bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning-based integration develops a neutrophil-derived signature for improving outcomes in hepatocellular carcinoma
Authors: Gong Qiming , Chen Xiaodan , Liu Fahui , Cao Yuhua
Published: July 2023

Introduction

The heterogeneity of tumor immune microenvironments is a major factor in poor prognosis among hepatocellular carcinoma (HCC) patients. Neutrophils have been identified as playing a critical role in the immune microenvironment of HCC based on recent single-cell studies. However, there is still a need to stratify HCC patients based on neutrophil heterogeneity. Therefore, developing an approach that efficiently describes "neutrophil characteristics" in HCC patients is crucial to guide clinical decision-making.

Methods

We stratified two cohorts of HCC patients into molecular subtypes associated with neutrophils using bulk-sequencing and single-cell sequencing data. Additionally, we constructed a new risk model by integrating machine learning analysis from 101 prediction models. We compared the biological and molecular features among patient subgroups to assess the model's effectiveness. Furthermore, an essential gene identified in this study was validated through molecular biology experiments.

Results

We stratified patients with HCC into subtypes that exhibited significant differences in prognosis, clinical pathological characteristics, inflammation-related pathways, levels of immune infiltration, and expression levels of immune genes. Furthermore, A risk model called the "neutrophil-derived signature" (NDS) was constructed using machine learning, consisting of 10 essential genes. The NDS's RiskScore demonstrated superior accuracy to clinical variables and correlated with higher malignancy degrees. RiskScore was an independent prognostic factor for overall survival and showed predictive value for HCC patient prognosis. Additionally, we observed associations between RiskScore and the efficacy of immune therapy and chemotherapy drugs.

Discussion

Our study highlights the critical role of neutrophils in the tumor microenvironment of HCC. The developed NDS is a powerful tool for assessing the risk and clinical treatment of HCC. Furthermore, we identified and analyzed the feasibility of the critical gene RTN3 in NDS as a molecular marker for HCC.
Identification of novel clusters of co-expressing cytokines in a diagnostic cytokine multiplex test
Authors: Polley Daniel J. , Latham Penny , Choi May Y. , Buhler Katherine A. , Fritzler Marvin J. , Fritzler Mark L.
Published: July 2023

Introduction

Cytokines are mediators of the immune system that are essential for the maintenance, development and resolution of immune responses. Beneficial immune responses depend on complex, interdependent networks of signaling and regulatory events in which individual cytokines influence the production and release of others. Since disruptions in these signaling networks are associated with a wide spectrum of diseases, cytokines have gained considerable interest as diagnostic, prognostic and precision therapy-relevant biomarkers. However, currently individual cytokines testing has limited value because the wider immune response context is often overlooked. The aim of this study was to identify specific cytokine signaling patterns associated with different diseases.

Methods

Unbiased clustering analyses were performed on a clinical cytokine multiplex test using a cohort of human plasma specimens drawn from individuals with known or suspected diseases for which cytokine profiling was considered clinically indicated by the attending physician.

Results and discussion

Seven clusters of co-expressing cytokines were identified, representing common patterns of immune activation. Common expression profiles of the cytokine clusters and preliminary associations of these profiles with specific diseases or disease categories were also identified. These findings increase our understanding of the immune environments underlying the clinical presentations of patients of inflammatory, autoimmune and neoplastic diseases, which could then improve diagnoses and the identification of evidence-based treatment targets.
scDual-Seq of Toxoplasma gondii-infected mouse BMDCs reveals heterogeneity and differential infection dynamics
Authors: Hildebrandt Franziska , Mohammed Mubasher , Dziedziech Alexis , Bhandage Amol K. , Divne Anna-Maria , Barrenäs Fredrik , Barragan Antonio , Henriksson Johan , Ankarklev Johan
Published: July 2023

