bluuebunny/crossref_metadata_2025 huggingface dataset:
Death, Dying, and End-of-Life Care Provision by Doctors and Nurses in the Emergency Department
Authors: Omoya Oluwatomilayo (Tomi) , De Bellis Anita , Breaden Katrina
Published: January 2022

There have been significant advancements in the fields of medicine, demography, and pathology. These disciplines have contributed to the classification and control of death and dying. People are now living longer with numerous comorbidities, and there is a significant aging population. Consequently, there have been increases in the numbers of people who present to emergency departments across Australia seeking access to care at the end of life. Emergency department staff must have the knowledge and skills required to provide end-of-life care in a setting that traditionally contradicts the goals of comfort care. With the increase in demand for end-of-life care in emergency departments, a gap exists in the experiences of how staff provide such care in this setting. As a result of this gap, it is important to understand the lived experiences of emergency department doctors and nurses who provide end-of-life care. The aim of this research is to understand the lived experiences of emergency department doctors and nurses concerning death, dying, and end-of-life care provision. Data were analyzed using Diekelmann's 7-step analysis to support Gadamer's phenomenological approach. Results indicate that challenges exist in the decision-making process of end-of-life care in emergency departments.
An Orientation to Aviation Psychiatry
Authors: Westermeyer Joseph , Puram Vikram
Published: January 2022

This report orients general psychiatrists to assessment and care for “safety sensitive” aviation workers. Our case study of 30 sequential aviation patients consists of demographic, clinical, and aviation characteristics plus a 10-year follow-up. Relatively few pilots and other aviation workers self-identified their psychiatric condition. Aviation outcomes associated with psychiatric disorder included personnel injury and/or aircraft damage (three cases), imminent risk without injury or damage (nine cases), impaired aviation functioning without imminent risk (15 cases), and neither risk nor psychiatric disorder or impairment (three cases). Mood, anxiety, and substance use disorders comprised the most common diagnoses. Ten years later, 23 patients were employed (21 in aviation); seven were disabled or deceased. General psychiatrists will find aviation cases clinically familiar but requiring added evaluation for aviation safety and potential interaction with the Federal Aviation Agency and airline supervisors.
Adolescent Social Functioning Deficits in Association With Adoptive Family Functioning and Genetic Risk for Schizophrenia Spectrum Disorders
Authors: Tikkanen Ville , Siira Virva , Wahlberg Karl-Erik , Hakko Helinä , Myllyaho Toni , Läksy Kristian , Roisko Riikka , Niemelä Mika , Räsänen Sami
Published: January 2022

Social functioning deficits (SFDs) during adolescence represent potential vulnerability indicators to schizophrenia spectrum disorders, but little is known about how both family environmental and genetic factors contribute to SFDs. The aim of this study was to examine the association of adoptees' adolescent social functioning with adoptive family functioning and adoptees' high (HR) or low (LR) genetic risk for schizophrenia spectrum disorders. The present subsample from the nationwide Finnish Adoptive Family Study of Schizophrenia included 88 HR and 83 LR adoptees. Adolescent social functioning was assessed using UCLA Social Attainment Survey. Assessment of adoptive family functioning was based on Global Family Ratings. Results indicated that dysfunctional family processes and high genetic risk for schizophrenia spectrum disorders contributed approximately equally to adoptees' adolescent social functioning. Our findings underscore the importance of functional family processes in adolescent social functioning, particularly in individuals at high genetic risk for severe psychiatric disorder.
Trajectories of disability in low back pain
Authors: Andersen Tonny E. , Karstoft Karen-Inge , Lauridsen Henrik H. , Manniche Claus
Published: January 2022

Introduction:

Low back pain (LBP) is the leading course of years lived with disability. Unfortunately, not much knowledge exists about distinct trajectories of recovery from disability after LBP and their potential psychological predictors.

Objectives:

Hence, the aim of the present study was to identify trajectories of functional disability in LBP and their potential baseline psychological predictors.

Methods:

A 1-year consecutive cohort (N = 1048) of patients with LBP referred to the Spine Centre if they have not improved satisfactorily from a course of treatment in primary care after 1 to 2 months were assessed by self-report questionnaires at their first visit and at 6- and 12-month follow-up. Data from patients who responded to the Roland Morris Disability Questionnaire at least twice (N = 747) were used to assess trajectories of functional disability by Latent Growth Mixture Modeling. The following measures were used as baseline predictors of the trajectories: Pain Intensity Numerical Rating Scales, Pain Catastrophizing Scale, Tampa Scale for Kinesiophobia, and Hospital Anxiety and Depression Scale.

Results:

Four distinct trajectories were identified: high-stable (22.0%), high-decreasing (20.4%), medium-stable (29.7%), and low-decreasing (27.9%). Using the low-decreasing trajectory as reference, baseline pain intensity, depressive symptoms, and pain-catastrophizing predicted membership of all 3 symptomatic trajectories. However, using the high-decreasing trajectory as reference, age, baseline pain intensity, and depression were predictors of the high-stable trajectory.

