bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response to renin-angiotensin system inhibitors in patients with IgA nephropathy
Authors: Wu Jianping , Wei Xiaona , Li Jiajia , Gan Yangang , Zhang Rui , Han Qianqian , Liang Peifen , Zeng Yuchun , Yang Qiongqiong
Published: August 2022

Background

Renin-angiotensin system inhibitors (RASi) are the first choice and basic therapy for the treatment of IgA nephropathy (IgAN) with proteinuria. However, approximately 40% of patients have no response to RASi treatment. The aim of this study was to screen potential biomarkers for predicting the treatment response of RASi in patients with IgAN.

Methods

We included IgAN patients who were treatment-naive. They received supportive treatment, including a maximum tolerant dose of RASi for 3 months. According to the degree of decrease in proteinuria after 3 months of follow-up, these patients were divided into a sensitive group and a resistant group. The plasma of the two groups of patients was collected, and the exosomes were extracted for high-throughput sequencing. The screening of hub genes was performed using a weighted gene co-expression network (WGCNA) and filtering differentially expressed genes (DEGs). We randomly selected 20 patients in the sensitive group and 20 patients in the resistant group for hub gene validation by real-time quantitative polymerase chain reaction (qRT−PCR). A receiver operating characteristic (ROC) curve was used to evaluate hub genes that predicted the efficacy of the RASi response among the 40 validation patients.

Results

After screening 370 IgAN patients according to the inclusion and exclusion criteria and the RASi treatment response evaluation, there were 38 patients in the sensitive group and 32 patients in the resistant group. IRAK1, ABCD1 and PLXNB3 were identified as hub genes by analyzing the high-throughput sequencing of the plasma exosomes of the two groups through WGCNA and DEGs screening. The sequencing data were consistent with the validation data showing that these three hub genes were upregulated in the resistant group compared with the sensitive group. The ROC curve indicated that IRAK1 was a good biomarker to predict the therapeutic response of RASi in patients with IgAN.

Conclusions

Plasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response of RASi in patients with IgAN.
Toxic epidermal necrolysis induced by sintilimab in a patient with advanced non-small cell lung cancer and comorbid pulmonary tuberculosis: A case report
Authors: Li Gang , Gong Sheng , Wang Ning , Yao Xiaojun
Published: August 2022

Immune checkpoint inhibitors (ICIs) have had a revolutionary effect on the treatment of patients with advanced non-small cell lung cancer (NSCLC), especially squamous cell lung cancer. However, ICIs may cause associated immune-related adverse events (ir-AEs). No case of sintilimab-induced toxic epidermal necrolysis (TEN) has been reported. In this report, we discussed a patient with advanced NSCLC and comorbid pulmonary tuberculosis who underwent immunotherapy and chemotherapy as neoadjuvant therapy and anti-tuberculosis therapy concurrently. Partial response (PR) of the tumor was achieved after three cycles of neoadjuvant therapy without cutaneous toxicities. Video-assisted thoracoscopic surgery (VATS) left lower lobectomy was performed successfully. Sintilimab and chemotherapy were administered as adjuvant therapy, after which the patient suffered severe TEN that rapidly progressed to cover >50% of the skin. TEN was associated with extensive rashes of the trunk and pruritus. With history of sintilimab use, clinical symptoms, and physical examination, TEN was diagnosed. Intravenous methylprednisolone and oral prednisone were administered until the patient totally recovered from the cutaneous toxicities caused by sintilimab. Monitoring of such rare but severe cutaneous toxicities is essential in patients who are treated with sintilimab.
Cascading effects of calanoid copepod functional groups on the biological carbon pump in the subtropical South Atlantic
Authors: Oliveira Lívia Dias Fernandes de , Bode-Dalby Maya , Schukat Anna , Auel Holger , Hagen Wilhelm
Published: August 2022

Life strategies, ecophysiological performances and diel vertical migration (DVM) of zooplankton key species affect the efficiency and strength of the biological carbon pump (BCP). However, it is unclear to what extent different functional groups affect the BCP. Depth-stratified day and night samples (0-800 m) from the subtropical South Atlantic were analyzed focusing on the calanoid copepod community. Calanoid abundance, biomass distribution and species-specific impact on the passive (fecal pellets) and active (via DVM) vertical flux of carbon were determined. Species were assigned to different migrant groups where, their contributions were estimated by using the proportion of the migratory community instead of simple day-night differences in biomass. This novel approach leads to more robust flux estimates, particularly for small sample sizes. According to migration ranges and day/night residence depth, functional groups were characterized, i.e. small- and large-scale epipelagic and mesopelagic migrants. Epipelagic small-scale migrants transported respiratory (1.5 mg C m-2 d-1) and fecal pellet (1.1 mg C m-2 d-1) carbon from the upper to the lower epipelagic zone, where the latter can fuel the microbial loop, and thus deep chlorophyll maxima, or be ingested by other zooplankton. Large-scale migrants actively transported up to 10.5 mg C m-2 d-1 of respiratory carbon from the epipelagic layer into the twilight zone. The majority was transported by Pleuromamma borealis (5.7 mg C m-2 d-1) into the upper mesopelagic. In addition, up to 8.0 mg C m-2 d-1 was potentially egested as fecal material by large-scale zone shifters. Mesopelagic migrants transported respiratory (0.2 mg C m-2 d-1) and fecal pellet carbon (0.1 mg C m-2 d-1) even deeper into the ocean. Community consumption of migrants in the epipelagic layer during the night was 98 mg C m-2 d-1, while non-migrants consumed 98-208 mg C m-2 d-1 in the epipelagic zone, with a potential subsequent egestion of 29-62 mg C m-2 d-1. This carbon may fuel omnivorous-detritivorous feeding, the microbial loop and/or may sink as fecal pellets. This case study shows how calanoid functional groups mediate carbon fluxes in the subtropical South Atlantic Ocean and demonstrates how detailed community analyses can elucidate the complexity of pelagic carbon budgets.
Long-term ecological trajectories of a disturbed Mediterranean coastal lagoon (Biguglia lagoon): Ecosystem-based approach and considering its resilience for conservation?
Authors: Ligorini Viviana , Malet Nathalie , Garrido Marie , Four Brian , Etourneau Sabrina , Leoncini Antoine Simon , Dufresne Christiane , Cecchi Philippe , Pasqualini Vanina
Published: August 2022

