bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine/chemokine profiles in people with recent infection by Mycobacterium tuberculosis
Authors: Herrera Mariana , Keynan Yoav , Lopez Lucelly , Marín Diana , Vélez Lázaro , McLaren Paul J. , Rueda Zulma Vanessa 
Published: May 2023

IntroductionThe risk of progression to tuberculosis disease is highest within the first year after M. tuberculosis infection (TBI). We hypothesize that people with newly acquired TBI have a unique cytokine/chemokine profile that could be used as a potential biomarker.MethodsWe evaluated socio-demographic variables and 18 cytokines/chemokines in plasma samples from a cohort of people deprived of liberty (PDL) in two Colombian prisons: 47 people diagnosed with pulmonary TB, 24 with new TBI, and 47 non-infected individuals. We performed a multinomial regression to identify the immune parameters that differentiate the groups.ResultsThe concentration of immune parameters changed over time and was affected by the time of incarceration. The concentration of sCD14, IL-18 and IP-10 differed between individuals with new TBI and short and long times of incarceration. Among people with short incarceration, high concentrations of MIP-3α were associated with a higher risk of a new TBI, and higher concentrations of Eotaxin were associated with a lower risk of a new TBI. Higher concentrations of sCD14 and TNF-α were associated with a higher risk of TB disease, and higher concentrations of IL-18 and MCP-1 were associated with a lower risk of TB disease.ConclusionsThere were cytokines/chemokines associated with new TBI and TB disease. However, the concentration of immune mediators varies by the time of incarceration among people with new TBI. Further studies should evaluate the changes of these and other cytokines/chemokines over time to understand the immune mechanisms across the spectrum of TB.
Control of enhancer and promoter activation in the type I interferon response by the histone demethylase Kdm4d/JMJD2d
Authors: Chandwani Rohit , Fang Terry C. , Dewell Scott , Tarakhovsky Alexander 
Published: May 2023

IntroductionTranscriptional activation depends on the interplay of chromatin modifiers to establish a permissive epigenetic landscape. While histone 3 lysine 9 (H3K9) methylation has long been associated with gene repression, there is limited evidence to support a role for H3K9 demethylases in gene activation.MethodsWe leveraged knockdown and overexpression of JMJD2d / Kdm4d in mouse embryonic fibroblasts, coupled with extensive epigenomic analysesm to decipher the role of histone 3 lysine 9 demethylases in the innate immune response.ResultsHere we describe the H3K9 demethylase Kdm4d/JMJD2d as a positive regulator of type I interferon responses. In mouse embryonic fibroblasts (MEFs), depletion of JMJD2d attenuates the transcriptional response, conferring increased viral susceptibility, while overexpression of the demethylase results in more robust IFN activation. We find that the underlying mechanism of JMJD2d in type I interferon responses consists of an effect both on the transcription of enhancer RNAs (eRNAs) and on dynamic H3K9me2 at associated promoters. In support of these findings, we establish that JMJD2d is associated with enhancer regions throughout the genome prior to stimulation but is redistributed to inducible promoters in conjunction with transcriptional activation.DiscussionTaken together, our data reveal JMJD2d as a chromatin modifier that connects enhancer transcription with promoter demethylation to modulate transcriptional responses.
Noninvasive mechanical destruction of liver tissue and tissue decellularisation by pressure-modulated shockwave histotripsy
Authors: Pahk Ki Joo , Heo Jeongmin , Joung Chanmin , Pahk Kisoo 
Published: May 2023

