bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-NMDAR encephalitis in Crohn’s disease undergoing long-term infliximab treatment: A case report
Authors: Oh Shin Ju , Kwon Young Nam , Lee Chang Kyun , Lee Jin San
Published: October 2022

Infliximab, a chimeric monoclonal antibody against anti-tumor necrosis factor-α (TNF-α), has revolutionized the management of inflammatory bowel disease. However, a recent nested case-control study showed that anti-TNF-α therapy exposure in patients with autoimmune diseases is associated with an increased risk of inflammatory central nervous system (CNS) events. A 27-year-old man diagnosed with Crohn’s disease at 17 years of age was referred to our clinic for suffering with Wernicke’s aphasia and the right-hand weakness over two weeks. Nine years of treatment for Crohn’s disease with infliximab anti-TNF-α therapy was well tolerated. An initial MRI revealed diffuse leptomeningeal enhancement along the bilateral cerebral sulci without any parenchymal abnormalities. Cerebrospinal fluid (CSF) and serum N-methyl-D-aspartate receptor (NMDAR) antibody testing yielded positive results. Anti-NMDAR encephalitis was diagnosed, and the patient was treated with rituximab. A follow-up brain MRI showed new multiple cerebral lesions in the left insular cortex and subcortical white matter of the left frontal and temporal gyri. Approximately 8 months after symptom onset, the CSF and serum NMDAR antibody converted to negative. Twelve months later, the patient fully recovered from anti-NMDAR encephalitis without any neurological deficits and is currently being treated with the anti-interleukin 12/23 agent ustekinumab for Crohn’s disease. This is the first report of not only a patient with infliximab-associated anti-NMDAR encephalitis in Crohn’s disease but also of an inflammatory non-demyelinating CNS event during long-term suppression of TNF-α. Our case highlights the need for clinicians to recognize the possibility of a paradoxical autoimmune response occurring with novel biological therapies.
Eosinophils in filarial infections: Inducers of protection or pathology?
Authors: Ehrens Alexandra , Hoerauf Achim , Hübner Marc P.
Published: October 2022

Filariae are parasitic roundworms, which can cause debilitating diseases such as lymphatic filariasis and onchocerciasis. Lymphatic filariasis, also known as elephantiasis, and onchocerciasis, commonly referred to as river blindness, can lead to stigmatizing pathologies and present a socio-economic burden for affected people and their endemic countries. Filariae typically induce a type 2 immune response, which is characterized by cytokines, i.e., IL-4, IL-5 and IL-13 as well as type 2 immune cells including alternatively activated macrophages, innate lymphoid cells and Th2 cells. However, the hallmark characteristic of filarial infections is a profound eosinophilia. Eosinophils are innate immune cells and pivotal in controlling helminth infections in general and filarial infections in particular. By modulating the function of other leukocytes, eosinophils support and drive type 2 immune responses. Moreover, as primary effector cells, eosinophils can directly attack filariae through the release of granules containing toxic cationic proteins with or without extracellular DNA traps. At the same time, eosinophils can be a driving force for filarial pathology as observed during tropical pulmonary eosinophilia in lymphatic filariasis, in dermatitis in onchocerciasis patients as well as adverse events after treatment of onchocerciasis patients with diethylcarbamazine. This review summarizes the latest findings of the importance of eosinophil effector functions including the role of eosinophil-derived proteins in controlling filarial infections and their impact on filarial pathology analyzing both human and experimental animal studies.
A review of spatial profiling technologies for characterizing the tumor microenvironment in immuno-oncology
Authors: Hu Bian , Sajid Muhammad , Lv Rong , Liu Lianxin , Sun Cheng
Published: October 2022

Interpreting the mechanisms and principles that govern gene activity and how these genes work according to -their cellular distribution in organisms has profound implications for cancer research. The latest technological advancements, such as imaging-based approaches and next-generation single-cell sequencing technologies, have established a platform for spatial transcriptomics to systematically quantify the expression of all or most genes in the entire tumor microenvironment and explore an array of disease milieus, particularly in tumors. Spatial profiling technologies permit the study of transcriptional activity at the spatial or single-cell level. This multidimensional classification of the transcriptomic and proteomic signatures of tumors, especially the associated immune and stromal cells, facilitates evaluation of tumor heterogeneity, details of the evolutionary trajectory of each tumor, and multifaceted interactions between each tumor cell and its microenvironment. Therefore, spatial profiling technologies may provide abundant and high-resolution information required for the description of clinical-related features in immuno-oncology. From this perspective, the present review will highlight the importance of spatial transcriptomic and spatial proteomics analysis along with the joint use of other sequencing technologies and their implications in cancers and immune-oncology. In the near future, advances in spatial profiling technologies will undoubtedly expand our understanding of tumor biology and highlight possible precision therapeutic targets for cancer patients.
Assessment of the progress toward elimination of lymphatic filariasis in the Federal Capital Territory- Abuja, Nigeria
Authors: Amanyi-Enegela Juliana Ajuma , Kumbur Joseph , Burn Nicholas , Sankar Girija , Davies Emmanuel , Ishaya Rinpan , Ogoshi Christopher , Ekweremadu Bright , Omoi Samuel , Qureshi Babar
Published: October 2022

