bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct responses of newly identified monocyte subsets to advanced gastrointestinal cancer and COVID-19
Authors: Rigamonti Alessandra , Castagna Alessandra , Viatore Marika , Colombo Federico Simone , Terzoli Sara , Peano Clelia , Marchesi Federica , Locati Massimo
Published: October 2022

Monocytes are critical cells of the immune system but their role as effectors is relatively poorly understood, as they have long been considered only as precursors of tissue macrophages or dendritic cells. Moreover, it is known that this cell type is heterogeneous, but our understanding of this aspect is limited to the broad classification in classical/intermediate/non-classical monocytes, commonly based on their expression of only two markers, i.e. CD14 and CD16. We deeply dissected the heterogeneity of human circulating monocytes in healthy donors by transcriptomic analysis at single-cell level and identified 9 distinct monocyte populations characterized each by a profile suggestive of specialized functions. The classical monocyte subset in fact included five distinct populations, each enriched for transcriptomic gene sets related to either inflammatory, neutrophil-like, interferon-related, and platelet-related pathways. Non-classical monocytes included two distinct populations, one of which marked specifically by elevated expression levels of complement components. Intermediate monocytes were not further divided in our analysis and were characterized by high levels of human leukocyte antigen (HLA) genes. Finally, we identified one cluster included in both classical and non-classical monocytes, characterized by a strong cytotoxic signature. These findings provided the rationale to exploit the relevance of newly identified monocyte populations in disease evolution. A machine learning approach was developed and applied to two single-cell transcriptome public datasets, from gastrointestinal cancer and Coronavirus disease 2019 (COVID-19) patients. The dissection of these datasets through our classification revealed that patients with advanced cancers showed a selective increase in monocytes enriched in platelet-related pathways. Of note, the signature associated with this population correlated with worse prognosis in gastric cancer patients. Conversely, after immunotherapy, the most activated population was composed of interferon-related monocytes, consistent with an upregulation in interferon-related genes in responder patients compared to non-responders. In COVID-19 patients we confirmed a global activated phenotype of the entire monocyte compartment, but our classification revealed that only cytotoxic monocytes are expanded during the disease progression. Collectively, this study unravels an unexpected complexity among human circulating monocytes and highlights the existence of specialized populations differently engaged depending on the pathological context.
Continuous renal replacement therapy attenuates polymorphonuclear myeloid-derived suppressor cell expansion in pediatric severe sepsis
Authors: Feng Shuyun , Cui Yun , Zhou Yiping , Shao Lujing , Miao Huijie , Dou Jiaying , Liu Tiantian , Wang Chunxia , Zhang Yucai
Published: October 2022

Background

Myeloid-derived suppressor cells (MDSCs) expansion is an important mechanism underlying immunosuppression during sepsis. Though continuous renal replacement therapy (CRRT) may attenuate hyperinflammatory response in sepsis, its role in regulating MDSCs is unknown. The aim of this study was to assess the potential role of CRRT involved in sepsis-induced MDSCs expansion in pediatric sepsis.

Method

The proportion of polymorphonuclear MDSCs (PMN-MDSCs) was detected before CRRT (pre-CRRT), at 24 hours after CRRT (CRRT 1st day) and on the 7th day after CRRT (CRRT 7th day). The correlation analyses were performed to elucidate the relationship of MDSCs with clinical indexes in sepsis.

Results

Totally 22 pediatric patients with sepsis were enrolled [median age 44 (IQR15, 83) months]. PMN-MDSCs were expanded in pediatric sepsis compared with healthy controls (4.30% vs. 0.37%, P=0.04). The proportion of PMN-MDSCs showed a decreased tendency on the CRRT 7th day compared with that on the CRRT 1st day in survivors (2.29% vs.5.32%, P = 0.088). There was no significant difference in the proportion of PMN-MDSCs between survivors and non-survivors before CRRT (4.51% vs. 3.33%, P=0.745). The levels of interleukin 6 (IL-6) was decreased on the CRRT 7th day compared with CRRT 1st day in survivors. In the subgroups of patients with significantly decreased IL-6 levels after CRRT, the proportion of PMN-MDSCs on the CRRT 7th day were also significantly decreased compared with that on the CRRT 1st day (2.21% vs. 6.67%, P = 0.033).

Conclusion

The proportion of PMN-MDSCs was down-regulated on the CRRT 7th day in survivors with sepsis. The reduced PMN-MDSCs expansion may relate to decreased IL-6 level.
Atopy as an independent predictor for long-term patient and graft survival after kidney transplantation
Authors: Porret Raphaël , Meier Raphaël P. H. , Mikulic Josip , Pascual Manuel , Aubert Vincent , Harr Thomas , Golshayan Déla , Muller Yannick D.
Published: October 2022

Background

Atopy is a genetic condition predisposing individuals to develop immunoglobulin E (IgE) against common allergens through T-helper 2 (Th2) polarization mechanisms. The impact of atopy on graft survival in solid organ transplantation is unknown.

Methodology

We analyzed 268 renal allograft recipients from the Swiss Transplant Cohort Study, a prospective multicenter cohort studying patients after solid organ transplantation, with a 9-year median follow-up (IQR 3.0). We used the Phadiatop assay to measure IgE antibodies against a mixture of common inhaled allergens (grass, tree, herbs, spores, animals, and mites) to identify pre-transplantation atopic patients (>0.35 KU/L).