IntroductionBoiling histotripsy (BH) is a promising High Intensity Focused Ultrasound (HIFU) technique that can be used to mechanically fractionate solid tumours at the HIFU focus noninvasively, promoting tumour immunity. Because of the occurrence of shock scattering phenomenon during BH process, the treatment accuracy of BH is, however, somewhat limited. To induce more localised and selective tissue destruction, the concept of pressure modulation has recently been proposed in our previous in vitro tissue phantom study. The aim of the present study was therefore to investigate whether this newly developed histotripsy approach termed pressure-modulated shockwave histotripsy (PSH) can be used to induce localised mechanical tissue fractionation in in vivo animal model.MethodsIn the present study, 8 Sprague Dawley rats underwent the PSH treatment and were sacrificed immediately after the exposure for morphological and histological analyses (paraffin embedded liver tissue sections were stained with H&amp;E and MT). Partially exteriorised rat’s left lateral liver lobe in vivo was exposed to a 2.0 MHz HIFU transducer with peak positive (P+) and negative (P-) pressures of 89.1 MPa and –14.6 MPa, a pulse length of 5 to 34 ms, a pressure modulation time at 4 ms where P+ and P- decreased to 29.9 MPa and – 9.6 MPa, a pulse repetition frequency of 1 Hz, a duty cycle of 1% and number of pulses of 1 to 20. Three lesions were produced on each animal. For comparison, the same exposure condition but no pressure modulation was also employed to create a number of lesions in the liver.Results and DiscussionExperimental results showed that a partial mechanical destruction of liver tissue in the form of an oval in the absence of thermal damage was clearly observed at the HIFU focus after the PSH exposure. With a single pulse length of 7 ms, a PSH lesion created in the liver was measured to be a length of 1.04 ± 0.04 mm and a width of 0.87 ± 0.21 mm which was 2.37 times in length (p = 0.027) and 1.35 times in width (p = 0.1295) smaller than a lesion produced by no pressure modulation approach (e.g., BH). It was also observed that the length of a PSH lesion gradually grew towards the opposite direction to the HIFU source along the axial direction with the PSH pulse length, eventually leading to the generation of an elongated lesion in the liver. In addition, our experimental results demonstrated the feasibility of inducing partial decellularisation effect where liver tissue was partially destructed with intact extracellular matrix (i.e., intact fibrillar collagen) with the shortest PSH pulse length. Taken together, these results suggest that PSH could be used to induce a highly localised tissue fractionation with a desired degree of mechanical damage from complete tissue fractionation to tissue decellularisation through controlling the dynamics of boiling bubbles without inducing the shock scattering effect.
Dysregulated early transcriptional signatures linked to mast cell and interferon responses are implicated in COVID-19 severity
Authors: MacCann Rachel , Leon Alejandro Abner Garcia , Gonzalez Gabriel , Carr Michael J. , Feeney Eoin R. , Yousif Obada , Cotter Aoife G. , de Barra Eoghan , Sadlier Corinna , Doran Peter , Mallon Patrick W. 
Published: May 2023

BackgroundDysregulated immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are thought to underlie the progression of coronavirus disease 2019 (COVID-19) to severe disease. We sought to determine whether early host immune-related gene expression could predict clinical progression to severe disease.MethodsWe analysed the expression of 579 immunological genes in peripheral blood mononuclear cells taken early after symptom onset using the NanoString nCounter and compared SARS-CoV-2 negative controls with SARS-CoV-2 positive subjects with mild (SARS+ Mild) and Moderate/Severe disease to evaluate disease outcomes. Biobanked plasma samples were also assessed for type I (IFN-α2a and IFN-β), type II (IFN-γ) and type III (IFN-λ1) interferons (IFNs) as well as 10 additional cytokines using multiplex immunoassays.ResultsWe identified 19 significantly deregulated genes in 62 SARS-CoV-2 positive subject samples within 5 days of symptom onset and 58 SARS-CoV-2 negative controls and found that type I interferon (IFN) signalling (MX1, IRF7, IFITM1, IFI35, STAT2, IRF4, PML, BST2, STAT1) and genes encoding proinflammatory cytokines (TNF, TNFSF4, PTGS2 and IL1B) were upregulated in both SARS+ groups. Moreover, we found that FCER1, involved in mast cell activation, was upregulated in the SARS+ Mild group but significantly downregulated in the SARS+ Moderate/Severe group. In both SARS+ groups we discovered elevated interferon type I IFN-α2a, type II IFN and type III IFN λ1 plasma levels together with higher IL-10 and IL-6. These results indicate that those with moderate or severe disease are characterised by deficiencies in a mast cell response together with IFN hyper-responsiveness, suggesting that early host antiviral immune responses could be a cause and not a consequence of severe COVID-19.ConclusionsThis study suggests that early host immune responses linking defects in mast cell activation with host interferon responses correlates with more severe outcomes in COVID-19. Further characterisation of this pathway could help inform better treatment for vulnerable individuals.
Association between diagnostic criteria for severe acute malnutrition and hospital mortality in children aged 6–59 months in the eastern Democratic Republic of Congo: the Lwiro cohort study
Authors: Ngaboyeka Gaylord , Bisimwa Ghislain , Neven Anouk , Mwene-Batu Pacifique , Kambale Richard , Kingwayi Petit Passy , Chiribagula Christian , Battisti Oreste , Dramaix Michèle , Donnen Philippe 
Published: May 2023