Lymphatic filariasis (LF) is a neglected tropical disease caused by threadlike worms (nematodes) that live in the lymphatic vessels of humans. Although three species of filarial parasites (Wuchereria bancrofti, Brugia malayi and Brugia timori) infect humans; 90% of infection is caused by Wuchereria Bancrofti and humans are its exclusive host. Nigeria is one of over 70 countries endemic for Lymphatic filariasis with an estimated 134 million people at the risk of infection. The Federal Capital Territory (FCT), which is endemic for LF, commenced mass drug administration (MDA) using ivermectin (IVM) and albendazole (ALB) in 2011. While MDA is continuing in two Area Councils, in 2020, we assessed the impact of MDA on LF prevalence in two area councils that had achieved five effective annual rounds of MDA. In 2010, a baseline mapping exercise was conducted in all six area councils of FCT-Abuja. The results revealed that four out of the six area councils were endemic for LF, with prevalence ranging from 1.0%-4.0%. The number of persons treated with ivermectin and albendazole in the four Area Councils was documented during annual MDA and population-based cluster surveys were conducted at least once in each area council during the five years of treatment, to verify the reported geographic and programme MDA coverage. This is the number treated divided by the total population eligible to receive treatment (usually <5years). The survey results confirmed that in two area councils (Abaji and Kuje) the coverage exceeded the target of 65% the while two other Councils did not reach the recommended coverage. A pre-transmission assessment survey (pre-TAS) was conducted in one sentinel site and at least one spot check site in Abaji and Kuje in 2019 and were found to have LF antigenemia (LF Ag) < 2% (range 0.0% to 1.99%). In 2020, transmission assessment surveys (TAS) were conducted in the two area councils that previously passed the Pre-transmission assessment survey. The results showed that the two Evaluation units had achieved the LF Ag threshold required to stop MDA. FCT has made significant progress towards LF elimination with two Area Councils qualifying to stop treatment. However, two other area councils still require a further two years of mass drug administration with effective MDA coverage before these area councils qualify for impact assessment.
Long-term ecological monitoring of reefs on Hawai’i Island (2003-2020): Characterization of a common cryptic crust, Ramicrusta hawaiiensis (Peyssonneliales, Rhodophyta)
Authors: Grady Bryant W. , Kittle Ronald P. , Pugh Ashley , Lamson Megan R. , Richards Joseph L. , Fredericq Suzanne , McDermid Karla J. , Allen Quintin , Asner Gregory P.
Published: October 2022

The recently described crustose calcifying red algal species Ramicrusta hawaiiensis, known only from mesophotic depths off Lehua Island, west of Kaua’i Island, was found in shallow benthic reef habitats (3-18 m deep) along the western coast of Hawai’i Island. Molecular and microscopy techniques were used for genetic confirmation and for detailed morphological and anatomical examination. Two independent benthic cover survey datasets collected from west Hawai’i Island were used to investigate temporal and geographic distribution of Ramicrusta. In both datasets, we report Ramicrusta at approximately 60% of the sites surveyed. Benthic cover for this alga varies among sites and among years and its presence in west Hawai’i is evident since at least 2003. These findings help to document Hawaiian coral reef ecosystem change and benthic community composition reshuffling. This study also emphasizes the critical importance of taxonomy and proper identification of macroalgal species to understand the potential for phase-shifts of dominant taxa in coral reef ecosystems after environmental disturbances and fluctuations in abiotic factors. In the last decade, members of the red algal order Peyssonneliales have increased in abundance and overgrown other benthic species in reef ecosystems in the Caribbean and tropical Pacific. The novel aspect of finding abundant Ramicrusta in much shallower water than originally described, the decadal presence of Ramicrusta, and its potential for competition with other benthic organisms make this research valuable to coral reef ecology and justify further investigation of Ramicrusta ecology and biology in the Hawaiian Islands and globally.
Effects of dietary methanolic extract of hyssop, Hyssopus officinalis, on growth performance, hepatic antioxidant, humoral and intestinal immunity, and intestinal bacteria of rainbow trout, Oncorhynchus mykiss
Authors: Yousefi Morteza , Hoseini Seyyed Morteza , Abtahi Behrooz , Vatnikov Yury Anatolyevich , Kulikov Evgeny Vladimirovich , Rodionova Natalya Yurievna
Published: October 2022

The aims of the present study were to assess the effects of Hyssop, Hyssopus officinalis, methanolic extract (HE) on growth performance, hepatic oxidative status, humoral and intestinal immunity, and intestinal bacteria of rainbow trout, Oncorhynchus mykiss. Fish were allocated into twelve tanks for four treatments, receiving diets containing 0, 100, 250, and 500 mg/kg HE for eight weeks. The results showed that dietary HE supplementation induced no significant differences in the growth performance, feed efficiency, and hematological parameters (P > 0.05). HE supplementation significantly increased total leukocyte count and the highest count was observed in 250 mg/kg HE treatment (P < 0.001). Fish in 250 and 500 mg/kg HE treatments exhibited significantly lower lymphocyte (P = 0.001) and higher neutrophil (P = 0.002) percentages; the former exhibited a significantly higher monocyte percentage (P = 0.021). Hepatic superoxide dismutase (100 and 250 mg/kg HE; P < 0.001), glutathione peroxidase (100 and 250 mg/kg HE; P = 0.001), glutathione reducatse (all HE treatments; P < 0.001), and reduced glutathione (250 mg/kg HE; P = 0.046) significantly increased, whereas hepatic malondialdehyde levels (250 and 500 mg/kg HE; P = 0.007) significantly decreased in HE-treated fish. Plasma total protein, albumin, globulin, lysozyme, and alternative complement significantly increased in 250 and 500 mg/kg HE treatments and plasma total Ig significantly increased in 250 mg/kg HE treatment. Quantitative real time PCR found no Streptococcus iniae, Lactococcus garvieae, Aeromonas hydrophila, Yersinia ruckeri, and Vibrio anguillarum in the fish intestines in any treatments. Lactobacillus sp. was detected in the fish intestinal samples, but there were no significant differences among the treatments (P = 0.352). Intestinal defensin (P = 0.044) and interleukin-1 beta (P = 0.0.035) expressions were significantly up-regulated in 100 mg/kg HE; intestinal interleukin-10 (P < 0.001) and tumor necrosis factor-alpha (P < 0.001) expressions were significantly up-regulated in 100 and 500 mg/kg HE; whereas, intestinal interleukin-6 expression was significantly (P = 0.009) up-regulated in 250 mg/kg HE treatments. It is concluded that HE is able to stimulate humoral and intestinal immune responses and hepatic antioxidant capacity. HE effective concentration in rainbow trout may be in the range of 100-250 mg/kg.
Economic feasibility of marine renewable energy: Review
Authors: Bhuiyan Miraj Ahmed , Hu Ping , Khare Vikas , Hamaguchi Yoshihiro , Thakur Barun Kumar , Rahman Muhammad Khalilur
Published: October 2022

