bluuebunny/crossref_metadata_2025 huggingface dataset:
Adult Osteosclerotic Metaphyseal Dysplasia With Progressive Osteonecrosis of the Jaws and Abnormal Bone Resorption Pattern Due to a LRRK1 Splice Site Mutation
Authors: Howaldt Antonia , Hennig Anna Floriane , Rolvien Tim , Rössler Uta , Stelzer Nina , Knaus Alexej , Böttger Sebastian , Zustin Jozef , Geißler Sven , Oheim Ralf , Amling Michael , Howaldt Hans-Peter , Kornak Uwe
Published: March 2020

Osteosclerotic metaphyseal dysplasia (OSMD) is a rare autosomal recessive sclerosing skeletal dysplasia. We report on a 34-year-old patient with sandwich vertebrae, platyspondyly, osteosclerosis of the tubular bones, pathologic fractures, and anemia. In the third decade, he developed osteonecrosis of the jaws, which was progressive in spite of repeated surgical treatment over a period of 11 years. An iliac crest bone biopsy revealed the presence of hypermineralized cartilage remnants, large multinucleated osteoclasts with abnormal morphology, and inadequate bone resorption typical for osteoclast-rich osteopetrosis. After exclusion of mutations in TCIRG1 and CLCN7 we performed trio-based exome sequencing. The novel homozygous splice-site mutation c.261G>A in the gene LRRK1 was found and co-segregated with the phenotype in the family. cDNA sequencing showed nearly complete skipping of exon 3 leading to a frameshift (p.Ala34Profs*33). Osteoclasts differentiated from the patient's peripheral blood monocytes were extremely large. Instead of resorption pits these cells were only capable of superficial erosion. Phosphorylation of L-plastin at position Ser5 was strongly reduced in patient-derived osteoclasts showing a loss of function of the mutated LRRK1 kinase protein. Our analysis indicates a strong overlap of LRRK1-related OSMD with other forms of intermediate osteopetrosis, but an exceptional abnormality of osteoclast resorption. Like in other osteoclast pathologies an increased risk for progressive osteonecrosis of the jaws should be considered in OSMD, an intermediate form of osteopetrosis. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
Identification of markers of depression and neurotoxicity in pesticide exposed agriculture workers
Authors: Kori Rajesh K. , Mandrah Kapil , Hasan Whidul , Patel Devendra K. , Roy Somendu K. , Yadav Rajesh S.
Published: March 2020

Earlier, we reported that chronic exposure to pesticides causes a reduction in the acetylcholinesterase activity and hematological and biochemical alterations in agriculture workers. In continuation with that, the present study aimed to investigate the pesticide‐induced neurochemical imbalance and its association with behavior alterations in agricultural workers. A significant increase in depressive symptoms, assessed by the Beck Depression Inventory‐II was observed in pesticide exposed workers as compared to the unexposed. A decrease in the level of dopamine in plasma and levels of dopamine, 3,4‐dihydroxyphenylacetic acid, homovanillic acids, norepinephrine, serotonin, and hydroxyindoleacetic acid in urine was also observed. An increase in the levels of MAO‐A and MAO‐B has also been observed in these individuals. The decreased levels of neurotransmitters in the blood and urine have been linked with increased levels of MAO and pesticide residues in plasma and urine. Furthermore, these changes were associated with a higher incidence of depression in agricultural workers.
MeCP2 epigenetically regulates alpha‐smooth muscle actin in human lung fibroblasts
Authors: Xiang Zheyi , Zhou Qingxian , Hu Min , Sanders Yan Y.
Published: March 2020

Background

A critical feature for fibroblasts differentiation into myofibroblasts is the expression of alpha‐smooth muscle actin (α‐SMA) during the tissue injury and repair process. The epigenetic mechanism, DNA methylation, is involved in regulating α‐SMA expression. It is not clear how methyl‐CpG‐binding protein 2 (MeCP2) interacts with CpG‐rich region in α‐SMA, and if the CpG methylation status would affect MeCP2 binding and regulation of α‐SMA expression.

Methods

The association of MeCP2 with α‐SMA CpG rich region were examined by chromatin immunoprecipitation (ChIP) assays in primary fibroblasts from idiopathic pulmonary fibrosis (IPF) and non‐IPF control individuals, and in the lung fibroblasts treated with profibrotic cytokine transforming growth factor β1 (TGF‐β1). The regulation of α‐SMA by MeCP2 was examined by knocking down MeCP2 with small interfering RNA (siRNA). To explore the effects of the DNA methylation status of the CpG rich region on α‐SMA expression, the cells were treated with DNA methyltransferase inhibitor, 5′‐azacytidine (5′‐aza). The expression of α‐SMA was examined by Western blot and quantitative polymerase chain reaction, the association with MeCP2 was assessed by ChIP assays, and the methylation status was checked by bisulfate sequencing.

Results

The human lung fibroblasts with increased α‐SMA showed an enriched association of MeCP2, while knockdown MeCP2 by siRNA reduced α‐SMA upregulation by TGF‐β1. The 5′‐Aza‐treated cells have decreased α‐SMA expression with reduced MeCP2 association. However, bisulfite sequencing revealed that most CpG sites are unmethylated despite the different expression levels of α‐SMA after being treated by TGF‐β1 or 5′‐aza.