Conclusion:

In particular, the finding of a high-stable trajectory characterized by high levels of baseline psychological distress is of potential clinical importance because psychological distress may be targeted by cognitive behavioral therapeutic approaches.
18F-FDG PET/CT Findings of G-CSF–Producing Gallbladder Cancer
Authors: Sasaki Fumi , Nakamoto Ryusuke , Tokunaga Koji , Ishida Ayami , Umeoka Shigeaki
Published: January 2022

We report a case of granulocyte colony-stimulating factor (G-CSF)–producing gallbladder cancer in a 64-year-old man. Contrast-enhanced CT showed an exophytic hypoattenuation mass with peripheral enhancement in the gallbladder. 18F-FDG PET/CT showed avid FDG uptake in the gallbladder mass and diffuse FDG uptake in the bone marrow. The patient was diagnosed with G-CSF–producing gallbladder cancer based on an elevated serum level of G-CSF and histological findings. G-CSF–producing tumors are associated with a poor prognosis because of rapid progression. Early and accurate diagnosis of G-CSF–producing tumors based on characteristic PET/CT findings is important to determine treatment strategies and improve prognosis of patients.
Quality and Safety in Healthcare, Part XCIV
Authors: Harolds Jay A.
Published: January 2022

For existing goods or services, Six Sigma uses the steps of DMAIC and the statistical analysis of data to decrease variation and errors, improve the value of an organization's outputs to the customers, and increase the profitability of the organization. In health care, in view of the training required and other issues, Six Sigma is best used for large complex problems, although it has also been applied successfully to smaller issues. Many examples of the use of Six Sigma and Lean Six Sigma in health care are reviewed.
18F-FDG PET/CT Findings in a Patient With Primary Primitive Neuroectodermal Tumor of the Lung
Authors: Chen Tao , Fan Jianzhong , Li Wenfei , Li Jianqi , Wu Caiyun
Published: January 2022

Primary primitive neuroectodermal tumor of the lung is an extremely rare and highly malignant neoplasm with a poor prognosis. A 49-year-old man presented with a dry cough and slight pain in the left chest for nearly 1 month. 18F-FDG PET/CT showed intense 18F-FDG uptake of the left inferior lung tumor and hypermetabolic mediastinal lymph nodes. Histopathology revealed primitive neuroectodermal tumor after CT-guided transthoracic needle biopsy of the left inferior lung mass was performed.
Socioeconomic disparities in epilepsy care
Authors: Blank Leah J.
Published: January 2022

Purpose of review

Epilepsy is a common, chronic neurologic disease with continued disparities in care. The COVID-19 pandemic and recent social movements have drawn greater attention to social determinants of health and our progress (or lack thereof) toward delivering more equitable care.

Recent findings

Recent studies continue to document racial and economic disparities in diagnosis, treatment, and overall care of epilepsy and associated conditions. Notably, an increasing number of studies are attempting to design healthcare pathways and other interventions to improve access and equity in epilepsy care.

The present literature highlights the importance of identifying and addressing the particular needs of vulnerable persons with epilepsy. Practitioners and researchers should continue to develop interventions aimed at improving care for all patients and, crucially, measure the impact of their changes to ensure that any interventions are truly advancing health equity.
Novel treatments in autism spectrum disorder
Authors: Baribeau Danielle , Vorstman Jacob , Anagnostou Evdokia
Published: January 2022

Purpose of review

There are currently no approved medications for the core symptoms of autism spectrum disorder (ASD), and only limited data on the management of co-occurring mental health and behavioural symptoms. The purpose of this review is to synthesize recent trials on novel treatments in ASD, with a focus on research trends in the past 2 years.

Recent findings

No new pharmacologic agents received regulatory approval for use in ASD. Several large randomized controlled trials (RCTs) had negative or ambiguous results (e.g. fluoxetine, oxytocin). A cross-over RCT of an oral cannabinoid suggested possible benefits for disruptive behaviours. Two large-scale multicentre trials of bumetanide were terminated early for lack of efficacy. Multicenter trials using repetitive transcranial magnetic stimulation are underway. Recent meta-analyses indicate that specific behavioural and psychological interventions can support social communication and treat anxiety. Numerous novel treatment targets informed by biological mechanisms are under investigation.

Recent data support the use of behavioural and psychological interventions for social communication and anxiety in ASD; data are more limited regarding pharmacotherapy for core and associated symptoms. Next steps include replication of early findings, trials of new molecular targets, and the identification of novel biomarkers, including genetic predictors, of treatment response.
Ovothiol ensures the correct developmental programme of the sea urchin
Paracentrotus lividus
embryo
Authors: Milito Alfonsina , Cocurullo Maria , Columbro Alfredo , Nonnis Simona , Tedeschi Gabriella , Castellano Immacolata , Arnone Maria Ina , Palumbo Anna
Published: January 2022

