bluuebunny/crossref_metadata_2025 huggingface dataset:
A Longitudinal Evaluation of Computed Tomography Radiation Incidents Within a Multisite NHS Trust
Authors: Adamson Helen Katie , Foster Beverley , Clarke Ruth , Scally Andrew , Snaith Beverly
Published: May 2022

Objectives

This single-center review explores trends in computed tomography “radiation incidents” and suggests strategies for improvement.

Method

A retrospective mixed-methods approach was used in this longitudinal evaluation of radiation incidents within a multisite NHS Trust in northern England. DATIX was interrogated at the Trust level to identify all records linked to radiation incident in computed tomography departments between January 1, 2015, and December 31, 2018.

Results

During the 4-year review period, 159,596 exams were performed at the Trust and a total of 133 incidents were recorded. This comprised 42.1% (n = 56) of radiation incidents, 43.6% (n = 58) of near-miss incidents, and 14.3% (n = 19) of repeat scans due to extravasation of contrast. The reported radiation incident rate was 0.08%. These data suggest an approximation of 1 incident per thousand cases. Most incidents were investigated using a “system approach,” and the reports highlighted the relevant action that had been taken to try and prevent recurrence of the incident. Qualitative data collected from the root cause analysis minutes demonstrated themes related to the contributory factors, incident analysis performed, and overall learning.

Conclusions

Computed tomography departments need to focus on a system approach instead of the “person approach” to identify areas where efficiencies can be implemented. Staff should feel open to discuss system inefficiencies that they experience and may highlight problems the management is unaware of. The reporting of all types of incidents, including near misses, should be encouraged, to foster an open culture and to expand learning.
The Stoplight Mobility Alert System for Safety and Prevention of Falls in Children With Physical and Cognitive Impairments
Authors: Mullen Joellan B. , Wirt Steven Z. , Moser Alana , Niedzwecki Christian
Published: May 2022

Objective(s)

This study aimed to decrease the rate of falls in children with cognitive and physical impairments on a pediatric acute inpatient rehabilitation unit (IRU) using a novel tool, the Stoplight Mobility Alert System (SMAS).

Methods

We conducted a pilot, prospective, quality improvement study in an 8-bed (increased to 12 beds; October 1, 2019) acute inpatient pediatric IRU at a level 1 trauma center. All patients admitted between October 1, 2012, and October 1, 2020, were included as participants. Interventions used were as follows: (1) SMAS, a colored alert system placed on door slides and in-room for visual cues (red, assistance/hands on; yellow, supervision/eyes on; green, independent/hands off), and (2) handouts and one-on-one education for staff and patients/families. Main outcome measures included fall rate on the IRU.

Results

Using the SMAS, the total fall rate decreased from 10.78 to 4.36 falls per 1000 patient-days. Longitudinally, the intrinsic fall rate decreased from 8.36 to 5.60 falls per 1000 patient-days, and the extrinsic fall rate decreased from 4.56 to 1.36 falls per 1000 patient-days.

Conclusions

The implementation of the SMAS is effective in decreasing total, intrinsic, and extrinsic fall rates in an acute pediatric inpatient rehabilitation program both acutely and longitudinally.
The impact of ankle-foot orthosis's plantarflexion resistance on knee adduction moment in people with chronic stroke
Authors: Kobayashi Toshiki , Hunt Grace , Orendurff Michael S. , Gao Fan , Singer Madeline L. , Foreman K. Bo
Published: May 2022

Background:

An ankle-foot orthosis (AFO) is used to assist gait of people with chronic stroke. It is widely accepted that AFO’s plantarflexion resistance affects sagittal knee moments during their gait. However, its effect on the coronal knee moment remains unclear. This study aimed to examine the effects of varying articulated AFO’s plantarflexion resistance on knee adduction moment in people with chronic stroke.

Methods:

Ten people with chronic stroke participated in this study. Gait performance was measured using a Vicon 3-dimensional motion capture system and a Bertec split-belt instrumented treadmill. The participants walked on the treadmill wearing an articulated AFO whose plantarflexion resistance could be systematically adjusted. The ankle joints were set to four distinct levels of plantarflexion resistance (S1 < S2 < S3 < S4). The coronal ankle and knee joint moment, center of pressure, and ground reaction force were analyzed using Visual3D.

Results:

The external knee adduction moment increased significantly (P < .001) and the position of the center of pressure trajectory shifted significantly (P = .003) in the medial direction as the plantarflexion resistance of the AFO was increased from the least resistive condition (S1) to the most resistive condition (S4). The maximum knee adduction moment (median [interquartile range]) was S1: 0.097 (−0.012 to 0.265) Nm/kg; S2: 0.136 (0.040 to 0.287) Nm/kg; S3: 0.160 (0.465 to 0.289) Nm/kg; and S4: 0.192 (0.080 to 0.288) Nm/kg.