Coastal lagoons are subjected to ever-increasing direct or indirect anthropic pressures and are inexorably deteriorating with serious issues regarding their resilience. In this paper, we assessed the functioning and evolution of the highly disturbed Biguglia coastal lagoon (Mediterranean Sea, Corsica) through an ecosystem-based approach (EBA), using multiple biotic and abiotic proxies (hydro-climatic context and eutrophication), considering its connectivity to sea and watershed and biological compartments (macrophytes, phytoplankton, and invasive species) and taking into account human influence (management actions and fishing activities). The aim of this work is firstly to provide a comprehensive analysis of its long-term (2000–2021) ecological evolution trajectory and then, based on these results, to anticipate management strategies for supporting its conservation and restoration, and the maintenance of ecosystem services it offers. Results revealed that while the lagoon showed these days a good capacity to recover after disturbance and absorb change, it recently exhibited considerable changes in its phytoplankton community composition, developed an increased susceptibility to biological invasion, and experienced a drastic reduction in fish stocks. The major interannual variations of the mean salinity, strongly dependent on management interventions beyond natural climatic variability, summarized this instability. In the future, the lagoon may no longer be able to cope with even small disturbances, which could then be sufficient to reach a breakpoint and tip the system permanently into undesired/degraded states. We demonstrated that local and punctual management actions are not always beneficial for the entire ecosystem or even detrimental in some instances. Such a retrospective ecosystem-based approach is fundamental for producing the holistic insights required to implement efficient integrated ecosystem management. This further helps enhance lagoon resilience and hence preserve its ecosystem services in the context of increasing global changes. Such lessons are useful anywhere for comparable ecosystems.
Tissue loss disease outbreak significantly alters the Southeast Florida stony coral assemblage
Authors: Hayes Nicole K. , Walton Charles J. , Gilliam David S.
Published: August 2022

A stony coral tissue loss disease (SCTLD) outbreak, first widely reported in 2014 in the Southeast Florida Ecosystem Conservation Area (Coral ECA), has continued to impact stony coral communities for more than seven years. Here, we utilize long-term (2012-2020) annual monitoring data from the Southeast Florida Reef Evaluation and Monitoring Project (SECREMP) to assess the impact of the SCTLD outbreak on the stony coral assemblage as well as spatiotemporal and ecological associated variation. SECREMP examines 22 permanent sites distributed along Florida’s Coral Reef from Miami-Dade County north to Martin County, Florida. We expand upon previously documented disease event-related regional impacts. Coral ECA SCTLD prevalence was greatest in 2016 coinciding with significant declines in coral live tissue area (LTA). Even though by 2018 SCTLD prevalence had dropped to < 1% and significant annual LTA declines were no longer recorded, upwards of 59% of stony coral total LTA in the Coral ECA was lost between 2015-2018. In this study, SCTLD was observed across all habitats and affected 11 stony coral species. Colony size did not preclude infection or mortality, with 25% of all infections occurring on colonies 5-14 cm in diameter. The indiscriminate nature of the disease and lack of size refugia has altered the stony coral population structure and assemblage composition. Since 2016, the coral assemblage has shifted towards smaller colonies, with a significant decrease in mean colony size. Juvenile corals, < 4 cm diameter, of many reef building, structurally-complex species were rarely documented, while eurytopic, generalist species dominated juvenile abundance. Although significant losses, altering ecosystem function, were documented, all species recorded prior to the disease event were present, albeit some only as juveniles. Our study adds to the growing body of evidence of the severity of the disease outbreak and precarious state of the stony coral assemblage in the Coral ECA. We show long-term monitoring projects provide invaluable opportunities to capture such spatiotemporal changes in coral assemblages and may identify potential indicators of recovery. While no stony coral species were completely lost from the monitored assemblage, the likelihood of recovery, to even a pre-outbreak state, is limited without immediate action addressing development related local stressors and climate change related global stressors.
Lactobacillus mucosae exerted different antiviral effects on respiratory syncytial virus infection in mice
Authors: Wang Qianwen , Fang Zhifeng , Li Lingzhi , Wang Hongchao , Zhu Jinlin , Zhang Pinghu , Lee Yuan-kun , Zhao Jianxin , Zhang Hao , Lu Wenwei , Chen Wei
Published: August 2022

