bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural history study of adults with Wolf–Hirschhorn syndrome 2: Patient‐reported outcomes study
Authors: Carey John C. , Lortz Amanda , Mendel Alyssa , Battaglia Agatino 
Published: May 2021

AbstractWolf–Hirschhorn syndrome (WHS) is a contiguous gene disorder consisting of prenatal and postnatal growth deficiency, distinctive craniofacial features, intellectual disability, and seizures. The condition is caused by a partial loss of material from the distal portion of the short arm of chromosome 4 (4p16.3). While there are many reports of individuals with WHS, useful data on long‐term survival and life status of adults with the syndrome are very limited. There are only 11 reports of individuals over the age of 18 years in the literature. Establishing the medical manifestations of adults with WHS would be helpful in establishing appropriate health supervision guidelines. This study was one component of a two‐part investigation on adults with WHS. This patient‐reported outcomes study (PROS) was accomplished by using the registry of rare diseases at Sanford Research, Coordination of Rare Diseases (CoRDS)at Sanford. Thirty family members or caretakers of 30 adults with WHS/4p‐ entered into the CoRDS registry and completed some or all of the survey data. Twelve caretakers completed the recently‐added survey on activities of daily living. Two of the individuals with WHS were partly independent while 10 required total care. The results provide novel information on daily life and independence in adults with WHS. Importantly, the majority of caretakers reported that the adults were in good health. The data from both parts of the study will contribute to our knowledge of the natural history of the syndrome and guide in establishing appropriate health supervision guidelines for adults with WHS.
A novel de novo intronic variant in ITPR1 causes Gillespie syndrome
Authors: Keehan Laura , Jiang Ming‐Ming , Li Xiaohui , Marom Ronit , Dai Hongzheng , Murdock David , Liu Pengfei , Hunter Jill V. , Heaney Jason D. , Robak Laurie , Emrick Lisa , Lotze Timothy , Blieden Lauren S. ,   Undiagnosed Diseases Network, Lewis Richard Alan , Levin Alex V. , Capasso Jenina , Craigen William J. , Rosenfeld Jill A. , Lee Brendan , Burrage Lindsay C. 
Published: May 2021

AbstractGillespie syndrome (GLSP) is characterized by bilateral symmetric partial aplasia of the iris presenting as a fixed and large pupil, cerebellar hypoplasia with ataxia, congenital hypotonia, and varying levels of intellectual disability. GLSP is caused by either biallelic or heterozygous, dominant‐negative, pathogenic variants in ITPR1. Here, we present a 5‐year‐old male with GLSP who was found to have a heterozygous, de novo intronic variant in ITPR1 (NM_001168272.1:c.5935‐17G > A) through genome sequencing (GS). Sanger sequencing of cDNA from this individual's fibroblasts showed the retention of 15 nucleotides from intron 45, which is predicted to cause an in‐frame insertion of five amino acids near the C‐terminal transmembrane domain of ITPR1. In addition, qPCR and cDNA sequencing demonstrated reduced expression of both ITPR1 alleles in fibroblasts when compared to parental samples. Given the close proximity of the predicted in‐frame amino acid insertion to the site of previously described heterozygous, de novo, dominant‐negative, pathogenic variants in GLSP, we predict that this variant also has a dominant‐negative effect on ITPR1 channel function. Overall, this is the first report of a de novo intronic variant causing GLSP, which emphasizes the utility of GS and cDNA studies for diagnosing patients with a clinical presentation of GLSP and negative clinical exome sequencing.
Facilitating the Ferration of Aromatic Substrates through Intramolecular Sodium Mediation
Authors: Maddock Lewis C. H. , Mu Manting , Kennedy Alan R. , García‐Melchor Max , Hevia Eva 
Published: May 2021

AbstractExploiting cooperative effects between Na and FeII centres present in tris(amide) ferrate complexes has led to the chemoselective ferration of pentafluorobenzene, benzene, toluene, anisole, and pyridine being realised at room temperature. The importance of this bimetallic partnership is demonstrated by neither the relevant sodium amide (NaHMDS or NaTMP) nor the FeII amide Fe(HMDS)2 efficiently metallating these substrates under the conditions of this study. By combining NMR studies with the isolation of key intermediates and DFT calculations, we offer a possible mechanism for how these reactions take place, uncovering a surprising reaction pathway in which the metals cooperate in a synchronised manner. Although the isolated products are formally the result of Fe‐H exchange, theoretical calculations indicate that the aromatic substrates undergo Na‐H exchange followed by fast intramolecular transmetallation to Fe, thus stabilizing the newly generated aryl fragment.
Chirality Transfer from an Innately Chiral Nanocrystal Core to a Nematic Liquid Crystal: Surface‐Modified Cellulose Nanocrystals
Authors: Gonçalves Diana P. N. , Hegmann Torsten 
Published: May 2021

