bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuro-PASC is characterized by enhanced CD4+ and diminished CD8+ T cell responses to SARS-CoV-2 Nucleocapsid protein
Authors: Visvabharathy Lavanya , Hanson Barbara A. , Orban Zachary S. , Lim Patrick H. , Palacio Nicole M. , Jimenez Millenia , Clark Jeffrey R. , Graham Edith L. , Liotta Eric M. , Tachas George , Penaloza-MacMaster Pablo , Koralnik Igor J.
Published: May 2023

Introduction

Many people with long COVID symptoms suffer from debilitating neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC). Although symptoms of Neuro-PASC are widely documented, it is still unclear whether PASC symptoms impact virus-specific immune responses. Therefore, we examined T cell and antibody responses to SARS-CoV-2 Nucleocapsid protein to identify activation signatures distinguishing Neuro-PASC patients from healthy COVID convalescents.

Results

We report that Neuro-PASC patients exhibit distinct immunological signatures composed of elevated CD4+ T cell responses and diminished CD8+ memory T cell activation toward the C-terminal region of SARS-CoV-2 Nucleocapsid protein when examined both functionally and using TCR sequencing. CD8+ T cell production of IL-6 correlated with increased plasma IL-6 levels as well as heightened severity of neurologic symptoms, including pain. Elevated plasma immunoregulatory and reduced pro-inflammatory and antiviral response signatures were evident in Neuro-PASC patients compared with COVID convalescent controls without lasting symptoms, correlating with worse neurocognitive dysfunction.

Discussion

We conclude that these data provide new insight into the impact of virus-specific cellular immunity on the pathogenesis of long COVID and pave the way for the rational design of predictive biomarkers and therapeutic interventions.
T cell receptor and B cell receptor exhibit unique signatures in tumor and adjacent non-tumor tissues of hepatocellular carcinoma
Authors: Xie Shi , Yan Rong , Zheng Anqi , Shi Mengfen , Tang Longqing , Li Xueying , Liu Jiabang , Gan Yifan , Wang Yu , Jiang Deke , Liu Li , Wu Hongkai , Wang Zhanhui
Published: May 2023

Background

The tumor microenvironment in hepatocellular carcinoma (HCC) is complicated. Tumor-infiltrating T and B cells play a pivotal role in anti-tumor immunity. T cell receptor (TCR) and B cell receptor (BCR) features may reflect the disease-associated antigen response.

Methods

By combining bulk TCR/BCR-sequencing, RNA-sequencing, whole exome-sequencing, and human leukocyte antigen-sequencing, we examined the immune repertoire (IR) features of tumor and adjacent non-tumor tissues obtained from 64 HCC patients.

Results

High IR heterogeneity with weak similarity was discovered between tumor and non-tumor tissues. Higher BCR diversity, richness, and somatic hypermutation (SHM) were found in non-tumor tissues, while TCRα and TCRβ diversity and richness were comparable or higher in tumor. Additionally, lower immune infiltration was found in tumor than non-tumor tissues; the microenvironment in tumor appeared to keep stably inhibited and changed slightly with tumor progression. Moreover, BCR SHM was stronger, whereas TCR/BCR diversity declined with HCC progression. Importantly, we found that higher IR evenness in tumor and lower TCR richness in non-tumor tissues indicated better survival in HCC patients. Collectively, the results revealed that TCR and BCR exhibited distinct features in tumor and non-tumor tissues.

Conclusions

We demonstrated that IR features vary between different tissues of HCC. IR features may represent a biomarker for the diagnosis and treatment of HCC patients, providing references for subsequent immunotherapy research and strategy selection.
Blocking autofluorescence in brain tissues affected by ischemic stroke, hemorrhagic stroke, or traumatic brain injury
Authors: Wang Shaoshuai , Ren Xiuhua , Wang Junmin , Peng Qinfeng , Niu Xiaoyu , Song Chunhua , Li Changsheng , Jiang Chao , Zang Weidong , Zille Marietta , Fan Xiaochong , Chen Xuemei , Wang Jian
Published: May 2023

Autofluorescence is frequently observed in animal tissues, interfering with an experimental analysis and leading to inaccurate results. Sudan black B (SBB) is a staining dye widely used in histological studies to eliminate autofluorescence. In this study, our objective was to characterize brain tissue autofluorescence present in three models of acute brain injury, including collagenase-induced intracerebral hemorrhage (ICH), traumatic brain injury (TBI), and middle cerebral artery occlusion, and to establish a simple method to block autofluorescence effectively. Using fluorescence microscopy, we examined autofluorescence in brain sections affected by ICH and TBI. In addition, we optimized a protocol to block autofluorescence with SBB pretreatment and evaluated the reduction in fluorescence intensity. Compared to untreated, pretreatment with SBB reduced brain tissue autofluorescence in the ICH model by 73.68% (FITC), 76.05% (Tx Red), and 71.88% (DAPI), respectively. In the TBI model, the ratio of pretreatment to untreated decreased by 56.85% (FITC), 44.28% (Tx Red), and 46.36% (DAPI), respectively. Furthermore, we tested the applicability of the protocol using immunofluorescence staining or Cyanine-5.5 labeling in the three models. SBB treatment is highly effective and can be applied to immunofluorescence and fluorescence label imaging techniques. SBB pretreatment effectively reduced background fluorescence but did not significantly reduce the specific fluorescence signal and greatly improved the signal-to-noise ratio of fluorescence imaging. In conclusion, the optimized SBB pretreatment protocol blocks brain section autofluorescence of the three acute brain injury models.
Cost-effectiveness analysis of toripalimab plus chemotherapy versus chemotherapy alone for advanced non-small cell lung cancer in China
Authors: Zhang Mengdie , Xu Kai , Lin Yingtao , Zhou Chongchong , Bao Yuwen , Zhang Lingli , Li Xin
Published: May 2023

