bluuebunny/crossref_metadata_2025_split huggingface dataset:
NET-Induced Carcinoid Heart Disease Affecting Both Tricuspid and Aortic Valves Due to Patent Foramen Ovale and Right/Left Shunt
Authors: Laschinsky Christina , Welsner Matthias , Mahabadi Amir A. , Lahner Harald , Hautzel Hubertus 
Published: January 2024

Abstract
Carcinoid heart disease (Hedinger syndrome) is a long-term consequence in hormone-active neuroendocrine tumors with hepatic metastases and carcinoid syndrome. Because of serotonin, excess multiple cardiac and pulmonary symptoms evolve, which are further complicated by a patent foramen ovale due to right-left shunting. We present a 53-year-old man with an ileum-neuroendocrine tumor including gross liver metastases and long-term stable disease who subsequently developed Hedinger syndrome. Initially experiencing progressive dyspnea, he eventually experienced severe hypoxemia due to patent foramen ovale. 99mTc-MAA lung perfusion scintigraphy quantitatively identified the right-left shunting, whereas 68Ga-FAPI-46 PET/CT characterized the typical fibrous heart valve thickening due to serotonin-induced fibroblast proliferative properties.
Interictal Electrical Source Imaging
Authors: Rampp Stefan , Müller-Voggel Nadia , Hamer Hajo , Doerfler Arnd , Brandner Sebastian , Buchfelder Michael 
Published: January 2024

Summary:Interictal electrical source imaging (ESI) determines the neuronal generators of epileptic activity in EEG occurring outside of seizures. It uses computational models to take anatomic and neuronal characteristics of the individual patient into account. The presented article provides an overview of application and clinical value of interictal ESI in patients with pharmacoresistant focal epilepsies undergoing evaluation for surgery. Neurophysiological constraints of interictal data are discussed and technical considerations are summarized. Typical indications are covered as well as issues of integration into clinical routine. Finally, an outlook on novel markers of epilepsy for interictal source analysis is presented. Interictal ESI provides diagnostic performance on par with other established methods, such as MRI, PET, or SPECT. Although its accuracy benefits from high-density recordings, it provides valuable information already when applied to EEG with only a limited number of electrodes with complete coverage. Novel oscillatory markers and the integration of frequency coupling and connectivity may further improve accuracy and efficiency.
Thyroid dysfunction and mortality in cardiovascular hospitalized patients
Authors: Frankel Meir , Bayya Feras , Munter Gabriel , Wolak Arik , Tolkin Lior , Barenhoz-Goultschin Orit , Asher Elad , Glikson Michael 
Published: January 2024

Background
Thyroid dysfunction (TD) is associated with increased cardiovascular morbidity and mortality. Early detection may influence the clinical management.

Objective
To determine the prevalence, predictors, and prognostic value of TD among hospitalized cardiac patients.

Methods
A retrospective analysis of a 12-year database consisting of nonselectively adult patients admitted to a Cardiology Department and who were all screened for serum thyroid-stimulation-hormone (TSH) levels . Statistical analysis of demographic and clinical characteristics, mortality and length of hospital stay (LOS) was performed.

Results
A total of 14369 patients were included in the study; mean age was 67 years, 38.3% females. 1465 patients (10.2%) had TD. The most frequent type of TD was mildly elevated TSH (5.4%) followed by mildly reduced TSH (2.1%), markedly elevated TSH (1.5%), and markedly reduced TSH (1.2%). Female gender, history of hypothyroidism, heart failure, atrial fibrillation, renal failure and amiodarone use were significantly associated with TD. During follow-up 2975 (20.7%) patients died. There was increased mortality in the mildly reduced TSH subgroup (hazard ratio [HR] =1.44), markedly elevated TSH subgroup (HR=1.40) and mildly elevated TSH subgroup (HR=1.27). LOS was longer for patients with TD; the longest stay was observed in the markedly elevated TSH subgroup (odds ratio=1.69).

