bluuebunny/crossref_metadata_2025 huggingface dataset:
A tri-specific killer engager against mesothelin targets NK cells towards lung cancer
Authors: Kennedy Philippa R. , Vallera Daniel A. , Ettestad Brianna , Hallstrom Caroline , Kodal Behiye , Todhunter Deborah A. , Bendzick Laura , Hinderlie Peter , Walker Joshua T. , Pulkrabek Brittany , Pastan Ira , Kratzke Robert A. , Fujioka Naomi , Miller Jeffrey S. , Felices Martin
Published: February 2023

New treatments are required to enhance current therapies for lung cancer. Mesothelin is a surface protein overexpressed in non-small cell lung cancer (NSCLC) that shows promise as an immunotherapeutic target in phase I clinical trials. However, the immunosuppressive environment in NSCLC may limit efficacy of these therapies. We applied time-of-flight mass cytometry to examine the state of circulating mononuclear cells in fourteen patients undergoing treatment for unresectable lung cancer. Six patients had earlier stage NSCLC (I-IVA) and eight had highly advanced NSCLC (IVB). The advanced NSCLC patients relapsed with greater frequency than the earlier stage patients. Before treatment, patients with very advanced NSCLC had a greater proportion of CD14- myeloid cells than patients with earlier NSCLC. These patients also had fewer circulating natural killer (NK) cells bearing an Fc receptor, CD16, which is crucial to antibody-dependent cellular cytotoxicity. We designed a high affinity tri-specific killer engager (TriKE®) to enhance NK cytotoxicity against mesothelin+ targets in this environment. The TriKE consisted of CD16 and mesothelin binding elements linked together by IL-15. TriKE enhanced proliferation of lung cancer patient NK cells in vitro. Lung cancer lines are refractory to NK cell killing, but the TriKE enhanced cytotoxicity and cytokine production by patient NK cells when challenged with tumor. Importantly, TriKE triggered NK cell responses from patients at all stages of disease and treatment, suggesting TriKE can enhance current therapies. These pre-clinical studies suggest mesothelin-targeted TriKE has the potential to overcome the immunosuppressive environment of NSCLC to treat disease.
Prognostic value of the immunohistochemical score based on four markers in head and neck squamous cell carcinoma
Authors: Xu Qing-Qing , Li Qing-Jie , Xu Zhen , Lan Li-Long , Hou Zan , Liu Juan , Lu LiXia , Chen Yuan-Yuan , Chen Run-Zhe , Wen Xin
Published: February 2023

Purpose

Head and neck squamous cell carcinoma (HNSCC) ranks sixth among all cancers globally regarding morbidity, and it has a poor prognosis, high mortality, and highly aggressive properties. In this study, we established a model for predicting prognosis based on immunohistochemical (IHC) scores.

Methods

Data on 402 HNSCC cases were collected, the glmnet Cox proportional hazards model was used, risk factors were analyzed for predicting the prognosis of survival, and the IHC score was established. We used the IHC score to predict disease-free survival (DFS) using training and independent validation cohorts, including 264 cases in total. Additionally, the accuracy of the IHC score and the TNM system (8th edition) was compared. A DFS prediction nomogram was established by combining the prognostic factors.

Results

The IHC scores included CK, Ki-67, p16, and p40 staining intensity. The concordance index and the Kaplan-Meier survival analysis showed that the IHC scores had high predictive power for HNSCC. Our results showed that the IHC score is an independent factor that can predict prognosis in a multivariate Cox regression analysis. When predicting DFS, the IHC score had a significantly higher value for the area under the ROC curve (AUC) than that of the TNM system. A nomogram was established and included the IHC score, age, tumor location, and the TNM stage. The calibration curves exhibited high consistency between the prognosis predicted by our nomogram and the actual prognosis.

Conclusions

The IHC score was more accurate than the eighth edition of the TNM system in predicting HNSCC prognosis. Therefore, combining the two methods can facilitate individualized patient consultation and care.
Salivary IgA subtypes as novel disease biomarkers in systemic lupus erythematosus
Authors: Romero-Ramírez Sandra , Sosa-Hernández Víctor A. , Cervantes-Díaz Rodrigo , Carrillo-Vázquez Daniel A. , Meza-Sánchez David E. , Núñez-Álvarez Carlos , Torres-Ruiz Jiram , Gómez-Martín Diana , Maravillas-Montero José L.
Published: February 2023

Introduction

Immunoglobulin A (IgA) is the main antibody isotype in body fluids such as tears, intestinal mucous, colostrum, and saliva. There are two subtypes of IgA in humans: IgA1, mainly present in blood and mucosal sites, and IgA2, preferentially expressed in mucosal sites like the colon. In clinical practice, immunoglobulins are typically measured in venous or capillary blood; however, alternative samples, including saliva, are now being considered, given their non-invasive and easy collection nature. Several autoimmune diseases have been related to diverse abnormalities in oral mucosal immunity, such as rheumatoid arthritis, Sjogren’s syndrome, and systemic lupus erythematosus (SLE).

Methods

We decided to evaluate the levels of both IgA subtypes in the saliva of SLE patients. A light chain capture-based ELISA measured specific IgA1 and IgA2 levels in a cohort of SLE patients compared with age and gender-matched healthy volunteers.

Results

Surprisingly, our results indicated that in the saliva of SLE patients, total IgA and IgA1 subtype were significantly elevated; we also found that salivary IgA levels, particularly IgA2, positively correlate with anti-dsDNA IgG antibody titers. Strikingly, we also detected the presence of salivary anti-nucleosome IgA antibodies in SLE patients, a feature not previously reported elsewhere.