Ovothiols are π-methyl-5-thiohistidines produced in great amounts in sea urchin eggs, where they can act as protective agents against the oxidative burst at fertilization and environmental stressors during development. Here we examined the biological relevance of ovothiol during the embryogenesis of the sea urchin
Paracentrotus lividus
by assessing the localization of the key biosynthetic enzyme OvoA, both at transcript and protein level, and perturbing its protein translation by morpholino antisense oligonucleotide-mediated knockdown experiments. In addition, we explored the possible involvement of ovothiol in the inflammatory response by assessing
ovoA
gene expression and protein localization following exposure to bacterial lipopolysaccharide. The results of the present study suggest that ovothiol may be a key regulator of cell proliferation in early developing embryos. Moreover, the localization of OvoA in key larval cells and tissues, in control and inflammatory conditions, suggests that ovothiol may ensure larval skeleton formation and mediate inflammatory processes triggered by bacterial infection. This work significantly contributes to the understanding of the biological function of ovothiols in marine organisms, and may provide new inspiration for the identification of the biological activities of ovothiols in humans, considering the pharmacological potential of these molecules.
Analysis of flow loss characteristics of slanted axial-flow pump device based on entropy production theory
Authors: Yang Fan , Li Zhongbin , Hu Wenzhu , Liu Chao , Jiang Dongjin , Liu Dongsheng , Nasr Ahmed
Published: January 2022

Slanted axial-flow pump devices are widely applied in urban water supply, irrigation and drainage engineering fields. The second law of thermodynamics is applied to investigate the flow loss characteristics of the 30° slanted axial-flow pump model according to the flow loss analysis method of entropy production theory, so that the hydraulic loss characteristics can be revealed in internal flow process of the slanted axial-flow pump. The three-dimensional numerical simulation of the whole flow conduit in slanted axial-flow pump was conducted and the entropy production increased in the flow process was calculated. The location and distribution characteristics of the flow loss of the pump were qualitatively analysed. The results show that the entropy production in impeller is the highest among the pump components. With the increase of flow rate, the proportion of the entropy production in impeller in total value of the pump device increases continuously. The wall entropy production of impeller, guide vane and outlet conduit are lower than the mainstream entropy production, and the mainstream entropy production occupies the dominant position. As the flow rate grows, the proportion of turbulent dissipation entropy production decreases, and the proportion of wall dissipation entropy production increases. At 0.8
Q
bep
, the proportion of turbulent dissipation entropy production is close to 74%, which is about 2.8 times that of wall entropy production. Under 1.2
Q
bep
condition, the proportion of turbulent dissipation entropy production is just 5.5% higher than that of wall dissipation entropy production.
Species-specific interactions in avian–bryophyte dispersal networks
Authors: Chmielewski Matthew W. , Eppley Sarah M.
Published: January 2022

Studies from seed plants have shown that animal dispersal fundamentally alters the success of plant dispersal, shaping community composition through time. Our understanding of this phenomenon in spore plants is comparatively limited. Though little is known about species-specific dispersal relationships between passerine birds and bryophytes, birds are particularly attractive as a potential bryophyte dispersal vector given their highly vagile nature as well as their association with bryophytes when foraging and building nests. We captured birds in Gifford Pinchot National Forest to sample their legs and tails for bryophyte propagules. We found 24 bryophyte species across 34 bird species. We examined the level of interaction specificity: (i) within the overall network to assess community level patterns; and (ii) at the plant species level to determine the effect of bird behaviour on network structure. We found that avian–bryophyte associations are constrained within the network, with species-specific and foraging guild effects on the variety of bryophytes found on bird species. Our findings suggest that diffuse bird–bryophyte dispersal networks are likely to be common in habitats where birds readily encounter bryophytes and that further work aimed at understanding individual bird–bryophyte species relationships may prove valuable in determining nuance within this newly described dispersal mechanism.
Walking with early dinosaurs: appendicular myology of the Late Triassic sauropodomorph
Thecodontosaurus antiquus
Authors: Ballell Antonio , Rayfield Emily J. , Benton Michael J.
Published: January 2022

Dinosaur evolution is marked by numerous independent shifts from bipedality to quadrupedality. Sauropodomorpha is one of the lineages that transitioned from small bipedal forms to graviportal quadrupeds, with an array of intermediate postural strategies evolving in non-sauropodan sauropodomorphs. This locomotor shift is reflected by multiple modifications of the appendicular skeleton, coupled with a drastic rearrangement of the limb musculature. Here, we describe the osteological correlates of appendicular muscle attachment of the Late Triassic sauropodomorph
Thecodontosaurus antiquus
from multiple well-preserved specimens and provide the first complete forelimb and hindlimb musculature reconstruction of an early-branching sauropodomorph. Comparisons with other sauropodomorphs and early dinosaurs reveal a unique combination of both plesiomorphic and derived musculoskeletal features. The diversity of appendicular osteological correlates among early dinosaurs and their relevance in muscle reconstruction are discussed. In line with previous evidence, aspects of the limb muscle arrangement, such as conspicuous correlates of lower limb extensors and flexors and low moment arms of hip extensors and flexors, suggest
Thecodontosaurus
was an agile biped. This reconstruction helps to elucidate the timing of important modifications of the appendicular musculature in the evolution of sauropodomorphs which facilitated the transition to quadrupedalism and contributed to their evolutionary success.
A double-population chaotic self-adaptive evolutionary dynamics model for the prediction of supercritical carbon dioxide solubility in polymers
Authors: Wu Yan , Zhang Hang , Li Meng-shan , Sheng Sheng , Wang Jun , Wu Fu-an
Published: January 2022

