bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct systemic immune networks define severe vs. mild COVID-19 in hematologic and solid cancer patients
Authors: Pignataro-Oshiro Flávio , Figueiredo Amanda B. , Galdino Nayane A. L. , Morais Katia L. P. , Dutra Walderez O. , Silva Bianca Grassi de Miranda , Feriani Diego , Abrantes Flávia de Azevedo , Silva Ivan Leonardo Avelino França e , Filho Jayr Schmidt , Framil Juliana Valéria de Souza , Cesca Marcelle Goldner , Riechelmann Rachel Simões Pimenta , Batista Marjorie V. , Gollob Kenneth J. 
Published: January 2023

IntroductionThe COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has impacted health across all sectors of society. A cytokine-release syndrome, combined with an inefficient response of innate immune cells to directly combat the virus, characterizes the severe form of COVID-19. While immune factors involved in the development of severe COVID-19 in the general population are becoming clearer, identification of the immune mechanisms behind severe disease in oncologic patients remains uncertain.MethodsHere we evaluated the systemic immune response through the analysis of soluble blood immune factors and anti-SARS-CoV-2 antibodies within the early days of a positive SARS-CoV-2 diagnostic in oncologic patients.ResultsIndividuals with hematologic malignancies that went on to die from COVID-19 displayed at diagnosis severe leukopenia, low antibody production against SARS-CoV-2 proteins, and elevated production of innate immune cell recruitment and activation factors. These patients also displayed correlation networks in which IL-2, IL-13, TNF-alpha, IFN-gamma, and FGF2 were the focal points. Hematologic cancer patients that showed highly networked and coordinated anti-SARS-CoV-2 antibody production, with central importance of IL-4, IL-5, IL-12A, IL-15, and IL-17A, presented only mild COVID-19. Conversely, solid tumor patients that had elevated levels of inflammatory cytokines IL-6, CXCL8, and lost the coordinate production of anti-virus antibodies developed severe COVID-19 and died. Patients that displayed positive correlation networks between anti-virus antibodies, and a regulatory axis involving IL-10 and inflammatory cytokines recovered from the disease. We also provided evidence that CXCL8 is a strong predictor of death for oncologic patients and could be an indicator of poor prognosis within days of the positive diagnostic of SARS-CoV-2 infection.ConclusionOur findings defined distinct systemic immune profiles associated with COVID-19 clinical outcome of patients with cancer and COVID-19. These systemic immune networks shed light on potential immune mechanisms involved in disease outcome, as well as identify potential clinically useful biomarkers.
Conversion therapy for advanced intrahepatic cholangiocarcinoma with lenvatinib and pembrolizumab combined with gemcitabine plus cisplatin: A case report and literature review
Authors: Zhang Wei , Luo Chu , Zhang Zun-Yi , Zhang Bi-Xiang , Chen Xiao-Ping 
Published: January 2023

BackgroundIntrahepatic cholangiocarcinoma (ICC) is a highly malignant biliary tumor. Patients with unresectable and advanced ICC have a poor prognosis with current gemcitabine-based chemotherapy. Combination therapy strategies based on immunotherapy have achieved promising results in various tumor types.Case presentationWe reported a patient with unresectable ICC who received lenvatinib and pembrolizumab in combination with gemcitabine plus cisplatin (GP) chemotherapy and subsequently underwent radical liver resection. A 46-year-old male with a history of chronic hepatitis B and hypertension was diagnosed with ICC. Multiple liver tumors with ring-like enhancement were detected on abdominal contrast-enhanced CT and MRI. Enlarged lymph nodes were found in the hilar and retroperitoneal areas. The tumor was clinically staged as T2N1M0 (stage IIIB). Lenvatinib and pembrolizumab in combination with GP chemotherapy were adopted as first-line treatments for the patient. After six cycles of scheduled treatment, the diameter of the largest liver lesion and the number of liver lesions were markedly reduced. The level of the tumor marker CA19-9 decreased to a normal range. A partial response according to the mRECIST criteria was achieved without severe toxicities. Non-anatomical liver resection (segment 4b, 5,6 + segment 7 + segment 8), cholecystectomy and hilar lymph node dissection were performed one month after stopping combination therapy. Pathological examination confirmed a diagnosis of moderate-to-poorly differentiated ICC with lymph node metastasis. The patient has survived 15 months following resection of the tumors, with no evidence of local recurrence or distant metastasis.ConclusionLenvatinib and anti-PD1 antibody pembrolizumab in combination with GP chemotherapy provided promising antitumor efficacy with reasonable tolerability, which may be a potentially feasible and safe conversion therapy strategy for patients with initially unresectable and advanced ICC.
Intratumoral STING activation causes durable immunogenic tumor eradication in the KP soft tissue sarcoma model
Authors: Marritt Kayla L. , Hildebrand Karys M. , Hildebrand Kurt N. , Singla Arvind K. , Zemp Franz J. , Mahoney Douglas J. , Jirik Frank R. , Monument Michael J. 
Published: January 2023