Background

Toripalimab is the first domestic anti-tumor programmed death 1 antibody marketed in China. The CHOICE-01 trial (identifier: NCT 03856411) demonstrated that toripalimab plus chemotherapy can significantly improve the clinical outcomes of advanced non-small cell lung cancer (NSCLC) patients. However, whether it is cost-effective remains unknown. Given the high cost of combination therapy, a cost-effectiveness analysis of toripalimab plus chemotherapy (TC) versus chemotherapy alone (PC) for the first-line treatment of patients with advanced NSCLC is required.

Methods

A partitioned survival model was adopted to predict the course of disease in advanced NSCLC patients on TC or PC from the perspective of the Chinese healthcare system over a 10-year horizon. The survival data were obtained from the CHOICE-01 clinical trial. Cost and utility values were obtained from local hospitals and kinds of literature. Based on these parameters, the incremental cost-effectiveness ratio (ICER) of TC vs. PC was measured, and one-way sensitivity analyses, probabilistic sensitivity analyses (PSA), and scenario analyses were performed to assess the robustness of the model.

Results

In the base case, TC was associated with an incremental cost of $18510 and an incremental quality-adjusted life year (QALY) of 0.57 compared with PC, resulting in an ICER of $32237/QALY which was lower than the willingness to pay (WTP) threshold ($37654/QALY), TC was cost-effective. The health utility value of progression-free survival, the price of toripalimab, and the cost of best supportive care were factors that significantly influenced the ICER, but no change in any of them could change the model result. TC showed a 90% probability of being a cost-effective option at a WTP threshold of $37,654/QALY. In the 20 and 30-year time horizons, the results remained unchanged and TC remained cost-effective when the second-line treatment was switched to docetaxel.

Conclusion

At a WTP threshold of $37,654 per QALY, TC was cost-effective compared to PC for patients with advanced NSCLC in China.
Incidence and risk factors of acute kidney injury in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis
Authors: Liu Caihong , Wei Wei , Yang Letian , Li Jian , Yi Cheng , Pu Yajun , Yin Ting , Na Feifei , Zhang Ling , Fu Ping , Zhao Yuliang
Published: May 2023

Background

The incidence and risk factors of acute kidney injury (AKI) in patients with malignancies receiving immune checkpoint inhibitors (ICIs) are being extensively reported with their widespread application.

Objective

This study aimed to quantify the incidence and identify risk factors of AKI in cancer patients treated with ICIs.

Methods

We searched the electronic databases of PubMed/Medline, Web of Science, Cochrane and Embase before 1 February 2023 on the incidence and risk factors of AKI in patients receiving ICIs and registered the protocol in PROSPERO (CRD42023391939). A random-effect meta-analysis was performed to quantify the pooled incidence estimate of AKI, identify risk factors with pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) and investigate the median latency period of ICI-AKI in patients treated with ICIs. Assessment of study quality, meta-regression, and sensitivity and publication bias analyses were conducted.

Results

In total, 27 studies consisting of 24048 participants were included in this systematic review and meta-analysis. The overall pooled incidence of AKI secondary to ICIs was 5.7% (95% CI: 3.7%-8.2%). Significant risk factors were older age (OR: 1.01, 95% CI: 1.00–1.03), preexisting chronic kidney disease (CKD) (OR: 2.90, 95% CI: 1.65–5.11), ipilimumab (OR: 2.66, 95% CI: 1.42–4.98), combination of ICIs (OR: 2.45, 95% CI: 1.40–4.31), extrarenal immune-related adverse events (irAEs) (OR: 2.34, 95% CI: 1.53-3.59), and proton pump inhibitor (PPI) (OR: 2.23, 95% CI: 1.88–2.64), nonsteroidal anti-inflammatory drug (NSAID) (OR: 2.61, 95% CI: 1.90–3.57), fluindione (OR: 6.48, 95% CI: 2.72–15.46), diuretic (OR: 1.78, 95% CI: 1.32–2.40) and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) (pooled OR: 1.76, 95% CI: 1.15–2.68) use. Median time from ICIs initiation to AKI was 108.07 days. Sensitivity and publication bias analyses indicated robust results for this study.

Conclusion

The occurrence of AKI following ICIs was not uncommon, with an incidence of 5.7% and a median time interval of 108.07 days after ICIs initiation. Older age, preexisting chronic kidney disease (CKD), ipilimumab, combined use of ICIs, extrarenal irAEs, and PPI, NSAID, fluindione, diuretics and ACEI/ARB use are risk factors for AKI in patients receiving ICIs.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42023391939.
Group 1 and group 2 hemagglutinin stalk antibody response according to age
Authors: Sánchez-de Prada Laura , Sanz-Muñoz Iván , Sun Weina , Palese Peter , Ortiz de Lejarazu Raúl , Eiros José María , García-Sastre Adolfo , Aydillo Teresa
Published: May 2023

Objective

Antibodies elicited by seasonal influenza vaccines mainly target the head of hemagglutinin (HA). However, antibodies against the stalk domain are cross-reactive and have been proven to play a role in reducing influenza disease severity. We investigated the induction of HA stalk-specific antibodies after seasonal influenza vaccination, considering the age of the cohorts.