Respiratory syncytial virus (RSV) infection is a constant threat to the health of young children, and this is mainly attributed to the lack of effective prevention strategies. This study aimed to determine whether Lactobacillus (L.) mucosae, a potential probiotic, could protect against respiratory viral infection in a mouse model. Naive 3–4-week-old BALB/c mice were orally administered with three L. mucosae strains (2.5 × 108 CFU/mouse) 7 days before RSV infection (105 TCID50/mouse). Results showed that all three strains inhibited RSV replication and reduced the proportions of inflammatory cells, including granulocytes and monocytes in the blood. The L. mucosae M104R01L3 treatment maintained stable weight in mice and increased interferon (IFN)-β and tumor necrosis factor (TNF)-α levels. The L. mucosae DCC1HL5 treatment increased interleukin (IL)-1β and IL-10 levels. Moreover, the M104R01L3 and DCC1HL5 strains increased the proportions of Akkermansia, Alistipes, and Anaeroplasma which contributed to the advantageous modulation of the gut microbiota. Besides, L. mucosae affected the gut levels of short-chain fatty acids (SCFAs) that are important for the antiviral response. L. mucosae 1,025 increased acetate, propionate, and butyrate levels, whereas L. mucosae M104R01L3 increased the level of acetate in the gut. L. mucosae M104R01L3 may protect against viral infection by upregulating the IFN-β levels in the lungs and its antiviral effect may be related to the increase of acetate levels in the gut. In conclusion, the three L. mucosae strains exerted antiviral effects against RSV infection by differentially regulating immune responses and intestinal micro-ecological balance. This study can provide a reference for studying the mechanisms underlying the antiviral effects of L. mucosae.
Mixed silage with Chinese cabbage waste enhances antioxidant ability by increasing ascorbate and aldarate metabolism through rumen Prevotellaceae UCG-004 in Hu sheep
Authors: Li Chuang , Chen Ning , Zhang Xingxing , Shahzad Khuram , Qi Ruxin , Zhang Zhenbin , Lu Zhiqi , Lu Yue , Yu Xiang , Zafar Muhammad Hammad , Wang Mengzhi , Liu Wujun
Published: August 2022

Silage is rich in nutrients, which can make up for the lack of seasonal roughage, and has a certain promotion effect on the intensive feeding of ruminants. In addition, silage can maintain the rumen function of ruminants to a certain extent and reduce the risk of rumen acidosis and abomasum translocation. The purpose of this study was to investigate the effects of the mixed silage of Chinese cabbage waste and rice straw (mixed silage) on antioxidant performance, rumen microbial population, and fermentation metabolism of Hu sheep. The 16 healthy Hu sheep (eight rams and eight ewes, 39.11 ± 1.16 kg, 5.5 months) were randomly divided into two groups (the control group and the mixed silage group) with eight animals (four rams and four ewes) in each group. The control group was fed with farm roughage (peanut seedlings, corn husk, and high grain shell) as forage, and the mixed silage group was fed with the mixed silage as forage. The results showed that the mixed silage had no effect on the growth performance of Hu sheep (p > 0.05). Ruminal butyric acid, total volatile fatty acids (TVFA), and ammonia nitrogen (NH3-N) concentration in the mixed silage group were increased, whereas the pH was decreased (p < 0.05). The blood and rumen total antioxidants capacity (T-AOC) concentration in the mixed silage group was higher, and the malondialdehyde (MDA) content in rumen, serum, liver, and kidney was lower than that in the control group (p < 0.05). PCoA and ANOSIM results of Illumina sequencing indicated that the mixed silage affected the bacterial composition of the rumen microbes. The mixed silage increased the proportion of Prevotellaceae UCG-004 which was in a positive correlation with Vitamin C (Vc). In addition, PICRUSt functional prediction analysis showed that ascorbate and aldarate metabolism were up-regulated in the mixed silage group (p < 0.05). In conclusion, higher contents of VC and acid detergent fiber (ADF) in the mixed silage were beneficial to the growth and reproduction of Prevotellaceae UCG-004, resulting in increased production of the butyric acid significantly upregulated the metabolism of ascorbate and aldarate metabolism, thereby improving the antioxidant properties of Hu sheep.
Nano-pesticidal potential of Cassia fistula (L.) leaf synthesized silver nanoparticles (Ag@CfL-NPs): Deciphering the phytopathogenic inhibition and growth augmentation in Solanum lycopersicum (L.)
Authors: Danish Mohammad , Shahid Mohammad , Ahamad Lukman , Raees Kashif , Atef Hatamleh Ashraf , Al-Dosary Munirah Abdullah , Mohamed Abdullah , Al-Wasel Yasmeen Abdulrhman , Singh Udai B. , Danish Subhan
Published: August 2022