This paper aims to comprehensively review the economic feasibility of Marine Renewable Energy. Five major continents are at different development stages of implementing MREs commercialization; Europe is in the most advanced, while Africa is at the initial stage. The Levelized Cost of Energy is usually used to make decisions and measure the plant’s economic feasibility. Literature suggests that MRE technology is still costly, and many emerging countries are sensitive to the income and use of MRE. Among various types of MREs, wind energy is the most feasible for many countries. Offshore wave energy is still at the pre-commercialization stage for many developing countries. Tidal energy plants can be economically viable depending on a reduction in investment cost and high capacity factors. Most of the world’s tidal flows have too low a speed to operate a turbine of commercial size for ocean thermal energy. In conclusion, the factors hindering MRE development are pointed out, and future challenges are discussed.
Sentiment analysis of tweets on alopecia areata, hidradenitis suppurativa, and psoriasis: Revealing the patient experience
Authors: Lee Irene Tai-Lin , Juang Sin-Ei , Chen Steven T. , Ko Christine , Ma Kevin Sheng-Kai
Published: October 2022

Background

Chronic dermatologic disorders can cause significant emotional distress. Sentiment analysis of disease-related tweets helps identify patients’ experiences of skin disease.

Objective

To analyze the expressed sentiments in tweets related to alopecia areata (AA), hidradenitis suppurativa (HS), and psoriasis (PsO) in comparison to fibromyalgia (FM).

Methods

This is a cross-sectional analysis of Twitter users’ expressed sentiment on AA, HS, PsO, and FM. Tweets related to the diseases of interest were identified with keywords and hashtags for one month (April, 2022) using the Twitter standard application programming interface (API). Text, account types, and numbers of retweets and likes were collected. The sentiment analysis was performed by the R “tidytext” package using the AFINN lexicon.

Results

A total of 1,505 tweets were randomly extracted, of which 243 (16.15%) referred to AA, 186 (12.36%) to HS, 510 (33.89%) to PsO, and 566 (37.61%) to FM. The mean sentiment score was −0.239 ± 2.90. AA, HS, and PsO had similar sentiment scores (p = 0.482). Although all skin conditions were associated with a negative polarity, their average was significantly less negative than FM (p < 0.0001). Tweets from private accounts were more negative, especially for AA (p = 0.0082). Words reflecting patients’ psychological states varied in different diseases. “Anxiety” was observed in posts on AA and FM but not posts on HS and PsO, while “crying” was frequently used in posts on HS. There was no definite correlation between the sentiment score and the number of retweets or likes, although negative AA tweets from public accounts received more retweets (p = 0.03511) and likes (p = 0.0228).

Conclusion

The use of Twitter sentiment analysis is a promising method to document patients’ experience of skin diseases, which may improve patient care through bridging misconceptions and knowledge gaps between patients and healthcare professionals.
Transmission of tetracycline resistance genes and microbiomes from manure-borne black soldier fly larvae frass to rhizosphere soil and pakchoi endophytes
Authors: Chen Jingyuan , Cai Yingfeng , Deng Weikang , Xing Sicheng , Liao Xindi
Published: October 2022

Manure treatment with black soldier fly larvae (BSFL) and BSFL frass application in crop land is a sustainable strategy; however, whether residual antibiotic resistance genes (ARGs) and their transmission risk are related to the manure BSFL treatment process is still unknown. In this paper, the effect of BSFL addition density on residual tetracycline resistance genes (TRGs) and transmission from frass to pakchoi was determined. The results showed that BSFL frass can provide sufficient nutrients for growth, improve the economic value of pakchoi, and reduce the risk of transmission of TRGs in chicken manure regardless of BSFL density. The potential hosts of the TRGs we detected were found in BSFL frass (Oblitimonas and Tissierella), rhizosphere soil (Mortierella and Fermentimonas), and pakchoi endophytes (Roseomonas). The present study concluded that BSFL frass produced by adding 100 BSFL per 100 g of chicken manure has the advantages of high value and low risk. These findings will provide important strategic guidance for animal manure disposal and theoretical support for preventing the transmission of TRGs in BSFL applications.
pH variation in medical implant biofilms: Causes, measurements, and its implications for antibiotic resistance
Authors: Behbahani Shayesteh Beladi , Kiridena Sachindra D. , Wijayaratna Uthpala N. , Taylor Cedric , Anker Jeffrey N. , Tzeng Tzuen-Rong Jeremy
Published: October 2022