Dendritic cells and macrophages are integral parts of the innate immune system and gatekeepers against infection. The protozoan pathogen, Toxoplasma gondii, is known to hijack host immune cells and modulate their immune response, making it a compelling model to study host-pathogen interactions. Here we utilize single cell Dual RNA-seq to parse out heterogeneous transcription of mouse bone marrow-derived dendritic cells (BMDCs) infected with two distinct genotypes of T. gondii parasites, over multiple time points post infection. We show that the BMDCs elicit differential responses towards T. gondii infection and that the two parasite lineages distinctly manipulate subpopulations of infected BMDCs. Co-expression networks define host and parasite genes, with implications for modulation of host immunity. Integrative analysis validates previously established immune pathways and additionally, suggests novel candidate genes involved in host-pathogen interactions. Altogether, this study provides a comprehensive resource for characterizing host-pathogen interplay at high-resolution.
Plasma metabolomic signatures of breast cancer
Authors: Xu Yali , Zhao Bin , Xu Zhu , Li Xiaogang , Sun Qiang
Published: July 2023

Background

Breast cancer is a common malignant tumor. A large number of medical evidence shows that breast cancer screening can improve the early diagnosis rate and reduce the mortality rate of breast cancer. In the present study, a wide range of targeted metabolomics profiling was conducted to investigate the plasma signatures of breast cancer.

Methods

A total of 86 patients with benign breast abnormalities (L group) and 143 patients with breast cancer (E group) were recruited. We collected their plasma samples and clinical information. Metabolomic analysis, based on the coverage of a wide range of targeted metabolomics was conducted with ultraperformance liquid chromatography- triple quadrupole-linear ion trap mass spectrometer (UPLC-QTRAP-MS).

Results

We identified 716 metabolites through widely-targeted metabolomics. Serotonergic synapse was the main different metabolic pathway. The fold change of 14 metabolites was considered significantly different (fold change <0.67 or fold change >2; p < 0.05). By combining all the 14 metabolites, we achieved differentiation of L group vs. E group (AUC = 0.792, 95%Cl: 0.662–0.809).

Conclusion

This study provided new insights into plasma biomarkers for differential diagnosis of benign abnormalities and breast cancer.
Register-based and genetic studies of Prader-Willi syndrome show a high frequency of gonadal tumors and a possible mechanism for tumorigenesis through imprinting relaxation
Authors: Maya-González Carolina , Wessman Sandra , Lagerstedt-Robinson Kristina , Taylan Fulya , Tesi Bianca , Kuchinskaya Ekaterina , McCluggage W. Glenn , Poluha Anna , Holm Stefan , Nergårdh Ricard , Díaz De Ståhl Teresita , Höybye Charlotte , Tettamanti Giorgio , Delgado-Vega Angelica Maria , Skarin Nordenvall Anna , Nordgren Ann
Published: July 2023

Prader-Willi syndrome (PWS) is a rare disease caused by a lack of expression of inherited imprinted genes in the paternally derived Prader-Willi critical region on chromosome 15q11.2-q13. It is characterized by poor feeding and hypotonia in infancy, intellectual disability, behavioral abnormalities, dysmorphic features, short stature, obesity, and hypogonadism. PWS is not a known cancer predisposition syndrome, but previous investigations regarding the prevalence of cancer in these patients suggest an increased risk of developing specific cancer types such as myeloid leukemia and testicular cancer. We present the results from a Swedish national population-based cohort study of 360 individuals with PWS and 18,000 matched comparisons. The overall frequency of cancer was not increased in our PWS cohort, but we found a high frequency of pediatric cancers. We also performed whole-genome sequencing of blood- and tumor-derived DNAs from a unilateral dysgerminoma in a 13-year-old girl with PWS who also developed bilateral ovarian sex cord tumors with annular tubules. In germline analysis, there were no additional findings apart from the 15q11.2-q13 deletion of the paternal allele, while a pathogenic activating KIT mutation was identified in the tumor. Additionally, methylation-specific multiplex ligation-dependent probe amplification revealed reduced methylation at the PWS locus in the dysgerminoma but not in the blood. In conclusion, our register-based study suggests an increased risk of cancer at a young age, especially testicular and ovarian tumors. We found no evidence of a general increase in cancer risk in patients with PWS. However, given our limited observational time, further studies with longer follow-up times are needed to clarify the lifetime cancer risk in PWS. We have also described the second case of locus-specific loss-of-imprinting in a germ cell tumor in PWS, suggesting a possible mechanism of carcinogenesis.
Targeting nuclear hormone receptors for the prevention of breast cancer
Authors: Moyer Cassandra L. , Brown Powel H.
Published: July 2023

