bluuebunny/crossref_metadata_2025 huggingface dataset:
GARS‐related disease in infantile spinal muscular atrophy: Implications for diagnosis and treatment
Authors: Markovitz Rebecca , Ghosh Rajarshi , Kuo Molly E. , Hong William , Lim Jaehyung , Bernes Saunder , Manberg Stephanie , Crosby Kathleen , Tanpaiboon Pranoot , Bharucha‐Goebel Diana , Bonnemann Carsten , Mohila Carrie A. , Mizerik Elizabeth , Woodbury Suzanne , Bi Weimin , Lotze Timothy , Antonellis Anthony , Xiao Rui , Potocki Lorraine
Published: March 2020

The majority of patients with spinal muscular atrophy (SMA) identified to date harbor a biallelic exonic deletion of SMN1. However, there have been reports of SMA‐like disorders that are independent of SMN1, including those due to pathogenic variants in the glycyl‐tRNA synthetase gene (GARS1). We report three unrelated patients with de novo variants in GARS1 that are associated with infantile‐onset SMA (iSMA). Patients were ascertained during inpatient hospital evaluations for complications of neuropathy. Evaluations were completed as indicated for clinical care and management and informed consent for publication was obtained. One newly identified, disease‐associated GARS1 variant, identified in two out of three patients, was analyzed by functional studies in yeast complementation assays. Genomic analyses by exome and/or gene panel and SMN1 copy number analysis of three patients identified two previously undescribed de novo missense variants in GARS1 and excluded SMN1 as the causative gene. Functional studies in yeast revealed that one of the de novo GARS1 variants results in a loss‐of‐function effect, consistent with other pathogenic GARS1 alleles. In sum, the patients' clinical presentation, assessments of previously identified GARS1 variants and functional assays in yeast suggest that the GARS1 variants described here cause iSMA. GARS1 variants have been previously associated with Charcot–Marie–Tooth disease (CMT2D) and distal SMA type V (dSMAV). Our findings expand the allelic heterogeneity of GARS‐associated disease and support that severe early‐onset SMA can be caused by variants in this gene. Distinguishing the SMA phenotype caused by SMN1 variants from that due to pathogenic variants in other genes such as GARS1 significantly alters approaches to treatment.
Documented skeletal collections in Greece: Composition, research, and future prospects
Authors: Nikita Efthymia
Published: March 2020

Documented skeletal collections constitute a key resource in forensic anthropological and bioarchaeological research as they allow both the development of methods for the estimation of various parameters of an individual's biological profile, and the examination of the accuracy of existing methods in different skeletal assemblages. The acknowledgement of the utility of documented collections is attested by the large number of such collections across the world. The current review will focus on two modern reference collections in Greece, briefly presenting their composition, the research projects in which they have been employed, and future prospects for their use.
Urinary glucose and ketone bodies as indicators of acute caffeine poisoning
Authors: Morita Seiji , Tsuji Tomoatsu , Amino Mari , Miura Naoya , Saito Takeshi , Nakagawa Yoshihide
Published: March 2020

Aim

In various countries, many fatal health problems have been reported due to high intake of caffeine‐rich energy drinks, tablets, and powders. In patients with acute caffeine poisoning, determination of blood caffeine concentration is an important yet difficult task. We aimed to assess whether the presence of glucose and ketone bodies in urine reflected the blood caffeine concentration in patients with acute caffeine poisoning.

Methods

From April 2010 to March 2018, 25 patients with an overdose of only caffeine‐rich tablets were admitted to our hospital. Their clinical features were investigated. In addition, we investigated whether the glucose and ketone bodies in the urine reflected blood caffeine concentration in 23 patients who underwent the urine qualitative test at admission.

Results

The majority of the patients were young healthy women, whose average caffeine ingestion was 15.6 ± 8.1 g. Initial urine examinations showed glucose in 60% (14/23) of patients and ketone bodies in 57% (13/23) of patients. Ketone bodies or glucose were found in 78% (18/23) of the patients. The correlation between blood caffeine concentration and urinary glucose was R = 0.625, blood caffeine concentration and ketone bodies was R = 0.596, and blood caffeine and both was R = 0.76.

Conclusion

Urine qualitative test is effective for differential diagnosis and severity assessment of acute caffeine poisoning in patients.
Conditional Copper‐Catalyzed Azide–Alkyne Cycloaddition by Catalyst Encapsulation
Authors: Brevé Tobias G. , Filius Mike , Araman Can , van der Helm Michelle P. , Hagedoorn Peter‐Leon , Joo Chirlmin , van Kasteren Sander I. , Eelkema Rienk
Published: March 2020

Supramolecular encapsulation is known to alter chemical properties of guest molecules. We have applied this strategy of molecular encapsulation to temporally control the catalytic activity of a stable copper(I)–carbene catalyst. Encapsulation of the copper(I)–carbene catalyst by the supramolecular host cucurbit[7]uril (CB[7]) resulted in the complete inactivation of a copper‐catalyzed alkyne–azide cycloaddition (CuAAC) reaction. The addition of a chemical signal achieved the near instantaneous activation of the catalyst, by releasing the catalyst from the inhibited CB[7] catalyst complex. To broaden the scope of our on‐demand CuAAC reaction, we demonstrated the protein labeling of vinculin with the copper(I)–carbene catalyst, to inhibit its activity by encapsulation with CB[7] and to initiate labeling at any moment by adding a specific signal molecule. Ultimately, this strategy allows for temporal control over copper‐catalyzed click chemistry, on small molecules as well as protein targets.
Synthesis and Reactivity of Organometallic Intermediates Relevant to Cobalt‐Catalyzed Hydroformylation
Authors: MacNeil Connor S. , Mendelsohn Lauren N. , Zhong Hongyu , Pabst Tyler P. , Chirik Paul J.
Published: March 2020