IntroductionSoft tissue sarcomas (STS) are highly metastatic, connective-tissue lineage solid cancers. Immunologically, sarcomas are frequently characterized by a paucity of tumor infiltrating lymphocytes and an immune suppressive microenvironment. Activation of the STING pathway can induce potent immune-driven anti-tumor responses within immunogenic solid tumors; however, this strategy has not been evaluated in immunologically cold sarcomas. Herein, we assessed the therapeutic response of intratumoral STING activation in an immunologically cold murine model of undifferentiated pleomorphic sarcoma (UPS).Materials and ResultsA single intratumoral injection of the murine STING agonist, DMXAA resulted in durable cure in up to 60% of UPS-bearing mice. In mice with synchronous lung metastases, STING activation within hindlimb tumors resulted in 50% cure in both anatomic sites. Surviving mice all rejected UPS re-challenge in the hindlimb and lung. Therapeutic efficacy of STING was inhibited by lymphocyte deficiency but unaffected by macrophage deficiency. Immune phenotyping demonstrated enrichment of lymphocytic responses in tumors at multiple timepoints following treatment. Immune checkpoint blockade enhanced survival following STING activation.DiscussionThese data suggest intratumoral activation of the STING pathway elicits local and systemic anti-tumor immune responses in a lymphocyte poor sarcoma model and deserves further evaluation as an adjunctive local and systemic treatment for sarcomas.
Leukemia-associated truncation of granulocyte colony-stimulating factor receptor impacts granulopoiesis throughout the life-course
Authors: Bulleeraz Vilasha , Goy Michelle , Basheer Faiza , Liongue Clifford , Ward Alister C. 
Published: January 2023

IntroductionThe granulocyte colony-stimulating factor receptor (G-CSFR), encoded by the CSF3R gene, is involved in the production and function of neutrophilic granulocytes. Somatic mutations in CSF3R leading to truncated G-CSFR forms are observed in acute myeloid leukemia (AML), particularly those subsequent to severe chronic neutropenia (SCN), as well as in a subset of patients with other leukemias.MethodsThis investigation introduced equivalent mutations into the zebrafish csf3r gene via genome editing and used a range of molecular and cellular techniques to understand the impact of these mutations on immune cells across the lifespan.ResultsZebrafish harboring truncated G-CSFRs showed significantly enhanced neutrophil production throughout successive waves of embryonic hematopoiesis and a neutrophil maturation defect in adults, with the mutations acting in a partially dominant manner.DiscussionThis study has elucidated new insights into the impact of G-CSFR truncations throughout the life-course and created a bone fide zebrafish model for further investigation.
Case report: Streptococcus pneumoniae pneumonia characterized by diffuse centrilobular nodules in both lungs
Authors: Zhang Fangqi , Qin Shaowen , Xia Fei , Mao Congzheng , Li Long 
Published: January 2023