Conclusion

Our data indicate that the methyl‐binding protein MeCP2 is critical for α‐SMA expression in human lung myofibroblast, and the DNA methylation status at the CpG rich region of α‐SMA is not a determinative factor for its inducible expression.
Ultrasound‐assisted efficient synthesis of polyfunctional 1,2,4‐triazoles as novel antibacterial and antioxidant agents
Authors: Dastmard Sahar , Mamaghani Manouchehr , Rassa Mehdi
Published: March 2020

Novel 4,5‐diphenyl‐1H‐imidazol‐1‐yl‐1H‐1,2,4‐triazole derivatives were synthesized using a facile and highly efficient, one‐pot, four‐component procedure in the presence of KHSO4 as an acidic catalyst under ultrasonic irradiations in short reaction times (10–25 min) and good to excellent yields (70–96%). The synthesized compounds were screened for their antibacterial activities against Gram‐negative (Escherichia coli, Pseudomonas aeruginosa) and Gram‐positive (Bacillus subtilis, Micrococcus luteus) bacteria, and their antioxidant activity was also evaluated. Some of the products showed potential antibacterial and high antioxidant activities.
Utilizing CRISPR/Cas9 technology to prepare lymphoblastoid cell lines harboring genetic mutations for generating quality control materials in genetic testing
Authors: Zhou Li , Li Rui , Zhang Runling , Peng Rongxue , Chen Kun , Gao Peng , Zhang Jiawei , Zhang Rui , Li Jinming
Published: March 2020

Background

To meet the requirements of the rapidly progressing genetic testing technologies in clinical laboratories, assuring the quality of genetic tests by utilizing appropriate quality control materials is of paramount importance. The CRISPR/Cas9 technology was used to prepare quality control materials because genome‐edited human cell lines are one of the major resources for quality control materials.

Methods

In this study, in vitro transcribed sgRNA were transfected into a Cas9‐expressing lymphoblastoid cell line (LCL)—by electroporation—to simulate the SEA‐type deletion observed in α‐thalassemia. The edited positive cell line was screened and identified by polymerase chain reaction (PCR) followed by Sanger sequencing. The whole‐genome sequencing was also performed to show evidence of predicted mutation.

Results

The results showed that electroporation of the in vitro transcribed gRNAs into stable Cas9‐expressing LCL was a more efficient gene‐editing technique as compared to plasmid‐mediated transfection, and that the positive rates could reach up to 35.9%. The predominance of indel sizes relative to the predicted deletion length was clustered between 10 and 0 bp. The results of whole‐genome sequencing also demonstrated the existence of SEA‐type deletion of α‐thalassemia.

Conclusions

Gene‐editing based on Cas9‐expressing LCL by electroporation of sgRNA was a more efficient approach to introduce mutations for generating quality control materials for genetic testing. The edited lymphoblastoid cell lines were feasible to serve as quality control materials in genetic testing.
Proteomics reveals different pathological processes of adipose tissue, liver, and skeletal muscle under insulin resistance
Authors: Li Yaqi , Ma Quantao , Li Pengfei , Wang Jingkang , Wang Min , Fan Yuanyuan , Wang Tieshan , Wang Chunguo , Wang Ting , Zhao Baosheng
Published: March 2020

Type 2 diabetes mellitus is the most common type of diabetes, and insulin resistance (IR) is its core pathological mechanism. Proteomics is an ingenious and promising Omics technology that can comprehensively describe the global protein expression profiling of body or specific tissue, and is widely applied to the study of molecular mechanisms of diseases. In this paper, we focused on insulin target organs: adipose tissue, liver, and skeletal muscle, and analyzed the different pathological processes of IR in these three tissues based on proteomics research. By literature studies, we proposed that the main pathological processes of IR among target organs were diverse, which showed unique characteristics and focuses. We further summarized the differential proteins in target organs which were verified to be related to IR, and discussed the proteins that may play key roles in the emphasized pathological processes, aiming at discovering potentially specific differential proteins of IR, and providing new ideas for pathological mechanism research of IR.
Glucose regulates hypoxia‐induced NLRP3 inflammasome activation in macrophages
Authors: Watanabe Sachiko , Usui‐Kawanishi Fumitake , Karasawa Tadayoshi , Kimura Hiroaki , Kamata Ryo , Komada Takanori , Inoue Yoshiyuki , Mise Nathan , Kasahara Tadashi , Takahashi Masafumi
Published: March 2020

Although the intimate linkage between hypoxia and inflammation is well known, the mechanism underlying this linkage has not been fully understood. Nucleotide‐binding oligomerization domain‐like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is an intracellular multiprotein complex that regulates interleukin‐1β (IL‐1β) secretion and pyroptosis, and is implicated in the pathogenesis of sterile inflammatory diseases. Here, we investigated the regulatory mechanism of NLRP3 inflammasome activation in response to hypoxia in macrophages. Severe hypoxia (0.1% O2) induced the processing of pro‐IL‐1β, pro‐caspase‐1, and gasdermin D, as well as the release of IL‐1β and lactate dehydrogenase in lipopolysaccharide (LPS)‐primed murine macrophages, indicating that hypoxia induces NLRP3 inflammasome‐driven inflammation and pyroptosis. NLRP3 deficiency and a specific caspase‐1 blockade inhibited hypoxia‐induced IL‐1β release. Hypoxia‐induced IL‐1β release and cell death were augmented under glucose deprivation, and an addition of glucose in the media negatively regulated hypoxia‐induced IL‐1β release. Under hypoxia and glucose deprivation, hypoxia‐induced glycolysis was not driven and subsequently, the intracellular adenosine triphosphates (ATPs) were depleted. Atomic absorption spectrometry analysis showed a reduction of intracellular K+ concentrations, indicating the K+ efflux occurring under hypoxia and glucose deprivation. Furthermore, hypoxia and glucose deprivation‐induced IL‐1β release was significantly prevented by inhibition of K+ efflux and KATP channel blockers. In vivo experiments further revealed that IL‐1β production was increased in LPS‐primed mice exposed to hypoxia (9.5% O2), which was prevented by a deficiency of NLRP3, an apoptosis‐associated speck‐like protein containing a caspase recruitment domain, and caspase‐1. Our results demonstrate that NLRP3 inflammasome can sense intracellular energy crisis as a danger signal induced by hypoxia and glucose deprivation, and provide new insights into the mechanism underlying hypoxia‐induced inflammation.
Benefits of hypothermia in neonatal arterial ischemic strokes: A preclinical study
Authors: Chevin Mathilde , Chabrier Stéphane , Dinomais Mickaël , Bedell Barry J. , Sébire Guillaume
Published: March 2020

