bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Satellite 1A analysis provides evidence of pericentromeric transcription
Authors: Lopes Mariana , Louzada Sandra , Ferreira Daniela , Veríssimo Gabriela , Eleutério Daniel , Gama-Carvalho Margarida , Chaves Raquel
Published: February 2023

Background

Pericentromeric regions of human chromosomes are composed of tandem-repeated and highly organized sequences named satellite DNAs. Human classical satellite DNAs are classified into three families named HSat1, HSat2, and HSat3, which have historically posed a challenge for the assembly of the human reference genome where they are misrepresented due to their repetitive nature. Although being known for a long time as the most AT-rich fraction of the human genome, classical satellite HSat1A has been disregarded in genomic and transcriptional studies, falling behind other human satellites in terms of functional knowledge. Here, we aim to characterize and provide an understanding on the biological relevance of HSat1A.

Results

The path followed herein trails with HSat1A isolation and cloning, followed by in silico analysis. Monomer copy number and expression data was obtained in a wide variety of human cell lines, with greatly varying profiles in tumoral/non-tumoral samples. HSat1A was mapped in human chromosomes and applied in in situ transcriptional assays. Additionally, it was possible to observe the nuclear organization of HSat1A transcripts and further characterize them by 3′ RACE-Seq. Size-varying polyadenylated HSat1A transcripts were detected, which possibly accounts for the intricate regulation of alternative polyadenylation.

Conclusion

As far as we know, this work pioneers HSat1A transcription studies. With the emergence of new human genome assemblies, acrocentric pericentromeres are becoming relevant characters in disease and other biological contexts. HSat1A sequences and associated noncoding RNAs will most certainly prove significant in the future of HSat research.
FZD1/KLF10-hsa-miR-4762-5p/miR-224-3p-circular RNAs axis as prognostic biomarkers and therapeutic targets for glioblastoma: a comprehensive report
Authors: Jia Fang , Zhang Lixia , Jiang Zhengye , Tan Guowei , Wang Zhanxiang
Published: February 2023

Background

The circular RNA (circRNA) plays a vital role in the pathogenesis of tumors as a competitive endogenous RNA (ceRNA). Given the high aggressiveness and fatality rate of glioblastoma (GBM) as well as poor prognosis, it is necessary to construct a circRNA-related ceRNA network for further studies on the mechanism of GBM and identify possible biomarkers as well as therapeutic drugs.

Methods

Three datasets from the gene expression omnibus (GEO) database were downloaded to distinguish differential circRNAs, microRNAs, and messenger RNAs respectively in GBM. With the help of GEPIA2, circBank, CSCD, TargetScan, miRDB, and miRTarBase databases, we established a circRNAs-related ceRNA network in GBM. Functional enrichments were employed to profile the most relevant mRNAs to indirectly clarify the mechanisms of the ceRNA network. Based on the expression profile data and survival information of GBM patients from the GEO and the cancer genome atlas (TCGA) databases, we performed survival analysis to select prognostic mRNAs and constructed a novel circRNA-miRNA-mRNA central regulatory subnetwork. The DGIdb database was used to find potential drug–gene interactions.

Results

The datasets obtained from the GEO and TCGA databases were analyzed, and 504 differentially expressed mRNAs (DEmRNAs), 71 differentially expressed microRNAs (DEmiRNAs), and 270 differentially expressed circRNAs (DEcircRNAs) were screened out. The novel ceRNA regulatory network included 22 circRNAs, 11 miRNAs, and 15 mRNAs. FZD1 and KLF10 were significantly correlated with the overall survival rate of patients with GBM (P < 0.05). The final survival subnetwork contained six circRNAs, two miRNAs, and two mRNAs. Two small-molecule compounds and one antibody could be used as therapeutic drugs for GBM. Interestingly, the Wnt signaling pathway appeared in both KEGG and GO functional terms.

Conclusions

Results of this study demonstrate that FZD1 and KLF10 may exert regulatory functions in GBM, and the ceRNA-mediated network could be a therapeutic strategy for GBM.
Competency profiles for evidence-informed policy-making (EIPM): a rapid review
Authors: Barreto Jorge Otávio Maia , Romão Davi Mamblona Marques , Setti Cecilia , Machado Maria Lúcia Teixeira , Riera Rachel , Gomes Romeu , da Silva Silvio Fernandes
Published: February 2023

Background

Evidence-informed policy-making (EIPM) requires a set of individual and organizational capacities, linked with background factors and needs. The identification of essential knowledge, skills and attitudes for EIPM can support the development of competency profiles and their application in different contexts.

Purpose

To identify elements of competency (knowledge, skills and attitudes) for EIPM, according to different professional profiles (researcher, health professional, decision-maker and citizen).

Methods

Rapid umbrella review. A structured search was conducted and later updated in two comprehensive repositories (BVSalud and PubMed). Review studies with distinctive designs were included, published from 2010 onwards, without language restrictions. Assessment of the methodological quality of the studies was not performed. A meta-aggregative narrative synthesis was used to report the findings.

Results

Ten reviews were included. A total of 37 elements of competency were identified, eight were categorized as knowledge, 19 as skills and 10 as attitudes. These elements were aggregated into four competency profiles: researcher, health professional, decision-maker and citizen. The competency profiles included different sets of EIPM-related knowledge, skills and attitudes.