BackgroundFew studies have assessed the relationship between weight-for-height (WHZ) and mid-upper arm circumference (MUAC) with hospital mortality considering confounders. The particularity of MUAC for age (MUACZ) is less documented.ObjectiveThis study aims to investigate this relationship in a region endemic for severe acute malnutrition (SAM).MethodsThis is a retrospective cohort based on a database of children admitted from 1987 to 2008 in South Kivu, eastern DRC. Our outcome was hospital mortality. To estimate the strength of the association between mortality and nutritional indices, the relative risk (RR) with its 95% confidence interval (95% CI) was calculated. In addition to univariate analyses, we constructed multivariate models from binomial regression.ResultsA total of 9,969 children aged 6 to 59 months were selected with a median age of 23 months. 40.9% had SAM (according to the criteria WHZ &lt; -3 and/or MUAC&lt;115 mm and/or the presence of nutritional edema) including 30.2% with nutritional edema and 35.2% had both SAM and chronic malnutrition. The overall hospital mortality was 8.0% and was higher at the beginning of data collection (17.9% in 1987). In univariate analyses, children with a WHZ &lt; -3 had a risk almost 3 times higher of dying than children without SAM. WHZ was more associated with in-hospital mortality than MUAC or MUACZ. Multivariate models confirmed the univariate results. The risk of death was also increased by the presence of edema.ConclusionIn our study, WHZ was the indicator more associated with hospital death compared with MUAC or MUACZ. As such, we recommend that all criteria shall continue to be used for admission to therapeutic SAM programs. Efforts should be encouraged to find simple tools allowing the community to accurately measure WHZ and MUACZ.
Sarcobesity, but not visceral fat, is an independent risk factor for complications after radical resection of colorectal cancer
Authors: Feng Zhewen , Pang Kai , Tian Mingwei , Gu Xiaozhe , Lin Huajun , Yang Xiaobao , Yang Yingchi , Zhang Zhongtao 
Published: May 2023

BackgroundThe influence of body composition on the outcome of colorectal cancer surgery is controversial. The aim of this study was to evaluate the effects of visceral obesity and sarcobesity on the incidence of total and surgical complications after radical resection of colorectal cancer.MethodsWe collected a total of 426 patients who underwent elective radical resection of colorectal cancer at Beijing Friendship Hospital, Capital Medical University from January 2017 to May 2018. According to the inclusion and exclusion criteria, 387 patients were finally included. A CT scan at the level of the L3-L4 intervertebral disk was selected to measure the values of visceral fat area and skeletal muscle area. Multivariate analysis was used to explore the independent risk/protective factors affecting postoperative complications.Results128 (33.1%) patients developed complications, and 44 (11.4%) patients developed major complications. Among them, 111 patients developed surgical complications and 21 developed medical complications. Visceral fat area (Z = −3.271, p = 0.001), total fat area (Z = −2.613, p = 0.009), visceral fat area to subcutaneous fat area ratio (V/S, Z = −2.633, p = 0.008), and sarcobesity index (Z = −2.282, p = 0.023) were significantly associated with total complications. Visceral fat area (Z = −2.119, p = 0.034) and V/S (Z = −2.010, p = 0.044) were significantly associated with total surgical complications. Sarcobesity index, smoking, stoma, blood loss, surgery time, and American Society of Anesthesiology (ASA) score were selected as risk factors for total postoperative complications according to LASSO regression. Multivariate logistic regression analysis suggested that sarcobesity index was an independent risk factor for postoperative total complications and surgical complications. Subgroup analysis suggested that albumin level was an independent protective factor for postoperative total complications in male patients. Smoking, operative time, and sarcobesity index were independent risk factors, and cholesterol was an independent protective factor for total postoperative complications in female patients.ConclusionIncreased sarcobesity index is an independent risk factor for postoperative complications in patients with colorectal cancer, while visceral fat area is not. For female patients, smoking, operation time, and obesity index are independent risk factors for postoperative complications, while cholesterol is an independent protective factor. For male patients, serum albumin is an independent protective factor for postoperative complications.
The efficacy and safety of lenvatinib plus transarterial chemoembolization in combination with PD-1 antibody in treatment of unresectable recurrent hepatocellular carcinoma: a case series report
Authors: Mu Chunyang , Shen Junyi , Zhu Xinrui , Peng Wei , Zhang Xiaoyun , Wen Tianfu 
Published: May 2023