Solubility of gas in polymers is an important physico-chemical property of foam materials and widely used in the preparation and modification of new materials. Under the conditions of high temperature and high pressure, the dissolution process is a nonlinear, non-equilibrium and dynamic process, so it is difficult to establish an accurate solubility calculation model. Inspired by particle dynamics and evolutionary algorithm, this paper proposes a hybrid model based on chaotic self-adaptive particle dynamics evolutionary algorithm (CSA-PD-EA), which can use the iterative process of particles in evolutionary algorithms at the dynamic level to simulate the mutual diffusion process of molecules during dissolution. The predicted solubility of supercritical CO
2
in poly(d,l-lactide-
co
-glycolide), poly(l-lactide) and poly(vinyl acetate) indicated that the comprehensive prediction performance of the CSA-PD-EA model was high. The calculation error and correlation coefficient were, respectively, 0.3842 and 0.9187. The CSA-PD-EA model showed prominent advantages in accuracy, efficiency and correlation over other computational models, and its calculation time was 4.144–15.012% of that of other dynamic models. The CSA-PD-EA model has wide application prospects in the computation of physical and chemical properties and can provide the basis for the theoretical calculation of multi-scale complex systems in chemistry, materials, biology and physics.
Explicit calculation method for cell alignment in non-circular geometries
Authors: Miyazako Hiroki , Nara Takaaki
Published: January 2022

The alignment of spindle-shaped cells in two-dimensional geometries induces singular points called topological defects, at which the alignment angle of the cell cannot be defined. To control defects related to biological roles such as cell apoptosis, calculation methods for predicting the defect positions are required. This study proposes an explicit calculation method for predicting cell alignment and defect positions in non-circular geometries. First, a complex potential is introduced to describe the alignment angles of cells, which is used to derive an explicit formula for cell alignment in a unit disc. Then, the derived formula for the unit disc is extended to the case for non-circular geometries using a numerical conformal mapping. Finally, the complex potential allows a calculation of the Frank elastic energy, which can be minimized with respect to the defect positions to predict their equilibrium state in the geometry. The proposed calculation method is used to demonstrate a numerical prediction of multiple defects in circular and non-circular geometries, which are consistent with previous experimental results.
Strategic pheromone signalling by mate searching females of the sexually cannibalistic spiderArgiope bruennichi
Authors: Weiss Katharina , Schneider Jutta M.
Published: January 2022

Reproduction often requires finding a mating partner. To this end, females of many arthropods advertise their presence to searching males via volatile chemical signals. Such pheromones are considered low-cost signals, although this notion is based on little evidence and has recently been challenged. Even when using comparatively low-cost signals, females should signal as little as possible to minimize costs while still ensuring mate attraction. Here, we test the strategic-signalling hypothesis usingArgiope bruennichi. In this orb-weaving spider, egg maturation commences with adult moult, and females that do not attract a male in time will lay a large batch of unfertilized eggs approximately three weeks after maturation. Using GC-MS analyses, we show that virgin females enhance their signalling effort, i.e. pheromone quantity per unit body mass, with increasing age and approaching oviposition. We further demonstrate that pheromone release is condition dependent, suggesting the occurrence of physiological costs. Mate choice assays revealed that pheromone quantity is the only predictor of female attractiveness for males. In support of the strategic-signalling hypothesis, pheromone signals by femaleA. bruennichibecome stronger with increased need as well as body condition, and might thus qualify as an honest signal of female quality.
Multiscale analysis of the randomization limits of the chromosomal gene organization between Lepidoptera and Diptera
Authors: Ranz José M. , González Pablo M. , Su Ryan N. , Bedford Sarah J. , Abreu-Goodger Cei , Markow Therese
Published: January 2022

How chromosome gene organization and gene content evolve among distantly related and structurally malleable genomes remains unresolved. This is particularly the case when considering different insect orders. We have compared the highly contiguous genome assemblies of the lepidopteranDanaus plexippusand the dipteranDrosophila melanogaster,which shared a common ancestor around 290 Ma. The gene content of 23 out of 30D. plexippuschromosomes was significantly associated with one or two of the six chromosomal elements of theDrosophilagenome, denoting common ancestry. Despite the phylogenetic distance, 9.6% of the 1-to-1 orthologues still reside within the same ancestral genome neighbourhood. Furthermore, the comparisonD. plexippus–Bombyx moriindicated that the rates of chromosome repatterning are lower in Lepidoptera than in Diptera, although still within the same order of magnitude. Concordantly, 14 developmental gene clusters showed a higher tendency to retain full or partial clustering inD. plexippus,further supporting that the physical association between the SuperHox and NK clusters existed in the ancestral bilaterian. Our results illuminate the scope and limits of the evolution of the gene organization and content of the ancestral chromosomes to the Lepidoptera and Diptera while helping reconstruct portions of the genome in their most recent common ancestor.
Stable isotope signals provide seasonal climatic markers for moss functional groups
Authors: Royles Jessica , Young Sophie , Griffiths Howard
Published: January 2022

