bluuebunny/crossref_metadata_2025 huggingface dataset:
A new set of 20 Multi‐InDel markers for forensic application
Authors: Liu Jinding , Zhang Xiuying , Zhang Xiaomeng , Li Wenyan , Gao Linlin , Li Jing , Wang Jiaqi , Liu Zidong , Liu Yao , Yan Jiangwei , Zhang Gengqian
Published: March 2022

Insertion/deletion markers (InDels) become an important marker for forensic medicine because of their compatible typing techniques with STRs and lower mutation rates. Recent years, a new kind of DNA marker named Multi‐InDel was reported as characterized by two or more tightly linked InDel loci within a short length of physical position, usually 200–300 nucleotides. Many pieces of research showed that Multi‐InDels had excellent application values in ancestry inference and forensic medicine. Since the identical number of insertion/deletion nucleotides of the InDel markers that composing the Multi‐InDel marker, the genotypes of most reported Multi‐InDels could not be directly typed by capillary electrophoresis (CE) due to the lack of length discrepancy among the composing InDel sequence. In this study, we applied a typing system of 20 Multi‐InDels including 41 InDels, whose genotypes could be deduced by CE and assessed their potential applications in forensic medicine. A total of 200 unrelated Chinese Han individuals and five mother‐child‐father trios with proven paternity with one STR locus transmission incompatibilities from Shanxi province were genotyped by the multiplex system. The results showed that a total of 70 specific alleles were observed, more than three alleles were observed in 19 loci and seven alleles were observed in one locus. The combined probability of exclusion and the combined power of discrimination were 0.992 and 0.99999999993, respectively. This study demonstrates their potential usefulness for individual identification and paternity tests. The development of Multi‐InDels provided another genetic tool inherent in higher polymorphic and lower mutation rates.
Yttrium‐dopedSn3O4two‐dimensionalelectron transport material for perovskite solar cells with efficiency over 23%
Authors: Li Sheng , Liu Jiale , Liu Shuang , Zhang Deyi , Liu Chao , Li Daiyu , Qi Jianhang , Hu Yue , Mei Anyi , Han Hongwei
Published: March 2022

The two‐dimensional mixed‐valence tin oxide Sn3O4with a low defect density of states and suitable energy band structure has shown great potential as the electron transport layer (ETL) for perovskite solar cells (PSCs). However, the electron density of Sn3O4is low and should be modulated to demonstrate its application for more efficient PSCs. Here, Sn3O4is doped with yttrium (Y) to optimize its electronic properties and improve the performance of PSCs based on Sn3O4ETL. The conductivity of Sn3O4is improved from 6.6 × 10−4to 2.05 × 10−3 S m−1with increased electron density by Y doping. Meanwhile, the Fermi level of Sn3O4is also upshifted after doping. The increased electron density and upshifted Fermi level enhance the electron extraction capability of Sn3O4and built‐in potential in PSCs. By doping the Sn3O4ETL with Y, the power conversion efficiency of PSCs is successfully boosted to 23.05%.

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How immigration affects the welfare state in the short and long run: Differences between social spending and policy generosity
Authors: Römer Friederike
Published: March 2022

To assess how immigration affects welfare states, studies have mainly used social expenditure as an indocator of welfare state strength, with inconclusive results. Furthermore, the relationship between immigration and different social policy fields has been mostly overlooked, and temporal dynamics have often been ignored. Using data on 21 OECD countries 1980–2010, this paper tests how immigration relates to (a) social expenditures, and (b) generosity of policy in regard to unemployment benefits and public pensions. Using dynamic and static panel models and controlling for relevant structural factors there is evidence for a robust and significant negative association between net migration and spending in the short term, with no evidence that migration increases social spending in later years. Some evidence is found for the compensation hypothesis, i.e., a positive association between net migration and unemployment generosity. A robust positive association was also found for net migration and pension generosity. There is thus little support that migration has a burdening or undermining effect on the welfare state.
Experimental investigation and numerical modeling of rocking cross laminated timber walls on a flexible foundation
Authors: Wichman Sarah , Berman Jeffrey W. , Pei Shiling
Published: March 2022

With recent developments of engineered wood products such as cross laminated timber, mass timber buildings in areas of high seismicity are becoming feasible and offer benefits such as faster construction and unique architectural features. It has also opened the door to creating seismically resilient lateral systems that sustain minor and reparable damage during large earthquakes. This paper presents a numerical modeling procedure for mass timber rocking wall lateral system with distributed spring elements to model base rocking. This modeling technique was validated by comparing the behavior with results from the full‐scale two‐story shake table test on a mass timber building with coupled CLT rocking walls completed as part of the NHERI TallWood Project. Although the lateral system performed better than expected during testing, it was determined that the flexibility of the foundation actually limited damage to the rocking wall panels. By adjusting the numerical model to represent a rigid foundation boundary condition, it was determined that the wall system would have experienced more damage, but would have still met design performance objectives had it been tested on a rigid foundation.
Electric vehicles charging in India: Infrastructure planning and policy aspects
Authors: Veerendra Arigela Satya , Ravindra Manam , Ramesh Adireddy , Manoz Kumar Reddy Karri , Punya Sekhar Chavali
Published: March 2022

