bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of glutaminase-1 in DLBCL potentiates venetoclax-induced antitumor activity by promoting oxidative stress
Authors: Gomez Solsona Beatriz , Horn Heike , Schmitt Anja , Xu Wendan , Bucher Philip , Heinrich Aylin , Kalmbach Sabrina , Kreienkamp Nina , Franke Maik , Wimmers Florian , Schuhknecht Laurentz , Rosenwald Andreas , Zampieri Mattia , Ott German , Lenz Georg , Schulze-Osthoff Klaus , Hailfinger Stephan 
Published: November 2023

Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults, but first-line immunochemotherapy fails to produce a durable response in about one-third of the patients. Because tumor cells often reprogram their metabolism, we investigated the importance of glutaminolysis, a pathway converting glutamine to generate energy and various metabolites, for the growth of DLBCL cells. Glutaminase-1 (GLS1) expression was robustly detected in DLBCL biopsy samples and cell lines. Both pharmacological inhibition and genetic knockdown of GLS1 induced cell death in DLBCL cells regardless of their subtype classification, whereas primary B cells remained unaffected. Interestingly, GLS1 inhibition resulted not only in reduced levels of intermediates of the tricarboxylic acid cycle but also in a strong mitochondrial accumulation of reactive oxygen species. Supplementation of DLBCL cells with α-ketoglutarate or with the antioxidant α-tocopherol mitigated oxidative stress and abrogated cell death upon GLS1 inhibition, indicating an essential role of glutaminolysis in the protection from oxidative stress. Furthermore, the combination of the GLS1 inhibitor CB-839 with the therapeutic BCL2 inhibitor ABT-199 not only induced massive reactive oxygen species (ROS) production but also exhibited highly synergistic cytotoxicity, suggesting that simultaneous targeting of GLS1 and BCL2 could represent a novel therapeutic strategy for patients with DLBCL.
Effects of IL-1β inhibition on anemia and clonal hematopoiesis in the randomized CANTOS trial
Authors: Woo Janghee , Lu Darlene , Lewandowski Andrew , Xu Huilei , Serrano Pablo , Healey Margaret , Yates Denise P. , Beste Michael T. , Libby Peter , Ridker Paul M. , Steensma David P. 
Published: November 2023

Abstract
Canakinumab, a monoclonal antibody targeting proinflammatory cytokine interleukin-1β (IL-1β), improved hemoglobin levels while preventing recurrent cardiovascular events in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). This cardiovascular (CV) preventive effect was greater in patients with TET2 mutations associated with clonal hematopoiesis (CH). The current proteogenomic analysis aimed to understand the clinical response to canakinumab and underlying proteomic profiles in the context of CH and anemia. The analysis included 4595 patients from the CANTOS study who received either canakinumab or placebo and evaluated multiplexed proteomics (4785 proteins) using SomaScan and targeted deep sequencing for CH mutations. Incident anemia was more common in the presence of CH mutations but reduced by canakinumab treatment. Canakinumab treatment was significantly associated with higher hemoglobin increment in patients with concurrent CH mutations and anemia than patients with CH mutations without anemia or without CH mutations. Compared with those without CH mutations, the presence of CH mutations was associated with proteomic signatures of inflammation and defense response to infection, as well as markers of high-risk CV disease which was further enhanced by the presence of anemia. Canakinumab suppressed hepcidin, proinflammatory cytokines, myeloid activation, and complement pathways, and reversed pathologically deregulated pathways to a greater extent in patients with CH mutations and anemia. These molecular findings provide evidence of the clinical use of IL-1β blockade and support further study of canakinumab for patients with concurrent anemia and CH mutations. This study was registered at www.clinicaltrials.gov as #NCT01327846.
Performance of the MeltPro TB assay as initial test for diagnosis of pulmonary tuberculosis with drug-resistance detection
Authors: Liu Zhi-bin , Cheng Li-ping , Pan Hong-qiu , Wu Xiao-cui , Lu Fu-hui , Cao Jie , Wang Lei , Wei Wei , Chen Hong-yu , Sha Wei , Sun Qin 
Published: November 2023

Abstract
Background
The MeltPro TB assay (MeltPro) is a molecular rapid diagnostic test designed for detecting resistance to antituberculosis drugs. However, the performance of MeltPro as an initial diagnostic test for simultaneously detecting the presence of Mycobacterium tuberculosis (MTB) and drug resistance has not been evaluated. This study aims to assess the performance of MeltPro as initial diagnostic test for simultaneous detection of MTB and drug resistance in clinical samples from patients with presumptive pulmonary tuberculosis (PTB).

