bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impacts of Workplace Environment on Coal Miners’ Emotion and Cognition Depicted in a Mouse Model
Authors: Li Lei , Wang Siwei , Huang Lu , Zhi Mei , Cai Qing , Fang Zihao , Yan Zhenguo , Xi Kaiwen , Feng Dayun
Published: June 2022

Most coal mine accidents are caused by the unsafe behavior of employees. Previous studies have shown that there is a significant connection among the working environment, the psychological state of employees, and unsafe behaviors. However, the internal biological mechanism has not been revealed. To explore the physiological and psychological alterations of coal mine workers and the underlying mechanisms that cause unsafe behaviors, the current study established a novel coal mine environment biological simulation (CEBS) model in mice. This model recreated the underground workplace environment facts in coal mines such as temperature, humidity, and noise, and mice were employed to receive these conditioning stresses according to the 8-h work. Animal behavior tests were performed to evaluate the evolution of the mental state including anxiety and depression, as well as the abilities of learning and memory during the 4-week environmental simulation. CEBS mice showed the adaptation process of anxiety from occurrence to stability in the process of environmental simulation, and also suffered from severe depression compared to the control mice. In addition, impaired spatial memory was also implicated in mice after 4-week CEBS. The behavior results of CEBS mice were consistent with the previous psychological investigation of coal workers. In summary, a novel mouse model was established in this study to depict the occurrence of negative emotions and impaired cognition in coal miners by simulating the underground workplace environment, which provided a basis for further exploring the biological mechanism of miners’ unsafe behavior.
Glial Cells and Brain Diseases: Inflammasomes as Relevant Pathological Entities
Authors: Mata-Martínez Esperanza , Díaz-Muñoz Mauricio , Vázquez-Cuevas Francisco G.
Published: June 2022

Inflammation mediated by the innate immune system is a physiopathological response to diverse detrimental circumstances such as microbe infections or tissular damage. The molecular events that underlie this response involve the assembly of multiprotein complexes known as inflammasomes. These assemblages are essentially formed by a stressor-sensing protein, an adapter protein and a non-apoptotic caspase (1 or 11). The coordinated aggregation of these components mediates the processing and release of pro-inflammatory interleukins (IL-β and IL-18) and cellular death by pyroptosis induction. The inflammatory response is essential for the defense of the organism; for example, it triggers tissue repair and the destruction of pathogen microbe infections. However, when inflammation is activated chronically, it promotes diverse pathologies in the lung, liver, brain and other organs. The nervous system is one of the main tissues where the inflammatory process has been characterized, and its implications in health and disease are starting to be understood. Thus, the regulation of inflammasomes in specific cellular types of the central nervous system needs to be thoroughly understood to innovate treatments for diverse pathologies. In this review, the presence and participation of inflammasomes in pathological conditions in different types of glial cells will be discussed.
Toward Reflective Spiking Neural Networks Exploiting Memristive Devices
Authors: Makarov Valeri A. , Lobov Sergey A. , Shchanikov Sergey , Mikhaylov Alexey , Kazantsev Viktor B.
Published: June 2022

The design of modern convolutional artificial neural networks (ANNs) composed of formal neurons copies the architecture of the visual cortex. Signals proceed through a hierarchy, where receptive fields become increasingly more complex and coding sparse. Nowadays, ANNs outperform humans in controlled pattern recognition tasks yet remain far behind in cognition. In part, it happens due to limited knowledge about the higher echelons of the brain hierarchy, where neurons actively generate predictions about what will happen next, i.e., the information processing jumps from reflex to reflection. In this study, we forecast that spiking neural networks (SNNs) can achieve the next qualitative leap. Reflective SNNs may take advantage of their intrinsic dynamics and mimic complex, not reflex-based, brain actions. They also enable a significant reduction in energy consumption. However, the training of SNNs is a challenging problem, strongly limiting their deployment. We then briefly overview new insights provided by the concept of a high-dimensional brain, which has been put forward to explain the potential power of single neurons in higher brain stations and deep SNN layers. Finally, we discuss the prospect of implementing neural networks in memristive systems. Such systems can densely pack on a chip 2D or 3D arrays of plastic synaptic contacts directly processing analog information. Thus, memristive devices are a good candidate for implementing in-memory and in-sensor computing. Then, memristive SNNs can diverge from the development of ANNs and build their niche, cognitive, or reflective computations.
Needs and Perceptions of Patients With Dystonia During the COVID-19 Pandemic: A Qualitative Framework Analysis of Survey Responses From Italy
Authors: Rispoli Vittorio , Díaz Crescitelli Matías Eduardo , Cavallieri Francesco , Antonelli Francesca , Meletti Stefano , Ghirotto Luca , Valzania Franco
Published: June 2022

Introduction:

The COVID-19 pandemic and its countermeasures have created changes in both life and healthcare. With the prioritization of COVID-19-related management, the risks and experiences of patients suffering from rare conditions, such as dystonia, during the pandemic remain understudied.

Materials and Methods

Using a framework analysis of a nationwide qualitative online survey, we sought to explore the perspectives of patients with dystonia on their clinical assistance and possible unmet needs during the first pandemic wave. An online survey consisting of 37 items (such as demographic characteristics, dystonia-related features, neurological service provision, therapeutic relationship with the neurologist, perceptions related to virus infection, perceptions about healthcare-related needs, work-related questions, requesting information, and seeking support during the pandemic) was carried out using both close and open-ended questions.

