bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal trends of COVID-19 antibodies in vaccinated healthcare workers undergoing repeated serological sampling: An individual-level analysis within 13 months in the ORCHESTRA cohort
Authors: Collatuzzo Giulia , De Palma Giuseppe , Violante Francesco S. , Porru Stefano , Larese Filon Francesca , Fabianova Eleonora , Violán Concepción , Vimercati Luigi , Leustean Mihaela , Rodriguez-Suarez Marta Maria , Sansone Emanuele , Sala Emma , Zunarelli Carlotta , Lodi Vittorio , Monaco Maria Grazia Lourdes , Spiteri Gianluca , Negro Corrado , Beresova Jana , Carrasco-Ribelles LucÌa A. , Tafuri Silvio , Asafo Shuffield S. , Ditano Giorgia , Abedini Mahsa , Boffetta Paolo 
Published: January 2023

Short summaryWe investigated changes in serologic measurements after COVID-19 vaccination in 19,422 subjects. An individual-level analysis was performed on standardized measurements. Age, infection, vaccine doses, time between doses and serologies, and vaccine type were associated with changes in serologic levels within 13 months.BackgroundPersistence of vaccine immunization is key for COVID-19 prevention.MethodsWe investigated the difference between two serologic measurements of anti-COVID-19 S1 antibodies in an individual-level analysis on 19,422 vaccinated healthcare workers (HCW) from Italy, Spain, Romania, and Slovakia, tested within 13 months from first dose. Differences in serologic levels were divided by the standard error of the cohort-specific distribution, obtaining standardized measurements. We fitted multivariate linear regression models to identify predictors of difference between two measurements.ResultsWe observed a progressively decreasing difference in serologic levels from &lt;30 days to 210–240 days. Age was associated with an increased difference in serologic levels. There was a greater difference between the two serologic measurements in infected HCW than in HCW who had never been infected; before the first measurement, infected HCW had a relative risk (RR) of 0.81 for one standard deviation in the difference [95% confidence interval (CI) 0.78–0.85]. The RRs for a 30-day increase in time between first dose and first serology, and between the two serologies, were 1.08 (95% CI 1.07–1.10) and 1.04 (95% CI 1.03–1.05), respectively. The first measurement was a strong predictor of subsequent antibody decrease (RR 1.60; 95% CI 1.56–1.64). Compared with Comirnaty, Spikevax (RR 0.83, 95% CI 0.75–0.92) and mixed vaccines (RR 0.61, 95% CI 0.51–0.74) were smaller decrease in serological level (RR 0.46; 95% CI 0.40–0.54).ConclusionsAge, COVID-19 infection, number of doses, time between first dose and first serology, time between serologies, and type of vaccine were associated with differences between the two serologic measurements within a 13-month period.
Immunotherapy or targeted therapy as the first-line strategies for unresectable hepatocellular carcinoma: A network meta-analysis and cost-effectiveness analysis
Authors: Liu Kun , Zhu Youwen , Zhu Hong 
Published: January 2023

IntroductionThe existence of many phase III randomized controlled trials (RCTs) of first-line treatment for unresectable hepatocellular carcinoma (HCC) puzzle doctors and patients in choosing the most effective treatment strategies. We aimed to assess the efficacy, safety, and cost-effectiveness of immunotherapy or targeted therapy as the first-line strategy for unresectable HCC.MethodsThe included clinical trials were retrieved from PubMed, Embase, the Cochrane library, and Web of Science databases, in which immunotherapy or targeted therapy was regarded as the first-line treatment for unresectable HCC, published in English between January 1, 2010, and September 20, 2022. We conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) from the Chinese payer’s perspective. Overall survival (OS), progression-free survival (PFS), the ranks of different treatments using P-score, and adverse events (AEs) were evaluated by NMA. Total costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-benefit ratio (ICER) were estimated from 15-year Markov models developed by CEA.ResultsWe identified 2,825 records, including 11,796 patients, from 15 RCTs. The NMA revealed that sintilimab plus a bevacizumab biosimilar (HR, 0.57; 95% CI, 0.43 to 0.75; P = 0.96) and camrelizumab plus rivoceranib (HR, 0.56; 95% CI, 0.41 to 0.66; P = 0.94) could lead to great improvements in OS and PFS compared with sorafenib-related survival. The CEA indicated that tislelizumab increased by 0.220 QALYs (0.312 LYs) and decreased by $1,938 compared with sorafenib, which yielded ICERs of -$8,809/QALY (-$2,612/LY). Sensitivity analysis showed that the model was stable.ConclusionSintilimab plus a bevacizumab biosimilar and camrelizumab plus rivoceranib significantly prolonged OS and PFS, respectively. Further considering the pharmacoeconomics factors, tislelizumab is the most cost-effective first-line treatment strategy for unresectable HCC in China.
Epidemiology and outcomes of hyponatremia in patients with COVID-19—A territory-wide study in Hong Kong
Authors: Chan Gordon Chun Kau , Wong Chun Ka , So Benjamin Y. F. , Ng Jack Kit Chung , Lui Grace Chung Yan , Szeto Cheuk Chun , Hung Ivan Fan Ngai , Tse Hung Fat , Tang Sydney C. W. , Chan Tak Mao , Chow Kai Ming , Yap Desmond Y. H. 
Published: January 2023

