bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating extracellular particles from severe COVID-19 patients show altered profiling and innate lymphoid cell-modulating ability
Authors: Forte Dorian , Pellegrino Roberto Maria , Trabanelli Sara , Tonetti Tommaso , Ricci Francesca , Cenerenti Mara , Comai Giorgia , Tazzari Pierluigi , Lazzarotto Tiziana , Buratta Sandra , Urbanelli Lorena , Narimanfar Ghazal , Alabed Husam B. R. , Mecucci Cristina , La Manna Gaetano , Emiliani Carla , Jandus Camilla , Ranieri Vito Marco , Cavo Michele , Catani Lucia , Palandri Francesca 
Published: May 2023

IntroductionExtracellular vesicles (EVs) and particles (EPs) represent reliable biomarkers for disease detection. Their role in the inflammatory microenvironment of severe COVID-19 patients is not well determined. Here, we characterized the immunophenotype, the lipidomic cargo and the functional activity of circulating EPs from severe COVID-19 patients (Co-19-EPs) and healthy controls (HC-EPs) correlating the data with the clinical parameters including the partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) and the sequential organ failure assessment (SOFA) score.MethodsPeripheral blood (PB) was collected from COVID-19 patients (n=10) and HC (n=10). EPs were purified from platelet-poor plasma by size exclusion chromatography (SEC) and ultrafiltration. Plasma cytokines and EPs were characterized by multiplex bead-based assay. Quantitative lipidomic profiling of EPs was performed by liquid chromatography/mass spectrometry combined with quadrupole time-of-flight (LC/MS Q-TOF). Innate lymphoid cells (ILC) were characterized by flow cytometry after co-cultures with HC-EPs or Co-19-EPs.ResultsWe observed that EPs from severe COVID-19 patients: 1) display an altered surface signature as assessed by multiplex protein analysis; 2) are characterized by distinct lipidomic profiling; 3) show correlations between lipidomic profiling and disease aggressiveness scores; 4) fail to dampen type 2 innate lymphoid cells (ILC2) cytokine secretion. As a consequence, ILC2 from severe COVID-19 patients show a more activated phenotype due to the presence of Co-19-EPs.DiscussionIn summary, these data highlight that abnormal circulating EPs promote ILC2-driven inflammatory signals in severe COVID-19 patients and support further exploration to unravel the role of EPs (and EVs) in COVID-19 pathogenesis.
Naproxen chemoprevention induces proliferation of cytotoxic lymphocytes in Lynch Syndrome colorectal mucosa
Authors: Bowen Charles M. , Deng Nan , Reyes-Uribe Laura , Parra Edwin Roger , Rocha Pedro , Solis Luisa M. , Wistuba Ignacio I. , Sepeda Valerie O. , Vornik Lana , Perloff Marjorie , Szabo Eva , Umar Asad , Sinha Krishna M. , Brown Powel H. , Vilar Eduardo 
Published: May 2023

BackgroundRecent clinical trial data from Lynch Syndrome (LS) carriers demonstrated that naproxen administered for 6-months is a safe primary chemoprevention that promotes activation of different resident immune cell types without increasing lymphoid cellularity. While intriguing, the precise immune cell types enriched by naproxen remained unanswered. Here, we have utilized cutting-edge technology to elucidate the immune cell types activated by naproxen in mucosal tissue of LS patients.MethodsNormal colorectal mucosa samples (pre- and post-treatment) from a subset of patients enrolled in the randomized and placebo-controlled ‘Naproxen Study’ were obtained and subjected to a tissue microarray for image mass cytometry (IMC) analysis. IMC data was processed using tissue segmentation and functional markers to ascertain cell type abundance. Computational outputs were then used to quantitatively compare immune cell abundance in pre- and post-naproxen specimens.ResultsUsing data-driven exploration, unsupervised clustering identified four populations of immune cell types with statistically significant changes between treatment and control groups. These four populations collectively describe a unique cell population of proliferating lymphocytes within mucosal samples from LS patients exposed to naproxen.ConclusionsOur findings show that daily exposure of naproxen promotes T-cell proliferation in the colonic mucosa, which paves way for developing combination of immunoprevention strategies including naproxen for LS patients.
Turicibacter and Acidaminococcus predict immune-related adverse events and efficacy of immune checkpoint inhibitor
Authors: Hamada Kazuyuki , Isobe Junya , Hattori Kouya , Hosonuma Masahiro , Baba Yuta , Murayama Masakazu , Narikawa Yoichiro , Toyoda Hitoshi , Funayama Eiji , Tajima Kohei , Shida Midori , Hirasawa Yuya , Tsurui Toshiaki , Ariizumi Hirotsugu , Ishiguro Tomoyuki , Suzuki Risako , Ohkuma Ryotaro , Kubota Yutaro , Sambe Takehiko , Tsuji Mayumi , Wada Satoshi , Kiuchi Yuji , Kobayashi Shinichi , Kuramasu Atsuo , Horiike Atsushi , Kim Yun-Gi , Tsunoda Takuya , Yoshimura Kiyoshi 
Published: May 2023

