bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasound-induced cavitation renders prostate cancer cells susceptible to hyperthermia: Analysis of potential cellular and molecular mechanisms
Authors: Hu Shaonan , Zhang Xinrui , Melzer Andreas , Landgraf Lisa 
Published: April 2023

Background: Focused ultrasound (FUS) has become an important non-invasive therapy for prostate tumor ablation via thermal effects in the clinic. The cavitation effect induced by FUS is applied for histotripsy, support drug delivery, and the induction of blood vessel destruction for cancer therapy. Numerous studies report that cavitation-induced sonoporation could provoke multiple anti-proliferative effects on cancer cells. Therefore, cavitation alone or in combination with thermal treatment is of great interest but research in this field is inadequate.Methods: Human prostate cancer cells (LNCap and PC-3) were exposed to 40 s cavitation using a FUS system, followed by water bath hyperthermia (HT). The clonogenic assay, WST-1 assay, and Transwell® invasion assay, respectively, were used to assess cancer cell clonogenic survival, metabolic activity, and invasion potential. Fluorescence microscopy using propidium iodide (PI) as a probe of cell membrane integrity was used to identify sonoporation. The H2A.X assay and Nicoletti test were conducted in the mechanism investigation to detect DNA double-strand breaks (DSBs) and cell cycle arrest. Immunofluorescence microscopy and flow cytometry were performed to determine the distribution and expression of 5α-reductase (SRD5A).Results: Short FUS shots with cavitation (FUS-Cav) in combination with HT resulted in, respectively, a 2.2, 2.3, and 2.8-fold decrease (LNCap) and a 2.0, 1.5, and 1.6-fold decrease (PC-3) in the clonogenic survival, cell invasiveness and metabolic activity of prostate cancer cells when compared to HT alone. FUS-Cav immediately induced sonoporation in 61.7% of LNCap cells, and the combination treatment led to a 1.4 (LNCap) and 1.6-fold (PC-3) increase in the number of DSBs compared to HT alone. Meanwhile, the combination therapy resulted in 26.68% of LNCap and 31.70% of PC-3 with cell cycle arrest in the Sub-G1 phase and 35.37% of PC-3 with cell cycle arrest in the G2/M phase. Additionally, the treatment of FUS-Cav combined with HT block the androgen receptor (AR) signal pathway by reducing the relative Type I 5α-reductase (SRD5A1) level to 38.28 ± 3.76% in LNCap cells, and decreasing the relative Type III 5α-reductase 3 (SRD5A3) level to 22.87 ± 4.88% in PC-3 cells, in contrast, the relative SRD5A level in untreated groups was set to 100%.Conclusion: FUS-induced cavitation increases the effects of HT by interrupting cancer cell membranes, inducing the DSBs and cell cycle arrest, and blocking the AR signal pathway of the prostate cancer cells, with the potential to be a promising adjuvant therapy in prostate cancer treatment.
Altered somatic hypermutation patterns in COVID-19 patients classifies disease severity
Authors: Safra Modi , Tamari Zvi , Polak Pazit , Shiber Shachaf , Matan Moshe , Karameh Hani , Helviz Yigal , Levy-Barda Adva , Yahalom Vered , Peretz Avi , Ben-Chetrit Eli , Brenner Baruch , Tuller Tamir , Gal-Tanamy Meital , Yaari Gur 
Published: April 2023

IntroductionThe success of the human body in fighting SARS-CoV2 infection relies on lymphocytes and their antigen receptors. Identifying and characterizing clinically relevant receptors is of utmost importance.MethodsWe report here the application of a machine learning approach, utilizing B cell receptor repertoire sequencing data from severely and mildly infected individuals with SARS-CoV2 compared with uninfected controls.ResultsIn contrast to previous studies, our approach successfully stratifies non-infected from infected individuals, as well as disease level of severity. The features that drive this classification are based on somatic hypermutation patterns, and point to alterations in the somatic hypermutation process in COVID-19 patients.DiscussionThese features may be used to build and adapt therapeutic strategies to COVID-19, in particular to quantitatively assess potential diagnostic and therapeutic antibodies. These results constitute a proof of concept for future epidemiological challenges.
Tilianin improves cognition in a vascular dementia rodent model by targeting miR-193b-3p/CaM- and miR-152-3p/CaMKIIα-mediated inflammatory and apoptotic pathways
Authors: Sun Ting , Tan Linjie , Liu Mimin , Zeng Li , Zhao Kaiyue , Cai Zhongdi , Sun Shengnan , Li Zhuorong , Liu Rui 
Published: April 2023