Results

Of 268 kidney transplant recipients, 66 individuals were atopic (24.6%). Atopic patients were significantly younger than non-atopic patients (49.6 vs 58.0 years old, P = 0.002). No significant difference was found for gender, cold/warm ischemia time, preformed donor-specific antibodies (DSA), HLA mismatches, induction and maintenance immunosuppressive therapy, CMV serostatus, or cause of kidney failure. Patient and graft survival at ten years of follow-up were significantly better in the atopic group, 95.2% versus 69.2% patient survival (P < 0.001), and 87.9% versus 60.8% graft survival (P < 0.001), respectively. A multivariate Cox analysis revealed that atopy predicted recipient and graft survival independently of age and living donor donation. Finally, we found similar rates of biopsy-proven acute cellular and antibody-mediated rejections between atopic and non-atopic recipients.

Conclusion

Atopy was associated with better long-term patient and graft survival, independently of age and living donor donation after kidney transplantation. Yet, atopy should not be used as a predictor for acute rejection.
An evolution of pontoon traps for cod fishing (Gadus morhua) in the southern Baltic Sea
Authors: Ljungberg Peter , Königson Sara , Lunneryd Sven-Gunnar
Published: October 2022

With increasing seal populations in the Baltic Sea comes growing interaction between seals and coastal fisheries. The impact of seals, mainly grey seal (Halichoerus grypus), on fisheries can be reduced by implementing of seal-safe fishing gear, which hinders seal access to catches. One successful solution is the introduction of a modified seal-safe trap net, the pontoon trap. In this study, pontoon traps were modified for use in cod (Gadus morhua) fisheries in the southern Baltic Sea. Three aspects of the pontoon trap design were tested for their effects on catch rates: (1) leader net mesh size; (2) leader net length; and (3) fish chamber position. The greatest catch rates were obtained using a leader net with a 100 mm center-knot to center-knot mesh-size on a bottom-set fish chamber while there was no difference in cod catch rates in relation to leader net length. There was no seal-induced damaged cod in the pontoon traps during any of the trials. Cod catch rates using the pontoon trap were also compared to those of the cod gillnet fishery in the same area. The comparison showed that during specific fishing occasions, multiple pontoon traps may have similar catch rates to gillnets.
Post-COVID-19 syndrome symptoms after mild and moderate SARS-CoV-2 infection
Authors: Al-Husinat Lou’i , Nusir Mokeem , Al-Gharaibeh Haitham , Alomari Amer A. , Smadi Mahmoud M. , Battaglini Denise , Pelosi Paolo
Published: October 2022

Background

Post-COVID-19 Syndrome (PCS) is characterized by residual symptoms following the initial recovery from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The prevalence of PCS is known to be the highest among severe and critical forms of the disease. However, the occurrence and risk factors for PCS after mild or moderate SARS-CoV-2 infection has not been extensively investigated.

Methods

Online and offline via both paper or mailed questionnaires distributed among Jordan collected between 1st and 21st August 2021, including a total number of 800 respondents, of whom 495 had previous mild to moderate COVID-19 infection. The Newcastle post-COVID syndrome Follow-up Screening Questionnaire was modified, translated, and used as a standard instrument for data collection regarding psychological, medical, and socio-economic symptoms post-infection. The primary outcome was the prevalence of PCS after mild to moderate COVID-19 in Jordan. Secondary outcome was the identification of PCS risk factors.

Results

The most common PCS symptom was mood disturbance followed by fatigue, anxiety, and myalgia. Female gender significantly increased the risk for multiple PCS symptoms. Age < 30 years was found to be an independent risk factor for myalgia (p = 0.001).

Conclusion

PCS is highly prevalent among COVID-19 survivors in Jordan, especially in females and patients with comorbidities. Planning physical and mental rehabilitation services is recommended for those patients with PCS symptoms after mild to moderate COVID-19 infection.
Optimization of the target strategy of perioperative infusion therapy based on monitoring data of central hemodynamics in order to prevent complications
Authors: Dmytriiev Dmytro , Nazarchuk Oleksandr , Melnychenko Mykola , Levchenko Bohdan
Published: October 2022

Enhanced Recovery After Surgery (ERAS) protocols are increasingly used in the perioperative period around the world. The concept of goal-directed fluid therapy (GDT) is a key element of the ERAS protocols. Inadequate perioperative infusion therapy can lead to a number of complications, including the development of an infectious process, namely surgical site infections, pneumonia, urinary tract infections. Optimal infusion therapy is difficult to achieve with standard parameters (e.g., heart rate, blood pressure, central venous pressure), so there are various methods of monitoring central hemodynamics – from invasive, minimally invasive to non-invasive. The latter are increasingly used in clinical practice. The current evidence base shows that perioperative management, specifically the use of GDT guided by real-time, continuous hemodynamic monitoring, helps clinicians maintain a patient’s optimal fluid balance. The manuscript presents the analytical data, which describe the benefits and basic principles of perioperative targeted infusion therapy based on central hemodynamic parameters to reduce the risk of complications.
Human health in peril: The need to upgrade medical education in light of COVID-19
Authors: Gatterer Lukas , Kriwan Fabian , Tanous Derrick , Wirnitzer Katharina
Published: October 2022