Results

Responses from 62 participants were collected, with most of them from the red zones in Italy, where they were confined indoors. Social isolation was a relevant stressor. Motor and non-motor symptoms increased with detrimental consequences for patients' job and daily functionality. Outpatient clinics and rehabilitation sessions were temporarily shut down, and even telephone/mail support was sparse. Despite efforts, patients felt alone in dealing with dystonia.

Conclusion

The first wave of the pandemic and its related restrictions had detrimental consequences for people living with dystonia, and their relevant needs remained unmet. These findings may contribute to implementing remedial healthcare provisions in this pandemic or in future pandemics.
Association Between Late-Onset Leukoencephalopathy With Vanishing White Matter and Compound Heterozygous EIF2B5 Gene Mutations: A Case Report and Review of the Literature
Authors: Kong Fanxin , Zheng Haotao , Liu Xuan , Lin Songjun , Wang Jianjun , Guo Zhouke
Published: June 2022

Leukoencephalopathy with vanishing white matter (LVWM) is an autosomal recessive disease. Ovarioleukodystrophy is defined as LVWM in females showing signs or symptoms of gradual ovarian failure. We present a 38-year-old female with ovarioleukodystrophy who showed status epilepticus, gait instability, slurred speech, abdominal tendon hyperreflexia, and ovarian failure. Abnormal EEG, characteristic magnetic resonance, and unreported EIF2B5 compound heterozygous mutations [c.1016G>A (p.R339Q) and c.1157G>A (p.G386D)] were found. Furthermore, the present report summarizes 20 female patients with adult-onset ovarioleukodystrophy and EIF2B5 gene mutations. In conclusion, a new genetic locus for LVWM was discovered. Compared with previous cases, mutations at different EIF2B5 sites might have different clinical manifestations and obvious clinical heterogeneity.
APOEε4 Genotype Is Related to Brain Amyloid Among Mexican Americans in the HABS-HD Study
Authors: O'Bryant Sid E. , Petersen Melissa , Hall James , Johnson Leigh
Published: June 2022

Introduction

Despite the fact that Hispanics are expected to experience the greatest increase in Alzheimer's disease (AD) and related dementias (ADRDs) by 2060, very little data is available regarding the fundamental biomarkers of AD among Mexican Americans who reflect the majority of Hispanics in the U.S. Here we sought to examine the link between APOEε4 genotype and brain amyloid among Mexican Americans as compared to non-Hispanic white participants from the Health & Aging Brain Study – Health Disparities (HABS-HD) cohort.

Methods

PET amyloid (florbetaben) data were analyzed from 105 Mexican American and 150 non-Hispanic white participants.

Results

Among Mexican Americans, APOEε4 genotype presence was associated with Global SUVR (p = 0.003) as well as amyloid burden in the frontal (p < 0.001), lateral parietal (p = 0.003), lateral temporal (p = 0.008) and anterior-posterior cingulate (p = 0.005) regions of interest (ROIs). Among non-Hispanic white participants, APOEε4 genotype presence was associated with Global SUVR (p < 0.001) as well as amyloid burden in the frontal (p < 0.001), lateral parietal (p < 0.001), lateral temporal (p < 0.001) and anterior-posterior cingulate (p < 0.001) regions of interest (ROIs). The association between APOEε4 genotype and cerebral amyloid was strongest among non-Hispanic white participants.

Discussion/Conclusion

Despite the fact that the APOEε4 genotype is significantly less frequent among Mexican Americans, its presence remains to be a significant risk factor among this group for AD pathological burden across all regions. Additional work is needed to understand the presence, progression, and clinical impact of brain amyloid among Mexican Americans.
Proton Magnetic Resonance Spectroscopy for the Early Diagnosis of Parkinson Disease in the Substantia Nigra and Globus Pallidus: A Meta-Analysis With Trial Sequential Analysis
Authors: Gu Wenbin , He Chen , Chen Juping , Li Junchen
Published: June 2022

This study aimed to investigate the metabolic changes in globus pallidus (GP) and substantia nigra (SN) during the early stage of Parkinson disease (PD) using magnetic resonance spectroscopy (MRS). PubMed, Embase, Web of Science, and Chinese National Knowledge Infrastructure were searched till November 2018. Eligible trials comparing early metabolic changes in GP and SN in patients with PD vs. controls were included. The mean differences with 95% confidence intervals were estimated with either fixed- or random-effects models using Review Manager 5.3 software. Trial sequential analysis was performed using TSA 0.9.5.10 beta software. Finally, 16 studies were selected from the search. Overall, the N-acetyl aspartate-to-creatine ratio showed a significant difference between patients with early-stage PD and healthy controls. The overall heterogeneity was P < 0.00001, I2 = 94% in GP and P = 0.0002, I2 = 74% in SN. The results revealed that MRS could be a more sensitive imaging biomarker in the diagnosis of early-stage PD.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=125731, registration number: CRD42019125731.
Absolute Reliability of Gait Parameters Acquired With Markerless Motion Capture in Living Domains
Authors: Riazati Sherveen , McGuirk Theresa E. , Perry Elliott S. , Sihanath Wandasun B. , Patten Carolynn
Published: June 2022

Purpose: To examine the between-day absolute reliability of gait parameters acquired with Theia3D markerless motion capture for use in biomechanical and clinical settings.