Following years, electric vehicles (EVs) are promising technology for shifting scattered exhaust emissions in mega‐cities to integrated power plants in rural areas, especially in urban areas. Transport sector electrification and increased popularity of EVs make scientists and researchers, search for charging stations. The ideal position, charge scheduling, and developed charging infrastructure are the primary concern for the large‐scale deployment of EVs. This paper describes the possible demand for EVs charging station infrastructure and challenges in the Indian situation. Along these lines, this study also provides the research community with the latest developments and research findings of charging infrastructure for EVs in India.
Burden and benefit—A mixed methods study of informal Amyotrophic Lateral Sclerosis caregivers in Ireland and the Netherlands
Authors: Kennedy Polly , Conroy Éilís , Heverin Mark , Leroi Iracema , Beelen Anita , van den Berg Leonard , Hardiman Orla , Galvin Miriam
Published: March 2022

Objectives

Amyotrophic Lateral Sclerosis (ALS) is a systemic and terminal disorder of the central nervous system which causes paralysis of limbs, respiratory and bulbar muscles, impacting on physical, communication, cognitive and behavioural functioning. Informal caregivers play a key role in the care of people with ALS. This study aimed to explore experiences of burden along with any beneficial aspects of caregiving in ALS. An understanding of both burden and benefit is important to support the informal caregiver and the person with ALS.

Methods/Design

This exploratory mixed methods study characterizes two groups of informal caregivers in Ireland (n = 76) and the Netherlands (n = 58). In a semi‐structured interview, quantitative data were collected in the form of standardized measures assessing psychological distress, quality of life and burden. Qualitative data were collected from an open ended question, in which caregivers identified positive aspects in their caregiving experience. These data types were purposefully mixed in the analysis and interpretation stages, to provide a greater depth of evidence through diverse research lenses.

Results

The caregiver cohorts were predominantly female (69%) and spouse/partners (84%) of the person with ALS. Greater levels of self‐assessed burden were found among the caregivers in the Netherlands (p < 0.05), and higher levels of quality of life among the cohort from Ireland (p < 0.05). Themes generated through qualitative analysis identified caregiver satisfaction, ability to meet the patient's needs and the (re) evaluation of meaning and existential aspects of life as positive aspects of caregiving. Existential factors were identified frequently by the caregivers in Ireland, and personal satisfaction and meeting their care recipient's needs by caregivers in the Netherlands. Three percent of all respondents reported there was nothing positive about caregiving.

Conclusions

Based on our findings, we suggest that both burden and the presence of positive factors should be evaluated and monitored. The possibility of concurrent positive and challenging experiences should be considered in the design and delivery of supportive interventions for informal caregivers.
Unsteady nanofluid flow between two spinning expanding disks with continuous vertical motion under the influence of modified Hall effect
Authors: Sk Md Tausif , Das Kalidas , Kundu Prabir K.
Published: March 2022

The principle aim of this article is to detect the effects of externally applied magnetic force in the nanofluid flow, flowing between two co‐axially rotating and expanding disks where the upper disk is continuously moving vertically upward and downward. Also, the modified Hall Effect has been considered as an effective factor of the flow. The lower disk is vertically static. The rotation and vertical motion of the disks create a three‐dimensional flow of nanofluid. Heat and mass density along with the motion of the flow has been analyzed under the variation in magnetic and Hall parameters. The findings have been compared with the results in Von Karman flow of nanofluid between two rotating and stretching disks. The velocity components have been largely influenced by magnetic and Hall parameters in case of downward movement of the upper disk. The fluid temperature is detected higher in case of upward velocity and lower in case of the downward motion of the upper disk. The heat transferability of the disks is effected differently at two different disks with the influence of magnetic force and Hall effect.
Insight into three‐dimensional flow of three different dynamics of nanofluids subject to thermal radiation: The case of water–cobalt ferrite, water–manganese–zinc ferrite, and water–magnetite
Authors: Khashi'ie Najiyah S. , Wahid Nur S. , Arifin Norihan Md , Pop Ioan
Published: March 2022

Magnetic nanofluids (MNFs) have been widely applied in both biomedical and environmental sectors along with the substantial growth of numerical and experimental studies. Hence, in view of the unique properties in MNFs, the aim of this study is to analyze numerically the three‐dimensional flow of MNFs (Fe3O4–water, CoFe2O4–water, Mn–ZnFe2O4–water) over a shrinking surface with suction and thermal radiation effects. The single‐phase nanofluid model is reduced into a system of ordinary differential equations by applying the similarity transformation. The results are then, obtained using the bvp4c solver in the Matlab software. The results reveal that for the shrinking case, the Mn–ZnFe2O4–water nanofluid has the maximum thermal rate followed by CoFe2O4–water and Fe3O4–water, respectively. Meanwhile, Fe3O4–water expands the separation value of boundary layer flow greater than other tested MNFs. Besides this, the suction parameter is also a contributing factor for the thermal enhancement of all MNFs.
Impact of irrigation on farm household diet quality: Evidence from Ethiopia
Authors: Ahmed Musa Hasen
Published: March 2022