Methods

A total of 166 individuals were recruited during the 2018 influenza vaccine campaign (IVC) and divided into groups: <50 (n = 14), 50–64 (n = 34), 65–79 (n = 61), and ≥80 (n = 57) years old. Stalk-specific antibodies were quantified by ELISA at day 0 and day 28 using recombinant viruses (cH6/1 and cH14/3) containing an HA head domain (H6 or H14) from wild bird origin with a stalk domain from human H1 or H3, respectively. The geometric mean titer (GMT) and the fold rise (GMFR) were calculated, and differences were assessed using ANOVA adjusted by the false discovery rate (FDR) and the Wilcoxon tests (p <0.05).

Results

All age groups elicited some level of increase in anti-stalk antibodies after receiving the influenza vaccine, except for the ≥80-year-old cohort. Additionally, <65-year-old vaccinees had higher group 1 antibody titers versus group 2 before and after vaccination. Similarly, vaccinees within the <50-year-old group showed a higher increase in anti-stalk antibody titers when compared to older individuals (≥80 years old), especially for group 1 anti-stalk antibodies.

Conclusion

Seasonal influenza vaccines can the induction of cross-reactive anti-stalk antibodies against group 1 and group 2 HAs. However, low responses were observed in older groups, highlighting the impact of immunosenescence in adequate humoral immune responses.
Targeting immune checkpoints on tumor-associated macrophages in tumor immunotherapy
Authors: Xu Shumin , Wang Chenyang , Yang Lingge , Wu Jiaji , Li Mengshu , Xiao Peng , Xu Zhiyong , Xu Yun , Wang Kai
Published: May 2023

Unprecedented breakthroughs have been made in cancer immunotherapy in recent years. Particularly immune checkpoint inhibitors have fostered hope for patients with cancer. However, immunotherapy still exhibits certain limitations, such as a low response rate, limited efficacy in certain populations, and adverse events in certain tumors. Therefore, exploring strategies that can improve clinical response rates in patients is crucial. Tumor-associated macrophages (TAMs) are the predominant immune cells that infiltrate the tumor microenvironment and express a variety of immune checkpoints that impact immune functions. Mounting evidence indicates that immune checkpoints in TAMs are closely associated with the prognosis of patients with tumors receiving immunotherapy. This review centers on the regulatory mechanisms governing immune checkpoint expression in macrophages and strategies aimed at improving immune checkpoint therapies. Our review provides insights into potential therapeutic targets to improve the efficacy of immune checkpoint blockade and key clues to developing novel tumor immunotherapies.
Macrophytes and water quality in a large Baltic lagoon: relevance, development and restoration perspectives
Authors: Schernewski Gerald , Friedland Rene , Paysen Simon , Bucas Martynas , Dahlke Sven , von Weber Mario
Published: May 2023

We combine historical and recent monitoring data with modeling to get a better insight into water quality development of the large Oder/Szczecin Lagoon at the German/Polish border in the southern Baltic Sea region and especially of the role of macrophytes. Data indicates that the system is eutrophic for centuries and a naturally eutrophic system. During the last decades, external nutrient loads decreased but still keep the system in a eutrophic state. The systems primary production is limited by light and nitrogen and cannot be sufficiently managed by external nutrient load reductions. We consider 36% macrophyte coverage of the lagoon area as potential historical maximum. Despite its shallowness the lagoon was never a macrophyte dominated, clear water system. About 31% of the lagoon area would be covered by macrophytes in a good ecological status according to the European Water Framework Directive. However, the existing water transparency targets seem too ambitious and not realistic. Changes in macrophyte coverage on water quality are restricted to near shore areas and hardly affect the open lagoon. Existing models require an improved representation of water transparency and effects on macrophyte colonization depth. Presently the patchy macrophyte coverage is only about 12% of the lagoon area. This low coverage and a relatively poor species composition results in a non-satisfactory state classification. However, ecologically valuable angiosperms and charophytes seem to recover. A strict avoidance of mechanical disturbances could be a measure to support macrophyte re-colonization. A systematic improvement of piscivorous fish stocks may be a supporting measure to reduce eutrophication. Restoration perspectives and consequences for environmental policies are discussed.
Best practices for operating underwater gliders in Atlantic Canada
Authors: von Oppeln-Bronikowski Nicolai , de Young Brad , Belzile Melany , Comeau Adam , Cyr Frédéric , Davis Richard , Emery Pamela , Richards Clark , Hebert David , Van Der Meer Jude
Published: May 2023