Conclusions

According to our results and upon necessary validation, IgA characterization in saliva could represent a potentially helpful tool in the clinical care of SLE patients with the advantage of being a more straightforward, faster, and safer method than manipulating blood samples.
Identification and validation of immune and oxidative stress-related diagnostic markers for diabetic nephropathy by WGCNA and machine learning
Authors: Xu Mingming , Zhou Hang , Hu Ping , Pan Yang , Wang Shangren , Liu Li , Liu Xiaoqiang
Published: February 2023

Background

Diabetic nephropathy (DN) is the primary cause of end-stage renal disease, but existing therapeutics are limited. Therefore, novel molecular pathways that contribute to DN therapy and diagnostics are urgently needed.

Methods

Based on the Gene Expression Omnibus (GEO) database and Limma R package, we identified differentially expressed genes of DN and downloaded oxidative stress-related genes based on the Genecard database. Then, immune and oxidative stress-related hub genes were screened by combined WGCNA, machine learning, and protein-protein interaction (PPI) networks and validated by external validation sets. We conducted ROC analysis to assess the diagnostic efficacy of hub genes. The correlation of hub genes with clinical characteristics was analyzed by the Nephroseq v5 database. To understand the cellular clustering of hub genes in DN, we performed single nucleus RNA sequencing through the KIT database.

Results

Ultimately, we screened three hub genes, namely CD36, ITGB2, and SLC1A3, which were all up-regulated. According to ROC analysis, all three demonstrated excellent diagnostic efficacy. Correlation analysis revealed that the expression of hub genes was significantly correlated with the deterioration of renal function, and the results of single nucleus RNA sequencing showed that hub genes were mainly clustered in endothelial cells and leukocyte clusters.

Conclusion

By combining three machine learning algorithms with WGCNA analysis, this research identified three hub genes that could serve as novel targets for the diagnosis and therapy of DN.
"Open Sesame" to the complexity of pattern recognition receptors of myeloid-derived suppressor cells in cancer
Authors: Wang Tian , Hu Yushu , Dusi Silvia , Qi Fang , Sartoris Silvia , Ugel Stefano , De Sanctis Francesco
Published: February 2023

Pattern recognition receptors are primitive sensors that arouse a preconfigured immune response to broad stimuli, including nonself pathogen-associated and autologous damage-associated molecular pattern molecules. These receptors are mainly expressed by innate myeloid cells, including granulocytes, monocytes, macrophages, and dendritic cells. Recent investigations have revealed new insights into these receptors as key players not only in triggering inflammation processes against pathogen invasion but also in mediating immune suppression in specific pathological states, including cancer. Myeloid-derived suppressor cells are preferentially expanded in many pathological conditions. This heterogeneous cell population includes immunosuppressive myeloid cells that are thought to be associated with poor prognosis and impaired response to immune therapies in various cancers. Identification of pattern recognition receptors and their ligands increases the understanding of immune-activating and immune-suppressive myeloid cell functions and sheds light on myeloid-derived suppressor cell differences from cognate granulocytes and monocytes in healthy conditions. This review summarizes the different expression, ligand recognition, signaling pathways, and cancer relations and identifies Toll-like receptors as potential new targets on myeloid-derived suppressor cells in cancer, which might help us to decipher the instruction codes for reverting suppressive myeloid cells toward an antitumor phenotype.
Autoimmune pancreatitis: A bibliometric analysis from 2002 to 2022
Authors: Zhang Xian-Da , Zhang Yao , Zhao Yi-Zhou , Zhou Chun-Hua , Zou Duo-Wu
Published: February 2023

Background/Objectives

Autoimmune pancreatitis (AIP) is a distinct form of pancreatic inflammatory disease that responds well to glucocorticoid therapy. Knowledge on AIP has rapidly evolved over the past two decades. Based on bibliometric analysis, this study aimed to assess the research status of AIP over the past two decades and determine the research focus and emerging topics.

Methods

AIP-related publications published between January 1, 2002, and June 6, 2022, were retrieved from the Web of Science Core Collection. Bibliometric data were analyzed using HisCite, VOSviewer, CiteSpace, and bibliometrix package. Annual output, leading countries/regions, active institutions and authors, core journals and references, and keywords of AIP were evaluated.

Results

Overall, 1,772 publications were retrieved from 501 journals by 6,767 authors from 63 countries/regions. Japan published articles on AIP the most (n=728, 41.1%), followed by the United States (n=336, 19%), Germany (n=147, 8.3%), China (n=127, 7%), and Italy (n=107, 6%). The top three most prolific authors were Terumi Kamisawa from Tokyo Metropolitan Komagome Hospital (n=117), Kazuichi Okazaki from Kansai Medical University (n=103), and Shigeyuki Kawa from Matsumoto Dental University (n=94). Pancreas was the most productive journal regarding AIP research (n=95), followed by the Journal of Gastroenterology (n=67), Internal Medicine (n=66), Pancreatology (n=63), and World Journal of Gastroenterology (n=62). “Diagnosis” was the most mentioned keyword. “Risk,” “malignancy,” “outcome,” “22-gauge needle,” and “fine-needle aspiration” were recognized as emerging topics.

