bluuebunny/crossref_metadata_2025_split huggingface dataset:
Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos
Authors: Lo Furno Elena , Busseau Isabelle , Aze Antoine , Lorenzi Claudio , Saghira Cima , Danzi Matt C , Zuchner Stephan , Maiorano Domenico 
Published: December 2021

Abstract
In early embryogenesis of fast cleaving embryos, DNA synthesis is short and surveillance mechanisms preserving genome integrity are inefficient, implying the possible generation of mutations. We have analyzed mutagenesis in Xenopus laevis and Drosophila melanogaster early embryos. We report the occurrence of a high mutation rate in Xenopus and show that it is dependent upon the translesion DNA synthesis (TLS) master regulator Rad18. Unexpectedly, we observed a homology-directed repair contribution of Rad18 in reducing the mutation load. Genetic invalidation of TLS in the pre-blastoderm Drosophila embryo resulted in reduction of both the hatching rate and single-nucleotide variations on pericentromeric heterochromatin in adult flies. Altogether, these findings indicate that during very early Xenopus and Drosophila embryos TLS strongly contributes to the high mutation rate. This may constitute a previously unforeseen source of genetic diversity contributing to the polymorphisms of each individual with implications for genome evolution and species adaptation.
A modular RNA interference system for multiplexed gene regulation
Authors: Dwijayanti Ari , Storch Marko , Stan Guy-Bart , Baldwin Geoff S 
Published: December 2021

Abstract
The rational design and realisation of simple-to-use genetic control elements that are modular, orthogonal and robust is essential to the construction of predictable and reliable biological systems of increasing complexity. To this effect, we introduce modular Artificial RNA interference (mARi), a rational, modular and extensible design framework that enables robust, portable and multiplexed post-transcriptional regulation of gene expression in Escherichia coli. The regulatory function of mARi was characterised in a range of relevant genetic contexts, demonstrating its independence from other genetic control elements and the gene of interest, and providing new insight into the design rules of RNA based regulation in E. coli, while a range of cellular contexts also demonstrated it to be independent of growth-phase and strain type. Importantly, the extensibility and orthogonality of mARi enables the simultaneous post-transcriptional regulation of multi-gene systems as both single-gene cassettes and poly-cistronic operons. To facilitate adoption, mARi was designed to be directly integrated into the modular BASIC DNA assembly framework. We anticipate that mARi-based genetic control within an extensible DNA assembly framework will facilitate metabolic engineering, layered genetic control, and advanced genetic circuit applications.
Modulating gene expression in breast cancer via DNA secondary structure and the CRISPR toolbox
Authors: Kretzmann Jessica A , Irving Kelly L , Smith Nicole M , Evans Cameron W 
Published: December 2021

Abstract
Breast cancer is the most commonly diagnosed malignancy in women, and while the survival prognosis of patients with early-stage, non-metastatic disease is ∼75%, recurrence poses a significant risk and advanced and/or metastatic breast cancer is incurable. A distinctive feature of advanced breast cancer is an unstable genome and altered gene expression patterns that result in disease heterogeneity. Transcription factors represent a unique therapeutic opportunity in breast cancer, since they are known regulators of gene expression, including gene expression involved in differentiation and cell death, which are themselves often mutated or dysregulated in cancer. While transcription factors have traditionally been viewed as ‘undruggable’, progress has been made in the development of small-molecule therapeutics to target relevant protein–protein, protein–DNA and enzymatic active sites, with varying levels of success. However, non-traditional approaches such as epigenetic editing, transcriptional control via CRISPR/dCas9 systems, and gene regulation through non-canonical nucleic acid secondary structures represent new directions yet to be fully explored. Here, we discuss these new approaches and current limitations in light of new therapeutic opportunities for breast cancers.
Differential analysis of binarized single-cell RNA sequencing data captures biological variation
Authors: Bouland Gerard A , Mahfouz Ahmed , Reinders Marcel J T 
Published: December 2021

Abstract
Single-cell RNA sequencing data is characterized by a large number of zero counts, yet there is growing evidence that these zeros reflect biological variation rather than technical artifacts. We propose to use binarized expression profiles to identify the effects of biological variation in single-cell RNA sequencing data. Using 16 publicly available and simulated datasets, we show that a binarized representation of single-cell expression data accurately represents biological variation and reveals the relative abundance of transcripts more robustly than counts.
Predicting Non-Adherence With Very Low Nicotine Content Cigarettes Among Adults With Serious Mental Illness Who Smoke
Authors: Reed Grace L , Colby Suzanne M , Sokolovsky Alexander W , Snell L Morgan , DeAtley Teresa , Tidey Jennifer W 
Published: December 2021

Abstract

Introduction
Reducing the nicotine content of cigarettes is a promising policy intervention to decrease cigarette dependence among people who smoke. Randomized trials support the potential efficacy of a reduced nicotine product standard for cigarettes. However, interpretation of such trials is challenged by incomplete adherence to the randomized treatment assignment, as some participants may continue to use commercial cigarettes not provided by the trial. The current study examined prevalence and predictors of non-adherence among trial participants with serious mental illness (SMI).

