bluuebunny/crossref_metadata_2025 huggingface dataset:
BrewerIX enables allelic expression analysis of imprinted and X-linked genes from bulk and single-cell transcriptomes
Authors: Martini Paolo , Sales Gabriele , Diamante Linda , Perrera Valentina , Colantuono Chiara , Riccardo Sara , Cacchiarelli Davide , Romualdi Chiara , Martello Graziano
Published: February 2022

Genomic imprinting and X chromosome inactivation (XCI) are two prototypical epigenetic mechanisms whereby a set of genes is expressed mono-allelically in order to fine-tune their expression levels. Defects in genomic imprinting have been observed in several neurodevelopmental disorders, in a wide range of tumours and in induced pluripotent stem cells (iPSCs). Single Nucleotide Variants (SNVs) are readily detectable by RNA-sequencing allowing the determination of whether imprinted or X-linked genes are aberrantly expressed from both alleles, although standardised analysis methods are still missing. We have developed a tool, named BrewerIX, that provides comprehensive information about the allelic expression of a large, manually-curated set of imprinted and X-linked genes. BrewerIX does not require programming skills, runs on a standard personal computer, and can analyze both bulk and single-cell transcriptomes of human and mouse cells directly from raw sequencing data. BrewerIX confirmed previous observations regarding the bi-allelic expression of some imprinted genes in naive pluripotent cells and extended them to preimplantation embryos. BrewerIX also identified misregulated imprinted genes in breast cancer cells and in human organoids and identified genes escaping XCI in human somatic cells. We believe BrewerIX will be useful for the study of genomic imprinting and XCI during development and reprogramming, and for detecting aberrations in cancer, iPSCs and organoids. Due to its ease of use to non-computational biologists, its implementation could become standard practice during sample assessment, thus raising the robustness and reproducibility of future studies.
TAQing2.0 for genome reorganization of asexual industrial yeasts by direct protein transfection
Authors: Yasukawa Taishi , Oda Arisa H. , Nakamura Takahiro , Masuo Naohisa , Tamura Miki , Yamasaki Yuriko , Imura Makoto , Yamada Takatomi , Ohta Kunihiro
Published: February 2022

Genomic rearrangements often generate phenotypic diversification. We previously reported the TAQing system where genomic rearrangements are induced via conditional activation of a restriction endonuclease in yeast and plant cells to produce mutants with marked phenotypic changes. Here we developed the TAQing2.0 system based on the direct delivery of endonucleases into the cell nucleus by cell-penetrating peptides. Using the optimized procedure, we introduce a heat-reactivatable endonuclease TaqI into an asexual industrial yeast (torula yeast), followed by a transient heat activation of TaqI. TAQing2.0 leads to generation of mutants with altered flocculation and morphological phenotypes, which exhibit changes in chromosomal size. Genome resequencing suggested that torula yeast is triploid with six chromosomes and the mutants have multiple rearrangements including translocations having the TaqI recognition sequence at the break points. Thus, TAQing2.0 is expected as a useful method to obtain various mutants with altered phenotypes without introducing foreign DNA into asexual industrial microorganisms.
Tunable metal contacts at layered black-arsenic/metal interface forming during metal deposition for device fabrication
Authors: Kundu Subhajit , Golani Prafful , Yun Hwanhui , Guo Silu , Youssef Khaled M. , Koester Steven J. , Mkhoyan K. Andre
Published: February 2022

Understanding the kinetics of interfacial reaction in the deposition of metal contacts on 2D materials is important for determining the level of contact tenability and the nature of the contact itself. Here, we find that some metals, when deposited onto layered black-arsenic films using e-beam evaporation, form a-few-nm thick distinct intermetallic layer and significantly change the nature of the metal contact. In the case of nickel, the intermetallic layer is Ni11As8, whereas in the cases of chromium and titanium they are CrAs and a-Ti3As, respectively, with their unique structural and electronic properties. We also find that temperature, which affects interatomic diffusion and interfacial reaction kinetics, can be used to control the thickness and crystallinity of the interfacial layer. In the field effect transistors with black-arsenic channel, due to the specifics of its formation, this interfacial layer introduces a second and more efficient edge-type charge transfer pathway from the metal into the black-arsenic. Such tunable interfacial metal contacts could provide new pathways for engineering highly efficient devices and device architectures.
Pacific decadal variability over the last 2000 years and implications for climatic risk
Authors: Vance Tessa R. , Kiem Anthony S. , Jong Lenneke M. , Roberts Jason L. , Plummer Christopher T. , Moy Andrew D. , Curran Mark A. J. , van Ommen Tas D.
Published: February 2022

The Interdecadal Pacific Oscillation, an index which defines decadal climate variability throughout the Pacific, is generally assumed to have positive and negative phases that each last 20-30 years. Here we present a 2000-year reconstruction of the Interdecadal Pacific Oscillation, obtained using information preserved in Antarctic ice cores, that shows negative phases are short (7 ± 5 years) and infrequent (occurring 10% of the time) departures from a predominantly neutral-positive state that lasts decades (61 ± 56 years). These findings suggest that Pacific Basin climate risk is poorly characterised due to over-representation of negative phases in post-1900 observations. We demonstrate the implications of this for eastern Australia, where drought risk is elevated during neutral-positive phases, and highlight the need for a re-evaluation of climate risk for all locations affected by the Interdecadal Pacific Oscillation. The initiation and future frequency of negative phases should also be a research priority given their prevalence in more recent centuries.
Post-GWAS functional analysis identifies CUX1 as a regulator of p16INK4a and cellular senescence
Authors: Jiang Danli , Sun Wei , Wu Ting , Zou Meijuan , Vasamsetti Sathish Babu , Zhang Xiaoyu , Zhao Yihan , Phillippi Julie A. , Sawalha Amr H. , Tavakoli Sina , Dutta Partha , Florentin Jonathan , Chan Stephen Y. , Tollison Tammy S. , Di Wu  , Cui Jing , Huntress Ian , Peng Xinxia , Finkel Toren , Li Gang
Published: February 2022