Living moss biomass and archival peat deposits represent key indicators of present and past climatic conditions, but prediction of future climatic impacts requires appropriate marker species to be characterized under a range of contemporary conditions. Stable isotope signals in high latitude moss deposits offer potential climatic proxies. Seasonal changes in δ13C and δ18O of organic material (cellulose) in representative functional groups, and associated photosynthetic activity (as chlorophyll fluorescence) have been compared across East Anglia, UK, as a function of tissue water content. Representative species from contrasting acid bog, heathland, and fen woodland habitats were selected for monthly sampling of recent growth tissues between spring 2017 and autumn 2018, with isotopic signals in purified cellulose compared with tissue water, precipitation, and nearby groundwater signals. Sphagnum and Polytrichum groups, which tend to dominate peat formation, provided contrasting and complementary indicators of seasonal variations in carbon assimilation. Cellulose δ18O signals fromSphagnumspp. demonstrate seasonal variations in source precipitation inputs; carbon isotope signals inPolytrichumspp. indicate evaporative demand and photosynthetic limitation.
Ornithinimicrobium laminariae sp. nov., isolated from the kelp Laminaria japonica
Authors: Cao Wen-Rui , Yu Xin-Ran , Sun Yuan-yuan , Jiang Ming-Yu , Xu Xiao-Dong , Li Ying-Jie
Published: January 2022

A Gram-stain-positive, aerobic, non-sporulating, yellow-pigmented and rod or cocci-shaped bacterium, designated Arc0846-15T, was isolated from the kelp Laminaria japonica. Strain Arc0846-15T was found to grow at 16–35 °C (optimum, 28 °C), at pH 6.0–9.5 (optimum, 7.0) and in the presence of 0–6 % (w/v) NaCl (optimum, 2 %). Cells were positive for catalase and negative for oxidase activity. Phylogenetic analyses, based on 16S rRNA gene sequence comparisons, revealed that the nearest phylogenetic neighbour strains of strain Arc0846-15T were

Ornithinimicrobium murale

01 Gi-040T (96.2 %),

Ornithinimicrobium kibberense

K22-20T (96.1 %) and

Ornithinimicrobium humiphilum

HKI 0124T (95.2 %). Based on phylogenomic analysis, the average nucleotide identity values between strain Arc0846-15T and the neighbour strains were 69.8, 69.7 and 69.8 %, respectively; the digital DNA–DNA hybridization values between strain Arc0846-15T and its three closest neighbour strains were 18.8, 19.1 and 19.3 %, respectively. The predominant menaquinone was MK-8 (H4). The dominant cellular fatty acids were C17 : 1
 ω8c, iso-C15 : 0, iso-C16 : 0 and C17 : 0. The polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, glycolipid, one unidentified aminolipid and four unidentified lipids. The DNA G+C content of strain Arc0846-15T was 61.6 mol% based on the whole genome sequence. Based on the phylogenetic and phenotypic characteristics, strain Arc0846-15T is considered to represent a novel species of the genus

Ornithinimicrobium

, for which the name Ornithinimicrobium laminariae sp. nov. is proposed, with Arc0846-15T (=KCTC 49655T=MCCC 1K06093T) as the type strain.
Wickerhamiella nakhonpathomensis f.a. sp. nov., a novel ascomycetous yeast species isolated from a mushroom and a flower in Thailand
Authors: Khunnamwong Pannida , Kingphadung Kanokwan , Lomthong Thanasak , Kanpiengjai Apinun , Khanongnuch Chartchai , Limtong Savitree
Published: January 2022

Strains SU22T (TBRC 14875T) and FLA11.5, representing a novel anamorphic yeast species, were respectively isolated from a fruiting body of a Coprinus species and an inflorescence of a Coffea species collected in Thailand. Analysis of the sequences of the D1/D2 domains of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) regions showed that the two strains differed by two nucleotide substitutions in the D1/D2 domains of the LSU rRNA gene and were identical in the ITS regions. Wickerhamiella drosophilae CBS 8459T was the most closely related species, but with 24–26 nucleotide substitutions in the D1/D2 domains of the LSU rRNA gene and 24 nucleotide substitutions in the ITS regions. A phylogenetic analysis, based on the sequences of the D1/D2 domains, indicated that the two strains represented a species in the genus Wickerhamiella which was distinct from other recognized species of the genus. Therefore, the two strains were assigned as a novel species, for which we propose the name Wickerhamiella nakhonpathomensis f.a. sp. nov. The holotype is TBRC 14875T (isotype PYCC 8914T). The MycoBank number of the novel species is MB 840833.
A protocol for locating and counting transgenic sequences from laboratory animals using a map-then-capture (MapCap) sequencing workflow: procedure and application of results
Authors: Dicke Sidney S. , Rubinstein C. Dustin , Speers James M. , Berres Mark E. , Pavelec Derek M. , Schueler Kathryn L. , Stapleton Donnie S. , Simonett Shane P. , Keller Mark P. , Attie Alan D. , Zanni Martin T.
Published: January 2022