Aims and Methods
Adults with SMI who smoke daily and were not trying to quit (N = 58) were randomized to receive very low nicotine content (VLNC) or normal nicotine content cigarettes over 6 weeks. We investigated predictors of biologically assessed non-adherence in participants assigned to VLNC cigarettes (n = 30). Predictors included subjective responses to VLNC cigarettes, baseline nicotine dependence and dependence motives, and psychiatric symptom severity. We fit a series of linear models regressing non-adherence metrics onto covariates (gender; menthol preference) and focal predictors.

Results
Nearly all participants (96%) were estimated to be less than completely adherent to VLNC cigarettes. Lower enjoyment ratings of respiratory tract sensations of VLNC cigarettes predicted a greater degree of non-adherence (b = −.40, SE = .14, 95% CI: −0.71, −0.10).

Conclusions
Less positive subjective response to smoking VLNC cigarettes was the only significant predictor of incomplete adherence among individuals with SMI, consistent with prior research in a general population sample. This suggests the potential for shared strategies to help different smoking populations adjust to a reduced nicotine product standard.

Implications
Results offer preliminary insight into potential barriers to adherence in SMI populations. Adherence might be enhanced by supplementing VLNC cigarettes with alternative sources of non-combusted nicotine, paired with educational campaigns to encourage quitting or switching to less harmful products. Future studies should replicate these analyses in a larger sample of individuals with SMI who smoke.
Functional Analyses of the Two Distinctive Types of Two-Pore Channels and the Slow Vacuolar Channel in Marchantia polymorpha
Authors: Hashimoto Kenji , Koselski Mateusz , Tsuboyama Shoko , Dziubinska Halina , Trębacz Kazimierz , Kuchitsu Kazuyuki 
Published: December 2021

Abstract
The two-pore channel (TPC) family is widely conserved in eukaryotes. Many vascular plants, including Arabidopsis and rice, possess a single TPC gene which functions as a slow vacuolar (SV) channel—voltage-dependent cation-permeable channel located in the vacuolar membrane (tonoplast). On the other hand, a liverwort Marchantia polymorpha genome encodes three TPC homologs: MpTPC1 is similar to TPCs in vascular plants (type 1 TPC), while MpTPC2 and MpTPC3 are classified into a distinctive group (type 2 TPC). Phylogenetic analysis suggested that the type 2 TPC emerged before the land colonization in plant evolution and was lost in vascular plants and hornworts. All of the three MpTPCs were shown to be localized at the tonoplast. We generated knockout mutants of tpc1, tpc2, tpc3 and tpc2 tpc3 double mutant by clustered regularly interspaced short palindromic repeats/Cas9 genome editing and performed patch-clamp analyses of isolated vacuoles. The SV channel activity was abolished in the Mptpc1 loss-of-function mutant (Mptpc1-1KO), while Mptpc2-1KO, Mptpc3-1KO and Mptpc2-2/tpc3-2KO double mutant exhibited similar activity to the wild type, indicating that MpTPC1 (type 1) is solely responsible for the SV channel activity. Activators of mammalian TPCs, phosphatidylinositol-3,5-bisphosphate and nicotinic acid adenine dinucleotide phosphate, did not affect the ion channel activity of any MpTPCs. These results indicate that the type 1 TPCs, which are well conserved in all land plant species, encode the SV channel, while the type 2 TPCs likely encode other tonoplast cation channel(s) distinct from the SV channel and animal TPCs.
Receptor-like cytoplasmic kinases PBL34/35/36 are required for CLE peptide-mediated signaling to maintain shoot apical meristem and root apical meristem homeostasis in Arabidopsis
Authors: Wang Wenping , Hu Chong , Li Xiaonan , Zhu Yafen , Tao Liang , Cui Yanwei , Deng Dingqian , Fan Xiaoxuan , Zhang Hong , Li Jia , Gou Xiaoping , Yi Jing 
Published: December 2021

