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Myeloid-derived suppressor cells (MDSCs) mobilize and migrate from bone marrow to peripheral tissues or immune organs, which is associated with poor prognosis in sepsis. Intervention of MDSCs might be a potential target for the effective treatment of sepsis. In the present study, we demonstrated that IL-1R1 blockade with either recombinant human IL-1R antagonist Anakinra or IL-1R1 deficiency had a protective effect on the liver injury in septic mice. The possible mechanism was that Anakinra treatment and IL-1R1 knockout inhibited the migration of MDSCs to the liver in sepsis, thus attenuating the immune suppression of MDSCs on effector T cells characterized with the decrease in proportion of CD4+ and CD8+ T cells. Furthermore, the switch from pro-inflammatory M1 macrophage to anti-inflammatory M2 phenotype and the ability of bacterial clearance in the liver of septic mice were enhanced obviously by Anakinra and IL-1R1 deficiency, which contributes to the attenuated liver injury. Taken together, these findings provide new ideas for revealing the relationship between IL-1R1 and MDSCs in sepsis, thereby providing a potentially effective target for ameliorating septic liver injury. • The blockade of IL-1R1 signaling showed a protective effect on the liver injury of septic mice. • IL-1R1 signaling blockade reduced the proportion of MDSCs in liver of septic mice. • The IL-1R1 blockade attenuated the immune suppression of MDSCs on T cells by inhibiting the migration of MDSCs to the liver. • The IL-1R1 blockade enhanced the ability of bacterial clearance in the liver of septic mice. The IL-1R1 blockade attenuated liver injury by promoting the switch of macrophages from M1 to M2 phenotype. [ABSTRACT FROM AUTHOR]

• Meta -analysis of 36 studies links certain chemokines to glioma risk. • Elevated CXCR4, CXCL12, CCL2, CCL18 correlate with high-grade gliomas. • CXCR4 expression linked to lower survival in glioma patients. • Study shows chemokines' role in glioma pathogenesis and prognosis. • Chemokine pathways in glioma may lead to new treatment options. Glioma is a primary tumor originating from the central nervous system, and despite ongoing efforts to improve treatment, its overall survival rate remains low. There are a limited number of reports regarding the clinical grading, prognostic impact, and utility of chemokines. Therefore, conducting a meta -analysis is necessary to obtain convincing and conclusive results. A comprehensive literature search was conducted using various databases, including PubMed, Web of Science, The Cochrane Library, Embase, Ovid Medline, CNKI, Wanfang Database, VIP, and CBM. The search encompassed articles published from the inception of the databases until March 2024. The estimated odds ratio (ORs), standard mean difference (SMDs), and hazard ratio (HR) with their corresponding 95% confidence intervals (95% CI) were calculated to assess the predictive value of chemokine and receptor levels in glioma risk. Additionally, heterogeneity tests and bias tests were performed to evaluate the reliability of the findings. This meta -analysis included a total of 36 studies, involving 2,480 patients diagnosed with glioma. The results revealed a significant association between the expression levels of CXCR4 (n = 8; OR = 22.28; 95 % CI = 11.47–43.30; p = 0.000), CXCL12 (n = 4; OR = 10.69; 95 % CI = 7.03–16.24; p = 0.000), CCL2 (n = 6; SMD = -0.83; 95 % CI = -0.98‐-0.67; p = 0.000), CXCL8 (n = 3; SMD = 0.75; 95 % CI = 0.47–1.04; p = 0.000), CXCR7 (n = 3; OR = 20.66; 95 % CI = 10.20–41.82; p = 0.000), CXCL10 (n = 2; SMD = 3.27; 95 % CI = 2.91–3.62; p = 0.000) and the risk of glioma. Additionally, a significant correlation was observed between CXCR4 (n = 8; OR = 4.39; 95 % CI = 3.04–6.32; p = 0.000), (n = 6; SMD = 1.37; 95 % CI = 1.09–1.65; p = 0.000), CXCL12 (n = 6; OR = 6.30; 95 % CI = 3.87–10.25; p = 0.000), (n = 5; ES = 2.25; 95 % CI = 1.15–3.34; p = 0.041), CCL2 (n = 3; OR = 9.65; 95 % CI = 4.55–20.45; p = 0.000), (n = 4; SMD = -1.47; 95 % CI = -1.68--1.26; p = 0.000), and CCL18 (n = 3; SMD = 1.62; 95 % CI = 1.30–1.93; p = 0.000) expression levels and high-grade glioma (grades 3-4). Furthermore, CXCR4 (HR = 2.38, 95 % CI = 1.66–3.40; p = 0.000) exhibited a strong correlation with poor overall survival (OS) rates in glioma patients. The findings of this study showed a robust association between elevated levels of CXCR4, CXCL12, CCL2, CXCL8, CXCL10 and CXCR7 with a higher risk of glioma. Furthermore, the WHO grading system was validated by the strong correlation shown between higher expression of CXCR4, CXCL12, CCL2, and CCL18 and WHO high-grade gliomas (grades 3-4). Furthermore, the results of the meta -analysis suggested that CXCR4 might be a helpful biomarker for predicting the worse prognosis of glioma patients. [ABSTRACT FROM AUTHOR]