Background

There is currently no targeted treatment available for neonatal arterial ischemic strokes (NAIS). Epidemiological studies demonstrated that perinatal infection/inflammation, peripartum hypoxia, and occlusion of the internal carotid tree are the main determinants of NAIS. The well‐established benefit of therapeutic hypothermia (HT) in neonatal encephalopathy due to diffuse hypoxia‐ischemia provides a rationale for the potential use of HT as a neuroprotective strategy in NAIS.

Methods

We used a rat model to reproduce the most prevalent human physiopathological scenario of NAIS. The neuroprotective effect of HT was measured by morphometric magnetic resonance imaging, [18F] fluorodeoxyglucose (FDG) metabolic activity by positron emission tomography/computed tomography, and behavioral tests.

Results

HT (a) prevented the occurrence of 44% of NAIS, (b) reduced the volume of strokes by 37%, (c) enhanced [18F] FDG metabolic activity within the territory of the occluded carotid artery, and (d) improved motor behavior. Both morphometric and metabolic techniques showed consistently that HT provided a neuroprotective effect located in the motor cortex, hippocampus, and caudate‐putamen.

Conclusion

Through combining anatomical, metabolic imaging, and behavioral studies, our study provides evidence of neuroprotective effects of HT in NAIS. These results are potentially translational to human NAIS.
Foliar micromorphology and its role in identification of the Apocynaceae taxa
Authors: Bashir Kalsoom , Sohail Aamir , Ali Usman , Ullah Asad , Ul Haq Zahoor , Gul Brekhna , Ullah Inam , Sunera  , Asghar Mehrina
Published: March 2020

In the present study, we evaluate the importance of foliar epidermal micromorphological characteristics of Apocyanaceae for accurate identification and classification. The species were collected from the University of Peshawar's main campus in the spring season to observe its qualitative and quantitative features. The length and width of guard cells, stomatal pore and subsidiary cells, trichomes, and crypts on both sides of the leaf were examined. Many species were observed to be hypostomatic. Plumeria rubra, Raulfia serpentine, Thevetia peruviana, Trachelospermum lucidum, Alstonia scholaris, and Catharanthus roseus demonstrated hypostomatic leaves. Nearly all the investigated species had anisocytic type of stomata only or in combination with other types of stomata on the upper and lower epidermis. Carissa carandas had anomocytic, anisocytic, and cyclocytic type of stomata on the upper epidermis, and the lower epidermis showed variations in stomatal type, such as anomocytic, stephanocytic, brachyparacytic, and hemiparacytic. Nerium oleander had no specific shape of stomata but showed stomatal crypts in which the stomata were enclosed inside many trichomes. The taxonomic key based on stomatal types, epidermal cells, stomatal index value, and statistical analysis, along with the variations in the epidermal cells, shows the link between the selected plants species, which will provide a baseline for future anatomical studies. This study highlights many undocumented micromorphological characteristics. The anatomical characteristics observed in this study will be helpful for taxonomic identification and species delimitation of the family Apocynaceae.
No association between binge eating disorder and severity of non‐alcoholic fatty liver disease in severely obese patients
Authors: Canivet Clémence M , Perney Pascal , Cherick Faredj , Orlowski Magalie , Patouraux Stéphanie , Bailly‐Maitre Béatrice , Tran Albert , Iannelli Antonio , Gual Philippe , Anty Rodolphe
Published: March 2020

Background and Aim

The main aim of this study was to evaluate if the binge eating disorders (BEDs) related to obesity were associated with the severity of non‐alcoholic fatty liver disease (NAFLD).

Methods

Severely obese patients who had been referred for bariatric surgery were included in this study at the Nice University Hospital. All patients underwent a liver biopsy at the time of surgery. Between 2008 and 2015, 388 patients had an assessable Bulimia Test (BULIT) self‐questionnaire at the time of surgery. A subgroup (n = 183), between 2011 and 2015, also responded to a Beck Depression Inventory, Hospital Anxiety and Depression Scale, and a Fatigue Impact Scale autoquestionnaire. A control group of 29 healthy people matched by age and gender was included.

Results

Among the 388 obese patients (median age 40 years, body mass index 41.7 kg/m2, 81% women), 14 patients had a “probable diagnosis” of BED, and 47 patients had a “high risk” of developing a BED according to the BULIT. Obese patients had significantly more severe BED, depression, anxiety, and fatigue compared to controls. Steatosis, non‐alcoholic steatohepatitis, or fibrosis was not associated with BED. Similarly, the severity of NAFLD was not associated with depression, anxiety, or fatigue.