BackgroundHyponatremia is common in COVID-19, but its epidemiology and impact on clinical outcomes in relation to different variants, especially the Omicron variant, requires further clarification.MethodsThis was a territory-wide retrospective study to investigate the epidemiology and outcomes of COVID-19 patients with hyponatremia from January 1, 2020 to March 31, 2022 in Hong Kong. The primary outcome was 30-day mortality of patients with COVID-19 and hyponatremia at presentation. Secondary outcomes included rate of hospitalization, intensive care unit (ICU) hospitalization, overall duration of hospitalization, and duration of ICU hospitalization.ResultsA total of 53,415 COVID-19 patients were included for analysis, of which 14,545 (27.2%) had hyponatremia at presentation. 9813 (67.5%), 2821 (19.4%), and 1911 (13.1%) had mild (130 to &lt;135 mmol/L), moderate (125 to &lt;130 mmol/L), and severe hyponatremia (&lt;125 mmol/L) at presentation respectively. Age, male sex, diabetes, active malignancy, white cell count, serum creatinine, hypoalbuminemia, C-reactive protein, and viral loads were independent predictors for hyponatremia in COVID-19 patients (P &lt; 0.001, for all). Hyponatremic patients had increased 30-day mortality (9.7 vs. 5.7%, P &lt; 0.001), prolonged hospitalization (11.9 ± 15.1 days vs. 11.5 ± 12.1 days, P &lt; 0.001), and more ICU admissions (7.0% vs. 3.3%, P &lt; 0.001). Patients diagnosed during the “fifth wave” Omicron BA.2 outbreak had 2.29-fold risk (95% CI 2.02–2.59, P &lt; 0.001) of presenting with hyponatremia compared to other waves.ConclusionHyponatremia is common among COVID-19 patients, and may serve as a prognostic indicator for unfavorable outcomes and increased healthcare utilization in the evolving COVID-19 outbreak.
Potential factors causing failure of whole plant nettle (Urtica cannabina) silages
Authors: Huang Rongzheng , Chen Yongcheng , Ma Chunhui , Chai Yuxin , Jia Shuan , Zhang Fanfan 
Published: January 2023

IntroductionNettle is kind of new feed resources and benefit for animal production. However, a few studies observed that quality of nettle silage was poor under naturally fermentation. Consider of microbial activity was the mainly factors for fermentation characteristics of silage.MethodsThus, the present study investigated the potential factors causing nettle silage failure through metabolome and bacterial community composition analyses during ensiling.ResultsDuring ensiling, the pH was &gt;6.22, and water-soluble carbohydrate and organic acid contents stabilized after 7 d. At the genus level, Enterococcus, Weissella, and Pediococcus were the dominant bacteria (relative abundance were 30.06–39.39, 17.29–23.34, and 3.13–7.22%, respectively), with stable trends, whereas Lactococcus and Enterobacter relative abundance decreased significantly over time (relative abundance were 5.68–13.96 and 3.86–24.1%, respectively). Lactobacillus relative abundance was &lt;1% during the entire ensiling period, and malic acid metabolic pathway was the most important pathway. Enterococcus, Pediococcus, and Weissella were negatively correlated with malic acid, with Lactobacillus displaying an opposite trend.DiscussionThe results suggested that Lactobacillus activity was the lowest among lactic acid bacteria (LAB) during ensiling, which is the main reason for nettle ensiling failure, and attributable to a low capacity to compete for fermentation substrates such as malic acid against other LAB during ensiling. Additionally, anti-bacteria activity of nettle probably inhibited Enterobacter activity during ensiling. Present study probably given a solution for improve nettle silage quality through addition with malic acid.
Impact of multidomain preventive strategies on functional brain connectivity in older adults with cognitive complaint: Subset from the Montpellier center of the ancillary MAPT-MRI study
Authors: Perus Lisa , Mangin Jean-François , Deverdun Jérémy , Gutierrez Laure-Anne , Gourieux Emmanuelle , Fischer Clara , Van Dokkum Liesjet E. H. , Manesco Clara , Busto Germain , Guyonnet Sophie , Vellas Bruno , Gabelle Audrey , Le Bars Emmanuelle ,   The MAPT/DSA group
Published: January 2023