Plant-based synthesis of silver nanoparticles (Ag-NPs) has emerged as a potential alternative to traditional chemical synthesis methods. In this context, the aim of the present study was to synthesize Ag-NPs from Cassia fistula (L.) leaf extract and to evaluate their nano-pesticidal potential against major phyto-pathogens of tomato. From the data, it was found that particle size of spherical C. fistula leaf synthesized (Ag@CfL-NPs) varied from 10 to 20 nm, with the average diameter of 16 nm. Ag@CfL-NPs were validated and characterized by UV-visible spectroscopy (surface resonance peak λmax = 430 nm), energy dispersive spectrophotometer (EDX), Fourier transform infrared (FTIR), and X-ray diffraction pattern (XRD), and electron microscopy; scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The FTIR spectra verified the participation of various living molecules (aromatic/aliphatic moieties and proteins) in synthesized Ag@CfL-NPs. The anti-phytopathogenic potential of Ag@CfL-NPs was assessed under in vitro conditions. Increasing doses of Ag@CfL-NPs exhibited an inhibitory effect against bacterial pathogen Pseudomonas syringae and 400 μg Ag@CfL-NPs ml–1 caused a reduction in cellular viability, altered bacterial morphology, and caused cellular death Furthermore, Ag@CfL-NPs reduced exopolysaccharides (EPS) production and biofilm formation by P. syringae Additionally, Ag@CfL-NPs showed pronounced antifungal activity against major fungal pathogens. At 400 μg Ag@CfL-NPs ml–1, sensitivity of tested fungi followed the order: Fusarium oxysporum (76%) > R. solani (65%) > Sarocladium (39%). Furthermore, 400 μg Ag@CfL-NPs ml–1 inhibited the egg-hatching and increased larval mortality of Meloidogyne incognita by 82 and 65%, respectively, over control. Moreover, pot studies were performed to assess the efficacy of Ag@CfL-NPs to phyto-pathogens using tomato (Solanum lycopersicum L.) as a model crop. The applied phyto-pathogens suppressed the biological, physiological, and oxidative-stress responsiveness of tomatoes. However, 100 mg Ag@CfL-NPs kg–1 improved overall performance and dramatically increased the root length, dry biomass, total chlorophyll, carotenoid, peroxidase (POD), and phenylalanine ammonia lyase (PAL) activity over pathogens-challenged tomatoes. This study is anticipated to serve as an essential indication for synthesis of efficient nano-control agents, which would aid in the management of fatal phyto-pathogens causing significant losses to agricultural productivity. Overall, our findings imply that Ag@CfL-NPs as nano-pesticides might be used in green agriculture to manage the diseases and promote plant health in a sustainable way.
Current progress of ferroptosis study in ovarian cancer
Authors: Tan Zhuomin , Huang Hui , Sun Wenyan , Li Ya , Jia Yinnong
Published: August 2022

Tumors are the leading cause of death all over the world, among which ovarian cancer ranks the third in gynecological malignancies. The current treatment for ovarian cancer is liable to develop chemotherapy resistance and high recurrence rate, in which a new strategy is demanded. Ferroptosis, a newly discovered manner of regulatory cell death, is shown to be induced by massive iron-dependent accumulation of lipid reactive oxygen species. With the in-depth study of ferroptosis, its associated mechanism with various tumors is gradually elucidated, including ovarian tumor, which probably promotes the application of ferroptosis in treating ovarian cancer. To this end, this review will focus on the history and current research progress of ferroptosis, especially its regulation mechanism, and its potential application as a novel treatment strategy for ovarian cancer.
Evaluating the immunogenicity of heparin and heparin derivatives by measuring their binding to platelet factor 4 using biolayer interferometry
Authors: Chen Qingqing , Li Fei , Wang Haoran , Bu Changkai , Shi Feng , Jin Lan , Zhang Qunye , Chi Lianli
Published: August 2022

Heparin (HP) is a polysaccharide that is widely used in the clinic as an anticoagulant. A major side effect associated with HP is the heparin-induced thrombocytopenia (HIT), which is initiated by the immune response to complex formed by HP and platelet factor 4 (PF4). Low molecular weight heparins (LMWHs) are the depolymerized version of HP, which have reduced risks of inducing HIT. However, it is still necessary to evaluate the immunogenicity of LMWHs to ensure their drug safety. Since HIT involves very complicated processes, the evaluation of HP and LMWH immunogenicity requires experiments from multiple aspects, of which the binding affinity between HP and PF4 is a key property to be monitored. Herein, we developed a novel competitive biolayer interferometry (BLI) method to investigate the binding affinity between HP and PF4. The influence of different domains in HP on its immunogenicity was compared for better understanding of the molecular mechanism of HP immunogenicity. Furthermore, the half maximal inhibitory concentration (IC50) of HP and LMWH can be measured by competitive combination, which is important for the quality control during the developing and manufacturing of HP and LMWH drugs.
Brain region-specific microglial and astrocytic activation in response to systemic lipopolysaccharides exposure
Authors: Brandi Edoardo , Torres-Garcia Laura , Svanbergsson Alexander , Haikal Caroline , Liu Di , Li Wen , Li Jia-Yi
Published: August 2022