Advancements in research have led to the steady decline of breast cancer mortality over the past thirty years. However, breast cancer incidence has continued to rise, resulting in an undue burden on healthcare costs and highlighting a great need for more effective breast cancer prevention strategies, including targeted chemo preventative agents. Efforts to understand the etiology of breast cancer have uncovered important roles for nuclear receptors in the development and progression of breast cancer. Targeted therapies to inhibit estrogen receptor (ER) and progesterone receptor (PR) signaling (selective ER modulators, aromatase inhibitors and selective PR modulators) have shown great promise for the treatment and prevention of hormone receptor (HR)-positive breast cancer. However, these drugs do not prevent HR-negative disease. Therefore, recent efforts have focused on novel targeted therapies with the potential to prevent both HR-positive and HR-negative breast cancer. Among these include drugs that target other nuclear receptors, such as retinoic acid receptor (RAR), retinoid X receptor (RXR) and vitamin D receptor (VDR). In this review we provide an overview of recent preclinical and clinical trials targeting members of the nuclear receptor superfamily for the prevention of breast cancer.
Impact of discontinuing non-pharmacological interventions on cognitive impairment in dementia patients by COVID-19 lockdown. A pilot observational, longitudinal, retrospective study carried out in an adult day center in Spain during the COVID-19 pandemic
Authors: Sánchez-Valdeón Leticia , Bello-Corral Laura , Mayo-Iscar Agustín , Fernández-Lázaro Diego , Seco-Calvo Jesús
Published: July 2023

Background

The lockdown imposed during the COVID-19 pandemic led to social isolation and prevented patients with dementia from receiving a suite of non-pharmacological interventions (NPIs) that prevent cognitive decline. This discontinuation of NPIs could substantially affect the mental health status of people with dementia in social care settings, such as adult day care centers (ADCs).

Propose

The study aimed to evaluate the effects of the COVID-19 lockdown on mental health and cognitive impairment in patients with dementia who could not attend their usual ADCs and did not receive our NPIs, based on World Health Organization (WHO) Guidelines.

Methods

Observational, longitudinal, retrospective study carried out in an adult day center in Spain and reported it in accordance with the Strengthening Reporting of Observational Studies in Epidemiology (STROBE) statement. Cognitive status was assessed using the Mini-Mental State Examination (MMSE) in 80 patients attending the ADC of the “Leonese Association of Dementia Patients” (León, Spain), who had been evaluated with this instrument before the COVID-19 lockdown.

Results

We observed a 0.4-point decrease in MMSE score/month (IQR = 1.4) during lockdown versus a 0.1-point decrease/month (IQR = 0.3) before this period (p = 0.038). Notably, this translated to >10-point decreases in MMSE score/year in 33.8% of participants during lockdown versus 5.5% earlier (p < 0.001). No statistically significant associations (p < 0.05) were found between the individual characteristics of the caregivers and the occurrence of the event.

