bluuebunny/crossref_metadata_2025_split huggingface dataset:
Na+/Ca2+ exchanger isoform 1 takes part to the Ca2+-related prosurvival pathway of SOD1 in primary motor neurons exposed to beta-methylamino-l-alanine
Authors: Petrozziello Tiziana , Boscia Francesca , Tedeschi Valentina , Pannaccione Anna , de Rosa Valeria , Corvino Angela , Severino Beatrice , Annunziato Lucio , Secondo Agnese 
Published: January 2022

Abstract
Background
The cycad neurotoxin beta-methylamino-l-alanine (L-BMAA), one of the environmental trigger factor for amyotrophic lateral sclerosis/Parkinson-dementia complex (ALS/PDC), may cause neurodegeneration by disrupting organellar Ca2+ homeostasis. Through the activation of Akt/ERK1/2 pathway, the Cu,Zn-superoxide dismutase (SOD1) and its non-metallated form, ApoSOD1, prevent endoplasmic reticulum (ER) stress-induced cell death in motor neurons exposed to L-BMAA. This occurs through the rapid increase of intracellular Ca2+ concentration ([Ca2+]i) in part flowing from the extracellular compartment and in part released from ER. However, the molecular components of this mechanism remain uncharacterized.

Methods
By an integrated approach consisting on the use of siRNA strategy, Western blotting, confocal double- labeling immunofluorescence, patch-clamp electrophysiology, and Fura 2-/SBFI-single-cell imaging, we explored in rat motor neuron-enriched cultures the involvement of the plasma membrane proteins Na+/Ca2+ exchanger (NCX) and purinergic P2X7 receptor as well as that of the intracellular cADP-ribose (cADPR) pathway, in the neuroprotective mechanism of SOD1.

Results
We showed that SOD1-induced [Ca2+]i rise was prevented neither by A430879, a P2X7 receptor specific antagonist or 8-bromo-cADPR, a cell permeant antagonist of cADP-ribose, but only by the pan inhibitor of NCX, CB-DMB. The same occurred for the ApoSOD1. Confocal double labeling immunofluorescence showed a huge expression of plasmalemmal NCX1 and intracellular NCX3 isoforms. Furthermore, we identified NCX1 reverse mode as the main mechanism responsible for the neuroprotective ER Ca2+ refilling elicited by SOD1 and ApoSOD1 through which they promoted translocation of active Akt in the nuclei of a subset of primary motor neurons. Finally, the activation of NCX1 by the specific agonist CN-PYB2 protected motor neurons from L-BMAA-induced cell death, mimicking the effect of SOD1.

Conclusion
Collectively, our data indicate that SOD1 and ApoSOD1 exert their neuroprotective effect by modulating ER Ca2+ content through the activation of NCX1 reverse mode and Akt nuclear translocation in a subset of primary motor neurons.
Sublethal enteroviral infection exacerbates disease progression in an ALS mouse model
Authors: Xue Yuan Chao , Liu Huitao , Mohamud Yasir , Bahreyni Amirhossein , Zhang Jingchun , Cashman Neil R. , Luo Honglin 
Published: January 2022

Abstract
Background
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the motor neuron system associated with both genetic and environmental risk factors. Infection with enteroviruses, including poliovirus and coxsackievirus, such as coxsackievirus B3 (CVB3), has been proposed as a possible causal/risk factor for ALS due to the evidence that enteroviruses can target motor neurons and establish a persistent infection in the central nervous system (CNS), and recent findings that enteroviral infection-induced molecular and pathological phenotypes closely resemble ALS. However, a causal relationship has not yet been affirmed.

Methods
Wild-type C57BL/6J and G85R mutant superoxide dismutase 1 (SOD1G85R) ALS mice were intracerebroventricularly infected with a sublethal dose of CVB3 or sham-infected. For a subset of mice, ribavirin (a broad-spectrum anti-RNA viral drug) was given subcutaneously during the acute or chronic stage of infection. Following viral infection, general activity and survival were monitored daily for up to week 60. Starting at week 20 post-infection (PI), motor functions were measured weekly. Mouse brains and/or spinal cords were harvested at day 10, week 20 and week 60 PI for histopathological evaluation of neurotoxicity, immunohistochemical staining of viral protein, neuroinflammatory/immune and ALS pathology markers, and NanoString and RT-qPCR analysis of inflammatory gene expression.