IntroductionImmune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown. MethodsWe investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs).ResultsThe genera Prevotella and Parabacteroides were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of Catenibacterium (P = 0.022) and Turicibacter (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of Desulfovibrion (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of Turicibacter (P = 0.001) and Acidaminococcus (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of Blautia (P = 0.013) and the unclassified Clostridiales (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, Acidaminococcus and Turicibacter (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, Blautia (P = 0.021) and Bilophila (P= 0.033) were statistically significantly more common in those without irAEs.DiscussionOur Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy.
Lipopolysaccharide-induced immune stress negatively regulates broiler chicken growth via the COX-2-PGE2-EP4 signaling pathway
Authors: Liu Kexin , Zhen Wenrui , Bai Dongying , Tan Haiqiu , He Xianglong , Li Yuqian , Liu Yanhao , Zhang Yi , Ito Koichi , Zhang Bingkun , Ma Yanbo 
Published: May 2023

AimsImmune stress in broiler chickens is characterized by the development of persistent pro-inflammatory responses that contribute to degradation of production performance. However, the underlying mechanisms that cause growth inhibition of broilers with immune stress are not well defined.MethodsA total of 252 1-day-old Arbor Acres(AA) broilers were randomly allocated to three groups with six replicates per group and 14 broilers per replicate. The three groups comprised a saline control group, an Lipopolysaccharide (LPS) (immune stress) group, and an LPS and celecoxib group corresponding to an immune stress group treated with a selective COX-2 inhibitor. Birds in LPS group and saline group were intraperitoneally injected with the same amount of LPS or saline from 14d of age for 3 consecutive days. And birds in the LPS and celecoxib group were given a single intraperitoneal injection of celecoxib 15 min prior to LPS injection at 14 d of age.ResultsThe feed intake and body weight gain of broilers were suppressed in response to immune stress induced by LPS which is an intrinsic component of the outer membrane of Gram-negative bacteria. Cyclooxygenase-2 (COX-2), a key enzyme that mediates prostaglandin synthesis, was up-regulated through MAPK-NF-κB pathways in activated microglia cells in broilers exposed to LPS. Subsequently, the binding of prostaglandin E2 (PGE2) to the EP4 receptor maintained the activation of microglia and promoted the secretion of cytokines interleukin-1β and interleukin-8, and chemokines CX3CL1 and CCL4. In addition, the expression of appetite suppressor proopiomelanocortin protein was increased and the levels of growth hormone-releasing hormone were reduced in the hypothalamus. These effects resulted in decreased expression of insulin-like growth factor in the serum of stressed broilers. In contrast, inhibition of COX-2 normalized pro-inflammatory cytokine levels and promoted the expression of Neuropeptide Y and growth hormone-releasing hormone in the hypothalamus which improved the growth performance of stressed broilers. Transcriptomic analysis of the hypothalamus of stressed broilers showed that inhibition of COX-2 activity significantly down-regulated the expression of the TLR1B, IRF7, LY96, MAP3K8, CX3CL1, and CCL4 genes in the MAPK-NF-κB signaling pathway.ConclusionThis study provides new evidence that immune stress mediates growth suppression in broilers by activating the COX-2-PGE2-EP4 signaling axis. Moreover, growth inhibition is reversed by inhibiting the activity of COX-2 under stressed conditions. These observations suggest new approaches for promoting the health of broiler chickens reared in intensive conditions.
Examining the neural mechanisms of rTMS: a naturalistic pilot study of acute and serial effects in pharmacoresistant depression
Authors: Cosmo Camila , Zandvakili Amin , Petrosino Nicholas J. , Toutain Thaise Graziele L. de O. , Miranda José Garcia Vivas , Philip Noah S. 
Published: May 2023