Conclusions:

This study demonstrated that varying AFO’s plantarflexion resistance altered the knee adduction moment, likely by altering the center of pressure trajectory while walking, in people with chronic stroke.
Convergence to precipitating quasi-geostrophic equations with phase changes: asymptotics and numerical assessment
Authors: Zhang Yeyu , Smith Leslie M. , Stechmann Samuel N.
Published: May 2022

The quasi-geostrophic (QG) equations play a crucial role in our understanding of atmospheric and oceanic fluid dynamics. Nevertheless, the traditional QG equations describe ‘dry’ dynamics that do not account for moisture and clouds. To move beyond the dry setting, precipitating QG (PQG) equations have been derived recently using formal asymptotics. Here, we investigate whether the moist Boussinesq equations with phase changes will converge to the PQG equations.
A priori
, it is possible that the nonlinearity at the phase interface (cloud edge) may complicate convergence. A numerical investigation of convergence or non-convergence is presented here. The numerical simulations consider cases of

ϵ
=
0.1

, 0.01 and 0.001, where

ϵ

is proportional to the Rossby and Froude numbers. In the numerical simulations, the magnitude of vertical velocity

w

(or other measures of imbalance and inertio-gravity waves) is seen to be approximately proportional to

ϵ

as

ϵ

decreases, which suggests convergence to PQG dynamics. These measures are quantified at a fixed time

T

that is

O
(
1
)

, and the numerical data also suggests the possibility of convergence at later times.

This article is part of the theme issue ‘Mathematical problems in physical fluid dynamics (part 2)’.
On the dynamics of point vortices for the two-dimensional Euler equation with
L

p

vorticity
Authors: Ceci Stefano , Seis Christian
Published: May 2022

We study the evolution of solutions to the two-dimensional Euler equations whose vorticity is sharply concentrated in the Wasserstein sense around a finite number of points. Under the assumption that the vorticity is merely

L
p

integrable for some

p
>
2

, we show that the evolving vortex regions remain concentrated around points, and these points are close to solutions to the Helmholtz–Kirchhoff point vortex system.

This article is part of the theme issue ‘Mathematical problems in physical fluid dynamics (part 2)’.
On the role of continuous symmetries in the solution of the three-dimensional Euler fluid equations and related models
Authors: Bustamante Miguel D.
Published: May 2022

We review and apply the continuous symmetry approach to find the solution of the three-dimensional Euler fluid equations in several instances of interest, via the construction of constants of motion and infinitesimal symmetries, without recourse to Noether’s theorem. We show that the vorticity field is a symmetry of the flow, so if the flow admits another symmetry then a Lie algebra of new symmetries can be constructed. For steady Euler flows this leads directly to the distinction of (non-)Beltrami flows: an example is given where the topology of the spatial manifold determines whether extra symmetries can be constructed. Next, we study the stagnation-point-type exact solution of the three-dimensional Euler fluid equations introduced by Gibbon
et al.
(Gibbon
et al.
1999
Physica D
132
, 497–510. (
doi:10.1016/S0167-2789(99)00067-6
)) along with a one-parameter generalization of it introduced by Mulungye
et al.
(Mulungye
et al.
2015
J. Fluid Mech.
771
, 468–502. (
doi:10.1017/jfm.2015.194
)). Applying the symmetry approach to these models allows for the explicit integration of the fields along pathlines, revealing a fine structure of blowup for the vorticity, its stretching rate and the back-to-labels map, depending on the value of the free parameter and on the initial conditions. Finally, we produce explicit blowup exponents and prefactors for a generic type of initial conditions.

This article is part of the theme issue ‘Mathematical problems in physical fluid dynamics (part 2)’.
Equations of motion for weakly compressible point vortices
Authors: Llewellyn Smith Stefan G. , Chu T. , Hu Z.
Published: May 2022

Equations of motion for compressible point vortices in the plane are obtained in the limit of small Mach number,
M
, using a Rayleigh–Jansen expansion and the method of Matched Asymptotic Expansions. The solution in the region between vortices is matched to solutions around each vortex core. The motion of the vortices is modified over long time scales

O
(

M
2

log
⁡

M

)

and

O
(

M
2

)

. Examples are given for co-rotating and co-propagating vortex pairs. The former show a correction to the rotation rate and, in general, to the centre and radius of rotation, while the latter recover the known result that the steady propagation velocity is unchanged. For unsteady configurations, the vortex solution matches to a far field in which acoustic waves are radiated.

This article is part of the theme issue ‘Mathematical problems in physical fluid dynamics (part 2)’.
Bacillus suaedae sp. nov., isolated from the stem of Suaeda aralocaspica in north-west China
Authors: Lei Rui-Feng , Ma Qin , Li Yu-Qian , Abudourousuli Dilireba , Wang Shuang , Rouzi Zulihumaer , Aosiman Muyesaier , An Deng-Di , Li Wen-Jun
Published: May 2022

A bacterial strain, designated YZJH907-2T, was isolated from the stem of Suaeda aralocaspica, collected from the southern edge of the Gurbantunggut desert, Xinjiang, PR China. Cells of strain YZJH907-2T were Gram-stain-positive, aerobic and rod-shaped. They formed white or colourless circular colonies with smooth convex surfaces. Strain YZJH907-2T grew at 4–50 °C (optimum, 28–30 °C), pH 7.0–10.0 (optimum, pH 8.0–9.0) and with 0–10 % (w/v) NaCl (optimum, 3–7 %). The genomic DNA G+C content of strain YZJH907-2T was 38.1 mol%. Phylogenetic analysis based on 16S rRNA gene sequence similarity showed that the strain was most closely related to

Bacillus alcalophilus

DSM 485T (97.37 %),

Bacillus kiskunsagensis

B16-24T (96.87 %) and

Bacillus bogoriensis

LBB3T (96.71 %). Average nucleotide identity values between YZJH907-2T and

B. alcalophilus

DSM 485Tand

B. bogoriensis

LBB3T were 69.2 and 69.0 %, respectively. Digital DNA–DNA hybridization values of YZJH907-2T with