In theory, irrigation could affect farm households' nutritional status in either direction. On the one hand, irrigation may improve nutritional status by boosting farm productivity and household income. On the other hand, it may deter diet quality by shifting farmers' attention from nutrition‐rich food to cash crops. This study examines the impact of irrigation schemes on farm households' nutritional status using nationally representative data from Ethiopia. Using the endogenous switching regression model, the study shows that irrigation improves diet quality. In addition, the study also identifies the production of micronutrient‐rich crops such as vegetables and fruit and the adoption of productivity‐enhancing inputs as the main pathways through which irrigation affects dietary quality. Hence, irrigation can be considered a viable instrument to enhance the diet quality of smallholders, and efforts should be made to tackle constraints that impede the adoption of irrigation technologies.
Guiding their Thinking: A Formative Study of Digital Source Evaluation
Authors: Walsh‐Moorman Beth , Pytash Kristine E.
Published: March 2022

Using pre‐ and post‐ intervention data, this formative study explores instructional moves designed to guide students' critical thinking as they engage in lateral reading and digital source evaluation. Working in a dual enrollment composition classroom, researchers identified and addressed three areas of need: considering context when determining source authority or credibility, developing skilled web searching strategies and engaging in complex and multi‐stepped lateral reading moves. Results demonstrated purposeful modeling and direct instruction of related digital skills positioned participants for more nuanced and developed thinking when engaging in digital source evaluation through lateral reading.
The effect and underlying mechanisms of titanium dioxide nanoparticles on glucose homeostasis: A literature review
Authors: Mohammadparast Vida , Mallard Beth L.
Published: March 2022

Titanium dioxide (TiO2) is used extensively as a white pigment in the food industry, personal care, and a variety of products of everyday use. Although TiO2has been categorized as a bioinert material, recent evidence has demonstrated different toxicity profiles of TiO2nanoparticles (NPs) and a potential health risk to humans. Studies indicated that titanium dioxide enters the systemic circulation and accumulates in the lungs, liver, kidneys, spleen, heart, and central nervous system and may cause oxidative stress and tissue damage in these vital organs. Recently, some studies have raised concerns about the possible detrimental effects of TiO2NPs on glucose homeostasis. However, the findings should be interpreted with caution due to the methodological issues. This article aims to evaluate current evidence regarding the effects of TiO2NPs on glucose homeostasis, including possible underlying mechanisms. Furthermore, the limitations of current studies are discussed, which may provide a comprehensive understanding and new perspectives for future studies in this field.
Value versus hyper growth and expected stock returns: In memory of Simon Benninga
Authors: Taussig Roi D.
Published: March 2022

This essay expands the theory on value versus growth stocks by adding another component to growth stocks. The new component is the substantial size growth (sg) (market capitalization growth). As shown in the financial literature, growth stock returns are lower than value stock returns. When sg is exploding, the growth stock returns are even substantially lower. This new variable is highly significant both statistically and economically.
Biological variation and reference change values of serum Mac‐2–binding protein glycosylation isomer (M2BPGi)
Authors: Choi Rihwa , Chun Gayoung , Go Unyeong , Lee Sang Gon , Lee Eun Hee
Published: March 2022

Background

Limited data are available with regard to biological variations of the Mac‐2–binding protein glycosylation isomer (M2BPGi), a liver fibrosis biomarker.

Methods

Long‐term biological variation of M2BPGi was investigated using longitudinally measured M2BPGi test results from healthy Korean adult subjects. One‐way analysis of variance (ANOVA) tests were used to calculate the reference change value (RCV) of M2BPGi based on biological variation estimates. Furthermore, asymmetric RCV was calculated according to a recent publication of the European Federation of Clinical Chemistry and Laboratory Medicine Working Group on Biological Variation and Task Group for the Biological Variation Database (EFLM TG‐BVD).

Results

A total of 363 test results from 174 Korean subjects undergoing general health checkups were requested from 13 local clinics and hospitals during a 38‐month period. The within‐subjects biological variation (CVI), between‐subject biological variation (CVG), analytical variation (CVA), RCV, and individuality index (II) values for serum M2BPGi were 23.3%, 30.0%, 4.3%, 65.6%, and 0.78, respectively. Asymmetric RCV calculated using formulae by a recent EFLM TG‐BVD publication ranged from −41.9 to 72.0%. Desirable analytical performance specifications for M2BPGi derived from biological variation were as follows: imprecision 11.6%, bias 9.6%, and total allowable error 28.7%.

Conclusions

RCV based on biological estimates may be helpful for evaluating and interpreting serial M2BPGi measurements by physicians and in clinical laboratories.
Alterations of gut microbiota‐derived metabolites in gestational diabetes mellitus and clinical significance
Authors: Gao Yajie , Chen Haimin , Li Jialin , Ren Shuaijun , Yang Zhenglun , Zhou Yuping , Xuan Rongrong
Published: March 2022

Background

The change in the characteristics of the gut microbiota is linked to gestational diabetes mellitus (GDM). However, whether and how the gut microbiota‐derived metabolites change in GDM is uncertain. Here, we aimed to determine associations between the gut microbiota‐derived metabolites and GDM.

Methods

Using targeted metabolomics approaches, 7 types of short‐chain fatty acids (SCFAs), 38 types of bile acids (BAs), and 5 types of trimethylamine N‐oxide (TMAO), and its derivatives of serum samples were obtained from pregnant women with GDM (n = 24), and healthy pregnant controls (HC, n = 28) were detected to identify the metabolic signature of GDM to investigate the potential biomarkers. Moreover, we assessed the associations between gut microbiota‐derived metabolites and clinical parameters.