Intermediates relevant to cobalt‐catalyzed alkene hydroformylation have been isolated and evaluated in fundamental organometallic transformations relevant to aldehyde formation. The 18‐electron (R,R)‐(iPrDuPhos)Co(CO)2H has been structurally characterized, and it promotes exclusive hydrogenation of styrene in the presence of 50 bar of H2/CO gas (1:1) at 100 °C. Deuterium‐labeling studies established reversible 2,1‐insertion of styrene into the Co−D bond of (R,R)‐(iPrDuPhos)Co(CO)2D. Whereas rapid β‐hydrogen elimination from cobalt alkyls occurred under an N2 atmosphere, alkylation of (R,R)‐(iPrDuPhos)Co(CO)2Cl in the presence of CO enabled the interception of (R,R)‐(iPrDuPhos)Co(CO)2C(O)CH2CH2Ph, which upon hydrogenolysis under 4 atm H2 produced the corresponding aldehyde and cobalt hydride, demonstrating the feasibility of elementary steps in hydroformylation. Both the hydride and chloride derivatives, (X=H−, Cl−), underwent exchange with free 13CO. Under reduced pressure, (R,R)‐(iPrDuPhos)Co(CO)2Cl underwent CO dissociation to form (R,R)‐(iPrDuPhos)Co(CO)Cl.
Photoenzymatic Hydrogenation of Heteroaromatic Olefins Using ‘Ene’‐Reductases with Photoredox Catalysts
Authors: Nakano Yuji , Black Michael J. , Meichan Andrew J. , Sandoval Braddock A. , Chung Megan M. , Biegasiewicz Kyle F. , Zhu Tianyu , Hyster Todd K.
Published: March 2020

Flavin‐dependent ‘ene’‐reductases (EREDs) are highly selective catalysts for the asymmetric reduction of activated alkenes. This function is, however, limited to enones, enoates, and nitroalkenes using the native hydride transfer mechanism. Here we demonstrate that EREDs can reduce vinyl pyridines when irradiated with visible light in the presence of a photoredox catalyst. Experimental evidence suggests the reaction proceeds via a radical mechanism where the vinyl pyridine is reduced to the corresponding neutral benzylic radical in solution. DFT calculations reveal this radical to be “dynamically stable”, suggesting it is sufficiently long‐lived to diffuse into the enzyme active site for stereoselective hydrogen atom transfer. This reduction mechanism is distinct from the native one, highlighting the opportunity to expand the synthetic capabilities of existing enzyme platforms by exploiting new mechanistic models.
An Aqueous Conducting Redox‐Polymer‐Based Proton Battery that Can Withstand Rapid Constant‐Voltage Charging and Sub‐Zero Temperatures
Authors: Strietzel Christian , Sterby Mia , Huang Hao , Strømme Maria , Emanuelsson Rikard , Sjödin Martin
Published: March 2020

Electrodes based on organic matter operating in aqueous electrolytes enable new approaches and technologies for assembling and utilizing batteries that are difficult to achieve with traditional electrode materials. Here, we report how thiophene‐based trimeric structures with naphthoquinone or hydroquinone redox‐active pendent groups can be processed in solution, deposited, dried and subsequently polymerized in solid state to form conductive (redox) polymer layers without any additives. Such post‐deposition polymerization offers efficient use of material, high mass loading (up to 10 mg cm−2) and good flexibility in the choice of substrate and coating method. By employing these materials as anode and cathode in an acidic aqueous electrolyte a rocking‐chair proton battery is built. The battery shows good cycling stability (85 % after 500 cycles), withstands rapid charging, with full capacity (60 mAh g−1) reached within 100 seconds, allows for direct integration with photovoltaics, and retains its favorable characteristics even at −24 °C.
On the Crucial Role of Isolated Electronic States in the Thermal Reaction of ReC+ with Dihydrogen
Authors: Li Jilai , Geng Caiyun , Weiske Thomas , Schwarz Helmut
Published: March 2020

Presented here is that isolated, long‐lived electronic states of ReC+ serve as the root cause for distinctly different reactivities of this diatomic ion in the thermal activation of dihydrogen. Detailed high‐level quantum chemical calculations support the experimental findings obtained in the highly diluted gas phase using FT‐ICR mass spectrometry. The origin for the existence of these long‐lived excited electronic states and the resulting implications for the varying mechanisms of dihydrogen splitting are addressed.
Edge detection for the buried archaeological structures with the geophysical image processing method in the Alabanda Ancient Cistern in Turkey
Authors: Karaaslan Hasan
Published: March 2020

Edge detection techniques are some of the most useful techniques to determine the lineaments of buried structures from magnetic data. In this context, many techniques have been designed by using the magnetic gradient tensor (MGT). In this work, eigenvalue analysis of the full MGT and a new normalized approach [normalized edge detector (NK)], which balances strong and weak amplitude anomalies simultaneously, was utilized to outline lineaments of the buried archaeological structures. Satisfactory results were obtained from noisy and noise free synthetic data which were generated from prism models. The techniques were implemented on the archaeological magnetic data acquired from a buried ancient cistern. In addition, three‐dimensional (3D) electrical resistivity tomography (ERT) inversion sections and two‐dimensional (2D) magnetic inversion section and tilt angle methods were used to compare them against the results of edge detection analysis. The results of the normalized eigenvalue analysis agreed closely with all techniques in detecting the lineaments of the buried archaeological structure. NK detected the lineaments of the buried structure more clearly than the tilt angle and had better resolution. All of the results have shown that eigenvalue analysis of the full MGT and especially the newly introduced approach NK can provide important information for archaeological studies.
Wilcoxon‐type rank‐sum statistics for selecting the best population: Some advances
Authors: Koutras Markos V. , Triantafyllou Ioannis S.
Published: March 2020