B. alcalophilus

DSM 485T and

B. bogoriensis

LBB3T were 19.6 and 20.4 %, respectively. The cell wall of strain YZJH907-2T contained meso-diaminopimelic acid, and the major and secondary isoprenoid quinones were MK-7 and MK-5, respectively. Results of fatty acids showed that anteiso-C15 : 0, iso-C15 : 0 and C16 : 0 were the predominant cellular fatty acids. Two-dimensional thin-layer chromatography analysis indicated that the polar lipids included diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, three unidentified phospholipids and two unidentified glycolipids. Based on the genomic, phylogenetic and phenotypic analyses, strain YZJH907-2T represented a novel species of the genus

Bacillus

, and thus the name Bacillus suaedae sp. nov. is proposed. The type strain is YZJH907-2T (=CGMCC 1.18763T=KCTC 43335T).
A novelde novoFEM1C variant is linked to neurodevelopmental disorder with absent speech, pyramidal signs, and limb ataxia
Authors: Dubey Abhishek Anil , Krygier Magdalena , Szulc Natalia A. , Rutkowska Karolina , Kosińska Joanna , Pollak Agnieszka , Rydzanicz Małgorzata , Kmieć Tomasz , Mazurkiewicz-Bełdzińska Maria , Pokrzywa Wojciech , Płoski Rafał
Published: May 2022

The principal component of the protein homeostasis network is the ubiquitin-proteasome system. Ubiquitination is mediated by an enzymatic cascade involving, i.e., E3 ubiquitin ligases, many of which belong to the cullin-RING ligases family. Genetic defects in the ubiquitin-proteasome system components, including cullin-RING ligases, are known causes of neurodevelopmental disorders. Using exome sequencing to diagnose a pediatric patient with developmental delay, pyramidal signs, and limb ataxia, we identified ade novomissense variant c.376G>C; p.(Asp126His) in theFEM1Cgene encoding a cullin-RING ligase substrate receptor. This variant alters a conserved amino acid located within a highly constrained coding region and is predicted as pathogenic by mostin silicotools. In addition, ade novo FEM1Cmutation of the same residue p.(Asp126Val) was associated with an undiagnosed developmental disorder, and the relevant variant (FEM1CAsp126Ala) was found to be functionally compromisedin vitro. Our computational analysis showed that FEM1CAsp126Hishampers protein substrate binding. To further assess its pathogenicity, we used the nematodeCaenorhabditis elegans. We found that the FEM-1Asp133Hisanimals (expressing variant homologous to theFEM1Cp.(Asp126Val)) had normal muscle architecture yet impaired mobility. Mutant worms were sensitive to the acetylcholinesterase inhibitor aldicarb but not levamisole (acetylcholine receptor agonist), showing that their disabled locomotion is caused by synaptic abnormalities and not muscle dysfunction. In conclusion, we provide the first evidence from an animal model suggesting that a mutation in the evolutionarily conserved FEM1C Asp126 position causes a neurodevelopmental disorder in humans.
Integrative analysis of the 3D genome and epigenome in mouse embryonic tissues
Authors: Yu Miao , Zemke Nathan R. , Chen Ziyin , Juric Ivan , Hu Rong , Raviram Ramya , Abnousi Armen , Fang Rongxin , Zhang Yanxiao , Gorkin David U. , Li Yang , Zhao Yuan , Lee Lindsay , Schmitt Anthony D. , Qiu Yunjiang , Dickel Diane E. , Visel Axel , Pennacchio Len A. , Hu Ming , Ren Bing
Published: May 2022

While a rich set of putative cis-regulatory sequences involved in mouse fetal development has been annotated recently based on chromatin accessibility and histone modification patterns, delineating their role in developmentally regulated gene expression continues to be challenging. To fill this gap, we mapped chromatin contacts between gene promoters and distal sequences genome-wide in seven mouse fetal tissues, and for one of them, across six developmental stages. We identified 248,620 long-range chromatin interactions centered at 14,138 protein-coding genes and characterized their tissue-to-tissue variations as well as developmental dynamics. Integrative analysis of the interactome with previous epigenome and transcriptome datasets from the same tissues revealed a strong correlation between the chromatin contacts and chromatin state at distal enhancers, as well as gene expression patterns at predicted target genes. We predicted target genes of 15,098 candidate enhancers, and used them to annotate target genes of homologous candidate enhancers in the human genome that harbor risk variants of human diseases. We present evidence that schizophrenia and other adult disease risk variants are frequently found in fetal enhancers, providing support for the hypothesis of fetal origins of adult diseases.
Ongoing Replication Stress Response and New Clonal T Cell Development Discriminate Between Liver and Lung Recurrence Sites and Patient Outcomes in Pancreatic Ductal Adenocarcinoma
Authors: Link Jason M. , Pelz Carl , Worth Patrick J. , Owen Sydney , Keith Dove , Langer Ellen M. , Grossblatt-Wait Alison , Creason Allison L. , Egger Julian , Holly Hannah , English Isabel , MacPherson Kevin , Tsuda Motoyuki , Goecks Jeremy , Demir Emek , Kardosh Adel , Lopez Charles D. , Sheppard Brett C. , Guimaraes Alex , Brinkerhoff Brian , Morgan Terry K. , Mills Gordon , Brody Jonathan , Sears Rosalie C.
Published: May 2022

Background and Aims

Metastatic pancreatic adenocarcinoma (mPDAC) is lethal, yet a subset of patients who have metastatic disease that spreads only to the lung have better outcomes. We identified unique transcriptomic and immune features that distinguish patients who develop metastases in the liver (liver cohort) versus those with lung-avid but liver-averse mPDAC (lung cohort).