Conclusions

Severely obese patients had more severe BED, depression, anxiety, and fatigue than lean subjects independent of the severity of NAFLD.
Short photoperiod restores ventral subicular lesion‐induced deficits in affective and socio‐cognitive behavior in male Wistar rats
Authors: Subhadeep Duttagupta , Srikumar Bettadapura N. , Shankaranarayana Rao Byrathnahalli S. , Kutty Bindu M.
Published: March 2020

Photoperiod (day‐length) has enduring effects on an organism's physiological functions like metabolism and behavioral phenotypes including cognition and affect. Circadian rhythm manipulations are potentially effective non‐pharmacological strategies in the management of central nervous system insults. In our previous study, we demonstrated the efficacy of short photoperiod regime (SPR; 06/18 hr light‐dark cycle) in establishing functional recovery in ventral subicular lesion (VSL) rats. The present study further demonstrates the efficacy of SPR in mitigating anxiety and depression as well as facilitating socio‐cognitive behavior in VSL rats. VSL elevated the basal plasma corticosterone levels, increased anxiety, anhedonia, and behavioral despair with decreased self‐care. The VSL rats also exhibited a considerable degree of impaired social cognition, in terms of altered social preference and social novelty. Exposure to SPR for 21 days mitigated the anxiety‐ and depressive‐like phenotypes as well as improved social cognition significantly. Thus, the study demonstrated the effectiveness of SPR strategy in reversing most of the behavioral deficits caused by VSL. SPR, perhaps, would have regulated the hypothalamo‐pituitary‐adrenal axis responsiveness as we observed a decrease in plasma corticosterone levels following SPR in VSL rats. The study implies the need for developing a task‐dependent SPR strategy to achieve complete behavioral recovery as the functional demands of each behavior is distinct. In summary, the study highlights the efficacy of photoperiod manipulation as a novel, non‐pharmacological approach in mitigating the affective and cognitive deficits associated with neuropsychiatric disorders such as bipolar disorder and Alzheimer's disease wherein circadian rhythm alterations are implicated.
An amalgam of pathogenic and beneficial endophytic fungi colonizing fourDendrobiumspecies from Meghalaya, India
Authors: Hajong Subarna , Kapoor Rupam
Published: March 2020

Endophytic fungi are known to play an important role in driving the evolution of plants by conferring adaptational advantages to their host through the production of secondary metabolites and phytohormones. In this study, we evaluated the diversity and phylogenetic relationship of endophytic fungal communities from fourDendrobiumspecies viz.,Dendrobium chrysanthum, Dendrobium heterocarpum, Dendrobium hookerianum, andDendrobium longicornuof Meghalaya, India. A total of 51 culturable endophytic fungi were isolated from the four selected orchid species. The isolates were identified based on nuclear large subunit sequences into 33 species. Approximately 91% of the isolates showed affinity to Ascomycetes, while 9% of the isolates showed BLAST search similarity to Basidiomycetes. The most common genera wereTrichodermaandXylaria. The most prevalent genera wereFusarium, which was detected in all the fourDendrobiumspecies followed byDiaporthe, which was present in threeDendrobiumspecies viz.,D. chrysanthum, D. hookerianum, andD. heterocarpum. The Shannon index value of endophytic fungal communities was the highest inD. chrysanthum(2.66), whileD. longicornu(1) had the highest Evenness index. The present study revealed that endophytic fungi in these orchids are an amalgam of pathogenic and beneficial fungi, which have, at the least, switched their lifestyle to asymptomatic endophyte in their host. To our knowledge, this is the first such report on the diversity of endophytic fungi in the four selectedDendrobiumspecies from Meghalaya, India.
Differentiated thyroid cancer and Hashimoto thyroiditis: Utility of the Afirma gene expression classifier
Authors: Papoian Vardan , Rosen Jennifer E. , Lee Wen , Wartofsky Leonard , Felger Erin A.
Published: March 2020

Background and Objectives

The Afirma gene expression classifier (AGEC) has not been tested or validated in a high‐risk group, such as patients with Hashimoto's thyroiditis (HT). We hypothesized that AGEC would perform worse in patients with HT.

Methods

A retrospective review of patient charts in a single academic institution who underwent thyroidectomy between 2012 and 2017 was conducted. Patients with HT who underwent AGEC were identified to calculate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

Results

We identified 69 patients with HT and atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) on cytology who underwent AGEC analysis. The mean age of AGEC cohort was 50 years (range, 26‐77 years) with 90% female. The median nodule size was 1.9 cm (interquartile range [IQR], 1.2‐2.7 cm). Of the 69 patients, 62 showed suspicious AGEC of which 26 showed TC on surgical pathology. Of the seven benign AGEC, two showed TC on surgical pathology. The sensitivity, specificity, PPV, and NPV were 93%, 12%, 42%, and 71%, respectively. Of the entire AGEC cohort, 17 (43%) showed multicentric disease.