Accumulation of senescent cells with age is an important driver of aging and age-related diseases. However, the mechanisms and signaling pathways that regulate senescence remain elusive. In this report, we performed post-genome-wide association studies (GWAS) functional studies on the CDKN2A/B locus, a locus known to be associated with multiple age-related diseases and overall human lifespan. We demonstrate that transcription factor CUX1 (Cut-Like Homeobox 1) specifically binds to an atherosclerosis-associated functional single-nucleotide polymorphism (fSNP) (rs1537371) within the locus and regulates the CDKN2A/B-encoded proteins p14ARF, p15INK4b and p16INK4a and the antisense noncoding RNA in the CDK4 (INK4) locus (ANRIL) in endothelial cells (ECs). Endothelial CUX1 expression correlates with telomeric length and is induced by both DNA-damaging agents and oxidative stress. Moreover, induction of CUX1 expression triggers both replicative and stress-induced senescence via activation of p16INK4a expression. Thus, our studies identify CUX1 as a regulator of p16INK4a-dependent endothelial senescence and a potential therapeutic target for atherosclerosis and other age-related diseases.
Epidemiological significance of the occurrence and persistence of rotaviruses in water and sewage: a critical review and proposal for routine microbiological monitoring
Authors: Omatola Cornelius A. , Olaniran Ademola O.
Published: February 2022

Globally, waterborne gastroenteritis attributable to rotaviruses is on the increase due to the rapid increase in population growth, poor socioeconomic conditions, and drastic changes in climatic conditions.
A sorbent containing pH-responsive chelating residues of aspartic and maleic acids for mitigation of toxic metal ions, cationic, and anionic dyes
Authors: Ali Shaikh A. , Mubarak Shuaib A. , Yaagoob Ibrahim Y. , Arshad Zeeshan , Mazumder Mohammad A. J.
Published: February 2022

Cycloterpolymerization of diallylaminoaspartic acid hydrochloride (I), maleic acid (II) and a cross-linker (III) afforded a new pH-responsive resin (IV), loaded with four CO2H and a chelating motif of NH+⋯CO2− in each repeating unit.
A time-resolved ratiometric luminescent anthrax biomarker nanosensor based on an Ir(iii) complex-doped coordination polymer network
Authors: Zhang Hui , Sun Meng , Wang Ying , Yin Li , Ma Dik-Lung , Leung Chung-Hang , Lu Lihua
Published: February 2022

An Ir(iii) complex-doped coordination polymer network (Ir(iii)@GMP–Eu3+) is fabricated for the ratiometric luminescent detection of anthrax biomarker 2,6-dipicolinic acid (DPA) through the analysis of time-resolved emission spectra (TRES).
Cyclic and linear dithienyl-anthryl vinylenes: synthesis, X-ray crystallography, spectroscopic properties, and photoinduced mechanical motions
Authors: Wu Pin-Rong , Wang Chi-Hsien , Chen Yi-Wen , Lin Yen-Jen , Ide Tomohito , Tsuchido Yoshitaka , Sei Yoshihisa , Horie Masaki
Published: February 2022

We report the synthesis of cyclic and linear dithienyl-anthryl vinylenes, exhibiting photoinduced conformational changes and photomechanical motions in solution and solid states, respectively.
Highly efficient thermally activated delayed fluorescence emitters with suppressed energy loss and a fast reverse intersystem crossing process
Authors: Zhang Xiao , Li Jiao-Yang , Zhang Kai , Ding Lei , Wang Chuan-Kui , Fung Man-Keung , Fan Jian
Published: February 2022

Thermally activated delayed fluorescence (TADF) emitters with low non-radiative decay and a fast reverse intersystem crossing (RISC) process are highly desirable for achieving efficient organic light-emitting diodes (OLEDs).
Defect healingviaa gradient cooling strategy for efficient all-inorganic perovskite solar cells
Authors: Lv Jiani , Zhao Wenning , Li Wenhui , Yu Jiatao , Zhang Mingzhe , Han Xiuxun , Tanaka Tooru
Published: February 2022

Structural defects in all-inorganic perovskite films can be partially healedviaa gradient cooling strategy.
A phenothiazine-fused electroactive bilayer helicene: design, synthesis, ACQ-to-AIE transformation and photophysical properties
Authors: Shivaji Babar Suraj , Boddula Rajamouli , Saeki Akinori , Singh Surya Prakash
Published: February 2022

Study of the photophysical, electrochemical and photoconductive properties of SPS-PY-PT and a comparative analysis with PY-PT-Un. In addition, the ACQ and AIE phenomena and time-resolved microwave conductivity (TRMC) are analysed.
Expression of concern: Self-assembled membrane manufactured by metal–organic framework (UiO-66) coated γ-Al2O3 for cleaning oily seawater
Authors: Fisher Laura
Published: February 2022