Strengths and limitations

This study is innovative because it aggregates different profiles of competency from a practical perspective, favouring the application of its results in different contexts to support EIPM. Methodological limitations are related to the shortcuts adopted in this review: complementary searches of the grey literature were not performed, and the study selection and data extraction were not conducted in duplicate.

Final considerations: conclusions and implications of the findings

EIPM requires the development of individual and organizational capacities. This rapid review contributes to the discussion on the institutionalization of EIPM in health systems. The competency profiles presented here can support discussions about the availability of capacity and the need for its development in different contexts.
Presence of depression and anxiety with distinct patterns of pharmacological treatments before the diagnosis of chronic fatigue syndrome: a population-based study in Taiwan
Authors: Chen Chi , Yip Hei-Tung , Leong Kam-Hang , Yao Wei-Cheng , Hung Chung-Lieh , Su Ching-Huang , Kuo Chien-Feng , Tsai Shin-Yi
Published: February 2023

Objective

An increased prevalence of psychiatric comorbidities (including depression and anxiety disorder) has been observed among patients with chronic fatigue syndrome (CFS). However, few studies have examined the presence of depression and anxiety disorder before the diagnosis of CFS. This study aimed to clarify the preexisting comorbidities and treatments associated with patients with subsequent CFS diagnosis in a population-based cohort in Taiwan.

Methods

An analysis utilizing the National Health Insurance Research Database of Taiwan was conducted. Participants included were 6303 patients with CFS newly diagnosed between 2000 and 2010 and 6303 age-/sex-matched controls.

Results

Compared with the control group, the CFS group had a higher prevalence of depression and anxiety disorder before the diagnosis of CFS. Sampled patients who took specific types of antidepressants, namely, selective serotonin reuptake inhibitors (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] 1.04–1.39), serotonin antagonists and reuptake inhibitors (SARI; aOR = 1.87, 95% CI 1.59–2.19), and tricyclic antidepressants (aOR = 1.46, 95% CI 1.09–1.95), had an increased risk of CFS. CFS risk was also higher among participants taking benzodiazepine, muscle relaxants, and analgesic drugs. A sub-group analysis revealed that SARI use was related to an increased risk of CFS in the depression, anxiety disorder, male, and female groups. In the depression and anxiety disorder groups, analgesic drug use was associated with an increased CFS risk. Nonpharmacological treatment administration differed between men and women.

Conclusion

This population-based retrospective cohort study revealed an increased risk of CFS among populations with preexisting depression and anxiety disorder, especially those taking SARI and analgesic drugs.
Genetic dissection of the impact of lncRNA AI662270 during the development of atherosclerosis
Authors: Hong Yang , Zhang Yue , Chen Hui , Tang Xueqing , Zhao Hongrui , Meng Ziyu , Jia Xueling , Liu Wenfeng , Li Xiaohan , Wang Lin , Zhong Xinrui , Bai Xuefeng , Sun Heyang , Kopylov Philipp , Afina Bestavashvili , Shchekochikhin Dmitry , Zhang Yong , Liu Xin , Fan Yuhua
Published: February 2023

Background

Atherosclerosis is driven by synergistic interactions between pathological biomechanical and lipid metabolic factors. Long noncoding RNAs (LncRNAs) have been implicated in atherogenesis. The purpose of this study was to investigate the potential mechanism of lncRNA AI662270 on macrophage cholesterol transport in atherosclerosis.

Methods

Apolipoprotein E deficiency (ApoE−/−) mice were fed a high fat diet for 16 weeks to construct atherosclerotic model, and the mice were injected with recombinant lentivirus carrying AI662270 gene to overexpress AI662270. Macrophages were cleared by liposomal clondronate in vivo. Fundamental experiments and functional assays, hematoxylin and eosin staining, oil red O staining and others, were performed to evaluate the function of AI662270 on atherogenesis. Peritoneal macrophages were treated with oxidized low density lipoprotein (ox-LDL) to simulate in vitro model. Mechanism assays, RNA-interacting protein immunoprecipitation, RNA–protein pulldown and others, were performed to study the regulatory mechanism of AI662270 in macrophages.

Results

The novel AI662270 was mainly enriched in macrophages, but not in endothelial cells, smooth muscle cells and fibroblasts of mouse atherosclerotic lesions and was upregulated by ox-LDL. Overexpression of AI662270 resulted in lipid accumulation, larger atherosclerotic plaques and cardiac dysfunction in vivo. After macrophages were removed, the pro-atherogenic effect of AI662270 disappeared. Downregulation of AI662270 in macrophages protected against foam cell formation by potentiating cholesterol efflux and reducing intracellular total cholesterol. The opposite effect was observed in macrophage-specific AI662270-overexpressed cells in vitro. AI662270 bound to adenosine triphosphate-binding cassette transporter A1 (Abca1) responsible for regulating cholesterol efflux in macrophages. Forced expression of AI662270 in macrophages decreased Abca1 expression. The reverse occurred when expression of AI662270 was repressed.