PurposeTo explore the safety and efficacy of lenvatinib in combination with trans-arterial chemoembolization (TACE) and programmed death receptor 1 (PD-1) antibody in the treatment of unresectable recurrent hepatocellular carcinoma (urHCC).Patients and methodsThe clinical data of 16 patients with unresectable recurrent hepatocellular carcinoma admitted to the Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, and received the conversion therapy of lenvatinib + TACE + PD-1 antibody between January 2019 and January 2022 were retrospectively analyzed.ResultsThere were 25% (4/16) patients suffering from grade 3 adverse events and no patients suffering from grade 4 or higher adverse events. After 4 months of treatment of 16 patients, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), two, five, three, and six cases were in complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), respectively, and the objective response rate (ORR) was 43.8% (7/16). The 1-year overall survival (OS) rate and 1-year progression-free survival (PFS) rate were 86.2% and 46.9%, respectively. In our subgroup analysis, the ORR of patients with multiple lesions reached up to 60%, which was higher than that of patients with single lesions.ConclusionsLenvatinib in combination with TACE and PD-1 antibody is safe and effective in the treatment of unresectable recurrent hepatocellular carcinoma.
PGM3 inhibition shows cooperative effects with erastin inducing pancreatic cancer cell death via activation of the unfolded protein response
Authors: Zerbato Barbara , Gobbi Maximilian , Ludwig Tobias , Brancato Virginia , Pessina Alex , Brambilla Luca , Wegner Andre , Chiaradonna Ferdinando 
Published: May 2023

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a poor patient prognosis. Remarkably, PDAC is one of the most aggressive and deadly tumor types and is notorious for its resistance to all types of treatment. PDAC resistance is frequently associated with a wide metabolic rewiring and in particular of the glycolytic branch named Hexosamine Biosynthetic Pathway (HBP).MethodsTranscriptional and bioinformatics analysis were performed to obtain information about the effect of the HBP inhibition in two cell models of PDAC. Cell count, western blot, HPLC and metabolomics analyses were used to determine the impact of the combined treatment between an HBP’s Phosphoglucomutase 3 (PGM3) enzyme inhibitor, named FR054, and erastin (ERA), a recognized ferroptosis inducer, on PDAC cell growth and survival.ResultsHere we show that the combined treatment applied to different PDAC cell lines induces a significant decrease in cell proliferation and a concurrent enhancement of cell death. Furthermore, we show that this combined treatment induces Unfolded Protein Response (UPR), NFE2 Like BZIP Transcription Factor 2 (NRF2) activation, a change in cellular redox state, a greater sensitivity to oxidative stress, a major dependence on glutamine metabolism, and finally ferroptosis cell death.ConclusionOur study discloses that HBP inhibition enhances, via UPR activation, the ERA effect and therefore might be a novel anticancer mechanism to be exploited as PDAC therapy.
The value of whole-volume apparent diffusion coefficient histogram analysis in preoperatively distinguishing intracranial solitary fibrous tumor and transitional meningioma
Authors: Wang Gang , Zhou Junlin 
Published: May 2023