IntroductionAlthough vascular dementia (VaD) is the second most prevalent form of dementia, there is currently a lack of effective treatments. Tilianin, isolated from the traditional drug Dracocephalum moldavica L., may protect against ischemic injury by inhibiting oxidative stress and inflammation via the CaMKII-related pathways but with weak affinity with the CaMKII molecule. microRNAs (miRNAs), functioning in post-transcriptional regulation of gene expression, may play a role in the pathological process of VaD via cognitive impairment, neuroinflammatory response, and neuronal dysfunction. This study aimed to investigate the role of tilianin in VaD therapy and the underlying mechanism through which tilianin regulates CaMKII signaling pathways based on miRNA-associated transcriptional action.MethodsRats with 2-vessel occlusion (2VO), a standard model of VaD, were treated with tilianin, vehicle control, and target overexpression or downregulation. High-throughput sequencing, qRT-PCR, and western blot analyses were utilized to identify the downstream target genes and signaling pathways of tilianin involved in VaD.ResultsOur results showed that tilianin ameliorated cognitive deficits, neurodegeneration, and microglial and astrocytic activation in rats with 2VO. Subsequent high-throughput sequencing and qRT-PCR analyses revealed that tilianin increased the downregulated miR-193b-3p and miR-152-3p levels in the cortex and hippocampus of 2VO rats. Mechanistically, miR-193b-3p targeting CaM and miR-152-3p targeting CaMKIIα were identified to play a role in VaD-associated pathology, inhibiting the p38 MAPK/NF--κB p65 pathway and decreasing TNF-α and IL-6 levels. Further gain- and loss-of-function experiments for these key genes showed that tilianin-exerted cognitive improvement by activating the p38 MAPK/NF--κB p65 and Bcl-2/Bax/caspase-3/PARP pathways in the brain of 2VO rats was abolished by miR-193b-3p and miR-152-3p inhibition. Moreover, CaM and CaMKIIα overexpression eliminated the elevated effects of miR-193b-3p and miR-152-3p on tilianin’s protection against ischemic injury through increased inflammatory reactions and apoptotic signaling.DiscussionTogether, these findings indicate that tilianin improves cognition by regulating the miR-193b-3p/CaM- and miR-152-3p/CaMKIIα-mediated inflammatory and apoptotic pathways, suggesting a potential small-molecule regulator of miRNA associated with inflammatory signaling for VaD treatment.
Pre-pandemic SARS-CoV-2-specific IFN-γ and antibody responses were low in Ugandan samples and significantly reduced in HIV-positive specimens
Authors: Nantambi Hellen , Sembera Jackson , Ankunda Violet , Ssali Ivan , Kalyebi Arthur Watelo , Oluka Gerald Kevin , Kato Laban , Ubaldo Bahemuka , Kibengo Freddie , Katende Joseph Ssebwana , Gombe Ben , Baine Claire , Odoch Geoffrey , Mugaba Susan , Sande Obondo James ,   The COVID-19 Immunoprofiling Team, Kaleebu Pontiano , Serwanga Jennifer 
Published: April 2023