Methods: Twenty-one (7 M,14 F) participants aged between 18 and 73 years were recruited in community locations to perform two walking tasks: self-selected and fastest-comfortable walking speed. Participants walked along a designated walkway on two separate days.Joint angle kinematics for the hip, knee, and ankle, for all planes of motion, and spatiotemporal parameters were extracted to determine absolute reliability between-days. For kinematics, absolute reliability was examined using: full curve analysis [root mean square difference (RMSD)] and discrete point analysis at defined gait events using standard error of measurement (SEM). The absolute reliability of spatiotemporal parameters was also examined using SEM and SEM%.

Results: Markerless motion capture produced low measurement error for kinematic full curve analysis with RMSDs ranging between 0.96° and 3.71° across all joints and planes for both walking tasks. Similarly, discrete point analysis within the gait cycle produced SEM values ranging between 0.91° and 3.25° for both sagittal and frontal plane angles of the hip, knee, and ankle. The highest measurement errors were observed in the transverse plane, with SEM >5° for ankle and knee range of motion. For the majority of spatiotemporal parameters, markerless motion capture produced low SEM values and SEM% below 10%.

Conclusion: Markerless motion capture using Theia3D offers reliable gait analysis suitable for biomechanical and clinical use.
Memory for the Future: Psychodynamic Approach to Time and Self Through the Default Network
Authors: Cieri Filippo
Published: June 2022

Time exists in us, and our self exists in time. Our self is affected and shaped by time to the point that a better understanding of the former can aid the understanding of the latter. Psychoanalysis works through self and time, where the self is composed of the biopsychosocial history (the past) of the individual and able to map a trajectory for the future. The psychoanalytic relationship starts from a “measurement”: an active process able to alter the system being measured—the self—continuously built over time. This manuscript, starts from the philosophical and scientific tradition of a proximity between time and self, suggesting a neural overlapping at the Default Network. A historical and scientific background will be introduced, proposing a multidisciplinary dimension that has characterized the birth of psychoanalysis (its past), influencing its present and future in the dialogue with physics and neuroscience. After a historical scientific introduction, a neuralentanglementbetween past and future at the Default Network level will be proposed, tracing a link with the self at the level of this network. This hypothesis will be supported by studies in cognitive neurosciences and functional neuroimaging which have used the resting state functional Magnetic Resonance Imaging. The ontogenetic development of time perception will be discussed, consistent with self-development and the Default Network’s function. The most common form of dementia, the Alzheimer’s Disease, in which the perception of time is brutally impaired together with a loss of the self’s functions will be proposed to support this idea. Finally, the potential theoretical and clinical significance for psychoanalysis and psychodynamic neurosciences, will be discussed.
Laterality and Sex Differences of Human Lateral Habenula Afferent and Efferent Fiber Tracts
Authors: Hitti Frederick L. , Parker Drew , Yang Andrew I. , Brem Steven , Verma Ragini
Published: June 2022

Introduction

The lateral habenula (LHb) is an epithalamic nucleus associated with negative valence and affective disorders. It receives input via the stria medullaris (SM) and sends output via the fasciculus retroflexus (FR). Here, we use tractography to reconstruct and characterize this pathway.

Methods

Multi-shell human diffusion magnetic resonance imaging (dMRI) data was obtained from the human connectome project (HCP) (n = 20, 10 males) and from healthy controls (n = 10, 6 males) scanned at our institution. We generated LHb afferents and efferents using probabilistic tractography by selecting the pallidum as the seed region and the ventral tegmental area as the output target.

Results

We were able to reconstruct the intended streamlines in all individuals from the HCP dataset and our dataset. Our technique also aided in identification of the LHb. In right-handed individuals, the streamlines were significantly more numerous in the left hemisphere (mean ratio 1.59 ± 0.09, p = 0.04). In left-handed individuals, there was no hemispheric asymmetry on average (mean ratio 1.00 ± 0.09, p = 1.0). Additionally, these streamlines were significantly more numerous in females than in males (619.9 ± 159.7 vs. 225.9 ± 66.03, p = 0.04).

Conclusion

We developed a method to reconstruct the SM and FR without manual identification of the LHb. This technique enables targeting of these fiber tracts as well as the LHb. Furthermore, we have demonstrated that there are sex and hemispheric differences in streamline number. These findings may have therapeutic implications and warrant further investigation.
Consciousness, Cognition and the Neuronal Cytoskeleton – A New Paradigm Needed in Neuroscience
Authors: Hameroff Stuart
Published: June 2022

Viewing the brain as a complex computer of simple neurons cannot account for consciousness nor essential features of cognition. Single cell organisms with no synapses perform purposeful intelligent functions using their cytoskeletal microtubules. A new paradigm is needed to view the brain as a scale-invariant hierarchy extending both upward from the level of neurons to larger and larger neuronal networks, but also downward, inward, to deeper, faster quantum and classical processes in cytoskeletal microtubules inside neurons. Evidence shows self-similar patterns of conductive resonances repeating in terahertz, gigahertz, megahertz, kilohertz and hertz frequency ranges in microtubules. These conductive resonances apparently originate in terahertz quantum dipole oscillations and optical interactions among pi electron resonance clouds of aromatic amino acid rings of tryptophan, phenylalanine and tyrosine within each tubulin, the component subunit of microtubules, and the brain’s most abundant protein. Evidence from cultured neuronal networks also now shows that gigahertz and megahertz oscillations in dendritic-somatic microtubules regulate specific firings of distal axonal branches, causally modulating membrane and synaptic activities. The brain should be viewed as a scale-invariant hierarchy, with quantum and classical processes critical to consciousness and cognition originating in microtubules inside neurons.
How Do Nutritional Warnings Work on Commercial Products? Results From a Hypothetical Choice Experiment
Authors: de Alcantara Marcela , Ares Gastón , Deliza Rosires
Published: June 2022