IntroductionPrevious studies have demonstrated the effectiveness of therapeutic repetitive transcranial magnetic stimulation (rTMS) to treat pharmacoresistant depression. Nevertheless, these trials have primarily focused on the therapeutic and neurophysiological effects of rTMS following a long-term treatment course. Identifying brain-based biomarkers of early rTMS therapeutic response remains an important unanswered question. In this pilot study, we examined the effects of rTMS on individuals with pharmacoresistant depression using a graph-based method, called Functional Cortical Networks (FCN), and serial electroencephalography (EEG). We hypothesized that changes in brain activity would occur early in treatment course.MethodsA total of 15 patients with pharmacoresistant depression underwent five rTMS sessions (5Hz over the left dorsolateral prefrontal cortex, 120%MT, up to 4,000 pulses/session). Five participants received additional rTMS treatment, up to 40 sessions. Resting EEG activity was measured at baseline and following every five sessions, using 64-channel EEG, for 10 minutes with eyes closed. An FCN model was constructed using time-varying graphs and motif synchronization. The primary outcome was acute changes in weighted-node degree. Secondary outcomes included serial FFT-based power spectral analysis and changes in depressive symptoms measured by the 9-Item Patient Health Questionnaire (PHQ-9) and the 30-item Inventory of Depressive Symptoms-Self Report (IDS-SR).ResultsWe found a significant acute effect over the left posterior area after five sessions, as evidenced by an increase in weighted-node degree of 37,824.59 (95% CI, 468.20 to 75,180.98) and a marginal enhancement in the left frontal region (t (14) = 2.0820,p= 0.056). One-way repeated measures ANOVA indicated a significant decrease in absolute beta power over the left prefrontal cortex (F (7, 28) = 2.37,p= 0.048) following ten rTMS sessions. Furthermore, a significant clinical improvement was observed following five rTMS sessions on both PHQ-9 (t (14) = 2.7093,p= 0.017) and IDS-SR (t (14) = 2.5278,p= 0.024) and progressed along the treatment course.DiscussionOur findings suggest that FCN models and serial EEG may contribute to a deeper understanding of mechanisms underlying rTMS treatment. Additional research is required to investigate the acute and serial effects of rTMS in pharmacoresistant depression and assess whether early EEG changes could serve as predictors of therapeutic rTMS response.
Multiple sclerosis and breast cancer risk: a meta-analysis of observational and Mendelian randomization studies
Authors: Fang Tian , Zhang Zhihao , Zhou Huijie , Wu Wanchun , Zou Liqun 
Published: May 2023

BackgroundSeveral observational studies have explored the relationships between multiple sclerosis (MS) and breast cancer; however, whether an association exists remains unknown.MethodsWe conducted a meta-analysis of observational studies and Mendelian randomization (MR) based on genetic variants to identify the relationship between MS and breast cancer. The observational studies were searched from PubMed, Embase, Web of Science, and Scopus to assess the relationship between MS and breast cancer from inception to 07 Nov 2022. Moreover, we explored the association between genetically pre-disposed MS and breast cancer risk based on an MR study. The summary analysis for MS from two separate databases [International Multiple Sclerosis Genetics Consortium (IMSGC), FinnGen] and the summary analysis for breast cancer from Breast Cancer Association Consortium.ResultsFifteen cohort studies involving 173,565 female MS patients were included in this meta-analysis. The correlation between MS and breast cancer was not statistically significant [relative ratio (RR) = 1.08, 95% confidence interval (CI) = 0.99–1.17]. In the MR analysis, we did not observe causal associations of genetically determined MS with breast cancer and its subtypes from both the IMSGC and FinnGen datasets.ConclusionThe meta-analysis of observational and MR based on genetic variants does not support the correlation between MS and breast cancer.
Clinical validation of the novel CLIA-CA-62 assay efficacy for early-stage breast cancer detection
Authors: Sekacheva Marina , Boroda Alexander , Fatyanova Anastasia , Rozhkov Alexander , Bagmet Nikolai 
Published: May 2023