The advent of implanted medical devices has greatly improved the quality of life and increased longevity. However, infection remains a significant risk because bacteria can colonize device surfaces and form biofilms that are resistant to antibiotics and the host’s immune system. Several factors contribute to this resistance, including heterogeneous biochemical and pH microenvironments that can affect bacterial growth and interfere with antibiotic biochemistry; dormant regions in the biofilm with low oxygen, pH, and metabolites; slow bacterial growth and division; and poor antibody penetration through the biofilm, which may also be regions with poor acid product clearance. Measuring pH in biofilms is thus key to understanding their biochemistry and offers potential routes to detect and treat latent infections. This review covers the causes of biofilm pH changes and simulations, general findings of metabolite-dependent pH gradients, methods for measuring pH in biofilms, effects of pH on biofilms, and pH-targeted antimicrobial-based approaches.
Biochemical and functional characterization of Brucella abortus cyclophilins: So similar, yet so different
Authors: Muruaga Emanuel J. , Briones Gabriel , Roset Mara S.
Published: October 2022

Brucella spp. are the etiological agent of animal and human brucellosis. We have reported previously that cyclophilins of Brucella (CypA and CypB) are upregulated within the intraphagosomal replicative niche and required for stress adaptation and host intracellular survival and virulence. Here, we characterize B. abortus cyclophilins, CypA, and CypB from a biochemical standpoint by studying their PPIase activity, chaperone activity, and oligomer formation. Even though CypA and CypB are very similar in sequence and share identical chaperone and PPIase activities, we were able to identify outstanding differential features between them. A series of differential peptide loops were predicted when comparing CypA and CypB, differences that might explain why specific antibodies (anti-CypA or anti-CypB) were able to discriminate between both cyclophilins without cross-reactivity. In addition, we identified the presence of critical amino acids in CypB, such as the Trp134 which is responsible for the cyclosporin A inhibition, and the Cys128 that leads to CypB homodimer formation by establishing a disulfide bond. Here, we demonstrated that CypB dimer formation was fully required for stress adaptation, survival within HeLa cells, and mouse infection in B. abortus. The presence of Trp134 and the Cys128 in CypB, which are not present in CypA, suggested that two different kinds of cyclophilins have evolved in Brucella, one with eukaryotic features (CypB), another (CypA) with similar features to Gram-negative cyclophilins.
Virus-like particles vaccines based on glycoprotein E0 and E2 of bovine viral diarrhea virus induce Humoral responses
Authors: Yang Ningning , Zhang Jiangwei , Xu Mingguo , Yi Jihai , Wang Zhen , Wang Yong , Chen Chuangfu
Published: October 2022

Bovine viral diarrhea/mucosal disease (BVD/MD) is a viral infectious disease that seriously endangers the health of cattle herds and brings serious economic losses to the global cattle industry. Virus-like particles (VLPs) are empty shell structures without viral nucleic acid, which are similar to natural virus particles in morphology and structure. Because of their strong immunogenicity and biological activity, some of them have been used as vaccines in clinical trials. In this study, we developed a strategy to generate BVDV (E0 + E2, E2 + E2) VLPs using an insect baculovirus expression vector system (BEVS). The VLPs obtained were detected by immunofluorescence assay (IFA), western blotting analyses and transmission electron microscope (TEM), and the results showed that VLPs of high purity were obtained. Mice immunized with VLPs (15  μg) and Freund’s adjuvant (100  μl) elicited higher BVDV-neutralizing antibody in comparison with Freund’s adjuvant control (p < 0.0001), and even on day 21 or 35 post-prime immunization, the neutralizing antibody levels of mice immunized with E0 + E2 or E2 + E2 VLPs were significantly higher compared with inactivated vaccine (p < 0.05). A subsequent challenge reveals that the viral loads of livers, kidneys, spleens, lungs and small intestines were significantly lower compared with control (p < 0.0001), and the viral loads of mice immunized with E0 + E2 or E2 + E2 VLPs in the small intestines were significantly lower compared with inactivated vaccine (p < 0.05). Thus, VLPs are a promising candidate vaccine and warrants further clinical evaluation.
Neural network learning using non-ideal resistive memory devices
Authors: Kim Youngseok , Gokmen Tayfun , Miyazoe Hiroyuki , Solomon Paul , Kim Seyoung , Ray Asit , Doevenspeck Jonas , Khan Raihan S. , Narayanan Vijay , Ando Takashi
Published: October 2022

We demonstrate a modified stochastic gradient (Tiki-Taka v2 or TTv2) algorithm for deep learning network training in a cross-bar array architecture based on ReRAM cells. There have been limited discussions on cross-bar arrays for training applications due to the challenges in the switching behavior of nonvolatile memory materials. TTv2 algorithm is known to overcome the device non-idealities for deep learning training. We demonstrate the feasibility of the algorithm for a linear regression task using 1R and 1T1R ReRAM devices. Using the measured device properties, we project the performance of a long short-term memory (LSTM) network with 78 K parameters. We show that TTv2 algorithm relaxes the criteria for symmetric device update response. In addition, further optimization of the algorithm increases noise robustness and significantly reduces the required number of states, thereby drastically improving the model accuracy even with non-ideal devices and achieving the test error close to that of the conventional learning algorithm with an ideal device.
The SON2A2 score: A novel grading scale for predicting hemorrhage and outcomes after thrombolysis
Authors: Ren Yu , He Zhongxiang , Du Xiaoyan , Liu Jie , Zhou Li , Bai Xue , Chen Yue , Wu Bowen , Song Xiaosong , Zhao Libo , Yang Qin
Published: October 2022

Objectives

This study aimed to develop a score including novel putative predictors for predicting the risk of sICH and outcomes after thrombolytic therapy with intravenous (IV) recombinant tissue-type plasminogen activator (r-tPA) in acute ischemic stroke patients.