Microglia cells are the macrophage population within the central nervous system, which acts as the first line of the immune defense. These cells present a high level of heterogeneity among different brain regions regarding morphology, cell density, transcriptomes, and expression of different inflammatory mediators. This region-specific heterogeneity may lead to different neuroinflammatory responses, influencing the regional involvement in several neurodegenerative diseases. In this study, we aimed to evaluate microglial response in 16 brain regions. We compared different aspects of the microglial response, such as the extension of their morphological changes, sensitivity, and ability to convert an acute inflammatory response to a chronic one. Then, we investigated the synaptic alterations followed by acute and chronic inflammation in substantia nigra. Moreover, we estimated the effect of partial ablation of fractalkine CX3C receptor 1 (CX3CR1) on microglial response. In the end, we briefly investigated astrocytic heterogeneity and activation. To evaluate microglial response in different brain regions and under the same stimulus, we induced a systemic inflammatory reaction through a single intraperitoneal (i.p.) injection of lipopolysaccharides (LPS). We performed our study using C57BL6 and CX3CR1+/GFP mice to investigate microglial response in different regions and the impact of CX3CR1 partial ablation. We conducted a topographic study quantifying microglia alterations in 16 brain regions through immunohistochemical examination and computational image analysis. Assessing Iba1-immunopositive profiles and the density of the microglia cells, we have observed significant differences in region-specific responses of microglia populations in all parameters considered. Our results underline the peculiar microglial inflammation in the substantia nigra pars reticulata (SNpr). Here and in concomitance with the acute inflammatory response, we observed a transient decrease of dopaminergic dendrites and an alteration of the striato-nigral projections. Additionally, we found a significant decrease in microglia response and the absence of chronic inflammation in CX3CR1+/GFP mice compared to the wild-type ones, suggesting the CX3C axis as a possible pharmacological target against neuroinflammation induced by an increase of systemic tumor necrosis factor-alpha (TNFα) or/and LPS. Finally, we investigated astrocytic heterogeneity in this model. We observed different distribution and morphology of GFAP-positive astrocytes, a heterogeneous response under inflammatory conditions, and a decrease in their activation in CX3CR1 partially ablated mice compared with C57BL6 mice. Altogether, our data confirm that microglia and astrocytes heterogeneity lead to a region-specific inflammatory response in presence of a systemic TNFα or/and LPS treatment.
In vivo imaging of tau deposition in Alzheimer’s disease using both [18F]-THK5317 and [18F]-S16: A pilot human study
Authors: Fu Liping , Zhang Jinming , Zhou Kaixiang , Zhang Xiaojun , Xie Hengge , Zhu Mingwei , Cui Mengchao , Wang Ruimin
Published: August 2022

Objective

To evaluate the effectiveness of a new tracer (S)-1-(4-(6-(dimethylamino)quinoxalin-2-yl)phenoxy)-3-fluoropropan-2-ol ([18F]-S16), in distinguishing patients with AD from HCs.

Methods

Paired [18F]-S16 and [18F]-THK5317 scans were acquired in five patients with AD, six HCs, one subject with a semantic variant of primary progressive aphasia (sv-PPA) and one subject with probable progressive supranuclear palsy (PSP). Dynamic PET scanning was performed over 90 min after injection of the tracers. Standardized uptake values (SUV) and cortical-to-cerebellum standardized uptake value ratios (SUVRs) were used for tau deposition semi-quantization. A voxel-based analysis was employed to assess the uptake difference between populations.

Results

[18F]-S16 exhibited excellent blood-brain-barrier penetration. AD patients showed increased cortical [18F]-THK5317 and [18F]-S16 binding. Compared to HCs, AD patients showed significantly increased cortical [18F]-S16 uptake in the bilateral occipital cortex, posterior cingulated cortex/precuneus, and lateral frontal cortex. Notable [18F]-S16 uptake was observed in the basal ganglia and brainstem compared to the neocortex. A substantial [18F]-S16 signal was detected in the basal ganglia and midbrain in a patient with probable PSP and in the bilateral anterior temporal cortex in a sv-PPA patient.

Conclusion

[18F]-S16 might be of help to detect tau protein in vivo.
Splitting of the magnetic encephalogram into «brain» and «non-brain» physiological signals based on the joint analysis of frequency-pattern functional tomograms and magnetic resonance images
Authors: Llinás Rodolfo R. , Rykunov Stanislav , Walton Kerry D. , Boyko Anna , Ustinin Mikhail
Published: August 2022

The article considers the problem of dividing the encephalography data into two time series, that generated by the brain and that generated by other electrical sources located in the human head. The magnetic encephalograms and magnetic resonance images of the head were recorded in the Center for Neuromagnetism at NYU Grossman School of Medicine. Data obtained at McGill University and Montreal University were also used. Recordings were made in a magnetically shielded room and the gradiometers were designed to suppress external noise, making it possible to eliminate them from the data analysis. Magnetic encephalograms were analyzed by the method of functional tomography, based on the Fourier transform and on the solution of inverse problem for all frequencies. In this method, one spatial position is assigned to each frequency component. Magnetic resonance images of the head were evaluated to annotate the space to be included in the analysis. The included space was divided into two parts: «brain» and «non-brain». The frequency components were classified by the feature of their inclusion in one or the other part. The set of frequencies, designated as «brain», represented the partial spectrum of the brain signal, while the set of frequencies designated as «non-brain», represented the partial spectrum of the physiological noise produced by the head. Both partial spectra shared the same frequency band. From the partial spectra, a time series of the «brain» area signal and «non-brain» area head noise were reconstructed. Summary spectral power of the signal was found to be ten times greater than the noise. The proposed method makes it possible to analyze in detail both the signal and the noise components of the encephalogram and to filter the magnetic encephalogram.
The influence of social signals on the self-experience of pain: A neuroimaging review
Authors: Sharvit Gil , Schweinhardt Petra
Published: August 2022