BackgroundStreptococcus pneumoniae (S. pneumoniae) is the most common pathogen in community-acquired pneumonia (CAP) and takes the form of lobar pneumonia as typical computed tomography (CT) findings. Various patterns of radiological manifestation have also been reported in patients with S. pneumoniae pneumonia; however, the appearance of diffuse centrilobular nodules in both lungs is rarely reported.Case presentationWe report the case of a patient with a history of chronic lymphocytic leukemia (CLL) for 9 years who presented with new-onset fever, cough, excess sputum, and shortness of breath for 1 week. He was given intravenous antibacterial (cephalosporin) treatment for 4 days, but his condition did not improve and dyspnea became more serious. The chest CT indicated diffuse centrilobular nodules in both lungs at admission. Patient’s bronchoalveolar (BAL) fluid was sent for metagenomic next-generation sequencing, which only supported a diagnosis of S. pneumoniae infection. His condition improved gradually after antimicrobial treatment (moxifloxacin) and a follow-up CT showed that the diffuse centrilobular nodules in both lungs were absorbed completely.ConclusionThis case highlights a rare CT presentation of S. pneumoniae pneumonia that should alert clinicians, so as to avoid taking unnecessary treatment measures.
Clinical characteristics, risk factors and diagnostic outcomes of patients presented with indeterminate biliary stricture: A multicenter study
Authors: Tag-Adeen Mohammed , Malak Mohamed , Abdel-Gawad Muhammad , Abu-Elfatth Ahmed , Eldamarawy Ramadan H. , Alzamzamy Ahmed , Elbasiony Mohamed , Elsharkawy Ramy M. , El-Raey Fathiya , Basiony Ahmed N. , Qasem Ahmed , Shady Zakarya , Abdelmohsen Ahmed S. , Abdeltawab Doaa , Farouk Mahmoud , Fouad Ola M. , Rabie Ahmed , Erian Abdul-Hakim , Sapra Ahlam , Shaibat-Alhamd Wael , Aboubakr Ashraf , Omran Dalia , Alboraie Mohamed 
Published: January 2023

Background and aimIndeterminate biliary stricture (IBS) is a frequently encountered clinical problem. In this study, we aimed to highlight the clinical characteristics, risk factors and diagnostic outcomes of patients presented with indeterminate biliary stricture.MethodA Retrospective multicenter study included all patients diagnosed with IBS in the participating centers between 2017 and 2021. Data regarding IBS such as presentations, patient characteristics, diagnostic and therapeutic modalities were collected from the patients' records and then were analyzed.ResultsData of 315 patients with IBS were retrospectively collected from 7 medical centers with mean age: 62.6 ± 11 years, females: 40.3% and smokers: 44.8%. For diagnosing stricture; Magnetic resonance imaging/Magnetic resonance cholangiopancreatography (MRI/MRCP) was the most frequently requested imaging modality in all patients, Contrast enhanced computerized tomography (CECT) in 85% and endoscopic ultrasound (EUS) in 23.8%. Tissue diagnosis of cholangiocarcinoma was achieved in 14% only. The used therapeutic modalities were endoscopic retrograde cholangiopancreatography (ERCP)/stenting in 70.5%, percutaneous trans-hepatic biliary drainage (PTD): 17.8%, EUS guided drainage: 0.3%, and surgical resection in 8%. The most frequent type of strictures was distal stricture in 181 patients, perihilar in 128 and intrahepatic in 6. Distal strictures had significant male predominance, with higher role for EUS for diagnosis and higher role for ERCP/stenting for drainage, while in the perihilar strictures, there was higher role for CECT and MRI/MRCP for diagnosis and more frequent use of PTD for drainage.ConclusionIndeterminate biliary stricture is a challenging clinical problem with lack of tissue diagnosis in most of cases mandates an urgent consensus diagnostic and treatment guidelines.
Establishment of an interdisciplinary vascular anomalies program in Tanzania, East Africa
Authors: Puhr-Westerheide Daniel , Masthoff Max , Shah Jay , Krechel Alina , Shemwetta Mwivano , Naif Azza A. , Ukweh Ofonime N. , Abdul Ziad , Sarkar Abizer , Baraka Balowa Musa , Malecela Furaha , Lekasio Praygod Justin , Rajab Latifa , Mungia Abbas , Sianga William , Manji Karim P. , Mbuguje Eric M. , Khoncarly Sarah , Minja Frank J. , Laage Gaupp Fabian M. , Wildgruber Moritz 
Published: January 2023