Conclusion

These findings reveal an essential role for AI662270 in atherosclerosis progression by regulating cholesterol efflux from macrophages.
Genetic models of cleavage-reduced and soluble TREM2 reveal distinct effects on myelination and microglia function in the cuprizone model
Authors: Beckmann Nicolau , Neuhaus Anna , Zurbruegg Stefan , Volkmer Pia , Patino Claudia , Joller Stefanie , Feuerbach Dominik , Doelemeyer Arno , Schweizer Tatjana , Rudin Stefan , Neumann Ulf , Berth Ramon , Frieauff Wilfried , Gasparini Fabrizio , Shimshek Derya R.
Published: February 2023

Triggering receptor expressed on myeloid cells 2 (TREM2) is a cell-surface immunoreceptor expressed on microglia, osteoclasts, dendritic cells and macrophages. Heterozygous loss-of-function mutations in TREM2, including mutations enhancing shedding form the cell surface, have been associated with myelin/neuronal loss and neuroinflammation in neurodegenerative diseases, such as Alzheimer`s disease and Frontotemporal Dementia. Using the cuprizone model, we investigated the involvement of soluble and cleavage-reduced TREM2 on central myelination processes in cleavage-reduced (TREM2-IPD), soluble-only (TREM2-sol), knockout (TREM2-KO) and wild-type (WT) mice. The TREM2-sol mouse is a new model with selective elimination of plasma membrane TREM2 and a reduced expression of soluble TREM2. In the acute cuprizone model demyelination and remyelination events were reflected by a T2-weighted signal intensity change in magnetic resonance imaging (MRI), most prominently in the external capsule (EC). In contrast to WT and TREM2-IPD, TREM2-sol and TREM2-KO showed an additional increase in MRI signal during the recovery phase. Histological analyses of TREM2-IPD animals revealed no recovery of neuroinflammation as well as of the lysosomal marker LAMP-1 and displayed enhanced cytokine/chemokine levels in the brain. TREM2-sol and, to a much lesser extent, TREM2-KO, however, despite presenting reduced levels of some cytokines/chemokines, showed persistent microgliosis and astrocytosis during recovery, with both homeostatic (TMEM119) as well as activated (LAMP-1) microglia markers increased. This was accompanied, specifically in the EC, by no myelin recovery, with appearance of myelin debris and axonal pathology, while oligodendrocytes recovered. In the chronic model consisting of 12-week cuprizone administration followed by 3-week recovery TREM2-IPD displayed sustained microgliosis and enhanced remyelination in the recovery phase. Taken together, our data suggest that sustained microglia activation led to increased remyelination, whereas microglia without plasma membrane TREM2 and only soluble TREM2 had reduced phagocytic activity despite efficient lysosomal function, as observed in bone marrow-derived macrophages, leading to a dysfunctional phenotype with improper myelin debris removal, lack of remyelination and axonal pathology following cuprizone intoxication.
An overview on the treatments and prevention against COVID-19
Authors: Panahi Yunes , Gorabi Armita Mahdavi , Talaei Sona , Beiraghdar Fatemeh , Akbarzadeh Abolfazl , Tarhriz Vahideh , Mellatyar Hassan
Published: February 2023

Background

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to plague the world. While COVID-19 is asymptomatic in most individuals, it can cause symptoms like pneumonia, ARDS (acute respiratory distress syndrome), and death in others. Although humans are currently being vaccinated with several COVID-19 candidate vaccines in many countries, however, the world still is relying on hygiene measures, social distancing, and approved drugs.

Result

There are many potential therapeutic agents to pharmacologically fight COVID-19: antiviral molecules, recombinant soluble angiotensin-converting enzyme 2 (ACE2), monoclonal antibodies, vaccines, corticosteroids, interferon therapies, and herbal agents. By an understanding of the SARS-CoV-2 structure and its infection mechanisms, several vaccine candidates are under development and some are currently in various phases of clinical trials.

Conclusion

This review describes potential therapeutic agents, including antiviral agents, biologic agents, anti-inflammatory agents, and herbal agents in the treatment of COVID-19 patients. In addition to reviewing the vaccine candidates that entered phases 4, 3, and 2/3 clinical trials, this review also discusses the various platforms that are used to develop the vaccine COVID-19.
Parents’ understanding and attitudes toward the use of the WeChat platform for postoperative follow-up management of children with congenital heart disease
Authors: Lin Wen-Hao , Chen Yu-Kun , Lin Shi-Hao , Cao Hua , Chen Qiang
Published: February 2023

Objective

This study aimed to investigate parents’ understanding and attitudes toward using the WeChat platform for postoperative follow-up management of children with congenital heart disease (CHD).

Methods

A total of 196 children with CHD were followed up using the WeChat platform. A self-designed questionnaire was administered to their parents at discharge.

Results

Only 188 parents completed the questionnaire. One hundred nineteen parents (63.3%) confirmed that they heard about using the WeChat platform for postoperative follow-up, and 104 (87.4%) of them expressed that they were willing to accept the WeChat platform for their follow-up. A total of 42 parents (35.3%) were willing to undergo a follow-up of 1 to 3 months, and 32 (26.8%) were willing to undergo a long-term follow-up. Eighty parents (67.2%) had a positive attitude toward the effect of the WeChat platform on follow-up. Parents in rural areas and those educated at the middle school level or below were more willing to engage with the WeChat platform for postoperative follow-up management (P < 0.05).