Transgenic rodent models for human diseases have been widely used over the past 50 years and are a mainstay of many biomedical research programs. Oftentimes the sequence of the transgenic segment of DNA is carefully designed but incorporation of this DNA into the host genome is less well understood. Structural variation and insertional mutagenesis may occur at transgenic insertion sites. Here, we present a robust workflow including identification of the transgene locus via selective Illumina sequencing followed by Cas9-mediated target DNA enrichment of the locus, which successfully identified beginning and end sites of a large transgenic insertion into a murine model for human amylin-induced type II diabetes. Enriched sequences were mapped via Oxford Nanopore sequencing. Although the insertion was too long for a single mapped genetic sequence to encompass, the method provided multiple insights relevant to the animal model: a minimum number of forward- and reverse-facing transcript copies as well as characterization of an inversion point within the insertion site. The insertion start point containing both murine and human DNA was used to identify and separate animals hemizygous for the transgenic insertion from homozygous animals. This identification could be performed early in the rodent life cycle prior to maturation (i.e. breeding age), thus allowing for management of colony phenotypes and eliminating the need to “genotype by phenotype” later on (onset of amylin-induced type II diabetes does not occur until ~8-10 weeks of age for this model). We further confirmed our homozygous diabetic mice function the same as colonies established in other labs and present full antibody and fluorescent-staining protocols (available in SI). Lastly, we note that, due to our genotyping, a novel animal was identified within our colony: non-diabetic homozygous mice. Indeed, only 37% of homozygous mice bred in our colony became diabetic.

AUTHOR SUMMARY (for broad audience)

Transgenic rodent models are important to studying human diseases. When creating a new rodent model, one may insert new DNA into a well-characterized background genome. However, it is oftentimes not known where the new DNA was incorporated, how many times it was incorporated, or if any coding sequences or regulatory elements within native DNA were disrupted. Here, we have developed a method to characterize transgenic animals, and have applied it to a popular model for studying human amylin-induced type II diabetes.
JAX Animal Behavior System (JABS): A genetics informed, end-to-end advanced behavioral phenotyping platform for the laboratory mouse
Authors: Choudhary Anshul , Geuther Brian Q. , Sproule Thomas J. , Beane Glen , Kohar Vivek , Trapszo Jarek , Kumar Vivek
Published: January 2022

Automated detection of complex animal behavior remains a challenge in neuroscience. Developments in computer vision have greatly advanced automated behavior detection and allow high-throughput preclinical and mechanistic studies. An integrated hardware and software solution is necessary to facilitate the adoption of these advances in the field of behavioral neurogenetics, particularly for non-computational laboratories. We have published a series of papers using an open field arena to annotate complex behaviors such as grooming, posture, and gait as well as higher-level constructs such as biological age and pain. Here, we present our, integrated rodent phenotyping platform, JAX Animal Behavior System (JABS), to the community for data acquisition, machine learning-based behavior annotation and classification, classifier sharing, and genetic analysis. The JABS Data Acquisition Module (JABS-DA) enables uniform data collection with its combination of 3D hardware designs and software for real-time monitoring and video data collection. JABS-Active Learning Module (JABS-AL) allows behavior annotation, classifier training, and validation. We introduce a novel graph-based framework (ethograph) that enables efficient boutwise comparison of JABS-AL classifiers. JABS-Analysis and Integration Module (JABS-AI), a web application, facilitates users to deploy and share any classifier that has been trained on JABS, reducing the effort required for behavior annotation. It supports the inference and sharing of the trained JABS classifiers and downstream genetic analyses (heritability and genetic correlation) on three curated datasets spanning 168 mouse strains that we are publicly releasing alongside this study. This enables the use of genetics as a guide to proper behavior classifier selection. This open-source tool is an ecosystem that allows the neuroscience and genetics community for shared advanced behavior analysis and reduces the barrier to entry into this new field.
Data-driven research on eczema: systematic characterization of the field and recommendations for the future
Authors: Duverdier A. , Custovic A. , Tanaka R.J.
Published: January 2022

Background

The past decade has seen a substantial rise in the employment of modern data-driven methods to study atopic dermatitis (AD) / eczema.

Objective

To summarise the past and future of data-driven AD research, and identify areas in the field that would benefit from the application of these methods.

Methods

We retrieved the publications that applied multivariate statistics (MS), artificial intelligence (AI, including machine learning-ML), and Bayesian statistics (BS) to AD and eczema research from the SCOPUS database over the last 50 years. We conducted a bibliometric analysis to highlight the publication trends and conceptual knowledge structure of the field, and applied topic modelling to retrieve the key topics in the literature.

Results

Five key themes of data-driven research on AD and eczema were identified: (1) allergic co-morbidities, (2) image analysis and classification, (3) disaggregation, (4) quality of life, and (5) risk factors and prevalence. ML&AI methods mapped to studies investigating quality of life, prevalence, risk factors, allergic co-morbidities and disaggregation of AD/eczema, but seldom in studies of therapies. MS was employed evenly between the topics, particularly in studies on risk factors and prevalence. BS was focused on three key topics: treatment, risk factors and allergy. The use of AD or eczema terms was not uniform, with studies applying ML&AI methods using the term eczema more often. Within MS, papers using cluster and factor analysis were often only identified with the term AD. In contrast, those using logistic regression and latent class/transition models were “eczema” papers.