Results

In our study, the gut microbiota‐derived metabolites signatures were significantly different between GDM and HC. Quantitative results showed the levels of isobutyric acid, isovaleric acid, valeric acid, caproic acid, GUDCA, THDCA + TUDCA, and LCA‐3S were significantly higher in GDM, but the level of TMAO and its derivatives did not change significantly. Some altered gut microbiota‐derived metabolites were significantly correlated with glucose and lipid levels. Receiver‐operating characteristic (ROC) analysis of generalized linear models showed that gut microbiota‐derived metabolites may be potential biomarkers of GDM.

Conclusion

This study highlights gut microbiota‐derived metabolites alterations in GDM and correlation of the clinical indicators, which provides a new direction for future studies aiming to novel serum biomarker for early detection or target of drug therapy of GDM.
Treatment success or failure? Using a narrative interview to supplement ROM
Authors: Ogles Benjamin M. , Goates‐Jones Melissa K. , Erekson David M.
Published: March 2022

Although routine outcome monitoring (ROM) has been demonstrated to improve therapy efficiency and effectiveness, categorizations of improvement or deterioration using ROM measures (typically global symptoms) may not always be consistent with the lived experience of the client. A recent line of investigation examines these discrepancies and recommends supplementing ROM with additional measures or narrative interviews. In this case study, we use qualitative analysis of a posttreatment interview to specifically examine the client's perspective of discordant outcome when ROM indicated that the client deteriorated during treatment and the client reported retrospective improvement. We find that the interview provides a unique and helpful narrative perspective that supplements ROM. Findings suggest it may be useful to supplement ROM with approaches that extend beyond global symptom measurement and that outcomes from aggregated patient‐focused research may be more complex than anticipated.
Study on multiplanar measurements of infant hips with three‐dimensional ultrasonography
Authors: He Jingnan , Cui Ligang , Chen Tao , Lyu Xuemin , Yu Jingmiao , Guo Wen , Wang Dandan , Qin Xiaoting , Zhao Yibing , Zhang Shumin
Published: March 2022

Purpose

An automatic evaluation technology based on artificial intelligence and three‐dimensional ultrasonography (3D US) is proposed for hip US inspection plane selection. This study aimed to evaluate the consistency of the α angle as measured using 3D US to select the section plane and two‐dimensional ultrasonography (2D US) to manually select the Graf image, as well as to explore the feasibility of diagnosing developmental dysplasia of the hip (DDH) using 3D US and reconstruction technology.

Methods

A total of 216 infant hips were included and assessed by doctors using 3D US layer‐by‐layer. The researchers used a computer to identify the coronal images that met the Graf standard and then compared the αX values obtained with the αG values measured artificially by 2D US.

Results

Compared with 2D US, 3D US more clearly showed the relative positions of the ilium, ischia, and pubis. The measured α value of the optimal section obtained by 3D US showed good agreement with the measured α value of the standard Graf section.

Conclusion

The artificial intelligence and 3D US‐based automatic evaluation technology for section selection and inspection for DDH showed good agreement with the Graf method based on standard sections.
Teeth out of proportion: Smaller horse and cattle breeds have comparatively larger teeth
Authors: Clauss Marcus , Heck Laura , Veitschegger Kristof , Geiger Madeleine
Published: March 2022

There are different descriptions of allometric relationships between important components of the mammalian skull. Craniofacial evolutionary allometry describes a pattern of increasing facial cranium in larger skulls. Another body of literature describes disproportionately larger teeth in smaller species or specimens, matching anecdotal observations with dental problems in dwarf breeds whose teeth appear “too large for their skulls.” We test the scaling of tooth row length with body size and skull length in a data set comprising 114 domestic horses (representing 40 breeds) and in another data set of 316 domestic cattle (of >60 breeds). We demonstrate that smaller skulls have a relatively longer tooth row in both horses and cattle; larger specimens have relatively shorter tooth rows. Whereas in horses, larger skulls have a relatively longer diastema, the distance of the mesial maxillary premolar to the premaxilla was proportional to cranium length in cattle. While the reasons for these patterns remain to be detected, they support the hypothesis that tooth size might be less “evolvable,” in terms of time required for changes, than body size. The pattern may affect (i) the selective breeding for dwarf breeds by setting minimum constraints for skull size, as described previously for domestic horses with the same data set; (ii) the susceptibility of small breeds for dental problems; and (iii) differences in chewing efficiency between breeds of different sizes. The findings support the existing concept that scaling of tooth to body size across taxa becomes more isometric the longer these taxa are separated in evolutionary time.
Cytokine responses to LPS in reprogrammed monocytes are associated with the transcription factor PU.1
Authors:   X-HiDE Consortium, Tuerxun Kedeye , Midtbö Kristine , Särndahl Eva , Vorontsov Egor , Karlsson Roger , Persson Alexander , Kruse Robert , Eklund Daniel
Published: March 2022