PurposeThe aim of this project is the sustainable implementation of a vascular anomalies (VA) program in Tanzania.Materials and methodsIn 2021 the first interdisciplinary VA program was initiated at Muhimbili National Hospital (MNH), Dar Es Salaam, Tanzania in a stepwise approach. During the planning phase the clinical need for minimally-invasive therapies of VAs and the preexisting structures were assessed by the local Interventional Radiology (IR) team at MNH. During the initiation phase, an IR team from two German VA centers joined the interdisciplinary team at MNH for clinical workup, image-guided procedures and follow-up. VA patients were recruited from existing patient records or seen at clinics as de novo presentations following nationwide advertisement. In the post-processing phase joined online conferences for follow-up and support in management of new patients were established. Further follow-up was supported by attending providers from other established VA centers, traveling to bolster the primary operators of MNH.ResultsThe first interdisciplinary VA program was successfully launched in Tanzania. Minimally-invasive treatments were successfully trained, by performing ultrasound-guided sclerotherapy with polidocanol and bleomycin in twelve patients with slow-flow malformations, one endovascular embolization of a high-flow malformation, and medical treatment of an aggressive infantile hemangioma. Regular online follow-up presentations have been initiated. Follow-up evaluation and required treatment was sustained when appropriate.ConclusionThe presented “hands-on” training set the ground for the first interdisciplinary VA program in Tanzania. This framework is expected to establish comprehensive and sustainable care of patients with VAs in East Africa and can serve as a blueprint for other sites.
LDMD: A database of microbes in human lung disease
Authors: Xu Li-Qun , Yang Jing , Liang Weicheng , Chen Jiang , Sun Zepeng , Zhang Qiang , Liu Xinlong , Qiao Feng , Li Jian 
Published: January 2023

BackgroundLungs were initially thought to be sterile. However, with the development of sequencing technologies, various commensal microorganisms, especially bacteria, have been observed in the lungs of healthy humans. Several studies have also linked lung microbes to infectious lung diseases. However, few databases have focused on the metagenomics of lungs to provide microbial compositions and corresponding metadata information. Such a database would be handy for researching and treating lung diseases.MethodsTo provide researchers with a preliminary understanding of lung microbes and their research methods, the LDMD collated nearly 10,000 studies in the literature covering over 30 diseases, gathered basic information such as the sources of lung microbe samples, sequencing methods, and processing software, as well as analyzed the metagenomic sequencing characteristics of lung microbes. Besides, the LDMD also contained data collected in our laboratory.ResultsIn this study, we established the Lung Disease Microorganisms Database (LDMD), a comprehensive database of microbes involved in lung disease. The LDMD offered sequence analysis capabilities, allowing users to upload their sequencing results, align them with the data collated in the database, and visually analyze the results.ConclusionIn conclusion, the LDMD possesses various functionalities that provide a convenient and comprehensive resource to study the lung metagenome and treat lung diseases.
Carbon dioxide equivalent emissions from corn silage fermentation
Authors: Krueger Lucas A. , Koester Lucas R. , Jones David F. , Spangler David A. 
Published: January 2023

The European Climate Law recently codified the goal for European climate neutrality by 2050, highlighting the need for sustainable farming practices within a robust and transparent carbon dioxide equivalent (CO2e) accounting system. In the present study, a series of equations were proposed for the estimation of CO2e emissions from corn silage fermentation. Systematic review of previous meta-analyses of corn silage fermentation identified the mean and standard deviation statistics for key model inputs of acetic acid, ethanol, lactic acid, ammonia, and volatile-corrected dry matter loss. Estimates of CO2e emissions were determined for a mock dataset comprising 1,000 iterations of randomly-generated values for each metric in accordance with mean and variance statistics of the source data. Estimates for CO2e emissions of corn silage based on meta-analysis review of laboratory experiments were 1.9 ± 5.6% (GWP20) and 0.2 ± 5.5% (GWP100) of silage dry matter. Furthermore, model results demonstrated a precedent for CO2 recycling by silage microorganisms, which was supported by genome annotation of strains belonging to common silage species. Linear model equations for GWP20 and GWP100 with inputs and outputs in mg kg−1 silage dry matter were developed, where inputs are acetic acid (A), ethanol (E), lactic acid (L), and volatile corrected dry matter loss (DV). Linear equations are (for GWP20; Eq. 11):GWP20=−3626.1−0.04343A+0.8011E−0.03173L+1.46573DVand for GWP100; Eq. 12:GWP100=−8526.10−0.22403A−0.11963E−0.03173L+1.46573DV.
Increased functional connectivity patterns in mild Alzheimer’s disease: A rsfMRI study
Authors: Penalba-Sánchez Lucía , Oliveira-Silva Patrícia , Sumich Alexander Luke , Cifre Ignacio 
Published: January 2023