IntroductionWe investigated whether prior SARS-CoV-2-specific IFN-γ and antibody responses in Ugandan COVID-19 pre-pandemic specimens aligned to this population's low disease severity.MethodsWe used nucleoprotein (N), spike (S), NTD, RBD, envelope, membrane, SD1/2-directed IFN-γ ELISpots, and an S- and N-IgG antibody ELISA to screen for SARS-CoV-2-specific cross-reactivity.ResultsHCoV-OC43-, HCoV-229E-, and SARS-CoV-2-specific IFN-γ occurred in 23, 15, and 17 of 104 specimens, respectively. Cross-reactive IgG was more common against the nucleoprotein (7/110, 15.5%; p = 0.0016, Fishers' Exact) than the spike (3/110, 2.72%). Specimens lacking anti-HuCoV antibodies had higher rates of pre-epidemic SARS-CoV-2-specific IFN-γ cross-reactivity (p-value = 0.00001, Fishers’ exact test), suggesting that exposure to additional factors not examined here might play a role. SARS-CoV-2-specific cross-reactive antibodies were significantly less common in HIV-positive specimens (p=0.017; Fishers' Exact test). Correlations between SARS-CoV-2- and HuCoV-specific IFN-γ responses were consistently weak in both HIV negative and positive specimens.DiscussionThese findings support the existence of pre-epidemic SARS-CoV-2-specific cellular and humoral cross-reactivity in this population. The data do not establish that these virus-specific IFN-γ and antibody responses are entirely specific to SARS-CoV-2. Inability of the antibodies to neutralise SARS-CoV-2 implies that prior exposure did not result in immunity. Correlations between SARS-CoV-2 and HuCoV-specific responses were consistently weak, suggesting that additional variables likely contributed to the pre-epidemic cross-reactivity patterns. The data suggests that surveillance efforts based on the nucleoprotein might overestimate the exposure to SARS-CoV-2 compared to inclusion of additional targets, like the spike protein. This study, while limited in scope, suggests that HIV-positive people are less likely than HIV-negative people to produce protective antibodies against SARS-CoV-2.
Immunochemotherapy achieved a complete response for metastatic adenocarcinoma of unknown primary based on gene expression profiling: a case report and review of the literature
Authors: Sheng Jin , Pan Hongming , Han Weidong 
Published: April 2023

BackgroundCancer of unknown primary (CUP) is a malignant and aggressive tumor whose primary origin is still unknown despite thorough evaluation. CUP can be life-threatening with a median overall survival of less than 1 year based on empirical chemotherapy. Gene detection technology advances the driver gene detection of malignant tumors and the appropriate precise therapy. Immunotherapy has ushered in a new era in cancer therapy, changing the way advanced tumors, including CUP, are treated. Combined with comprehensive clinical and pathological investigations, molecular analysis of the original tissue and detection of potential driver mutations may provide therapeutic recommendations for CUP.Case presentationA 52-year-old female was admitted to hospital for dull abdominal pain, with peripancreatic lesions below the caudate lobe of the liver and posterior peritoneal lymph nodes enlargement. Conventional biopsy under endoscopic ultrasonography and laparoscopic biopsy both revealed poorly differentiated adenocarcinoma based on immunohistochemical series. To help identify tumor origin and molecular characteristics, 90-gene expression assay, tumor gene expression profiling with Next-generation sequencing (NGS) method and Immunohistochemical expression of PD-L1 were employed. Although no gastroesophageal lesions discovered by gastroenteroscopy, the 90-gene expression assay yielded a similarity score and prompted the most likely primary site was gastric/esophagus cancer. NGS revealed high TMB (19.3mutations/Mb) but no druggable driver genes identified. The Dako PD-L1 22C3 assay IHC assay for PD-L1 expression revealed a tumor proportion score (TPS) of 35%. Given the presence of negative predictive biomarkers for immunotherapy, including adenomatous polyposis coli (APC) c.646C&gt;T mutation at exon 7 and Janus kinase 1(JAK1), the patient received immunochemotherapy instead of immunotherapy alone. She was successfully treated with nivolumab plus carboplatin and albumin-bound nanoparticle paclitaxel for six cycles and nivolumab maintenance, which achieved a complete response (CR) maintained for 2 years without severe adverse events.ConclusionsThis case highlights the value of multidisciplinary diagnosis and individual precision treatment in CUP. Further investigation is needed as an individualized treatment approach combining immunotherapy and chemotherapy based on tumor molecular characteristics and immunotherapy predictors is expected to improve the outcome of CUP therapy.
Association between unintended pregnancy and maternal antenatal care services use in Ethiopia: analysis of Ethiopian demographic and health survey 2016
Authors: Yalew Ayalnesh Zemene , Olayemi Oladapo O. , Yalew Alemayehu Worku 
Published: April 2023