Conclusions

We observed a lower NPV for AGEC to rule out thyroid cancer in patients with HT, which reduces the utility of the test for this population.
TNFSF14, a novel target of miR‐326, facilitates airway remodeling in airway smooth muscle cells via inducing extracellular matrix protein deposition and proliferation
Authors: Zhang Hui , Yan Huan‐Li , Li Xiang‐Yu , Guo Yi‐Nan
Published: March 2020

As a common chronic respiratory disease, the incidence of asthma is increasing in recent years worldwide. Airway remodeling is the primary pathological basis of refractory asthma, but the studies about the underlying mechanism of airway remodeling was a lack. In the study, we aimed to investigate the effects and mechanisms of miR‐326 on airway remodeling in airway smooth muscle cells (ASMCs). The results showed that transforming growth factor‐β1 (TGF‐β1) accelerated matrix protein deposition by increasing the expression levels of collagen I and fibronectin, and promoted proliferative ability of ASMCs. However, miR‐326 was significantly downregulated in TGF‐β1‐treated ASMCs. MiR‐326 mimics robustly decreased the collagen I and fibronectin levels and inhibited cell proliferation of TGF‐β1‐treated ASMCs. Luciferase assay investigated that tumor necrosis factor superfamily member 14 (TNFSF14) was a direct target of miR‐326. The expression of TNFSF14 was negatively regulated by miR‐326. Moreover, exogenous TNFSF14 effectively reversed the inhibitory effects of miR‐326 overexpression on the expression levels of collagen I and fibronectin, and promoted cell proliferation of TGF‐β1‐treated ASMCs. In conclusion, miR‐326 suppressed matrix protein deposition and cell proliferation of TGF‐β1‐treated ASMCs via inhibiting TNFSF14. MiR‐326 might be a promising novel therapeutic target for asthma.
Predicting Obstructive Sleep Apnea Status With the Reflux Symptom Index in a Sleep Study Population
Authors: Teklu Meron , Gouveia Christopher J. , Yalamanchili Amulya , Ghadersohi Saied , Price Caroline P. E. , Bove Michiel , Attarian Hrayr P , Tan Bruce K.
Published: March 2020

Objectives/Hypothesis

Otolaryngologic symptoms of obstructive sleep apnea (OSA) and their diagnostic utility are not well studied. We aimed to elucidate the prevalence of otolaryngologic symptoms among patients being evaluated for OSA. Given findings that the Reflux Symptom Index (RSI) was strongly associated with OSA status, we evaluated the diagnostic utility of the RSI for predicting OSA status.

Study Design

Cross‐sectional.

Methods

We recruited 101 adults presenting for ambulatory polysomnograms to the Northwestern Sleep Disorders Center from July 2017 to July 2018. The Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Leicester Cough Questionnaire (LCQ), RSI, Gastroesophageal Reflux Disease Questionnaire, Sino‐Nasal Outcome Test‐22, Nasal Obstruction Symptom Evaluation, Eustachian Tube Dysfunction Questionnaire 7, and Headache Impact Test were administered. Polysomnogram results were subsequently obtained. Patients with OSA (apnea‐hypopnea index ≥ 5) and without OSA were compared.

Results

Of the 101 participants, 98 had valid sleep study results. Of those, 72 were diagnosed with OSA and 26 were not. The two groups differed significantly in age and body mass index (BMI). Of the questionnaires, only the RSI and LCQ means differed significantly, with worse symptoms in the OSA group (P = .003 and .014, respectively). Upon univariate regression, age, BMI, and RSI were associated with OSA status. Using regression coefficients, a clinical score of 2 (RSI) + 1.5 (BMI) + age yielded a diagnostic model (C‐statistic = 0.807, P < .001). A threshold score of 104.21 was 76.4% sensitive and 73.1% specific.

Conclusions

Patients with OSA have worse symptoms of laryngopharyngeal reflux as measured by the RSI. The addition of the RSI to the recognized factors of age and BMI improves diagnostic utility for OSA.

Level of Evidence

2 Laryngoscope, 2020
Effect of engineered nanoparticles on soil biota: Do they improve the soil quality and crop production or jeopardize them?
Authors: Pérez‐Hernández Hermes , Fernández‐Luqueño Fabián , Huerta‐Lwanga Esperanza , Mendoza‐Vega Jorge , Álvarez‐Solís José David
Published: March 2020

Nanoscience and nanotechnology have been shown to have the capacity to help study, manipulation,design, and synthesis of new nano‐sized materials to manufacture new products with desirable features never seen before. The unique properties of materials at nanoscale opens an excellent possibility for nanotechnology to be used in soil environmental remediation, and water, and air decontamination. In crop management, nanomaterials are used to regulate the controlled release of nutrients, fertilizers, and pesticides. However, it is not only necessary to expose the positive effects by the application of the nanomaterials but also to demonstrate the impacts on soil and nontarget organisms (plants, mesofauna, macrofauna, and soil microbiota). In this context, pieces of evidence on the adverse effects of engineered nanoparticles (ENP) on the physicochemical and biological properties of soils are discussed in this paper. We have found a diversity of contradictory results. The summaries, findings, and conclusions of most of the investigations support the need to understand the biological or physicochemical transformation and transport of ENP in soil, and in the plant‐organism relationship. Better understanding regarding the soil biota coupled with the ecological ENP behavior could ensure the safe use of ENP. Nanomaterials can change the physicochemical and biological properties of the soils; consequently, long‐term in situ field trials are required, and meanwhile, land‐application of nanomaterials should be limited to scientific experiments to fill knowledge gaps to not jeopardize the global food production or the environment and worldwide human health.
Intelligent 4D CT sequence scanning (i4DCT): First scanner prototype implementation and phantom measurements of automated breathing signal‐guided 4D CT
Authors: Werner René , Sentker Thilo , Madesta Frederic , Schwarz Annette , Vornehm Marc , Gauer Tobias , Hofmann Christian
Published: March 2020

Purpose

Four‐dimensional (4D) computed tomography (CT) imaging is an essential part of current 4D radiotherapy treatment planning workflows, but clinical 4D CT images are often affected by artifacts. The artifacts are mainly caused by breathing irregularity during data acquisition, which leads to projection data coverage issues for currently available commercial 4D CT protocols. It was proposed to improve projection data coverage by online respiratory signal analysis and signal‐guided CT tube control, but related work was always theoretical and presented as pure in silico studies. The present work demonstrates a first CT prototype implementation along with respective phantom measurements for the recently introduced intelligent 4D CT (i4DCT) sequence scanning concept (https://doi.org/10.1002/mp.13632).