In the present paper, we establish two Erdélyi-type integrals for Saran's hypergeometric function F K , which has applications in specific branches of applied physics and statistics (see below). We employ methods based on the k-dimensional fractional integration by parts to obtain our main integral identities. The first integral generalizes Koschmieder's result and the second integral extends one of Erdélyi's classical hypergeometric integral. Some useful special cases and important remarks are also discussed. [ABSTRACT FROM AUTHOR]

Immunosuppressive myeloid-derived suppressor cells (MDSCs) continuously expand and lead to poor outcome during sepsis. The activation of liver X receptor (LXR) can mitigate sepsis-induced liver and myocardial damage. This study aims to determine whether LXR plays a protective role in sepsis by regulating MDSCs. Cecal ligation and puncture(CLP)was used to induce sepsis in mice. The mice were then treated with LXR agonist GW3965 (3 mg/kg) or vehicle 1 h, 6 h, 12 h, 24 h, 48 h, 72 h postoperatively. The effect of LXR on the survival rate and multi-organ injury induced by sepsis was evaluated by survival analysis, histological staining, biochemical analysis and ELISAs. The percentages of MDSCs and T cells were detected using flow cytometry. The mRNA expressions of LXR and ATP-binding cassette transporter A1 (ABCA1) were measured using real-time quantitative PCR (RT-qPCR). ABCA1 protein level was determined using immunofluorescence staining. LXR agonist GW3965 treatment improved the survival of septic mice, accompanied by reduced multi-organ injury and a decreased level of inflammatory cytokines. Furthermore, GW3965 treatment decreased MDSCs abundance in spleen by boosting the apoptosis of spleen MDSCs, therefore ameliorating their immunosuppressive activity. Meanwhile, bacteria clearance in tissues was enhanced after the GW3965 administration in septic mice. Mechanistically, GW3965 activated LXRβ and its downstream target ABCA1 to initiate the apoptosis of spleen MDSCs. These findings provide new insights into the relationship between LXR and MDSCs in sepsis, thus revealing a potentially effective approach to target the immunosuppression of sepsis. [ABSTRACT FROM AUTHOR]

HMGA2::NCOR2 keratin-positive giant cell tumors in children with response to imatinib in an infant [ABSTRACT FROM AUTHOR]

This article discusses a rare form of tumor predisposition called atypical teratoid/rhabdoid tumor (ATRT) that arises in the setting of germline ring chromosome 22. ATRT is a type of embryonal neoplasm characterized by the inactivation of the SMARCB1 gene. Germline ring chromosome 22, although not directly affecting SMARCB1, can lead to somatic mosaicism for monosomy chromosome 22, increasing the risk of ATRT. The article presents two cases of ATRT associated with germline ring chromosome 22 and provides detailed molecular characterization of the tumors. It also highlights the potential clinical manifestations and suggests considering germline karyotype and chromosomal microarray for ATRT patients with dysmorphic features, developmental delay, or disproportionate growth. Additionally, the article reports the first case of multiple meningiomas occurring in a long-term survivor of ATRT with germline ring chromosome 22, which predisposes to both SMARCB1 and NF2 deficient tumors. The authors emphasize the need for clinical monitoring in patients with germline ring chromosome 22 and suggest considering germline chromosomal microarray for all ATRT patients with loss of chromosome 22 observed in the tumor. [Extracted from the article]