Expression of concern for ‘Self-assembled membrane manufactured by metal–organic framework (UiO-66) coated γ-Al2O3 for cleaning oily seawater’ by Cunlong Li et al., RSC Adv., 2019, 9, 10702–10714, DOI: 10.1039/C9RA00521H.
Band gap alignment of structured microporous graphitic carbons by N doping and its influence on photocatalytic overall water splitting
Authors: Rendón-Patiño Alejandra , Torres Ferran , Primo Ana , García Hermenegildo
Published: February 2022

N-doped graphitic carbon derived from α-cyclodextrin generate 1.8 mmol H2 g−1 in 4 h under solar light irradiation in the presence of CH3OH.
The Reliability of Telepractice Administration of the Western Aphasia Battery–Revised in Persons With Primary Progressive Aphasia
Authors: Rao Leela A. , Roberts Angela C. , Schafer Rhiana , Rademaker Alfred , Blaze Erin , Esparza Marissa , Salley Elizabeth , Coventry Christina , Weintraub Sandra , Mesulam M.-Marsel , Rogalski Emily
Published: February 2022

Purpose:

The use of telepractice in the field of communication disorders offers an opportunity to provide care for those with primary progressive aphasia (PPA). The Western Aphasia Battery–Revised (WAB-R) is used for differential diagnosis, to assess severity of aphasia, and to identify a language profile of strengths and challenges. Telehealth administration of the WAB-R is supported for those with chronic aphasia due to stroke but has not yet been systematically explored in neurodegenerative dementia syndromes. To fill this gap, in-person and telehealth performance on the WAB-R from participants with mild to moderate PPA was compared.

Method:

Nineteen participants with mild to moderate PPA were administered the WAB-R in person and over videoconferencing. Videoconferencing administration included modifications to the testing protocol to ensure smooth completion of the assessment. Subtest and Aphasia Quotient (WAB-AQ) summary scores were compared using concordance coefficients to measure the relationship between the administration modes.

Results:

In-person and telehealth scores showed strong concordance for the WAB-AQ, Auditory Verbal Comprehension subtest, and Naming & Word Finding subtest. The Spontaneous Speech test summary score had slightly lower concordance, indicating the need for caution when comparing these scores across administration modes.

Conclusion:

These findings support extending the use of telehealth administration of the WAB-R via videoconferencing to those with mild to moderate PPA given appropriate modifications to testing protocol.
A method to calculate the thermal efficiency of any closed-loop curve
Authors: Thompson Avery
Published: February 2022

A newly devised general formalism for the efficiency calculation means any thermodynamic cycle can be easily solved.
Pairing metal phosphates with atomic layer deposition for specialized applications
Authors: Green Leigh Ann
Published: February 2022

Comprehensive review highlights mechanisms and potential uses for this technical pairing.
Chemsex questions: what are we actually asking?
Authors: Crozier Brendan , Sayer Nathan , Varma Rick
Published: February 2022

Among men who have sex with men (MSM), sexualised drug use (SDU) is related to high risk sexual behaviour and a higher chance of contracting STIs. Chemsex, a subset of SDU, has a particularly high risk factor for STIs. We describe the implementation of a new question about Chemsex for first time clients attending Sydney Sexual Health Centre through a retrospective review of electronic medical records. Between 1 December 2018 and 30 November 2019, 227 MSM reported engaging in ‘Chemsex’. 74 respondents (33%) had a specific drug used during sex noted. Of these, the majority (52, 70%; 95% CI 60–81) used a drug commonly associated with Chemsex (crystal methamphetamine, gamma-hydroxybutyrate, or mephedrone), however, a sizeable minority (22, 30%; 95% CI 19–40) only described a drug not commonly associated with Chemsex. The question asked appeared to be more broadly interpreted as SDU. Broad SDU questions, not just questions on Chemsex, may be more appropriate for identifying risk behaviours in MSM in clinical contexts.
Homeless Encampments, Hotels, and Equitable Access to Public Space: Socially Sustainable Post-Pandemic Public Spaces in British Columbia, Canada
Authors: Broderick Lliam Anthony
Published: February 2022

The COVID-19 pandemic has exacerbated existing social inequities (
de la Barre et al., 2020
;
Fenley, 2020
;
Perri et al., 2020
). The closure of drop-in services and community centres, reduced access to public spaces, and a reduction in resources has had a negative impact on marginalized populations (
Perri et al., 2020
). Moreover, these tumultuous circumstances have led to increased numbers of persons setting up encampments and clustering in public space across British Columbia, Canada (British Columbia Ministry of Health, 2020b).

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Vancouver Island University World Leisure Centre of Excellence

© Lliam Anthony Broderick 2021
Placemaking through Deep Cultural Mapping: The Where is Here? Project
Authors: Vaugeois Nicole L. , Rosser Sunny , Karsten Sharon , Williams Alanna , Shaw Pam
Published: February 2022

One of the most visible avenues used by small cities to retain competitiveness can be seen in the attempts to revitalize their downtown areas to create places and spaces enjoyed and valued by residents and visitors. Formerly recognized as the heart or centre of small cities, many downtown areas have suffered due to urban sprawl and a loss of connectedness or familiarity among new residents. While efforts to address downtown revitalization are evident such as the creation of public spaces, events and support for small businesses, there remains a need to understand if, and how, residents in small cities value their downtown areas.