Conclusions

Although the WeChat platform is an essential tool for daily communication, its application in postoperative follow-up management is still under study. Most parents who participated in the follow-up study had a positive attitude toward the WeChat platform, especially those in rural areas and with lower education levels.
Exploiting RIG-I-like receptor pathway for cancer immunotherapy
Authors: Jiang Yangfu , Zhang Hongying , Wang Jiao , Chen Jinzhu , Guo Zeyu , Liu Yongliang , Hua Hui
Published: February 2023

RIG-I-like receptors (RLRs) are intracellular pattern recognition receptors that detect viral or bacterial infection and induce host innate immune responses. The RLRs family comprises retinoic acid-inducible gene 1 (RIG-I), melanoma differentiation-associated gene 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2) that have distinctive features. These receptors not only recognize RNA intermediates from viruses and bacteria, but also interact with endogenous RNA such as the mislocalized mitochondrial RNA, the aberrantly reactivated repetitive or transposable elements in the human genome. Evasion of RLRs-mediated immune response may lead to sustained infection, defective host immunity and carcinogenesis. Therapeutic targeting RLRs may not only provoke anti-infection effects, but also induce anticancer immunity or sensitize “immune-cold” tumors to immune checkpoint blockade. In this review, we summarize the current knowledge of RLRs signaling and discuss the rationale for therapeutic targeting RLRs in cancer. We describe how RLRs can be activated by synthetic RNA, oncolytic viruses, viral mimicry and radio-chemotherapy, and how the RNA agonists of RLRs can be systemically delivered in vivo. The integration of RLRs agonism with RNA interference or CAR-T cells provides new dimensions that complement cancer immunotherapy. Moreover, we update the progress of recent clinical trials for cancer therapy involving RLRs activation and immune modulation. Further studies of the mechanisms underlying RLRs signaling will shed new light on the development of cancer therapeutics. Manipulation of RLRs signaling represents an opportunity for clinically relevant cancer therapy. Addressing the challenges in this field will help develop future generations of cancer immunotherapy.
Retraction Note: HnRNP A1 - mediated alternative splicing of CCDC50 contributes to cancer progression of clear cell renal cell carcinoma via ZNF395
Authors: Sun Guoliang , Zhou Hui , Chen Ke , Zeng Jin , Zhang Yangjun , Yan Libin , Yao Weimin , Hu Junhui , Wang Tao , Xing Jinchun , Xiao Kefeng , Wu Lily , Ye Zhangqun , Xu Hua
Published: February 2023

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-020-01606-x.
Evaluation and comparison of different breast cancer prognosis scores based on gene expression data
Authors: Chowdhury Avirup , Pharoah Paul D. , Rueda Oscar M.
Published: February 2023

Background

Breast cancer is one of the three most common cancers worldwide and is the most common malignancy in women. Treatment approaches for breast cancer are diverse and varied. Clinicians must balance risks and benefits when deciding treatments, and models have been developed to support this decision-making. Genomic risk scores (GRSs) may offer greater clinical value than standard clinicopathological models, but there is limited evidence as to whether these models perform better than the current clinical standard of care.

Methods

PREDICT and GRSs were adapted using data from the original papers. Univariable Cox proportional hazards models were produced with breast cancer-specific survival (BCSS) as the outcome. Independent predictors of BCSS were used to build multivariable models with PREDICT. Signatures which provided independent prognostic information in multivariable models were incorporated into the PREDICT algorithm and assessed for calibration, discrimination and reclassification.

Results

EndoPredict, MammaPrint and Prosigna demonstrated prognostic power independent of PREDICT in multivariable models for ER-positive patients; no score predicted BCSS in ER-negative patients. Incorporating these models into PREDICT had only a modest impact upon calibration (with absolute improvements of 0.2–0.8%), discrimination (with no statistically significant c-index improvements) and reclassification (with 4–10% of patients being reclassified).

Conclusion

Addition of GRSs to PREDICT had limited impact on model fit or treatment received. This analysis does not support widespread adoption of current GRSs based on our implementations of commercial products.
Identification of candidate genes and pathways associated with juvenile idiopathic arthritis by integrative transcriptome-wide association studies and mRNA expression profiles
Authors: Feng Ruoyang , Lu Mengnan , Yin Chunyan , Xu Ke , Liu Lin , Xu Peng
Published: February 2023

Aim

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood, with genetic susceptibility and pathological processes such as autoimmunity and autoinflammation, but its pathogenesis is unclear. We conducted a transcriptome-wide association study (TWAS) using expression interpolation from a large-scale genome-wide association study (GWAS) dataset to identify genes, biological pathways, and environmental chemicals associated with JIA.

Methods

We obtained published GWAS data on JIA for TWAS and used mRNA expression profiling to validate the genes identified by TWAS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. A protein–protein interaction (PPI) network was generated, and central genes were obtained using Molecular Complex Detection (MCODE). Finally, chemical gene expression datasets were obtained from the Comparative Toxicogenomics database for chemical genome enrichment analysis.

Results

TWAS identified 1481 genes associated with JIA, and 154 differentially expressed genes were identified based on mRNA expression profiles. After comparing the results of TWAS and mRNA expression profiles, we obtained eight overlapping genes. GO and KEGG enrichment analyses of the genes identified by TWAS yielded 163 pathways, and PPI network analysis as well as MCODE resolution identified a total of eight clusters. Through chemical gene set enrichment analysis, 287 environmental chemicals associated with JIA were identified.