PurposeTo investigate the value of whole-volume apparent diffusion coefficient (ADC) histogram analysis in preoperatively distinguishing intracranial solitary fibrous tumors (SFT) from transitional meningiomas (TM), thereby assisting the establishment of the treatment protocol.MethodsPreoperative diffusion-weighted imaging datasets of 24 patients with SFT and 28 patients with TM were used to extract whole-volume ADC histogram parameters, including variance, skewness, kurtosis, and mean, as well as 1st (AP1), 10th (AP10), 50th (AP50), 90th (AP90), and 99th (AP99) percentiles of ADC using MaZda software. The independent t-test or Mann–Whitney U test was used to compare the differences between ADC histogram parameters of SFT and TM. Receiver operating characteristic (ROC) curves were generated to evaluate the performance of significant ADC histogram parameters. Spearman’s correlation coefficients were calculated to evaluate correlations between these parameters and the Ki-67 expression levels.ResultsSFT exhibited significantly higher variance, and lower AP1 and AP10 (all P &lt; 0.05) than TM. The best diagnostic performance was obtained by variance, with an area under the ROC curve of 0.848 (0.722–0.933). However, there was no significant difference in skewness, kurtosis, mean, or other percentiles of ADC between the two groups (all P &gt; 0.05). Significant correlations were also observed between the Ki-67 proliferation index and variance (r = 0.519), AP1 (r = -0.425), and AP10 (r = -0.372) (all P &lt; 0.05).ConclusionWhole-volume ADC histogram analysis is a feasible tool for non-invasive preoperative discrimination between intracranial SFT and TM, with variance being the most promising prospective parameter.
Excavation of diagnostic biomarkers and construction of prognostic model for clear cell renal cell carcinoma based on urine proteomics
Authors: Yang Yiren , Pang Qingyang , Hua Meimian , Huangfu Zhao , Yan Rui , Liu Wenqiang , Zhang Wei , Shi Xiaolei , Xu Yifan , Shi Jiazi 
Published: May 2023

PurposeClear cell renal cell carcinoma (ccRCC) is the most common pathology type in kidney cancer. However, the prognosis of advanced ccRCC is unsatisfactory. Thus, early diagnosis becomes one of the most important research priorities of ccRCC. However, currently available studies about ccRCC lack urine-related further studies. In this study, we applied proteomics to search urinary biomarkers to assist early diagnosis of ccRCC. In addition, we constructed a prognostic model to assist judge patients’ prognosis.Materials and methodsUrine which was used to perform 4D label-free quantitative proteomics was collected from 12 ccRCC patients and 11 non-tumor patients with no urinary system diseases. The urine of 12 patients with ccRCC confirmed by pathological examination after surgery was collected before operatoin. Bioinformatics analysis was used to describe the urinary proteomics landscape of these patients with ccRCC. The top ten proteins with the highest expression content were selected as the basis for subsequent validation. Urine from 46 ccRCC patients and 45 control patients were collected to use for verification by enzyme linked immunosorbent assay (ELISA). In order to assess the prognostic value of urine proteomics, a prognostic model was constructed by COX regression analysis on the intersection of RNA-sequencing data in The Cancer Genome Atlas (TCGA) database and our urine proteomic data.Results133 proteins differentially expressed in the urinary samples were found and 85 proteins (Fold Change, FC&gt;1.5) were identified up-regulated while 48 down-regulated (FC&lt;0.5). Top 10 proteins including S100A14, PKHD1L1, FABP4, ITIH2, C3, C8G, C2, ATF6, ANGPTL6, F13B were performed ELISA to verify. The results showed that PKHD1L1, ANGPTL6, FABP4 and C3 were statistically significant (P&lt;0.05). We performed multivariate logistic regression analysis and plotted a nomogram. Receiver operating characteristic (ROC) curve indicted that the diagnostic efficiency of combined indicators is satisfactory (Aare under curve, AUC=0.835). Furthermore, the prognostic value of the urine proteomics was explored through the intersection between urine proteomics and TCGA RNA-seq data. Thus, COX regression analysis showed that VSIG4, HLA-DRA, SERPINF1, and IGLV2-23 were statistically significant (P&lt;0.05).ConclusionOur study indicated that the application of urine proteomics to explore diagnostic biomarkers and to construct prognostic models of renal clear cell carcinoma is of certain clinical value. PKHD1L1, ANGPTL6, FABP4 and C3 can assist to diagnose ccRCC. The prognostic model constituted of VSIG4, HLA-DRA, SERPINF1, and IGLV2-23 can significantly predict the prognosis of ccRCC patients, but this still needs more clinical trials to verify.