Conclusion

Japan was the leading country in AIP research. Research papers were mainly published in specialized journals. Diagnosis was the research focus. Long-term outcomes and pancreatic tissue acquisition were recognized as research frontiers for AIP.
Site fidelity and population parameters of pantropical spotted dolphins in the Eastern Caribbean through photographic identification
Authors: Courtin Baptiste , Millon Cédric , Feunteun Aurore , Safi Morjane , Duporge Nathalie , Bolaños-Jiménez Jaime , Barragán-Barrera Dalia C. , Bouveret Laurent , de Montgolfier Benjamin
Published: February 2023

The Agoa protected marine area, located in the French West Indies, eastern Caribbean, holds several cetacean species, of which the pantropical spotted dolphinStenella attenuatais the most commonly observed. This species is the focus of whale-watching activities off the leeward coasts of Guadeloupe and Martinique, which has allowed the development of a citizen science program to characterize individuals through the collection of photographic data. Here, we conducted a photo-identification study with a sample of 115,705 photos collected between 2014 and 2019, in which 290 marked individuals (179 in Guadeloupe and 111 in Martinique) were identified. Based on an Agglomerative Hierarchical Classification (AHC) analysis, dolphins from each island were separated into two residency clusters. The Catch–Mark–Release (CMR) POPAN statistical model for open populations estimated the pantropical spotted dolphin populations in Guadeloupe and Martinique at 657 (95% CI: 525–821) and 336 (95% CI: 253–446) individuals for frequent users, respectively, while occasional visitors were estimated at 3,063 (95% CI: 2,133–4,398) and 1,443 (95% CI: 1,024–2,033), respectively. The Martinique population tended to use a reduced coastal area and appeared to be smaller and stable, while the Guadeloupe population showed a slight decline in abundance throughout the study period. These results showed that the leeward coasts of Guadeloupe and Martinique are of particular importance for pantropical spotted dolphin populations, highlighting the need for continued monitoring through both scientific and citizen science programs to fill information gaps on this species in the eastern Caribbean.
On the impingement of heat transfer using swirled air jets
Authors: Kotb Ashraf , Askar Hamada , Saad Hany
Published: February 2023

Experimental analyses were conducted under identical experimental conditions on the heat transfer between a constant heat flux flat plate and a round air jet for both conventional and swirled jets. Vane-type swirl generators inserted at the nozzle exit were used to produce a swirl. The experimental measurements were performed at a fixed Reynolds number value (Re = 23,000) calculated on the jet tube’s inside diameter. A comparison between conventional air jets and swirl jets with swirl numbers of S = 0, 0.19, 0.42, and 0.72 was presented for the different nozzle-to-plate spacings Z/D = 2, 6, and 10. The results show that heat transfer to the plate decreases when the nozzle-to-plate distance increases. In addition, increasing the swirl number S increases heat transfer uniformity but decreases global heat transfer. At the low plate-to-jet distance Z/D = 2, the point of maximum heat transfer is shifted to a radial position depending on the swirl number. Also, for both Z/D = 6 and 10, the stagnation point and stagnation region heat-transfer enhances only for swirl numbers 0 and 0.19.
Patients’ experiences with virtual group gut-directed hypnotherapy: A qualitative study
Authors: Gerson Jessica , Tawde Prianca , Ghiasian Ghoncheh , Salwen-Deremer Jessica K.
Published: February 2023

Background

Hypnotherapy is a useful treatment for a variety of gastrointestinal conditions. While there is strong evidence for delivering other treatments virtually and in groups, there is no research thus far on delivering hypnotherapy in this format. Given the growth of both psychogastroenterology and telehealth, these methods should be explored as they have great potential for increasing access and cost-effectiveness of intervention.

Aims

This qualitative study was developed to help understand patients experiences in virtual, group-based, gut-directed hypnotherapy (GDH) in two different institutions.

Methods

Authors developed a qualitative interview with the assistance of two patient partners and then recruited patients from New York University and Dartmouth Health to participate. Interviews were completed one-on-one with patients who started and then completed GDH (≥5 visits) and who did not complete GDH (≤3 visits). Data were coded and then analyzed using thematic analysis.

Results

Twenty-one patients from NYU and Dartmouth participated in qualitative interviews. Broadly, patients reported coming to GDH because they believed in the importance of the mind-body connection or were desperate for treatment. Regardless of why patients came to GDH, they generally reported positive outcomes for GI symptoms and for other physical and mental health conditions. Most patients appreciated the group and virtual formats, though some concerns about inflexible schedules and lack of anonymity were voiced. Despite these concerns, there was broad support for virtual, group-based GDH and general excitement for behavioral health programming.

Conclusion

Virtual, group-based GDH is an acceptable treatment for patients from rural and urban settings. Given the possible improvements in access and cost-effectiveness that this treatment modality can provide, GI practices may want to consider it in lieu of or in addition to the traditional one-on-one treatment format. Barriers and facilitators and recommendations for practice are discussed.
Staphylococcus aureus ST1 promotes persistent urinary tract infection by highly expressing the urease
Authors: Xu Kai , Wang Yanan , Jian Ying , Chen Tianchi , Liu Qian , Wang Hua , Li Min , He Lei
Published: February 2023