Conclusion

By integrating TWAS and mRNA expression profiles, genes, biological pathways, and environmental chemicals associated with JIA were identified. Our findings provide new insights into the pathogenesis of JIA, including candidate genetic and environmental factors contributing to its onset and progression.
Assessment of residual gastric volume using point-of-care ultrasonography in adult patients who underwent elective surgery
Authors: Chaitra T.S. , Palta Sanjeev , Saroa Richa , Jindal Swati , Jain Aditi
Published: February 2023

Background

Aspiration pneumonitis remains a dreaded complication that may lead to almost 9% of anaesthesia-related deaths. The presence of gastric contents has always been a contributing factor to an increased risk of aspiration. Preoperative gastric ultrasound has been suggested as a modality for determining residual volume in special populations and conditions. We conducted an observational study to determine the gastric residual volume in preoperative patients of elective surgery with gastric ultrasound and to study its correlation with patient factors.

Methods

We enrolled 411 patients in the age group of 18–80 with ASA-PS I and II having BMI less than 35 kg/m2. Patients with prior gastrointestinal surgery and parturients were excluded from the present study. Gastric antrum in both supine and right lateral decubitus positions was measured using USG in the immediate preoperative period, and gastric residual volume was calculated, which was subsequently correlated with various patient factors.

Results

On qualitative assessment, 97 and 118 patients were observed to have distended stomachs in the supine and right lateral decubitus positions, respectively. On quantitative assessment, 336 had safe GRV, 60 patients were classified as having a low risk of aspiration (GRV < 1.5 ml/kg) while 13 had a high risk of aspiration (> 1.5 ml/kg). Eight patients with a fasting duration of more than ten hours and five who fasted between 6 and 10 h had a gastric residual volume of more than 1.5 ml/h. Patients who were premedicated with histamine blockers had a statistically significant higher antral cross-sectional area (p-value − 0.022*) and GRV (p-value − 0.018*) in the right lateral decubitus position compared to patients who had taken proton pump inhibitors (PPIs). As BMI increased, there was a statistically significant (p-value < 0.001) increase in mean antral CSA in both supine and right lateral decubitus positions. There was a statistically significant association found between type 2 diabetes (p-value 0.045*) with antral grade.

Discussion

Patients can have significant residual volume (> 1.5 ml/kg) despite adequate fasting, and preoperative gastric ultrasound can help in assessing the same and guiding perioperative airway management. PPIs are more effective in reducing gastric residual volume as compared to histamine blockers. Patients with a BMI of more than 30 and type 2 diabetes mellitus have significant correlation with increased gastric residual volume mandating preoperative gastric ultrasound assessment for effective management.

Conclusions

Patients with BMI over 30 and type 2 diabetes may benefit from POCGUS to guide perioperative airway management by stratifying GRV.

Trial registration Name of registry-Clinical Trial Registry of India. Trial registration number-2020/03/024083. Date of registration-19.3.2020. URL-http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=39961&EncHid=&userName=
Sex-divergent effects on the NAD+-dependent deacetylase sirtuin signaling across the olfactory–entorhinal–amygdaloid axis in Alzheimer’s and Parkinson’s diseases
Authors: Cartas-Cejudo Paz , Lachén-Montes Mercedes , Ferrer Isidro , Fernández-Irigoyen Joaquín , Santamaría Enrique
Published: February 2023

Background

Smell impairment is one of the earliest features in Alzheimer’s (AD) and Parkinson’s diseases (PD). Due to sex differences exist in terms of smell and olfactory structures as well as in the prevalence and manifestation of both neurological syndromes, we have applied olfactory proteomics to favor the discovery of novel sex-biased physio-pathological mechanisms and potential therapeutic targets associated with olfactory dysfunction.

Methods

SWATH-MS (sequential window acquisition of all theoretical fragment ion spectra mass spectrometry) and bioinformatic workflows were applied in 57 post-mortem olfactory tracts (OT) derived from controls with no known neurological history (n = 6F/11M), AD (n = 4F/13M) and PD (n = 7F/16M) subjects. Complementary molecular analyses by Western-blotting were performed in the olfactory bulb (OB), entorhinal cortex (EC) and amygdala areas.

Results

327 and 151 OT differentially expressed proteins (DEPs) were observed in AD women and AD men, respectively (35 DEPs in common). With respect to PD, 198 DEPs were identified in PD women, whereas 95 DEPs were detected in PD men (20 DEPs in common). This proteome dyshomeostasis induced a disruption in OT protein interaction networks and widespread sex-dependent pathway perturbations in a disease-specific manner, among them Sirtuin (SIRT) signaling. SIRT1, SIRT2, SIRT3 and SIRT5 protein levels unveiled a tangled expression profile across the olfactory–entorhinal–amygdaloid axis, evidencing disease-, sex- and brain structure-dependent changes in olfactory protein acetylation.