AbstractThe vast majority of nanomaterials studied in light of their ability to transmit chirality to or amplify their chirality in a surrounding medium, constitute an achiral core with chirality solely installed at the surface by conjugation or encapsulation with optically active ligands. Here we present the inverse approach focusing on surface‐modified cellulose nanocrystals (CNCs) with core chirality at both the molecular and the morphological level to quantify transmission and amplification of core chirality through space using a host nematic liquid crystal (N‐LC) as reporter. We find that CNCs functionalized at the surface with achiral molecules, structurally related to the N‐LC, exhibit better N‐LC solubility, thereby serving as highly efficient chiral inducers. Moreover, functionalization with chiral molecules only marginally enhances the efficacy of helical distortion in the host N‐LC matrix, indicating the high propensity of CNCs to transfer chirality from an inherently chiral core.
Long‐term failure of transversely loaded glass/iPP
Authors: Erartsın Ozan , Arntz Stijn A. J. J. , Troisi Enrico M. , Pastukhov Leonid V. , van Drongelen Martin , Warnet Laurent , Govaert Leon E. 
Published: May 2021

AbstractHerein, temperature‐dependent long‐term behavior of polypropylene and its transversely loaded unidirectional glass fiber reinforced composite is investigated and a lifetime prediction method is proposed, which is based on the observed long‐term failure mechanisms. Furthermore, the effect of cooling rate during processing on the time‐dependent behavior is addressed. The composite is revealed to exhibit multiple molecular deformation mechanisms, similar to neat polypropylene, which is modeled using the Ree–Eyring approach. Failure kinetics under constant‐strain‐rate and creep tests are found to be identical and switching from creep to cyclic loading decelerates the failure, which are signs of plasticity‐controlled failure. Hence, lifetime is predicted well by using a lifetime prediction methodology for the plasticity‐controlled failure which combines the Ree–Eyring approach and the concept of critical strain. A change in the cooling rate alters the deformation and failure kinetics: lower cooling rates promote embrittlement.
A shot in the dark for conservation: Evidence of illegal commerce in endemic and threatened species of elasmobranch at a public fish market in southern Brazil
Authors: Cruz Vanessa Paes da , Adachi Aisni Mayumi Corrêa de Lima , Ribeiro Giovana da Silva , Oliveira Pablo Henrique de , Oliveira Cláudio de , Oriano Junior Rinaldo , Freitas Renato Hajenius Aché de , Foresti Fausto 
Published: May 2021

Abstract

The illegal sale of endangered elasmobranchs has been recorded in a number of different Brazilian states, where sharks and rays are being marketed primarily as ‘cação’ or ‘viola’. Brazil is ranked among the top 10 nations worldwide that harvest most sharks, causing an immeasurable impact on the local elasmobranch populations.
The present study applied the DNA barcoding technique, based on the cytochrome C oxidase subunit I gene, for the molecular identification of the elasmobranch species sold as processed products under the generic names of ‘cação’, ‘mangona’, ‘azul’, ‘cambeva’, ‘fiuso’ and ‘lombo preto’, in the fish market of the city of Florianópolis, capital of the state of Santa Catarina, Brazil.
Nine elasmobranch species were identified in the 56 samples analysed, including six sharks and three rays, representing six families, the Carcharhinidae, Sphyrnidae, Squatinidae, Arhynchobatidae, Myliobatidae and Gymnuridae. Prionace glauca, identified in more than half (56%) of the samples analysed, is listed as Near Threatened by the International Union for the Conservation of Nature.
Six species identified in the present study, Sphyrna zygaena, Sphyrna lewini, Squatina guggenheim, Carcharhinus signatus, Gymnura altavela and Rioraja agassizii, are under some level of risk of extinction, while two others (Rhizoprionodon lalandii and Myliobatis goodei) are listed as Data Deficient.
Our results indicate that the commercial exploitation of endemic sharks and rays at risk of extinction is commonplace in southern Brazil. This reinforces the need for more systematic monitoring of the trade in fishery products and more effective application of the environmental legislation and conservation programmes.
Pyridine‐derived VEGFR‐2 inhibitors: Rational design, synthesis, anticancer evaluations, in silico ADMET profile, and molecular docking
Authors: Saleh Nashwa M. , Abdel‐Rahman Adel A.‐H. , Omar Asmaa M. , Khalifa Mohamed M. , El‐Adl Khaled 
Published: May 2021