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A publication of the World Leisure Centre of Excellence

© Nicole L. Vaugeois, Sunny Rosser, Sharon Karsten, Alanna Williams and Pam Shaw 2016
A Leisure Professional Association’s Structural Change, to Remain Relevant to its Members as well as in its Support of the Profession – Part 1
Authors: James J. Joy , Weddell Melissa S.
Published: February 2022

North Carolina Recreation and Park Association (NCRPA), a leisure and recreation professional association, recognized its need to transition from a traditional professional association model to a new model that engaged members and professionals in the field, provided opportunities for volunteer involvement that are short and long-term, and become relevant in a fast-changing world.

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A publication of Vancouver Island University World Leisure Centre of Excellence Main image: City skyline of Charlotte North Carolina from Marshall Park (iStock)

© J. Joy James and Melissa S. Weddell 2016
Characterisation and mitigation of renewable droughts in the Australian National Electricity Market
Authors: Boston Andy , Bongers Geoffrey D , Bongers Nathan
Published: February 2022

In a decarbonising world, the electricity generation mix in Australia’s National Electricity Market (NEM) is likely to be heavily dependent on wind and solar. Designing an electricity system dominated by variable renewable energy generation requires careful examination of periods of low renewable output to ensure storage or other back up generation is sufficient to avoid loss of load. This study uses 15 years of climate and electricity demand data to examine the frequency and nature of the occurrence of low renewable periods. It examines strategies for their mitigation so that unserved energy standards are not breached. We have found that the winter period, May to August, is the time where the NEM is at greatest risk of loss of load. This winter period is when the demand in southern Australian states is higher, solar generation is lower and a series of low wind periods can drain storage. It has been demonstrated that any proposed generation mix reliant on renewable energy generation should be stress tested across a low wind winter, like the complex winter of 2010, not just a single isolated low wind period. Storage was found to be ideal to provide energy for a few hours overnight, but firm dispatchable thermal generation is likely to be a lower cost option than long term storage for extended low wind periods. Diversifying generation with the addition of offshore wind may reduce the need for storage, although the need for floating wind turbines may make this alternative too expensive to add any value in the Australian context.
Time-series analysis of recent antihyperglycemic medication prescribing trends for a diverse sample of Medicare enrollees with type 2 diabetes mellitus in an integrated health system
Authors: Miller Michael J , DiNucci Anna J , Jalalzai Rabia , Rabinovich Nonna , Roblin Douglas W
Published: February 2022

Purpose

Despite high type 2 diabetes mellitus (T2DM) prevalence in Medicare enrollees, newer therapeutic options, and revised treatment guidelines, little is known about US antihyperglycemic prescribing trends after 2015. This research describes recent monthly antihyperglycemic prescribing trends in a large, diverse population of Medicare enrollees from the US Mid-Atlantic region.

Methods

Encounter data (July 2018-July 2020) for Medicare enrollees 65 years of age or older with T2DM were extracted from electronic health records of a large integrated health system. Descriptive time-series regression models were estimated to describe monthly prescribing rates (ie, prescription orders per 100 eligible plan members with T2DM) overall and by medication subgroups for all-eligible and continuously-eligible samples. Trends in monthly prescription orders per 100 eligible plan members with T2DM were reported.

Results

The monthly all-eligible member sample (n > 22,000) exhibited an overall positive baseline monthly prescribing rate of 23.88 T2DM medication orders per 100 members with T2DM and a significant positive monthly prescribing rate trend (ie, change) of 0.12 T2DM medication orders per 100 members with T2DM (P < 0.05). Subgroup T2DM medication order rates per 100 members with T2DM at baseline were 16.28 for first-generation medications, 3.87 for human insulins, 3.04 for insulin analogs, 0.58 for second-generation medications, and 0.11 for combination medications. Human insulins, insulin analogs, and second-generation medications had positive monthly trends (P < 0.05). Among second-generation medications, sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists had positive monthly trends (P < 0.05). Continuously eligible members with T2DM (n = 19,185) had no significant overall monthly prescribing trend; however, human insulins, insulin analogs, and second-generation medications and the SGLT-2 inhibitor class had positive monthly prescribing trends (P < 0.05).

Conclusion

In a diverse Medicare sample, this study observed increasing monthly trends for second-generation medications, human insulins, and insulin analogs consistent with emerging evidence. Among second-generation medications, SGLT-2 inhibitors became the most commonly prescribed over time.
Evaluating hematology/oncology clinical pharmacist activities via self-reported work sampling
Authors: Lee Julia S , Nickman Nancy A , Pace Makala
Published: February 2022

Purpose

Hematology/oncology clinical pharmacists’ work activities have been described in previous literature, but time spent on pharmacist tasks has not been well characterized. Random work sampling (WS) is a form of activity assessment to determine the proportion of time spent in various types of work. Based on results from previous WS evaluations at University of Utah and its Huntsman Cancer Hospital, activities were changed to maximize time dedicated to clinical activities and pharmacists’ benefit to providers and patients in both inpatient and ambulatory care settings. Therefore, updated random WS evaluations were completed during spring 2019 and fall 2020.

Methods

Personal digital assistant (PDA) devices were used to record hematology/oncology clinical pharmacists’ onsite or remote location and work activity data. Data were collected 8 times per hour on weekdays, with a goal of 275 observations per pharmacist. Results were then classified as clinical, professional, or technical activities.