Conclusion
The prevalence of TD in hospitalized cardiac patients is 10.2%. TD is associated with an increased mortality rate and LOS. Consequently, routine screening for thyroid function in this population is advisable, particularly for selected high-risk subgroups. Future studies are needed to determine whether optimizing thyroid function can improve survival in these patients.
Postoperative Global Period Cost Reduction Using 3 Successive Risk-Stratified Pancreatectomy Clinical Pathways
Authors: Azimuddin Ahad , Tzeng Ching-Wei D , Prakash Laura R , Bruno Morgan L , Arvide Elsa M , Dewhurst Whitney L , Newhook Timothy E , Kim Michael P , Ikoma Naruhiko , Snyder Rebecca A , Lee Jeffrey E , Perrier Nancy D , Katz Matthew HG , Maxwell Jessica E 
Published: January 2024

BACKGROUND:We hypothesized that iterative revisions of our original 2016 risk-stratified pancreatectomy clinical pathways would be associated with decreased 90-day perioperative costs.STUDY DESIGN:From a single-institution retrospective cohort study of consecutive patients with 3 iterations: “version 1” (V1) (October 2016 to January 2019), V2 (February 2019 to October 2020), and V3 (November 2020 to February 2022), institutional data were aggregated using revenue codes and adjusted to constant 2022-dollar value. Grand total perioperative costs (primary endpoint) were the sum of pancreatectomy, inpatient care, readmission, and 90-day global outpatient care. Proprietary hospital-based costs were converted to ratios using the mean cost of all hospital operations as the denominator.RESULTS:Of 814 patients, pathway V1 included 363, V2 229, and V3 222 patients. Accordion Grade 3+ complications decreased with each iteration (V1: 28.4%, V2: 22.7%, and V3: 15.3%). Median length of stay decreased (V1: 6 days, interquartile range [IQR] 5 to 8; V2: 5 [IQR 4 to 6]; and V3: 5 [IQR 4 to 6]) without an increase in readmissions. Ninety-day global perioperative costs decreased by 32% (V1 cost ratio 12.6, V2 10.9, and V3 8.6). Reduction of the index hospitalization cost was associated with the greatest savings (−31%: 9.4, 8.3, and 6.5). Outpatient care costs decreased consistently (1.58, 1.41, and 1.04). When combining readmission and all outpatient costs, total “postdischarge” costs decreased (3.17, 2.59, and 2.13). Component costs of the index hospitalization that were associated with the greatest savings were room or board costs (−55%: 1.74, 1.14, and 0.79) and pharmacy costs (−61%: 2.20, 1.61, and 0.87; all p < 0.001).CONCLUSIONS:Three iterative risk-stratified pancreatectomy clinical pathway refinements were associated with a 32% global period cost savings, driven by reduced index hospitalization costs. This successful learning health system model could be externally validated at other institutions performing abdominal cancer surgery.
Acidovorax benzenivorans sp. nov., a novel aromatic hydrocarbon-degrading bacterium isolated from a xylene-degrading enrichment culture
Authors: Bedics Anna , Táncsics András , Banerjee Sinchan , Tóth Erika , Harkai Péter , Gottschall Gerda Georgina , Bóka Károly , Kriszt Balázs 
Published: January 2024

A Gram-stain-negative strain, designated as D2M1T was isolated from xylene-degrading enrichment culture and characterized using a polyphasic approach to determine its taxonomic position. The 16S rRNA gene sequence analysis revealed that strain D2M1T belongs to the genus

Acidovorax

, with the highest 16S rRNA gene similarity to

Acidovorax delafieldii

DSM 64T (99.93 %), followed by

Acidovorax radicis

DSM 23535T (98.77 %) and

Acidovorax kalamii

MTCC 12652T (98.76 %). The draft genome sequence of strain D2M1T is 5.49 Mb long, and the G+C content of the genome is 64.2 mol%. Orthologous average nucleotide identity and digital DNA–DNA hybridization relatedness values between strain D2M1T and its closest relatives were below the threshold values for species demarcation confirming that strain D2M1T is distinctly separated from its closest relatives. The whole genome analysis of the strain revealed a phenol degradation gene cluster, encoding a multicomponent phenol hydroxylase (mPH) together with a complete meta-cleavage pathway including an I.2.C-type catechol 2,3-dioxygenase (C23O) gene. The strain was able to degrade benzene and ethylbenzene as sole sources of carbon and energy under aerobic and microaerobic conditions. Cells were facultatively aerobic rods and motile with a single polar flagellum. The predominant fatty acids (>10 % of the total) of strain D2M1T were summed feature 3 (C16 : 1
ω7c/C16 : 1
ω6c), C16 : 0 and summed feature 8 (C18 : 1
ω7c/C18 : 1
ω6c). The major ubiquinone of strain D2M1T was Q8, while the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Based on polyphasic data, it is concluded that strain D2M1T represents a novel species of the genus