AbstractNovel pyridine‐derived compounds (5–19) were designed and synthesized, and their anticancer activities were evaluated against HepG2 and MCF‐7 cells, targeting the VEGFR‐2 enzyme. Compounds 10, 9, 8, and 15 were found to be the most potent derivatives against the two cancer cell lines, HepG2 and MCF‐7, respectively, with IC50 = 4.25 and 6.08 µM, 4.68 and 11.06 µM, 4.34 and 10.29 µM, and 6.37 and 12.83 µM. Compound 10 displayed higher activity against HepG2 cells than sorafenib (IC50 = 9.18 and 5.47 µM, respectively) and doxorubicin (IC50 = 7.94 and 8.07 µM, respectively). It also showed higher activity than doxorubicin against MCF‐7 cells, but lower activity than sorafenib. Compounds 9, 8, and 15 displayed higher activities than sorafenib and doxorubicin against HepG2 cells but exhibited lower activities against MCF‐7 cells. Compound 10 potently inhibited VEGFR‐2 at an IC50 value of 0.12 µM, which is nearly equipotent to sorafenib (IC50 = 0.10 µM). Compounds 8 and 9 exhibited very good activity with the same IC50 value of 0.13 µM. The six most potent derivatives, 6, 9, 8, 10, 15, and 18, were tested for their cytotoxicity against normal Vero cells. Compounds 6, 8, 9, 10, 15, and 18 are, respectively, 1.13, 3.74, 4.18, 3.64, 2.81, and 2.00 times more toxic to HepG2 and 2.06, 1.58, 1.76, 2.54, 1.40, and 2.69 times more toxic to MCF‐7 breast cancer cells than in normal Vero cells.
Atomistic De‐novo Inhibitor Generation‐Guided Drug Repurposing for SARS‐CoV‐2 Spike Protein with Free‐Energy Validation by Well‐Tempered Metadynamics
Authors: Chowdhury Rituparno , Sai Sreyas Adury Venkata , Vijay Amal , Singh Reman K. , Mukherjee Arnab 
Published: May 2021

AbstractComputational drug design is increasingly becoming important with new and unforeseen diseases like COVID‐19. In this study, we present a new computational de novo drug design and repurposing method and applied it to find plausible drug candidates for the receptor binding domain (RBD) of SARS‐CoV‐2 (COVID‐19). Our study comprises three steps: atom‐by‐atom generation of new molecules around a receptor, structural similarity mapping to existing approved and investigational drugs, and validation of their binding strengths to the viral spike proteins based on rigorous all‐atom, explicit‐water well‐tempered metadynamics free energy calculations. By choosing the receptor binding domain of the viral spike protein, we showed that some of our new molecules and some of the repurposable drugs have stronger binding to RBD than hACE2. To validate our approach, we also calculated the free energy of hACE2 and RBD, and found it to be in an excellent agreement with experiments. These pool of drugs will allow strategic repurposing against COVID‐19 for a particular prevailing conditions.
Immer wieder neu denken – Der Ingenieur und Hochschullehrer Stefan Polónyi † (1930–2021)
Authors: Bollinger Klaus , Hauke Bernhard , Kloft Harald 
Published: May 2021

AbstractDer Ingenieur und Hochschullehrer Univ.‐Prof. em. Dr.‐Ing. E.h. mult. Stefan Polónyi ist am 9. April 2021 in Köln verstorben. Der nachfolgende Beitrag ist ein gekürztes Essay aus dem Jahrbuch Ingenieurbaukunst 2021. Dieser Beitrag erscheint auch in den Ernst & Sohn‐Zeitschriften Bautechnik Heft 5 und Stahlbau Heft 5.
Positive allometry of sexually selected traits: Do metabolic maintenance costs play an important role?
Authors: Somjee Ummat 
Published: May 2021