While we might leave the COVID-19 pandemic behind, future health professionals are still confronted with another global phenomenon: the increasing pandemic of non-communicable diseases (NCDs). Both issues are strongly interwoven, yet current medical education fails to address their syndemic nature accordingly. There is scientific consensus that (i) most emerging infectious diseases are zoonotic, (ii) the overexploitation of earth's resources for animal protein production (i.e., tropical deforestation) rapidly escalates human contact with unknown pathogens, and (iii) people following a healthy plant-based diet present fewer rates of NCDs as well as severe illness and mortality from COVID-19. A shift toward whole food plant-based nutrition in the general population thus holds the potential to tackle both public health threats. We are convinced that it is every physician's responsibility to care for individual, public, and global health issues; however, future health professionals are not trained and educated regarding the health potential of plants and plant-based diets. The COVID-19 pandemic has demonstrated the urgent need for a “prevention first” approach. Therefore, in order to upgrade medical education worldwide and protect current and future human health properly, greater medical professional awareness of evidence on plant-based diets is urgently needed in classes, universities, and hospitals.
Experimental and natural infections of white-tailed sea eagles (Haliaeetus albicilla) with high pathogenicity avian influenza virus of H5 subtype
Authors: Fujimoto Yoshikazu , Ogasawara Kohei , Isoda Norikazu , Hatai Hitoshi , Okuya Kosuke , Watanabe Yukiko , Takada Ayato , Sakoda Yoshihiro , Saito Keisuke , Ozawa Makoto
Published: October 2022

White-tailed sea eagle (Haliaeetus albicilla), a regionally rare species of raptor, is threatened in several countries. To assess the risk of H5 high pathogenicity avian influenza (HPAI) viral infection in rare bird species, we performed experimental infections with a GS/GD96-lineage H5N6 HPAI virus of clade 2.3.4.4e in white-tailed sea eagles. Additionally, during the winter of 2020–2021 in Japan, we accidentally encountered a white-tailed sea eagle that had a fatal outcome due to natural infection with a GS/GD96-lineage H5N8 HPAI virus of clade 2.3.4.4b, allowing us to compare experimental and natural infections in the same rare raptor species. Our experiments demonstrated the susceptibility of white-tailed sea eagles to the GS/GD96-lineage H5 HPAI virus with efficient replication in systemic organs. The potential for the viruses to spread within the white-tailed sea eagle population through indirect transmission was also confirmed. Comprehensive comparisons of both viral distribution and histopathological observations between experimentally and naturally infected white-tailed sea eagles imply that viral replication in the brain is responsible for the disease severity and mortality in this species. These findings provide novel insights into the risk assessment of H5 HPAI viral infection in white-tailed sea eagles, proper diagnostic procedures, potential risks to artificially fed eagle populations and persons handling superficially healthy eagles, potential impact of intragastric infection on eagle outcomes, and possibility of severity of the disease being attributed to viral replication in the brain.
A therapeutic chimeric IgG/IgA expressed by CHO cells for oral treatment of PED in piglets
Authors: Xiao Yan , Zhang Yunjing , Wang Zhiyan , Zhao Wenyin , Xu Xin , Chen Xiao , Tan Feifei , Sun Zhe , Huang Baicheng , Tian Kegong
Published: October 2022

Immunoglobulin A (IgA) of sows is critically important for assessing piglets’ protective capacity against porcine epidemic diarrhea virus (PEDV). Here, we report a therapeutic chimeric anti-PEDV IgG/IgA expressed by Chinese hamster ovary (CHO) cells for oral treatment of PED. The chimeric anti-PEDV IgG/IgA was produced by the CHO cell lines, in which the heavy chain was constructed by combining the VH, Cγ1 and hinge regions of PEDV IgG mAb 8A3, and the Cα2 and Cα3 domains of a Mus musculus immunoglobulin alpha chain. The chimeric anti-PEDV IgG/IgA could neutralize the strains of CV777 (G1), P014 (G2) and HN1303 (G2)in vitroeffectively, showing broad-spectrum neutralization activity. Thein vivochallenge experiments demonstrated that chimeric anti-PEDV IgG/IgA (9C4) produced in the CHO cell supernatant could alleviate clinical diarrhea symptoms of the PEDV infection in piglets. In general, our study showed that chimeric anti-PEDV IgG/IgA produced from CHO cell line supernatants effectively alleviates PEDV infection in piglets, which also gives the foundation for the construction of fully functional secretory IgA by the J chain introduction to maximize the antibody therapeutic effect.
Proteomic analysis of s-acylated proteins in human retinal pigment epithelial cells and the role of palmitoylation of Niemann-Pick type C1 protein in cholesterol transport
Authors: Li Jia Kai , Rao Yu Qing , Koh Siew Kwan , Zhao Peiquan , Zhou Lei , Li Jing
Published: October 2022