Ocean gliders are versatile tools for making ocean observations. This paper summarizes the experience, of nearly two decades, of glider observing activity in Atlantic Canada. It reviews key considerations for operating gliders based on the experience and the lessons learned. This paper has three main goals: 1. To provide new and emerging glider users with guidance and considerations for developing a glider program. 2. Review the literature on sensor development for gliders and the use of gliders. 3. To highlight different mission scenarios that include enough practical considerations to support operating gliders. The use of gliders is rapidly expanding, but the documentation and consolidation of best practices for their operational use in Atlantic Canada remains underdeveloped. This summary provides a guide that should be helpful both to new and experienced glider operators and potential users, to observe the oceanography of this region and addresses regional challenges. We believe documenting our experience will be also helpful to the global glider community. We summarize the most critical considerations of utilizing gliders. We review the issues specific to the platform use and concerns about how to optimize the use of key sensors to contribute to an oceanographic observing program.
The effects of microplastic on the thermal profile of sand: implications for marine turtle nesting grounds
Authors: Fuentes Mariana M. P. B. , Beckwidth Valencia , Ware Matthew
Published: May 2023

Introduction

Microplastics (i.e., plastic debris smaller than 5mm) found in coastal areas can impact the marine habitat used by endangered species since they may alter sand properties including temperature and permeability. Such alterations may pose a significant threat to marine turtle populations as nest productivity, sexual development, and hatchling fitness are dependent on conditions within the nest, which incubate in the sand. Given that there is a record of microplastic presence at marine turtle nesting sites, this study was conducted to explore the potential influence of microplastics on the thermal profile of sediment typical of marine turtle nesting habitat.

Methods

The experiment was conducted at the Florida State University Coastal and Marine Laboratory where the temperatures of containers of sand mixed with 5-30% v/v of either black or white microplastics were recorded from July to September 2018.

Results

The addition of microplastics in the sand resulted in an increase in temperature – 0.017°C for each 1% v/v increase in microplastic. However, the color of the microplastic did not have a significant effect on sand temperature. Overall, the container with 30% v/v black particles had the highest mean temperature increase of 0.58°C (± 0.34°C) over the control.

Discussion

The results obtained from this study indicate that extreme concentrations of microplastics could be an issue for marine turtles as any changes in sand temperature may affect the sex ratio of hatchlings and/or alter nest productivity.
Genetic footprints of Quaternary glacial cycles over the patterns of population diversity and structure in three Nacella (Patellogastropoda: Nacellidae) species across the Magellan province in southern South America
Authors: González-Wevar Claudio A. , de Aranzamendi María Carla , Segovia Nicolás I. , Rosenfeld Sebastián , Maturana Claudia S. , Molina Cristian Ríos , Brickle Paul , Gardenal Cristina N. , Bastida Ricardo , Poulin Elie
Published: May 2023

Quaternary glaciations severely altered landscape/seascape at high latitudes and had major consequences on species geographical ranges, population sizes, genetic differentiation and speciation rates. The Magellan province in southern South America, constitutes an interesting area to evaluate the effect of glaciations over near-shore marine benthic organisms. Existing data have showed clear signatures of population genetic bottlenecks during glacial maxima followed by recent recolonizations and expansions during the interglacial. Here, we present new population-based analyses in species of the patellogastropod genus Nacella (N. deaurata, N. magellanica, and N. mytilina). The species N. magellanica and N. deaurata inhabit rocky ecosystems while N. mytilina lives closely associated with kelps. The analyzed species exhibit narrow bathymetric ranges and consequently should have been severely affected by recurrent glacial cycles. We performed phylogeographic and demographic analyses in Nacella species including different localities across their respective distributions in the Magellan province including the Falkland/Malvinas Islands (F/M). Genetic analyses showed that all Nacella species exhibited low levels of genetic diversity, the presence of single dominant broadly distributed haplotypes, lack of correlation between geographical and genetic distance, and recent demographic growths, which are evidence supporting rapid postglacial expansions. Such results may have been facilitated by larval and/or rafting-mediated dispersal following the Cape Horn Current System. The three species showed strong and significant differentiation between F/M and southern Pacific margin (SPM) populations including localities across the Strait of Magellan and Cape Horn. Haplotype genealogies and mismatch analyses recognized older and more complex demographic histories in the F/M than in South America. Different glaciological histories between SPM and F/M may be responsible of the marked phylogeographic structure in the analyzed species of Nacella. Alternatively, as previously proposed, the F/M represent a glacial refugium for Nacella species (sink area), as well as a secondary contact zone where endemic haplotypes are found together with recently arrived South American ones. Historical and contemporary processes, contrasting glacial histories between the analyzed areas, as well as life history traits of the analyzed organisms are main factors explaining current phylogeographic patterns of shallow Magellan marine benthic organisms.
Efficacy and safety of fondaparinux in preventing venous thromboembolism in Chinese cancer patients: a single-arm, multicenter, retrospective study
Authors: Wang Lei , Su Zhong , Xie Chunying , Li Ruijun , Pan Wei , Xu Lu , Chen Fei , Cheng Gang
Published: May 2023

Objective

Fondaparinux is a synthetic anticoagulant for the prevention of venous thromboembolism (VTE), and its administration in Chinese cancer patients is rarely reported. This study aimed to assess the efficacy and safety of fondaparinux in preventing VTE in Chinese cancer patients.

Methods

A total of 224 cancer patients who received fondaparinux treatment were reviewed in this single-arm, multicenter, retrospective study. Meanwhile, VTE, bleeding, death, and adverse events of those patients in the hospital and at 1 month after treatment (M1) were retrieved, respectively.