BackgroundAlzheimer’s disease (AD) is the most common age-related neurodegenerative disorder. In view of our rapidly aging population, there is an urgent need to identify Alzheimer’s disease (AD) at an early stage. A potential way to do so is by assessing the functional connectivity (FC), i.e., the statistical dependency between two or more brain regions, through novel analysis techniques.MethodsIn the present study, we assessed the static and dynamic FC using different approaches. A resting state (rs)fMRI dataset from the Alzheimer’s disease neuroimaging initiative (ADNI) was used (n = 128). The blood-oxygen-level-dependent (BOLD) signals from 116 regions of 4 groups of participants, i.e., healthy controls (HC; n = 35), early mild cognitive impairment (EMCI; n = 29), late mild cognitive impairment (LMCI; n = 30), and Alzheimer’s disease (AD; n = 34) were extracted and analyzed. FC and dynamic FC were extracted using Pearson’s correlation, sliding-windows correlation analysis (SWA), and the point process analysis (PPA). Additionally, graph theory measures to explore network segregation and integration were computed.ResultsOur results showed a longer characteristic path length and a decreased degree of EMCI in comparison to the other groups. Additionally, an increased FC in several regions in LMCI and AD in contrast to HC and EMCI was detected. These results suggest a maladaptive short-term mechanism to maintain cognition.ConclusionThe increased pattern of FC in several regions in LMCI and AD is observable in all the analyses; however, the PPA enabled us to reduce the computational demands and offered new specific dynamic FC findings.
Dimorphic glioblastoma with glial and epithelioid phenotypes: Clonal evolution and immune selection
Authors: Mondia Mark Willy L. , Kritselis Michael A. , Donahue John E. , Elinzano Heinrich , Sarangi Sasmit , Bryant David , Capelletti Marzia , Korn W. Michael , Yu Esther , Yan Sherry , Toms Steven A. , Wong Eric T. 
Published: January 2023

PurposeEpithelioid glioblastoma is an unusual histologic variant of malignant glioma. The present study investigates both the genomic and transcriptomic determinants that may promote the development of this tumor.MethodsWhole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were performed on an epithelioid glioblastoma, along with a specific bioinformatic pipeline to generate electronic karyotyping and investigate the tumor immune microenvironment. Microdissected sections containing typical glioblastoma features and epithelioid morphology were analyzed separately using the same methodologies.ResultsAn epithelioid glioblastoma, with immunopositivity for GFAP, Olig-2, and ATRX but negative for IDH-1 and p53, was identified. The tumor cell content from microdissection was estimated to be 85–90% for both histologic tumor components. WES revealed that both glioma and epithelioid sections contained identical point mutations in PTEN, RB1, TERT promoter, and TP53. Electronic karyotype analysis also revealed similar chromosomal copy number alterations, but the epithelioid component showed additional abnormalities that were not found in the glioblastoma component. The tumor immune microenvironments were strikingly different and WTS revealed high levels of transcripts from myeloid cells as well as M1 and M2 macrophages in the glioma section, while transcripts from CD4+ lymphocytes and NK cells predominated in the epithelioid section.ConclusionEpithelioid glioblastoma may be genomically more unstable and oncogenically more advanced, harboring an increased number of mutations and karyotype abnormalities, compared to typical glioblastomas. The tumor immune microenvironment is also different.