A large body of evidence assessing the effectiveness of front-of-package (FOP) nutrition labeling exists. Most experimental studies have been conducted with fictitious products. However, consumers’ perception depends on several products extrinsic factors such as brand. Understanding how strong brand associations influence the effectiveness of FOP nutrition labeling schemes may be crucial to informing policymaking. In this context, the aim of this work was to evaluate the effect of five different variants of nutritional warnings labels (black magnifier, red magnifier, black octagon, black triangle, and red circle) on consumers’ choice of commercial products, compared with two FOP nutrition labeling schemes: the guidelines daily amounts (GDAs) system and the traffic light system (TLS). An online randomized controlled trial with 1,932 participants was used to evaluate the effect of FOP nutrition labeling on participants’ choices in eight sets of three commercial products, available in the Brazilian marketplace. A multinomial logistic regression model was used to evaluate the influence of FOP nutrition labeling on participants’ likelihood of selecting the different products in the choice task. Results showed that nutritional warnings and the TLS significantly increased the likelihood of selecting none of the products instead of the least healthful product, or a healthier product, in at least one of the product categories compared with the GDA. Warnings tended to have a larger effect, suggesting their potential to encourage healthier food choices.
Blood–Brain Barrier Permeability Study of Potential Neuroprotective Compounds Recovered From Plants and Agri-Food by-Products
Authors: Sánchez-Martínez José David , Valdés Alberto , Gallego Rocio , Suárez-Montenegro Zully Jimena , Alarcón Marina , Ibañez Elena , Alvarez-Rivera Gerardo , Cifuentes Alejandro
Published: June 2022

Plants and agri-food by-products represent a wide and renewable source of bioactive compounds with neuroprotective properties. In this research, various green extraction techniques were employed to recover bioactive molecules from Kalanchoe daigremontiana (kalanchoe), epicarp of Cyphomandra betacea (tamarillo), and cooperage woods from Robinia pseudoacacia (acacia) and Nothofagus pumilio (lenga), as well as a reference extract (positive control) from Rosmarinus officinalis L. (rosemary). The neuroprotective capacity of these plant extracts was evaluated in a set of in vitro assays, including enzymatic [acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and lipoxygenase (LOX)] and antioxidant [ABTS, and reactive oxygen and nitrogen species (ROS and RNS)] bioactivity tests. Extracts were also submitted to a parallel artificial membrane permeability assay mimicking the blood–brain barrier (PAMPA-BBB) and to two cell viability assays in HK-2 and SH-SY5Y cell lines. Comprehensive phytochemical profiling based on liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS) analysis showed enriched content of phenolic and terpenoid compounds in the target extracts. Moreover, in vitro bioactivity tests showed promising neuroprotective capacity, particularly for supercritical-fluid extraction (SFE) extract from acacia (ABTS IC50 = 0.11 μg ml−1; ROS IC50 = 1.56 μg ml−1; AChE IC50 = 4.23 μg ml−1; BChE IC50 = 1.20 μg ml−1; and LOX IC50 = 4.37 μg ml−1), whereas PAMPA-BBB assays revealed high perfusion capacity of some representative compounds, such as phenolic acids or flavonoids. Regarding cytotoxic assays, tamarillo and rosemary SFE extracts can be considered as non-toxic, acacia SFE extract and lenga pressurized liquid extraction (PLE) extract as mild-cytotoxic, and kalanchoe as highly toxic extracts. The obtained results demonstrate the great potential of the studied biomass extracts to be transformed into valuable food additives, food supplements, or nutraceuticals with promising neuroprotective properties.
Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma: Where Do We Go?
Authors: Wang Chenqi , Tan Guang , Zhang Jie , Fan Bin , Chen Yunlong , Chen Dan , Yang Lili , Chen Xiang , Duan Qingzhu , Maimaiti Feiliyan , Du Jian , Lin Zhikun , Gu Jiangning , Luo Haifeng
Published: June 2022

The incidence of pancreatic ductal adenocarcinoma (PDAC) has been on the rise in recent years; however, its clinical diagnosis and treatment remain challenging. Although surgical resection remains the only chance for long-term patient survival, the likelihood of initial resectability is no higher than 20%. Neoadjuvant therapy (NAT) in PDAC aims to transform the proportion of inoperable PDACs into operable cases and reduce the likelihood of recurrence to improve overall survival. Ongoing phase 3 clinical trial aims to validate the role of NAT in PDAC therapy, including prolongation of survival, increased R0 resection, and a higher proportion of negative lymph nodes. Controversies surrounding the role of NAT in PDAC treatment include applicability to different stages of PDAC, chemotherapy regimens, radiation, duration of treatment, and assessment of effect. This review aims to summarize the current progress and controversies of NAT in PDAC.
Construction of a Novel Prognostic Model in Lung Adenocarcinoma Based on 7-Methylguanosine-Related Gene Signatures
Authors: Lu Fei , Gao Jingyan , Hou Yu , Cao Ke , Xia Yaoxiong , Chen Zhengting , Yu Hui , Chang Li , Li Wenhui
Published: June 2022