Methods
A retrospective analysis was conducted on 1283 patients with presumptive PTB from two clinical centers, out of which 875 were diagnosed with PTB. The diagnostic accuracy of MeltPro, Xpert MTB/RIF (Xpert), and MGIT 960 for PTB detection was evaluated. Rifampicin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (STR), and fluoroquinolone (FQ) resistance were detected using MeltPro, with Xpert and/or the broth microdilution plate method (MYCOTB) results as references.

Results
For the diagnosis of PTB, MeltPro showed a sensitivity of 69.0%, which was similar to Xpert (72.7%; P > 0.05) and higher than MGIT (58.1%; P < 0.001). The specificity of MeltPro was 97.1%, similar to Xpert (98.0%; P > 0.05). In smear-negative patients, MeltPro's sensitivity was 50.9%, similar to Xpert (56.5%; P > 0.05), and higher than MGIT (33.1%; P < 0.001). Based on Xpert and/or MYCOTB results, MeltPro exhibited a sensitivity and specificity of 98.3% and 99.2%, respectively, for detecting RIF resistance. Based on MYCOTB results, MeltPro's sensitivity for detecting resistance to INH, EMB, STR, and FQ was 96.4%, 89.1%, 97.5%, and 90.3%, respectively, with specificities of 96.0%, 96.0%, 95.2%, and 99.4%, respectively.

Conclusion
The MeltPro TB assay could potentially be an effective alternative as the initial test for rapid diagnosis of PTB with drug-resistance detection in clinical practice.
An Improved Time-Domain Inverse Technique for Localization and Quantification of Rotating Sound Sources
Authors: Zhang Xiaozheng , Li Yinlong , Zhang Yongbin , Bi Chuanxing , Li Jinghao , Xu Liang 
Published: November 2023

AbstractThe time-domain inverse technique based on the time-domain rotating equivalent source method has been proposed to localize and quantify rotating sound sources. However, this technique encounters two problems to be addressed: one is the time-consuming process of solving the transcendental equation at each time step, and the other is the difficulty of controlling the instability problem due to the time-varying transfer matrix. In view of that, an improved technique is proposed in this paper to resolve these two problems. In the improved technique, a de-Dopplerization method in the time-domain rotating reference frame is first applied to eliminate the Doppler effect caused by the source rotation in the measured pressure signals, and then the restored pressure signals without the Doppler effect are used as the inputs of the time-domain stationary equivalent source method to locate and quantify sound sources. Compared with the original technique, the improved technique can avoid solving the transcendental equation at each time step, and facilitate the treatment of the instability problem because the transfer matrix does not change with time. Numerical simulation and experimental results show that the improved technique can eliminate the Doppler effect effectively, and then localize and quantify the rotating nonstationary or broadband sources accurately. The results also demonstrate that the improved technique can guarantee a more stable reconstruction and compute more efficiently than the original one.
Genomic formation of Tibeto-Burman speaking populations in Guizhou, Southwest China
Authors: Chen Jinwen , Zhang Han , Yang Meiqing , Wang Rui , Zhang Hongling , Ren Zheng , Wang Qiyan , Liu Yubo , Chen Jing , Ji Jingyan , Zhao Jing , He Guanglin , Guo Jianxin , Zhu Kongyang , Yang Xiaomin , Ma Hao , Wang Chuan-Chao , Huang Jiang 
Published: November 2023

AbstractSino-Tibetan is the most prominent language family in East Asia. Previous genetic studies mainly focused on the Tibetan and Han Chinese populations. However, due to the sparse sampling, the genetic structure and admixture history of Tibeto-Burman-speaking populations in the low-altitude region of Southwest China still need to be clarified. We collected DNA from 157 individuals from four Tibeto-Burman-speaking groups from the Guizhou province in Southwest China. We genotyped the samples at about 700,000 genome-wide single nucleotide polymorphisms. Our results indicate that the genetic variation of the four Tibeto-Burman-speaking groups in Guizhou is at the intermediate position in the modern Tibetan-Tai-Kadai/Austronesian genetic cline. This suggests that the formation of Tibetan-Burman groups involved a large-scale gene flow from lowland southern Chinese. The southern ancestry could be further modelled as deriving from Vietnam’s Late Neolithic-related inland Southeast Asia agricultural populations and Taiwan’s Iron Age-related coastal rice-farming populations. Compared to the Tibeto-Burman speakers in the Tibetan-Yi Corridor reported previously, the Tibeto-Burman groups in the Guizhou region received additional gene flow from the southeast coastal area of China. We show a difference between the genetic profiles of the Tibeto-Burman speakers of the Tibetan-Yi Corridor and the Guizhou province. Vast mountain ranges and rivers in Southwest China may have decelerated the westward expansion of the southeast coastal East Asians. Our results demonstrate the complex genetic profile in the Guizhou region in Southwest China and support the multiple waves of human migration in the southern area of East Asia.
Cingulate white matter mediates the effects of fecal Ruminococcus on neuropsychiatric symptoms in patients with amyloid-positive amnestic mild cognitive impairment
Authors: Hung Chun-Che , Chao Yi-Ping , Lee Yejin , Huang Chi-Wei , Huang Shu-Hua , Chang Chiung-Chih , Cheng Chia-Hsiung 
Published: November 2023