Staphylococcus aureus (SA) is a relatively uncommon cause of urinary tract infections (UTIs) in the general population. Although rare, S. aureus-induced UTIs are prone to potentially life-threatening invasive infections such as bacteremia. To investigate the molecular epidemiology, phenotypic characteristics, and pathophysiology of S. aureus-induced UTIs, we analyzed non-repetitive 4,405 S. aureus isolates collected from various clinical sources from 2008 to 2020 from a general hospital in Shanghai, China. Among these, 193 isolates (4.38%) were cultivated from the midstream urine specimens. Epidemiological analysis showed UTI-derived ST1 (UTI-ST1) and UTI-ST5 are the primary sequence types of UTI-SA. Furthermore, we randomly selected 10 isolates from each of the UTI-ST1, non-UTI-ST1 (nUTI-ST1), and UTI-ST5 groups to characterize their in vitro and in vivo phenotypes. The in vitro phenotypic assays revealed that UTI-ST1 exhibits an obvious decline in hemolysis of human red blood cells and increased biofilm and adhesion in the urea-supplemented medium, compared to the medium without urea, while UTI-ST5 and nUTI-ST1 did not show significant differences between the biofilm-forming and adhesion abilities. In addition, the UTI-ST1 displayed intense urease activities by highly expressing urease genes, indicating the potential role of urease in UTI-ST1 survival and persistence. Furthermore, in vitro virulence assays using the UTI-ST1 ureC mutant showed no significant difference in the hemolytic and biofilm-forming phenotypes in the presence or absence of urea in the tryptic soy broth (TSB) medium. The in vivo UTI model also showed that the CFU of the UTI-ST1 ureC mutant rapidly reduced during UTI pathogenesis 72 h post-infection, while UTI-ST1 and UTI-ST5 persisted in the urine of the infected mice. Furthermore, the phenotypes and the urease expression of UTI-ST1 were found to be potentially regulated by the Agr system with the change in environmental pH. In summary, our results provide important insights into the role of urease in S. aureus-induced UTI pathogenesis in promoting bacterial persistence in the nutrient-limiting urinary microenvironment.
Composition and biodiversity of soil and root-associated microbiome in Vitis vinifera cultivar Lambrusco distinguish the microbial terroir of the Lambrusco DOC protected designation of origin area on a local scale
Authors: Nanetti Enrico , Palladino Giorgia , Scicchitano Daniel , Trapella Giulia , Cinti Nicolò , Fabbrini Marco , Cozzi Alice , Accetta Giovanni , Tassini Carlo , Iannaccone Luigi , Candela Marco , Rampelli Simone
Published: February 2023

Introduction

Wines produced from the same grape cultivars but in different locations possess distinctive qualities leading to different consumer’s appreciation, preferences, and thus purchase choices. Here, we explore the possible importance of microbiomes at the soil–plant interface as a determinant of the terroir properties in grapevine production, which confer specific growth performances and wine chemo-sensory properties at the local scale.

Methods

In particular, we investigated the variation in microbial communities associated with the roots of Vitis vinifera cultivar Lambrusco, as well as with surrounding bulk soils, in different vineyards across the “Consorzio Tutela Lambrusco DOC” protected designation of origin area (PDO, Emilia Romagna, Italy), considering viticultural sites located both inside and outside the consortium in two different seasons (June and November 2021).

Results

According to our findings, rhizospheric and soil microbiomes show significant structural differences in relation to the sampling site, regardless of seasonality, while endophytic microbiomes seem to be completely unaffected by such variables. Furthermore, a deeper insight into the microbial terroir of PDO areas highlighted the presence of some rhizospheric microorganisms enriched inside the consortium and characterizing the PDO regardless of both sampling season and farming strategy. These include Bacillus, Paenibacillus, and Azospirillum, which are all well-known plant growth-promoting bacteria.

Discussion

Taken together, our results suggest a connection between soil and root microbiomes of V. vinifera cultivar Lambrusco and the local designation of origin, emphasizing the potential role of PDO-enriched plant growth-promoting bacteria in vine growing and final quality of the Lambrusco DOC wine.
Dynamics of soil microbiome throughout the cultivation life cycle of morel (Morchella sextelata)
Authors: Zhang Chen , Shi Xiaofei , Zhang Jiexiong , Zhang Yesheng , Wang Wen
Published: February 2023

Although Morchella sextelata (morel) is a well-known, edible, and medicinal fungus widely cultivated in China, the dynamics and roles of its soil microbiome during cultivation are unclear. Using rhizosphere soil samples collected throughout the M. sextelata cultivation life cycle, we conducted a high-throughput metagenomic sequencing analysis, with an emphasis on variations in soil microbial composition, characteristic biomarkers, and ecological functions. We found that microbial relative abundance, alpha diversity, and structure varied significantly among fungal growth stages. A total of 47 stage-associated biomarkers were identified through a linear discriminant analysis of effect size. In addition, horizontal comparison of soil microbiomes exhibiting successful and failed primordium formation further confirmed primordium-associated microbes with possible key roles in primordium formation. A microbial function analysis revealed that nutrient metabolism-related pathways were enriched during mycelium and fruiting body stages, whereas the signal transduction pathway was enriched during the primordium stage. This result indicates that diverse microbes are required at different growth stages of M. sextelata. Our research has revealed the dynamic scenario of the soil microbiome throughout the cultivation life cycle of M. sextelata. The high-resolution microbial profiles uncovered in the present study provide novel insights that should contribute to the improvement of morel cultivation using microbial inoculants.
Using the Jurkat reporter T cell line for evaluating the functionality of novel chimeric antigen receptors
Authors: Jahan Farhana , Koski Jan , Schenkwein Diana , Ylä-Herttuala Seppo , Göös Helka , Huuskonen Sini , Varjosalo Markku , Maliniemi Pilvi , Leitner Judith , Steinberger Peter , Bühring Hans-Jörg , Vettenranta Kim , Korhonen Matti
Published: February 2023

Background: T cells that are genetically modified with chimeric antigen receptor (CAR) hold promise for immunotherapy of cancer. Currently, there are intense efforts to improve the safety and efficacy of CAR T cell therapies against liquid and solid tumors. Earlier we designed a novel CAR backbone (FiCAR) where the spacer is derived from immunoglobulin (Ig) -like domains of the signal-regulatory protein alpha (SIRPα). However, the analysis of novel CAR using primary T cells is slow and laborious.