Results
We found that sublethal infection (mimicking chronic infection) of SOD1G85R ALS mice with CVB3 resulted in early onset and progressive motor dysfunction, and shortened lifespan, while similar viral infection in C57BL/6J, the background strain of SOD1G85R mice, did not significantly affect motor function and mortality as compared to mock infection within the timeframe of the current study (60 weeks PI). Furthermore, we showed that CVB3 infection led to a significant increase in proinflammatory gene expression and immune cell infiltration and induced ALS-related pathologies (i.e., TAR DNA-binding protein 43 (TDP-43) pathology and neuronal damage) in the CNS of both SOD1G85R and C57BL/6J mice. Finally, we discovered that early (day 1) but not late (day 15) administration of ribavirin could rescue ALS-like neuropathology and symptoms induced by CVB3 infection.

Conclusions
Our study identifies a new risk factor that contributes to early onset and accelerated progression of ALS and offers opportunities for the development of novel targeted therapies.
As long as (I think) my husband agrees…: role of perceived partner approval in contraceptive use among couples living in military camps in Kinshasa, DRC
Authors: Hernandez Julie H. , Babazadeh Saleh , Anglewicz Philip A. , Akilimali Pierre Z. 
Published: January 2022

Abstract
Background
Male partner’s approval is a key determinant of contraceptive use for women living in Sub-Saharan Africa and improving men’s support and couple communication is a cornerstone of family planning programs. However, approval is often only measured through the women’s perception of their partner’s opinion.

Methods
This study conducted in Kinshasa compares contraceptive approval variables from matched male and female partners (n = 252 couples) to establish the frequency of (in)accurate perceptions by the woman, then test their association with modern contraceptive use. Additional regressions estimate individual and couple variables associated with (in)correct perceptions.

Results
Results confirm women are poorly aware of their partner’s opinion but indicate that perceived approval or disapproval by the woman is a much stronger determinant of modern contraceptive use than her partner’s actual opinion. Higher educational achievement from the woman is the strongest driver of misunderstanding her partner’s approval.

Conclusions
Women’s perceptions of partner’s approval are much stronger determinant of contraceptive use than the latter’s actual opinion, and stereotyping men’s opinion of family planning is a common error of appreciation. However, findings also suggest these misunderstandings might serve women’s capacity to negotiate contraceptive use.
Pollinating fig wasps’ simple solutions to complex sex ratio problems: a review
Authors: Greeff Jaco M. , Kjellberg Finn 
Published: January 2022

AbstractLocal mate competition (LMC) favours female biased clutch sex ratios because it reduces competition between brothers and provides extra mating opportunities for sons. Fig wasps seem to fit LMC model assumptions and lay female-biased sex ratios as predicted. These female biased sex ratios increase fitness greatly. In line with predictions, their sex ratios become less female-biased as the number of mothers laying in the same fig increases. However, this variation results in comparatively small fitness benefits compared to just biased ratios and data suggest substantial mismatches with LMC theory. The mismatches are due to several factors. (1) Multiple foundresses typically lay too many daughters. (2) Single foundress sex ratios are explained by sequential oviposition and ladies-last models. (3) Mortality that typically exceeds 10% may decouple the link between primary sex ratios, the focus of model predictions, and secondary sex ratios of adult wasps that are counted by researchers. (4) Model assumptions are frequently violated: (a) clutch sizes are unequal, (b) oviposition may not be simultaneous (c) cryptic/multiple wasp species inhabit the same host, (d) foundress numbers are systematically undercounted, (e) inbreeding coefficient calculations are inaccurate, and (f) male wasps sometimes disperse. These data and calculations suggest that alternative explanations must be considered seriously. Substantial data show that wasps typically lay most of their male eggs first followed by mostly female eggs require a new approach. These “slope” strategies result in more accurate sex ratios that are automatically adjusted to foundress number, own and relative clutch sizes and to sequential clutches. This effect will alter sex ratios in all species once the egg capacity of a fig is crossed or when interference reduces clutch sizes. In addition to this passive response, the females of about half the studied species have a conditional response that reduces female bias under higher foundress numbers by laying more sons. Therefore, wasps seem to use a very simple strategy that increases their fitness. Natural selection could have optimized parameters of the slope strategy and possibly the existence of the slope strategy itself. Variation in the slope strategy that is the result of natural selection is adaptive. Research should therefore focus on quantifying variables of this slope strategy. Currently, it is unclear how much of the variation is adaptive as opposed to being coincidental by-products.Graphical Abstract
Characterization of stroke-related upper limb motor impairments across various upper limb activities by use of kinematic core set measures
Authors: Schwarz Anne , Bhagubai Miguel M. C. , Nies Saskia H. G. , Held Jeremia P. O. , Veltink Peter H. , Buurke Jaap H. , Luft Andreas R. 
Published: January 2022