Methods

Intelligent 4D CT was implemented on the Siemens SOMATOM go platform. Four‐dimensional CT measurements were performed using the CIRS motion phantom. Motion curves were programmed to systematically vary from regular to very irregular, covering typical irregular patterns that are known to result in image artifacts using standard 4D CT imaging protocols. Corresponding measurements were performed using i4DCT and routine spiral 4D CT with similar imaging parameters (e.g., mAs setting and gantry rotation time, retrospective ten‐phase reconstruction) to allow for a direct comparison of the image data.

Results

Following technological implementation of i4DCT on the clinical CT scanner platform, 4D CT motion artifacts were significantly reduced for all investigated levels of breathing irregularity when compared to routine spiral 4D CT scanning.

Conclusions

The present study confirms feasibility of fully automated respiratory signal‐guided 4D CT scanning by means of a first implementation of i4DCT on a CT scanner. The measurements thereby support the conclusions of respective in silico studies and demonstrate that respiratory signal‐guided 4D CT (here: i4DCT) is ready for integration into clinical CT scanners.
Franklins gläserne Engelszungen
Authors: Mathelitsch Leopold , Verovnik Ivo
Published: March 2020

Gläser zum Singen zu bringen ist ein beliebter Kneipensport. Das physikalische Prinzip nutzen die Glasharfe und die von Benjamin Franklin erfundene Glasharmonika, die im 18. und 19. Jahrhundert populär waren. Der über den Rand streichende Finger versetzt das Glas über den Haftgleiteffekt in ein glockenähnliches Schwingen. Das Klangspektrum entspricht fast einer harmonischen Schwingung.
Ionenstrahlen erzeugen periodische, magnetische Domänenstrukturen
Authors: Nord Magnus , McGrouther Damien , Potzger Kay , Bali Rantej
Published: March 2020

Bei der Ausbildung magnetischer Domänen in Nanostrukturen spielt die magnetische Anisotropie eine wesentliche Rolle. Sie kann durch die äußere Form der magnetischen Struktur, aber auch durch Verzerrungen im Kristallgitter beeinflusst werden. In einem Material, dessen magnetische Eigenschaften durch Ionenbestrahlung verändert werden, lassen sich beide Beiträge gleichzeitig erzeugen. Dieses Phänomen hat unsere Gruppe am Helmholtz‐Zentrum Dresden‐Rossendorf (HZDR) ausgenutzt, um Domänenstrukturen gezielt einzustellen [1].
Satellitendaten enthüllen Erdstruktur unter der Antarktis
Authors: Pappa Folker , Ebbing Jörg
Published: March 2020

Die geophysikalischen Eigenschaften der Erdkruste und des Erdmantels unter dem Kontinent Antarktika sind noch immer relativ schlecht erforscht. Mithilfe von Satellitendaten des Gravitationsfelds der Erde konnten nun Dichte‐ und Temperaturverteilung unterhalb der Antarktis neu abgeschätzt werden. Die Ergebnisse helfen unter anderem dazu, Ausgleichsbewegungen der festen Erde als Reaktion auf Eismassenveränderungen besser zu modellieren.
Atomkerne besitzen Neutronenhüllen
Authors: Neff Thomas
Published: March 2020

Vor 50 Jahren gelang der erste Nachweis von Neutronenhüllen in Atomkernen. Heute wird dieses Phänomen sowohl experimentell als auch theoretisch detailliert untersucht. Es ist auch für die Astrophysik bedeutend.
Finite‐time optimal control for interconnected nonlinear systems
Authors: Li Yongming , Yang Tingting , Liu Lu , Feng Gang , Tong Shaocheng
Published: March 2020

This work addresses the finite‐time optimal control problem for a class of interconnected nonlinear systems with powers of positive odd rational numbers. A series of homogeneous controllers, which are capable of guaranteeing the local finite‐time stability of the closed‐loop systems, are first developed using the adding one power integrator method and backstepping technique. Then, the nested saturation controllers are further proposed to achieve global finite‐time stability. Furthermore, the corresponding design parameters are optimized, and thus, an optimal controller is obtained. A numerical simulation example is finally given to illustrate the effectiveness of the proposed control strategy.
Pth moment regional stability/stabilization and generalized pole assignment of linear stochastic systems: Based on the generalized ‐representation method
Authors: Zhang Huasheng , Xia Jianwei , Shen Hao , Zhang Baoyong , Wang Zhen
Published: March 2020