Conclusions

Alteration in the OT proteostasis was more severe in AD than in PD. Moreover, protein expression changes were more abundant in women than men independent of the neurological syndrome. Mechanistically, the tangled SIRT profile observed across the olfactory pathway-associated brain regions in AD and PD indicates differential NAD (+)-dependent deacetylase mechanisms between women and men. All these data shed new light on differential olfactory mechanisms across AD and PD, pointing out that the evaluation of the feasibility of emerging sirtuin-based therapies against neurodegenerative diseases should be considered with caution, including further sex dimension analyses in vivo and in clinical studies.
Metabolic reprogramming in colorectal cancer: regulatory networks and therapy
Authors: Zhang Jieping , Zou Shaomin , Fang Lekun
Published: February 2023

With high prevalence and mortality, together with metabolic reprogramming, colorectal cancer is a leading cause of cancer-related death. Metabolic reprogramming gives tumors the capacity for long-term cell proliferation, making it a distinguishing feature of cancer. Energy and intermediate metabolites produced by metabolic reprogramming fuel the rapid growth of cancer cells. Aberrant metabolic enzyme-mediated tumor metabolism is regulated at multiple levels. Notably, tumor metabolism is affected by nutrient levels, cell interactions, and transcriptional and posttranscriptional regulation. Understanding the crosstalk between metabolic enzymes and colorectal carcinogenesis factors is particularly important to advance research for targeted cancer therapy strategies via the investigation into the aberrant regulation of metabolic pathways. Hence, the abnormal roles and regulation of metabolic enzymes in recent years are reviewed in this paper, which provides an overview of targeted inhibitors for targeting metabolic enzymes in colorectal cancer that have been identified through tumor research or clinical trials.
Snapshot depth–spectral imaging based on image mapping and light field
Authors: Ding Xiaoming , Hu Liang , Zhou Shubo , Wang Xiaocheng , Li Yupeng , Han Tingting , Lu Dunqiang , Che Guowei
Published: February 2023

Depth–spectral imaging (DSI) is an emerging technology which can obtain and reconstruct the spatial, spectral and depth information of a scene simultaneously. Conventionally, DSI system usually relies on scanning process, multi-sensors or compressed sensing framework to modulate and acquire the entire information. This paper proposes a novel snapshot DSI architecture based on image mapping and light field framework by using a single format detector. Specifically, we acquire the depth – spectral information in two steps. Firstly, an image mapper is utilized to slice and reflect the first image to different directions which is a spatial modulation processing. The modulated light wave is then dispersed by a direct vision prism. After re-collection, the sliced dispersed light wave is recorded by a light field sensor. Complimentary, we also propose a reconstruction strategy to recover the spatial depth – spectral hypercube effectively. We establish a mathematical model to describe the light wave distribution on every optical facet. Through simulations, we generate the aliasing raw spectral light field data. Under the reconstruction strategy, we design an algorithm to recover the hypercube accurately. Also, we make an analysis about the spatial and spectral resolution of the reconstructed data, the evaluation results conform the expectation.
Altered glycosylation profiles of serum IgG in Takayasu arteritis
Authors: Liu Lingyu , Li Jing , Yang Yunjiao , Hu Chaojun , Tian Xinping
Published: February 2023

Background

Takayasu arteritis (TAK) is an autoimmune inflammatory disorder with an undefined etiology. This study aimed to characterize the glycosylation profiles of serum immunoglobulin G (IgG) in patients with TAK.

Methods

Lectin microarrays containing 56 types of lectins were used to detect the glycan levels of serum IgG in 164 patients with TAK, 128 patients with atherosclerosis used as disease controls (DCs), and 100 healthy controls (HCs). Differentially altered glycosylation patterns between TAK and control groups as well as between TAK subgroups were identified and further validated by lectin blot. The classification performance of the TAK-specific glycosylation change was measured by receiver-operating characteristic (ROC) curve analysis.

Results

Lectin microarray analysis revealed significantly increased N-Acetylgalactosamine (GalNAc) levels in the TAK group compared to the DC and HC groups (all p < 0.01). For TAK subgroups, significantly decreased mannosylation was observed in patients with active TAK compared to patients with inactive disease (p < 0.01). These differences were validated by lectin blot. In addition, GalNAc levels exhibited a considerable potential for discriminating patients with TAK from patients with atherosclerosis, with an area under the curve of 0.749 (p < 0.001), a sensitivity of 71.7%, and a specificity of 73.8%.

Conclusions

Serum IgG in patients with TAK displayed disease-specific glycosylation alterations. Aberrant GalNAc glycosylation showed substantial value as a diagnostic biomarker. The potential proinflammatory properties of the abnormal glycans may provide new insights into the role of humoral immunity in the pathogenesis of TAK.
Guiding officers to deflect citizens to treatment: an examination of police department policies in Illinois
Authors: Reichert Jessica , Adams Sharyn , Taylor Jirka , del Pozo Brandon
Published: February 2023

Background

The U.S. overdose crisis has motivated police departments to enact policies allowing officers to directly deflect individuals to substance use disorder treatment and other services shown to reduce recidivism and subsequent overdose risk, as well as refer people who voluntarily present at police facilities with a desire for treatment. As a new way of operating, and one that relies on an officer’s use of discretion for successful implementation, the practice benefits from guidance through written directives, training, and supervisory support. However, there is little information on the establishment, content, and execution of police department deflection policies, which hampers the implementation and dissemination of this promising practice.

We analyzed 16 policies of Illinois police department deflection programs. Using content analysis methodology, we coded the policies for language and terminology, as well as program components and procedures. We aimed to examine how the policies were written, as well as the content intending to guide officers in their work.