Methods

We used clinical data from the Oregon Pancreas Tissue Registry to identify PDAC patients with liver and/or lung metastases. Gene expression and genomic alteration data from 290 PDAC tumors were used to identify features unique to patients from the liver and lung cohorts. In parallel, T cell receptor sequencing data from 289 patients were used to identify immune features unique to patients in the lung cohort.

Results

Lung cohort patients had better survival outcomes than liver cohort patients. Primary tumors from patients in the liver cohort expressed a novel gene signature associated with ongoing replication stress (RS) response predictive of poor patient outcome independent from known subtypes. In contrast, patients with tumors lacking the RS response signature survived longer, especially if their tumors had alterations in DNA damage repair genes. A subset of patients in the lung cohort demonstrated new T cell clonal development in their primary and metastatic tumors leading to diverse peripheral blood TCR repertoires.

Conclusion

Liver-avid metastatic PDAC is associated with an ongoing RS response, whereas tumors lacking the RS response with ongoing T cell clonal responses may have unique vulnerabilities allowing long-term survival in patients with lung-avid, liver-averse metastatic PDAC.
Synovial fibroblasts assume distinct functional identities and secrete R-spondin 2 to drive osteoarthritis
Authors: Knights Alexander J. , Farrell Easton C. , Ellis Olivia M. , Lammlin Lindsey , Junginger Lucas M. , Rzeczycki Phillip M. , Bergman Rachel F. , Pervez Rida , Cruz Monique , Samani Alexa A. , Wu Chia-Lung , Hankenson Kurt D. , Maerz Tristan
Published: May 2022

Objectives

Synovium is acutely affected following joint trauma and contributes to post-traumatic osteoarthritis (PTOA) progression. Little is known about discrete cell types and molecular mechanisms in PTOA synovium. We aimed to describe synovial cell populations and their dynamics in PTOA, with a focus on fibroblasts. We also sought to define mechanisms of synovial Wnt/β-catenin signaling, given its emerging importance in arthritis.

Methods

We subjected mice to non-invasive anterior cruciate ligament rupture as a model of human joint injury. We performed single-cell RNA-sequencing to assess synovial cell populations, subjected Wnt-GFP reporter mice to joint injury to study Wnt-active cells, and performed intra-articular injections of the Wnt agonist R-spondin 2 (Rspo2) to assess whether gain-of-function induced pathologies characteristic of PTOA. Lastly, we used cultured fibroblasts, macrophages, and chondrocytes to study how Rspo2 orchestrates crosstalk between joint cell types.

Results

We uncovered seven distinct functional subsets of synovial fibroblasts in healthy and injured synovium, and defined their temporal dynamics in early and established PTOA. Wnt/β-catenin signaling was overactive in PTOA synovium, and Rspo2 was strongly induced after injury and secreted exclusively by Prg4hilining fibroblasts. Trajectory analyses predicted that Prg4hilining fibroblasts arise from a pool of Dpp4+ mesenchymal progenitors in synovium, with SOX5 identified as a potential regulator of this emergence. We also showed that Rspo2 orchestrated pathological crosstalk between synovial fibroblasts, macrophages, and chondrocytes.

Conclusions

Synovial fibroblasts assume distinct functional identities during PTOA, and Prg4hilining fibroblasts secrete the Wnt agonist Rspo2 to drive pathological crosstalk in the joint after injury.
Characteristics of intestinal microflora and dysbiosis in relation to the disease duration in patients with Meniere’s disease
Authors: Mochizuki Fumihiro , Komori Manabu , Sasano Yoshiyuki , Ito Yusuke , Hoffer Michael E , Koizuka Izumi
Published: May 2022

Hypothesis

Dysbiosis of the intestinal microflora has been reported in stress-induced depression and irritable colitis, a similar abnormality may also occur in stress-triggered Meniere’s disease.

Background

Meniere’s disease is an intractable disease characterized by paroxysms of intense rotatory dizziness, hearing loss, and other auditory symptoms. It is believed to be caused by endolymphatic hydrops of the vestibule and cochlea. The diagnosis of Meniere’s disease is based on the diagnostic criteria established by the Barany Society and AAO-HNS and Journal of Vestibular Research as definite or probable cases. Endolymphatic hydrops identification using cochlear contrast-enhanced MRI (hybrid of reversed image of positive endolymph signal and native image of positive perilymph signal [HYDROPS]) is an objective test for Meniere’s disease, enabling reliable diagnosis of this disease.

Methods

We investigated the gut microbiota of 10 patients (6 males and 4 females, mean age 49.6 ± 8.1 years) who met the diagnostic criteria for a unilateral definite case of Meniere’s disease using the diagnostic criteria of the Journal of Vestibular Research, and who also had significant endolymphatic hydrops on the affected side on HYDROPS. Intestinal microbiota tests were performed on these 10 patients and the results were evaluated in relation to the duration of disease, results of audiometry of the affected side, and DHI (Dizziness Handicap Inventory) score.

Results

A significant negative correlation was found between the disease duration and Shannon diversity index and Faith’s phylogenetic diversity, which indicated dysbiosis of the intestinal microflora. No correlation was found between the indicators of microbial diversity and the results of audiometry or the DHI on the affected side. Dysbiosis of the intestinal microbiota worsened with increasing duration of Meniere’s disease. Moreover,Akkermansia muciniphilawas not detected in any patient with Meniere’s disease.

Conclusions.