Palmitoylation is a dynamic process that regulates the activity of the modified proteins. Retinal pigment epithelial (RPE) cells play pivotal roles in the visual cycle and maintaining healthy photoreceptor cells. Dysfunctional RPE cells are often associated with degenerative retinal diseases. The aim of the study was to identify potentially palmitoylated proteins in human RPE cells. By using the detergent-resistant membrane, we found 312 potentially palmitoylated peptides which corresponded to 192 proteins in RPE cells, including 55 new candidate proteins which were not reported before. Gene enrichment analysis highlighted significant enrichment of palmitoylated proteins in cell-matrix adhesion, cell-cell recognition, protein cellular localization, and translation, among others. We further studied the effect of 3 potential palmitoylation sites (Cys 799, 900, and 816) of Niemann-Pick type C1 protein (NPC1) on cholesterol accumulation. We found that mutation of any single Cys alone had no significant effect on intracellular cholesterol accumulation while simultaneous mutation of Cys799 and 800 caused significant cholesterol accumulation in the late endosome. No further cholesterol accumulation was observed by adding another mutation at Cys 816. However, the mutation did not alter the cellular localization of the protein. Conclusion: PRE cells have an abundant number of palmitoylated proteins which are involved in cellular processes critical to visual function. The palmitoylation at Cys799 and 800 was needed for cholesterol export, but not the intracellular localization of NPC1.
Identification of potential drug targets for vascular dementia and carotid plaques by analyzing underlying molecular signatures shared by them
Authors: Shu Jun , Ren Yiqing , Tan Wen , Wei Wenshi , Zhang Li , Chang Jie
Published: October 2022

Background

Vascular dementia (VaD) and carotid atherosclerotic plaques are common in the elderly population, conferring a heavy burden on families and society. Accumulating evidence indicates carotid atherosclerotic plaques to be a risk factor for VaD. However, the underlying mechanisms for this association are mainly unknown.

Materials and methods

We analyzed temporal cortex gene expression data of the GSE122063 dataset and gene expression data of the GSE163154 dataset to identify commonly differentially expressed genes (DEGs). Then we performed functional enrichment analysis, immune cell infiltration and evaluation, correlation analysis between differentially expressed immune-related genes (DEIRGs) and immune cells, receiver operating characteristic (ROC) analysis, and drug-gene analysis.

Results

We identified 41 overlapped DEGs between the VaD and carotid atherosclerosis plaque datasets. Functional enrichment analyses revealed that these overlapped DEGs were mainly enriched in inflammatory and immune-related processes. Immunocyte infiltration and evaluation results showed that M0 macrophages, M2 macrophages, and T cells gamma delta had a dominant abundance in carotid atherosclerosis plaque samples, and M0 macrophages showed a significantly different infiltration percentage between the early and advanced stage plaques group. Resting CD4 memory T cells, M2 macrophages, and naive B cells were the top three highest infiltrating fractions in VaD. Furthermore, B cells and NK cells showed a different infiltration percentage between VaD and matched controls. We identified 12 DEIRGs, and the result of correlation analysis revealed that these DEIRGs were closely related to differentially expressed immune cells. We identified five key DEIRGs based on ROC analysis. The drug-gene interaction analysis showed that four drugs (avacopan, CCX354, BMS-817399, and ASK-8007) could be potential drugs for VaD and carotid atherosclerotic plaques treatment.

Conclusion

Collectively, these findings indicated that inflammatory and immune-related processes be a crucial common pathophysiological mechanism shared by VaD and carotid plaques. This study might provide new insights into common molecular mechanisms between VaD and carotid plaques and potential targets for the treatment.
Risk scores of incident mild cognitive impairment in a Beijing community-based older cohort
Authors: Li Xin , Xia Jianan , Li Yumeng , Xu Kai , Chen Kewei , Zhang Junying , Li He , Zhang Zhanjun
Published: October 2022

Objective: It is very important to identify individuals who are at greatest risk for mild cognitive impairment (MCI) to potentially mitigate or minimize risk factors early in its course. We created a practical MCI risk scoring system and provided individualized estimates of MCI risk.

Methods: Using data from 9,000 older adults recruited for the Beijing Ageing Brain Rejuvenation Initiative, we investigated the association of the baseline demographic, medical history, lifestyle and cognitive data with MCI status based on logistic modeling and established risk score (RS) models 1 and 2 for MCI. We evaluated model performance by computing the area under the receiver operating characteristic (ROC) curve (AUC). Finally, RS model 3 was further confirmed and improved based on longitudinal outcome data from the progression of MCI in a sub-cohort who had an average 3-year follow-up.

Results: A total of 1,174 subjects (19.8%) were diagnosed with MCI at baseline, and 72 (7.8%) of 849 developed MCI in the follow-up. The AUC values of RS models 1 and 2 were between 0.64 and 0.70 based on baseline age, education, cerebrovascular disease, intelligence and physical activities. Adding baseline memory and language performance, the AUC of RS model 3 more accurately predicted MCI conversion (AUC = 0.785).

Conclusion: A combination of risk factors is predictive of the likelihood of MCI. Identifying the RSs may be useful to clinicians as they evaluate their patients and to researchers as they design trials to study possible early non-pharmaceutical interventions to reduce the risk of MCI and dementia.
Mastication stimuli enhance the learning ability of weaning-stage rats, altering the hippocampal neuron transcriptome and micromorphology
Authors: Yasuoka Akihito , Nagai Toshitada , Lee Seonmi , Miyaguchi Hitonari , Saito Yoshikazu , Abe Keiko , Asakura Tomiko
Published: October 2022