Results

We found the policies and programs had notable differences in length, detail, terminology, and reading level. Only one policy mentioned the use of any type of addiction treatment medication, many used stigmatizing language (e.g., “abuse” and “addict”), and few mentioned “harm reduction” or training in the practice of deflection. Many policies restricted participation in deflection (i.e., no minors, outstanding warrants, current withdrawal symptoms), and critically, a majority of policies allowed police officers to exclude people from participation based on their own judgment.

Conclusions

We recommend police departments consider the readability of their policies and reduce barriers to deflection program participation to engage a larger pool of citizens in need of substance use disorder treatment. Since there is limited research on police policies generally, and the field of deflection is relatively new, this study offers insight into the content of different department policies and more specifically, how officers are directed to operate deflection programs.
Probing into the influence of EFL learners’ self-assessment and evaluation apprehension in predicting their personal best goals and self-efficacy skills: a structural equation modeling
Authors: Ismail Sayed M. , Heydarnejad Tahereh
Published: February 2023

Effective instruction and assessment are greatly affected by many factors. The ever-growing literature on assessment outlined some cognitive, social, and emotional factors that directly or indirectly influence the learners’ academic achievement. In spite of the rosy literature on assessment, the possible interplay among the Core of Self-assessment (CSA), the Student Evaluation Apprehension (SEA), the Personal Best Goal (PBG), and Self-efficacy (SE) were untouched. To this end, this study intended to propose a model to disclose the association between CSA, SEA, PBG, and SE in higher education. Therefore, the Core of Self-assessment Questionnaire (CSAQ), the Student Evaluation Apprehension Scale (SEAS), the Personal Best Goal Scale (PBGS), and the Self-efficacy Scale (SES) were administered to 467 Iranian EFL university students at MA level. The results of confirmatory factor analysis (CFA) and structural equation modelling (SEM) indicated that CSA and SEA can contribute to PBG and SE. It means that learners’ investment in CSA and positive SEA can flourish and upgrade goal-settings and sense of efficacy beliefs among EFL university students. The implications and suggestions for future avenues are also discussed.
Exploring the relationship between process data and contextual variables among Scandinavian students on PISA 2012 mathematics tasks
Authors: Costa Denise Reis , Chen Chia-Wen
Published: February 2023

Given the ongoing development of computer-based tasks, there has been increasing interest in modelling students’ behaviour indicators from log file data with contextual variables collected via questionnaires. In this work, we apply a latent regression model to analyse the relationship between latent constructs (i.e., performance, speed, and exploration behaviour) and contextual variables among Scandinavian students (i.e., Norway, Sweden, and Denmark) during their completion of three interactive mathematics tasks in the 2012 Program for International Student Assessment (PISA). The purpose of this study is threefold: (1) to investigate whether a factor model is adequate for explaining the relationship between extracted process indicators from log files and students’ performance on the three items; (2) to evaluate whether measurement invariance holds for the three analysed countries; and (3) to determine how well contextual variables [i.e., a student’s background, availability, use of information and communication technology (ICT) resources, and learning conditions for mathematical literacy] correlate with the model’s latent constructs. Our findings reveal that a three-factor CFA model is well-suited to the analysed data and that a weak measurement invariance model performs best. By including contextual variables in the modelling, we also highlight the differences in Scandinavian students’ profiles. Specifically, higher economic social cultural status (ESCS) consistently led to higher math proficiency across all three countries. Norway did not show any gender differences in math proficiency, response time, or exploration behaviours. Experience with math tasks at school led to more exploration behaviours across all three countries. Swedish and Norwegian students who had more experience with pure math tasks at school were likely to obtain higher mathematics achievement scores and tended to interact more frequently with the testing platform when answering the three math items. When Danish students had higher ICT scores (i.e., more ICT resources available at school and home), they had lower response accuracy. There was, however, no effect of ICT on the three factors among Swedish and Norwegian students. Finally, we also discuss the implications and limitations of this study.
Image caption generation using Visual Attention Prediction and Contextual Spatial Relation Extraction
Authors: Sasibhooshan Reshmi , Kumaraswamy Suresh , Sasidharan Santhoshkumar
Published: February 2023

Automatic caption generation with attention mechanisms aims at generating more descriptive captions containing coarser to finer semantic contents in the image. In this work, we use an encoder-decoder framework employing Wavelet transform based Convolutional Neural Network (WCNN) with two level discrete wavelet decomposition for extracting the visual feature maps highlighting the spatial, spectral and semantic details from the image. The Visual Attention Prediction Network (VAPN) computes both channel and spatial attention for obtaining visually attentive features. In addition to these, local features are also taken into account by considering the contextual spatial relationship between the different objects. The probability of the appropriate word prediction is achieved by combining the aforementioned architecture with Long Short Term Memory (LSTM) decoder network. Experiments are conducted on three benchmark datasets—Flickr8K, Flickr30K and MSCOCO datasets and the evaluation results prove the improved performance of the proposed model with CIDEr score of 124.2.
Extracorporeal membrane oxygenation for COVID-19-related acute respiratory distress syndrome: a narrative review
Authors: Alessandri Francesco , Di Nardo Matteo , Ramanathan Kollengode , Brodie Daniel , MacLaren Graeme
Published: February 2023