Methods

All patients with acute ischemic stroke treated with IV r-tPA at three university-based hospitals in Chongqing, China, from 2014 to 2019 were retrospectively studied. Potential risk factors associated with sICH (NINDS criteria) were determined with multivariate logistic regression, and we developed our score according to the magnitude of logistic regression coefficients. The score was validated in another independent cohort. Area under the receiver operating characteristic curve (AUC-ROC) was used to assess the performance of the score. Calibration was evaluated using the Hosmer–Lemeshow goodness-of-fit method.

Results

The SON2A2 score (0 to 8 points) consisted of history of smoking (no = 1, yes = 0, β = 0.81), onset-to-needle time (≥3.5 = 1,<3.5=0, β = 0.74), NIH Stroke Scale on admission (>10 = 2, ≤10 = 0, β = 1.22), neutrophil percentage (≥80.0% = 1, <80% = 0, β = 0.81), ASPECT score (≤11 = 2, >11 = 0, β = 1.30), and age (>65 years = 1, ≤65 years = 0, β = 0.89). The SON2A2 score was strongly associated with sICH (OR 1.98; 95%CI 1.675–2.34) and poor outcomes (OR 1.89; 95%CI 1.68–2.13). AUC-ROC in the derivation cohort was 0.82 (95%CI 0.77–0.86). Similar results were obtained in the validation cohort. The Hosmer–Lemeshow test revealed that predicted and observed event rates in derivation and validation cohorts were very close.

Conclusion

The SON2A2 score is a simple, efficient, quick, and easy-to-perform scale for predicting the risk of sICH and outcome after intravenous r-tPA thrombolysis within 4.5 h in patients with ischemic stroke, and risk assessment using this test has the potential for early and personalized management of this disease in high-risk patients.
Preoperative peripheral blood inflammatory markers especially the fibrinogen-to-lymphocyte ratio and novel FLR-N score predict the prognosis of patients with early-stage resectable extrahepatic cholangiocarcinoma
Authors: Li Shijie , Zhang Xingli , Lou Changjie , Gu Yuanlong , Zhao Juan
Published: October 2022

Background

Systemic inflammation is important in the development of extrahepatic cholangiocarcinoma (ECC). The aim of this study was to compare the prognostic power of preoperative peripheral blood inflammatory markers and the novel FLR-N score in patients with resectable ECC.

Methods

A total of 140 patients with resectable ECC and 140 healthy controls (HCs) were recruited for the study. The Mann−Whitney U test was used to evaluate the differences in inflammatory markers between groups. Kaplan−Meier and Cox regression analyses were used to evaluate the prognostic power of preoperative fibrinogen, albumin, prealbumin, bilirubin, neutrophils, lymphocytes, monocytes, platelets, fibrinogen-to-lymphocyte ratio (FLR), fibrinogen-to-albumin ratio (FAR), fibrinogen-to-prealbumin ratio (FPR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), FLR-neutrophil (FLR-N) score, and CA19-9 in patients with resectable ECC. Nomogram was developed based on the results of multivariate Cox analyses.

Results

Patients with resectable ECC had significantly higher levels of neutrophils, monocytes, fibrinogen, FLR, FAR, FPR, NLR, PLR, and MLR and lower levels of lymphocytes, albumin, and prealbumin than HCs (all P < 0.01). Albumin, prealbumin, and FPR had a good ability to distinguish between ECC patients with total bilirubin < 34 µmol/L and HCs (AUCs of 0.820, 0.827, and 0.836, respectively). Kaplan−Meier analysis showed that high neutrophil, fibrinogen, FLR, FAR, PLR, MLR, and FLR-N score values were associated with poor survival in patients with resectable ECC. Multivariate analyses indicated that neutrophils (P = 0.022), FLR (P = 0.040), FLR-N score (P < 0.0001), and positive lymph node metastasis (P = 0.016) were independent factors for overall survival (OS). Nomogram were developed to predict OS for patients with ECC.

Conclusion

The prognostic roles of inflammatory markers in patients with resectable ECC were different. The preoperative neutrophil count, FLR and FLR-N score could serve as noninvasive markers for predicting the prognosis of resectable ECC.
Cross-disease communication between cancer and heart failure provides a rational approach to prevention and treatment of both diseases
Authors: Takada Shingo , Kinugawa Shintaro , Handa Haruka , Yokota Takashi , Sabe Hisataka
Published: October 2022

Accumulating clinical data have demonstrated a clear positive association between cancer and cardiac disorders, particularly chronic heart failure (CHF). These two diseases can be mutual drivers of each other, and hence frequently co-occur in patients. The immune system is the core mechanism that eliminates transformed cells from our bodies. However, immune cells often play distinct or even conflicting roles in cancer and CHF. Moreover, CHF alters the properties of immune cells, particularly those of regulatory T cells. Our previous study showed that the oxidative phosphorylation capacity of peripheral blood mononuclear cells is impaired in CHF, leading to the increased production of reactive oxygen species. Therefore, the co-occurrence of cancer and CHF becomes a serious problem, affecting the treatment of both diseases, and consequently negatively affecting patient survival rates. To date, few methods have been identified that effectively treat both diseases at the same time. Mitochondria activity may change in immune cells during their activation and exhaustion, and in CHF. Mitochondria activity is also largely affected in myocardia in CHF. We here focus on the mitochondrial abnormalities of immune cells in cancer and CHF, and discuss possible ways to treat cancer and CHF at the same time by targeting mitochondrial abnormalities. Many cancer cells are inevitably produced daily in our bodies, mostly owing to enzymatic nucleotide errors of DNA replication and repair. Therefore, the possibility of ways to prevent cancer by preventing the onset of heart failure will also be discussed.
Serum cytokines predict efficacy and toxicity, but are not useful for disease monitoring in lung cancer treated with PD-(L)1 inhibitors
Authors: Schindler Hannah , Lusky Fabienne , Daniello Lea , Elshiaty Mariam , Gaissmaier Lena , Benesova Karolina , Souto-Carneiro Margarida , Angeles Arlou Kristina , Janke Florian , Eichhorn Florian , Kazdal Daniel , Schneider Marc , Liersch Stephan , Klemm Sarah , Schnitzler Paul , Stenzinger Albrecht , Sültmann Holger , Thomas Michael , Christopoulos Petros
Published: October 2022