Increasing evidence has implicated the modification of 7-methylguanosine (m7G), a type of RNA modification, in tumor progression. However, no comprehensive analysis to date has summarized the predicted role of m7G-related gene signatures in lung adenocarcinoma (LUAD). Herein, we aimed to develop a novel prognostic model in LUAD based on m7G-related gene signatures. The LUAD transcriptome profiling data and corresponding clinical data were acquired from the Cancer Genome Atlas (TCGA) and two Gene Expression Omnibus datasets. After screening, we first obtained 29 m7G-related genes, most of which were upregulated in tumor tissues and negatively associated with overall survival (OS). According to the expression similarity of m7G-related genes, the combined samples from the TCGA-LUAD and GSE68465 datasets were further classified as two clusters that exhibit distinct OS rates and genetic heterogeneity. Then, we constructed a novel prognostic model involving four genes by using 130 differentially expressed genes among the two clusters. The combined samples were randomly divided into a training cohort and an internal validation cohort in a 1:1 ratio, and the GSE72094 dataset was used as an external validation cohort. The samples were divided into high- and low-risk groups. We demonstrated that a higher risk score was an independent negative prognostic factor and predicted poor OS. A nomogram was further constructed to better predict the survival of LUAD patients. Functional enrichment analyses indicated that cell cycle and DNA replication-related biological processes and pathways were enriched in the high-risk group. More importantly, the low-risk group had greater infiltration and enrichment of most immune cells, as well as higher ESTIMATE, immune, and stromal scores. In addition, the high-risk group had a lower TIDE score and higher expressions of most immune checkpoint-related genes. We finally noticed that patients in the high-risk group were more sensitive to chemotherapeutic agents commonly used in LUAD. In conclusion, we herein summarized for the first time the alterations and prognostic role of m7G-related genes in LUAD and then constructed a prognostic model based on m7G-related gene signatures that could accurately and stably predict survival and guide individualized treatment decision-making in LUAD patients.
Increased Methyl-CpG-Binding Domain Protein 2 Promotes Cigarette Smoke-Induced Pulmonary Hypertension
Authors: Wu Jixing , Huang Qian , Li Qinghai , Gu Yiya , Zhan Yuan , Wang Ting , Chen Jinkun , Zeng Zhilin , Lv Yongman , Zhao Jianping , Xia Jie , Xie Jungang
Published: June 2022

Pulmonary hypertension (PH) is a chronic vascular proliferative disorder. While cigarette smoke (CS) plays a vital part in PH related to chronic obstructive pulmonary disease (COPD). Methyl-CpG-Binding Domain Protein 2 (MBD2) has been linked to multiple proliferative diseases. However, the specific mechanisms of MBD2 in CS-induced PH remain to be elucidated. Herein, the differential expression of MBD2 was tested between the controls and the PH patients’ pulmonary arteries, CS-exposed rat models’ pulmonary arteries, and primary human pulmonary artery smooth muscle cells (HPASMCs) following cigarette smoke extract (CSE) stimulation. As a result, PH patients and CS-induced rats and HPASMCs showed an increase in MBD2 protein expression compared with the controls. Then, MBD2 silencing was used to investigate the function of MBD2 on CSE-induced HPASMCs’ proliferation, migration, and cell cycle progression. As a consequence, CSE could induce HPASMCs’ increased proliferation and migration, and cell cycle transition, which were suppressed by MBD2 interference. Furthermore, RNA-seq, ChIP-qPCR, and MassARRAY were conducted to find out the downstream mechanisms of MBD2 for CS-induced pulmonary vascular remodeling. Subsequently, RNA-seq revealed MBD2 might affect the transcription of BMP2 gene, which furtherly altered the expression of BMP2 protein. ChIP-qPCR demonstrated MBD2 could bind BMP2’s promotor. MassARRAY indicated that MBD2 itself could not directly affect DNA methylation. In sum, our results indicate that increased MBD2 expression promotes CS-induced pulmonary vascular remodeling. The fundamental mechanisms may be that MBD2 can bind BMP2’s promoter and downregulate its expression. Thus, MBD2 may promote the occurrence of the CS-induced PH.
PRKCI Mediates Radiosensitivity via the Hedgehog/GLI1 Pathway in Cervical Cancer
Authors: Wu Zhuna , Huang Chunxian , Li Ruixin , Li Hui , Lu Huaiwu , Lin Zhongqiu
Published: June 2022

Objective

Insensitivity to radiotherapy accounts for the majority of therapeutic failures in cervical cancer (CC) patients who undergo radical radiotherapy. We aimed to elucidate the molecular mechanisms underlying radiosensitivity to identify methods to improve the overall 5-year survival rate. The atypical protein kinase C iota (aPKCι) gene PRKCI exhibits tumor-specific copy number amplification (CNA) in CC. We investigated how PRKCI decreases radiosensitivity in CC and assessed the interplay between PRKCI and the Hedgehog (Hh)/GLI1 pathway in the present research.

Methods

The biological functions of PRKCI in CC radiosensitivity were explored through immunohistochemistry, colony formation, Cell Counting Kit-8 (CCK-8), cell cycle, apoptosis assays, and xenograft models. qRT-PCR, Western blotting analysis, and immunofluorescence assays were utilized to evaluate the interplay between PRKCI and the Hh/GLI1 pathway and its mechanism in PRKCI-decreased radiosensitivity in CC. Furthermore, the effect of auranofin (AF), a selective inhibitor of PKCι, on CC cells was explored through biochemical assays in vitro and in vivo.