Conclusion

The reported declines in MMSE scores reveal a significant acceleration of cognitive decline during the period of inactivity. This could suggest that our NPIs, focused on slowing cognitive decline, are beneficial and, therefore, necessary in patients with dementia.
Dissecting contributions of individual systemic inflammatory response syndrome criteria from a prospective algorithm to the prediction and diagnosis of sepsis in a polytrauma cohort
Authors: Schefzik Roman , Hahn Bianka , Schneider-Lindner Verena
Published: July 2023

Background

Sepsis is the leading cause of death in intensive care units (ICUs), and its timely detection and treatment improve clinical outcome and survival. Systemic inflammatory response syndrome (SIRS) refers to the concurrent fulfillment of at least two out of the following four clinical criteria: tachycardia, tachypnea, abnormal body temperature, and abnormal leukocyte count. While SIRS was controversially abandoned from the current sepsis definition, a dynamic SIRS representation still has potential for sepsis prediction and diagnosis.

Objective

We retrospectively elucidate the individual contributions of the SIRS criteria in a polytrauma cohort from the post-surgical ICU of University Medical Center Mannheim (Germany).

Methods

We used a dynamic and prospective SIRS algorithm tailored to the ICU setting by accounting for catecholamine therapy and mechanical ventilation. Two clinically relevant tasks are considered: (i) sepsis prediction using the first 24 h after admission to our ICU, and (ii) sepsis diagnosis using the last 24 h before sepsis onset and a time point of comparable ICU treatment duration for controls, respectively. We determine the importance of individual SIRS criteria by systematically varying criteria weights when summarizing the SIRS algorithm output with SIRS descriptors and assessing the classification performance of the resulting logistic regression models using a specifically developed ranking score.

Results

Our models perform better for the diagnosis than the prediction task (maximum AUROC 0.816 vs. 0.693). Risk models containing only the SIRS level average mostly show reasonable performance across criteria weights, with prediction and diagnosis AUROCs ranging from 0.455 (weight on leukocyte criterion only) to 0.693 and 0.619 to 0.800, respectively. For sepsis prediction, temperature and tachypnea are the most important SIRS criteria, whereas the leukocytes criterion is least important and potentially even counterproductive. For sepsis diagnosis, all SIRS criteria are relevant, with the temperature criterion being most influential.

Conclusion

SIRS is relevant for sepsis prediction and diagnosis in polytrauma, and no criterion should a priori be omitted. Hence, the original expert-defined SIRS criteria are valid, capturing important sepsis risk determinants. Our prospective SIRS algorithm provides dynamic determination of SIRS criteria and descriptors, allowing their integration in sepsis risk models also in other settings.
The difference in the composition of gut microbiota is greater among bats of different phylogenies than among those with different dietary habits
Authors: Guo Min , Xie Siwei , Wang Junhua , Zhang Yuzhi , He Xiangyang , Luo Pengfei , Deng Jin , Zhou Chunhui , Qin Jiao , Huang Chen , Zhang Libiao
Published: July 2023

Bats have a very long evolutionary history and are highly differentiated in their physiological functions. Results of recent studies suggest effects of some host factors (e.g., phylogeny and dietary habit) on their gut microbiota. In this study, we examined the gut microbial compositions of 18 different species of bats. Results showed that Firmicutes, Gammaproteobacteria, and Actinobacteria were dominant in all fecal samples of bats. However, the difference in the diversity of gut microbiota among bats of different phylogenies was notable (p = 0.06). Various species of Firmicutes, Actinobacteria, and Gammaproteobacteria were found to contribute to the majority of variations in gut microbiota of all bats examined, and Aeromonas species were much more abundant in bats that feed on both insects and fish than in those of insectivores. The abundance of various species of Clostridium, Euryarchaeota, and ancient bacterial phyla was found to vary among bats of different phylogenies, and various species of Vibrio varied significantly among bats with different dietary habits. No significant difference in the number of genes involved in various metabolic pathways was detected among bats of different phylogenies, but the abundance of genes involved in 5 metabolic pathways, including transcription; replication, recombination, and repair; amino acid transport and metabolism; and signal transduction mechanisms, was different among bats with different dietary habits. The abundance of genes in 3 metabolic pathways, including those involved in stilbenoid, diarylheptanoid, and gingerol biosynthesis, was found to be different between insectivorous bats and bats that feed on both insects and fish. Results of this study suggest a weak association between dietary habit and gut microbiota in most bats but a notable difference in gut microbiota among bats of different phylogenies.
Membrane proteome of the thermoalkaliphile Caldalkalibacillus thermarum TA2.A1
Authors: de Jong Samuel I. , Sorokin Dimitry Y. , van Loosdrecht Mark C. M. , Pabst Martin , McMillan Duncan G. G.
Published: July 2023