This paper investigates pth moment regional stability, stabilization, and generalized pole assignment of stochastic systems, which are most useful in many specific systems and applications. With the help of the generalized ‐representation method, the necessary and sufficient conditions of pth moment regional stability and stabilization of stochastic systems are addressed. Meanwhile, the generalized pole assignment of stochastic systems is also considered. Finally, two examples are presented to show the effectiveness of the proposed methods.
Reference databases, primer choice, and assay sensitivity for environmental metabarcoding: Lessons learnt from a re‐evaluation of an eDNA fish assessment in the Volga headwaters
Authors: Schenekar Tamara , Schletterer Martin , Lecaudey Laurène A. , Weiss Steven J.
Published: March 2020

Biodiversity monitoring via environmental DNA, particularly metabarcoding, is evolving into a powerful assessment tool for riverine systems. However, for metabarcoding to be fully integrated into standardized monitoring programmes, some current challenges concerning sampling design, laboratory workflow, and data analysis need to be overcome. Here, we review some of these major challenges and potential solutions. We further illustrate three potential pitfalls, namely the choice of suitable metabarcoding primers, the necessity of complete reference databases, and varying assay sensitivities, by a reappraisal of our‐own recently carried out metabarcoding study in the Volga headwaters. TaqMan qPCRs had detected catfish (Silurus glanis) and European eel (Anguilla anguilla), whereas metabarcoding had not, in the same samples. Furthermore, after extending the genetic reference database by 12 additional species and re‐analysing the metabarcoding data, we additionally detected the Siberian spiny loach (Cobitis sibirica) and Ukrainian brook lamprey (Eudontomyzon mariae) and reassigned the operational taxonomic units previously assigned to Misgurnus fossilis to Cobitis sibirica. In silico analysis of metabarcoding primer efficiencies revealed considerable variability among primer pairs and among target species, which could lead to strong primer bias and potential false‐negatives in metabarcoding studies if not properly compensated for. These results highlight some of the pitfalls of eDNA‐metabarcoding as a means of monitoring fish biodiversity in large rivers, which need to be considered in order to fully unleash the full potential of these approaches for freshwater biodiversity monitoring.
Silver‐Laden Black Phosphorus Nanosheets for an Efficient In Vivo Antimicrobial Application
Authors: Liang Meijuan , Zhang Minyi , Yu Shanshan , Wu Qiong , Ma Kang , Chen Yingying , Liu Xiaoqing , Li Chunsen , Wang Fuan
Published: March 2020

Nanobactericides represent one of the most efficient and promising strategies for eliminating bacterial infection considering the increasing resistance threats of conventional antibiotics. Black phosphorus (BP) is the most exciting postgraphene layered 2D nanomaterial with convincing physiochemical properties, yet the study of BP‐based antibiotics is still in its infancy. Here, a compact silver nanoparticle (AgNP)–doped black phosphorus nanosheet (BPN) is constructed to synergistically enhance solar disinfection through the promoted reactive oxygen species (ROS) photogeneration, which is attributed to the improved electron–hole separation and recombination of BPNs as revealed from the systematic experimental studies. An in‐depth density functional theory (DFT) calculation confirms that the integrated AgNPs provide a preferred site for facilitating the adsorption and activation of O2, thus promoting the more efficient and robust ROS generation on BPN–AgNP nanohybrids. Besides the enhanced photoinduced ROS, the anchored AgNPs simultaneously lead to a dramatically increased affinity toward bacteria, which facilitates a synergetic pathogen inactivation. Significantly, the convincing antimicrobial BPN–AgNP contributes to the prominent wound healing and antimicrobial ability in vivo with minimized biological burden. This sophisticated design of new 2D nanohybrids opens a new avenue for further exploiting BP‐based nanohybrids in portable bandage and broad‐spectrum disinfection applications.
What drives new product innovation in China? An integrative strategy tripod approach
Authors: Heredia Jorge , Yang Xiaohua , Flores Alejandro , Rubiños Cathy , Heredia Walter
Published: March 2020

This study explores the determinants that drive new product innovation by employing the integrative strategy tripod approach. We analyze data from the World Bank Enterprise Survey on 1,692 manufacturing firms in China using a novel methodological approach (a fuzzy set qualitative comparative analysis) that focuses on multiple conjectural causations. Interestingly, our findings suggest that R&D investment alone is not a sufficient condition to facilitate a firm's product innovation, but stable government policy is a necessary condition for R&D investment. Even with a low level of R&D investments, it can achieve innovation if those investments are made in conjunction with high technology information system investments for supporting customer relationships. Finally, we find that when firms perceive informal competition to be a significant obstacle to their operations and R&D investment, they tend to engage in corrupt actions to create innovation. Implications for research and practice are provided.
Subsidized to change? The impact of R&D policy on regional technological diversification
Authors: Mewes Lars , Broekel Tom
Published: March 2020

Previous research shows ample evidence that regional diversification is strongly path dependent, as regions are more likely to diversify into related than unrelated activities. In this paper, we ask whether contemporary innovation policy in form of R&D subsidies intervenes in the process of regional diversification. We focus on R&D subsidies and assess whether they cement existing path dependent developments, or whether they help in breaking these by facilitating unrelated diversification. To investigate the role of R&D policy in the process of regional technological diversification, we link information on R&D subsidies with patent data and analyze the diversification of 141 German labor-market regions into new technology classes between 1991 and 2010. Our findings suggest that R&D subsidies positively influence regional technological diversification. In addition, we find significant differences between types of subsidy. Subsidized joint R&D projects have a larger effect on the entry probabilities of technologies than subsidized R&D projects conducted by single organizations. To some extent, collaborative R&D can even compensate for missing relatedness by facilitating diversification into unrelated technologies.
Clinical translation of 18F-fluoropivalate – a PET tracer for imaging short-chain fatty acid metabolism: safety, biodistribution, and dosimetry in fed and fasted healthy volunteers
Authors: Dubash Suraiya R. , Keat Nicholas , Kozlowski Kasia , Barnes Chris , Allott Louis , Brickute Diana , Hill Sam , Huiban Mickael , Barwick Tara D. , Kenny Laura , Aboagye Eric O.
Published: March 2020