Results

We found that high PRKCI expression was responsible for decreased survival in CC. PRKCI was intimately associated with radiation-triggered alterations in proliferation, the cell cycle, apoptosis, and xenograft growth. The Hh/GLI1 pathway was activated when PRKCI expression was altered. PRKCI functions downstream of the Hh/GLI1 pathway to phosphorylate and activate the transcription factor GLI1. AF acts as a radiosensitizer and showed biological effects in vitro and in vivo.

Conclusions

PRKCI is a therapeutic target for regulating radiosensitivity in CC. This molecule regulates radiosensitivity by modulating GLI1 relocalization and phosphorylation in CC via the Hh/GLI1 pathway.
Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series
Authors: Yang Chuanwei , Cui Yong , Ren Xiaohui , Li Ming , Yu Kefu , Shen Shaoping , Jiang Haihui , Li Mingxiao , Zhang Xiaokang , Zhao Xuzhe , Zhu Qinghui , Lin Song
Published: June 2022

Background

Relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL) is an intractable situation without sound treatment. Bruton’s tyrosine kinase (BTK) represents an attractive drug target in PCNSL. Orelabrutinib is a new-generation BTK inhibitor with high cerebrospinal fluid (CSF) concentration. This study aimed to evaluate the efficacy and safety of orelabrutinib-containing combination therapy in patients with r/r PCNSL.

Methods

We retrospectively analyzed r/r PCNSL patients who received combination therapy with rituximab, high-dose methotrexate, temozolomide, orelabrutinib and lenalidomide, and further explored the relationship between the efficacy and genetic characteristics.

Results

A total of fifteen patients were included in this retrospective study. The overall response rate (ORR) was 86.7%, the complete remission (CR) rate was 73.3% and the disease control rate (DCR) was 93.3%. Among 13 responders, 9 patients are still receiving oral orelabrutinib and lenalidomide. The most common adverse event (AEs) was transaminase increase (66.7%). No grade 4 AE or drug-related death was reported. Genomic sequencing showed that patients who responded to orelabrutinib had abnormal NF-κB activation, while those who had no response were mainly enriched with transcriptional misregulation. Patients who had mutations in TLR, BCR, or NF-κB pathway achieved complete or partial response to the orelabrutinib-containing therapy. Moreover, the blood and cerebrospinal fluid circulating tumor DNA (ctDNA) were closely associated with tumor recurrence and treatment response and sustained tumor responses correlated with the clearance of ctDNA.

Conclusion

Orelabrutinib-containing regimen was effective and well-tolerated in patients with r/r PCNSL. Genome sequencing of tumor samples could help to screen patients who may respond to the orelabrutinib-containing regimen, and liquid biopsy may contribute to tracing tumor burden and monitoring treatment response.
Applications and Achievements of Single-Cell Sequencing in Gastrointestinal Cancer
Authors: Xie Zhenliang , Li Jincheng , Huang Pu , Zhang Ye , Yang Jingkuan , Liu Kangdong , Jiang Yanan
Published: June 2022

Gastrointestinal cancer represents a public health concern that seriously endangers human health. The emerging single-cell sequencing (SCS) technologies are different from the large-scale sequencing technologies which provide inaccurate data. SCS is a powerful tool for deciphering the single-cell resolutions of cellular and molecular landscapes, revealing the features of single-cell genomes, transcriptomes, and epigenomes. Recently, SCS has been applied in the field of gastrointestinal cancer research for clarifying the origin and heterogeneity of gastrointestinal cancer, acquiring micro-environmental information, and improving diagnostic and treatment methods. This review outlines the applications of SCS in gastrointestinal cancer research and summarizes the most recent advances in the field.
Episodic Memories Among Irritable Bowel Syndrome (IBS) Patients: An Important Aspect of the IBS Symptom Experience
Authors: Sayuk Gregory S. , North Carol S. , Pollio David E. , Gott Britt M. , Alpers David H.
Published: June 2022

Objective:

Some IBS patients possess detailed memories of the events surrounding their bowel symptom onset (“episodic memories”). In this exploratory study we sought to: (1) examine memory relationship with gastrointestinal (GI) symptom severity, extraintestinal symptoms, and mood; (2) qualitatively explore memory valence and content in IBS patients with or without episodic memories.

Methods

Referral IBS patients n = 29; age 47.0± 2.2 years, 79.3% female) enrolled in this cross-sectional, mixed methods research study. Participants completed validated specific memory instruments [Autobiographical Memory Test (AMT), Sentence Completion for Events from the Past Test (SCEPT)] and relevant questionnaires [IBS symptoms 10-cm visual analog scale); SF-36 Health-related quality of life (HRQOL); Perley-Guze and PHQ-15/12: somatization; Beck Depression/Anxiety Inventories). Qualitative analysis examined the content and valence of general memories.

Results

14/29 (48.3%) of IBS subjects endorsed episodic memories of IBS symptom onset, often GI infections/enteritis (35.7%). Recall of the exact year (69%) and month (60%) of symptom onset were common. Episodic memories were associated with greater IBS symptom severity/bother, higher anxiety/depression, and poorer HRQOL. Though AMT and SCEPT memory specificity were not different based on episodic memories, overgeneralization to negatively-valenced cues in the AMT was associated with more severe IBS in those without episodic memory. Qualitative analysis revealed no observable differences in topic focus of IBS patients with and without episodic memories.