Mastication stimuli are known to relieve senile dementia in human and animal studies. However, few studies have focused on its effect on weaning-stage animals and the underlying molecular processes. In this study, 3-week-old male rats were raised on a powdered (P-group) or chow (C-group) diet for 8 days, and their behavior was examined using the Y-maze and novel object recognition tests. In the Y-maze test, the C-group rats showed a larger alternation ratio than the P-group rats. In the novel object recognition test, the C-group rats exhibited a significantly larger discrimination index for novel objects than for familiar objects, but the P-group rats did not. We then compared the hippocampal neuron morphology and transcriptome between the groups. C-group rats exhibited larger dendrite branch numbers in the apical dendrites of pyramidal cells in the cornu ammonis 1 (CA1) region and a larger spine density in the basal dendrites of CA1 neurons than the P-group rats. Using DNA microarray analysis, we identified 621 (P < C) and 96 (P > C) genes that were differentially expressed between the groups. These genes were enriched in functional terms related to dendrite growth and included the Igf2, RhoA, and Rho GEF genes, most of which were upregulated in the C-group. These results suggest that the mastication stimuli during the weaning period can enhance the learning ability of rats by increasing the dendrite branches of hippocampal CA1 neurons and by regulating genes related to dendrite growth.
The effectiveness and safety of acupuncture for chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis
Authors: Xu Zhonghang , Wang Xingbo , Wu Yuanyu , Wang Chengbing , Fang Xuedong
Published: October 2022

Objectives

This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of acupuncture on chemotherapy-induced peripheral neuropathy (CIPN).

Methods

We searched for relevant randomized controlled trials (RCTs) in PubMed, Cochrane Library, and Embase databases from their inception to 1 April 2022. The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), Brief Pain Inventory-Short Form (BPI-SF), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30), Numerical Rating Scale (NRS), and adverse events were the outcome measures. All studies had at least one of these outcome measures. Mean differences (MDs) with 95% confidence intervals (CIs) were assessed in the meta-analysis using the RevMan 5.3 software.

Results

Five studies were included in the analysis. The results showed that acupuncture and placebo acupuncture were not significantly different in reducing chemotherapy-induced neurotoxicity and functional disability (random-effects estimates; MD: 4.30; 95% CI: −0.85~9.45; P = 0.10; I2 = 74%). Acupuncture was better than placebo acupuncture in reducing pain severity and pain interference with patients' daily function (fixed-effect estimates; MD: −1.14; 95% CI: 1.87 to −0.42; P = 0.002; I2 = 13%). Acupuncture was not significantly different from placebo acupuncture in relieving CIPN symptoms (MD: −0.81; 95% CI: −2.02 to 0.40, P = 0.19). Acupuncture improved quality of life better than placebo acupuncture (MD: 10.10; 95% CI: 12.34 to 17.86, P = 0.01). No severe adverse events were recorded in all five studies.

Conclusion

This meta-analysis suggests that acupuncture may be more effective and safer in reducing pain severity and pain interference with patients' daily function than placebo acupuncture. Additionally, acupuncture may improve the quality of life of patients with CIPN. However, large sample size studies are needed to confirm this conclusion.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=324930, identifier: CRD42022324930.
Tracking axon initial segment plasticity using high-density microelectrode arrays: A computational study
Authors: Kumar Sreedhar S. , Gänswein Tobias , Buccino Alessio P. , Xue Xiaohan , Bartram Julian , Emmenegger Vishalini , Hierlemann Andreas
Published: October 2022

Despite being composed of highly plastic neurons with extensive positive feedback, the nervous system maintains stable overall function. To keep activity within bounds, it relies on a set of negative feedback mechanisms that can induce stabilizing adjustments and that are collectively termed “homeostatic plasticity.” Recently, a highly excitable microdomain, located at the proximal end of the axon—the axon initial segment (AIS)—was found to exhibit structural modifications in response to activity perturbations. Though AIS plasticity appears to serve a homeostatic purpose, many aspects governing its expression and its functional role in regulating neuronal excitability remain elusive. A central challenge in studying the phenomenon is the rich heterogeneity of its expression (distal/proximal relocation, shortening, lengthening) and the variability of its functional role. A potential solution is to track AISs of a large number of neurons over time and attempt to induce structural plasticity in them. To this end, a promising approach is to use extracellular electrophysiological readouts to track a large number of neurons at high spatiotemporal resolution by means of high-density microelectrode arrays (HD-MEAs). However, an analysis framework that reliably identifies specific activity signatures that uniquely map on to underlying microstructural changes is missing. In this study, we assessed the feasibility of such a task and used the distal relocation of the AIS as an exemplary problem. We used sophisticated computational models to systematically explore the relationship between incremental changes in AIS positions and the specific consequences observed in simulated extracellular field potentials. An ensemble of feature changes in the extracellular fields that reliably characterize AIS plasticity was identified. We trained models that could detect these signatures with remarkable accuracy. Based on these findings, we propose a hybrid analysis framework that could potentially enable high-throughput experimental studies of activity-dependent AIS plasticity using HD-MEAs.
Young female participants show blunted placebo effects associated with blunted responses to a cue predicting a safe stimulus in the right dorsolateral prefrontal cortex
Authors: Iwama Yudai , Takamoto Kouichi , Hibi Daisuke , Nishimaru Hiroshi , Matsumoto Jumpei , Setogawa Tsuyoshi , Nishijo Hisao
Published: October 2022