Acidovorax

, for which the name of Acidovorax benzenivorans sp. nov. is proposed. The type strain of the species is strain D2M1T (=DSM 115238T=NCAIM B.02679T).
Intraoperative Ablation Control Based on Real-time Necrosis Monitoring Feedback: Numerical Evaluation
Authors: Murakami Ryo , Mori Satoshi , Zhang Haichong K. 
Published: January 2024

AbstractAblation therapy is a type of minimally invasive treatment, utilized for various organs including the brain, heart, and kidneys. The accuracy of the ablation process is critically important to avoid both insufficient and excessive ablation, which may result in compromised efficacy or complications. The thermal ablation is formulated by two theoretical models: the heat transfer (HT) and necrosis formation (NF) models. In modern medical practices, feed-forward (FF) and temperature feedback (TFB) controls are primarily used as ablation control methodologies. FF involves pre-therapy procedure planning based on previous experiences and theoretical knowledge without monitoring the intraoperative tissue response, hence, it can’t compensate for discrepancies in the assumed HT or NF models. These discrepancies can arise due to individual patient’s tissue characteristic differences and specific environmental conditions. Conversely, TFB control is based on the intraoperative temperature profile. It estimates the resulting heat damage based on the monitored temperature distribution and assumed NF model. Therefore, TFB can make necessary adjustments even if there is an error in the assumed HT model. TFB is thus seen as a more robust control method against modeling errors in the HT model. Still, TFB is limited as it assumes a fixed NF model, irrespective of the patient or the ablation technique used. An ideal solution to these limitations would be to actively monitor heat damage to the tissue during the operation and utilize this data to control ablation. This strategy is defined as necrosis feedback (NFB) in this study. Such real-time necrosis monitoring modalities making NFB possible are emerging, however, there is an absence of a generalized study that discusses the integration and quantifies the significance of the real-time necrosis monitor techniques for ablation therapy. Such an investigation is expected to clarify the universal principles of how these techniques would improve ablation therapy. In this study, we examine the potential of NFB in suppressing errors associated with the NF model as NFB is theoretically capable of monitoring and suppressing the errors associated with the NF models in its closed control loop. We simulate and compare the performances of TFB and NFB with artificially generated modeling errors using the finite element method (FEM). The results show that NFB provides more accurate ablation control than TFB when NF-oriented errors are applied, indicating NFB’s potential to improve the ablation control accuracy and highlighting the value of the ongoing research to make real-time necrosis monitoring a clinically viable option.
Loss of dihydroceramide desaturase drives neurodegeneration by disrupting endoplasmic reticulum and lipid droplet homeostasis in glial cells
Authors: Zhu Yuqing , Cho Kevin , Lacin Haluk , Zhu Yi , DiPaola Jose T. , Wilson Beth A. , Patti Gary J. , Skeath James B. 
Published: January 2024

ABSTRACTDihydroceramide desaturases convert dihydroceramides to ceramides, the precursors of all complex sphingolipids. Reduction of DEGS1 dihydroceramide desaturase function causes pediatric neurodegenerative disorder hypomyelinating leukodystrophy-18 (HLD-18). We discovered thatinfertile crescent (ifc), theDrosophila DEGS1homolog, is expressed primarily in glial cells to promote CNS development by guarding against neurodegeneration. Loss ofifccauses massive dihydroceramide accumulation and severe morphological defects in cortex glia, including endoplasmic reticulum (ER) expansion, failure of neuronal ensheathment, and lipid droplet depletion. RNAi knockdown of the upstream ceramide synthaseschlankin glia ofifcmutants rescues ER expansion, suggesting dihydroceramide accumulation in the ER drives this phenotype. RNAi knockdown ofifcin glia but not neurons drives neuronal cell death, suggesting thatifcfunction in glia promotes neuronal survival. Our work identifies glia as the primary site of disease progression in HLD-18 and may inform on juvenile forms of ALS, which also feature elevated dihydroceramide levels.
A Lipidomics Approach to Determine the Role of Lipids and its Crosstalk with Autophagy in Lung Cancer Metastasis
Authors: da Silva Rosa Simone C. , Alizadeh Javad , Vitorino Rui , Surendran Arun , Ravandi Amir , Kidane Biniam , Ghavami Saeid 
Published: January 2024