Conclusions

IBS patients often endorse episodic memories associated with symptom onset, and this recall seems to associate with more severe symptoms. Overgeneralization responses to negative stimuli may lead to worse bowel symptoms in those without episodic memories. IBS memory specificity may associate with qualitative differences in processing psychosocial experiences and might be important to IBS pathophysiology.
Reference Values of Noninvasive Myocardial Work Indices Measured by Echocardiography in Healthy Children
Authors: Cui Cunying , Zheng Qiang , Li Yanan , Huang Danqing , Hu Yanbing , Wang Ying , Liu Rujie , Liu Lin , Zhang Lianzhong
Published: June 2022

Backgroud

Noninvasive myocardial work, estimated by left ventricular (LV) pressure-strain loop (PSL), has been introduced for assessing LV myocardial performance. Based on both blood pressure and speckle-tracking derived strain data, noninvasive myocardial work is considered to be less load-dependent than global longitudinal strain (GLS). In some conditions, such as hypertension or aortic coarctation, the increased afterload will affect strain measurements, and myocardial work can serve as a more robust metric.

Objective

We prospectively recruited healthy children to explore the relationship between myocardial work indices and body size parameters, and to determine the reference values of noninvasive myocardial work indices in healthy children.

Methods

183 healthy children (aged 1–18 years, males: 52.5%) were enrolled in the study. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE), were assessed by LVPSL and compared according to age and sex.

Results

The mean for GWI was 1,448.7 ± 265.0 mm Hg%, 1,859.8 ± 290.7 mm Hg% for GCW, and the median (interquartile range) for GWW was 54.0 (33.0–82.0) mm Hg% and 97.0 (95.0–99.0) % for GWE. male had greater GWI and GCW) than female (1,572.5 ± 250.2 mm Hg% vs. 1,312.2 ± 208.7 mm Hg% and 1,944.3 ± 299.2 mm Hg% vs. 1,766.6 ± 251.5 mm Hg%, respectively, all P < 0.001). GWI and GCW were significantly correlated with baseline parameters, including age, height, weight, BSA, body mass index, heart rate, and blood pressure. After indexed to BSA, GWI (BSA), GCW (BSA) remained significantly negatively correlated with age (P < 0.001).

Conclusions

we proposed the normal reference values and regression equations for GWI and GCW based on age and BSA in healthy children. This might provide a basis of reference for the evaluation of cardiac function in children with cardiopulmonary disease.
Challenges and Opportunities With Routinely Collected Data on the Utilization of Cancer Medicines. Perspectives From Health Authority Personnel Across 18 European Countries
Authors: Pisana Alice , Wettermark Björn , Kurdi Amanj , Tubic Biljana , Pontes Caridad , Zara Corinne , Van Ganse Eric , Petrova Guenka , Mardare Ileana , Fürst Jurij , Roig-Izquierdo Marta , Melien Oyvind , Bonanno Patricia Vella , Banzi Rita , Marković-Peković Vanda , Mitkova Zornitsa , Godman Brian
Published: June 2022

Background: Rising expenditure for new cancer medicines is accelerating concerns that their costs will become unsustainable for universal healthcare access. Moreover, early market access of new oncology medicines lacking appropriate clinical evaluation generates uncertainty over their cost-effectiveness and increases expenditure for unknown health gain. Patient-level data can complement clinical trials and generate better evidence on the effectiveness, safety and outcomes of these new medicines in routine care. This can support policy decisions including funding. Consequently, there is a need for improving datasets for establishing real-world outcomes of newly launched oncology medicines.

Aim: To outline the types of available datasets for collecting patient-level data for oncology among different European countries. Additionally, to highlight concerns regarding the use and availability of such data from a health authority perspective as well as possibilities for cross-national collaboration to improve data collection and inform decision-making.

Methods: A mixed methods approach was undertaken through a cross-sectional questionnaire followed-up by a focus group discussion. Participants were selected by purposive sampling to represent stakeholders across different European countries and healthcare settings. Descriptive statistics were used to analyze quantifiable questions, whilst content analysis was employed for open-ended questions.

Results: 25 respondents across 18 European countries provided their insights on the types of datasets collecting oncology data, including hospital records, cancer, prescription and medicine registers. The most available is expenditure data whilst data concerning effectiveness, safety and outcomes is less available, and there are concerns with data validity. A major constraint to data collection is the lack of comprehensive registries and limited data on effectiveness, safety and outcomes of new medicines. Data ownership limits data accessibility as well as possibilities for linkage, and data collection is time-consuming, necessitating dedicated staff and better systems to facilitate the process. Cross-national collaboration is challenging but the engagement of multiple stakeholders is a key step to reach common goals through research.

Conclusion: This study acts as a starting point for future research on patient-level databases for oncology across Europe. Future recommendations will require continued engagement in research, building on current initiatives and involving multiple stakeholders to establish guidelines and commitments for transparency and data sharing.
Bismuth Reduces Cisplatin-Induced Nephrotoxicity Via Enhancing Glutathione Conjugation and Vesicular Transport
Authors: Jiang Hui , Hong Yifan , Fan Guorong
Published: June 2022