Myeloid-derived suppressor cells (MDSCs) are functionally immunosuppressive cells that arise and expand during extensive inflammatory conditions by increased hematopoietic output or reprogramming of immune cells. In sepsis, an increase of circulating MDSCs is associated with adverse outcomes, but unique traits that can be used to identify increased activity of MDSCs are lacking. By using endotoxin tolerance as a model of sepsis-induced monocytic MDSCs (M-MDSC-like cells), this study aims to identify the mediator and transcriptional regulator profile associated with M-MDSC activity. After analyzing 180 inflammation-associated proteins, a profile of differentially expressed cytokines was found in M-MDSC-like cells versus normal monocytes stimulated with LPS. These cytokines were associated with 5 candidate transcription factors, where particularly PU.1 showed differential expression on both transcriptional and protein levels in M-MDSC-like cells. Furthermore, inhibition of PU.1 led to increased production of CXCL5 and CCL8 in M-MDSC-like cells indicating its role in regulating the ability of M-MDSC-like cells to recruit other immune cells. Taken together, the study identifies a unique profile in the pattern of immune mediators defining M-MDSC activity upon LPS stimulation, which offers a functional link to their contribution to immunosuppression.
Prospective Evaluation of Virtual MR Elastography With Diffusion‐Weighted Imaging in Subjects With Nonalcoholic Fatty Liver Disease
Authors: Hanniman Elyisha , Costa Andreu F. , Bowen Chris V. , Abdolell Mohamed , Stueck Ashley , McLeod Magnus , Peltekian Kevork , Rioux James , Clarke Sharon E.
Published: March 2022

Background

Non‐alcoholic fatty liver disease (NAFLD) is increasingly common worldwide and can lead to the development of cirrhosis, liver failure and cancer. Virtual magnetic resonance elastography (VMRE), which is based on a shifted apparent diffusion coefficient (sADC), is a potential noninvasive method to assess liver fibrosis without the specialized hardware and expertise required to implement traditional MR elastography (MRE). Although hepatic steatosis is known to confound ADC measurements, previous studies using VMRE have not corrected for hepatic fat fraction.

Purpose

To compare VMRE, corrected for the confounding effects of unsuppressed fat signal, to MRE and biopsy in subjects with suspected NAFLD.

Study Type

Prospective, cross‐sectional.

Population

A total of 49 adult subjects with suspected NAFLD (18 male; median age 55 years, range 33–74 years) who underwent liver biopsy.

Field strength/Sequence

 3T, diffusion‐weighted spin echo planar, chemical‐shift encoded (IDEAL IQ) and MRE sequences.

Assessment

Two observers drew regions of interest on sADC, proton density fat fraction and MRE‐derived stiffness maps. Fat‐corrected sADC values were used to calculate the diffusion‐based shear modulus according to the VMRE method. Predicted fibrosis stage for MRE and VMRE was determined using previously published cut‐off values.

Statistical Tests

The relationship between VMRE and MRE was assessed with least‐squares linear regression (coefficient of determination, R2). Agreement between MRE and VMRE‐predicted fibrosis stage was evaluated with a kappa coefficient and accuracy compared using McNemar's test. A one‐way ANOVA determined if the fat‐corrected sADC (VMRE) and MRE differed by fibrosis stage. A P value < 0.05 was considered statistically significant.

Results

Least squares regression of VMRE vs. MRE revealed R2 = 0.046 and a slope that was not significantly different from zero (P = 0.14). There was no agreement between MRE and VMRE‐predicted fibrosis stage (kappa = −0.01). The proportion of correctly predicted fibrosis stage was significantly higher for MRE compared to VMRE. MRE was significantly associated with fibrosis stage, but fat‐corrected sADC was not (P = 0.24).

Data Conclusion

Fat‐corrected VMRE was not associated with fibrosis stage in NAFLD. Further investigation is required if VMRE is to be considered in subjects with NAFLD.

Evidence Level

1

Technical Efficacy

Stage 2
“Ghost peaks” of olmesartan medoxomil: Two solution degradation products of olmesartan medoxomil via oxidation mediated by metal ions
Authors: Huang Minxia , Yao Beiyang , Jiang Manhua , Sun Fuzhou , You Jinsong , Huang Fangfang , Zhao Yanping , Wu Shuming , He Xinqian , Song Xuezhi
Published: March 2022

Two unknown solution degradants were found during the dissolution testing in 0.1‐M HCl for olmesartan medoxomil (OLM) tablets. The structure of the degradants was identified and characterized by liquid chromatography–ultraviolet (LC–UV), liquid chromatography with tandem mass spectrometry (LC–MS/MS), and nuclear magnetic resonance (NMR) and demonstrated to be cyclization of tetrazole and benzene in the olmesartan (OL) and OLM structures. A series of studies including stress studies, simulation studies, and mechanism‐based studies were performed to reveal the potential mechanisms that lead to the formation of the unknown degradants. The study results demonstrated that the degradation was catalyzed with radicals that originated from the metal ions leached from the inner surface of high‐performance liquid chromatography (HPLC) glass vials with dissolved oxygen under acidic condition. Prerinsing the glass vials with acidic solution dissolved with EDTA can effectively avoid the generation of such oxidative impurities. The present work provides new insights into the understanding of degradation pathways of OLM, which might support the development of OLM tablets.
A mass spectrometry‐based non‐radioactive differential radial capillary action of ligand assay (DRaCALA) to assess ligand binding to proteins
Authors: Cimdins‐Ahne Annika , Chernobrovkin Alexey , Kim Soo‐Kyoung , Lee Vincent T. , Zubarev Roman A. , Römling Ute
Published: March 2022