Proteomics has greatly advanced the understanding of the cellular biochemistry of microorganisms. The thermoalkaliphile Caldalkalibacillus thermarum TA2.A1 is an organism of interest for studies into how alkaliphiles adapt to their extreme lifestyles, as it can grow from pH 7.5 to pH 11. Within most classes of microbes, the membrane-bound electron transport chain (ETC) enables a great degree of adaptability and is a key part of metabolic adaptation. Knowing what membrane proteins are generally expressed is crucial as a benchmark for further studies. Unfortunately, membrane proteins are the category of proteins hardest to detect using conventional cellular proteomics protocols. In part, this is due to the hydrophobicity of membrane proteins as well as their general lower absolute abundance, which hinders detection. Here, we performed a combination of whole cell lysate proteomics and proteomics of membrane extracts solubilised with either SDS or FOS-choline-12 at various temperatures. The combined methods led to the detection of 158 membrane proteins containing at least a single transmembrane helix (TMH). Within this data set we revealed a full oxidative phosphorylation pathway as well as an alternative NADH dehydrogenase type II (Ndh-2) and a microaerophilic cytochrome oxidase ba3. We also observed C. thermarum TA2.A1 expressing transporters for ectoine and glycine betaine, compounds that are known osmolytes that may assist in maintaining a near neutral internal pH when the external pH is highly alkaline.
Wilder than intense: higher frequency, variability, and viral flows of porcine circovirus 3 in wild boars and rural farms compared to intensive ones in northern Italy
Authors: Franzo Giovanni , Faustini Giulia , Legnardi Matteo , Berto Giacomo , Dal Maso Mariangela , Genna Viviana , Menandro Maria Luisa , Poletto Francesca , Cecchinato Mattia , Drigo Michele , Tucciarone Claudia Maria
Published: July 2023

Introduction

Porcine circovirus 3 (PCV-3) was firstly reported in 2017. Although evidence of its pathogenic role has been provided, its clinical relevance seems lower than Porcine circovirus 2 (PCV-2), as well as its evolutionary rate. Different studies have reported a high PCV-3 prevalence in wild boars, sometimes higher than the one observed in commercial pigs. Nevertheless, to date, few studies have objectively investigated the relationships between these populations when inhabiting the same area. Moreover, the role of small-scale, backyard pig production in PCV-3 epidemiology is still obscure.

Methods

The present study investigated PCV-3 occurrence in 216 samples collected from the same area of Northern Italy from commercial and rural pigs, and wild boars. PCV-3 presence was tested by qPCR and complete genome or ORF2 sequences were obtained when possible and analysed using a combination of statistical, phylogenetic and phylodynamic approaches.

Results

A higher infection risk in wild boars and rural pigs compared to the commercial ones was demonstrated. The phylodynamic analysis confirmed a larger viral population size in wild and rural populations and estimated a preferential viral flow from these populations to commercial pigs. A significant flow from wild to rural animals was also proven. The analysis of the Italian sequences and the comparison with a broader international reference dataset highlighted the circulation of a highly divergent clade in Italian rural pigs and wild boars only.