In this article, we introduce three new nonparametric procedures for testing the equality of two lifetime distributions. The proposed testing processes are based on appropriately modified Wilcoxon‐type rank‐sum statistics. The exact null distribution of these statistics is studied and closed formulae for the corresponding exact probability of correct selection of the best population are derived for the class of Lehmann alternatives. A detailed numerical study is carried out to elucidate the performance of the proposed testing schemes. For illustration purposes, a real data application is presented in some detail.
Metallocenyl 7‐ACA Conjugates: Antibacterial Activity Studies and Atomic‐Resolution X‐ray Crystal Structure with CTX‐M β‐Lactamase
Authors: Lewandowski Eric M. , Szczupak Łukasz , Kowalczyk Aleksandra , Mendoza Gracia , Arruebo Manuel , Jacobs Lian M. C. , Stączek Paweł , Chen Yu , Kowalski Konrad
Published: March 2020

The conjugation of organometallic groups to current β‐lactam antibiotics is a field of increasing study due to the ability of certain organometallic groups to enhance the antibiotic potency of these drugs. Herein, we report the antibacterial properties of two metallocenyl (ferrocenyl and ruthenocenyl) 7‐aminocephalosporanic acid (7‐ACA) antibiotic conjugates. Continuing a trend we found in our previous studies, the ruthenocenyl conjugate showed greater antibacterial activity than its ferrocenyl counterpart. Compared with the previously published 7‐aminodesacetoxycephalosporanic acid (7‐ADCA) conjugates, the 3‐acetyloxymethyl group significantly improved the compounds’ activity. Furthermore, the Rc‐7‐ACA compound was more active against clinical Staphylococcus aureus isolates than the ampicillin reference. Noticeably, neither of the two new compounds showed an undesirable toxic effect in HeLa and L929 cells at the concentrations at which they displayed strong antibacterial effects. The antibacterial activity of the two metallocenyl 7‐ACA derivatives was further confirmed by scanning electron microscopy (SEM). SEM micrographs showed that bacteria treated with metallocenyl 7‐ACA derivatives feature cell wall damage and morphology changes. Using a CTX‐M‐14 β‐lactamase competition assay based on nitrocefin hydrolysis, we showed that the Rc‐7‐ACA bound more favorably to CTX‐M‐14 than its ferrocenyl counterpart, again confirming the superiority of the ruthenocenyl moiety over the ferrocenyl one in interacting with proteins. We also report a 1.47 Å resolution crystal structure of Rc‐7‐ACA in complex with the CTX‐M‐14 E166A mutant, an enzyme sharing a similar active site configuration with penicillin‐binding proteins, the molecular target of β‐lactam antibiotics. These results strengthen the case for the antibacterial utility of the Rc and Fc groups.
Surface Display of Complex Enzymes by in Situ SpyCatcher‐SpyTag Interaction
Authors: Gallus Sabrina , Peschke Theo , Paulsen Malte , Burgahn Teresa , Niemeyer Christof M. , Rabe Kersten S.
Published: March 2020

The display of complex proteins on the surface of cells is of great importance for protein engineering and other fields of biotechnology. Herein, we describe a modular approach, in which the membrane anchor protein Lpp‐OmpA and a protein of interest (passenger) are expressed independently as genetically fused SpyCatcher and SpyTag units and assembled in situ by post‐translational coupling. Using fluorescent proteins, we first demonstrate that this strategy allows the construct to be installed on the surface of E. coli cells. The scope of our approach was then demonstrated by using three different functional enzymes, the stereoselective ketoreductase Gre2p, the homotetrameric glucose 1‐dehydrogenase GDH, and the bulky heme‐ and diflavin‐containing cytochrome P450 BM3 (BM3). In all cases, the SpyCatcher‐SpyTag method enabled the generation of functional whole‐cell biocatalysts, even for the bulky BM3, which could not be displayed by conventional fusion with Lpp‐OmpA. Furthermore, by using a GDH variant carrying an internal SpyTag, the system could be used to display an enzyme with unmodified N‐ and C‐termini.
Electrochemistry of Tri‐substituted Porphyrins with β‐Appended Ethyl Acetoacetate and Acetylacetone in Neutral and Basic Nonaqueous Solvents
Authors: Fang Yuanyuan , Yadav Inderpal , Osterloh W. Ryan , Chaudhri Nivedita , Sankar Muniappan , Kadish Karl M.
Published: March 2020