Discrimination of cues predicting non-nociceptive/nociceptive stimuli is essential for predicting whether a non-painful or painful stimulus will be administered and for eliciting placebo/nocebo (pain reduction/pain enhancement) effects. Dysfunction of the neural system involved in placebo effects has been implicated in the pathology of chronic pain, while female sex is one of the important risk factors for development of chronic pain in young adults. The dorsolateral prefrontal cortex (dl-PFC) is suggested to be involved in placebo effects and is sensitive to sex and age. In this study, to examine the neural mechanisms by which sex and age alter placebo and nocebo effects, we analyzed cerebral hemodynamic activities in the dl-PFC in different sex and age groups during a differential conditioning task. During the training session, two different sounds were followed by low- and high-intensity electrical shocks. In the following recording session, electrical shocks, the intensity of which was mismatched to the sounds, were occasionally administered to elicit placebo and nocebo effects. In young female participants, both placebo effects and hemodynamic responses to the conditioned sounds in the right dl-PFC were significantly lower than those in elderly female participants, while there were no age differences in male participants. The hemodynamic responses to the sound paired with the safe stimulus in the right dl-PFC were significantly correlated with placebo effects, except in the young female group. These results suggest that blunted placebo effects in the young female participants are ascribed to blunted responses to the sound associated with the safe stimulus in the right dl-PFC, and that sex- and age-related factors may alter the responsiveness of the right dl-PFC to associative cues predicting a safe stimulus.
Face shape processing via visual-to-auditory sensory substitution activates regions within the face processing networks in the absence of visual experience
Authors: Arbel Roni , Heimler Benedetta , Amedi Amir
Published: October 2022

Previous evidence suggests that visual experience is crucial for the emergence and tuning of the typical neural system for face recognition. To challenge this conclusion, we trained congenitally blind adults to recognize faces via visual-to-auditory sensory-substitution (SDD). Our results showed a preference for trained faces over other SSD-conveyed visual categories in the fusiform gyrus and in other known face-responsive-regions of the deprived ventral visual stream. We also observed a parametric modulation in the same cortical regions, for face orientation (upright vs. inverted) and face novelty (trained vs. untrained). Our results strengthen the conclusion that there is a predisposition for sensory-independent and computation-specific processing in specific cortical regions that can be retained in life-long sensory deprivation, independently of previous perceptual experience. They also highlight that if the right training is provided, such cortical preference maintains its tuning to what were considered visual-specific face features.
Deep learning-based computed tomography image segmentation and volume measurement of intracerebral hemorrhage
Authors: Peng Qi , Chen Xingcai , Zhang Chao , Li Wenyan , Liu Jingjing , Shi Tingxin , Wu Yi , Feng Hua , Nian Yongjian , Hu Rong
Published: October 2022

The study aims to enhance the accuracy and practicability of CT image segmentation and volume measurement of ICH by using deep learning technology. A dataset including the brain CT images and clinical data of 1,027 patients with spontaneous ICHs treated from January 2010 to December 2020 were retrospectively analyzed, and a deep segmentation network (AttFocusNet) integrating the focus structure and the attention gate (AG) mechanism is proposed to enable automatic, accurate CT image segmentation and volume measurement of ICHs. In internal validation set, experimental results showed that AttFocusNet achieved a Dice coefficient of 0.908, an intersection-over-union (IoU) of 0.874, a sensitivity of 0.913, a positive predictive value (PPV) of 0.957, and a 95% Hausdorff distance (HD95) (mm) of 5.960. The intraclass correlation coefficient (ICC) of the ICH volume measurement between AttFocusNet and the ground truth was 0.997. The average time of per case achieved by AttFocusNet, Coniglobus formula and manual segmentation is 5.6, 47.7, and 170.1 s. In the two external validation sets, AttFocusNet achieved a Dice coefficient of 0.889 and 0.911, respectively, an IoU of 0.800 and 0.836, respectively, a sensitivity of 0.817 and 0.849, respectively, a PPV of 0.976 and 0.981, respectively, and a HD95 of 5.331 and 4.220, respectively. The ICC of the ICH volume measurement between AttFocusNet and the ground truth were 0.939 and 0.956, respectively. The proposed segmentation network AttFocusNet significantly outperforms the Coniglobus formula in terms of ICH segmentation and volume measurement by acquiring measurement results closer to the true ICH volume and significantly reducing the clinical workload.
Neural synchrony in cortical networks: mechanisms and implications for neural information processing and coding
Authors: Gansel Kai S.
Published: October 2022

Synchronization of neuronal discharges on the millisecond scale has long been recognized as a prevalent and functionally important attribute of neural activity. In this article, I review classical concepts and corresponding evidence of the mechanisms that govern the synchronization of distributed discharges in cortical networks and relate those mechanisms to their possible roles in coding and cognitive functions. To accommodate the need for a selective, directed synchronization of cells, I propose that synchronous firing of distributed neurons is a natural consequence of spike-timing-dependent plasticity (STDP) that associates cells repetitively receiving temporally coherent input: the “synchrony through synaptic plasticity” hypothesis. Neurons that are excited by a repeated sequence of synaptic inputs may learn to selectively respond to the onset of this sequence through synaptic plasticity. Multiple neurons receiving coherent input could thus actively synchronize their firing by learning to selectively respond at corresponding temporal positions. The hypothesis makes several predictions: first, the position of the cells in the network, as well as the source of their input signals, would be irrelevant as long as their input signals arrive simultaneously; second, repeating discharge patterns should get compressed until all or some part of the signals are synchronized; and third, this compression should be accompanied by a sparsening of signals. In this way, selective groups of cells could emerge that would respond to some recurring event with synchronous firing. Such a learned response pattern could further be modulated by synchronous network oscillations that provide a dynamic, flexible context for the synaptic integration of distributed signals. I conclude by suggesting experimental approaches to further test this new hypothesis.
Characteristic columnar connectivity caters to cortical computation: Replication, simulation, and evaluation of a microcircuit model
Authors: Schulte to Brinke Tobias , Duarte Renato , Morrison Abigail
Published: October 2022