Discussion

Overall, the present study results demonstrate the role of non-commercial pig populations in PCV-3 maintenance, epidemiology and evolution, which could represent a threat to intensive farming.
rTMS in mental health disorders
Authors: Richter Kneginja , Kellner Stefanie , Licht Christiane
Published: July 2023

Transcranial magnetic stimulation (TMS) is an innovative and non-invasive technique used in the diagnosis and treatment of psychiatric and neurological disorders. Repetitive TMS (rTMS) can modulate neuronal activity, neuroplasticity and arousal of the waking and sleeping brain, and, more generally, overall mental health. Numerous studies have examined the predictors of the efficacy of rTMS on clinical outcome variables in various psychiatric disorders. These predictors often encompass the stimulated brain region’s location, electroencephalogram (EEG) activity patterns, potential morphological and neurophysiological anomalies, and individual patient’s response to treatment. Most commonly, rTMS is used in awake patients with depression, catatonia, and tinnitus. Interestingly, rTMS has also shown promise in inducing slow-wave oscillations in insomnia patients, opening avenues for future research into the potential beneficial effects of these oscillations on reports of non-restorative sleep. Furthermore, neurophysiological measures emerge as potential, disease-specific biomarkers, aiding in predicting treatment response and monitoring post-treatment changes. The study posits the convergence of neurophysiological biomarkers and individually tailored rTMS treatments as a gateway to a new era in psychiatric care. The potential of rTMS to induce slow-wave activity also surfaces as a significant contribution to personalized treatment approaches. Further investigations are called for to validate the imaging and electrophysiological biomarkers associated with rTMS. In conclusion, the potential for rTMS to significantly redefine treatment strategies through personalized approaches could enhance the outcomes in neuropsychiatric disorders.
Case report: Atypical Parkinsonism following SARS-CoV-2 infection
Authors: Polverino Paola , De Santis Tiziana , Perdixi Elena , Chiò Adriano , Albanese Alberto
Published: July 2023

A wide range of neurological manifestations have been reported during the COVID-19 pandemic, including a variety of Parkinsonian cases. The association of numerous viruses with the development of persistent or transient Parkinsonism has been well-documented. We observed a patient who developed a levodopa non-responsive Parkinsonian syndrome with dysautonomia during a prolonged stay at home for COVID-19. Although the temporal proximity of the emerging Parkinsonian features with a COVID-19 diagnosis suggested a causal relationship, we considered the possibility of a coincidental occurrence of multiple system atrophy. We discuss the patient's clinical features in relation to the established clinical diagnostic criteria and review differential diagnoses as well as the role of SARS-CoV-2 infection.
Sport dependent effects on the sensory control of balance during upright posture: a comparison between professional horseback riders, judokas and non-athletes
Authors: Viseu Jean-Philippe , Yiou Eric , Morin Pierre-Olivier , Olivier Agnès
Published: July 2023

Introduction

Compared to judokas (JU) and non-athletes (NA), horseback riders (HR) may develop specific changes in their sensory control of balance.

Methods

Thirty-four international-level JU, twenty-seven international-level HR and twenty-one NA participated. Participants stood upright on a plateform (static condition) or on a seesaw device with an instability along the mediolateral (ML) or the anteroposterior (AP) direction (dynamic conditions). These conditions were carried out with eyes opened (EO) or closed (EC), and with (wF) or without a foam (nF). Experimental variables included conventional (linear), non-linear center-of-pressure (COP) parameters, Romberg Quotient (RQ) and Plantar Quotient (PQ).

Results

Group effects. COP Surface (COPS) and standard deviation of COP along AP (SDY) were lower in HR than in JU in Static. SD Y was lower in HR than in JU in Dynamic AP. COP velocity (COPV) was lower in both HR and JU than in NA in Static and Dynamic. Sample entropy along AP and ML (SampEnY and SampEnX) were higher in HR than in JU in Static. SampEnY was higher in HR than in JU in Dynamic ML. Sensory effects. In EC, COPV was lower in JU than in NA in Dynamic AP, and lower in JU than in both HR and NA in Dynamic ML. In EO, COPV was lower in both JU and HR than in NA in Dynamic ML. RQ applied to COPS was lower in JU than in both HR and NA in Dynamic AP, and lower in JU than in HR in Dynamic ML. RQ applied to COPV was lower in JU than in both HR and NA in Static and Dynamic. PQ applied to COPS was higher in JU than in both HR and NA in Dynamic ML.