Conclusions

Research areas that could benefit from the application of data-driven methods include the study of the pathogenesis of the condition and related risk factors, its disaggregation into validated subtypes, and personalized severity management and prognosis. We highlight Bayesian statistics as a new and promising approach in AD and eczema research.
Understanding evolution of COVID-19 driven mortality rate
Authors: Bhaumik Ishika , Sinha-Ray Suman , Chaudhary Anshul , Srivastava Abhishek , Kodgire Prashant
Published: January 2022

Objective

COVID-19 has resulted in the death of almost 4 million people till date1. However, the mortality rate across countries seems to be vastly different irrespective of their respective socio-economic backgrounds. It is well known now that COVID-19 is an acute inflammatory infectious disease that gets complicated by type-I interferon response2,3. However, the precise reason for variations in COVID-19 related mortality rates is unknown. A detailed understanding behind the evolution of mortality rate around the globe is needed.

Methods

In this article, we show that a biological science guided machine learning-based approach can predict the evolution of mortality rates across countries. We collected the publicly available data of all the countries in the world with regard to the mortality rate and the relevant biological and socio-economical causes. The data was analyzed using a novel FFT driven machine learning algorithm.

Results

Our results demonstrate how COVID-19 related mortality rate is closely dependent on a multitude of socio-economic factors (population density, GDP per capita, global health index and population above 65 years of age), environmental (PM2.5 air pollution) and lifestyle aka food habits (meat consumption per capita, alcohol consumption per capita, dairy product consumption per capita and sugar consumption per capita). Interestingly, we found that individually these parameters show no visible trend that can be generalized with mortality.

Conclusions

We anticipate that our work will initiate conversations between health officials, policymakers and world leaders towards providing preventative measures against COVID-19 and future coronavirus-based diseases and endemics/ pandemics by taking a holistic view.
Automatic colorectal cancer screening using deep-learning on spatial light interference microscopy data
Authors: Zhang Jingfang K. , Fanous Michael , Sobh Nahil , Balla Andre , Popescu Gabriel
Published: January 2022

The surgical pathology workflow currently adopted in the clinic uses staining to reveal tissue architecture within thin sections. A trained pathologist then conducts a visual examination of these slices and, as the investigation is based on an empirical assessment, a certain amount of subjectivity is unavoidable. Furthermore, the reliance on such external contrast agents like hematoxylin and eosin (H&E), albeit a well-established method, makes it difficult to standardize color balance, staining strength, and imaging conditions, hindering automated computational analysis. In response to these challenges, we applied spatial light interference microscopy (SLIM), a label-free method that generates contrast based on the intrinsic tissue refractive index signatures. Thus, we reduce human bias and make the image data comparable across instruments and clinics. We applied a Mask R-CNN deep learning algorithm to the SLIM data to achieve an automated colorectal cancer screening procedure, i.e., classifying normal vs. cancer specimens. Our results obtained on a tissue microarray consisting of specimens from 132 patients, resulted in 91% accuracy for gland detection, 99.71% accuracy in gland-level classification, and 97% accuracy in core-level classification. A SLIM tissue scanner accompanied by an application-specific deep learning algorithm may become a valuable clinical tool, enabling faster and more accurate assessment by the pathologist.
Time to commencement of effective treatment in patients with drug-resistant tuberculosis diagnosed in the Torres Strait / Papua New Guinea cross-border region
Authors: Foster J’Belle , Mendez Diana , Marais Ben J. , Peniyamina Dunstan , McBryde Emma S.
Published: January 2022

Introduction

Delays between self-reported symptom onset and commencement of effective treatment contribute to ongoing tuberculosis (TB) transmission, which is a particular concern in patients with drug-resistant (DR)-TB. We assessed improvements in time to commencement of effective treatment in patients diagnosed with DR-TB in the Torres Strait / Papua New Guinea cross-border region.

Methods

All laboratory-confirmed DR-TB cases diagnosed in the Torres Strait between 1 March 2000 and 31 March 2020 were reviewed. We assessed the total time from self-reported onset of symptoms to effective treatment commencement in different programmatic time periods. Pairwise analyses and time to event proportional hazard calculations were used to explore the association between delays in median time to effective treatment, and selected variables. Data were further analysed to examine predictors of excessive treatment delay.

Results

The median number of days from self-reported onset of symptoms to effective treatment commencement was 124 days (interquartile range 51-214) over two decades. Between 2006 and 2012, most (57%) cases exceeded this ‘grand median’ while the median ‘time to treat’ in the most recent time period (2016-2020) was significantly reduced to 29 days (p<0.001). Although there was a reduction in the median ‘time to treat’ with the introduction of Xpert MTB/RIF (135 days pre-Xpert vs 67 days post-Xpert) this was not statistically significant (p0.07). Establishment of the Torres and Cape TB Control Unit on Thursday Island (2016-2020) was significantly associated with reduced treatment delay, compared to previous TB program period (2000-2005p<0.04; 2006-2012p<0.001).