Bismuth drugs have long been used against gastrointestinal diseases, especially the gastric infection of Helicobacter pylori. Cisplatin is a widely used anticancer drug that tends to accumulate at renal proximal tubules and causes severe nephrotoxicity. It was found that bismuth pretreatment reduces cisplatin-induced nephrotoxicity, but the mechanism of action remains unclear. To understand bismuth’s effect on renal tubules, we profiled the proteomic changes in human proximal tubular cells (HK-2) upon bismuth treatment. We found that bismuth induced massive glutathione biosynthesis, glutathione S-transferase activity, and vesicular transportation, which compartmentalizes bismuth to the vesicles and forms bismuth–sulfur nanoparticles. The timing of glutathione induction concurs that of bismuth-induced cisplatin toxicity mitigation in HK-2, and bismuth enhanced cisplatin sequestration to vesicles and incorporation into bismuth–sulfur nanoparticles. Finally, we found that bismuth mitigates the toxicity of general soft metal compounds but not hard metal compounds or oxidants. It suggests that instead of through oxidative stress reduction, bismuth reduces cisplatin-induced toxicity by direct sequestration.
Changes of Physicochemical Properties and Immunomodulatory Activity of Polysaccharides During Processing of Polygonum multiflorum Thunb
Authors: Gu Donglin , Wang Ying , Jin Hongyu , Kang Shuai , Liu Yue , Zan Ke , Fan Jing , Wei Feng , Ma Shuangcheng
Published: June 2022

The roots of Polygonum multiflorum Thunb (PM) have a long history of usage in traditional Chinese medicine and are still widely utilized today. PM in raw or processed form has different biological activities and is commonly used to treat different diseases. Polysaccharides are the main component of PM, and it is unclear whether their physicochemical properties and activities change after processing. In this study, the polysaccharides from thirty-one raw PM (RPMPs) and nine processed PM (PPMPs) were extracted, and the physicochemical properties and immunomodulatory activity in vitro of polysaccharide samples were evaluated. Results showed that RPMPs and PPMPs had significant differences in physicochemical properties. RPMPs and PPMPs were both composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose. However, RPMPs and PPMPs had significant differences in their yields, molecular weight (Mw), and the molar ratio of Glc/GalA (p < 0.05), which can be used to distinguish raw and processed PM. The fingerprint of monosaccharide composition was analyzed by chemometrics, and it was further demonstrated that Glc and GalA could be used as differential markers. The immunomodulatory activity assays indicated that RPMPs and PPMPs could significantly enhance phagocytosis and mRNA expression of cytokines in RAW 264.7 cells. In addition, the immunomodulatory activity of PPMPs with lower Mw was significantly better than that of RPMPs. This study furthers the understanding of the polysaccharides from raw and processed PM and provides a reference for improving the quality standard of PM.
A Ubiquitous Collective Tragedy in Transport
Authors: Prieto Curiel Rafael , González Ramírez Humberto , Bishop Steven
Published: June 2022

A tragedy of the commons is said to occur when individuals act only in their own interest but, in so doing, create a collective state of a group that is less than optimal due to uncoordinated action. Here, we explore the individual decision-making processes of commuters using various forms of transport within a city, forming a modal share which is then built into a dynamical model using travel time as the key variable. From a randomised start in the distribution of the modal share, assuming that some individuals change their commuting method, favouring lower travel times, we show that a stable modal share is reached corresponding to an equilibrium in the model. Considering the average travel time for all commuters within the city, we show that an optimal result is achieved only if the direct and induced factors and the number of users are equal for all transport modes. For asymmetric factors, the equilibrium reached is always sub-optimal, leading to city travel trajectories being “tragic”, meaning that individuals choose a faster commuting time but create a slower urban mobility as a collective result. Hence, the city evolves, producing longer average commuting times. It is also shown that if a new mode of transport has a small baseline commuting time but has a high induced impact for other users, then introducing it might result in a counter-intuitive result producing more congestion, rather than less.
Eastward Jet Lag is Associated with Impaired Performance and Game Outcome in the National Basketball Association
Authors: Leota Josh , Hoffman Daniel , Czeisler Mark É. , Mascaro Luis , Drummond Sean P.A. , Anderson Clare , Rajaratnam Shantha M.W. , Facer-Childs Elise R.
Published: June 2022

Objectives: Elite athletes are often required to travel across time zones for national and international competitions, causing frequent jet lag. The aim of this study was to examine whether the direction of travel-related jet lag is associated with performance in the National Basketball Association (NBA), and if so, to explore potential mechanisms.

Methods: Ten seasons comprising of 11,481 games of NBA data from the 2011/2012 to the 2020/2021 regular season were analyzed using multi-level mixed models with one fixed factor (three levels; jet lag direction: eastward vs westward vs no jet lag) and three random factors (team, opponent, game time). Predicted circadian resynchronization rate was accounted for, and home and away games were analysed separately. Mediation analyses were performed to examine potential mechanisms.

Results: Among home teams, eastward (but not westward) jet lag was associated with reduced winning (Δ (i.e., change) = −6.03%, p = 0.051, marginal), points differential (Δ = −1.29 points, p = 0.015), rebound differential (Δ = −1.29 rebounds, p < 0.0001), and effective field goal percentage differential (Δ = −1.2%, p < 0.01). As the magnitude of eastward jet lag increased, home team points differential decreased (2 h Δ = −4.53 points, p < 0.05; 1 h Δ = −0.72 points, p = 0.07). No significant associations were found between jet lag and away team performance.

Conclusion: Eastward jet lag was associated with impaired performance for home (but not away) teams. Sleep and circadian disruption associated with advancing phase following eastward travel may have significant adverse consequences on performance in the NBA, particularly when recovery time is limited. Sports organisations could consider chronobiology-informed scheduling and interventions to maximise recovery and performance of their athletes.