AbstractSexual selection drives the evolution of some of the most exaggerated traits in nature. Studies on sexual selection often focus on the size of these traits relative to body size, but few focus on energetic maintenance costs of the tissues that compose them, and the ways in which these costs vary with body size. The relationships between energy use and body size have consequences that may allow large individuals to invest disproportionally more in sexually selected structures, or lead to the reduced per‐gram maintenance cost of enlarged structures. Although sexually selected traits can incur energetic maintenance costs, these costs are not universally high; they are dependent on the relative mass and metabolic activity of tissues associated with them. Energetic costs of maintenance may play a pervasive yet little‐explored role in shaping the relative scaling of sexually selected traits across diverse taxa. Also see the video abstract here: https://youtu.be/JyuoQIeA33Q
Close relationships in Parkinson´s disease patients with device‐aided therapy
Authors: Scharfenort Monica , Timpka Jonathan , Sahlström Thomas , Henriksen Tove , Nyholm Dag , Odin Per 
Published: May 2021

AbstractObjectivesDeep brain stimulation, continuous subcutaneous apomorphine infusion, and levodopa–carbidopa intestinal gel infusion, together called device‐aided therapies (DAT), are introduced when oral and transdermal pharmacotherapy are not enough for a satisfactory control of Parkinson's disease (PD) symptoms. Solid relationships are central to an individual's well‐being, but the impact of close relationships in advanced PD remains underexplored. The aim of this study was to investigate the development of close relationships between PD patients and their partners following the initiation of DAT and to examine the relationship structures in these relationships.Materials and MethodsThis was a retrospective quantitative multicenter pilot study wherein 41 couples, patients with advanced PD and their partners, retrospectively rated their relationship satisfaction before the start of DAT, after one year of DAT and at the time of the interview. The couples also answered the Experiences in Close Relationships—Questionnaire of Relational Structures (ECR‐RS).ResultsPartners more often report changes in relationship satisfaction than patients between baseline and both 1 year after start of DAT (p = .049) and last evaluation (p = .041). The ECR‐RS data reported significantly higher avoidance score for partners (p = .005) and significantly higher anxiety score for patients (p = .024).ConclusionsThe close relationship wherein one part has PD and receives DAT has a high risk of being unequal. Prospective studies are needed for further clarification of the interplay between advanced PD, DAT, and close relationships, this in order to improve pre‐ and postinterventional support for PD patients receiving DAT, as well as their partners.
Site‐Specific Selenocysteine Incorporation into Proteins by Genetic Engineering
Authors: Wang Yuchuan , Liu Pengcheng , Chang Jiao , Xu Yunping , Wang Jiangyun 
Published: May 2021

AbstractSelenocysteine (Sec), a rare naturally proteinogenic amino acid, is the major form of essential trace element selenium in living organisms. Selenoproteins, with one or several Sec residues, are found in all three domains of life. Many selenoproteins play a role in critical cellular functions such as maintaining cell redox homeostasis. Sec is usually encoded by an in‐frame stop codon UGA in the selenoprotein mRNA, and its incorporation in vivo is highly species‐dependent and requires the reprogramming of translation. This mechanistic complexity of selenoprotein synthesis poses a big challenge to produce synthetic selenoproteins. To understand the functions of natural as well as engineered selenoproteins, many strategies have recently been developed to overcome the inherent barrier for recombinant selenoprotein production. In this review, we will describe the progress in selenoprotein production methodology.
Examining the amino acid composition, secondary structure, and physicochemical and functional properties of proteins isolated from local lentil landraces of Anatolia
Authors: Gunes Zeynep Saliha , Can Karaca Asli 
Published: May 2021

AbstractBackground and objectivesProviding information on protein structure and functionality is essential for evaluating the potential of specific agricultural commodities to be utilized as plant‐based protein sources. Amino acid composition, secondary structure, surface charge, thermal, and functional properties of proteins isolated from five local lentil landraces were investigated. Secondary objective of the study was to investigate if a relationship exists between the amino acid composition and the physicochemical or functional properties of the isolates.FindingsAspartic acid and glutamic acid were found to be the dominant amino acids in the isolates while they were poor in methionine. Denaturation temperatures of isolates ranged between 96–108°C and their secondary structure mainly consisted of β‐sheet. Emulsion capacity, emulsifying activity (EAI), and emulsion stability indices (ESI) of isolates were found to be between 403.8–468.2 g oil/g protein, 18.8–24.2 m2/g, and 43.4–125.5 min, respectively. Foaming capacity of the isolates changed between 71% and 91% whereas their least gelation concentration varied between 110 and 150 g/L.ConclusionsYusufhan isolate which had relatively higher acidic amino acid content showed the highest net charge and solubility at acidic pH. Tigris isolate which had higher hydrophobic amino acid content compared to the other isolates showed relatively high thermal stability, EAI and ESI.Significance and noveltyFindings of the study make a contribution toward the potential use of local lentil landraces as sources for extracting protein‐based ingredients.
Monitoring Immunotherapy With Optical Molecular Imaging
Authors: Xu Li , Wang Youjuan , Ma Yuan , Huan Shuangyan , Song Guosheng 
Published: May 2021