Results

The in-hospital VTE rate was 0.45% and there was no (0.00%) VTE occurrence at M1. The in-hospital bleeding rate was 2.68%, among which the major bleeding rate was 2.23% and the minor bleeding rate was 0.45%. Moreover, the bleeding rate at M1 was 0.90%, among which both the major and minor bleeding rates were 0.45%. The in-hospital death rate was 0.45% and the death rate at M1 was 0.90%. Furthermore, the total rate of adverse events was 14.73%, including nausea and vomiting (3.13%), gastrointestinal reactions (2.23%), and reduced white blood cells (1.34%).

Conclusion

Fondaparinux could effectively prevent VTE with low bleeding risk and acceptable tolerance in cancer patients.
Development and validation of an endoplasmic reticulum stress-related molecular prognostic model for breast cancer
Authors: Fan Pengyu , Wang Jiajia , Li Ruolei , Chang Kexin , Liu Liuyin , Wang Yaping , Wang Zhe , Zhang Bo , Ji Cheng , Zhang Jian , Chen Suning , Ling Rui
Published: May 2023

Background

Breast cancer is the most frequently diagnosed cancer and a leading cause of cancer-related death in women. Endoplasmic reticulum stress (ERS) plays a crucial role in the pathogenesis of several malignancies. However, the prognostic value of ERS-related genes in breast cancer has not been thoroughly investigated.

Methods

We downloaded and analyzed expression profiling data for breast invasive carcinoma samples in The Cancer Genome Atlas-Breast Invasive Carcinoma (TCGA-BRCA) and identified 23 ERS-related genes differentially expressed between the normal breast tissue and primary breast tumor tissues. We constructed and validated risk models using external test datasets. We assessed the differences in sensitivity to common antitumor drugs between high- and low-scoring groups using the Genomics of Drug Sensitivity in Cancer (GDSC) database, evaluated the sensitivity of patients in high- and low-scoring groups to immunotherapy using the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm, and assessed immune and stromal cell infiltration in the tumor microenvironment (TME) using the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm. We also analyzed the expression of independent factors in the prognostic model using the Western-blot analysis for correlation in relation to breast cancer.

Results

Using multivariate Cox analysis, FBXO6, PMAIP1, ERP27, and CHAC1 were identified as independent prognostic factors in patients with breast cancer. The risk score in our model was defined as the endoplasmic reticulum score (ERScore). ERScore had high predictive power for overall survival in patients with breast cancer. The high-ERScore group exhibited a worse prognosis, lower drug sensitivity, and lower immunotherapy response and immune infiltration than did the low-ERScore group. Conclusions based on ERScore were consistent with Western-blot results.

Conclusion

We constructed and validated for the first time an endoplasmic reticulum stress-related molecular prognostic model for breast cancer with reliable predictive properties and good sensitivity, as an important addition to the prognostic prediction model for breast cancer.
Effects of alkalization therapy on hepatocellular carcinoma: a retrospective study
Authors: Isowa Masahide , Hamaguchi Reo , Narui Ryoko , Morikawa Hiromasa , Wada Hiromi
Published: May 2023

Background

In hepatocellular carcinoma (HCC) patients, is difficult to prevent recurrence even when remission is achieved. In addition, even with the advent of drugs that are effective for the treatment of HCC, a satisfactory extension of patient survival has not been achieved. To overcome this situation, we hypothesized that the combination of alkalization therapy with standard treatments will improve the prognosis of HCC. We here report the clinical results of HCC patients treated with alkalization therapy at our clinic.

Patients and methods

Patients with HCC treated at Karasuma Wada Clinic (in Kyoto, Japan), from January 1, 2013, to December 31, 2020 were analyzed. Overall survival (OS) from both the time of diagnosis and the start of alkalization therapy for each patient was compared. The mean urine pH was also calculated as a surrogate marker of tumor microenvironment pH, and OS from the start of alkalization therapy was compared between patients with a mean urine pH of ≥ 7.0 and those with a mean urine pH of < 7.0.

Results

Twenty-three men and six women were included in the analysis, with a mean age at diagnosis of 64.1 years (range: 37–87 years). Seven of the 29 patients had extrahepatic metastases. Patients were divided into two groups according to their mean urine pH after the initiation of alkalization therapy: 12 of the 29 patients had a mean urine pH of ≥ 7.0, and 17 had a mean urine pH of < 7.0. The median OS from diagnosis was 95.6 months (95% confidence interval [CI] = 24.7-not reached), and from the start of alkalization therapy was 42.3 months (95% CI = 8.93-not reached). The median OS from the start of alkalization therapy in patients with a urine pH of ≥ 7.0 was not reached (n = 12, 95% CI = 3.0-not reached), which was significantly longer than that in patients with a pH of < 7.0 (15.4 months, n = 17, 95% CI = 5.8-not reached, p < 0.05).