BackgroundWithout organized screening programs up to 60-70% of breast cancers are diagnosed at advanced stages that have significantly lower five-year survival rate and poorer outcomes, which is a serious global public health problem. The purpose of the blind clinical study was the assessment of the novel in-vitro diagnostic chemiluminescent CLIA-CA-62 assay for early-stage breast cancer detection.MethodsBlind serum samples of 196 BC patients with known TNM staging, 85% with DCIS, Stage I &amp; IIA, and 73 healthy control subjects were analyzed with the CLIA-CA-62 and CA 15-3 ELISA assays. Results were also compared to the pathology findings and to published data from mammography, MRI, ultrasound, and multi-cancer early detection test (MCED).ResultsThe CLIA-CA-62 overall sensitivity for BC was 92% (100% for DCIS) at 93% specificity and it decreased in invasive stages (Stage I=97%, Stage II=85% and Stage III=83%). For the CA 15-3 assay sensitivity was 27-46% at 80% specificity. Sensitivity for mammography was 63-80% at 60% specificity, depending on the stage and the parenchymal density.ConclusionThese results demonstrate that CLIA-CA-62 immunoassay could prove useful as a supplement to current mammography screening and other imaging methods, thus increasing the diagnostic sensitivity in DCIS and Stage I breast cancer detection.
WIPI2 enhances the vulnerability of colorectal cancer cells to erastin via bioinformatics analysis and experimental verification
Authors: Yu Liying , Luo Yan , Ding Xile , Tang Miaomiao , Gao Huan , Zhang Renfang , Chen Mingfu , Liu Yuchen , Chen Qiongxia , Ouyang Yanli , Wang Xiang , Zhen Hongyan 
Published: May 2023

IntroductionWD Repeat Domain Phosphoinositide Interacting 2 (WIPI2) is a WD repeat protein that interacts with phosphatidylinositol and regulates multiprotein complexes by providing a b-propeller platform for synchronous and reversible protein-protein interactions assembled proteins. Ferroptosis is a novel iron-dependent form of cell death. It is usually accompanied with the accumulation of membrane lipid peroxides. Our study is to focus on investigating the effect of WIPI2 on the growth and ferroptosis of colorectal cancer (CRC) cells and its potential mechanism.MethodsWe analyzed the expression of WIPI2 in colorectal cancer versus normal tissues through The Cancer Genome Atlas (TCGA), and the relationship between clinical traits and WIPI2 expression and prognosis was assessed by univariate and multifactorial cox analysis. Next, we constructed the siRNAs targeting the WIPI2 sequence si-WIPI2 to further investigate the mechanism of WIPI2 in CRC cells through vitro experiments.ResultsPublic data from the TCGA platform showed that WIPI2 expression was significantly elevated in colorectal cancer tissues compared to paracancerous tissues, and high WIPI2 expressionpredicted poor prognosis for CRC patients. Moreover, we found that the knockdown of WIPI2 expression could inhibit the growth and proliferation of HCT116 and HT29 cells. Furthermore, we found that the expression level of ACSL4 decreased and that of GPX4 increased when WIPI2 was knocked down, suggesting that WIPI2 can potentially positively regulate CRC ferroptosis. Meanwhile, both NC and si groups were able to further inhibit cell growth activity, as well as increase WIPI2 and decrease GPX4 expression when treated with Erastin, but the rate of cell viability inhibition and the trend of protein changes were more significantly in the NC group than si groups, which indicated that Erastin induced CRC ferroptosis through the WIPI2/GPX4 pathway thereby enhancing the sensitivity of colorectal cancer cells to Erastin.ConclusionsOur study suggested that WIPI2 had a promotional effect on the growth of colorectal cancer cells, and it also played an important role in the ferroptosis pathway.
Nonbacterial and bacterial osteomyelitis in children: a case–control retrospective study
Authors: Kostik Mikhail M. , Maletin Alexey S. , Petukhova Veronika V. , Mushkin Alexander Yu. 
Published: May 2023