Despite the small number of cases in this study (n = 10), the findings indicate the possibility of abnormalities of the intestinal microflora in Meniere’s disease.
Insulin docking within the open hemichannel of connexin 43 may reduce risk of amyotrophic lateral sclerosis
Authors: Lehrer Steven , Rheinstein Peter H.
Published: May 2022

Background

Type 2 diabetes (T2D), characterized by hyperinsulinemia, protects motor neurons against amyotrophic lateral sclerosis (ALS). Type 1 diabetes and a total lack of insulin are associated with increased risk of ALS. Connexin 43 (Cx43), an astrocyte protein, operates as an open pore via which toxic substances from the astrocytes reach the motor neurons.

Methods

In the current study we performed molecular docking of insulin with monomeric Cx31, monomeric Cx43, and hexameric Cx31 to assess whether insulin might affect the pore. Hexameric Cx31 and hexameric Cx43 have hemichannels composed of 6 subunits that work as transmembrane channels, binding together to form gap junction intercellular channels that open and close. We used the program AutoDock Vina Extended for the molecular docking study.

Results

Cx31 shares amino acid and structural similarity to Cx43 and insulin docks to the same position of the N-terminal domain of monomeric Cx31 and monomeric Cx43. Insulin docks within the open hemichannel of hexameric Cx31, potentially blocking it. The block may be responsible for the protective relationship of T2D to ALS.

Conclusion

Insulin, especially intranasal insulin, might be a treatment for ALS. An insulin secretogogue such as oral sulfonylurea or glinide might also be of value.
Atomic protein structure refinement using all-atom graph representations and SE(3)-equivariant graph neural networks
Authors: Wu Tianqi , Cheng Jianlin
Published: May 2022

Three-dimensional (3D) protein structures reveal the fundamental information about protein function. The state-of-art protein structure prediction methods such as Alphafold are being widely used to predict structures of uncharacterized proteins in biomedical research. There is a significant need to further improve the quality and nativeness of the predicted structures to enhance their usability. Current machine learning methods of refining protein structures focus mostly on improving the backbone quality of predicted structures without effectively leveraging and enhancing the conformation of all atoms including side-chain, while molecular simulation methods are computationally intensive and time-consuming.

In this work, we develop ATOMRefine, a deep learning-based, end-to-end, all-atom protein structural model refinement method. It uses a SE(3)-equivariant graph transformer network that is equivariant to the rotation and translation of 3D structures in conjunction with a novel graph representation of all atoms to directly refine protein atomic coordinates of all the atoms in a predicted tertiary structure represented as a molecular graph. The method is first trained and tested on the structural models in AlphafoldDB whose experimental structures are known, and then blindly tested on 69 CASP14 regular targets and 7 CASP14 refinement targets. ATOMRefine improves the quality of both backbone atoms and all-atom conformation of the initial structural models generated by AlphaFold. It also performs better than the state-of-the-art refinement methods in multiple evaluation metrics including an all-atom model quality score – the MolProbity score based on the analysis of all-atom contacts, bond length, atom clashes, torsion angles, and side-chain rotamers. As ATOMRefine can refine a protein structure quickly, it provides a viable, fast solution for improving protein geometry and fixing structural errors of predicted structures through direct coordinate refinement.
New hypotheses of cell type diversity and novelty from comparative single cell and nuclei transcriptomics in echinoderms
Authors: Meyer Anne , Ku Carolyn , Hatleberg William , Telmer Cheryl A. , Hinman Veronica
Published: May 2022

Cell types are the fundamental building blocks of metazoan biodiversity and offer a powerful perspective for inferring evolutionary phenomena. With the development of single-cell transcriptomic techniques, new definitions of cell types are emerging. This allows a conceptual reassessment of traditional definitions of novel cell types and their evolution. Research in echinoderms, particularly sea star and sea urchin embryos have contributed significantly to understanding the evolution of novel cell types, in particular the primary mesenchyme cells (PMCs) and pigment cells that are found in sea urchin but not sea star embryos. This paper outlines the development of a gene expression atlas for the bat star, Patiria miniata, using single nuclear RNA sequencing (snRNA-seq) of embryonic stages. The atlas revealed 22 cell clusters covering all expected cell types from the endoderm, mesoderm and ectoderm germ layers. In particular, four distinct neural clusters, an immune cluster, and distinct right and left coelom clusters were revealed as distinct cell states. A comparison with Strongylocentrotus purpuratus embryo single cell transcriptomes was performed using 1:1 orthologs to anchor and then compare gene expression patterns. S. purpuratus primordial germ cell equivalents were not detected in P. minata, while the left coelom of P. miniata has no equivalent cell cluster in S. purpuratus. Pigment cells of S. purpuratus map to clusters containing immune mesenchyme and neural cells of P. miniata, while the PMCs of S. purpuratus are revealed as orthologous to the right coelom cluster of P. miniata. These results suggest a new interpretation of the evolution of these well-studied cell types and a reflection on the definition of novel cell types.
Effects of anti-fibrotic standard of care drugs on senescent human lung fibroblasts
Authors: Garcia Stephanie B. , Hohmann Miriam S. , Coelho Ana Lucia , Verri Waldiceu A. , Hogaboam Cory M.
Published: May 2022

Rationale

Cellular senescence is crucial in the progression of idiopathic pulmonary fibrosis (IPF), but it is yet unclear whether the standard-of-care (SOC) drugs nintedanib and pirfenidone have senolytic properties.

Objectives

We attempted to illuminate the effects of SOC drugs on senescent normal and IPF lung fibroblasts in vitro.

Methods

Colorimetric/fluorimetric assays, qRT-PCR, and western blotting were used to evaluate the effect of SOC drugs on senescent normal and IPF lung fibroblasts.