Methods: To explore the versatility of the CAR backbone, we designed a set of variant FiCARs with different spacer lengths and targeting antigens. To expedite the analysis of the novel CARs, we transduced the FiCAR genes using lentiviruses into Jurkat reporter T cells carrying fluorescent reporter genes. The expression of fluorescent markers in response to FiCAR engagement with targets was analyzed by flow cytometry, and cytotoxicity was evaluated using killing assays. Furthermore, the killing mechanisms that are employed by FiCAR-equipped Jurkat T cells were investigated by flow cytometry, and the intracellular pathways involved in signaling by FiCAR were analyzed by phosphoproteomic analysis using mass spectrometry.

Results: Seven different CARs were designed and transduced into Jurkat reporter cells. We show that the SIRPα derived FiCARs can be detected by flow cytometry using the SE12B6A4 antibody recognizing SIRPα. Furthermore, FiCAR engagement leads to robust activation of NFκβ and NFAT signaling, as demonstrated by the expression of the fluorescent reporter genes. Interestingly, the Jurkat reporter system also revealed tonic signaling by a HER-2 targeting FiCAR. FiCAR-equipped Jurkat T cells were cytotoxic in cocultures with target cells and target cell engagement lead to an upregulation of CD107a on the Jurkat reporter T cell surface. Phosphoproteomic analyses confirmed signal transduction via the intracellular CD28/CD3ζ sequences upon the interaction of the FiCAR1 with its antigen. In addition, downstream signaling of CD3ζ/ZAP70- SLP-76-PLCγ, PI3K–AKT–NFκB pathways and activation of NFAT and AP-1 were observed.

Conclusion: We conclude that the FiCAR backbone can be shortened and lengthened at will by engineering it with one to three SIRPα derived Ig-like domains, and the FiCARs are functional when equipped with different single chain variable fragment target binding domains. The Jurkat reporter system expedites the analysis of novel CARs as to their expression, signaling function, evaluation of tonic signaling issues and cytotoxic activity.
Characterizing cellular membrane partitioning of DMSO using low-temperature Raman spectroscopy
Authors: Louwagie Troy , Wagner Madeline , Li Rui , Yu Guanglin , Petersen Ashley , Hubel Allison
Published: February 2023

Additives that help cells survive the stresses of freezing and thawing are known as cryoprotective agents (CPAs). Two different types of CPAs have been identified: penetrating and non-penetrating. Common penetrating CPAs include dimethylsulfoxide (DMSO) and glycerol. The location of a CPA (intracelluar or extracellular) is important for understanding the molecular mechanisms of action for the agent. Low-temperature Raman spectroscopy is a label-free method of detecting the location of CPAs at low temperature with high spatial resolution and chemical specificity. To this end, cells cryopreserved in DMSO using a variety of cooling rates and DMSO concentrations and imaged using Raman spectroscopy were analyzed using automated image analysis to determine the partitioning ratio (concentration of DMSO outside/concentration of DMSO inside the cell). The partitioning ratio was roughly 1 for Jurkat cells frozen at 1°C/min in varying concentrations of DMSO with the exception of 1% DMSO which had a partitioning ratio of 0.2. The partitioning ratio increased from 1 to 1.3 as the cooling rate increased from 1°C to 5°C/min. Different cell types, specifically sensory neurons cells and human induced pluripotent stem cells, exhibited differences in partitioning ratio when frozen in 10% DMSO and 1°C/min suggesting that differences in freezing response may result from differences in solute partitioning. The presence of intracellular ice changed the distribution of DMSO inside the cell and also the partitioning ratio.
Correlation between retinal structure and brain multimodal magnetic resonance imaging in patients with Alzheimer’s disease
Authors: Hao Xiaoli , Zhang Weiwei , Jiao Bin , Yang Qijie , Zhang Xinyue , Chen Ruiting , Wang Xin , Xiao Xuewen , Zhu Yuan , Liao Weihua , Wang Dongcui , Shen Lu
Published: February 2023

Background

The retina imaging and brain magnetic resonance imaging (MRI) can both reflect early changes in Alzheimer’s disease (AD) and may serve as potential biomarker for early diagnosis, but their correlation and the internal mechanism of retinal structural changes remain unclear. This study aimed to explore the possible correlation between retinal structure and visual pathway, brain structure, intrinsic activity changes in AD patients, as well as to build a classification model to identify AD patients.

Methods

In the study, 49 AD patients and 48 healthy controls (HCs) were enrolled. Retinal images were obtained by optical coherence tomography (OCT). Multimodal MRI sequences of all subjects were collected. Spearman correlation analysis and multiple linear regression models were used to assess the correlation between OCT parameters and multimodal MRI findings. The diagnostic value of combination of retinal imaging and brain multimodal MRI was assessed by performing a receiver operating characteristic (ROC) curve.