IntroductionUnintended pregnancy disproportionately affects women in low and middle-income countries including Ethiopia. Previous studies identified the magnitude and negative health outcomes of unintended pregnancy. However, studies that examined the relationship between antenatal care (ANC) utilization and unintended pregnancy are scarce.ObjectiveThis study aimed to examine the relationship between unintended pregnancy and ANC utilization in Ethiopia.MethodsThis is a cross-sectional study conducted using the fourth and most recent Ethiopian Demographic Health Survey (EDHS) data. The study comprised a weighted sample of 7,271 women with last alive birth and responded to questions on unintended pregnancy and ANC use. The association between unintended pregnancy and ANC uptake was determined using multilevel logistic regression models adjusted for possible confounders. Finally p &lt; 5% was considered significant.ResultsUnintended pregnancy accounted for nearly a quarter of all pregnancies (26.5%). After adjusting for confounders, a 33% (AOR: 0.67; 95% CI, 0.57–0.79) lower odds of at least one ANC uptake and a 17% (AOR: 0.83; 95% CI, 0.70–0.99) lower odds of early ANC booking were found among women who had unintended pregnancy compared to women with intended pregnancy. However, this study founds no association (AOR: 0.88; 95% CI, 0.74, 1.04) between unintended pregnancy and four or more ANC visits.ConclusionOur study found that having unintended pregnancy was associated with a 17 and 33% reduction in early initiation and use of ANC services, respectively. Policies and programs designed to intervene against barriers to early initiation and use of ANC should consider unintended pregnancy.
A novel approach for automatic segmentation of prostate and its lesion regions on magnetic resonance imaging
Authors: Ren Huipeng , Ren Chengjuan , Guo Ziyu , Zhang Guangnan , Luo Xiaohui , Ren Zhuanqin , Tian Hongzhe , Li Wei , Yuan Hao , Hao Lele , Wang Jiacheng , Zhang Ming 
Published: April 2023

ObjectiveTo develop an accurate and automatic segmentation model based on convolution neural network to segment the prostate and its lesion regions.MethodsOf all 180 subjects, 122 healthy individuals and 58 patients with prostate cancer were included. For each subject, all slices of the prostate were comprised in the DWIs. A novel DCNN is proposed to automatically segment the prostate and its lesion regions. This model is inspired by the U-Net model with the encoding-decoding path as the backbone, importing dense block, attention mechanism techniques, and group norm-Atrous Spatial Pyramidal Pooling. Data augmentation was used to avoid overfitting in training. In the experimental phase, the data set was randomly divided into a training (70%), testing set (30%). four-fold cross-validation methods were used to obtain results for each metric.ResultsThe proposed model achieved in terms of Iou, Dice score, accuracy, sensitivity, 95% Hausdorff Distance, 86.82%,93.90%, 94.11%, 93.8%,7.84 for the prostate, 79.2%, 89.51%, 88.43%,89.31%,8.39 for lesion region in segmentation. Compared to the state-of-the-art models, FCN, U-Net, U-Net++, and ResU-Net, the segmentation model achieved more promising results.ConclusionThe proposed model yielded excellent performance in accurate and automatic segmentation of the prostate and lesion regions, revealing that the novel deep convolutional neural network could be used in clinical disease treatment and diagnosis.
Feasibility and safety of expandable mediastinoscopic and laparoscopic radical esophagectomy
Authors: Zhang Weidong , Cui Dong , Shi Kefeng , Chen Maolin , Zhang Binbin , Qian Rulin 
Published: April 2023

BackgroundAt present, minimally invasive radical esophagectomy is the main surgical method for esophageal cancer treatment, but it has inherent limitations. We have developed a novel method of radical esophagectomy without thoracotomy to improve this situation, namely, by using EMLE. We evaluated the feasibility and safety of expandable mediastinoscopic and laparoscopic radical esophagectomy (EMLE) through a retrospective analysis.MethodsFrom January 2019 to June 2022, we successfully performed 106 cases of radical resection of esophageal cancer with this new surgical technique, gradually improved the surgical path, and recorded the perioperative data and postoperative complications of all patients.ResultsThe operation was successfully performed in all patients except for two patients who required a switch to open surgery. The mean operation time was 171.11 ± 33.29 min and the mean intraoperative blood loss was 93.53 ± 56.32 ml. The mean number of removed lymph nodes was 23.59 ± 5.42. The postoperative complications included pneumonia (3.77%), recurrent laryngeal nerve palsy (1.89%), anastomotic leak (14.15%), pleural effusion (5.66%), chylothorax (2.83%), and reoperation (4.72%). All complications were graded I–III per the Clavien–Dindo classification. No perioperative death was recorded.ConclusionExpandable mediastinoscopic and laparoscopic radical esophagectomy is feasible for radical resection of esophageal cancer, with good therapeutic effect and safety. Because of its minimal impact on patients and convenient operation, it is a novel surgical option for patients with esophageal cancer and is expected to become a standard surgical method for radical esophagectomy in the future.
RETRACTED: Prognostic influence of PD-1/PD-L1 suppressors in combination with chemotherapeutic agents for non-small cell pulmonary carcinoma: system review and meta-analysis
Authors: Shen Min , Lu Chunxia , Gao Jie 
Published: April 2023