PurposeOsteomyelitis is a group of bone infectious (bacterial osteomyeilitis—BO) and noninfectious inflammatory diseases (nonbacterial osteomyelitis—NBO) with similar clinical, radiology, and laboratory features. Many patients with NBO are misdiagnosed as BO and receive unnecessary antibiotics and surgery. Our study aimed to compare clinical and laboratory features of NBO and BO in children, to define key discriminative criteria, and to create an NBO diagnostic score (NBODS).MethodsThe retrospective multicenter cohort study included clinical, laboratory, and instrumental information about histologically confirmed NBO (n = 91) and BO (n = 31). The variables allowed us to differentiate both conditions used to construct and validate the NBO DS.ResultsThe main differences between NBO and BO are as follows: onset age—7.3 (2.5; 10.6) vs. 10.5 (6.5; 12.7) years (p = 0.03), frequency of fever (34.1% vs. 90.6%, p = 0.0000001), symptomatic arthritis (67% vs. 28.1%, p = 0.0001), monofocal involvement (28.6% vs. 100%, p = 0.0000001), spine (32% vs. 6%, p = 0.004), femur (41% vs. 13%, p = 0.004), foot bones (40% vs. 13%, p = 0.005), clavicula (11% vs. 0%, p = 0.05), and sternum (11% vs. 0%, p = 0.039) involvement. The following four criteria are included in the NBO DS: CRP ≤ 55 mg/l (56 points), multifocal involvement (27 points), femur involvement (17 points), and neutrophil bands ≤ 220 cell/μl (15 points). The sum &gt; 17 points allowed to differentiate NBO from BO with a sensitivity of 89.0% and a specificity of 96.9%.ConclusionThe diagnostic criteria may help discriminate NBO and BO and avoid excessive antibacterial treatment and surgery.
Resting-state heart rate variability, level of stress and resilience in internet gaming disorder and alcohol use disorder
Authors: Park Jong Hu , Yoo So Young , Park Hye Yoon , Choi Jung-Seok 
Published: May 2023

Stress and resilience are involved in the pathophysiology of addictive disorders, and heart rate variability (HRV) is an index of an individual’s global capability to regulate psychological responses. In this study, we aimed to identify transdiagnostic and disorder-specific markers in people with addictive disorders by analyzing resting-state HRV and associations with the levels of stress and resilience. We compared relevant data between patients with internet gaming disorder (IGD) and/or alcohol use disorder (AUD) and healthy controls (HCs). In all, 163 adults aged 18–35 years (53 with IGD, 49 with AUD, 61 HCs) participated. The levels of stress and resilience were measured using the Psychosocial Wellbeing Index and the Connor-Davidson Resilience Scale, respectively. The HRV was obtained from each participant during a 5 min resting-state. The IGD and AUD patients exhibited increased levels of stress and decreased resilience compared to the HCs. Patients with either addictive disorder exhibited a lower standard deviation of the normal-to-normal beat interval (SDNN) index [SDNNi] compared to HCs even after adjusting for clinical variables such as depression, anxiety, and impulsivity. In multiple comparison tests among the three groups, the AUD group had lower HRV than HCs, but no differences were observed among the groups after adjusting for the clinical variables. The HRV indices were correlated with the levels of stress, resilience, and disease severity. In conclusion, IGD and AUD patients exhibit lower HRV as indicated by the SDNNi compared to HCs, revealing their vulnerability to stress as well as a common transdiagnostic marker of addiction.
Fresh Gastrodia elata Blume alleviates simulated weightlessness-induced cognitive impairment by regulating inflammatory and apoptosis-related pathways
Authors: Zhang Yiwen , Huang Hong , Yao Caihong , Sun Xinran , He Qinghu , Choudharyc Muhammad Iqbal , Chen Shanguang , Liu Xinmin , Jiang Ning 
Published: May 2023

In aerospace medicine, the influence of microgravity on cognition has always been a risk factor threatening astronauts’ health. The traditional medicinal plant and food material Gastrodia elata Blume has been used as a therapeutic drug for neurological diseases for a long time due to its unique neuroprotective effect. To study the effect of fresh Gastrodia elata Blume (FG) on cognitive impairment caused by microgravity, hindlimb unloading (HU) was used to stimulate weightlessness in mice. The fresh Gastrodia elata Blume (0.5 g/kg or 1.0 g/kg) was intragastrically administered daily to mice exposed to HU and behavioral tests were conducted after four weeks to detect the cognitive status of animals. The behavioral tests results showed that fresh Gastrodia elata Blume therapy significantly improved the performance of mice in the object location recognition test, Step-Down test, and Morris Water Maze test, including short-term and long-term spatial memory. According to the biochemical test results, fresh Gastrodia elata Blume administration not only reduced serum factor levels of oxidative stress but also maintained the balance of pro-inflammatory and anti-inflammatory factors in the hippocampus, reversing the abnormal increase of NLRP3 and NF-κB. The apoptosis-related proteins were downregulated which may be related to the activation of the PI3K/AKT/mTOR pathway by fresh Gastrodia elata Blume therapy, and the abnormal changes of synapse-related protein and glutamate neurotransmitter were corrected. These results identify the improvement effect of fresh Gastrodia elata Blume as a new application form of Gastrodia elata Blume on cognitive impairment caused by simulated weightlessness and advance our understanding of the mechanism of fresh Gastrodia elata Blume on the neuroprotective effect.