Results

SOC drugs did not induce apoptosis in the absence of death ligands in either normal or IPF senescent cells. Nintedanib increased caspase-3 activity in the presence of Fas Ligand (FasL) in normal but not in IPF senescent fibroblasts. Conversely, nintedanib enhanced B cell lymphoma (Bcl)-2 expression in senescent IPF lung fibroblasts. Moreover, in senescent IPF cells, pirfenidone alone induced mixed lineage kinase domain-like pseudokinase (MLKL) phosphorylation, provoking necroptosis. However, fragmented gasdermin D, indicating pyroptosis, was not detected under any condition. In addition, SOC drugs increased transcript levels of fibrotic and senescence markers in senescent IPF fibroblasts, whereas D+Q inhibited all these markers. Finally, D+Q enhanced growth differentiation factor 15 (GDF15) transcript and protein levels in both normal and IPF senescent fibroblasts.

Conclusions

In the presence and absence of the extrinsic pro-apoptotic ligands, SOC drugs failed to trigger apoptosis in senescent fibroblasts, possibly due to enhanced Bcl-2 levels and the activation of the necroptosis pathway. SOC drugs elevated fibrotic and senescence markers in IPF lung fibroblasts. Together, these data demonstrated the inefficacy of SOC in targeting senescent cells. Further investigation is required to fully elucidate the therapeutic implications of SOC drugs on other senescent cell types in IPF.
Heterologous expression of a lycophyte protein enhances angiosperm seedling vigor
Authors: Koh Samuel W.H. , Bascom Carlisle S. , Berenguer Eduardo , Ingram Gwyneth , Estelle Mark , Hardtke Christian S.
Published: May 2022

Seedling vigor is a key agronomic trait that determines juvenile plant performance. Angiosperm seeds develop inside fruits and are connected to the mother plant through vascular tissues. Their formation requires plant-specific genes, such as BREVIS RADIX (BRX) in Arabidopsis thaliana roots. BRX family proteins are found throughout the angiosperms but also occur in non-vascular bryophytes and non-seed lycophytes. They consist of four conserved domains, including the tandem “BRX-domains”. We found that bryophyte or lycophyte BRX homologs can only partially substitute for Arabidopsis BRX (AtBRX) because they miss key features in the linker between the BRX-domains. Intriguingly however, expression of a BRX homolog from the lycophyte Selaginella moellendorffii (SmBRX) in A. thaliana wildtype background confers robustly enhanced root growth vigor that persists throughout the life cycle. This effect can be traced back to a substantial increase in seed and embryo size, and can be reproduced with a modified, “SmBRX-like” variant of AtBRX. Our results thus suggest that BRX variants could serve as biotechnological tools to boost seedling vigor and shed light on the activity of ancient, non-angiosperm BRX family proteins.
Replicative Instability Drives Cancer Progression
Authors: Morris Benjamin B. , Smith Jason P. , Zhang Qi , Jiang Zhijie , Hampton Oliver A. , Churchman Michelle L. , Arnold Susanne M. , Owen Dwight H. , Gray Jhanelle E. , Dillon Patrick M. , Soliman Hatem H. , Stover Daniel G. , Colman Howard , Chakravarti Arnab , Shain Kenneth H. , Silva Ariosto S. , Villano John L. , Vogelbaum Michael A. , Borges Virginia F. , Akerley Wallace L. , Gentzler Ryan D. , Hall Richard D. , Matsen Cindy B. , Ulrich C. M. , Post Andrew R. , Nix David A. , Singer Eric A. , Larner James M. , Stukenberg P. Todd , Jones David R. , Mayo Marty W.
Published: May 2022

In the past decade, defective DNA repair has been increasingly linked with cancer progression. Human tumors with markers of defective DNA repair and increased replication stress have been shown to exhibit genomic instability and poor survival rates across tumor types. Here we utilize-omics data from two independent consortia to identify the genetic underpinnings of replication stress, therapy resistance, and primary carcinoma to brain metastasis in BRCA wildtype tumors. In doing so, we have defined a new pan-cancer class of tumors characterized by replicative instability (RIN). RIN is defined by genomic evolution secondary to replicative challenge. Our data supports a model whereby defective single-strand break repair, translesion synthesis, and non-homologous end joining effectors drive RIN. Collectively, we find that RIN accelerates cancer progression by driving copy number alterations and transcriptional program rewiring that promote tumor evolution.

Statement of Significance

Defining the genetic basis of genomic instability with wildtype BRCA repair effectors is a significant unmet need in cancer research. Here we identify and characterize a pan-cancer cohort of tumors driven by replicative instability (RIN). We find that RIN drives therapy resistance and distant metastases across multiple tumor types.
Messenger-RNA Modification Standards and Machine Learning Models Facilitate Absolute Site-Specific Pseudouridine Quantification
Authors: Makhamreh Amr , Tavakoli Sepideh , Gamper Howard , Nabizadehmashhadtoroghi Mohammad , Fallahi Ali , Hou Ya-Ming , Rouhanifard Sara H. , Wanunu Meni
Published: May 2022