Results

Compared with HCs, retinal thickness and multimodal MRI findings of AD patients were significantly altered (p < 0.05). Significant correlations were presented between the fractional anisotropy (FA) value of optic tract and mean retinal thickness, macular volume, macular ganglion cell layer (GCL) thickness, inner plexiform layer (IPL) thickness in AD patients (p < 0.01). The fractional amplitude of low frequency fluctuations (fALFF) value of primary visual cortex (V1) was correlated with temporal quadrant peripapillary retinal nerve fiber layer (pRNFL) thickness (p < 0.05). The model combining thickness of GCL and temporal quadrant pRNFL, volume of hippocampus and lateral geniculate nucleus, and age showed the best performance to identify AD patients [area under the curve (AUC) = 0.936, sensitivity = 89.1%, specificity = 87.0%].

Conclusion

Our study demonstrated that retinal structure change was related to the loss of integrity of white matter fiber tracts in the visual pathway and the decreased LGN volume and functional metabolism of V1 in AD patients. Trans-synaptic axonal retrograde lesions may be the underlying mechanism. Combining retinal imaging and multimodal MRI may provide new insight into the mechanism of retinal structural changes in AD and may serve as new target for early auxiliary diagnosis of AD.
Flow diverters in the treatment of unruptured vertebral artery dissecting aneurysm: A single-center experience
Authors: Lu Xiaoyang , Zhang Yuansheng , Zhou Hu , Jian Lipeng , Yin Shi , Li Tao , Huang Wei
Published: February 2023

Objective

To evaluate the efficacy and safety of flow diverters (FD) in the treatment of vertebral artery dissecting aneurysm (VADA).

Methods

A total of 16 patients with 17 unruptured VADAs treated with FD from January 2017 to May 2021 were included. Data of clinical outcomes and radiographic examination were collected and assessed by the modified Rankin Scale (mRS) and O'Kelly-Marotta (OKM) grading scale.

Results

All patients were treated with a single FD. No perioperative complications occurred. The mean age was 55.1 years old. The mean size of the aneurysm was 10.4 mm. All patients had a favorable occlusion (OKM D + C3) result and the complete occlusion rate in the 6th month was 66.7% (OKM D). The mean clinical follow-up time was 7.8 months, and all patients had a good clinical outcome (mRS = 0). No procedure-related complication occurred at the last follow-up time.

Conclusion

FD is an effective and safe tool for treating unruptured VADA. Long-term prospective studies with a large sample are still needed to confirm these findings in the future.
The clinical and neurocognitive functional changes with awake brain mapping for gliomas invading eloquent areas: Institutional experience and the utility of The Montreal Cognitive Assessment
Authors: Wang Yuan , Guo Shaochun , Wang Na , Liu Jinghui , Chen Fan , Zhai Yulong , Wang Yue , Jiao Yang , Zhao Wenjian , Fan Chao , Xue Yanrong , Gao GuoDong , Ji Peigang , Wang Liang
Published: February 2023

Objective

Awake craniotomy with intraoperative brain functional mapping effectively reduces the potential risk of neurological deficits in patients with glioma invading the eloquent areas. However, glioma patients frequently present with impaired neurocognitive function. The present study aimed to investigate the neurocognitive and functional outcomes of glioma patients after awake brain mapping and assess the experience of a tertiary neurosurgical center in China over eight years.

Methods

This retrospective study included 80 patients who underwent awake brain mapping for gliomas invading the eloquent cortex between January 2013 and December 2021. Clinical and surgical factors, such as the extent of resection (EOR), perioperative Karnofsky Performance Score (KPS), progression-free survival (PFS), and overall survival (OS), were evaluated. We also used the Montreal Cognitive Assessment (MoCA) to assess the neurocognitive status changes.

Results

The most frequently observed location of glioma was the frontal lobe (33/80, 41.25%), whereas the tumor primarily invaded the language-related cortex (36/80, 45%). Most patients had supratotal resection (11/80, 13.75%) and total resection (45/80, 56.25%). The median PFS was 43.2 months, and the median OS was 48.9 months in our cohort. The transient (less than seven days) neurological deficit rate was 17.5%, whereas the rate of persistent deficit (lasting for three months) was 15%. At three months of follow-up, most patients (72/80, 90%) had KPS scores > 80. Meanwhile, compared to the preoperative baseline tests, the changes in MoCA scores presented significant improvements at discharge and three months follow-up tests.

Conclusion

Awake brain mapping is a feasible and safe method for treating glioma invading the eloquent cortex, with the benefit of minimizing neurological deficits, increasing EOR, and extending survival time. The results of MoCA test indicated that brain mapping plays a critical role in preserving neurocognitive function during tumor resection.
Humoral Effect of SARS-CoV-2 mRNA vaccination with booster dose in solid tumor patients with different anticancer treatments
Authors: Piubelli Chiara , Valerio Matteo , Verzè Matteo , Nicolis Fabrizio , Mantoan Carlotta , Zamboni Sonia , Perandin Francesca , Rizzi Eleonora , Tais Stefano , Degani Monica , Caldrer Sara , Gobbi Federico Giovanni , Bisoffi Zeno , Gori Stefania
Published: February 2023

Introduction

Cancer patients are at risk for serious complications in case of SARS-CoV-2 infection. In these patients SARS-CoV-2 vaccination is strongly recommended, with the preferential use of mRNA vaccines. The antibody response in cancer patients is variable, depending on the type of cancer and antitumoral treatment. In solid tumor patients an antibody response similar to healthy subjects has been confirmed after the second dose. Only few studies explored the duration of immunization after the two doses and the effect of the third dose.

Methods

In our study we explored a cohort of 273 solid tumor patients at different stages and treated with different anticancer therapies.