The electrochemistry of β‐substituted tetraphenylporphyrins with a single ethyl acetoacetate (EAA), acetylacetone (acac), or ethyl acetate (EA) group and two antipodal H, Br or Ph groups was investigated in CH2Cl2 containing 0.1 M tetrabutylammonium perchlorate (TBAP) before and after addition of base to solution in the form of tetrabutylammonium hydroxide (TBAOH). The tri‐substituted porphyrins in their neutral form are represented as MTPP(EAA)X2, MTPP(acac)X2 and MTPP(EA)X2, where TPP is the dianion of tetraphenylporphyrin, M=H2, NiII, CuII or ZnII and X=H, Br or Ph. The singly reduced porphyrins are relatively stable on the cyclic voltammetry timescale, but this is not the case for the doubly reduced EAA and acac derivatives, which are highly reactive at room temperature, leading to a porphyrin product assigned as containing a deprotonated EAA− or acac− (enolate) substituent. Enolate‐appended porphyrins were also generated in‐situ by the addition of TBAOH, resulting in mono‐anionic porphyrins that are harder to reduce by 110–160 mV as compared to the neutral compounds with the same β‐substituents, suggesting a high degree of interaction between the deprotonated EAA− or acac− substituent and the porphyrin π‐ring system. The chemically or electrochemically generated enolate‐appended porphyrin could also be irreversibly oxidized by one electron at peak potentials between 0.10 and 0.30 V; the exact value depending upon solvent and type of β‐diketo substituent.
Synthesis and Photophysical Properties of T‐Shaped Coinage‐Metal Complexes
Authors: Kleinhans George , Chan Alan K.‐W. , Leung Ming‐Yi , Liles David C. , Fernandes Manuel A. , Yam Vivian W.‐W. , Fernández Israel , Bezuidenhout Daniela I.
Published: March 2020

The photophysical properties of a series of T‐shaped coinage d10 metal complexes, supported by a bis(mesoionic carbene)carbazolide (CNC) pincer ligand, are explored. The series includes a rare new example of a tridentate T‐shaped AgI complex. Post‐complexation modification of the AuI complex provides access to a linear cationic AuI complex following ligand alkylation, or the first example of a cationic square planar AuIII−F complex from electrophilic attack on the metal centre. Emissions ranging from blue (CuI) to orange (AgI) are obtained, with variable contributions of thermally‐dependent fluorescence and phosphorescence to the observed photoluminescence. Green emissions are observed for all three gold complexes (neutral T‐shaped AuI, cationic linear AuI and square planar cationic AuIII). The higher quantum yield and longer decay lifetime of the linear gold(I) complex are indicative of increased phosphorescence contribution.
Untersuchung von Polymerablagerungen während der Synthese in einem Wärmeübertrager
Authors: Hohlen Annika , Augustin Wolfgang , Scholl Stephan
Published: March 2020

Zur Untersuchung der unerwünschten Belagbildung von Polymeren auf wärmeübertragenden Oberflächen (Polymerisationsfouling) wird das Ablagerungsverhalten eines Vinylacetat/Vinylester‐Copolymers während der Emulsionspolymerisation untersucht. Hierbei sollen grundlegende Unterschiede zum Ablagerungsverhalten eines bereits reagierten Vinylacetat/Ethylen‐Copolymers identifiziert werden. Für einen qualitativen Vergleich wird die Ablagerungstopographie mithilfe eines Digitalmikroskops bestimmt. Für die quantitative Berechnung wird der Foulingwiderstand aus der Masse sowie der Schichthöhe des abgelagerten Materials berechnet. Der Polymerisationsgrad beeinflusst das Ablagerungsverhalten insb. die Topographie. Das bereits ausreagierte Stoffsystem weist eine größere Foulingmasse sowie eine deutlich ausgeprägtere, kraterförmige Ablagerungstopographie auf, wohingegen während des Polymerisationsfoulings eine optisch deutlich andere, tropfenförmige Topographie entsteht.
Nativity, ethnic enclave residence, and breast cancer survival among Latinas: Variations between California and Texas
Authors: Shariff‐Marco Salma , Gomez Scarlett Lin , Canchola Alison J. , Fullington Hannah , Hughes Amy E. , Zhu Hong , Pruitt Sandi L.
Published: March 2020

Background

Among Latinas with breast cancer, residence in an ethnic enclave may be associated with survival. However, findings from prior studies are inconsistent.

Methods

The authors conducted parallel analyses of California and Texas cancer registry data for adult (aged ≥18 years) Latinas who were diagnosed with invasive breast cancer from 1996 to 2005, with follow‐up through 2014. Existing indices applied to tract‐level 2000 US Census data were used to measure Latinx enclaves and neighborhood socioeconomic status (nSES). Multivariable Cox proportional hazard models were fit for all‐cause and breast cancer–specific survival adjusted for year of diagnosis, patient age, nativity (with multiple imputation), tumor stage, histology, grade, size, and clustering by census tract.

Results

Among 38,858 Latinas, the majority (61.3% in California and 70.5% in Texas) lived in enclaves. In fully adjusted models for both states, foreign‐born women were found to be more likely to die of breast cancer and all causes when compared with US‐born women. Living in enclaves and in neighborhoods with higher SES were found to be independently associated with improved survival from both causes. When combined into a 4‐level variable, those in low nSES nonenclaves had worse survival for both causes compared with those living in low nSES enclaves and, in the all‐cause but not breast cancer–specific models, those in high nSES neighborhoods, regardless of enclave status, had improved survival from all causes.

Conclusions

Applying the same methods across 2 states eliminated previously published inconsistent associations between enclave residence and breast cancer survival. Future studies should identify specific protective effects of enclave residence to inform interventions.
Don't waste other people's time
Authors: Hodges Dawn Z.
Published: March 2020

One of the worst things a leader, manager, or boss can do, in my opinion, is waste their employees’ time. By doing so, you are keeping your employees from being productive.
Fine‐needle aspiration cytology for the diagnosis of solid basaloid adenoid cystic carcinoma of the breast: Its role, limitation, and perspective
Authors: Noda Yuri , Nakanishi Yuko , Nishimae Ayaka , Takahashi Hiroyo , Oshiro Chiya , Inaji Hideo , Yamasaki Masaru
Published: March 2020