Enzyme-mediated chemical modifications to mRNA are important for fine-tuning gene expression, but they are challenging to quantify due to low copy number and limited tools for accurate detection. Existing studies have typically focused on the identification and impact of adenine modifications on mRNA (m6A and inosine) due to the availability of analytical methods. The pseudouridine (Ψ) mRNA modification is also highly abundant but difficult to detect and quantify because there is no available antibody, it is mass silent, and maintains canonical basepairing with adenine. Nanopores may be used to directly identify Ψ sites in RNAs using a systematically miscalled base, however, this approach is not quantitative and highly sequence dependent. In this work, we apply supervised machine learning models that are trained on sequence-specific, synthetic controls to endogenous transcriptome data and achieve the first quantitative Ψ occupancy measurement in human mRNAs. Our supervised machine learning models reveal that for every site studied, different signal parameters are required to maximize Ψ classification accuracy. We show that applying our model is critical for quantification, especially in low-abundance mRNAs. Our engine can be used to profile Ψ-occupancy across cell types and cell states, thus providing critical insights about physiological relevance of Ψ modification to mRNAs.
Independent regulation of mtDNA quantity and quality resets the mitochondrial genome in C. elegans primordial germ cells
Authors: Schwartz Aaron Z.A. , Tsyba Nikita , Abdu Yusuff , Patel Maulik R. , Nance Jeremy
Published: May 2022

Mitochondria contain an independent genome, called mtDNA, which contains essential metabolic genes. Although mtDNA mutations occur at high frequency, they are inherited infrequently, indicating that germline mechanisms limit their accumulation. To determine how germline mtDNA is regulated, we examined the control of mtDNA quantity and quality in C. elegans primordial germ cells (PGCs). We show that PGCs generate a bottleneck in mtDNA number by segregating mitochondria into lobe-like protrusions that are cannibalized by adjacent cells, reducing mtDNA content two-fold. As PGCs exit quiescence and divide, mtDNAs replicate to maintain a set point of ∼200 mtDNAs per germline stem cell. Whereas PGC lobe cannibalism eliminates mtDNAs stochastically, we show that the kinase PINK1, operating independently of Parkin and autophagy, preferentially reduces the fraction of mutant mtDNAs. Thus, PGCs employ parallel mechanisms to control both the quantity and quality of the founding population of germline mtDNAs.
Draft genome of six Cuban Anolis lizards and insights into genetic changes during the diversification
Authors: Kanamori Shunsuke , Díaz Luis M. , Cádiz Antonio , Yamaguchi Katsushi , Shigenobu Shuji , Kawata Masakado
Published: May 2022

The detection of various type of genomic variants and their accumulation processes during species diversification and adaptive radiation is important for understanding the molecular and genetic basis of evolution. Anolis lizards in the West Indies are good models for studying the mechanism of the evolution because of the repeated evolution of their morphology and the ecology. In this study, we performed de novo genome assembly of six Cuban Anolis lizards with different ecomorphs and thermal habitats (Anolis isolepis, Anolis allisoni, Anolis porcatus, Anolis allogus, Anolis homolechis, and Anolis sagrei). As a result, we obtained six novel draft genomes with relatively long and high gene completeness, with scaffold N50 ranging from 5.56–39.79 Mb, and vertebrate Benchmarking Universal Single-Copy Orthologs completeness ranging from 77.5% to 86.9%. Subsequently, we performed comparative analysis of genomic contents including those of mainland Anolis lizards to estimate genetic variations that had emerged and accumulated during the diversification of Anolis lizards. Comparing the repeat element compositions and repeat landscapes revealed differences in the accumulation process between Cuban trunk-crown and trunk-ground species, LTR accumulation observed only in A. carolinensis, and separate expansions of several families of LINE in each of Cuban trunk-ground species. The analysis of duplicated genes suggested that the proportional difference of duplicated gene number among Cuban Anolis lizards may be associated to the difference of their habitat range. Furthermore, Pairwise Sequentially Markovian Coalescent analysis proposed that the effective population sizes of each species might have been affected by Cuba’s geohistory. Hence, these six novel draft genome assemblies and detected genetic variations can be a springboard for the further genetic elucidation of the Anolis lizard’s diversification.

Significance

Anolis lizard in the West Indies is excellent model for studying the mechanisms of speciation and adaptive evolution. Still, due to a lack of genome assemblies, genetic variations and accumulation process of them involved in the diversification remain largely unexplored. In this study, we reported the novel genome assemblies of six Cuban Anolis lizards and analyzed evolution of genome contents. From comparative genomic analysis and inferences of genetic variation accumulation process, we detected species- and lineage-specific transposon accumulation processes and gene copy number evolution, considered to be associated with the adaptation to their habitats. Additionally, we estimated past effective population sizes and the results suggested its relationship to Cuba’s geohistory.
Impact valuations in social finance: emic and polyvocal stakeholder accounts
Authors: Ruff Kate , Nappert Pier-Luc , Graham Cameron
Published: May 2022

Purpose

This paper aims to understand how social finance and impact measurement experts include stakeholders' voices in valuations of social and environmental impact.

Design/methodology/approach

The paper used the content analysis of an online discussion forum where experts discussed impact valuation approaches.

Findings

Many experts seek impact valuations that take into account the experiences of those whose lives are most affected. Ideally, these accounts need to be emic to (in the language of) those stakeholders, and polyvocal (representing many different stakeholders' voices). However, these experts also seek to effect systemic change by encouraging mainstream financial markets to use social and environmental valuations in their decision-making. These experts consider full plurality too complex to be useable by financial markets, so the experts argue in favor of etic valuations (stated in the language of investors), to appeal to mainstream finance, while endeavoring nonetheless to represent multiple stakeholders' voices. The authors identify two discursive strategies used to resolve this tension: effacing of differences between diverse stakeholders, and overstating the universality of money as a common language.

Social implications

The terms emic and polyvocal provide experts with nuanced ways to understand “stakeholder voice.” The authors hope these nuances inspire new insights and strategies and help the community with their goal of bridging to mainstream finance.