AbstractBackgroundUpper limb kinematic assessments provide quantifiable information on qualitative movement behavior and limitations after stroke. A comprehensive characterization of spatiotemporal kinematics of stroke subjects during upper limb daily living activities is lacking. Herein, kinematic expressions were investigated with respect to different movement types and impairment levels for the entire task as well as for motion subphases.MethodChronic stroke subjects with upper limb movement impairments and healthy subjects performed a set of daily living activities including gesture and grasp movements. Kinematic measures of trunk displacement, shoulder flexion/extension, shoulder abduction/adduction, elbow flexion/extension, forearm pronation/supination, wrist flexion/extension, movement time, hand peak velocity, number of velocity peaks (NVP), and spectral arc length (SPARC) were extracted for the whole movement as well as the subphases of reaching distally and proximally. The effects of the factors gesture versus grasp movements, and the impairment level on the kinematics of the whole task were tested. Similarities considering the metrics expressions and relations were investigated for the subphases of reaching proximally and distally between tasks and subgroups.ResultsData of 26 stroke and 5 healthy subjects were included. Gesture and grasp movements were differently expressed across subjects. Gestures were performed with larger shoulder motions besides higher peak velocity. Grasp movements were expressed by larger trunk, forearm, and wrist motions. Trunk displacement, movement time, and NVP increased and shoulder flexion/extension decreased significantly with increased impairment level. Across tasks, phases of reaching distally were comparable in terms of trunk displacement, shoulder motions and peak velocity, while reaching proximally showed comparable expressions in trunk motions. Consistent metric relations during reaching distally were found between shoulder flexion/extension, elbow flexion/extension, peak velocity, and between movement time, NVP, and SPARC. Reaching proximally revealed reproducible correlations between forearm pronation/supination and wrist flexion/extension, movement time and NVP.ConclusionSpatiotemporal differences between gestures versus grasp movements and between different impairment levels were confirmed. The consistencies of metric expressions during movement subphases across tasks can be useful for linking kinematic assessment standards and daily living measures in future research and performing task and study comparisons.Trial registration: ClinicalTrials.gov Identifier NCT03135093. Registered 26 April 2017,https://clinicaltrials.gov/ct2/show/NCT03135093.
The follicular lymphoma epigenome regulates its microenvironment
Authors: Amin Rada , Braza Mounia S. 
Published: January 2022