Conclusions

The addition of alkalization therapy to standard therapies may be associated with more favorable outcomes in HCC patients with increased urine pH after alkalization therapy.
The pro-tumorigenic cytokine IL-32 has a high turnover in multiple myeloma cells due to proteolysis regulated by oxygen-sensing cysteine dioxygenase and deubiquitinating enzymes
Authors: Kastnes Martin , Aass Kristin Roseth , Bouma Siri Anshushaug , Årseth Charlotte , Zahoor Muhammad , Yurchenko Mariia , Standal Therese
Published: May 2023

IL-32 is a pro-inflammatory cytokine expressed by several types of cancer cells and immune cells. Currently, no treatment targeting IL-32 is available, and its intracellular and exosomal localization make IL-32 less accessible to drugs. We previously showed that hypoxia promotes IL-32 expression through HIF1α in multiple myeloma cells. Here, we demonstrate that high-speed translation and ubiquitin-dependent proteasomal degradation lead to a rapid IL-32 protein turnover. We find that IL-32 protein half-life is regulated by the oxygen-sensing cysteine-dioxygenase ADO and that deubiquitinases actively remove ubiquitin from IL-32 and promote protein stability. Deubiquitinase inhibitors promoted the degradation of IL-32 and may represent a strategy for reducing IL-32 levels in multiple myeloma. The fast turnover and enzymatic deubiquitination of IL-32 are conserved in primary human T cells; thus, deubiquitinase inhibitors may also affect T-cell responses in various diseases.
Development and verification of prognostic nomogram for ampullary carcinoma based on the SEER database
Authors: Tang Nan , Chen Zeng-Yin , Yang Zhen , Shang He-Zhen , Shi Guang-Jun
Published: May 2023

Background

Ampullary carcinoma (AC) is a rare cancer of the digestive system that occurs in the ampulla at the junction of the bile duct and pancreatic duct. However, there is a lack of predictive models for overall survival (OS) and disease -specific survival (DSS) in AC. This study aimed to develop a prognostic nomogram for patients with AC using data from the Surveillance, Epidemiology, and End Results Program (SEER) database.

Methods

Data from 891 patients between 2004 and 2019 were downloaded and extracted from the SEER database. They were randomly divided into the development group (70%) and the verification group (30%), and then univariate and multivariate Cox proportional hazards regression, respectively, was used to explore the possible risk factors of AC. The factors significantly related to OS and DSS were used to establish the nomogram, which was assessed via the concordance index (C-index), and calibration curve. An internal validation was conducted to test the accuracy and effectiveness of the nomogram. Kaplan–Meier calculation was used to predict the further OS and DSS status of these patients.

Results

On multivariate Cox proportional hazards regression, the independent prognostic risk factors associated with OS were age, surgery, chemotherapy, regional node positive (RNP),extension range and distant metastasis with a moderate C-index of 0.731 (95% confidence interval (CI): 0.719-0.744) and 0.766 (95% CI: 0.747-0.785) in the development and verification groups, respectively. While, marital status, surgery, chemotherapy, regional node positive (RNP),extension range and distant metastasis were significantly linked to AC patients’ DSS, which have a better C-index of 0.756 (95% confidence interval (CI): 0.741-0.770) and 0.781 (95% CI: 0.757-0.805) in the development and verification groups. Both the survival calibration curves of 3- and 5-year OS and DSS brought out a high consistency.

Conclusion

Our study yielded a satisfactory nomogram showing the survival of AC patients, which may help clinicians to assess the situation of AC patients and implement further treatment.
Comprehensive analysis of the complete mitochondrial genomes of three Coptis species (C. chinensis, C. deltoidea and C. omeiensis): the important medicinal plants in China
Authors: Zhong Furong , Ke Wenjia , Li Yirou , Chen Xiaoyan , Zhou Tao , Xu Binjie , Qi Luming , Yan Zhuyun , Ma Yuntong
Published: May 2023

Coptis plants (Ranunculaceae) contain high levels of isoquinoline alkaloids and have a long history of medicinal use. Coptis species are of great value in pharmaceutical industries and scientific research. Mitochondria are considered as one of the central units for receiving stress signals and arranging immediate responses. Comprehensive characterizations of plant mitogenomes are imperative for revealing the relationship between mitochondria, elucidating biological functions of mitochondria and understanding the environmental adaptation mechanisms of plants. Here, the mitochondrial genomes of C. chinensis, C. deltoidea and C. omeiensis were assembled through the Nanopore and Illumina sequencing platform for the first time. The genome organization, gene number, RNA editing sites, repeat sequences, gene migration from chloroplast to mitochondria were compared. The mitogenomes of C. chinensis, C. deltoidea and C. omeiensis have six, two, two circular-mapping molecules with the total length of 1,425,403 bp, 1,520,338 bp and 1,152,812 bp, respectively. The complete mitogenomes harbors 68-86 predicted functional genes including 39-51 PCGs, 26-35 tRNAs and 2-5 rRNAs. C. deltoidea mitogenome host the most abundant repeat sequences, while C. chinensis mitogenome has the largest number of transferred fragments from its chloroplasts. The large repeat sequences and foreign sequences in the mitochondrial genomes of Coptis species were related to substantial rearrangements, changes in relative position of genes and multiple copy genes. Further comparative analysis illustrated that the PCGs under selected pressure in mitochondrial genomes of the three Coptis species mainly belong to the mitochondrial complex I (NADH dehydrogenase). Heat stress adversely affected the mitochondrial complex I and V, antioxidant enzyme system, ROS accumulation and ATP production of the three Coptis species. The activation of antioxidant enzymes, increase of T-AOC and maintenance of low ROS accumulation in C. chinensis under heat stress were suggested as the factors for its thermal acclimation and normal growth at lower altitudes. This study provides comprehensive information on the Coptis mitogenomes and is of great importance to elucidate the mitochondrial functions, understand the different thermal acclimation mechanisms of Coptis plants, and breed heat-tolerant varieties.
Estimation of morphological variation in seed traits of Sophora moorcroftiana using digital image analysis
Authors: Dong Rui , Guo Qiqiang , Li Huie , Li Jiangrong , Zuo Weiwei , Long Cha
Published: May 2023