Conclusion

Results showed that the effects of sport expertise on postural control could only be revealed with specific COP variables and were directionally oriented and sport-dependant. HR seem to rely more on vision than JU, thus revealing that the contribution of the sensory inputs to balance control is also sport-dependent. Results open up new knowledge on the specificity of sport practice on multisensory balance information during upright posture.
Electrophysiological model of human temporal contrast sensitivity based on SSVEP
Authors: Tsoneva Tsvetomira , Garcia-Molina Gary , Desain Peter
Published: July 2023

The present study aims to connect the psychophysical research on the human visual perception of flicker with the neurophysiological research on steady-state visual evoked potentials (SSVEPs) in the context of their application needs and current technological developments. In four experiments, we investigated whether a temporal contrast sensitivity model could be established based on the electrophysiological responses to repetitive visual stimulation and, if so, how this model compares to the psychophysical models of flicker visibility. We used data from 62 observers viewing periodic flicker at a range of frequencies and modulation depths sampled around the perceptual visibility thresholds. The resulting temporal contrast sensitivity curve (TCSC) was similar in shape to its psychophysical counterpart, confirming that the human visual system is most sensitive to repetitive visual stimulation at frequencies between 10 and 20 Hz. The electrophysiological TCSC, however, was below the psychophysical TCSC measured in our experiments for lower frequencies (1–50 Hz), crossed it when the frequency was 50 Hz, and stayed above while decreasing at a slower rate for frequencies in the gamma range (40–60 Hz). This finding provides evidence that SSVEPs could be measured even without the conscious perception of flicker, particularly at frequencies above 50 Hz. The cortical and perceptual mechanisms that apply at higher temporal frequencies, however, do not seem to directly translate to lower frequencies. The presence of harmonics, which show better response for many frequencies, suggests non-linear processing in the visual system. These findings are important for the potential applications of SSVEPs in studying, assisting, or augmenting human cognitive and sensorimotor functions.
Recent advances in analysis of capsaicin and its effects on metabolic pathways by mass spectrometry
Authors: Peng Zifang , Zhang Wenfen , Zhang Xu , Mao Jian , Zhang Qidong , Zhao Wuduo , Zhang Shusheng , Xie Jianping
Published: July 2023

Capsaicin is the main food active component in Capsicum that has gained considerable attention due to its broad biological activities, including antioxidation, anti-inflammation, anti-tumor, weight regulation, cardiac protection, anti-calculi, and diurnal-circadian regulation. The potent biological effects of capsaicin are intimately related to metabolic pathways such as lipid metabolism, energy metabolism, and antioxidant stress. Mass spectrometry (MS) has emerged as an effective tool for deciphering the mechanisms underlying capsaicin metabolism and its biological impacts. However, it remains challenging to accurately identify and quantify capsaicin and its self-metabolites in complex food and biological samples, and to integrate multi-omics data generated from MS. In this work, we summarized recent advances in the detection of capsaicin and its self-metabolites using MS and discussed the relevant MS-based studies of metabolic pathways. Furthermore, we discussed current issues and future directions in this field. In-depth studies of capsaicin metabolism and its physiological functions based on MS is anticipated to yield new insights and methods for preventing and treating a wide range of diseases.
Development and validation of risk prediction model for sarcopenia in patients with colorectal cancer
Authors: Zhang Ying , Zhu Yongjian
Published: July 2023

Objectives

Sarcopenia is associated with a poor prognosis in patients with colorectal cancer. However, the clinical factors that lead to colorectal cancer patients with sarcopenia are still unclear. The objective of this study is to develop and validate a nomogram for predicting the occurrence of sarcopenia and to provide healthcare professionals with a reliable tool for early identification of high-risk patients with colorectal cancer associated sarcopenia.

