL group, n = 32; control group, n = 39). There was no statistically significant difference in the olfactory fossa depth in the two groups. The OC width and volume in the PIOL group was found to be significantly increased than that in the control group (P < .001 for both).

Conclusions

Patients with PIOL had increased OC width and volume than the healthy controls. An extra‐wide olfactory cleft may be a predisposing factor in the pathogenesis of PIOL.

Level of Evidence

4 Laryngoscope, 131:5–9, 2021
A note on the differences found between examining whole water vs. phytoplankton net (52 μm mesh) samples to characterize abundance and community composition of tintinnid ciliates (marine microzooplankton)
Authors: Dolan John R. , Marro Sophie
Published: February 2020

Most tintinnid species have a shortest linear dimension < 50 μm. Hence, a priori, nets of mesh sizes ≥ 50 μm will likely under‐sample most tintinnid species. However, studies often appear (23 since 2015) using sampling with nets of meshes sizes ≥ 50 μm, reporting both tintinnid concentrations, and community composition. How biased are results from using coarse mesh nets? We provide a comparison of whole water vs. net sampling based on fortuitous, that is, unplanned, parallel sampling. Pairs of samples from a standard monitoring station in the Bay of Villefranche (N.W. Mediterranean Sea) taken on 44 dates from 2013 to 2018 were compared. Tintinnids were enumerated in settled material from a water column sample, an integration of six discrete depth samples between 5 and 70 m, prepared for analysis of phytoplankton composition and in material from a plankton net (52 μm mesh) tow from 70 to 0 m, taken the same day. Despite the large confidence limits due to low raw cell counts from whole water samples, cell concentration estimates were about an order of magnitude higher than those from plankton net samples and frequently biomass estimates as well. Community composition also differed. The most common species in whole water samples were small (diameter ≤ 20 μm), and some common forms were absent, or nearly, from the net samples. We show that, while valuable for collecting larger and rarer species, coarse net samples do not yield robust estimations of overall concentrations, nor allow identification of the dominant tintinnid species.