Researchers in cognitive neuroscience have investigated extensively how psychological factors shape the processing and perception of pain using behavioral, physiological, and neuroimaging methods. However, social influences of pain, an essential part of biopsychosocial pain models, have received relatively little attention. This is particularly true for the neurobiological mechanisms underlying social modulations on pain. Therefore, this review discusses the findings of recent neuroimaging studies measuring the effects of social manipulations on pain perception (e.g., verbal and non-verbal social signals, social interaction style, conformity, social support, and sociocultural mediators). Finally, a schematic summary of the different social modulatory themes is presented.
Acute symptomatic seizures and status epilepticus in older adults: A narrative review focusing on management and outcomes
Authors: Kong Wan Yee , Marawar Rohit
Published: August 2022

A clear narrative of acute symptomatic seizures (ASyS) in older adults is lacking. Older adults (≥60 years) have the highest incidence of seizures of all age groups and necessitate a tailored approach. ASyS has a bimodal peak in infancy and old age (82.3–123.2/100,000/year after 65 years of age). ASyS can represent half of the new-onset seizures in older adults and can progress to acute symptomatic status epilepticus (ASySE) in 52–72% of the patients. Common etiologies for ASyS in older adults include acute stroke and metabolic disturbances. For ASySE, common etiologies are acute stroke and anoxic brain injury (ABI). Initial testing for ASyS should be consistent with the most common and urgent etiologies. A 20-min electroencephalogram (EEG) is less sensitive in older adults than in younger adults and might not help predict chronic epilepsy. The prolonged postictal phase is an additional challenge for acute management. Studies note that 30% of older adults with ASyS subsequently develop epilepsy. The risk of wrongly equating ASyS as the first seizure of epilepsy is higher in older adults due to the increased long-term challenges with chronic anti-seizure medication (ASM) treatment. Specific challenges to managing ASyS in older adults are related to their chronic comorbidities and polypharmacy. It is unclear if the prognosis of ASyS is dependent on the underlying etiology. Short-term mortality is 1.6 to 3.6 times higher than younger adults. ASySE has high short-term mortality, especially when it is secondary to acute stroke. An acute symptomatic etiology of ASySE had five times increased risk of short-term mortality compared to other types of etiology.
Theory of Mind in migraine and medication-overuse headache: A cross-sectional study
Authors: Romozzi Marina , Di Tella Sonia , Rollo Eleonora , Quintieri Paolo , Silveri Maria Caterina , Vollono Catello , Calabresi Paolo
Published: August 2022

Background

Theory of Mind (ToM) is the ability to predict and anticipate others' behaviors through the mental state attribution process. This study aims to investigate the ToM in patients with medication-overuse headache (MOH) and episodic migraine (EM) and to compare it with healthy controls (HC).

Methods

This study enrolled patients with MOH, patients with EM, and HC. ToM was assessed through the Theory of Mind Assessment Scale (ThOMAS), which includes four subscales: Scale A, I-Me, Scale B, Other-Self, Scale C, I-Other, and Scale D, Other-Me, through the Reading the Mind in the Eyes test (RMET), which measures complex emotion recognition, and through the Toronto Alexithymia Scale (TAS-20), which measures alexithymia. Concomitant psychiatric disturbances were evaluated through the Hamilton Anxiety Rating Scale, the Hamilton Depression Rating Scale, and the Dissociative Experiences Scale-II.

Results

The study involved 21 patients with EM, 22 patients with MOH, and 18 HC. In all the four subscales of the ThOMAS, there was a significant difference between HC, EM, and MOH patients: Scale A (p = 0.009), Scale B (p = 0.004), Scale C (p = 0.039), and Scale D (p = 0.008). In the RMET, MOH patients had worse performances than EM patients and HC (p = 0.039). MOH group exhibited higher levels of alexithymia when compared to the HC (p = 0.033) and higher levels of anxiety than HC (p = 0.001).

Conclusion

MOH patients showed a subtle psychopathological pattern characterized by impaired social adaptation.
Neuroinflammation in early, late and recovery stages in a progressive parkinsonism model in rats
Authors: Cunha Debora M. G. , Becegato Marcela , Meurer Ywlliane S. R. , Lima Alvaro C. , Gonçalves Narriman , Bioni Vinícius S. , Engi Sheila A. , Bianchi Paula C. , Cruz Fabio C. , Santos Jose R. , Silva Regina H.
Published: August 2022

Parkinson’s disease (PD) is characterized by motor and non-motor signs, which are accompanied by progressive degeneration of dopaminergic neurons in the substantia nigra. Although the exact causes are unknown, evidence links this neuronal loss with neuroinflammation and oxidative stress. Repeated treatment with a low dose of reserpine—inhibitor of VMAT2—has been proposed as a progressive pharmacological model of PD. The aim of this study was to investigate whether this model replicates the neuroinflammation characteristic of this disease. Six-month-old Wistar rats received repeated subcutaneous injections of reserpine (0.1 mg/kg) or vehicle on alternate days. Animals were euthanized after 5, 10, or 15 injections, or 20 days after the 15th injection. Catalepsy tests (motor assessment) were conducted across treatment. Brains were collected at the end of each treatment period for immunohistochemical and RT-PCR analyzes. Reserpine induced a significant progressive increase in catalepsy duration. We also found decreased immunostaining for tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNpc) and increased GFAP + cells in the SNpc and dorsal striatum after 10 and 15 reserpine injections. Phenotyping microglial M1 and M2 markers showed increased number of CD11b + cells and percentage of CD11b + /iNOS + cells in reserpine-treated animals after 15 injections, which is compatible with tissue damage and production of cytotoxic factors. In addition, increased CD11b + /ArgI + cells were found 20 days after the last reserpine injection, together with an increment in IL-10 gene expression in the dorsal striatum, which is indicative of tissue repair or regeneration. Reserpine also induced increases in striatal interleukin TNF-alpha mRNA levels in early stages. In view of these results, we conclude that reserpine-induced progressive parkinsonism model leads to neuroinflammation in regions involved in the pathophysiology of PD, which is reversed 20 days after the last injection. These findings reveal that withdrawal period, together with the shift of microglial phenotypes from the pro-inflammatory to the anti-inflammatory stage, may be important for the study of the mechanisms involved in reversing this condition, with potential clinical applicability.
Characteristics of sound localization in children with unilateral microtia and atresia and predictors of localization improvement when using a bone conduction device
Authors: Liu Yujie , Zhao Chunli , Yang Lin , Chen Peiwei , Yang Jinsong , Wang Danni , Ren Ran , Li Ying , Zhao Shouqin , Gong Shusheng
Published: August 2022