IntroductionThe impact of multi-domain preventive interventions on older adults, in particular on those with higher risk to develop Alzheimer's disease (AD), could be beneficial, as it may delay cognitive decline. However, the precise mechanism of such positive impact is not fully understood and may involve brain reserve and adaptability of brain functional connectivity (FC).MethodsTo determine the effect of multidomain interventions (involving physical activity, cognitive training, nutritional counseling alone or in combination with omega-3 fatty acid supplementation and vs. a placebo) on the brain, longitudinal FC changes were assessed after 36 months of intervention on 100 older adults (above 70 year-old) with subjective cognitive complaints.ResultsNo global change in FC was detected after uni or multidomain preventive interventions. However, an effect of omega-3 fatty acid supplementation dependent on cognitive decline status was underlined for frontoparietal, salience, visual and sensorimotor networks FC. These findings were independent of the cortical thickness and vascular burden.DiscussionThese results emphasize the importance of patient stratification, based on risk factors, for preventive interventions.
Cancer treatment induces neuroinflammation and behavioral deficits in mice
Authors: Demos-Davies Kimberly , Lawrence Jessica , Rogich Allison , Lind Erin , Seelig Davis 
Published: January 2023

Introduction: Cancer survivors are increasingly diagnosed with a syndrome of neurocognitive dysfunction termed cancer-related cognitive impairment (CRCI). Chemotherapy and radiation therapy have been implicated in CRCI; however, its underlying pathogenesis remains unclear, hindering effective prevention or treatment.Methods: We used the hairless strain SKH1 (11–12-week-old) and treated the mice with radiation to the right hindlimb, doxorubicin (a chemotherapy agent), concurrent radiation, and doxorubicin, or no treatment (control). Neurocognition was evaluated via standardized behavioral testing following treatment. Mice were subsequently humanely euthanized, and plasma and brains were collected to identify inflammatory changes.Results: Mice treated with radiation, doxorubicin, or both radiation and doxorubicin demonstrated equivalent hippocampal dependent memory deficits and significant increases in activated microglia and astrocytes compared to control mice. Doxorubicin-treated mice had significantly increased plasma IL-6 and failed to gain weight compared to control mice over the study period.Discussion: This study demonstrates that non-brain directed radiation induces both gliosis and neurocognitive deficits. Moreover, this work presents the first characterization of SKH1 mice as a relevant and facile animal model of CRCI. This study provides a platform from which to build further studies to identify potential key targets that contribute to CRCI such that strategies can be developed to mitigate unintended neuropathologic consequences associated with anticancer treatment.
The effect of exercise on walking economy in patients with chronic neurological conditions: A systematic review and meta-analysis
Authors: Liu Bowen , Yu Jingxuan , Fan Qiwei , Hao Fengwei , Wu Jinlong , Xiao Wen , Yu Fengyu , Ren Zhanbing 
Published: January 2023

IntroductionTo investigate the effect of exercise on the walking economy (WE) of patients with chronic neurological conditions (CNCs) and to determine the type of physical activity that best improves the WE of patients with CNCs.MethodsFour electronic databases were searched until December 2022 (Web of Science, PubMed, Cochrane, and CINAHL). Studies were screened using the following inclusion criteria: 1. randomized controlled or non-randomized controlled trials; 2. exercise interventions &gt;4 weeks in duration; 3. patients aged ≥18 years with a diagnosis of CNCs. 4. walking economy of patients measured before and after the intervention. The PEDro scale was used to assess the methodological quality of the included studies.Results and discussionTwenty-two studies met the inclusion criteria. Meta-analysis results showed that exercise significantly improved WE (g = −0.352, 95% CI, −0.625 to −0.078, P = 0.012). Subgroup analysis revealed that patients who received exercise showed better WE compared with those who underwent no control intervention (g = −0.474, 95% CI, −0.636 to −0.311, P &lt; 0.001). However, exercise therapy did not show a significant improvement of WE compared with control groups (g = −0.192, 95% CI, −0.451 to 0.067, P = 0.146). In addition, we found that endurance combined with resistance, high-intensity intermittent, and other training modalities resulted in better WE compared with the pre-intervention. Of these, interval training has the greatest effect on improving WE. In conclusion, exercise can improve WE in patients with CNCs. More randomized controlled trials are necessary for the future.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022361455, identifier: CRD42022361455.
Decitabine improves MMS-induced retinal photoreceptor cell damage by targeting DNMT3A and DNMT3B
Authors: Ji Yanli , Zhao Meng , Qiao Xiaomeng , Peng Guang-Hua 
Published: January 2023