Results

In 2019, 9,079 observations were recorded by 31 onsite pharmacists. In 2020, 28 pharmacists recorded 8,803 observations (5,524 during onsite work and 3,279 during remote work). The overall distribution of pharmacists’ work activities remained stable between 2019 and 2020, with 89% of activities classified as clinical or professional. Pharmacists spent a smaller proportion of time on in-person communication in 2020, balanced by increases in chart review and text-based communication. Onsite pharmacists reported a larger proportion of clinical activities, while remote pharmacists reported a larger proportion of professional activities.

Conclusion

Continued WS assessment of work activity patterns will allow identification of opportunities to streamline workflows, maximize pharmacist engagement in clinical activities, and development of remote work policy.
Single-cell RNA sequencing data analysis based on non-uniformε−neighborhood network
Authors: Jia Junbo , Chen Luonan
Published: February 2022

Motivation

Single-cell RNA sequencing (scRNA-seq) technology provides the possibility to study cell heterogeneity and cell development on the resolution of individual cells. Arguably, three of the most important computational targets on scRNA-seq data analysis are data visualization, cell clustering and trajectory inference. Although a substantial number of algorithms have been developed, most of them do not treat the three targets in a systematic or consistent manner.

Results

In this article, we propose an efficient scRNA-seq analysis framework, which accomplishes the three targets consistently by non-uniform ε−neighborhood (NEN) network. First, a network is generated by our NEN method, which combines the advantages of both k-nearest neighbors (KNN) and ε−neighborhood (EN) to represent the manifold that data points reside in gene space. Then from such a network, we use its layout, its community and further its shortest path to achieve the purpose of scRNA-seq data visualization, clustering and trajectory inference. The results on both synthetic and real datasets indicate that our NEN method not only can visually provide the global topological structure of a dataset accurately compared with t-SNE (t-Distributed Stochastic Neighbor Embedding) and UMAP (Uniform Manifold Approximation and Projection), but also has superior performances on clustering and pseudotime ordering of cells over the existing approaches.

Availability and implementation

This analysis method has been made into a python package called ccnet and is freely available at https://github.com/Just-Jia/ccNet.

Supplementary information

Supplementary data are available at Bioinformatics online.
The largest digital database of fern and lycopod records from Honduras: spatial, temporal and collector biases
Authors: Batke Sven P , Dallimore Thom , Reyes-Chávez Johan , Maradiaga Rina Fabiola Diaz , Somers Edward , Jones Indiana , Atkinson Wendy , Acosta Lilian Ferrufino , Reid Geraldine
Published: February 2022

Honduras is one of the least botanically studied countries in Central America. Most of the scientific botanical information for Honduras is housed in globally distributed herbaria, an often-under-used resource. A recently published checklist of ferns and lycopods from Honduras indicated that for the 713 taxa, often few distribution data are available and that we still do not know where fern and lycopod collections have taken place in the past. Therefore, the aims of this work were to (1) bring together for the first time a comprehensive inventory of fern and lycopod records from international herbaria and to (2) identify spatial, temporal and collector biases of these collections. Published and unpublished herbarium inventories of ferns and lycopod records were accessed from 2212 global herbaria. Of these, 39 hosted Honduran fern and lycopod collections. The final database included 22 194 herbarium records. Spatial and idiosyncratic collection biases are shown, with collections hotspots in areas such the Department of Francisco Morazán near the TEFH and Escuela Agrícola Panamericana (EAP) herbaria, in Celaque National Park near the city of San Pedro Sula and Tela and Lancetilla Botanical Garden. This unique database deposited at EAP, TEFH, LIV and Edge Hill University will enable Hondurans to share information to support the protection, restoration and sustainable use of their ecosystems.
A map of neurofilament light chain species in brain and cerebrospinal fluid and alterations in Alzheimer’s disease
Authors: Budelier Melissa M. , He Yingxin , Barthelemy Nicolas R. , Jiang Hong , Li Yan , Park Ethan , Henson Rachel L. , Schindler Suzanne E. , Holtzman David M. , Bateman Randall J.
Published: February 2022

Neurofilament light is a well-established marker of both acute and chronic neuronal damage and is increased in multiple neurodegenerative diseases. However, the protein is not well characterized in brain tissue or body fluids, and it is unknown what neurofilament light species are detected by commercial assays and whether additional species exist. We developed an immunoprecipitation-mass spectrometry assay using custom antibodies targeting various neurofilament light domains, including antibodies targeting Coil 1A/1B of the rod domain (HJ30.13), Coil 2B of the rod domain (HJ30.4) and the tail region (HJ30.11). We utilized our assay to characterize neurofilament light in brain tissue and CSF of individuals with Alzheimer’s disease dementia and healthy controls. We then validated a quantitative version of our assay and measured neurofilament light concentrations using both our quantitative immunoprecipitation-mass spectrometry assay and the commercially available immunoassay from Uman diagnostics in individuals with and without Alzheimer’s disease dementia. Our validation cohort included CSF samples from 30 symptomatic amyloid-positive participants, 16 asymptomatic amyloid-positive participants, 10 symptomatic amyloid-negative participants and 25 amyloid-negative controls. We identified at least three major neurofilament light species in CSF, including N-terminal and C-terminal truncations, and a C-terminal fragment containing the tail domain. No full-length neurofilament light was identified in CSF. This contrasts with brain tissue, which contained mostly full-length neurofilament and a C-terminal tail domain fragment. We observed an increase in neurofilament light concentrations in individuals with Alzheimer’s disease compared with healthy controls, with larger differences for some neurofilament light species than for others. The largest differences were observed for neurofilament light fragments including NfL165 (in Coil 1B), NfL324 (in Coil 2B) and NfL530 (in the C-terminal tail domain). The Uman immunoassay correlated most with NfL324. This study provides a comprehensive evaluation of neurofilament light in brain and CSF and enables future investigations of neurofilament light biology and utility as a biomarker.
Historical mitochondrial genome introgression confounds species delimitation: evidence from phylogenetic inference in theOdorrana grahamispecies complex
Authors: Yuan Zhiyong , Wu Dongyi , Wen Yang , Xu Wei , Gao Wei , Dahn Hollis A , Liu Xiaolong , Jin Jieqiong , Yu Chuanxin , Xiao Heng , Che Jing
Published: February 2022