AbstractShoot apical meristem (SAM) and root apical meristem (RAM) homeostasis is tightly regulated by CLAVATA3 (CLV3)/EMBRYO SURROUNDING REGION-related (CLE) peptide signaling. However, the intracellular signaling components after CLV3 is perceived by the CLV1–CLV3-INSENSITIVE KINASE (CIK) receptor complex and CLE25/26/45 are sensed by the BARELY ANY MERISTEM (BAM)–CIK receptor complex are unknown. Here, we report that PBS1-LIKE34/35/36 (PBL34/35/36), a clade of receptor-like cytoplasmic kinases, are required for both CLV3-mediated signaling in the SAM and CLE25/26/45-mediated signaling in the RAM. Physiological assays showed that the SAM and RAM of pbl34 pbl35 pbl36 were resistant to CLV3 and CLE25/26/45 treatment, respectively. Genetic analyses indicated that pbl34 pbl35 pbl36 greatly enhanced the SAM defects of clv2 and rpk2 but not clv1, and did not show additive effects with bam3 and cik2 in the RAM. Further biochemical assays revealed that PBL34/35/36 interacted with CLV1, BAM1/3, and CIKs, and were phosphorylated by CLV1 and BAM1. All these results suggest that PBL34/35/36 act downstream of CLV1 and BAM1/3 to mediate the CLV3 and CLE25/26/45 signals in maintaining SAM and RAM homeostasis, respectively. Our findings shed light on how CLE signals are transmitted intracellularly after being perceived by cell surface receptor complexes.
A Novel circUBR4/miR-491-5p/NRP2 ceRNA Network Regulates Oxidized Low-density Lipoprotein-induced Proliferation and Migration in Vascular Smooth Muscle Cells
Authors: Peng Huaiyu , Liu Shunfan , Li Yi , Wang Chengyang , Zhong Yongjin 
Published: December 2021

Abstract:
Vascular smooth muscle cells (VSMCs) play critical roles in the progression of atherosclerosis. Circular RNA (circRNA) ubiquitin protein ligase E3 component n-recognin 4 (circUBR4) has been shown to regulate VSMC migration and proliferation. In this study, we sought to identify the mechanism in the regulation of circUBR4. CircUBR4, microRNA (miR)-491-5p, and Neuropilin-2 (NRP2) were quantified by quantitative real-time polymerase chain reaction (PCR) and western blot. Cell proliferation was evaluated by Cell Counting Kit-8 and 5-Ethynyl-2′-Deoxyuridine assays. Cell migration was examined by wound-healing and transwell invasion assays. The direct relationship between miR-491-5p and circUBR4 or NRP2 was validated by dual-luciferase reporter and RNA immunoprecipitation assays. Our data indicated that in VSMCs, ox-LDL induced circUBR4 expression. Silencing endogenous circUBR4 attenuated VSMC proliferation and migration induced by ox-LDL. Mechanistically, circUBR4 targeted miR-491-5p by pairing to miR-491-5p. Moreover, miR-491-5p was identified as a downstream mediator of circUBR4 function in ox-LDL–treated VSMCs. NRP2 was a direct target of miR-491-5p, and circUBR4 acted as a competing endogenous RNA for miR-491-5p to regulate NRP2 expression. In addition, NRP2 was a functionally downstream effector of miR-491-5p in regulating ox-LDL–evoked VSMC proliferation and migration. Our findings identify a new competing endogenous RNA network, the circUBR4/miR-491-5p/NRP2 axis, for the regulation of circUBR4 in VSMC migration and proliferation.
Should all patients undergoing genetic testing for hereditary breast cancer syndromes be offered a multigene panel?
Authors: Silver Erica L. , Niell-Swiller Mariana 
Published: December 2021

Purpose of review
We aim to demonstrate why multigene panel testing (MGPT) is the superior testing option for individuals undergoing hereditary cancer genetic testing. We will outline the clinical benefits and possible limitations of MGPT for individuals at risk for a hereditary cancer syndrome.

Recent findings
The use of MGPT increases the identification of individuals with hereditary cancer syndromes. Recent studies continue to prove that MGPT is a superior option to single gene/or syndrome testing. MGPT is a cost-effective testing approach for those meeting criteria for genetic testing. Individuals interested in MGPT should understand the benefits and limitations of this approach, including an increase in variant identification and possible incidental findings. MGPT also increases the number of individuals who would benefit from cascade testing.