The neocortex, and with it the mammalian brain, achieves a level of computational efficiency like no other existing computational engine. A deeper understanding of its building blocks (cortical microcircuits), and their underlying computational principles is thus of paramount interest. To this end, we need reproducible computational models that can be analyzed, modified, extended and quantitatively compared. In this study, we further that aim by providing a replication of a seminal cortical column model. This model consists of noisy Hodgkin-Huxley neurons connected by dynamic synapses, whose connectivity scheme is based on empirical findings from intracellular recordings. Our analysis confirms the key original finding that the specific, data-based connectivity structure enhances the computational performance compared to a variety of alternatively structured control circuits. For this comparison, we use tasks based on spike patterns and rates that require the systems not only to have simple classification capabilities, but also to retain information over time and to be able to compute nonlinear functions. Going beyond the scope of the original study, we demonstrate that this finding is independent of the complexity of the neuron model, which further strengthens the argument that it is the connectivity which is crucial. Finally, a detailed analysis of the memory capabilities of the circuits reveals a stereotypical memory profile common across all circuit variants. Notably, the circuit with laminar structure does not retain stimulus any longer than any other circuit type. We therefore conclude that the model's computational advantage lies in a sharper representation of the stimuli.
Molecular mechanism of acetylsalicylic acid in improving learning and memory impairment in APP/PS1 transgenic mice by inhibiting the abnormal cell cycle re-entry of neurons
Authors: Guan Pei-Pei , Ding Wei-Yan , Wang Pu
Published: October 2022

Alzheimer’s disease (AD) is a neurodegenerative disorder accompanied by the loss and apoptosis of neurons. Neurons abnormally enter the cell cycle, which results in neuronal apoptosis during the course of AD development and progression. However, the mechanisms underlying cell cycle re-entry have been poorly studied. Using neuroblastoma (N) 2aSW and APP/PS1 transgenic (Tg) mice as in vitro and in vivo AD models, we found that the expression of cyclin-dependent kinase (CDK)1/2/4 and cyclin A2/B1/D3/E1 was increased while the protein expression of p18 and p21 was decreased, which led to enhanced cell cycle re-entry in a β-amyloid protein (Aβ)-dependent mechanism. By preparing and treating with the temperature-sensitive chitosan-encapsulated drug delivery system (CS), the abnormal expression of CDK1/2/4, cyclin A2/B1/D3/E1 and p18/21 was partially restored by acetylsalicylic acid (ASA), which decreased the apoptosis of neurons in APP/PS1 Tg mice. Moreover, CDK4 and p21 mediated the effects of ASA on activating transcription factor (TF) EB via peroxisome proliferator-activated receptor (PPAR) α, thus leading to the uptake of Aβ by astrocytes in a low-density lipoprotein receptor (Ldlr)-dependent mechanism. Moreover, the mechanisms of Aβ-degrading mechanisms are activated, including the production of microtubule-associated protein light chain (LC) 3II and Lamp2 protein by ASA in a PPARα-activated TFEB-dependent manner. All these actions contribute to decreasing the production and deposition of Aβ, thus leading to improved cognitive decline in APP/PS1 Tg mice.
Triglyceride to high-density lipoprotein cholesterol ratio and total cholesterol to high-density lipoprotein cholesterol ratio and risk of benign prostatic hyperplasia in Chinese male subjects
Authors: Zhu Chen , Wu Juan , Wu Yixian , Guo Wen , Lu Jing , Zhu Wenfang , Li Xiaona , Xu Nianzhen , Zhang Qun
Published: October 2022

Background

Lipid metabolism disorders contribute to the risk factor of prostatic hyperplasia. Lipid ratios have also attracted a lot of attention. Yet, research about the correlation of lipid ratios with prostatic hyperplasia is limited. Hence, the aim of this study was to investigate the association of lipid ratios with the risk of benign prostatic hyperplasia (BPH) in Chinese male subjects.

Methods

Healthy men who underwent routine health check-ups from January 2017 to December 2019 were recruited. Twenty-four thousand nine hundred sixty-two individuals were finally enrolled in this research. Binary logistic regression analysis was performed to investigate the relationship between lipid ratios and BPH in Chinese adults.

Results

After health examinations for more than 2 years, 18.46% of subjects were ascertained as incident BPH cases. Higher age, body mass index (BMI), prostate-specific antigen (PSA), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio, and lower high-density lipoprotein cholesterol (HDL-C) were significantly associated with BPH risk, while total cholesterol (TC) was not significant. When quartiles of TG/HDL-C and TC/HDL-C were analyzed in multivariable model, higher TG/HDL-C and TC/HDL-C were associated with a risk of BPH (odds ratio [OR] = 2.11; 95% confidence interval [CI]: 1.89, 2.36; P-trend < 0.001; and OR = 1.67; 95% CI: 1.50, 1.85; P-trend < 0.001, respectively). In addition, stratified analyses based on the general population exhibited that with increasing age (≥35 years) the relationship of TG/HDL-C ratio with BPH risk was dominantly positive (all P-trend < 0.001, P-interaction = 0.001), and significant associations were also found in blood pressure strata and FBG strata (all P-trend < 0.001), except men with BMI ≥ 28 kg/m2 were slightly weakened (OR = 2.01, 95% CI: 1.41, 2.85; P-trend = 0.04). Moreover, there were significant associations between quartiles of TC/HDL-C and the risk of BPH was observed mainly in age 55–64 years, BMI 18.5–23.9 Kg/m2, blood pressure strata, and FBG strata. However, the P-value for a linear trend among those with BMI ≥ 28 Kg/m2 in which participants at the highest quartile of TC/HDL-C had an OR of 1.45 (95% CI: 1.09, 1.93) was 0.594. Additionally, higher TG/HDL-C ratio (≥0.65) may be a risk factor for BPH in China adults of different age decades (≥35 years) with normal TG and HDL-C.