Binding of ligands to macromolecules changes their physicochemical and enzymatic characteristics. Cyclic di‐GMP is a second messenger involved in motility/sessility and acute/chronic infection life style transition. Although the GGDEF domain, predominantly a diguanylate cyclase, represents one of the most abundant bacterial domain superfamilies, the number of cyclic di‐GMP receptors falls short. To facilitate screening for cyclic di‐nucleotide binding proteins, we describe a non‐radioactive, matrix‐assisted laser desorption and ionization time‐of‐flight (MALDI‐TOF)‐based modification of the widely applied differential radial capillary action of ligand assay (DRaCALA). The results of this assay suggest that the diguanylate cyclase/phosphodiesterase variant YciRFec101, but not selected catalytic mutants, bind cyclic di‐GMP.

Highlights

Cyclic di‐nucleotides are ubiquitous second messengers in bacteria. However, few receptors have been identified.

Previous screening of cell lysates by differential radial capillary action of ligand assay (DRaCALA) using radioactive ligand identified cyclic di‐nucleotide binding proteins.

A MALDI‐TOF‐based DRaCALA was developed to detect cyclic di‐nucleotide binding as a non‐radioactive alternative.

Known cyclic di‐GMP binding proteins were verified and potential cyclic di‐GMP binding proteins were identified.
Long noncoding RNA expression analysis in Crimean Congo hemorrhagic fever patients
Authors: Arslan Serdal , Bakir Mehmet , Bayyurt Burcu , Aydemir Eylem I. , Kinaci Kenan , Engin Aynur
Published: March 2022

Crimean Congo hemorrhagic fever (CCHF) is an acute viral infection that can cause death. The detection of host transcriptome is important for understanding differences in the pathogenesis of the disease. Long noncoding RNAs (lncRNAs) regulate gene expression in different biological processes. They have also emerged as key molecules for therapeutic targets. We investigated the lncRNA gene expression profiles by utilizing the microarray for the first time in CCHF. LncRNAs were determined by the comparisons between case‐control, fatal case‐control, and fatal case‐nonfatal cases. Quantitative polymerase chain reaction was applied to validate the microarray results of some lncRNAs. In our study, 39 lncRNAs (5 downregulated and 34 upregulated) were found to be significantly regulated in the cases when compared to the controls (p < 0.05; FC ≥ 2). One hundred ten lncRNAs exhibited a statistically significant difference between fatal cases and controls. FER1L4, ECRP, and LOC100133669 are important lncRNAs in both case and fatal case groups compared with controls. These lncRNAs may be considered important therapeutic targets for the CCHF in further studies.
Wet season rainfall onset and flash drought: The case of the northern Australian wet season
Authors: Lisonbee Joel , Ribbe Joachim , Otkin Jason A. , Pudmenzky Christa
Published: March 2022

In this paper, we report on the frequency of false onsets of wet season rainfall in the case of the Northern Australian wet season and investigate the role of large‐scale tropical climate processes such as the El Niño–Southern Oscillation, Indian Ocean Dipole (IOD) and Madden–Julian Oscillation. A false onset occurs when a wet season rainfall onset criterion is met, but follow‐up rainfall is not received for weeks or months later. Our analysis of wet season rainfall data from 1950 through 2020 shows a false onset occurs, on average, between 20 and 30% of wet seasons across all of northern Australia. This increases at a regional and local level such as at Darwin, the Northern Territory (NT), and parts of Queensland's north coast to over 50%. Seasonal climate influences, such as a La Niña pattern and a negative IOD that typically expedite the wet season rainfall onset, also increase the likelihood of a false onset over northern Australia. Our analysis also finds that periods of false onsets can sometimes, but not always, coincide with periods of rapid soil moisture depletion. The false rainfall onsets that develop into flash drought can be potentially disruptive and costly and are of potential significance for agriculture and fire management in northern Australia, and in other monsoonal climates that also typically experience a slow build‐up to the seasonal monsoon. In conclusion, effective rainfall indicates that many seasons experience ‘false onsets’ with dry conditions after early rainfall. We propose that false onsets are a physical characteristic of the climate of northern Australia which occurs with relatively high frequency. In addition, these false onsets may sometimes co‐occur with a flash drought.
Fecal sphingolipids predict parenteral nutrition–associated cholestasis in the neonatal intensive care unit
Authors: Moutinho Thomas J. , Powers Deborah A. , Hanson Gabriel F. , Levy Shira , Baveja Rajiv , Hefner Isabel , Mohamed Masouma , Abdelghani Alaa , Baker Robin L. , Papin Jason A. , Moore Sean R. , Hourigan Suchitra K.
Published: March 2022

Background

Parenteral nutrition–associated cholestasis (PNAC) in the neonatal intensive care unit (NICU) causes significant morbidity and associated healthcare costs. Laboratory detection of PNAC currently relies on elevated serum conjugated bilirubin levels in the aftermath of impaired bile flow. Here, we sought to identify fecal biomarkers, which when integrated with clinical data, would better predict risk for developing PNAC.