IntroductionRetinitis pigmentosa (RP) is a group of neurodegenerative retinopathies causing blindness due to progressive and irreversible photoreceptor cell death. The alkylating agent methyl methanesulfonate (MMS) can induce selective photoreceptor cell death, which is used to establish RP animal models. MMS induces DNA base damage by adding alkyl groups to DNA, and epigenetic modifications influence DNA damage response. Here, we aimed to explore the relationship between DNA methylation and DNA damage response in dying photoreceptors of RP.MethodsThe mouse RP model was established by a single intraperitoneal injection of MMS. The retinal structure and function were assessed by H&amp;E, OCT, TUNEL, and ERG at several time points. The expression of DNA methylation regulators was assessed by qPCR and Western blot. DNMT inhibitor 5-aza-dC was applied to inhibit the activity of DNA methyltransferases and improve the retinal photoreceptor damage.ResultsThe outer nuclear layer (ONL) and IS/OS layer were significantly thinner and the retinal function was impaired after MMS treatment. The cell death was mainly located in the ONL. The retinal damage induced by MMS was accompanied by hyperexpression of DNMT3A/3B. The application of DNMT inhibitor 5-aza-dC could suppress the expression level of DNMT3A/3B, resulting in the remission of MMS-induced photoreceptor cell damage. The ONL and IS/OS layers were thicker than that of the control group, and the retinal function was partially restored. This protective effect of 5-aza-dC was associated with the down-regulated expression of DNMT3A/3B.ConclusionThese findings identified a functional role of DNMT3A/3B in MMS-induced photoreceptor cell damage and provided novel evidence to support DNMTs as potential therapeutic targets in retinal degenerative diseases.Graphical Abstract
Human macrophage-engineered vesicles for utilization in ovarian cancer treatment
Authors: Schweer David , Anand Namrata , Anderson Abigail , McCorkle J. Robert , Neupane Khaga , Nail Alexandra N. , Harvey Brock , Hill Kristen S. , Ueland Frederick , Richards Christopher , Kolesar Jill 
Published: January 2023

BackgroundOvarian cancer is a deadly female malignancy with a high rate of recurrent and chemotherapy-resistant disease. Tumor-associated macrophages (TAMs) are a significant component of the tumor microenvironment and include high levels of M2-protumor macrophages that promote chemoresistance and metastatic spread. M2 macrophages can be converted to M1 anti-tumor macrophages, representing a novel therapeutic approach. Vesicles engineered from M1 macrophages (MEVs) are a novel method for converting M2 macrophages to M1 phenotype-like macrophages.MethodsMacrophages were isolated and cultured from human peripheral blood mononuclear cells. Macrophages were stimulated to M1 or M2 phenotypes utilizing LPS/IFN-γ and IL-4/IL-13, respectively. M1 MEVs were generated with nitrogen cavitation and ultracentrifugation. Co-culture of ovarian cancer cells with macrophages and M1 MEVs was followed by cytokine, PCR, and cell viability analysis. Murine macrophage cell line, RAW264.7 cells were cultured and used to generate M1 MEVs for use in ovarian cancer xenograft models.ResultsM1 MEVs can effectively convert M2 macrophages to an M1-like state both in isolation and when co-cultured with ovarian cancer cells in vitro, resulting in a reduced ovarian cancer cell viability. Additionally, RAW264.7 M1 MEVs can localize to ovarian cancer tumor xenografts in mice.ConclusionHuman M1 MEVs can repolarize M2 macrophages to a M1 state and have anti-cancer activity against ovarian cancer cell lines. RAW264.7 M1 MEVs localize to tumor xenografts in vivo murine models.
Suppression of head and neck cancer cell survival and cisplatin resistance by GRP78 small molecule inhibitor YUM70
Authors: Yamamoto Vicky , Wang Bintao , Lee Amy S. 
Published: January 2023

BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer-related death worldwide. Surgical resection, radiation and chemotherapy are the mainstay of HNSCC treatment but are often unsatisfactory. Cisplatin is a commonly used chemotherapy in HNSCC; however, cisplatin resistance is a major cause of relapse and death. The 78-kD glucose-regulated protein (GRP78) is the master regulator of the unfolded protein response (UPR) and is implicated in therapeutic resistance in cancer. The role of GRP78 in cisplatin resistance in HNSCC remains unclear. YUM70 is a newly discovered hydroxyquinoline analogue and found to be an inhibitor of GRP78. The effect of YUM70 in HNSCC cell lines is unknown.MethodKnockdown of GRP78 by siRNAs was performed to investigate the effect of GRP78 reduction in endoplasmic reticulum (ER)-stress induced and general apoptosis. Western blots examining apoptotic markers were performed on three HPV-negative HNSCC cell lines. WST-1 assay was performed to determine cell viability. In reverse, we utilized AA147, an ER proteostasis regulator to upregulate GRP78, and apoptotic markers and cell viability were determined. To test the ability of YUM70 to reverse cisplatin resistance, cisplatin-resistant HNSCC cell lines were generated by prolonged, repeated exposure to increasing concentrations of cisplatin. Colony formation assay using the cisplatin-resistant HNSCC cell line was performed to assess the in vitro reproductive cell survival. Furthermore, to test the ability of YUM70 to reverse cisplatin resistance in a physiologically relevant system, we subjected the 3D spheroids of the cisplatin-resistant HNSCC cell line to cisplatin treatment with or without YUM70 and monitored the onset of apoptosis.ResultsReduction of GRP78 level induced HNSCC cell death while GRP78 upregulation conferred higher resistance to cisplatin. Combined cisplatin and YUM70 treatment increased apoptotic markers in the cisplatin-resistant HNSCC cell line, associating with reduced cell viability and clonogenicity. The combination treatment also increased apoptotic markers in the 3D spheroid model.ConclusionThe GRP78 inhibitor YUM70 reduced HNSCC cell viability and re-sensitized cisplatin-resistant HNSCC cell line in both 2D and 3D spheroid models, suggesting the potential use of YUM70 in the treatment of HNSCC, including cisplatin-resistant HNSCC.
Prognostic value of Siglec-15 expression in patients with solid tumors: A meta-analysis
Authors: Jiang Kui-Ying , Qi Li-Li , Liu Xin-Bo , Wang Yong , Wang Ling 
Published: January 2023

BackgroundSiglec-15 is expressed in a variety of cancers. However, the role of Siglec-15 in the prognosis of cancer patients remains controversial. Therefore, we conducted a meta-analysis to clarify the potential prognostic value of Siglec-15 in solid tumors.MethodsThe PubMed, Web of Science, Embase and CNKI databases were comprehensively searched to identify studies assessing the effect of Siglec-15 on the survival of cancer patients. Hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS), progression-free survival (PFS) and disease-specific survival (DSS) from individual studies were evaluated.ResultsThe data from 13 observational studies consisting of 1376 patients were summarized. Elevated baseline Siglec-15 expression was significantly correlated with poor OS (pooled HR = 1.28, 95% CI: 1.05–1.56; P = 0.013). However, high Siglec-15 expression predicted a significantly better DSS (pooled HR = 0.73 (95% CI: 0.57–0.94; P = 0.015) but not PFS (pooled HR = 1.49, 95% CI: 0.46–4.87; P=0.510). In addition, high Siglec-15 expression was not associated with PD-L1 (OR=0.64, 95% CI: 0.42–0.95; P = 0.028). High Siglec-15 expression was associated with male sex (OR = 1.39, 95% CI: 1.05-1.84; P = 0.022), larger tumor size (OR = 1.896, 95% CI: 1.26-2.9; P = 0.002), and advanced tumor-node-metastasis (TNM) stage (OR = 1.84; 95% CI: 1.19-2.84; P =0.006) in solid tumors.ConclusionsThis updated study suggested the expression of Siglec-15 is significantly associated with poor outcomes in human solid tumors, but further studies are needed to determine the prognostic value of Siglec-15 in solid tumors.