AbstractImmunotherapy is an effective way to mobilize the body‘s own immune system to confront tumor cells. However, the efficacy of immunotherapy is affected by tumor heterogeneity, and the low therapeutic response to immunotherapy may lead to negative outcomes, which reinforces the urgency for early benefit predictors. Evaluating the infiltration of immune cells in solid tumors and metabolism changes of tumors provide potential response targets for monitoring immune response. Non‐invasive imaging identifying prognostic biomarkers can select the beneficiaries of targeted immunotherapy from non‐responses. Quantitative biomarkers may eventually improve the cancer management, help customize individual treatment plans and predict the treatment outcomes. In this review, we summarize the non‐invasive optical molecular imaging methods for monitoring immunotherapy. With the combination of imaging and immunotherapy, the prediction of immunotherapy response may promote the development of precision medicine.
Conditional disease‐free survival rates and their associated determinants in patients with epithelial ovarian cancer: A 15‐year retrospective cohort study
Authors: Ebrahimi Vahid , Khalafi‐Nezhad Abolfazl , Ahmadpour Fatemeh , Jowkar Zahra 
Published: May 2021

AbstractBackgroundThe most common type of ovarian cancer (OC) is epithelial ovarian cancer (EOC) which is the most lethal gynecologic malignancy in adult women.AimThis study aimed to determine the conditional disease‐free survival (CDFS) rates and their associated determinants in patients with EOC.Methods and resultsThe clinical and demographic data of 335 patients with confirmed EOC at Motahari Clinic (Shiraz, Iran) were retrospectively reviewed and analyzed. Traditional DFS (TDFS) and CDFS were calculated using the Kaplan–Meier method and cumulative DFS estimates, respectively. To evaluate the effects of the prognostic determinants on the DFS of the patients, a multiple covariate Cox analysis using the landmarking method was applied.The 1‐ and 3‐year TDFSs were 81.1% and 47.0%, respectively, and decreased over time. At baseline, a higher stage tumor and endometrioid histology were associated with a higher risk of recurrence when compared to stage I and other histological subtypes, respectively. The hazard of recurrence for older women (age ≥55 years) was approximately twice and three times more than that of women aged <45 years at 1‐ and 3‐year landmark time points, respectively.ConclusionThe age at diagnosis, defined by a cut‐off of 55 years, was a prognostic factor for the CDFS of EOC women. Moreover, patients with advanced‐stage EOC (ASEOC) (stages III and IV) and endometrioid histology had poorer CDFSs compared to those with early‐stage EOC (ESEOC) (stages I and II) and other histological types. In ESEOC patients with age at diagnosis of >55 years, CDFS gradually decreased in 3 years after remission which should be considered for follow‐up care decision‐making.
Artificial neural networks as clinical decision support systems
Authors: Shafi Imran , Ansari Sana , Din Sadia , Jeon Gwanggil , Paul Anand 
Published: May 2021

SummaryIn the last decade, artificial intelligent systems based on neural networks have gradually become primary source for clinical decision support systems (CDSS) and are being used in diverse areas of medical diagnosis, classification, and prediction. An artificial neural network (ANN) consists of a large number of processing units which performs the computation in a parallel and distributed environment. They learn the pattern from the examples provided to it and then generalize based on the concepts they have learned while training. This paper presents a review of the current status of ANN and its variants as CDSS in various medical disciplines. The work focuses and describes the methods making use of simple ANN and use of real‐time approaches based on big data using ANN in cloud computing environment for various medical applications. Critical analysis of various methods based on smart approaches indicates that feed‐forward back propagation ANN performs sufficiently better in the domain of medicines with a high degree of accuracy.