Abstract
Background
Microbiota-gut-brain axis interacts with one another to regulate brain functions. However, whether the impacts of gut dysbiosis on limbic white matter (WM) tracts contribute to the neuropsychiatric symptoms (NPS) in patients with amyloid-positive amnestic mild cognitive impairment (aMCI+), have not been explored yet. This study aimed to investigate the mediation effects of limbic WM integrity on the association between gut microbiota and NPS in patients with aMCI+.

Methods
Twenty patients with aMCI + and 20 healthy controls (HCs) were enrolled. All subjects underwent neuropsychological assessments and their microbial compositions were characterized using 16S rRNA Miseq sequencing technique. Amyloid deposition inspected by positron emission tomography imaging and limbic WM tracts (i.e., fornix, cingulum, and uncinate fasciculus) detected by diffusion tensor imaging were additionally measured in patients with aMCI+. We employed a regression-based mediation analysis using Hayes’s PROCESS macro in this study.

Results
The relative abundance of genera Ruminococcus and Lactococcus was significantly decreased in patients with aMCI + versus HCs. The relative abundance of Ruminococcus was negatively correlated with affective symptom cluster in the aMCI + group. Notably, this association was mediated by WM integrity of the left cingulate gyrus.

Conclusions
Our findings suggest Ruminococcus as a potential target for the management of affective impairments in patients with aMCI+.
Delayed diagnosis of Lemierre’s syndrome in a patient with severe coronavirus disease 2019: importance of comprehensive oral and neck examination – a case report
Authors: Miura Tomotaka , Fukuda Hirotsugu , Kawada Hiroshi , Kaga Tetsuro , Matsuo Masayuki , Sakai Tsutomu , Yoshida Shozo , Okada Hideshi , Ogura Shinji , Tetsuka Nobuyuki 
Published: November 2023

Abstract
Background
Given the widespread prevalence of the coronavirus disease 2019 (COVID-19), oral and neck examinations tend to be avoided in patients with suspected or confirmed COVID-19. This might delay the diagnosis of conditions such as Lemierre’s syndrome, which involves symptoms resembling COVID-19-related throat manifestations.

Case presentation
A 24-year-old man without any underlying conditions was diagnosed with COVID-19 7 days before presentation. He was admitted to another hospital 1 day before presentation with severe COVID-19 and suspected bacterial pneumonia; accordingly, he was started on treatment with remdesivir and meropenem. Owing to bacteremic complications, the patient was transferred to our hospital for intensive care. On the sixth day, the patient experienced hemoptysis; further, a computed tomography (CT) scan revealed new pulmonary artery pseudoaneurysms. Successful embolization was performed to achieve hemostasis. In blood cultures conducted at the previous hospital, Fusobacterium nucleatum was isolated, suggesting a cervical origin of the infection. A neck CT scan confirmed a peritonsillar abscess and left internal jugular vein thrombus; accordingly, he was diagnosed with Lemierre’s syndrome. The treatment was switched to ampicillin/sulbactam, based on the drug susceptibility results. After 6 weeks of treatment, the patient completely recovered without complications.

Conclusion
This case highlights the significance of thorough oral and neck examinations in patients with suspected or diagnosed COVID-19 for the detection of throat and neck symptoms caused by other conditions.
Prediction of subsolid pulmonary nodule growth rate using radiomics
Authors: Ma Zong Jing , Ma Zhuang Xuan , Sun Ying Li , Li De Chun , Jin Liang , Gao Pan , Li Cheng , Li Ming 
Published: November 2023

Abstract
Background
Pulmonary nodule growth rate assessment is critical in the management of subsolid pulmonary nodules (SSNs) during clinical follow-up. The present study aimed to develop a model to predict the growth rate of SSNs.