Background

Fatty acids derived de novo or taken up from the extracellular space are an essential source of nutrient for cell growth and proliferation. Radiopharmaceuticals including 11C-acetate, and 18F-FAC (2-18F-fluoroacetate), have previously been used to study short-chain fatty acid (SCFA) metabolism. We developed 18F-fluoropivalate (18F-FPIA; 3-18F-fluoro-2,2-dimethylpropionic acid) bearing a gem-dimethyl substituent to assert metabolic stability for studying SCFA metabolism. We report the safety, biodistribution, and internal radiation dosimetry profile of 18F-FPIA in 24 healthy volunteers and the effect of dietary conditions.

Materials and methods

Healthy volunteer male and female subjects were enrolled (n = 24), and grouped into 12 fed and 12 fasted. Non-esterified fatty acids (NEFA) and carnitine blood measurements were assessed. Subjects received 159.48 MBq (range, 47.31–164.66 MBq) of 18F-FPIA. Radiochemical purity was > 99%. Safety data were obtained during and 24 h after radiotracer administration. Subjects underwent detailed multiple whole-body PET/CT scanning with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated using OLINDA 1.1.

Results

All subjects tolerated 18F-FPIA with no adverse events. Over 90% of radiotracer was present in plasma at 60 min post-injection. The organs receiving highest absorbed dose (in mGy/MBq) were the liver (0.070 ± 0.023), kidneys (0.043 ± 0.013), gallbladder wall (0.026 ± 0.003), and urinary bladder (0.021 ± 0.004); otherwise there was low tissue uptake. The calculated effective dose using mean organ residence times over all 24 subjects was 0.0154 mSv/MBq (SD ± 0.0010). No differences in biodistribution or dosimetry were seen in fed and fasted subjects, though systemic NEFA and carnitine levels reflected fasted and fed states.

Conclusion

The favourable safety, imaging, and dosimetric profile makes 18F-FPIA a promising candidate radiotracer for tracing SCFA metabolism.
Performance determination of high-purity N2-PSA-plants
Authors: Marcinek A. , Guderian J. , Bathen D.
Published: March 2020

The global demand on highly purified gases provided by energy-efficient separation processes grows steadily since decades. An example of particular industrial relevance is nitrogen generated by pressure swing adsorption from compressed air. A kinetically based separation of oxygen from nitrogen is possible by means of carbon molecular sieves (CMS) since oxygen adsorbs remarkably faster in CMS than nitrogen. Even high product purities (5–1000 ppm O2) are easily achievable in commercial generators. However, only a few studies present experimental findings in this purity range. That comes as no surprise, since experimental conditions are not standardised and the determination of N2-PSA performance indicators still creates an experimental challenge. Moreover, the design of the set-up remarkably influences the experimental results. Thus it is the motivation of this study to develop a multi-step strategy, comprising the definition of a reference process, the derivation of explicit and implicit performance indicators based on either flow meter readings or macroscopic material balances, a verification strategy for experimentally obtained data, and an error consideration, which advices accuracy requirements for analysers and flow meters. The effect of cycle time and operating temperature on the performance indicators is exemplarily studied at high purities by means of the proposed strategy.
Cybervetting job applicants on social media: the new normal?
Authors: Jacobson Jenna , Gruzd Anatoliy
Published: March 2020

With the introduction of new information communication technologies, employers are increasingly engaging in social media screening, also known as cybervetting, as part of their hiring process. Our research, using an online survey with 482 participants, investigates young people’s concerns with their publicly available social media data being used in the context of job hiring. Grounded in stakeholder theory, we analyze the relationship between young people’s concerns with social media screening and their gender, job seeking status, privacy concerns, and social media use. We find that young people are generally not comfortable with social media screening. A key finding of this research is that concern for privacy for public information on social media cannot be fully explained by some “traditional” variables in privacy research. The research extends stakeholder theory to identify how social media data ethics should be inextricably linked to organizational practices. The findings have theoretical implications for a rich conceptualization of stakeholders in an age of social media and practical implications for organizations engaging in cybervetting.
The Big Bang is a Coordinate Singularity for $$k = -1$$ Inflationary FLRW Spacetimes
Authors: Ling Eric
Published: March 2020

We show that the big bang is a coordinate singularity for a large class of$$k = -1$$k=-1inflationary FLRW spacetimes which we have dubbed ‘Milne-like.’ By introducing a new set of coordinates, the big bang appears as a past boundary of the universe where the metric is no longer degenerate—a result which has already been investigated in the context of vacuum decay (Coleman and De Luccia in Phys Rev D 21:3305–3315, 1980). We generalize their results and approach the problem from a more mathematical perspective. Similar to how investigating the geometrical properties of the$$r = 2m$$r=2mevent horizon in Schwarzschild led to a better understanding of black holes, we believe that investigating the geometrical properties of the big bang coordinate singularity for Milne-like spacetimes could lead to a better understanding of cosmology. We show how the mathematics of these spacetimes may help illuminate certain issues associated with dark energy, dark matter, and the universe’s missing antimatter.