Summary
MGPT should be considered as the standard approach to hereditary cancer genetic testing as opposed to single gene or single syndrome testing. MGPT identifies a larger proportion of individuals with a hereditary cancer syndrome and leads to better management and improved uptake of cascade testing.
VISION-RELATED MALPRACTICE INVOLVING PRISONERS
Authors: Jeng Franklin , Bonnell Alyssa C. , O'Neil Erin C. , Mehran Nikki A. , Kolomeyer Natasha N. , Brucker Alexander J. , Kolomeyer Anton M. 
Published: December 2021

Purpose:
To characterize vision-related malpractice litigation involving prisoners.

Methods:
Retrospective legal database review using the Westlaw database was performed to identify vision-related malpractice lawsuits involving prisoners in the United States from 1914 to 2020. Main outcomes and measurements were allegations of malpractice, verdicts, and settlements.

Results:
Sixty-four vision-related malpractice lawsuits involving prisoners were identified. Mean defendant age was 49 years (range, 28–74 years). Fifty-seven percent of the defendants were ophthalmologists and 43% were optometrists. The cases were most commonly from the South and Midwest (n = 19 [30%] for each). Allegations of malpractice included inadequate medical care or treatment refusal (n = 21 [33%]), failure to treat fully leading to continued suffering (n = 18 [28%]), and delay in treatment or referral (n = 17 [27%]). Retina-related diagnoses were most common (n = 18 [28%]). Forty-six (72%) cases were closed, 14 (22%) were open, and four (6.3%) were partially closed. Only two (3.1%) cases were decided in favor of the plaintiff. The most common reason for an unsuccessful suit was lack of deliberate indifference by the eye care professional (n = 21 [46%]).

Conclusion:
The most common reasons for vision-related malpractice brought forth by prisoners were inadequate or incomplete eye care and treatment refusal. Retina was the most commonly involved subspecialty. However, the success rate of these suits was extremely low.
Repeatability and Agreement of Horizontal Corneal Diameter Measurements Between Scanning-Slit Topography, Dual Rotating Scheimpflug Camera With Placido Disc Tomography, Placido Disc Topography, and Optical Coherence Tomography
Authors: Namkung Soobin , Boyle Alexander Buckenham , Li Ye , Gokul Akilesh , McGhee Charles , Ziaei Mohammed 
Published: December 2021

Purpose:
The purpose of this study was to assess the repeatability and agreement of horizontal white-to-white (WTW) measurements using 4 different imaging modalities including a slit-scanning elevation topographer, dual rotating Scheimpflug camera and Placido Disc tomographer, Placido Disc topographer, and anterior segment optical coherence (OCT) tomographer.

Methods:
In this prospective study, 33 eyes of 33 healthy subjects were scanned 3 times using each of the Orbscan IIz, Sirius, Nidek OPD III, and DRI OCT Triton devices and WTW measurements were recorded. Repeatability was assessed using the intraclass correlation coefficient (ICC), and agreement was analyzed using Bland–Altman plots.

Results:
Mean WTW values obtained from the Orbscan IIz, Sirius, Nidek, and DRI OCT Triton devices were 11.76 ± 0.41, 12.10 ± 0.45, 12.14 ± 0.41, and 12.40 ± 0.48 mm, respectively. Overall, there was high repeatability, with the ICC >0.86 for all devices. The Sirius showed the highest repeatability (ICC = 0.993), and the Nidek the lowest (ICC = 0.870). All pairwise comparison showed significant differences in the mean WTW measurements (P < 0.01) except between Sirius and Nidek (P = 0.27). Mean differences showed that the DRI OCT Triton had the highest WTW values, followed by Nidek, Sirius, and finally by Orbscan, which provided the lowest measurements. All pairwise comparisons had wide limits of agreements (between 0.60 and 0.80 mm).

Conclusions:
In healthy subjects the 4 devices demonstrated high repeatability in WTW measurement. However, a poor agreement between the devices suggests that they should not be used interchangeably for WTW measurements in clinical practice.
911 Calls for Emergency Medical Services in Heart Failure
Authors: Jung Miyeon , Hays Laura M. , Pang Peter S. , Newhouse Robin P. , Arkins Thomas P. , O'Donnell Daniel , Cook Ryan , Gradus-Pizlo Irmina , McAdams Ellen , Pressler Susan J. 
Published: December 2021

Background
Heart failure (HF) is a common condition leading to activation of emergency medical services (EMS).