AbstractFollicular lymphoma (FL) is a B-cell non-Hodgkin lymphoma of germinal center (GC) origin with a distinctive tumor microenvironment (TME) and a unique spectrum of mutations. Despite the important therapeutic advances, FL is still incurable. During B-cell development, the GC reaction is a complex multistep process in which epigenetic regulators dynamically induce or suppress transcriptional programs. In FL, epigenetic gene mutations perturb the regulation of these programs, changing GC B-cell function and skewing differentiation towards tumor cells and altering the microenvironment interactions. FL pathogenesis and malignant transformation are promoted by epigenetic reprogramming of GC B cells that alters the immunological synapse and niche. Despite the extensive characterization of FL epigenetic signature and TME, the functional consequences of epigenetic dysregulation on TME and niche plasticity need to be better characterized. In this review, first we describe the most frequent epigenomic alterations in FL (KMT2D, CREBBP and EZH2) that affect the immunological niche, and their potential consequences on the informational transfer between tumor B cells and their microenvironment. Then, we discuss the latest progress to harness epigenetic targets for inhibiting the FL microenvironment. Finally, we highlight unexplored research areas and outstanding questions that should be considered for a successful long-term treatment of FL.
Using synthetic chromosome controls to evaluate the sequencing of difficult regions within the human genome
Authors: Reis Andre L. M. , Deveson Ira W. , Madala Bindu Swapna , Wong Ted , Barker Chris , Xu Joshua , Lennon Niall , Tong Weida , Mercer Tim R. ,   on behalf of the SEQC2 Consortium
Published: January 2022

AbstractBackgroundNext-generation sequencing (NGS) can identify mutations in the human genome that cause disease and has been widely adopted in clinical diagnosis. However, the human genome contains many polymorphic, low-complexity, and repetitive regions that are difficult to sequence and analyze. Despite their difficulty, these regions include many clinically important sequences that can inform the treatment of human diseases and improve the diagnostic yield of NGS.ResultsTo evaluate the accuracy by which these difficult regions are analyzed with NGS, we built an in silico decoy chromosome, along with corresponding synthetic DNA reference controls, that encode difficult and clinically important human genome regions, including repeats, microsatellites, HLA genes, and immune receptors. These controls provide a known ground-truth reference against which to measure the performance of diverse sequencing technologies, reagents, and bioinformatic tools. Using this approach, we provide a comprehensive evaluation of short- and long-read sequencing instruments, library preparation methods, and software tools and identify the errors and systematic bias that confound our resolution of these remaining difficult regions.ConclusionsThis study provides an analytical validation of diagnosis using NGS in difficult regions of the human genome and highlights the challenges that remain to resolve these difficult regions.
The SMARTscreen Trial: a randomised controlled trial investigating the efficacy of a GP-endorsed narrative SMS to increase participation in the Australian National Bowel Cancer Screening Program
Authors: Wood Anna , Emery Jon D. , Jenkins Mark , Chondros Patty , Campbell Tina , Wenkart Edweana , O’Reilly Clare , Cowie Tony , Dixon Ian , Toner Julie , Khalajzadeh Hourieh , Gutierrez Javiera Martinez , Govan Linda , Buckle Gemma , McIntosh Jennifer G. 
Published: January 2022

Abstract
Background
Increasing participation in the Australian National Bowel Cancer Screening Program (NBCSP) is the most efficient and cost-effective way of reducing mortality associated with colorectal cancer by detecting and treating early-stage disease. Currently, only 44% of Australians aged 50–74 years complete the NBCSP. This efficacy trial aims to test whether this SMS intervention is an effective method for increasing participation in the NBCSP. Furthermore, a process evaluation will explore the barriers and facilitators to sending the SMS from general practice.

Methods
We will recruit 20 general practices in the western region of Victoria, Australia to participate in a cluster randomised controlled trial. General practices will be randomly allocated with a 1:1 ratio to either a control or intervention group. Established general practice software will be used to identify patients aged 50 to 60 years old who are due to receive a NBCSP kit in the next month. The SMS intervention includes GP endorsement and links to narrative messages about the benefits of and instructions on how to complete the NBCSP kit. It will be sent from intervention general practices to eligible patients prior to receiving the NBCSP kit. We require 1400 eligible patients to provide 80% power with a two-sided 5% significance level to detect a 10% increase in CRC screening participation in the intervention group compared to the control group. Our primary outcome is the difference in the proportion of eligible patients who completed a faecal occult blood test (FOBT) between the intervention and control group for up to 12 months after the SMS was sent, as recorded in their electronic medical record (EMR). A process evaluation using interview data collected from general practice staff (GP, practice managers, nurses) and patients will explore the feasibility and acceptability of sending and receiving a SMS to prompt completing a NBCSP kit.