Conclusion

Minimising TB treatment delay in remote settings like the Torres Strait / Papua New Guinea cross-border region requires effective decentralised diagnosis and management structures. The results of this study suggest that the establishment of the Torres and Cape TB Control Unit on Thursday Island significantly improved time to commencement of effective TB treatment. Possible contributing factors include better TB education, cross-border communication and patient-centred care.
Use of unstructured text in prognostic clinical prediction models: a systematic review
Authors: Seinen Tom M. , Fridgeirsson Egill , Ioannou Solomon , Jeannetot Daniel , John Luis H. , Kors Jan A. , Markus Aniek F. , Pera Victor , Rekkas Alexandros , Williams Ross D. , Yang Cynthia , van Mulligen Erik , Rijnbeek Peter R.
Published: January 2022

Objective

This systematic review aims to assess how information from unstructured clinical text is used to develop and validate prognostic risk prediction models. We summarize the prediction problems and methodological landscape and assess whether using unstructured clinical text data in addition to more commonly used structured data improves the prediction performance.

Materials and Methods

We searched Embase, MEDLINE, Web of Science, and Google Scholar to identify studies that developed prognostic risk prediction models using unstructured clinical text data published in the period from January 2005 to March 2021. Data items were extracted, analyzed, and a meta-analysis of the model performance was carried out to assess the added value of text to structured-data models.

Results

We identified 126 studies that described 145 clinical prediction problems. Combining text and structured data improved model performance, compared to using only text or only structured data. In these studies, a wide variety of dense and sparse numeric text representations were combined with both deep learning and more traditional machine learning methods. External validation, public availability, and explainability of the developed models was limited.

Conclusion

Overall, the use of unstructured clinical text data in the development of prognostic prediction models has been found beneficial in addition to structured data in most studies. The EHR text data is a source of valuable information for prediction model development and should not be neglected. We suggest a future focus on explainability and external validation of the developed models, promoting robust and trustworthy prediction models in clinical practice.
Systematic recovery of building plumbing-associated microbial communities after extended periods of altered water demand during the COVID-19 pandemic
Authors: Vosloo Solize , Huo Linxuan , Chauhan Umang , Cotto Irmarie , Gincley Benjamin , Vilardi Katherine J , Yoon Byungman , Pieper Kelsey J , Stubbins Aron , Pinto Ameet
Published: January 2022

Building closures related to the coronavirus disease (COVID-19) pandemic resulted in increased water stagnation in commercial building plumbing systems that heightened concerns related to the microbiological safety of drinking water post re-opening. The exact impact of extended periods of reduced water demand on water quality is currently unknown due to the unprecedented nature of widespread building closures. We analyzed 420 tap water samples over a period of six months, starting the month of phased reopening (i.e., June 2020), from sites at three commercial buildings that were subjected to reduced capacity due to COVID-19 social distancing policies and four occupied residential households. Direct and derived flow cytometric measures along with water chemistry characterization were used to evaluate changes in plumbing-associated microbial communities with extended periods of altered water demand. Our results indicate that prolonged building closures impacted microbial communities in commercial buildings as indicated by increases in microbial cell counts, encompassing greater proportion cells with high nucleic acids. While flushing reduced cell counts and increased disinfection residuals, the microbial community composition in commercial buildings were still distinct from those at residential households. Nonetheless, increased water demand post-reopening enhanced systematic recovery over a period of months, as microbial community fingerprints in commercial buildings converged with those in residential households. Overall, our findings suggest that sustained and gradual increases in water demand may play a more important role in the recovery of building plumbing-associated microbial communities as compared to short-term flushing, after extended periods of altered water demand that result in reduced flow volumes.
Disruption of the MYC Super-Enhancer Complex by Dual Targeting of FLT3 and LSD1 in Acute Myeloid Leukemia
Authors: Yashar William M. , Curtiss Brittany M. , Coleman Daniel J. , Van-Campen Jake , Kong Garth , Macaraeg Jommel , Estabrook Joseph , Demir Emek , Long Nicola , Bottomly Dan , McWeeney Shannon K. , Tyner Jeffrey W. , Druker Brian J. , Maxson Julia E. , Braun Theodore P.
Published: January 2022

Mutations in Fms-like tyrosine kinase 3 (FLT3) are common drivers in acute myeloid leukemia (AML) yet FLT3 inhibitors only provide modest clinical benefit. Prior work has shown that inhibitors of lysine-specific demethylase 1 (LSD1) enhance kinase inhibitor activity in AML. Here we show that combined LSD1 and FLT3 inhibition induces synergistic cell death in FLT3-mutant AML. Multi-omic profiling revealed that the drug combination disrupts STAT5, LSD1, and GFI1 binding at the MYC blood super-enhancer, suppressing super-enhancer activation as well as MYC expression and activity. The drug combination simultaneously results in the accumulation of repressive H3K9me1 methylation, an LSD1 substrate, at MYC target genes. We validated these findings in 72 primary AML samples with the nearly every sample demonstrating synergistic responses to the drug combination. Collectively, these studies provide preclinical rationale for the investigation of dual FLT3/LSD1 inhibition in a clinical trial.