Introduction

PD-(L)1 inhibitors (IO) have improved the prognosis of non-small-cell lung cancer (NSCLC), but more reliable predictors of efficacy and immune-related adverse events (irAE) are urgently needed. Cytokines are important effector molecules of the immune system, whose potential clinical utility as biomarkers remains unclear.

Methods

Serum samples from patients with advanced NSCLC receiving IO either alone in the first (1L, n=46) and subsequent lines (n=50), or combined with chemotherapy (ICT, n=108) were analyzed along with age-matched healthy controls (n=15) at baseline, after 1 and 4 therapy cycles, and at disease progression (PD). Patients were stratified in rapid progressors (RP, progression-free survival [PFS] <120 days), and long-term responders (LR, PFS >200 days). Cytometric bead arrays were used for high-throughput quantification of 20 cytokines and other promising serum markers based on extensive search of the current literature.

Results

Untreated NSCLC patients had increased levels of various cytokines and chemokines, like IL-6, IL-8, IL-10, CCL5, G-CSF, ICAM-1, TNF-RI and VEGF (fold change [FC]=1.4-261, p=0.026-9x10-7) compared to age-matched controls, many of which fell under ICT (FC=0.2-0.6, p=0.014-0.002), but not under IO monotherapy. Lower baseline levels of TNF-RI were associated with longer PFS (hazard ratio [HR]= 0.42-0.54; p=0.014-0.009) and overall survival (HR=0.28-0.34, p=0.004-0.001) after both ICT and IO monotherapy. Development of irAE was associated with higher baseline levels of several cytokines, in particular of IL-1β and angiogenin (FC=7-9, p=0.009-0.0002). In contrast, changes under treatment were very subtle, there were no serum correlates of radiologic PD, and no association between dynamic changes in cytokine concentrations and clinical outcome. No relationship was noted between the patients’ serologic CMV status and serum cytokine levels.

Conclusions

Untreated NSCLC is characterized by increased blood levels of several pro-inflammatory and angiogenic effectors, which decrease under ICT. Baseline serum cytokine levels could be exploited for improved prediction of subsequent IO benefit (in particular TNF-RI) and development of irAE (e.g. IL-1β or angiogenin), but they are not suitable for longitudinal disease monitoring. The potential utility of IL-1/IL-1β inhibitors in the management and/or prevention of irAE in NSCLC warrants investigation.
Papillary renal neoplasm with reverse polarity with a favorable prognosis: Two cases report and literature review
Authors: Yuzhi Zuo , Zhen Liang , Yu Xiao , Boju Pan , Weigang Yan , Xingcheng Wu
Published: October 2022

Background

Papillary Renal Neoplasm (PRN) with polarity inversion is a less common subtype of kidney cancer with an apparently recognizable morphology, distinct immunohistochemical profiles, and frequent KRAS mutations. It has been estimated to account 4% of previously diagnosed PRN.

Case presentation

This is a retrospective case report of two patients diagnosed with PRNRP. Two males were found to have kidney mass accidentally through imaging examination in clinic. Both of the patients had no obvious discomfort and abnormal test indicators. Subsequently, they underwent partial nephrectomy in our center by the same surgeon and followed up closely with an impressive clinical outcome. The pathology reports indicated that their pathological features were consistent with PRNRP. The HE staining showed a monolayer of papillary or tubular structures, with small nuclei away from the cytoplasmic top of the basement membrane. The immunohistochemical results were GATA3 (+), vimentin (-).

Conclusion

Our case reports and literature review suggested that PRNRP should be separated from traditional PRN and partial nephrectomy is a robust modality for PRNRP. The morphological, immunohistochemical, and genetic information of the cases we presented would provide important material for PRNRP to become a distinct category with benign clinical outcome.
Case report: Individualized treatment of advanced breast cancer with the use of the patient-derived tumor-like cell cluster model
Authors: Xia Wenjie , Chen Wuzhen , Fang Shan , Wu Jun , Zhang Jingxia , Yuan Hongjun
Published: October 2022

Breast cancer is one of the most common tumors in women. Despite various treatments, the survival of patients with advanced breast cancer is still disappointing. Furthermore, finding an effective individualized treatment for different kinds of patients is a thorny problem. Patient-derived tumor-like cell clusters were reported to be used for personalized drug testing in cancer therapy and had a prediction accuracy of 93%. However, there is still a lack of case reports about its application in the individualized treatment of breast cancer patients. Here, we described four cases of individualized treatment for advanced breast cancer using the patient-derived tumor-like cell cluster model (PTC model). In these four cases, the PTC model showed a good predictive effect. The tumor size was reduced significantly or even disappeared completely through clinical, radiological, or pathological evaluation with the help of the PTC model for selecting an individualized therapy regimen. Furthermore, the drug sensitivity test results of the PTC model were consistent with pathological molecular typing and the actual clinical drug resistance of the patients. In summary, our case report first evaluated the application value of the PTC model in advanced breast cancer, and the PTC model might be used as an efficient tool for drug resistance screening and for selecting a better personalized treatment, although further study is needed to prove the validity and stability of the PTC model in drug screening.
Relevance of the TRIAP1/p53 axis in colon cancer cell proliferation and adaptation to glutamine deprivation
Authors: Nedara Kenza , Reinhardt Camille , Lebraud Emilie , Arena Giuseppe , Gracia Céline , Buard Valérie , Pioche-Durieu Catherine , Castelli Florence , Colsch Benoit , Bénit Paule , Rustin Pierre , Albaud Benoit , Gestraud Pierre , Baulande Sylvain , Servant Nicolas , Deutsch Eric , Verbavatz Jean-Marc , Brenner Catherine , Milliat Fabien , Modjtahedi Nazanine
Published: October 2022