Sophora moorcroftianais a leguminous plant endemic to the Qinghai-Tibet Plateau. It has excellent abiotic stress tolerance and is considered an ideal species for local ecological restoration. However, the lack of genetic diversity in the seed traits ofS. moorcroftianahinders its conservation and utilization on the plateau. Therefore, in this study, genotypic variation and phenotypic correlations were estimated for nine seed traits among 15 accessions ofS. moorcroftianaover two years, 2014 and 2019, respectively from 15 sample points. All traits evaluated showed significant (P< 0.05) genotypic variation. In 2014, accession mean repeatability was high for seed perimeter, length, width, and thickness, and 100-seed weight. In 2019, mean repeatability for seed perimeter and thickness, and 100-seed weight were high. The estimates of mean repeatability for seed traits across the two years ranged from 0.382 for seed length to 0.781 for seed thickness. Pattern analysis showed that 100-seed weight was significantly positively correlated with traits such as seed perimeter, length, width, and thickness, and identified populations with breeding pool potential. In the biplot, principal components 1 and 2 explained 55.22% and 26.72% of the total variation in seed traits, respectively. These accessions could produce breeding populations for recurrent selection to developS. moorcroftianavarieties suitable for restoring the fragile ecological environment of the Qinghai-Tibet Plateau.
Ammonium-nitrate mixtures dominated by NH4+-N promote the growth of pecan (Carya illinoinensis) through enhanced N uptake and assimilation
Authors: Chen Mengyun , Zhu Kaikai , Xie Junyi , Liu Junping , Qiao Zhenbing , Tan Pengpeng , Peng Fangren
Published: May 2023

Nitrogen (N) limits plant productivity, and its uptake and assimilation may be regulated by N sources, N assimilating enzymes, and N assimilation genes. Mastering the regulatory mechanisms of N uptake and assimilation is a key way to improve plant nitrogen use efficiency (NUE). However, it is poorly known how these factors interact to influence the growth process of pecans. In this study, the growth, nutrient uptake and N assimilation characteristics of pecan were analyzed by aeroponic cultivation at varying NH4 +/NO3 − ratios (0/0, 0/100,25/75, 50/50, 75/25,100/0 as CK, T1, T2, T3, T4, and T5). The results showed that T4 and T5 treatments optimally promoted the growth, nutrient uptake and N assimilating enzyme activities of pecan, which significantly increased aboveground biomass, average relative growth rate (RGR), root area, root activity, free amino acid (FAA) and total organic carbon (TOC) concentrations, nitrate reductase (NR), nitrite reductase (NiR), glutamine synthetase (GS), glutamate synthase (Fd-GOGAT and NADH-GOGAT), and glutamate dehydrogenase (GDH) activities. According to the qRT-PCR results, most of the N assimilation genes were expressed at higher levels in leaves and were mainly significantly up-regulated under T1 and T4 treatments. Correlation analysis showed that a correlation between N assimilating enzymes and N assimilating genes did not necessarily exist. The results of partial least squares path model (PLS-PM) analysis indicated that N assimilation genes could affect the growth of pecan by regulating N assimilation enzymes and nutrients. In summary, we suggested that the NH4 +/NO3 − ratio of 75:25 was more beneficial to improve the growth and NUE of pecan. Meanwhile, we believe that the determination of plant N assimilation capacity should be the result of a comprehensive analysis of N concentration, N assimilation enzymes and related genes.
VLSD—An Efficient Subgroup Discovery Algorithm Based on Equivalence Classes and Optimistic Estimate
Authors: Lopez-Martinez-Carrasco Antonio , Juarez Jose M. , Campos Manuel , Canovas-Segura Bernardo
Published: May 2023

Subgroup Discovery (SD) is a supervised data mining technique for identifying a set of relations (subgroups) among attributes from a dataset with respect to a target attribute. Two key components of this technique are (i) the metric used to quantify a subgroup extracted, called quality measure, and (ii) the search strategy used, which determines how the search space is explored and how the subgroups are obtained. The proposal made in this work consists of two parts, (1) a new and efficient SD algorithm which is based on the equivalence class exploration strategy, and which uses a pruning based on optimistic estimate, and (2) a data structure used when implementing the algorithm in order to compute subgroup refinements easily and efficiently. One of the most important advantages of this algorithm is its easy parallelization. We have tested the performance of our SD algorithm with respect to some other well-known state-of-the-art SD algorithms in terms of runtime, max memory usage, subgroups selected, and nodes visited. This was completed using a collection of standard, well-known, and popular datasets obtained from the relevant literature. The results confirmed that our algorithm is more efficient than the other algorithms considered.
Japan’s Corporate Governance Transformation: Convergence or Reconfiguration?
Authors: Renou Theo , Carraz René , Burger-Helmchen Thierry
Published: May 2023