Objective
The aim of this study was to describe reasons given by persons with HF, family members, or other caregivers for requesting EMS activation during 911 calls.

Methods
In this descriptive qualitative study, a content analysis was performed on transcribed audio files of 383 EMS requests involving 383 persons with HF in the community.

Results
One hundred forty-seven calls (38.4%) were placed by the family members, 75 (19.6%) were placed by the patients, 56 (14.6%) were placed by healthcare workers or personnel from living facilities, and the remaining calls (n = 105, 27.4%) were placed by others (eg, friends, neighbors, officers). Three broad categories of symptoms, signs, and events were identified as the reasons for an EMS request. Frequently reported symptoms were breathing problems (55.4%), chest pain (18.3%), and other pain (eg, head, extremities) (16.7%). Signs included decreased consciousness (15.4%), swelling (5.7%), and bleeding (5.0%). The reported events involved falls (8.1%), heart attack (6.3%), hypoxic episodes (6.0%), stroke (5.2%), and post–hospital-discharge complications (4.7%). In most calls (74.9%), multiple reasons were reported and a combination of symptoms, signs, and events were identified. Heart failure diagnosis was mentioned in fewer than 10% of the calls.

Conclusions
Overall, symptoms and signs of HF exacerbation were common reasons to activate 911 calls. Falls were frequently reported. Under the duress of the emergent situations surrounding the 911 call, callers rarely mentioned the existence of HF. Interventions are needed to guide patients with HF and their family members to promote the management of HF to reduce EMS activation as well as to activate EMS quickly for acute changes in HF conditions.
The Heterogeneity of Physical and Anxiety Symptoms and Quality of Life Among Patients With Heart Failure
Authors: Ye Yi , Mei Jiaojiao , Zhang Jie , Zhao Qiuge , Fan Xiuzhen 
Published: December 2021

Background
Patients with heart failure (HF) experience a severe burden of symptoms and reduced quality of life (QoL). However, little is known about the heterogeneity of these symptoms and the association with QoL.

Objectives
The aims of this study were to conduct a latent class analysis on co-occurring physical and anxiety symptoms and to determine whether the underlying subgroups differ regarding the QoL among patients with HF.

Methods
The authors of this cross-sectional study recruited 329 patients with HF from 2 hospitals. Patients' symptoms and QoL were self-reported, and data were analyzed using latent class analysis, χ2 test, analysis of variance, and hierarchical linear regression analysis.

Results
Three latent classes (all low, all high, and high physical-partial anxiety) were identified based on the occurrence of patients' physical and anxiety symptoms. Patients with a lower body mass index, a worse New York Heart Association class, and a longer disease duration were more likely to belong to the all-high class. Hierarchical linear regression analysis showed that distinct subgroups (all low vs all high: β = −0.299, P < .001; all low vs high physical-partial anxiety: β = −0.228, P < .001) were significantly associated with the physical summary component score for QoL. Likewise, distinct subgroups (all low vs all high: β = −0.509, P < .001; all low vs high physical-partial anxiety: β = −0.128, P = .012) were significantly associated with the mental summary component score for QoL.

Conclusions
Patients with HF showed heterogeneity in physical and anxiety symptoms; the subgroup with severe symptoms exhibited a poor QoL. The associations between symptom subgroups and QoL require targeted symptom-based interventions.
Facemask Use During High Intensity Interval Exercise in Temperate and Hot Environments
Authors: Wells Andrew , Fennel Zachary , Ducharme Jeremy , Masoud Abdulaziz , Houck Jonathan , Bellovary Bryanne , Deyhle Michael , Hsiao Yu Yu , Amorim Fabiano , Mermier Christine 
Published: December 2021

Objective:
The purpose of this study was to investigate the effects of surgical mask use during high intensity interval exercise (HIIE) on physiological and perceptual responses in hot and temperate environments.

Methods:
In a randomized fashion, 10 healthy participants completed two HIIE sessions in a 36°C hot (HUE-HOT) and two HIIE sessions in a 23°C temperate environment (HIIE-TEMP) while wearing (MASK) and not wearing a surgical mask (CON).

Results:
No differences in physiological variables were found between MASK and CON during HIIE. An increase in perceived dyspnea and average RPE was found comparing MASK and CON. Interaction effects showed the greatest changes in perceived dyspnea and average RPE occurred in the HIIE-HOT/MASK condition.

Conclusion:
Wearing a surgical mask during HIIE increases the perception of dyspnea and exertion with the greatest effect occurring in hot environments.