This study aimed to determine the characteristics of sound localization in children with unilateral microtia and atresia (UMA) and the influence of a non-surgical bone conduction device (BCD). Hearing benefits were evaluated by the word recognition score (WRS), speech reception threshold, the international outcome inventory for hearing aids (IOI-HA), and the Speech, Spatial, and Qualities of Hearing Test for Parent (SSQ-P). Sound localization was measured using broadband noise stimuli randomly played from seven loudspeakers at different stimulus levels [65, 70, and 75 dB sound pressure levels (SPLs)]. The average unaided WRS and speech-to-noise ratio (SNR) for UMA patients was 18.27 ± 14.63 % and −5 ± 1.18 dB SPL, and the average aided WRS and SNR conspicuously changed to 85.45 ± 7.38 % and −7.73 ± 1.42 dB SPL, respectively. The mean IOI-HA score was 4.57 ± 0.73. Compared to the unaided condition, the mean SSQ-P score in each domain improved from 7.08 ± 2.5, 4.86 ± 2.27, and 6.59 ± 1.4 to 8.72 ± 0.95, 7.61 ± 1.52, and 8.55 ± 1.09, respectively. In the sound localization test, some children with UMA were able to detect sound sources quite well and the sound localization abilities did not deteriorate with the non-surgical BCD. Our study concludes that for children with UMA, the non-surgical BCD provided a definite benefit on speech recognition and high satisfaction without deteriorating their sound localization abilities. It is an efficient and safe solution for the early hearing intervention of these patients.
Chemogenetic modulation of sensory afferents induces locomotor changes and plasticity after spinal cord injury
Authors: Eisdorfer Jaclyn T. , Sobotka-Briner Hannah , Schramfield Susan , Moukarzel George , Chen Jie , Campion Thomas J. , Smit Rupert , Rauscher Bradley C. , Lemay Michel A. , Smith George M. , Spence Andrew J.
Published: August 2022

Neuromodulatory therapies for spinal cord injury (SCI) such as electrical epidural stimulation (EES) are increasingly effective at improving patient outcomes. These improvements are thought to be due, at least in part, to plasticity in neuronal circuits. Precisely which circuits are influenced and which afferent classes are most effective in stimulating change remain important open questions. Genetic tools, such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), support targeted and reversible neuromodulation as well as histological characterization of manipulated neurons. We therefore transduced and activated lumbar large diameter peripheral afferents with excitatory (hM3Dq) DREADDs, in a manner analogous to EES, in a rat hemisection model, to begin to trace plasticity and observe concomitant locomotor changes. Chronic DREADDs activation, coupled with thrice weekly treadmill training, was observed to increase afferent fluorescent labeling within motor pools and Clarke's column when compared to control animals. This plasticity may underlie kinematic differences that we observed across stages of recovery, including an increased and less variable hindquarters height in DREADDs animals, shorter step durations, a more flexed ankle joint early in recovery, a less variable ankle joint angle in swing phase, but a more variable hip joint angle. Withdrawal of DREADDs agonist, clozapine-N-oxide (CNO) left these kinematic differences largely unaffected; suggesting that DREADDs activation is not necessary for them later in recovery. However, we observed an intermittent “buckling” phenomenon in DREADDs animals without CNO activation, that did not occur with CNO re-administration. Future studies could use more refined genetic targeted of specific afferent classes, and utilize muscle recordings to find where afferent modulation is most influential in altering motor output.
Preparation and identification of anti-breast cancer cells peptides released from yak milk casein
Authors: Gu Haofeng , Liang Lei , Zhu Ziwei , Mao Xueying
Published: August 2022