Solid basaloid adenoid cystic carcinoma (SB‐AdCC) is a subtype of breast AdCC which shows more aggressive clinical behavior than other subtypes. Fine‐needle aspiration (FNA) cytology is a useful diagnostic tool for breast malignancies. However, most of the diagnostic cytological characteristics of AdCC are not present in SB‐AdCC and cytomorphological studies of this subtype are limited. Here, we evaluated the utility of FNA in the diagnosis of SB‐AdCC of the breast. A search of the pathology archives of our institutions for FNA specimens of histologically confirmed SB‐AdCC between 2012 and 2019 identified four patients with SB‐AdCC of the breast. All patients were female and the average age was 60 years. Cytologically, one case was classified as malignant, two as indeterminate, and one as unsatisfactory. Smears had low to moderate cellularity. All smears showed ribbon‐like material surrounding the clusters and a vertical nuclear arrangement toward the peripheral rim. Hyaline globules appeared only in one case. Cells in all cases showed an oval, angular, and spindle shape hyperchromatic nuclei with mild to severe atypia, and also dispersed naked nuclei similar to the cells of the clusters were detected in one case. In histological sections, these cytological findings were compatible with the histological findings and divergent histological differentiation was detected. Diagnosing of few cellular smears of SB‐AdCC is difficult whereas the features of peripheral rim of the clusters, naked nuclei, and the divergent differentiation may be important for diagnosing SB‐AdCC of the breast.
Generation of an Fsp1 (fibroblast‐specific protein 1)‐Flpo transgenic mouse strain
Authors: Cardot‐Ruffino Victoire , Chauvet Véronique , Caligaris Cassandre , Bertrand‐Chapel Adrien , Chuvin Nicolas , Pommier Roxane M. , Valcourt Ulrich , Vincent David , Martel Sylvie , Aires Sophie , Kaniewski Bastien , Dubus Pierre , Cassier Philippe , Sentis Stéphanie , Bartholin Laurent
Published: March 2020

Recombination systems represent a major breakthrough in the field of genetic model engineering. The Flp recombinases (Flp, Flpe, and Flpo) bind and cleave DNA Frt sites. We created a transgenic mouse strain ([Fsp1‐Flpo]) expressing the Flpo recombinase in fibroblasts. This strain was obtained by random insertion inside mouse zygotes after pronuclear injection. Flpo expression was placed under the control of the promoter of Fsp1 (fibroblast‐specific protein 1) gene, whose expression starts after gastrulation at Day 8.5 in cells of mesenchymal origin. We verified the correct expression and function of the Flpo enzyme by several ex vivo and in vivo approaches. The [Fsp1‐Flpo] strain represents a genuine tool to further target the recombination of transgenes with Frt sites specifically in cells of mesenchymal origin or with a fibroblastic phenotype.
Liquid biopsy technologies based on membrane microfluidics: High‐yield purification and selective quantification of biomarkers in nanocarriers
Authors: Wang Ceming , Senapati Satyajyoti , Chang Hsueh‐Chia
Published: March 2020

Liquid biopsy, screening cancer non‐invasively and frequently by detecting and quantifying molecular markers in physiological fluids, would significantly improve cancer survival rate but it remains a distant goal. The key obstacles presented by the highly heterogeneous samples are rapid/high‐yield purification and precise/selective marker capture by their antibody and oligo probes. As irregular expressions of these molecular biomarkers are the key signals, quantifying only those from the cancer cells would greatly enhance the performance of the screening tests. The recent discovery that the biomarkers are carried by nanocarriers, such as exosomes, with cell‐specific membrane proteins suggests that such selection may be possible, although a new suite of fractionation and quantification technologies would need to be developed. Although under‐appreciated, membrane microfluidics has made considerable contributions to resolving these issues. We review the progress made so far, based on ion‐selective, track‐etched, and gel membranes and advanced electrophoretic and nano‐filtration designs, in this perspective and suggest future directions.
Probabilistic analysis of security attacks in cloud environment using hidden Markov models
Authors: Al‐Karaki Jamal N. , Gawanmeh Amjad , Almalkawi Islam T. , Alfandi Omar
Published: March 2020

The rapidly growing cloud computing paradigm provides a cost‐effective platform for storing, sharing, and delivering data and computation through internet connectivity. However, one of the biggest barriers for massive cloud adoption is the growing cybersecurity threats/risks that influence its confidence and feasibility. Existing threat models for clouds may not be able to capture complex attacks. For example, an attacker may combine multiple security vulnerabilities into an intelligent, persistent, and sequence of attack behaviors that will continuously act to compromise the target on clouds. Hence, new models for detection of complex and diversified network attacks are needed. In this article, we introduce an effective threat modeling approach that has the ability to predict and detect the probability of occurrence of various security threats and attacks within the cloud environment using hidden Markov models (HMMs). The HMM is a powerful statistical analysis technique and is used to create a probability matrix based on the sensitivity of the data and possible system components that can be attacked. In addition, the HMM is used to provide supplemental information to discover a trend attack pattern from the implicit (or hidden) raw data. The proposed model is trained to identify anomalous sequences or threats so that accurate and up‐to‐date information on risk exposure of cloud‐hosted services are properly detected. The proposed model would act as an underlying framework and a guiding tool for cloud systems security experts and administrators to secure processes and services over the cloud. The performance evaluation shows the effectiveness of the proposed approach to find attack probability and the number of correctly detected attacks in the presence of multiple attack scenarios.
Advancing the Measurement of Collective Community Capacity and the Evaluation of Community Capacity‐Building Models
Authors: Hargreaves Margaret Barnwell , Coffee‐Borden Brandon , Verbitsky‐Savitz Natalya
Published: March 2020