CIC-rearranged sarcomas are newly defined undifferentiated soft tissue tumors with CIC-associated fusions, and dismal prognosis. CIC fusions activate PEA3 family genes, ETV1/4/5, leading to tumorigenesis and progression. We report two high-grade CNS sarcomas of unclear histological diagnosis and one disseminated tumor of unknown origin with novel fusions and similar gene-expression/methylation patterns without CIC rearrangement. All three patients were infants with aggressive diseases, and two experienced rapid disease deterioration and death. Whole-transcriptome sequencing identified an ATXN1-NUTM2A fusion in the two CNS tumors and an ATXN1L-NUTM2A fusion in case 3. ETV1/4/5 and WT1 overexpression were observed in all three cases. Methylation analyses predicted CIC-rearranged sarcoma for all cases. Retrospective IHC staining on case 2 demonstrated ETV4 and WT1 overexpression. ATXN1 and ATXN1L interact with CIC forming a transcription repressor complex. We propose that ATXN1/ATXN1L-associated fusions disrupt their interaction with CIC and decrease the transcription repressor complex, leading to downstream PEA3 family gene overexpression. These three cases with novel ATXN1/ATXN1L-associated fusions and features of CIC-rearranged sarcomas may further expand the scope of "CIC-rearranged" sarcomas to include non-CIC rearrangements. Additional cases are needed to demonstrate if ATXN1/ATXN1L-NUTM2A fusions are associated with younger age and more aggressive diseases. [ABSTRACT FROM AUTHOR]

Prefabricated steel structures are being promoted in China as an important measure to reduce building carbon emissions (CEs). Currently, high-quality carbon emission factors and calculation methods that identify the sources of CEs from construction process are lacking. This study proposed a process-based method for calculating on-site construction CEs and empirically demonstrated its feasibility using a case of a multistory steel structure with typical column-beam systems. Six construction processes comprising 38 subprocesses were first categorized, then the energy and materials consumed for each subprocess were determined to obtain the first-hand CE parameters. The CEs from hoisting the first- and second-section columns were 10.52 kgCO 2 /column and 14.41 kgCO 2 /column, respectively, and the CEs from their installation were in the range 38.16–69.18 kgCO 2 /column. The CEs from hoisting the primary and secondary beams using a car crane were 7.73 kgCO 2 /beam and 4.52 kgCO 2 /beam, respectively, with lower CEs of 2.40 kgCO 2 /beam and 2.22 kgCO 2 /beam, respectively when a tower crane was used for hoisting. The 14 connection types used to install the primary beams and the 11 connection types used to install the secondary beams had CEs of 13.84–125.96 kgCO 2 /beam and 10.39–43.49 kgCO 2 /beam, respectively. The total on-site construction CE was subsequently calculated by summing the CEs from each process. This method was able to track the CE sources for each construction process and their contributions to identify those with high CE intensities. In addition, the case study was evaluated to provide specific feedback on the current national standard for calculating CEs from building construction. • Proposed method for calculating steel construction carbon emissions. • Conducted on-site case study to determine process-specific carbon emissions. • Considered fuel, electricity, and material consumptions. • Evaluated the results to critique the current national calculation standard. • Gave suggestions to improve calculation for on-site construction carbon emissions. [ABSTRACT FROM AUTHOR]