Methods
A total of 273 growing SSNs with clinical information and 857 computed tomography (CT) scans were retrospectively analyzed. The images were randomly divided into training and validation sets. All images were categorized into fast-growth (volume doubling time (VDT) ≤ 400 days) and slow-growth (VDT > 400 days) groups. Models for predicting the growth rate of SSNs were developed using radiomics and clinical features. The models’ performance was evaluated using the area under the curve (AUC) values for the receiver operating characteristic curve.

Results
The fast- and slow-growth groups included 108 and 749 scans, respectively, and 10 radiomics features and three radiographic features (nodule density, presence of spiculation, and presence of vascular changes) were selected to predict the growth rate of SSNs. The nomogram integrating radiomics and radiographic features (AUC = 0.928 and AUC = 0.905, respectively) performed better than the radiographic (AUC = 0.668 and AUC = 0.689, respectively) and radiomics (AUC = 0.888 and AUC = 0.816, respectively) models alone in both the training and validation sets.

Conclusion
The nomogram model developed by combining radiomics with radiographic features can predict the growth rate of SSNs more accurately than traditional radiographic models. It can also optimize clinical treatment decisions for patients with SSNs and improve their long-term management.
Glomerular lipidosis as a feature of renal-limited macrophage activation syndrome in a transplanted kidney: a case report
Authors: Sugisaki Kentaro , Uchida Takahiro , Iwama Sachiko , Okihara Masaaki , Akashi Isao , Kihara Yu , Konno Osamu , Kuroda Masayuki , Koike Junki , Iwamoto Hitoshi , Oda Takashi 
Published: November 2023

Abstract
Background
Glomerular lipidosis is a rare histological feature presenting the extensive glomerular accumulation of lipids with or without histiocytic infiltration, which develops under various conditions. Among its various etiologies, macrophage activation syndrome (MAS) is a condition reported to be associated with histiocytic glomerular lipidosis. Here we describe the first case of glomerular lipidosis observed in a renal allograft that histologically mimicked histiocytic glomerulopathy owing to MAS.

Case presentation
A 42-year-old man underwent successful living-donor kidney transplantation. However, middle-grade proteinuria and increased serum triglyceride levels indicative of type V hyperlipidemia developed rapidly thereafter. An allograft biopsy performed 6 months after the transplantation showed extensive glomerular infiltration of CD68+ foam cells (histiocytes) intermingled with many CD3+ T-cells (predominantly CD8+ cells). Furthermore, frequent contact between glomerular T-cells and histiocytes, and the existence of activated CD8+ cells (CD8+, HLA-DR+ cells) were observed by double immunostaining. There was no clinicopathological data suggesting lipoprotein glomerulopathy or lecithin cholesterol acyltransferase deficiency, both of which are well-known causes of glomerular lipidosis. The histological findings were relatively similar to those of histiocytic glomerulopathy caused by MAS. As systemic manifestations of MAS, such as fever, pancytopenia, coagulation abnormalities, hyperferritinemia, increased liver enzyme levels, hepatosplenomegaly, and lymphadenopathy were minimal, this patient was clinicopathologically diagnosed as having renal-limited MAS. Although optimal treatment strategies for MAS in kidney transplant patients remains unclear, we strengthened lipid-lowering therapy using pemafibrate, without modifying the amount of immunosuppressants. Serum triglyceride levels were normalized with this treatment; however, the patient’s extensive proteinuria and renal dysfunction did not improve. Biopsy analysis at 1 year after the transplantation demonstrated the disappearance of glomerular foamy changes, but the number of glomerular infiltrating cells remained similar.

Conclusion
To our knowledge, this is the first reported case of glomerular lipidosis in a transplanted kidney. Increased interaction-activation of histiocytes (macrophages) and CD8+ T-cells, the key pathogenic feature of MAS, was observed in the glomeruli of this patient, who did not demonstrate overt systemic manifestations, suggesting a pathological condition of renal-limited MAS. The clinical effects of triglyceride-lowering therapy were limited, suggesting that hypertriglyceridemia was not the cause of but rather may be a consequence of renal-limited MAS.
Trajectories of immune-related serum proteins and quality of life in patients with pancreatic and other periampullary cancer: the CHAMP study
Authors: Hau Sofie Olsson , Svensson Maja , Petersson Alexandra , Eberhard Jakob , Jirström Karin 
Published: November 2023