Although more communities, practitioners, and policymakers are recognizing the value of community capacity‐building initiatives, more valid, reliable, and pragmatic measures of collective community capacity are needed to evaluate the effectiveness of such efforts. Over the past 6 years, there has been significant work to advance the measurement and evaluation of collective community capacity‐building initiatives. Accomplishments include the design, testing, and implementation of the Adverse Childhood Experiences (ACEs) and Resilience Collective Community Capacity (ARC3) Survey; the adaptation of the ARC3 Survey for a broader range of community capacity‐building initiatives such as the Collective Community Capacity (C3) Survey; and testing of the C3 Survey in over thirty communities in the United States, Canada, and United Kingdom. These advances will produce more valid, reliable, and pragmatic measures and community capacity‐building models that will contribute to the theory and practice of community‐level change. This chapter highlights work completed over 6 years to develop and test a valid and reliable measure of collective community capacity.
Finding the Impact: Methods for Assessing the Contribution of Collective Impact to Systems and Population Change in a Multi‐Site Study
Authors: Stachowiak Sarah , Lynn Jewlya , Akey Terri
Published: March 2020

John Kania and Mark Kramer put forward “Collective Impact” in 2011 as a framework for organizing multi‐sector collaborative efforts to achieve change at scale. The collective impact theory of change posits that by establishing and implementing its five conditions, groups can achieve meaningful systems changes to create long‐term gains in social and environmental conditions. While significant scale uptake has occurred, questions have remained about the degree to which collective impact, as an approach, actually works to achieve change at scale. In 2017, ORS Impact and Spark Policy Institute embarked on an evaluation effort to understand the degree to which the collective impact approach contributed to population‐level change across many sites. We sought to answer this question with as much rigor as possible, without attempting to simplify the complexity of the context, the variability of implementation of collective impact, or the many interim changes needed to see the impact at scale. This chapter shares the essential methods our research team used. We do not seek to share the findings; instead, we hope that others can learn from and use these methods to continue to strengthen the sector's understanding of when, how, and why different collaborative efforts work or do not. In addition to describing the key methods, the authors will reflect on considerations, lessons learned, and recommendations to other evaluators who might seek to answer similar questions or use similar tools and methods.
Shelf life estimation of Blackberry (Rubus glaucus Benth) with bacterial cellulose film coating from Komagataeibacter xylinus
Authors: Toscano Ávila Jonatan A. , Terán David A. , Debut Alexis , Vizuete Karla , Martínez Josefina , Cerda‐Mejía Liliana A.
Published: March 2020

The Castile blackberry (Rubus glaucus Benth) is an Andean crop with nutritional and antioxidant properties. The intake of this fruit potentiates the immune system and reduces the risk of developing degenerative and cardiovascular diseases. However, the Castile blackberry is one of the most perishable fruits due to its high respiration rate and the lack of protectant peel, making this fruit susceptible to microbial attack and rapid deterioration. The objective of this research was to estimate the shelf life of Castile blackberry (R. glaucus Benth) with bacterial cellulose coating from Komagataeibacter xylinus, in order to improve the physicochemical and nutritional characteristics. Blackberries with bacterial cellulose coating at 4°C have extended its shelf life to 9 days and preserved the initial characteristics of texture, color, smell, and taste.
A case of female adrenoleukodystrophy carrier with insidious neurogenic bladder
Authors: Obara Koji , Abe Erika , Shimozawa Nobuyuki , Toyoshima Itaru
Published: March 2020

A 65‐year‐old woman with mutation of the ABCD1 gene for adrenoleukodystrophy (ALD) was admitted to our hospital with a urinary tract infection. Abdominal computed tomography showed dilation of the urinary tract. Although she had noticed pollakisuria since her forties, she had not been followed up by any medical institutions until we diagnosed her as a female carrier with ALD. ALD is an X‐linked pattern of inheritance that typically affects males, but many female carriers actually present slowly progressive myelopathy and neuropathy. Therefore, it is important to identify female carriers with ALD and treat them at the earliest stage possible.
Novel tris(5‐aryl‐1H‐tetrazol‐1‐yl)methanes and 2‐dichloromethyl‐5‐aryl‐2H‐tetrazoles and noncovalent interactions in their crystal structure
Authors: Mikolaichuk Olga V. , Protas Aleksandra V. , Popova Elena A. , Mikherdov Alexander S. , Kornyakov Ilya V. , Trifonov Rostislav E.
Published: March 2020

A series of tris(5‐aryl‐1H‐tetrazol‐1‐yl)methanes (3a‐3g) and 2‐dichloromethyl‐5‐aryl‐2H‐tetrazoles (4a‐4d) were synthesized by reaction of 5‐aryl‐NH‐tetrazoles with trichloromethane in strong aqueous basic condition. The compounds obtained were fully characterized by means of HRESI‐MS, 1H and 13C{1H} NMR spectroscopies, as well as by single‐crystal X‐ray diffraction (for 3a, 3b, 4d). Inspection of the X‐ray diffraction data and Hirshfeld surface analysis for tris(5‐aryl‐1H‐tetrazol‐1‐yl)methanes 3a,b and 2‐dichloromethyl‐5‐aryl‐2H‐tetrazole 4d showed the presence of noncovalent π‐hole•••lone pair and π‐hole•••π interactions involving electrophilic tetrazole carbon atom.
Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID‐19
Authors: Gao Yong , Li Tuantuan , Han Mingfeng , Li Xiuyong , Wu Dong , Xu Yuanhong , Zhu Yulin , Liu Yan , Wang Xiaowu , Wang Linding
Published: March 2020