A growing body of evidence supports the use of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) refractory to maximal medical therapy. ARDS may develop in a proportion of patients hospitalized for coronavirus disease 2019 (COVID-19) and ECMO may be used to manage patients refractory to maximal medical therapy to mitigate the risk of ventilator-induced lung injury and provide lung rest while awaiting recovery. The mortality of COVID-19-related ARDS was variously reassessed during the pandemic. Veno-venous (VV) ECMO was the default choice to manage refractory respiratory failure; however, with concomitant severe right ventricular dysfunction, venoarterial (VA) ECMO or mechanical right ventricular assist devices with extracorporeal gas exchange (Oxy-RVAD) were also considered. ECMO has also been used to manage special populations such as pregnant women, pediatric patients affected by severe forms of COVID-19, and, in cases with persistent and seemingly irreversible respiratory failure, as a bridge to successful lung transplantation. In this narrative review, we outline and summarize the most recent evidence that has emerged on ECMO use in different patient populations with COVID-19-related ARDS.
Satisfactory outcomes of patellar tendon reconstruction using achilles’ tendon allograft with bone block after infected total knee arthroplasty
Authors: Kyriakidis Theofylaktos , Pitsilos Charalampos , Hernigou Jacques , Verdonk René , Hantes Michael
Published: February 2023

Purpose

Extensor mechanism disruption is an uncommon and devastating complication after total knee arthroplasty. It negatively affects patients’ quality of life and leads to significant functional limitations and the inability to stand and walk. The purpose of the present study was to evaluate the outcomes of the extensor mechanism reconstruction using Achilles’ tendon allograft after infected total knee arthroplasty. It was hypothesized that it is a safe procedure and that patients will present good clinical and functional results.

Methods

Ten patients treated for infra‐patellar extensor mechanism disruption after infected total knee arthroplasty were prospectively followed for two years. The mean age of patients was 70.8 (range 55–85), with a median BMI of 28.72 ± 2.2 kg/m2. All patients underwent reconstruction using a fresh frozen Achilles tendon allograft. Preoperative and postoperative evaluation included knee‐related clinical and functional assessment based on objective and subjective scores, including the knee flexion, the extension lag, the Knee Society Score (KSS) clinical and functional, and the visual analog scale (VAS) for pain at 12 and 24 months. Radiological evaluation was also performed using the Caton‐Deschamps index. Reported complications were also recorded.

Results

Clinical and functional outcomes recorded significant improvements (p < 0.05) at the final follow‐up compared with baseline as follows: Knee flexion was improved from 66° ± 4.8 to 99.7° ± 3.9, and the extension lag was decreased from 28.3° ± 4.4 to 9° ± 2.7. The mean KSS clinical and functional were also improved from 22.6 ± 7.9 to 73.4 ± 3.9 and from 10 ± 13.8 to 55 ± 13.8, respectively. The VAS for pain was decreased from 8.1 ± 1.2 to 1.9 ± 1.2. The Caton‐Deschamps index demonstrated a tendency to patella Alta. Two treatment failures were recorded, one patellar dislocation and one re‐rupture revised to arthrodesis.

Conclusions

Extensor mechanism reconstruction using Achilles’ tendon allograft after infected total knee arthroplasty is an efficient and safe procedure for infra‐patellar disruption. The present study’s findings demonstrate that most of the patients (80%) presented significant clinical and functional improvement at two‐year follow‐up.
A revised compartmental model for biokinetics and dosimetry of 2-[18F]FDG
Authors: Kamp Alexandra , Andersson Martin , Leide-Svegborn Sigrid , Noβke Dietmar , Mattsson Sören , Giussani Augusto
Published: February 2023

Background

The aim was to review available biokinetic data, collect own experimental data, and propose an updated compartmental model for 2-[18F]FDG in the frame of the revision of the ICRP report on dose coefficients for radiopharmaceuticals used in diagnostic nuclear medicine.

Methods

The compartmental model was developed based on published biokinetic data for 2-[18F]FDG. Additional data on urinary excretion in 23 patients (11 males, 12 females) undergoing whole-body PET/CT examinations were obtained within this study. The unknown biokinetic model parameters were derived using the software SAAM II and verified with a modified version of IDAC-Iodide. Dose coefficients for reference adults were calculated with the programme IDAC-Dose 2.1. A dynamic bladder model was employed for urinary bladder dosimetry.

Results

The proposed model consists of following compartments: blood, heart wall, brain, liver, lungs, pancreas, spleen, kidneys, urinary bladder content and a generic pool compartment “Other”. The latter was introduced to account for 2-[18F]FDG in body organ and tissues besides the explicitly modelled ones. The model predictions showed a good agreement with experimental data. Urinary bladder wall received the highest absorbed dose coefficient of 7.5E−02 mGy/MBq under the assumption of initial urine volume of 100 ml, first voiding at 45 min p.i. and 3.75 h voiding intervals thereafter. The effective dose coefficient calculated according to the current dosimetry framework of ICRP amounted to 1.7E−02 mSv/MBq, compared to 1.9E−02 mSv/MBq in ICRP Publication 128.

Conclusion

A compartmental model for 2-[18F]FDG was proposed and will be used to replace the descriptive biokinetic model of ICRP Publication 128. The revised model and the provided dose coefficients are expected to improve reference dosimetry for patients administered with 2-[18F]FDG.