BackgroundLung cancer is a common malignant tumor, which is seriously harmful to human life and health. Nowadays, it has gradually become one of the best treatments for non-small cell lung cancer (NSCLC) to combine immunotherapy and chemotherapy, and its clinical efficacy is preliminary. Nevertheless, substantial differences exist between various studies and various indicators. Despite their unconvincing results, high-quality research evidence is needed to support them. In this case, further correlative studies are necessary to investigate the prognostic outcomes of PD-1/PD-L1 suppressors in combination with chemotherapeutic drugs in NSCLC.MethodsThe online public databases were searchable for the clinical trials that consisted of NSCLC patients who had concluded their chemotherapy and who had accepted PD-1/PD-L1 suppressors. The time-span of the search spanned from the beginning to the end of the database. Two investigators retrieved the data independently. RevMan 5.3 statistical software was utilized for the assessment of bias risk. The software followed the Cochrane Handbook 5.3 guidelines.ResultsThere were seven clinically controlled studies with 2781 NSCLC samples finally included in this study. A meta-analysis of the post-treatment overall response rate (ORR) was undertaken. A remarkably higher ORR rate was observed in the study group (p&lt;0.05). Study participants had a noticeably longer PFS (HR=0.61, 95% CI=0.54-0.70, P&lt;0.00001). Study participants had markedly longer overall survival (OS) (HR=0.651, 95% CI=0.52-0.82, P&lt;0.05). The incidence of adverse events (AEs) of Grade 3 or above was not clinically clearly different (P&gt;0.05), as demonstrated by the incidence of AEs. The funnel plots were separately charted in accordance with ORR rate, PFE, OS, and Grade 3 AEs. The majority of the funnel plots were symmetrical and a minority of funnel plots were asymmetrical, indicating the heterogeneity of research and the limited evidence available may lead to some publication bias in the contained literature.ConclusionThe combined PD-1/PD-L1 inhibitors with conventional chemotherapy can dramatically elevate the prognosis of NSCLC patients, obviously enhancing the ORR rate and prolonging their PFS and OS. Furthermore, it was found that adding PD-1/PD-L1 inhibitors to conventional chemotherapy did not result in any additional adverse effects.
Kruppel-like factor 8 regulates triple negative breast cancer stem cell-like activity
Authors: Le Minh Giang , Esquea Emily M. , Dhameliya Tejsi T. , Merzy Jessica , Lee Mi-Hye , Ball Lauren E. , Reginato Mauricio J. 
Published: April 2023

IntroductionBreast tumor development is regulated by a sub-population of breast cancer cells, termed cancer stem-like cells (CSC), which are capable of self-renewing and differentiating, and are involved in promoting breast cancer invasion, metastasis, drug resistance and relapse. CSCs are highly adaptable, capable of reprogramming their own metabolism and signaling activity in response to stimuli within the tumor microenvironment. Recently, the nutrient sensor O-GlcNAc transferase (OGT) and O-GlcNAcylation was shown to be enriched in CSC populations, where it promotes the stemness and tumorigenesis of breast cancer cells in vitro and in vivo. This enrichment was associated with upregulation of the transcription factor Kruppel-like-factor 8 (KLF8) suggesting a potential role of KLF8 in regulating CSCs properties.MethodsTriple-negative breast cancer cells were genetically modified to generate KLF8 overexpressing or KLF8 knock-down cells. Cancer cells, control or with altered KLF8 expression were analyzed to assess mammosphere formation efficiency, CSCs frequency and expression of CSCs factors. Tumor growth in vivo of control or KLF8 knock-down cells was assessed by fat-pad injection of these cell in immunocompromised mice.ResultsHere, we show that KLF8 is required and sufficient for regulating CSC phenotypes and regulating transcription factors SOX2, NANOG, OCT4 and c-MYC. KLF8 levels are associated with chemoresistance in triple negative breast cancer patients and overexpression in breast cancer cells increased paclitaxel resistance. KLF8 and OGT co-regulate each other to form a feed-forward loop to promote CSCs phenotype and mammosphere formation of breast cancer cells.DiscussionThese results suggest a critical role of KLF8 and OGT in promoting CSCs and cancer progression, that may serve as potential targets for developing strategy to target CSCs specifically.