Conclusions

TG/HDL-C and TC/HDL-C were associated with BPH risk, TG/HDL-C was a powerful independent risk factor for BPH in Chinese adults, and higher TG/HDL-C ratio should be valued in male subjects with normal TG and HDL-C levels.
Cancer patients and COVID-19 vaccination, from safety to protocol adherence: A real-life setting report
Authors: Lamtai Haitam , Boutayeb Saber , Mrabti Hind , El Ghissassi Ibrahim , Errihani Hassan
Published: October 2022

Background

The SARS-CoV-2 pandemic has slowed down cancer prevention and treatment strategies; consequently, cancer patients are prioritized to get the COVID-19 vaccines. Being constantly threatened by a new outbreak, the dive within the immunogenicity response is of great value; nonetheless, evaluating the side effects of these vaccines on fragile patients will assure their adherence to the vaccination protocol.

Objectives

This study sets out to investigate the adverse events reported about the vaccine according to its doses and types, and to compare the prevalence and severity of toxicities across two subgroups of cancer patients, those who received the injection during active therapy cycles, and those who have not started the therapy yet at vaccination time, moreover, this paper examines the will and commitment of this population to the vaccination schemes.

Methods

This is an observational, retrospective, cohort study, in which we conducted a semi-constructed interview with 415 random solid cancer patients treated at the National Institute of Oncology in Morocco. The assessment of adverse events was carried out with a standardized scale.

Results

Eleven months after the launch of the campaign, 75.2% of patients received at least one dose of the vaccine. Altogether, the analysis demonstrates a significant difference between the adverse effects reported post the second dose compared to the first one (p=0.004; odds ratio=2 [95% CI: 1.23 - 3.31]). Besides, the results indicate an increase in the rank of the severity of systemic events (p<0.001, r=0.28) after the second dose, but not for the local events (p=0.92, r=0.005). In the adjusted subgroup analysis, no effect was detected linking active therapy with the occurrence of toxicity (p=0.51, v=0.04) as well as with the level of severity reported after both; the first and second dose. Due to the fear of interactions with the therapy, we noticed a significant trend to delay the booster dose among the participants who completed the initial vaccine protocol.

Conclusion

A considerable body of evidence exists to persuade cancer patients to take the Coronavirus vaccines, and to also follow their vaccination schemes under the supervision of their treating physicians.
Classifying primary central nervous system lymphoma from glioblastoma using deep learning and radiomics based machine learning approach - a systematic review and meta-analysis
Authors: Guha Amrita , Goda Jayant S. , Dasgupta Archya , Mahajan Abhishek , Halder Soutik , Gawde Jeetendra , Talole Sanjay
Published: October 2022

Background

Glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL) are common in elderly yet difficult to differentiate on MRI. Their management and prognosis are quite different. Recent surge of interest in predictive analytics, using machine learning (ML) from radiomic features and deep learning (DL) for diagnosing, predicting response and prognosticating disease has evinced interest among radiologists and clinicians. The objective of this systematic review and meta-analysis was to evaluate the deep learning & ML algorithms in classifying PCNSL from GBM.

Methods

The authors performed a systematic review of the literature from MEDLINE, EMBASE and the Cochrane central trials register for the search strategy in accordance with PRISMA guidelines to select and evaluate studies that included themes of ML, DL, AI, GBM, PCNSL. All studies reporting on ML algorithms or DL that for differentiating PCNSL from GBM on MR imaging were included. These studies were further narrowed down to focus on works published between 2018 and 2021. Two researchers independently conducted the literature screening, database extraction and risk bias assessment. The extracted data was synthesised and analysed by forest plots. Outcomes assessed were test characteristics such as accuracy, sensitivity, specificity and balanced accuracy.

Results

Ten articles meeting the eligibility criteria were identified addressing use of ML and DL in training and validation classifiers to distinguish PCNSL from GBM on MR imaging. The total sample size was 1311 in the included studies. ML approach was used in 6 studies while DL in 4 studies. The lowest reported sensitivity was 80%, while the highest reported sensitivity was 99% in studies in which ML and DL was directly compared with the gold standard histopathology. The lowest reported specificity was 87% while the highest reported specificity was 100%. The highest reported balanced accuracy was 100% and the lowest was 84%.

Conclusions

Extensive search of the database revealed a limited number of studies that have applied ML or DL to differentiate PCNSL from GBM. Of the currently published studies, Both DL & ML algorithms have demonstrated encouraging results and certainly have the potential to aid neurooncologists in taking preoperative decisions in the future leading to not only reduction in morbidities but also be cost effective.