Results and Discussion

Our analysis demonstrated that the persistence of the neutralizing antibody and the humoral response after the booster dose of vaccine was not dependent on either the tumor type, the stage or type of anticancer treatment.
The evolving use of measurable residual disease in chronic lymphocytic leukemia clinical trials
Authors: Fisher A. , Goradia H. , Martinez-Calle N. , Patten PEM. , Munir T.
Published: February 2023

Measurable residual disease (MRD) status in chronic lymphocytic leukemia (CLL), assessed on and after treatment, correlates with increased progression-free and overall survival benefit. More recently, MRD assessment has been included in large clinical trials as a primary outcome and is increasingly used in routine practice as a prognostic tool, a therapeutic goal, and potentially a trigger for early intervention. Modern therapy for CLL delivers prolonged remissions, causing readout of traditional trial outcomes such as progression-free and overall survival to be inherently delayed. This represents a barrier for the rapid incorporation of novel drugs to the overall therapeutic armamentarium. MRD offers a dynamic and robust platform for the assessment of treatment efficacy in CLL, complementing traditional outcome measures and accelerating access to novel drugs. Here, we provide a comprehensive review of recent major clinical trials of CLL therapy, focusing on small-molecule inhibitors and monoclonal antibody combinations that have recently emerged as the standard frontline and relapse treatment options. We explore the assessment and reporting of MRD (including novel techniques) and the challenges of standardization and provide a comprehensive review of the relevance and adequacy of MRD as a clinical trial endpoint. We further discuss the impact that MRD data have on clinical decision-making and how it can influence a patient’s experience. Finally, we evaluate how upcoming trial design and clinical practice are evolving in the face of MRD-driven outcomes.
Wogonin induces ferroptosis in pancreatic cancer cells by inhibiting the Nrf2/GPX4 axis
Authors: Liu Xing , Peng Xinhui , Cen Shuai , Yang Cuiting , Ma Zhijie , Shi Xinyuan
Published: February 2023

Pancreatic cancer is a common gastrointestinal tract malignancy. Currently, the therapeutic strategies for pancreatic cancers include surgery, radiotherapy, and chemotherapy; however, the surgical procedure is invasive, and the overall curative outcomes are poor. Furthermore, pancreatic cancers are usually asymptomatic during early stages and have a high degree of malignancy, along with a high rate of recurrence and metastasis, thereby increasing the risk of mortality. Studies have shown that ferroptosis regulates cell proliferation and tumour growth and reduces drug resistance. Hence, ferroptosis could play a role in preventing and treating cancers. Wogonin is a flavonoid with anticancer activity against various cancers, including pancreatic cancer. It is extracted from the root of Scutellaria baicalensis Georgi. In this study, we show that wogonin inhibits the survival and proliferation of human pancreatic cancer cell lines and induces cell death. We performed RNA-sequencing and analysed the differentially expressed gene and potential molecular mechanism to determine if wogonin reduced cell survival via ferroptosis. Our results showed that wogonin upregulates the levels of Fe2+, lipid peroxidation and superoxide and decreases the protein expression levels of ferroptosis suppressor genes, and downregulates level of glutathione in pancreatic cancer cells. In addition, ferroptosis inhibitors rescue the ferroptosis-related events induced by wogonin, thereby confirming the role of ferroptosis. A significant increase in ferroptosis-related events was observed after treatment with both wogonin and ferroptosis inducer. These results show that wogonin could significantly reduces pancreatic cancer cell proliferation and induce ferroptosis via the Nrf2/GPX4 axis. Therefore, wogonin could be potentially used for treating patients with pancreatic cancer.
Classification molecular subtypes of hepatocellular carcinoma based on PRMT-related genes
Authors: Liu Liwen , Hu Qiuyue , Zhang Yize , Sun Xiangyi , Sun Ranran , Ren Zhigang
Published: February 2023

Background: Recent studies highlighted the functional role of protein arginine methyltransferases (PRMTs) catalyzing the methylation of protein arginine in malignant progression of various tumors. Stratification the subtypes of hepatocellular carcinoma (HCC) is fundamental for exploring effective treatment strategies. Here, we aim to conduct a comprehensive analysis of PRMTs with bioinformatic tools to identify novel biomarkers for HCC subtypes classification and prognosis prediction, which may be potential ideal targets for therapeutic intervention.

Methods: The expression profiling of PRMTs in HCC tissues was evaluated based on the data of TCGA-LIHC cohort, and further validated in HCC TMA cohort and HCC cell lines. HCC was systematically classified based on PRMT family related genes. Subsequently, the differentially expressed genes (DEGs) between molecular subtypes were identified, and prognostic risk model were constructed using least absolute shrinkage and selection operator (LASSO) and Cox regression analysis to evaluate the prognosis, gene mutation, clinical features, immunophenotype, immunotherapeutic effect and antineoplastic drug sensitivity of HCC.

Results: PRMTs expression was markedly altered both in HCC tissues and HCC cell lines. Three molecular subtypes with distinct immunophenotype were generated. 11 PRMT-related genes were enrolled to establish prognostic model, which presented with high accuracy in predicting the prognosis of two risk groups in the training, validation, and immunotherapy cohort, respectively. Additionally, the two risk groups showed significant difference in immunotherapeutic efficacy. Further, the sensitivity of 72 anticancer drugs was identified using prognostic risk model.