Methods

Using untargeted metabolomics in 200 serial stool samples from 60 infants, we applied statistical and machine learning approaches to identify clinical features and metabolic biomarkers with the greatest associative potential for risk of developing PNAC. Stools were collected prospectively from infants receiving PN with soybean oil–based lipid emulsion at a level IV NICU.

Results

Low birth weight, extreme prematurity, longer duration of PN, and greater number of antibiotic courses were all risk factors for PNAC (P < 0.05). We identified 78 stool biomarkers with early predictive potential (P < 0.05). From these 78 biomarkers, we further identified 12 sphingomyelin lipids with high association for the development of PNAC in precholestasis stool samples when combined with birth anthropometry.

Conclusion

We demonstrate the potential for stool metabolomics to enhance early identification of PNAC risk. Earlier detection of high‐risk infants would empower proactive mitigation with alterations to PN for at‐risk infants and optimization of energy nutrition with PN for infants at lower risk.
VECTOR: Very deep convolutional autoencoders for non‐resonant background removal in broadband coherent anti‐Stokes Raman scattering
Authors: Wang Zhengwei , O' Dwyer Kevin , Muddiman Ryan , Ward Tomas , Camp Charles H. , Hennelly Bryan M.
Published: March 2022

Rapid label‐free spectroscopy of biological and chemical specimen via molecular vibration through means of broadband coherent anti‐Stokes Raman scattering (B‐CARS) could serve as a basis for a robust diagnostic platform for a wide range of applications. A limiting factor of CARS is the presence of a non‐resonant background (NRB) signal, endemic to the technique. This background is multiplicative with the chemically resonant signal, meaning the perturbation it generates cannot be accounted for simply. Although several numerical approaches exist to account for and remove the NRB, they generally require some estimate of the NRB in the form of a separate measurement. In this paper, we propose a deep neural network architecture called Very dEep Convolutional auTOencodeRs (VECTOR), which retrieves the analytical Raman‐like spectrum from CARS spectra through training of simulated noisy CARS spectra, without the need for an NRB reference measurement. VECTOR is composed of an encoder and a decoder. The encoder aims to compress the input to a lower dimensional latent representation without losing critical information. The decoder learns to reconstruct the input from the compressed representation. We also introduce skip connection that bypass from the encoder to the decoder, which benefits the reconstruction performance for deeper networks. We conduct abundant experiments to compare our proposed VECTOR to previous approaches in the literature, including the widely applied Kramers–Kronig method, as well as two another recently proposed methods that also use neural networks.
Strategies for crop nutraceutical content enhancement, a review
Authors: Martinez‐Alvarado Lucio , Acosta‐Estrada Beatriz A. , Marilena Antunes‐Ricardo
Published: March 2022

The increase in cardiovascular and degenerative diseases around the world, in addition to other metabolic alterations derived from an inadequate diet, have highlighted the need to consume more nutritious and healthy foods, that can also provide added value in the prevention of diseases. In this sense, nutraceutical‐rich functional foods have become a sustained growing market derived from consumer demands. Different strategies have been developed to enhance the content of nutraceuticals compounds in crops and end products, as well as to increase the bioavailability of them. These strategies have been grouped in biofortification techniques (e.g., foliar, and soil application of nutrients, germination, and soaking of seeds, genetic modification of plants and crops) and techniques for nutraceutical enrichment (e.g., fermentation of food byproducts, nanoparticles, and induced post‐harvest stress). The utilization of these techniques thrives a new approach for novel biofortified, and nutraceutical enriched foods that meet the needs of the most demanding and health‐conscious consumers.
Contribution of the diverse experimental models to unravelling the biological scope of dietary (poly)phenols
Authors: Agulló Vicente , Moreno Diego A , Domínguez‐Perles Raúl , García‐Viguera Cristina
Published: March 2022

The health benefits associated with (poly)phenols need to be supported by robust and insightful information on their biological effects. The use ofin vitro,ex vivo, andin vivomodels is crucial to demonstrate functionalities in specific targets. In this regard, bioaccessibility, bioavailability, and tissue/organ distribution need to be fully understood and established. In addition, the structure–function relationships, concerning both descriptive and mechanistic information, between specific compounds and therapeutic objectives, need to be supported by results obtained fromin vivostudies. Nevertheless, these studies are not always possible or have some limitations, particularly concerning the mechanistic information explaining the health benefits provided that should be covered with complementary experimental models. Based on these premises, this review aims to overview the contribution of the separate experimental approaches to gain insights into the bioaccessibility, bioavailability, and bioactivity of (poly)phenols. To achieve this objective, recent evidence available on the linkage of healthy/functional foods with the incidence of non‐communicable pathologies is presented. The different experimental approaches provide complementary information that allows advances to be applied to the knowledge gained on the functional properties and mechanistic facts responsible for the health attributions of polyphenols. © 2022 The Authors.Journal of The Science of Food and Agriculturepublished by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
The impact of the COVID‐19 pandemic on melanoma diagnoses
Authors: Weltler Patrick , Rappersberger Klemens , Filzmoser Peter , Vujic Igor
Published: March 2022

Introduction

We investigated whether governmental measures and lockdowns during the COVID‐19 pandemic had an impact on the number and histopathologic stages of melanoma.