Summary/AbstractNon-small cell lung cancer (NSCLC) is among the most malignant tumors with high propensity for metastasis and is the leading cause of cancer-related death globally. Most patients present with regional and distant metastasis, associated with poor prognosis. Lipids may play an essential role in either activating or inhibiting detachment-induced apoptosis (anoikis), where the latter is a crucial mechanism to prevent metastasis, and it may have a cross-talk with autophagy. Autophagy has been shown to be induced in various human cancer metastasis, modulating tumor cell motility and invasion, cancer cell differentiation, resistance to anoikis, and epithelial to mesenchymal transition. Hence, it may play a crucial role in the transition of benign to malignant phenotypes, the core of metastasis initiation. Here, we provide a method we have established in our laboratory for detecting of lipids in attached and detached non-small lung cancer cells and show how to analyze lipidomics data to find its correlation with autophagy-related pathways.Graphical abstractWorkflow of A549 attached and detached cell culture. Cells are collected, lipids are extracted and subjected to LC/MS processing. Next, lipidomics resulting data is analyzed through various steps involving utilization of Metaboanlyst, HDMB, Swiss Target Prediction, and String.
HortGenome Search Engine, a universal genomic search engine for horticultural crops
Authors: Wang Sen , Wei Shangxiao , Deng Yuling , Wu Shaoyuan , Peng Haixu , Qing You , Zhai Xuyang , Zhou Shijie , Li Jinrong , Li Hua , Feng Yijian , Yi Yating , Li Rui , Zhang Hui , Wang Yiding , Zhang Renlong , Ning Lu , Yao YunCong , Fei Zhangjun , Zheng Yi 
Published: January 2024

AbstractHorticultural crops comprising fruit, vegetable, ornamental, beverage, medicinal and aromatic plants play essential roles in food security and human health, as well as landscaping. With the advances of sequencing technologies, genomes for hundreds of horticultural crops have been deciphered in recent years, providing a basis for understanding gene functions and regulatory networks and for the improvement of horticultural crops. However, these valuable genomic data are scattered in warehouses with various complex searching and displaying strategies, which increases learning and usage costs and makes comparative and functional genomic analyses across different horticultural crops very challenging. To this end, we have developed a lightweight universal search engine, HortGenome Search Engine (HSE;http://hort.moilab.net), which allows querying genes, functional annotations, protein domains, homologs, and other gene-related functional information of more than 400 horticultural crops. In addition, four commonly used tools, including ‘BLAST’, ‘Batch Query’, ‘Enrichment analysis’, and ‘Synteny Viewer’, have been developed for efficient mining and analysis of these genomic data.
Antigen non-specific CD8+T cells accelerate cognitive decline in aged mice following respiratory coronavirus infection
Authors: Reagin Katie L. , Lee Rae-Ling , Cocciolone Loren , Funk Kristen E. 
Published: January 2024

AbstractPrimarily a respiratory infection, numerous patients infected with SARS-CoV-2 present with neurologic symptoms, some continuing long after viral clearance as a persistent symptomatic phase termed “long COVID”. Advanced age increases the risk of severe disease, as well as incidence of long COVID. We hypothesized that perturbations in the aged immune response predispose elderly individuals to severe coronavirus infection and post-infectious sequelae. Using a murine model of respiratory coronavirus, mouse hepatitis virus strain A59 (MHV-A59), we found that aging increased clinical illness and lethality to MHV infection, with aged animals harboring increased virus in the brain during acute infection. This was coupled with an unexpected increase in activated CD8+T cells within the brains of aged animals but reduced antigen specificity of those CD8+T cells. Aged animals demonstrated spatial learning impairment following MHV infection, which correlated with increased neuronal cell death and reduced neuronal regeneration in aged hippocampus. Using primary cell culture, we demonstrated that activated CD8+T cells induce neuronal death, independent of antigen-specificity. Specifically, higher levels of CD8+T cell-derived IFN-γ correlated with neuronal death. These results support the evidence that CD8+T cells in the brain directly contribute to cognitive dysfunction following coronavirus infection in aged individuals.eTOC summaryUsing a murine model of respiratory coronavirus infection, we show that aging amplifies post-infectious cognitive dysfunction due to activated CD8+T cells that secrete IFN-γ in the brain. These data provide evidence that CD8+T cells in the brain negatively impact post-infectious cognitive function.
Nicotine enhances the stemness and tumorigenicity in intestinal stem cells via Hippo-YAP/TAZ and Notch signal pathway
Authors: Isotani Ryosuke , Igarashi Masaki , Miura Masaomi , Naruse Kyoko , Kuranami Satoshi , Katoh Manami , Nomura Seitaro , Yamauchi Toshimasa 
Published: January 2024

SUMMARYCigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited. In this study, we demonstrate that NIC increases the abundance and proliferative activity of intestinal stem cells (ISCs) in vivo and ex vivo. Moreover, NIC induces Yes-associated protein (YAP) /Transcriptional coactivator with PDZ-binding motif (TAZ) and Notch signaling in ISCs via α7-nicotinic acetylcholine receptor (nAchR) and protein kinase C (PKC) activation; this effect was not detected in Paneth cells. The inhibition of Notch signaling by dibenzazepine (DBZ) nullified the effects of NIC on ISCs. NIC enhances in vivo tumor formation from ISCs after loss of the tumor suppressor gene Apc, DBZ inhibited NIC-induced tumor growth. Hence, this study identifies a NIC-triggered pathway regulating the stemness and tumorigenicity of ISCs and suggests the use of DBZ as a potential therapeutic strategy for treating intestinal tumors.
Integrated Analyses of Multi-omic Data Derived from Paired Primary Lung Cancer and Brain Metastasis Reveals the Metabolic Vulnerability as a Novel Therapeutic Target
Authors: Duan Hao , Ren Jianlan , Wei Shiyou , Li Chuan , Wang Zhenning , Li Meichen , Wei Zhi , Yang Zhenyu , Liu Yu , Xie Yuan , Wu Suwen , Hu Wanming , Guo Chengcheng , Zhang Xiangheng , Liang Lun , Yu Chengwei , Mou Yanhao , Jiang Yu , Li Houde , Sugarman Eric , Deek Rebecca A. , Chen Zexin , Chen Likun , Chen Yaohui , Yao Maojin , Liu Lunxu , Zhang Gao , Mou Yonggao 
Published: January 2024

AbstractLung cancer brain metastases (LC-BrMs) are frequently associated with dismal mortality rates in patients with lung cancer; however, standard of care therapies for LC-BrMs are still limited in their efficacy. A deep understanding of molecular mechanisms and tumor microenvironment of LC-BrMs will provide us with new insights into developing novel therapeutics for treating patients with LC-BrMs. Here, we performed integrated analyses of genomic, transcriptomic, proteomic and metabolomic data which were derived from a total number of 174 patients with paired and unpaired primary lung cancer and LC-BrM, spanning four published and two newly generated patient cohorts on both bulk and single cell levels. We uncovered that LC-BrMs exhibited significantly higher intra-tumor heterogeneity. We also observed that mutations in a subset of genes were almost always shared by both primary lung cancers and LC-BrM lesions, includingTTN, TP53, MUC16, LRP1B, RYR2, and EGFR. In addition, the genome-wide landscape of somatic copy number alterations was similar between primary lung cancers and LC-BrM lesions. Nevertheless, several regions of focal amplification were significantly enriched in LC-BrMs, including 5p15.33 and 20q13.33. Intriguingly, integrated analyses of transcriptomic, proteomic and metabolomic data revealed mitochondrial-specific metabolism was activated but tumor immune microenvironment was suppressed in LC-BrMs. Subsequently, we validated our results by conducting real-time quantitative reverse transcription PCR experiments, immunohistochemistry and multiplexed immunofluorescence staining of patients’ paired tumor specimens. Patients with a higher expression of mitochondrial metabolism genes but a lower expression of immune genes in their LC-BrM lesions tended to have a worse survival outcome. Therapeutically, targeting oxidative phosphorylation with gamitrinib in patient-derived organoids specific to LC-BrMs induced apoptosis and inhibited cell proliferation. The combination of gamitrinib plus anti-PD-1 immunotherapy significantly improved survival of mice bearing LC-BrMs. In conclusion, our findings not only provide comprehensive and integrated perspectives of molecular underpinnings of LC-BrMs but also contribute to the development of a potential, rationale-based combinatorial therapeutic strategy with the goal of translating it into clinical trials for patients with LC-BrMs.