Conclusion: In summary, our findings stratified HCC into three subtypes based on the PRMT-related genes. The prognostic model established in this work provide novel insights into the exploration of related therapeutic approaches in treating HCC.
3.2 kW, 0.22 nm narrow-linewidth MOPA configuration fiber laser with a homemade polarization-maintaining Yb-doped fiber
Authors: Liao Shibiao , Luo Tao , Xiao Runheng , Cheng Junjie , Shu Chang , Zhang Zhilun , Zhou Yanyan , Xing Yingbin , Li Haiqing , Peng Jinggang , Dai Nengli , Li Jinyan
Published: February 2023

In this work, a narrow-linewidth linearly polarized fiber amplifier with a record output power of 3.2 kW was achieved based on a homemade polarization-maintaining Yb-doped fiber corresponding to a slope efficiency of 79% and a 3 dB linewidth of 0.2227 nm. By examining various numerical aperture (NA) PMYDFs, the experimental investigation on expanding mode instability (MI) threshold in PM fiber amplifiers was put on display. And the results reveal that the MI threshold is enhanced by more than 370 W for every 0.004 decrease in core numerical aperture. Increasing the seed linewidth from 0.0454 nm to 0.0976 nm by adding 200 m polarization maintaining Ge-doped fiber the stimulated Brillouin scattering threshold increased from 805 W to above 3.2 kW. By applying the MI suppression method, a double-eight-shaped aluminum plate was adopted to coil the gain fiber, and the MI threshold increased by more than 1100 W.
Research and application of Rayleigh wave extraction method based on microtremors signal analysis
Authors: Du Qingling , Pan Yanhui , Xin Youyang
Published: February 2023

This study investigates the method and application of single-channel, three-component microtremor signal co-directional Rayleigh surface-wave extraction. The research focuses on filtering linear polarization waves using polarizability wave and phase-difference filtering, which were analyzed based on both simulated data and real microtremor signals. Additionally, the study examines the use of time-frequency analysis to analyze microtremor signals and identify Rayleigh wave propagation direction. The combination of these methods leads to a set of procedures for extracting high-SNR co-directional Rayleigh surface waves from microtremor signals, which was applied to the elliptical polarizability imaging method. Results indicate that the proposed data processing process effectively filters linear polarization waves and accurately determines the propagation direction of the Rayleigh wave, leading to significant improvement in the accuracy of elliptical polarizability exploration results. This provides a reference for obtaining high signal-to-noise ratio data in microtremor Rayleigh wave seismic exploration.
Fungal identification in peanuts seeds through multispectral images: Technological advances to enhance sanitary quality
Authors: Sudki Julia Marconato , Fonseca de Oliveira Gustavo Roberto , de Medeiros André Dantas , Mastrangelo Thiago , Arthur Valter , Amaral da Silva Edvaldo Aparecido , Mastrangelo Clíssia Barboza
Published: February 2023

The sanitary quality of seed is essential in agriculture. This is because pathogenic fungi compromise seed physiological quality and prevent the formation of plants in the field, which causes losses to farmers. Multispectral images technologies coupled with machine learning algorithms can optimize the identification of healthy peanut seeds, greatly improving the sanitary quality. The objective was to verify whether multispectral images technologies and artificial intelligence tools are effective for discriminating pathogenic fungi in tropical peanut seeds. For this purpose, dry peanut seeds infected by fungi (A. flavus, A. niger, Penicillium sp., and Rhizopus sp.) were used to acquire images at different wavelengths (365 to 970 nm). Multispectral markers of peanut seed health quality were found. The incubation period of 216 h was the one that most contributed to discriminating healthy seeds from those containing fungi through multispectral images. Texture (Percent Run), color (CIELab L*) and reflectance (490 nm) were highly effective in discriminating the sanitary quality of peanut seeds. Machine learning algorithms (LDA, MLP, RF, and SVM) demonstrated high accuracy in autonomous detection of seed health status (90 to 100%). Thus, multispectral images coupled with machine learning algorithms are effective for screening peanut seeds with superior sanitary quality.
Combating ozone stress through N fertilization: A case study of Indian bean (Dolichos lablab L.)
Authors: Sahoo Ansuman , Madheshiya Parvati , Mishra Ashish Kumar , Tiwari Supriya
Published: February 2023

The present study investigates the efficiency of nitrogen (N) amendments in the management of ozone (O3) stress in two varieties (Kashi Sheetal and Kashi Harittima) of Indian bean (Dolichos lablabL.). Two O3concentrations, ambient (44.9 ppb) and elevated (74.64 ppb) were used, and each O3concentration has 3 nitrogen (N) dose treatments viz recommended (N1), 1.5 times recommended (N2), 2 times recommended (N3) and no nitrogen, which served as control (C). The experiment concluded Kashi Sheetal as O3tolerant, as compared to Kashi Harittima. N amendments were effective in the partial amelioration of O3stress, with N2 being the most effective nitrogen dose, at both ambient and elevated O3concentrations. Kashi Sheetal has been determined to be O3tolerant due to greater endogenous levels of H2O2accumulation and enzymatic antioxidant contents with O3exposure. The O3-sensitive variety, Kashi Harittima, responded more positively to N treatments, at both O3concentrations. The positive effect of N amendments is attributed to the stimulated antioxidative enzyme activity, rather than the biophysical processes like stomatal conductance. Strengthened defense upon N amendments was attributed to the enhanced activities of APX and GR in Kashi Sheetal, while in Kashi Harittima, the two enzymes (APX and GR) were coupled by SOD and CAT as well, during the reproductive phase. Yield (weight of seeds plant-1) increments upon N (N2) amendments were higher in Kashi Harittima (O3sensitive), as compared to Kashi Sheetal (O3tolerant) at both ambient and elevated O3concentration, due to higher antioxidant enzymatic response and greater rate of photosynthesis in the former.