Yak milk casein (YMC) is the main protein in the yak milk. Peptides released from Yak milk casein (YMC) have multiple bioactivities, including anti-inflammation and immune-regulation, suggesting that these peptides might be able to inhibit cancer theoretically. However, the anti-cancer peptides from YMC have only been sparsely studied. Breast carcinoma is the most common carcinoma in women worldwide. Thus, the paper herein was to identify yak milk casein (YMC)-derived anti-breast cancer peptides via gel filtration, reversed phase high-performance liquid chromatography (RP-HPLC) and liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI MS/MS) for the first time. The inhibitory effects of the hydrolysates on the cell viabilities, cell cycles and apoptosis of breast cancer cells were evaluated with a cck8 kit and a flow cytometry. The result showed that YMC hydrolysates (YMCH) obtained by united hydrolyzation with trypsin (3 h) and alkaline protease (3 h) displayed the highest cell viability inhibition rate for MCF7 (20.74 ± 1.39%) and MDA-MB-231 (26.73 ± 2.87%) cells. Three peptides were identified in the RP-HPLC subfraction F3-4, and a nonapeptide (TPVVVPPFL) showed the most potent inhibitory effects on both cancer cells and displayed good gastrointestinal stability. TPVVVPPFL could induce G2-M cell cycle arrest in MCF7 cells and S cell arrest in MDA-MB-231 cells and induce apoptosis in both cancer cells. Moreover, in silico analysis indicated that the peptide had non-toxic and no inhibitory roles on P4502D6-enzyme. Together, this study shows that YMC is a good source of anti-breast cancer cells peptides.
Socioeconomic deprivation and survival outcomes in primary central nervous system lymphomas
Authors: Deng Xiangyang , Yang Xionggang , Yang Chunlei , Chen Kezhu , Ren Junwei , Zeng Jun , Zhang Quan , Li Tianwen , Tang Qisheng , Zhu Jianhong
Published: August 2022

Objective

To our knowledge, the impact of area-level socioeconomic status (SES) has not yet been described in primary central nervous system lymphomas (PCNSLs). Current study sought to explore the association of socioeconomic deprivation, measured using the Area Deprivation Index (ADI), with PCNSL outcomes.

Methods

The Surveillance, Epidemiology, and End Results (SEER) database was used to identify PCNSL patients diagnosed between 2006 and 2015 for our analyses. The impact of ADI on overall survival (OS) and cancer-specific survival (CSS) were investigated. Survival analyses were conducted using Kaplan-Meier method with log-rank tests. The Inverse Probability Weighting (IPW) analysis and multivariate cox proportional hazards regression analysis were employed to make covariate adjustments. Multiple mediation analysis (MMA) was performed to estimate the mediating effects.

Results

A total of 3159 PCNSL patients classified into low and high ADI subgroups according to the median ADI score were studied. The Kaplan-Meier analyses showed that low ADI was significantly associated with higher OS rates (HR 1.15, 95%CI 1.06-1.26, P<0.01) and CSS rates (HR 1.15, 95%CI 1.05-1.27, P<0.01). Similar results were observed in analyses adjusted via IPW and multivariate cox methods. Subgroup analyses revealed that ADI could remain a prognostic indictor among different subsets. MMA revealed that several factors including chemotherapy and HIV status making up about 40% of the overall effect, mediated PCNSL survival disparities related to the ADI. Finally, multivariable logistic regression analysis showed that ADI as well as several other factors were independently related to receipt of chemotherapy.

Conclusions

Our study highlights the role of area-level SES in prognosis of PCNSLs. And several factors including chemotherapy and HIV status of PCNSL patents contributed to the CSS disparities between ADI subgroups were uncovered by MMA. Such relationships would highlight the importance of policies development to enhance healthcare delivery and promote awareness of HIV prevention and treatment in low-resource neighborhoods.
Machine learning prediction of prostate cancer from transrectal ultrasound video clips
Authors: Wang Kai , Chen Peizhe , Feng Bojian , Tu Jing , Hu Zhengbiao , Zhang Maoliang , Yang Jie , Zhan Ying , Yao Jincao , Xu Dong
Published: August 2022

Objective

To build a machine learning (ML) prediction model for prostate cancer (PCa) from transrectal ultrasound video clips of the whole prostate gland, diagnostic performance was compared with magnetic resonance imaging (MRI).

Methods

We systematically collated data from 501 patients—276 with prostate cancer and 225 with benign lesions. From a final selection of 231 patients (118 with prostate cancer and 113 with benign lesions), we randomly chose 170 for the purpose of training and validating a machine learning model, while using the remaining 61 to test a derived model. We extracted 851 features from ultrasound video clips. After dimensionality reduction with the least absolute shrinkage and selection operator (LASSO) regression, 14 features were finally selected and the support vector machine (SVM) and random forest (RF) algorithms were used to establish radiomics models based on those features. In addition, we creatively proposed a machine learning models aided diagnosis algorithm (MLAD) composed of SVM, RF, and radiologists’ diagnosis based on MRI to evaluate the performance of ML models in computer-aided diagnosis (CAD). We evaluated the area under the curve (AUC) as well as the sensitivity, specificity, and precision of the ML models and radiologists’ diagnosis based on MRI by employing receiver operator characteristic curve (ROC) analysis.

Results

The AUC, sensitivity, specificity, and precision of the SVM in the diagnosis of PCa in the validation set and the test set were 0.78, 63%, 80%; 0.75, 65%, and 67%, respectively. Additionally, the SVM model was found to be superior to senior radiologists’ (SR, more than 10 years of experience) diagnosis based on MRI (AUC, 0.78 vs. 0.75 in the validation set and 0.75 vs. 0.72 in the test set), and the difference was statistically significant (p< 0.05).

Conclusion

The prediction model constructed by the ML algorithm has good diagnostic efficiency for prostate cancer. The SVM model’s diagnostic efficiency is superior to that of MRI, as it has a more focused application value. Overall, these prediction models can aid radiologists in making better diagnoses.