Species delimitation is essential to informing conservation policy and understanding ecological and evolutionary processes. Most of our recent gains in knowledge on animal diversity rely on morphological characteristics and mitochondrial (mt) DNA variation. Concordant results based on both have led to an unprecedented acceleration in the identification of new species and enriched the field of taxonomy. However, discordances are also found commonly between morphological and mtDNA evidence. This confounds species delimitation, especially when gene flow or mt genome introgression has occurred. Here, we illustrate how mt genome introgression among species of the Odorrana grahami complex confounds species delimitation using the combined evidence of morphological characters, mt variation, and thousands of nuclear single-nucleotide polymorphisms (SNPs) from genotyping-by-sequencing (GBS). Fifty-eight samples across the distribution of the O. grahami complex were included. The mtDNA matrilineal genealogy indicated 2 clades, with O. grahami and Odorrana junlianensis clustered together. In contrast, all nuclear evidence including gene trees, species trees, and genetic structure analyses based on GBS data support 3 species with distinct genetic clusters. These 3 distinct genetic clusters also correspond to distinct morphological characters. They affirm the distinct taxonomic entities of both O. grahami and O. junlianensis, as well as a third clade distinct from either. Which species the third clade belongs to remains unclear and will require further testing. The nuclear genomic loci contradict the COI evidence, with indications of rampant historical mt genome introgression among the species of the O. grahami complex. These discordant signals previously confused species delimitation efforts in this group. Based on these findings, we recommend the integration of independent data, especially nuclear genomic evidence, in species delimitation so as to be robust against the pitfalls of mt introgression.
Coronavirus disease 2019-associated coronary endotheliitis and thrombotic microangiopathy causing cardiogenic shock: a case report
Authors: Valiton Valérian , Bendjelid Karim , Pache Jean-Claude , Roffi Marco , Meyer Philippe
Published: February 2022

Background

Coronavirus disease 2019 (COVID-19) primarily affects the respiratory tract but serious cardiovascular complications have been reported. Up to one-third of patients admitted to the intensive care unit may develop an acute myocardial injury, characterized by cardiac troponin elevation. However, the pathology underlying COVID-19-associated myocardial injury has rarely been reported.

Case summary

Three days after being diagnosed for a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a 52-year-old woman without a notable past medical history developed cardiogenic shock with severely reduced left ventricular ejection fraction (LVEF) at 25%. Coronary angiography was normal. Endomyocardial biopsy demonstrated coronary endotheliitis with multiple microvascular thromboses but no lymphocytic infiltrate and a negative polymerase chain reaction for SARS-CoV-2. The patient was implanted with a short-term LV assist device (Impella CP®, Abiomed, Aachen, Germany) and treated with therapeutic anticoagulation. She suffered from concomitant respiratory failure that required 14 days of orotracheal intubation, 10 days of dexamethasone, and broad-spectrum antibiotics. Clinical outcome was favourable with weaning of the Impella device after 6 days and full recovery of LVEF (65%) at 30 days. Cardiac magnetic resonance performed at Day 30 showed no evidence of myocarditis or scars and confirmed the normalization of LVEF.

Discussion

This case highlights how COVID-19-associated coronary endotheliitis and thrombotic microangiopathy, in the absence of myocarditis, may induce transient severe LV dysfunction and cardiogenic shock.
Endothelial superoxide dismutase 2 is decreased in sickle cell disease and regulates fibronectin processing
Authors: Dosunmu-Ogunbi Atinuke , Yuan Shuai , Shiwarski Daniel J , Tashman Joshua W , Reynolds Michael , Feinberg Adam , Novelli Enrico M , Shiva Sruti , Straub Adam C
Published: February 2022

Sickle cell disease (SCD) is a genetic red blood cell disorder characterized by increased reactive oxygen species (ROS) and a concordant reduction in antioxidant capacity in the endothelium. Superoxide dismutase 2 (SOD2) is a mitochondrial-localized enzyme that catalyzes the dismutation of superoxide to hydrogen peroxide. Decreased peripheral blood expression of SOD2 is correlated with increased hemolysis and cardiomyopathy in SCD. Here, we report for the first time that endothelial cells exhibit reduced SOD2 protein expression in the pulmonary endothelium of SCD patients. To investigate the impact of decreased SOD2 expression in the endothelium, SOD2 was knocked down in human pulmonary microvascular endothelial cells (hPMVECs). We found that SOD2 deficiency in hPMVECs results in endothelial cell dysfunction, including reduced cellular adhesion, diminished migration, integrin protein dysregulation, and disruption of permeability. Furthermore, we uncover that SOD2 mediates changes in endothelial cell function via processing of fibronectin through its inability to facilitate dimerization. These results demonstrate that endothelial cells are deficient in SOD2 expression in SCD patients and suggest a novel pathway for SOD2 in regulating fibronectin processing.
The Disability Employment Gap
Authors: Vabulas Geena
Published: February 2022