Childhood cancers present numerous challenges for variant interpretation in a clinical context due to their rarity, low mutation burden, and diversity of unique molecular alterations, many of which are not found in adult cancers. Consequently, variants associated with childhood tumors are under-represented in public cancer databases. Thus, a focused and directed effort is needed for the structured curation of genetic variant data to document diagnostic, prognostic, therapeutic, and hereditary-risk variants for childhood cancers. The ClinGen Somatic Pediatric Cancer Taskforce (PCT) seeks to address these challenges through multiple initiatives. By extensively analyzing the WHO Classification of Tumours Online: Paediatric Tumours volume and reviewing NCCN Guidelines, the PCT created a master list of key genomic alterations (n=975) in pediatric brain, solid, or hematologic malignancies (>180 ICD-O-3.2 diagnoses) that are drivers or have clinical impact to prioritize genes for curation in the CIViC (civicdb.org) knowledgebase. The PCT developed a pediatric specific curation Standard Operating Procedure for the entry of evidence into CIViC to instruct curators on how to tag pediatric evidence based on age of onset and the selection of the most appropriate ICD-O-3.2 disease. In collaboration with the Human Disease Ontology (DO; disease-ontology.org), 464 hematologic and brain cancer ICD-O-3.2 terms have been added to the DO to aid curated disease selection. To aid curators, the natural language processing methods of CIViCmine (bionlp.bcgsc.ca/civicmine) have been adapted to better recognize publications with pediatric evidence. Our efforts support the public dissemination of high-quality childhood cancer focused variant interpretations in the CIViC knowledgebase. [ABSTRACT FROM AUTHOR]

The Sarcoma Working Group of the Cancer Genomics Consortium (CGC) aims to understand the current state of diagnostic testing for pediatric sarcomas and the challenges faced in the field. We conducted a survey of CGC general constituents and American Cytogenetics Forum members (CYTOGN-L@LISTSERV.SC.EDU) in April/May 2022. In total, 46 responses were received, predominantly from university/academic/teaching hospitals (n=45) in the United States (n=41) and Canada (n=5). Respondents reported diverse roles including laboratory directors (n=25), pathologists (n=15), oncologists (n=3), and laboratory technologists (n=3). While most participants reported having in-house FISH (n=40) and/or conventional karyotyping (n=28) assays available for pediatric sarcomas, less than 40% of laboratories offer microarray and/or comprehensive NGS testing clinically. Detailed information on methodology and reported variant types will be discussed. When asked about genetic testing conundrums faced in their practice, the most common response was the scarcity of testing algorithm guidelines (n=12). Additional recurring challenges included: lack of support for new test development and issues with sendout testing (n=6), insufficient knowledge to interpret and act on results (n=4) or when to perform germline testing (n=3), limited tissue for comprehensive testing (n=3), and insurance/reimbursement complications (n=3). To address gaps in guidance for testing, the Workgroup is preparing a manuscript that will report survey results, provide practical scenario-based examples informed by the survey results and supported by literature evidence, and discuss testing options in resource-limited settings for the diagnostic workup of pediatric sarcomas. Areas of focus include but are not limited to NTRK -rearranged tumors and relevant germline testing in pediatric sarcomas. [ABSTRACT FROM AUTHOR]

Teriparatide is a commonly used drug indicated for the treatment of osteoporosis in postmenopausal women. Teriparatide can also upregulate Ang-1 expression through the AC/PKA signaling pathway to promote angiogenesis. At present, promoting angiogenesis is a promising but unrealized strategy for the treatment of ischemic cerebral infarction. However, there are few studies on the application of teriparatide in the treatment of cerebral infarction. We used teriparatide to treat ischemic cerebral infarction in rats and obtained three major findings. First, teriparatide can promote angiogenesis, reduce cerebral infarct size, and increase cerebral perfusion by upregulating Ang-1 expression. Second, teriparatide can promote the expression of HO1, SOD2 and inhibit the production of pro-inflammatory cytokines IL-1β, IL-6 by upregulating Nrf2 expression. Third, we further found that teriparatide can mitigate blood-brain barrier disruption and brain edema by downregulating the expressions of MMP9, Ang-2 and AQP4. Our results indicate that teriparatide is neuroprotective through multiple mechanisms of action that include promoting angiogenesis, inhibiting oxidative stress and neuroinflammation, protecting blood-brain barrier, and reducing brain edema. [Display omitted] • Teriparatide promotes angiogenesis by upregulating Ang-1 expression. • Teriparatide plays a crucial role in inhibiting oxidative stress and anti-neuroinflammation. • Teriparatide can mitigate blood-brain barrier disruption and brain edema. [ABSTRACT FROM AUTHOR]