Japanese firms have historically followed a country-specific model of corporate governance. Yet, Japan has had to adapt its corporate model over the last 30 years, along with the transformation of distinctive characteristics of Japanese capitalism in the same period. We review the historical evolution of Japanese corporate governance over the last three decades with a specific emphasis on the changes in the capital structure of major companies and the efforts to correct ineffective board of directors monitoring. By doing this, we investigate to what extent specific Japanese corporate governance features may explain the nation’s economic situation over this period. Thereby, we try to clarify the influences that have presided over recent corporate governance reforms in Japan despite the existence of managerial failures and corporate scandals. This paper places itself into the debate over the diversity of capitalism as it portrays the specificities, differences, and converging trends of Japanese corporate governance practices.
Including the Excluded: Sense-Making and Job Crafting as Drivers of Dialogical Change Management in Italian Universities for Refugees’ Inclusion
Authors: Ceschel Federico , Limata Plinio , Marchegiani Lucia
Published: May 2023

Higher Education Institutions (HEIs) are increasingly called to substantiate their impact on society in terms of inclusivity and social sustainability, as prioritized in the pursuit of the “Third Mission” (TM). Today, HEIs are confronted with the demand to ensure refugees’ inclusivity. However, how administrative and teaching staff enact such change within the organization to match the TM goals is under-investigated. This study explores the adoption of the European Qualification Passport for Refugees (EQPR) as an instrument for universities to pursue the TM in Italy. By adopting a theoretical sense-making approach, we find that the individual role of the staff in fostering organizational change depends on the adopted “emergent” approach to change and on internal factors, such as individual perceptions and experiences. This study contributes to the literature by showing contradictory aspects of the HEIs’ pursuit of the TM. It sheds light on the interplay between different dimensions and grounded processes of sense-making.
Thermal Simulations of Drilling of Cryogenic Lunar Soils Containing Water Ice
Authors: Cui Jinsheng , Chen Baoxian , Liu Sibo , Zhao Deming , Zhang Weiwei
Published: May 2023

Water ice is an important water source in lunar polar soil. Drilling and sampling lunar polar soil are important engineering tasks of lunar exploration. In view of the influence of temperature rise on the quality of samples obtained by drilling, the heat transfer and temperature rise in drilled ice-containing lunar soil were investigated. In this study, a thermal simulation model for drilling lunar soil was established based on the discrete element method (DEM). Simulations of the drilling temperature of lunar soil containing ice at 3–5% were performed assuming normal pressure and low temperature. After validating the feasibility and accuracy of the simulation method, the temperatures of the drilling tools and lunar soil were analyzed. Furthermore, drilling in a vacuum was simulated as well, and the results indicated that ice sublimation was negligible for reasonable drilling procedures in the current study.
MLFAnet: A Tomato Disease Classification Method Focusing on OOD Generalization
Authors: Li Dasen , Yin Zhendong , Zhao Yanlong , Zhao Wudi , Li Jiqing
Published: May 2023

Tomato disease classification based on images of leaves has received wide attention recently. As one of the best tomato disease classification methods, the convolutional neural network (CNN) has an immense impact due to its impressive performance. However, better performance is verified by independent identical distribution (IID) samples of tomato disease, which breaks down dramatically on out-of-distribution (OOD) classification tasks. In this paper, we investigated the corruption shifts, which was a vital component of OOD, and proposed a tomato disease classification method to improve the performance of corruption shift generalization. We first adopted discrete cosine transform (DCT) to obtain the low-frequency components. Then, the weight of the feature map was calculated by multiple low-frequency components, in order to reduce the influence of high-frequency variation caused by corrupted perturbation. The proposed method, termed as a multiple low-frequency attention network (MLFAnet), was verified by the benchmarking of ImageNet-C. The accuracy result and generalization performance confirmed the effectiveness of MLFAnet. The satisfactory generalization performance of our proposed classification method provides a reliable tool for the diagnosis of tomato disease.
Comparing Two Methods of Leaf Area Index Estimation for Rice (Oryza sativa L.) Using In-Field Spectroradiometric Measurements and Multispectral Satellite Images
Authors: Serrano Reyes Jorge , Jiménez José Ulises , Quirós-McIntire Evelyn Itzel , Sanchez-Galan Javier E. , Fábrega José R.
Published: May 2023

This work presents a remote sensing application to estimate the leaf area index (LAI) in two rice (Oryza sativa L.) varieties (IDIAP 52-05 and IDIAP FL 137-11), as a proxy for crop performance. In-field, homogeneous spectroradiometric measurements (350–1050 nm) were carried in two campaigns (June–November 2017 and January–March 2018), on a private farm, TESKO, located in Juan Hombrón, Coclé Province, Panama. The spectral fingerprint of IDIAP 52-05 plants was collected in four dates (47, 67, 82 and 116 days after sowing), according to known phenological stages of rice plant growth. Moreover, true LAI or green leaf area was measured from representative plants and compared to LAI calculated from normalized PlanetScope multi-spectral satellite images (selected according to dates close to the in-field collection). Two distinct estimation models were used to establish the relationships of measured LAI and two vegetational spectral indices (NDVI and MTVI2). The results show that the MTVI2 based model has a slightly higher predictive ability of true LAI (R2 = 0.92, RMSE = 2.20), than the NDVI model. Furthermore, the satellite images collected were corrected and satellite LAI was contrasted with true LAI, achieving in average 18% for Model 2 for MTVI2, with the NDVI (Model 1) corrected model having a smaller error around 13%. This work provides an important advance in precision agriculture, specifically in the monitoring of total crop growth via LAI for rice crops in the Republic of Panama.