Discussion
This efficacy trial will provide initial trial evidence of the utility of an SMS narrative intervention to increase participation in the NBCSP. The results will inform decisions about the need for and design of a larger, multi-state trial of this SMS intervention to determine its cost-effectiveness and future implementation.

Trial registration
Australian New Zealand Clinical Trials Registry ACTRN12620001020976. Registered on 17 October 2020.
A lepidic gene signature predicts patient prognosis and sensitivity to immunotherapy in lung adenocarcinoma
Authors: Nguyen Thinh T. , Lee Hyun-Sung , Burt Bryan M. , Wu Jia , Zhang Jianjun , Amos Christopher I. , Cheng Chao 
Published: January 2022

Abstract
Background
Lung adenocarcinoma, the most common type of lung cancer, has a high level of morphologic heterogeneity and is composed of tumor cells of multiple histological subtypes. It has been reported that immune cell infiltration significantly impacts clinical outcomes of patients with lung adenocarcinoma. However, it is unclear whether histologic subtyping can reflect the tumor immune microenvironment, and whether histologic subtyping can be applied for therapeutic stratification of the current standard of care.

Methods
We inferred immune cell infiltration levels using a histological subtype-specific gene expression dataset. From differential gene expression analysis between different histological subtypes, we developed two gene signatures to computationally determine the relative abundance of lepidic and solid components (denoted as the L-score and S-score, respectively) in lung adenocarcinoma samples. These signatures enabled us to investigate the relationship between histological composition and clinical outcomes in lung adenocarcinoma using previously published datasets.

Results
We found dramatic immunological differences among histological subtypes. Differential gene expression analysis showed that the lepidic and solid subtypes could be differentiated based on their gene expression patterns while the other subtypes shared similar gene expression patterns. Our results indicated that higher L-scores were associated with prolonged survival, and higher S-scores were associated with shortened survival. L-scores and S-scores were also correlated with global genomic features such as tumor mutation burdens and driver genomic events. Interestingly, we observed significantly decreased L-scores and increased S-scores in lung adenocarcinoma samples with EGFR gene amplification but not in samples with EGFR gene mutations. In lung cancer cell lines, we observed significant correlations between L-scores and cell sensitivity to a number of targeted drugs including EGFR inhibitors. Moreover, lung cancer patients with higher L-scores were more likely to benefit from immune checkpoint blockade therapy.

Conclusions
Our findings provided further insights into evaluating histology composition in lung adenocarcinoma. The established signatures reflected that lepidic and solid subtypes in lung adenocarcinoma would be associated with prognosis, genomic features, and responses to targeted therapy and immunotherapy. The signatures therefore suggested potential clinical translation in predicting patient survival and treatment responses. In addition, our framework can be applied to other types of cancer with heterogeneous histological subtypes.
Computed tomography in traumatic orbital emergencies: a pictorial essay—imaging findings, tips, and report flowchart
Authors: Cellina Michaela , Cè Maurizio , Marziali Sara , Irmici Giovanni , Gibelli Daniele , Oliva Giancarlo , Carrafiello Gianpaolo 
Published: January 2022

AbstractComputed tomography (CT) is considered the gold standard technique for the assessment of trauma patients with suspected involvement of the eye and orbit. These traumas can result in dramatic consequences to visual function, ocular motility, and aesthetics. CT is a quick and widely available imaging modality, which provides a detailed evaluation of the orbital bony and soft tissue structures, an accurate assessment of the globes, and is used to guide the patients’ treatment planning. For a timely and accurate diagnosis, radiologists should be aware of fracture patterns and possible associated complications, ocular detachments and hemorrhages, and different appearances of intraorbital foreign bodies. This educational review aims to describe all post-traumatic orbital abnormalities that can be identified on CT, providing a list of tips and a diagnostic flowchart to help radiologists deal with this complex condition.