Methods

The number and thickness (Breslow) of all diagnosed melanomas per day, month, or period at the ‘Institute for Pathology in the Centre’ in 2019 and 2020 were compared. For 2020, we defined four time periods: Period 1: 1 January–15 March; Period 2: 16 March–15 May (Lockdown 1); Period 3: 16 May–2 November; Period 4: 3 November–7 December (Lockdown 2).

Results

We found similar melanoma numbers in 2019 (577) and 2020 (608). The mean number of diagnoses per day during Lockdown 1 (Period 2) was significantly lower (0.87 melanomas/day; p = 0.005) when compared to the respective time periods in 2019 and to the other three periods in 2020 (Period 1: 1.65 melanomas/day, Period 3: 1.77 melanomas/day, and Period 4: 2.49 melanomas/day). Tumour thickness in July 2020 (1.9 mm) was significantly higher (p = 0.02) than in July 2019 (1.1 mm).

Discussion

The significant lower number of histopathologic diagnoses of melanoma during ‘Lockdown 1’ may be explained by postponed or missed patient consultations. This assumption is supported by the demonstration of a higher tumour thickness in July and August 2020, compared to 2019.
Recent Advances in Polymer Microneedles for Drug Transdermal Delivery: Design Strategies and Applications
Authors: Wang Rui , Jiang Guohua , Aharodnikau Uladzislau E. , Yunusov Khaydar , Sun Yanfang , Liu Tianqi , Solomevich Sergey O.
Published: March 2022

In recent years, transdermal drug delivery based on microneedles (MNs) technology has received extensive attention, which offers a safer and painless alternative to hypodermic needle injections. They can pierce the stratum corneum and deliver drugs to the epidermis and dermis‐structures of skin, showing prominent properties such as minimally invasiveness, bypassing first‐pass metabolism, and can be self‐administered. A range of materials has been used to fabricate MNs, such as silicon, metal, glass, and polymers. Among them, polymer MNs have gained increasing attention from pharmaceutical and cosmetic companies as one of the promising drug delivery methods. MN products have recently become available on the market, and some of them are under evaluation for efficacy and safety. This paper focuses on the current state of polymer MNs in drug transdermal delivery. The materials and methods for the fabrication of polymer MNs and their drug administration are described. The recent progress of polymer MNs for treatment of cancer, vaccine delivery, blood glucose regulation, androgenetic alopecia, obesity, tissue healing, myocardial infarction, and gout are reviewed. The challenges of MNs technology are summarized and the future development trend of MNs is also prospected.
Impact of corrosion on mechanical properties of additively manufactured Invar 36
Authors: Heine B. , Kah A. , Sedlmajer M. , Ocker C. , Merkel M.
Published: March 2022

Invar alloys are used for high‐precision applications due to their invariance of the coefficient of thermal expansion over a temperature range up to about 250 °C. The present study determines the mechanical and corrosive properties of Invar 36 (64 % Iron – 36 % Nickel) specimens produced by laser powder bed fusion. Tensile specimens were fabricated to investigate the mechanical properties. The influence of a horizontal and vertical building orientation is considered. An apparent mechanical anisotropy depending on the respective building is observed. Based on this, further tensile specimens were stored in a hydrochloric acid pickling solution, a sulphate buffer solution and a sodium chloride solution to analyse the corrosion behaviour. The findings after eight weeks in the individual media show that outsourcing the Invar 36 specimens in a sulphate buffer solution results in significant changes in the mechanical properties, especially fracture elongation.
Supply chain ethics and transparency: An agent‐based model approach with Q‐learning agents
Authors: Park Daehyeon , Ryu Doojin
Published: March 2022

This study examines suppliers' decision making regarding supply chain ethics and transparency using an agent‐based model with Q‐learning agents. A supplier may not accurately identify the demand for its product because the impact of supply chain ethics on the market is opaque. Thus, we define each supplier as a Q‐learning agent that learns via an iterative game process. Our simulation results show that suppliers maintain low levels of ethics and transparency, which is a collusion behavior. Several suppliers deviate from collusion, but most of the suppliers collude to manage the supply chain unethically and opaquely.
Institutional logics and the multiorganizational governance arrangements of humanitarian INGOs
Authors: Beagles Jonathan E.
Published: March 2022

Governance within the growing number of multiorganizational international nongovernmental organization (INGO) families in the humanitarian sector is challenging. Ideas are evolving about what the objectives of humanitarian INGOs should be, what the most appropriate means of achieving these objectives are, and how best to demonstrate effectiveness and integrity to others. Within this context, scholars observe that choices in governance approaches are driven largely by internal politics within the bounds of legitimacy, leading some to refer to INGOs as principled‐instrumentalists. However, we know little about the principles bounding these instrumental choices. Drawing from an institutional logics perspective, this paper compares the multiorganizational governance arrangements of 40 humanitarian INGO families with the values they espouse in their statements of values, principles, or beliefs. The idea being that these statements of values can serve as a window into the logics guiding organizational decision‐making and provide the basis for how power is enacted and strategies chosen within these social settings. These findings have the potential to help leaders of multisite nonprofits make sense of the ways changing values, beliefs, and logics are prompting their organizations to reconsider how they balance inherent management tensions.