Research by the All-Party Parliamentary Group for Assistive Technology highlights how tech can remove barriers to employment for disabled people, writes Geena Vabulas, Policy Manager for Assistive and Accessible Technology at Policy Connect.
IT in the organisation
Authors: Runciman Brian
Published: February 2022

Do IT professionals agree with IT leaders’ assessments of the direction their organisations should take in the next 12 months? What issues do each group consider to be important? Brian Runciman MBCS takes a first look at the new BCS survey: ‘IT in the organisation 2022’.
Mentoring
Authors: Yetim Adem
Published: February 2022

Adem Yetim CITP CEng FBCS, shares mentorship goals for a sustainable world.
How to Make Hybrid Work, Through Inclusion of All
Authors: Pullan Penny
Published: February 2022

Hybrid teams are more challenging to manage than purely virtual ones, but they can be successful – with the right leadership, explains Dr Penny Pullan MBCS.
How to Be a Successful Product Manager: The First 90 Days
Authors: Dickenson Andrew
Published: February 2022

The first three months in a new product management role are crucial to set the tone for the entire business, as Andrew Dickenson, Founding Director of Product Focus, explains.
“Who Wants to Know all this Stuff?!”
Authors: Alkhatib Sami , Kelly Ryan , Waycott Jenny , Buchanan George , Grobler Marthie , Wang Shuo
Published: February 2022

The paper, ‘“Who Wants to Know all this Stuff?!”: Understanding Older Adults’ Privacy Concerns in Aged Care Monitoring Devices’, by Sami Alkhatib, Ryan Kelly, Jenny Waycott, George Buchanan, Marthie Grobler and Shuo Wang, published in Interacting with Computers (November 2021), explores the use of care technology and the privacy concerns of older people.
Compassionate use of meropenem/vaborbactam for infections caused by KPC-producing Klebsiella pneumoniae: a multicentre study
Authors: Tumbarello Mario , Raffaelli Francesca , Cascio Antonio , Falcone Marco , Signorini Liana , Mussini Cristina , De Rosa Francesco Giuseppe , Losito Angela Raffaella , De Pascale Gennaro , Pascale Renato , Giacobbe Daniele Roberto , Oliva Alessandra , Farese Alberto , Morelli Paola , Tiseo Giusy , Meschiari Marianna , Del Giacomo Paola , Montagnani Francesca , Fabbiani Massimiliano , Vargas Joel , Spanu Teresa , Bassetti Matteo , Venditti Mario , Viale Pierluigi
Published: February 2022

Objectives

To explore the real-life performance of meropenem/vaborbactam for treating serious KPC-producing Klebsiella pneumoniae infections, including those resistant to ceftazidime/avibactam.

Methods

A retrospective observational cohort study was conducted in 12 Italian hospitals. Enrolled patients had K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) infections (59.5% of which were ceftazidime/avibactam resistant). Patients who received ≥72 h of meropenem/vaborbactam therapy (with or without other antimicrobials) in a compassionate-use setting were included.

Results

The 37 infections (all hospital-acquired) were mainly bacteraemic (BSIs, n = 23) or lower respiratory tract infections (LRTIs, n = 10). Clinical cure was achieved in 28 (75.6%) cases and microbiologically confirmed in all 25 with follow-up cultures. Three (10.7%) of the 28 clinical cures (all BSIs, 2/3 microbiologically confirmed) were followed by in-hospital recurrences after meropenem/vaborbactam was discontinued (median interval: 18 days). All three recurrences were susceptible to meropenem/vaborbactam and successfully managed with meropenem/vaborbactam combined with colistin or fosfomycin. Nine patients (24.3%) (all with BSIs or LRTIs) died in hospital with persistent signs of infection. Most were aged over 60 years, with high comorbidity burdens and INCREMENT scores ≥8. Only one had received meropenem/vaborbactam monotherapy. Six began meropenem/vaborbactam therapy >48 h after infection onset. Outcomes were unrelated to the isolate’s ceftazidime/avibactam susceptibility status. The single adverse event observed consisted of severe leukopenia with thrombocytopenia.

Conclusions

With the well-known limitations of real-life retrospective studies, our results support previous findings indicating that meropenem/vaborbactam therapy will be a safe, effective tool for managing serious KPC-Kp infections, including the increasing proportion displaying resistance to ceftazidime/avibactam.
Development of Kudzu (Pueraria Montana var. lobata) Reference Materials for the Determination of Isoflavones and Toxic Elements
Authors: Lippert J Andreas , Rimmer Catherine A , Phillips Melissa M , Nelson Michael A , Barber Charles A , Wood Laura J , Long Stephen E , Bryan Colleen E , Sharpless Katherine E , Yen James , Kuszak Adam J , Wise Stephen A
Published: February 2022

Background

In collaboration with the Office of Dietary Supplements at the National Institutes of Health, the National Institute of Standards and Technology issued a suite of botanical matrix reference materials (RMs) and Standard Reference Material® (SRM) for determination of isoflavones and toxic elements in kudzu dietary supplement ingredients.