Human TRIAP1 (TP53-regulated inhibitor of apoptosis 1; also known as p53CSV for p53-inducible cell survival factor) is the homolog of yeast Mdm35, a well-known chaperone that interacts with the Ups/PRELI family proteins and participates in the intramitochondrial transfer of lipids for the synthesis of cardiolipin (CL) and phosphatidylethanolamine. Although recent reports indicate that TRIAP1 is a prosurvival factor abnormally overexpressed in various types of cancer, knowledge about its molecular and metabolic function in human cells is still elusive. It is therefore critical to understand the metabolic and proliferative advantages that TRIAP1 expression provides to cancer cells. Here, in a colorectal cancer cell model, we report that the expression of TRIAP1 supports cancer cell proliferation and tumorigenesis. Depletion of TRIAP1 perturbed the mitochondrial ultrastructure, without a major impact on CL levels and mitochondrial activity. TRIAP1 depletion caused extramitochondrial perturbations resulting in changes in the endoplasmic reticulum-dependent lipid homeostasis and induction of a p53-mediated stress response. Furthermore, we observed that TRIAP1 depletion conferred a robust p53-mediated resistance to the metabolic stress caused by glutamine deprivation. These findings highlight the importance of TRIAP1 in tumorigenesis and indicate that the loss of TRIAP1 has extramitochondrial consequences that could impact on the metabolic plasticity of cancer cells and their response to conditions of nutrient deprivation.
Development of a salivary autoantibody biomarker panel for diagnosis of oral cavity squamous cell carcinoma
Authors: Hsueh Pei-Chun , Chang Kai-Ping , Liu Hao-Ping , Chiang Wei-Fan , Chan Xiu-Ya , Hung Chu-Mi , Chu Lichieh Julie , Wu Chih-Ching
Published: October 2022

Oral cavity squamous cell carcinoma (OSCC) is a destructive disease with increasing incidence. OSCC is usually diagnosed at an advanced stage, which leads to poor outcomes of OSCC patients. Currently, there is a lack of biomarkers with sufficient effectiveness in early diagnosis of OSCC. To ameliorate OSCC screening, we evaluated the performances of salivary autoantibodies (auto-Abs) to nine proteins (ANXA2, CA2, ISG15, KNG1, MMP1, MMP3, PRDX2, SPARC, and HSPA5) as OSCC biomarkers. A multiplexed immunoassay using a fluorescence bead-based suspension array system was established for simultaneous assessment of the salivary levels of the above nine auto-Abs and a known OSCC-associated auto-Ab, anti-p53. Compared to healthy individuals (n = 140), the salivary levels of nine auto-Abs were significantly elevated in OSCC patients (n = 160). Notably, the salivary levels of the 10 auto-Abs in the early-stage OSCC patients (n = 102) were higher than that in the healthy group. Most importantly, utilizing a marker panel consisting of anti-MMP3, anti-PRDX2, anti-SPARC, and anti-HSPA5 for detection of early-stage OSCC achieved a sensitivity of 63.8% with a specificity of 90%. Collectively, herein we established a multiplex auto-Ab platform for OSCC screening, and demonstrated a four-auto-Ab panel which shows clinical applicability for early diagnosis of OSCC.
Disparities in access to care among patients with appendiceal or colorectal cancer and peritoneal metastases: A medicare insurance-based study in the United States
Authors: Aquina Christopher T. , Brown Zachary J. , Beane Joal D. , Ejaz Aslam , Cloyd Jordan M. , Eng Oliver S. , Monson John R.T. , Ruff Samantha M. , Kasumova Gyulnara G. , Adam Mohamed O. , Obeng-Gyasi Samilia , Pawlik Timothy M. , Kim Alex C.
Published: October 2022

Background

Prior studies attempting to identify disparities in the care of patients with appendiceal (AC) or colorectal cancer (CRC) with peritoneal metastasis (PM) are limited to single-institution, highly selected patient populations. This observational cohort study sought to identify factors associated with specialty care for Medicare beneficiaries with AC/CRC-PM.

Materials and methods

Patients >65 years old in the United States diagnosed with AC/CRC and isolated PM were identified within the Medicare Standard Analytic File (2013-2017). Mixed-effects analyses assessed patient factors associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) and outpatient consultation with a peritoneal surface malignancy (PSM) surgeon, and Cox proportional-hazards analysis compared 3-year overall survival (OS) between patients receiving CRS/HIPEC versus systemic therapy alone.

Results

Among 7,653 patients, only 250 (3.3%) underwent CRS/HIPEC. Among those individuals who did not undergo CRS/HIPEC (N=7,403), only 475 (6.4%) had outpatient consultation with a PSM surgeon. Patient factors independently associated with lower odds of CRS/HIPEC and PSM surgery consultation included older age, greater comorbidity burden, higher social vulnerability index, and further distance from a PSM center (p<0.05). CRS/HIPEC was independently associated with better 3-year OS compared with systemic therapy alone (HR=0.29, 95%CI=0.21-0.38).