AbstractBackgroundThere is still a profound lack of efficient therapeutic strategies against pancreatic and other periampullary adenocarcinoma. Surgery is seldom possible, leaving palliative chemotherapy the only option for most patients. Chemotherapy treatment is however often accompanied by serious side-effects, and the identification of biomarkers for early prediction of disease and treatment-associated symptoms could help alleviate patient suffering. This study investigated the dynamic interrelationship between immune-related serum proteins, routine biomarkers, and health-related quality of life (HRQoL) factors during chemotherapy treatment of patients enrolled in the prospective, observational study Chemotherapy, Host response And Molecular dynamics in Periampullary cancer (CHAMP).MethodsProximity extension assay was applied to analyse 92 immune-associated proteins in longitudinal serum samples from 75 patients, 18 treated with curative and 57 with palliative intent. HRQoL data were available from all patients at baseline (BL), from 41 patients at three months, and from 23 patients at six months. Information on routine laboratory parameters albumin, CA19-9, CEA and CRP were collected from medical charts.ResultsIn total nine proteins; chemokine (C–C motif) ligand 23 (CCL23), cluster of differentiation 4 (CD4), cluster of differentiation 28 (CD28), decorin (DCN), galectin-1 (Gal-1), granzyme B (GZMB), granzyme H (GZMH), matrix metallopeptidase 7 (MMP7), and monocyte chemotactic protein-1 (MCP-1) were strongly correlated (Spearman’s Rho ≤ -0.6 or ≥ 0.6) with either cognitive functioning (DCN), emotional functioning (DCN, MCP-1), dyspnoea (CD28, GZMB, GZMH) or insomnia (CCL23, CD4, Gal-1, MMP7) during treatment. Associations between routine laboratory parameters (CA 19–9, CA-125, CRP, CEA and albumin) and HRQoL factors were overall weaker. None of the investigated proteins were associated with pain.ConclusionsThis is, to our knowledge, the first study exploring associations between serum biomarkers and HRQoL in patients with pancreatic or other periampullary cancer, and some findings merit further validation. The associations of DCN and MCP-1with impaired cognitive and/or emotional functioning are of particular interest, given their established link to various neurodegenerative conditions. Chemotherapy is known to cause persistent cognitive dysfunction with effects on memory and executive function, referred to as “chemo brain”. It would therefore be of great value to identify biomarkers for early detection and management of this debilitating condition.Trial registrationClinical Trial Registration: NCT03724994.
Measurement of the apical anatomy of immature maxillary central incisors using cone-beam computed tomography
Authors: Wang Linlin , Qin Xiurong , Pang Yongzhi , Ma Yuxin , Fan Mingru , Tian Hongsheng 
Published: November 2023

Abstract
Objective
To investigate the CBCT findings of the apical anatomy of immature maxillary central incisors.

Methods
CBCT images of 100 immature maxillary central incisors in Nolla 8 and 100 immature maxillary central incisors in Nolla 9 were collected. The mesiodistal and carniocaudal diameters of the apical foramen of immature maxillary central incisors were measured by software included with CBCT, as well as the mesiodistal, carniocaudal and facioligual diameters of the apical shadow. The apical shadow and apical foramen diameters were compared between Nolla 8 and Nolla 9. Data were analyzed using the MedCalc software package.

Results
For immature maxillary central incisors, the mesiodistal and facioligual diameters of the apical foramen were 2.75±0.68 mm and 3.28±0.74 mm in Nolla 8 and 1.50±0.51 mm and 1.92±0.79 mm in Nolla 9. The mesiodistal, facioligual and carniocaudal diameters of the apical shadow were 3.84±0.73 mm, 4.49±0.68 mm and 3.41±1.27 mm in Nolla 8 and 2.76±0.60 mm, 3.41±0.80 mm and 2.06±0.65 mm in Nolla 9, respectively.

Conclusions
The immature maxillary central incisors in Nolla 8 have a larger apical shadow and apical foramen than those in Nolla 9. The apical region of the maxillary central incisors in Nolla 8 was more likely to have a broad, blurred lamina dura. With the development of the apical foramen, the lamina dura in the apical region tended to be clear and sharp.

Clinical significance
To our knowledge, this is the first study to radiologically analyse the in vivo anatomy of the apical foramen and apical shadow of immature maxillary central incisors. The results of this study provide a more detailed understanding of the apical anatomy of the immature maxillary central incisor for the diagnosis and treatment of apical lesions.