The role of clinical laboratory data in the differential diagnosis of the severe forms of COVID‐19 has not been definitely established. The aim of this study was to look for the warning index in severe COVID‐19 patients. We investigated 43 adult patients with COVID‐19. The patients were classified into mild group (28 patients) and severe group (15 patients). A comparison of the hematological parameters between the mild and severe groups showed significant differences in interleukin‐6 (IL‐6), d‐dimer (d‐D), glucose, thrombin time, fibrinogen, and C‐reactive protein (P < .05). The optimal threshold and area under the receiver operator characteristic curve (ROC) of IL‐6 were 24.3 and 0.795 µg/L, respectively, while those of d‐D were 0.28 and 0.750 µg/L, respectively. The area under the ROC curve of IL‐6 combined with d‐D was 0.840. The specificity of predicting the severity of COVID‐19 during IL‐6 and d‐D tandem testing was up to 93.3%, while the sensitivity of IL‐6 and d‐D by parallel test in the severe COVID‐19 was 96.4%. IL‐6 and d‐D were closely related to the occurrence of severe COVID‐19 in the adult patients, and their combined detection had the highest specificity and sensitivity for early prediction of the severity of COVID‐19 patients, which has important clinical value.
Magnetic molecularly imprinted specific solid‐phase extraction for determination of dihydroquercetin from Larix griffithiana using HPLC
Authors: Ma Xingbin , Zhang Xukun , Lin Hongling , Abd El‐Aty A. M. , Rabah Tsdan , Liu Xiaoxi , Yu Zhichao , Yong Yanhong , Ju Xianghong , She Yongxin
Published: March 2020

The naturally occurring quercetin flavonoid, dihydroquercetin, is widely distributed in plant tissues and has a variety of biological activities. Herein, a magnetic molecularly imprinted solid‐phase extraction was tailor made for selective determination of dihydroquercetin in Larix griffithiana using high‐performance liquid chromatography. Amino‐functionalized core‐shell magnetic nanoparticles were prepared and characterized using scanning electron microscopy, transmission electron microscopy, vibrating sample magnetometry, and infrared spectroscopy. The polymer had an average diameter of 250 ± 2.56 nm and exhibited good stability and adsorption for template molecule, which is enriched by hydrogen bonding interaction. Multiple factors for extraction, including loading, washing, elution solvents, and extraction time, were optimized. The limit of detection was 1.23 μg/g. The precision determined at various concentration of dihydroquercetin was less than 4% and the mean recovery was between 74.64 and 101.80%. It has therefore been shown that this protocol can be used as an alternative extraction to quantify dihydroquercetin in L. griffithiana and purify quercetin flavonoid from other complex matrices.
Role of Platelet‐Derived Growth Factor on the Fibrosis Process in Thyroid Carcinoma
Authors: Gu Jiying , Hu Wenjie , Liu Yang , Zhang Xuemei , Yuan Lin , Du Lianfang , Bai Min
Published: March 2020

Objectives

We aimed to determine the correlation between fibrosis and elastic values in papillary thyroid carcinoma (PTC) by shear wave elastography and to evaluate the effect of platelet‐derived growth factor (PDGF) on the fibrosis process.

Methods

Small interfering RNA (siRNA)‐PDGF and normal BCPAP cell lines were injected subcutaneously into the backs of nude mice. The elastic values of all tumors were measured by shear wave elastography. The content of collagen fibers and the expression of PDGF and type IV collagen (COL4) were evaluated by Masson staining and western blotting.

Results

There were 32 tumors in the control group and 30 tumors in the siRNA‐PDGF group. The tumors were divided into 4 subgroups based on maximum diameters of the tumors. The mean elastic values ± SD (Emean, 29.79 ± 11.04 kPa; Emin, 16.98 ± 7.51 kPa, Emax, 39.99 ± 15.30 kPa; and SD, 5.92 ± 2.00 kPa) in the siRNA‐PDGF group were lower than in the control group (Emean, 35.73 ± 18.49 kPa; Emin, 23.65 ± 14.92 kPa, Emax, 45.73 ± 22.88 kPa; and SD, 6.02 ± 3.38 kPa). The content of collagen fibers and the expression of platelet‐derived growth factor B (PDGFB) and COL4 proteins in the siRNA‐PDGF group were lower than in the control group (11.43% ± 6.99% and 19.80% ± 11.70%; P = .010; 0.14 ± 0.06 and 0.27 ± 0.10; P = .002; and 0.11 ± 0.06 and 0.15 ± 0.07; P = .101). The elastic values, collagen fiber content, and PDGFB and COL4 in the 4 subgroups gradually increased with the maximum diameter of tumors.

Conclusions

There was a positive correlation among PDGF, tumor stiffness, and fibrosis in the growth of PTC. Thus, PDGF might play an important role in the development of PTC.
Self‐Perceived Hearing Status Creates an Unrealized Barrier to Hearing Healthcare Utilization
Authors: Angara Prashant , Tsang Darren C. , Hoffer Michael E. , Snapp Hillary A.
Published: March 2020

Objective

To examine sociodemographic and audiometric factors associated with hearing aid (HA) uptake in adults with hearing loss (HL), and to investigate the role of self‐perceived hearing status on pursuit of hearing treatment. The relationship between self‐perceived hearing status and HA adoption has not been reported in a nationally representative sample of United States (US) adults.

Study Design

Cross‐sectional analysis of nationwide household health survey.

Methods

Audiometric and questionnaire data from the 2005 to 2012 National Health and Nutrition Examination Survey cycles were used to examine trends in untreated HL and HA adoption in US adults. Adjusted odds ratios for HA adoption were calculated for individuals with measured HL.