Objective

RM 8650 Pueraria montana var. lobata (Kudzu) Rhizome, SRM 3268 Pueraria montana var. lobata (Kudzu) Extract, and RM 8652 Kudzu-Containing Solid Oral Dosage Form were issued with values assigned for isoflavones (puerarin, daidzin, and daidzein), toxic elements (arsenic, cadmium, and lead), and selenium.

Methods

Isoflavone values were assigned using liquid chromatography with UV absorbance or mass spectrometry detection. Element values were assigned using inductively coupled plasma mass spectrometry and results from an interlaboratory comparison exercise.

Results

Mass fractions for puerarin were 32.2 ± 3.2 mg/g, 128 ± 13 mg/g, and 68.2 ± 6.9 mg/g in RM 8650, SRM 3268, and RM 8652, respectively. Arsenic increases from 156 ± 14 ng/g to 849 ± 83 ng/g and cadmium decreases from 348 ± 14 ng/g to 82.1 ± 4.9 ng/g from rhizome to extract.

Conclusion

The kudzu RM/SRM suite complements previously issued soy-related SRMs with values assigned for isoflavones, which have been studied for their potential health benefits, and expands the analytical resource by providing values for puerarin, an isoflavone not found in soy.

Highlights

The three new kudzurmaterials are for use in the determination of isoflavones, toxic elements, and selenium. For the isoflavones, these new kudzu materials provide higher levels of daidzin and daidzein than existing soy-related SRMs, and they provide a value for an isoflavone not in existing SRMs (puerarin). Toxic elements in RM 8650 and SRM 3268 provide new botanical matrixes for use by dietary supplement manufacturers for the verification of the safety of their raw materials.
Pediatric Burn Care in the Developing World: Where Are the Gaps in Research and What Can Be Done?
Authors: Bresler Richard Mark , Barksdale Elizabeth , Hansen Erik Nels
Published: February 2022

Burns are the fourth most common cause of injury worldwide. The burden of burn injury is largely carried by low- and middle-income countries (LMICs) with children in these regions being particularly vulnerable to burns. The purpose of this scoping review is to identify knowledge gaps in global pediatric burn care experience in an effort to help prioritize future research. Using the 6-stage Arksey and O’Malley framework for conducting a scoping review, pediatric burn care literature was reviewed over a 10-year period from 2010 to 2020. Studies from low-resource settings were included and categorized by geographic location, study patient population, study type, type of burn, and level of evidence. Of 107 included studies, 34% and 49% originated from LMICs in South Asia and Sub-Saharan Africa, respectively. Qualitative/observational (73%) and epidemiological single-center (20%) publications comprised the majority of included papers. The majority (95%) of all papers regardless of geographical location were lower levels of evidence (Level 3 or below). Our study identified four primary knowledge gaps: 1) a paucity of high-quality studies to guide burn care in LMICs; 2) an under-representation of articles from certain geographical locations; 3) few therapeutic and economic articles to guide resource allocation; and 4) a lack of articles with long-term patient follow-up. Efforts to address these disparities could help reduce the pediatric burn burden of disease in resource-poor settings.
Analytical technique for self-absorption structure of iron L-emission spectra obtained by soft X-ray emission spectrometer
Authors: Yokoyama Takaomi D , Takahashi Hideyuki , Koshiya Shogo , Murano Takanori , Terauchi Masami
Published: February 2022

The method deriving the L self-absorption spectrum from Lα,β emission spectra obtained at different accelerating voltages has been optimized for analyzing the chemical state of Fe in solid materials. Fe Lα,β emission spectra obtained are fitted using Pseudo-Voigt functions and normalized by the integrated intensity of each Fe Ll line, which is not affected by L2,3 absorption edge. The self-absorption spectrum is calculated by dividing the normalized intensity profile collected at low accelerating voltage by that collected at a higher accelerating voltage. The obtained profile is referred to as soft X-ray self-absorption structure (SX-SAS). This method is applied to six Fe-based materials (Fe metal, FeO, Fe3O4, Fe2O3, FeS and FeS2) to observe different chemical states of Fe in those materials. By comparing the self-absorption spectra of iron oxides, one can observe the L3 absorption peak structure shows a shift to the higher energy side as ferric (3+) Fe increases with respect to ferrous (+2) Fe. The intensity profiles of self-absorption spectra of metallic Fe and FeS2 shows shoulder structures between the L3 and L2 absorption peaks, which were not observed in spectra of Fe oxides. These results indicate that the SX-SAS technique is useful to examine X-ray absorption structure as a means to understand the chemical states of transition metal elements.
Composing Local Contexts
Authors: Barker Chris
Published: February 2022

An expression’s presuppositions must be satisfied by its local context, that is, by the utterance context updated with the content of expressions that have already been evaluated. Traditional dynamic approaches track local context by remaking clause denotations into context update functions. This requires crafting for each semantic operator an update recipe that is not fully determined by its truth conditions, failing to capture how local contexts depend only on truth conditions and order of evaluation. In other theories, computing local contexts involves reasoning about the set of all possible grammatical syntactic completions, which relocates local contexts outside of the semantics. I show how to build local contexts systematically and uniformly as part of the composition of ordinary truth conditions. The result is a minimalist dynamic semantics in which the only thing that is dynamically tracked is the semantic content of what has already been said.