Conclusion

An exceedingly small proportion of Medicare beneficiaries with AC/CRC-PM undergo CRS/HIPEC or even have an outpatient consultation with a PSM surgeon. Significant disparities in treatment and access to care exist for patients with higher levels of social vulnerability and those that live further away from a PSM center. Future research and interventions should focus on improving access to care for these at-risk patient populations.
Case report: Diarrhea-associated hemolytic uremic syndrome in the Era of COVID-19
Authors: Richardson Gina M. , Su Sharon W. , Iragorri Sandra
Published: October 2022

Over the past two years, a growing number of SARS-CoV-2 infection-associated clinical pediatric phenotypes have been identified, including a hemolytic uremic syndrome (HUS) form of thrombotic microangiopathy. Oregon’s high prevalence of Shiga toxin-producing Escherichia coli (STEC) infections gives it a unique perspective to discuss the impact of COVID-19 and HUS. We seek to highlight SARS-CoV-2 as a potential new infectious etiology of severe diarrhea-associated HUS, based on two cases from Portland, Oregon, occurring in non-COVID-19 immunized children. The first case is a previously healthy ten-year-old who presented with SARS-CoV-2 infection and bloody diarrhea after an appendectomy, followed by full-blown oligo-anuric HUS. Second is a previously healthy six-year-old who presented with short-lived bloody diarrhea, rapidly evolving to HUS, and who tested positive for COVID-19 via polymerase chain reaction and STEC toxins one and two. These two cases highlight two main points. First, SARS-CoV-2 must be included in the differential diagnosis of diarrhea-associated HUS, either as the sole agent or concurrent with a STEC infection. Second, when managing STEC gastroenteritis the recommendation has been to maintain excellent hydration as a strategy to prevent the progression to oligo-anuric acute kidney injury and HUS. This strategy may need to be re-evaluated in a patient with SARS-CoV-2 infection or co-infection.
Zebrafish as a platform to evaluate the potential of lipidic nanoemulsions for gene therapy in cancer
Authors: Cascallar María , Hurtado Pablo , Lores Saínza , Pensado-López Alba , Quelle-Regaldie Ana , Sánchez Laura , Piñeiro Roberto , de la Fuente María
Published: October 2022

Gene therapy is a promising therapeutic approach that has experienced significant groth in recent decades, with gene nanomedicines reaching the clinics. However, it is still necessary to continue developing novel vectors able to carry, protect, and release the nucleic acids into the target cells, to respond to the widespread demand for new gene therapies to address current unmet clinical needs. We propose here the use of zebrafish embryos as an in vivo platform to evaluate the potential of newly developed nanosystems for gene therapy applications in cancer treatment. Zebrafish embryos have several advantages such as low maintenance costs, transparency, robustness, and a high homology with the human genome. In this work, a new type of putrescine-sphingomyelin nanosystems (PSN), specifically designed for cancer gene therapy applications, was successfully characterized and demonstrated its potential for delivery of plasmid DNA (pDNA) and miRNA (miR). On one hand, we were able to validate a regulatory effect of the PSN/miR on gene expression after injection in embryos of 0 hpf. Additionally, experiments proved the potential of the model to study the transport of the associated nucleic acids (pDNA and miR) upon incubation in zebrafish water. The biodistribution of PSN/pDNA and PSN/miR in vivo was also assessed after microinjection into the zebrafish vasculature, demonstrating that the nucleic acids remained associated with the PSN in an in vivo environment, and could successfully reach disseminated cancer cells in zebrafish xenografts. Altogether, these results demonstrate the potential of zebrafish as an in vivo model to evaluate nanotechnology-based gene therapies for cancer treatment, as well as the capacity of the developed versatile PSN formulation for gene therapy applications.
Danshensu methyl ester enhances autophagy to attenuate pulmonary fibrosis by targeting lncIAPF–HuR complex
Authors: Zhu Qi , Wang Jing , Ji Yunxia , Luan Jianlin , Yue Dayong , Liu Weili , Li Hongbo , Zhang Jinjin , Qu Guiwu , Lv Changjun , Song Xiaodong
Published: October 2022

Pulmonary fibrosis is an irreversible fibrotic process that has a high mortality rate and limited treatment options; thus, developing a novel therapeutic drug is critical. In this study, we synthesized danshensu methyl ester (DME) and explored its anti-pulmonary fibrotic ability on TGF-β1-stimulated lung fibroblast in vitro and on bleomycin-induced pulmonary fibrosis in vivo. Results showed that DME decreased the expression of differentiation-related proteins, including fibroblast activation protein 1 (FAP1) and S100 calcium-binding protein A4 (S100A4), and fibrotic markers, such as a-SMA, vimentin, and collagen in vivo and in vitro. In addition, DME markedly repressed myofibroblast proliferation and migration. Mechanistically, chromatin immunoprecipitation–PCR, RNA immunoprecipitation, half-life, and other experiments revealed that DME inhibited activating transcription factor 3 expression via TGF-β1 signal transduction leading to a decrease in lncIAPF transcription and stability. Moreover, DME blocked human antigen R (HuR) nucleocytoplasmic translocation and promoted its degradation via downregulating lncIAPF, which markedly decreased the expression of HuR target genes such as negative autophagic regulators (EZH2, STAT1, and FOXK1). Collectively, our results demonstrated that DME enhanced autophagy to attenuate pulmonary fibrosis via downregulating the lncIAPF–HuR-mediated autophagic axis and the lncIAPF–HuR complex can be the target for drug action.