Originality/value

The paper presents a theoretical framework for describing plurality in impact valuations and examines the challenges of bridging from social finance, which seeks to give voice and representation to those whose lives are most affected, to mainstream finance.
Centers of data appropriation: evidence from a Nordic hotel chain
Authors: Knudsen Dan-Richard , Bourmistrov Anatoli , Kaarbøe Katarina
Published: May 2022

Purpose

Research suggests that centers of calculation, empowered by accounting inscriptions, are similar to maps: they provide a useful, albeit simplified, version of reality. The purposes of this paper are to examine whether and how digital platforms change the nature of centers of calculation, and to improve the understanding of the relationship between digital platforms and accounting.

Design/methodology/approach

An in-depth, single case-study design is used to empirically investigate how a Nordic hotel chain competed with global online travel agencies (OTAs) in the quest for the “new oil”—customer data.

Findings

The paper demonstrates how the case organization created a local alternative to global digital platforms with the aim of acquiring customer data, thereby moving from a center of calculation (CoC) to what authors label a “center of data appropriation” (CDA). While CoCs are guided by accounting inscriptions that enable “mapping”, CDAs are constructed around accounting inscriptions with other properties that enable digital “mirrors” of the economic domain. The authors find that this has two governing effects. First, multiple centers emerge that compete for access to the periphery. Second, future forms of competition can follow dynamic trajectories, where mutual dependence between CDAs may lead to coopetition.

Originality/value

Scholars have suggested that surveillance capitalism creates market-power imbalances. This study indicates that the transformation of local organizations into CDAs enables them to challenge global digital-platform organizations. Therefore, authors argue that local organizations may retain some market power by establishing local CDAs.
Role of monetary policy in economic growth and development: from theory to empirical evidence
Authors: Mehar Muhammad Ayub
Published: May 2022

Purpose

This article examines the effects of credit to private sector on the business and trade activities. The effectiveness of rapid expansion in public and private borrowing through state's intervention after COVID-19 pandemic has been assessed in this study.

Design/methodology/approach

The model to determine the role of credit expansion is based on four equations estimated through panel least square technique on 18 years data of 186 countries.

Findings

It is concluded that credit to private sector and external debt improve the investment in infrastructure, which is a significant determinant of gross domestic product growth. Empirical evidences corroborate that higher number of firms using banks to finance their investment and the volume of broad money determine the magnitude of credit to private sector.

Originality/value

This study explores some new evidences and aspects of the credit financing which have not been discussed in this way before.
Mapping the landscape of organizational theories for future research themes in supply chain risk management
Authors: Yildiz Çankaya Sibel , Can Saglam Yesim , Sezen Bülent
Published: May 2022

Purpose

The aim of this conceptual study is to analyze the effects of state-of-the-art research streams on supply chain risk management (SCRM) based on organizational theoretical background and direct future research toward the use of other related organizational theories. This paper seeks to provide a framework for understanding various organizational theories that can impact the understanding of SCRM.

Design/methodology/approach

A systematic literature review on articles published from 1998 to 2020 was conducted manually in the following databases: Emerald, Science Direct, Taylor & Francis Online, and Wiley online library. Among these articles, the paper by Smeltzer and Siferd (1998) is the first article published on the topic. Therefore, that serves as a starting point for the papers' analysis. A total of 109 articles have been selected and reviewed in detail.

Findings

The results of the study indicate that the articles which utilize theories in SCRM research have been mostly published in the last three years. The quantitative and case studies have been prevalently applied methods in the articles. In total, 34 theories are listed from the investigated articles. The four commonly studied theories among these are the information processing theory, transaction cost theory, contingency theory, and resource-based view.

Originality/value

This paper is the pioneer in the sense that the paper specifically and directly reviews the SCRM literature in terms of organizational theory usage. For future research, this study offers a diffusion of innovation (DOI) theory that explains the factors which can affect the adoption or diffusion of SCRM practices.
The role of cultural identity in acceptance of wine innovations in wine regions
Authors: Reinares-Lara Eva , Pelegrín-Borondo Jorge , Olarte-Pascual Cristina , Oruezabala Gwenaelle
Published: May 2022

Purpose

Wine culture is an increasingly important reality for the development of wine regions that can foster a sense of cultural identity (CI). With the aim of guiding marketing in the wine market and segmenting demand, this study aims to introduce the moderating role of wine-related cultural identity (WCI) in a Cognitive-Affective-Normative (CAN) model to explain purchase intention for innovations.

Design/methodology/approach

This quantitative study was conducted in Spain, the country with the largest acreage of vineyards in the world. Specifically, a personal survey was applied to a sample of 1,126 potential buyers of a wine innovation in Rioja, the Spanish wine region with the longest tradition.

Findings

(1) WCI moderates acceptance of a wine innovation; (2) WCI levels generate new segments: Enoculturalists (44.67%), who have a strong WCI, Intermediate Enoculturalists (38.90%), with an intermediate WCI and Non-Enoculturalists (16.43%), who have no WCI; and (3) the CAN model strongly explains the behavior of Non-Enoculturalists (R2 = 0.81).

Originality/value

The originality of the research lies in the opportunity to test a technical innovation in wine production in a region characterized by a strong wine-growing tradition. Despite growing interest in local products, no study has yet examined the moderating role of CI in a new food acceptance model as proposed here. The findings have important theoretical and practical implications, as they identify new groups for targeting innovation-related actions and reactivating wine consumption in keeping with new consumer trends.