Results

Of 5230 respondents, 26.1% had measurable HL, of which only 16.0% correctly self‐identified their hearing status, and only 17.7% used an HA. Age, higher education, severe hearing impairments, and recent hearing evaluations, were positively associated with HA adoption.

Conclusion

Hearing loss is a global public health concern placing significant economic burden on both the individual and society. Self‐reported hearing status is not a reliable indicator for HL, and measured HL is not correlated with increased rates of treatment. Recent hearing evaluation is positively associated with increased rates of treatment. Routine hearing assessment will help to better identify those with HL and improve access to hearing treatment.

Level of Evidence

III Laryngoscope, 131:E289–E295, 2021
Physical rehabilitation in patients with head and neck cancer: Impact on health‐related quality of life and suitability of a post‐treatment program
Authors: Sandmæl Jon Arne , Bye Asta , Solheim Tora S. , Balstad Trude R. , Thorsen Lene , Skovlund Eva , Kaasa Stein , Lund Jo‐Åsmund , Oldervoll Line
Published: March 2020

Objective

Physical rehabilitation programs hold the potential to mitigate deterioration in health‐related quality of life (HRQoL) in patients with head and neck cancer. The objective was to assess development in relevant domains of HRQoL following a physical exercise and nutrition intervention administrated during or after treatment.

Methods

In a pilot study, 41 patients were randomized to resistance training and oral nutritional supplements during (EN‐DUR, n = 20) or after (EN‐AF, n = 21) radiotherapy. Global health status/QoL (GHS) and physical functioning (PF) were measured by the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire at baseline, week 6, and week 14. Differences between the groups were assessed by analysis of covariance. A difference of ≥10 points in GHS and PF was interpreted as clinically relevant.

Results

No statistically significant differences were detected between the groups; however, clinically relevant changes and differences in GHS and PF were observed. From baseline to week 6, GHS decreased 9 points in the EN‐DUR group and 23 points in the EN‐AF group and PF decreased 13 points and 21 points, respectively. From week 6 to week 14, GHS increased 14 points in the EN‐DUR group and 26 points EN‐AF group and PF did not change (0 points) in the EN‐DUR group and increased 16 points in the EN‐AF group.

Conclusion

The findings from the present pilot study are promising and indicate that a physical rehabilitation program may have a positive impact on HRQoL during treatment and enhance recovery after treatment. A definitive randomized trial is warranted.

Level of Evidence

1b—Individual randomized controlled trial.
Influence of T5 heat treatment on the microstructure and lubricated wear behavior of ternary ZnAl40Cu2 and quaternary ZnAl40Cu2Si2.5 alloys
Authors: Bican O. , Savaşkan T.
Published: March 2020

A ternary ZnAl40Cu2 and a quaternary ZnAl40Cu2Si2.5 alloys were produced by permanent mold casting and subjected to T5 heat treatment at a temperature of 150 °C for 24 hours. The structural, mechanical and lubricated wear properties of these alloys were investigated in the as‐cast and heat‐treated conditions and the results were compared with those of SAE 65 (CuSn12) plain bearing bronze. Microstructure of the ternary alloy consisted of aluminum‐rich α, eutectoid conversion product of α+η and ϵ phase located in the interdendritic channels. In addition to these phases, silicon particles were observed in the microstructure of the quaternary alloy. T5 heat treatment caused a considerable amount of reduction in the hardness, tensile strength and wear resistance of ZnAl40‐based ternary and quaternary alloys, but improved their ductility and stability. These alloys in the as‐cast and heat‐treated conditions exhibited lower wear volume or higher wear resistance than SAE 65 bearing bronze. Among the experimental alloys, the optimum mechanical properties and wear performance were obtained from ZnAl40Cu2Si2.5 alloy in both as‐cast and heat‐treated conditions. Adhesion appeared to be the main wear mechanism for the ZnAl40‐based alloys, but abrasion dominated the wear of SAE 65 bronze.
Calculation of lockbolt joints in mechanical engineering
Authors: Schwarz M. , Glienke R. , Wegener F. , Blunk C. , Henkel K.‐M.
Published: March 2020

Lockbolts become increasingly important for modern mechanical engineering. The advantageous notch effect in consequence of a softer groove geometry, the larger stress cross section for the same nominal diameter and a lower scattering of preload results in the potential for increasing the load capacity of lockbolt systems in mechanical joints in comparison to conventional bolted joints. Consequently costs can be reduced with structural adjustments in mechanical engineering. These include the reduction of the required nominal diameter and consequently the reduction of component dimensions. Furthermore savings in manufacturing and assembly as well as cost reduction for maintenance are possible. For the calculation of lockbolt systems in mechanical joints the Technical Bulletin DVS‐EFB 3435–2 is available now for design and calculation engineers. The Technical Bulletin allows to calculate joints with lockbolt systems according to VDI 2230 – Part 1 [1, 2]. This paper presents joints with lockbolts in mechanical engineering. At first, the lockbolt technology and the assembly preload of the lockbolts will be introduced. After that the structural behavior of joints with lockbolts under static and alternating load will be presented. Finally, the modified calculation steps according to the VDI 2230 – Part 1 will be demonstrated [2].
Aggregation equations with gradient potential as Radon measure and initial data in Besov‐Morrey spaces
Authors: Suleiman Marta L. , Precioso Juliana C. , Prokopczyk Andréa C.
Published: March 2020

In this work, we present conditions to obtain a global‐in‐time existence of solutions to a class of nonlinear viscous transport equations describing aggregation phenomena in biology with sufficiently small initial data in Besov‐Morrey spaces and gradient potential as a Radon measure. We also study the self‐similarity and asymptotic stability of solutions at large times.