Methods

A total of 359 patients diagnosed with colorectal cancer from July 2021 to May 2022 were included. All patients were randomly divided into a training (n = 287) cohort and a validation cohort (n = 72) at the ratio of 80/20. Univariate and multivariate logistic analysis were performed to evaluate the factors associated with sarcopenia. The diagnostic nomogram of sarcopenia in patients with colorectal cancer was constructed in the training cohort and validated in the validation cohort. Various evaluation metrics were employed to assess the performance of the developed nomogram, including the ROC curve, calibration curve, and Hosmer-Lemeshow test.

Results

Smoking history, drinking history, diabetes, TNM stage, nutritional status, and physical activity were included in the nomogram for the prediction of sarcopenia. The diagnostic nomograms demonstrated excellent discrimination, with AUC values of 0.971 and 0.922 in the training and validation cohorts, respectively. Moreover, the calibration performance of the nomogram is also excellent, as evidenced by the Hosmer-Lemeshow test result of 0.886.

Conclusions

The nomogram consisting of preoperative factors was able to successfully predict the occurrence of sarcopenia in colorectal cancer patients, aiding in the early identification of high-risk patients and facilitating timely implementation of appropriate intervention measures.
Research trends and hot spots in global nanotechnology applications in liver cancer: a bibliometric and visual analysis (2000-2022)
Authors: Jin Xi , Zhao Jingwei , Li Hongshuang , Zheng Mengting , Shao Jiao , Chen Zhanguo
Published: July 2023

Background

Liver cancer (LC) is one of the most common malignancies. Currently, nanotechnology has made great progress in LC research, and many studies on LC nanotechnology have been published. This study aims to discuss the current status, hot spots, and research trends in this field through bibliometric analysis.

Methods

The Web of Science Core Collection (WoSCC) database was searched for papers related to hepatocellular carcinoma (HCC) included from January 2000 to November 2022, and its research hotspots and trends were visualized and analyzed with the help of VOSviewer. In addition, a search was conducted to find LC papers related to nanotechnology. Then we used the visual analysis software VOSviewer and CiteSpace to evaluate the contributions of countries/regions, authors, and journals related to the topic and analyze keywords to understand the research priorities and hot spots in the field as well as the development direction.

Results

There are 1908 papers in the highly cited literature on LC, and its research hotspots are pathogenesis, risk factors, and survival rate. The literature on the application of nanotechnology in LC had 921 papers. Among them, China (n=560, 60.8%) and the United States (n=170, 18.5%) were the countries with the highest number of published papers. Wang Yan (n=11) and Llovet JM (n=131) were the first authors and co-cited authors, respectively. The International Journal of Nanomedicine was the most prolific academic journal (n=41). In addition to “hepatocellular carcinoma” and “nanoparticles”, the most frequent keyword was “drug delivery”. In recent years, “metastasis” and “diagnosis” appeared in the keyword bursts. This indicates that the application of nanoparticles in the early diagnosis and drug delivery of LC (including liver metastasis) has a good prospect.

Conclusion

Nanotechnology has received more and more attention in the medical field in recent years. As nanoparticles are easily localized in organelles and cells, they can increase drug permeability in tumor tissues, improve drug delivery efficiency and reduce drug toxicity. Our research results were the first scientific evaluation of the application of nanotechnology in LC, providing scholars with research hotspots and development trends.
Rituximab in steroid-refractory immune-related pancreatitis: a case report
Authors: Santoro Armando , Masini Silvia , Cavina Raffaele , Tronconi Maria Chiara , De Vincenzo Fabio
Published: July 2023

The use of immune checkpoint inhibitors (ICIs) for treating several types of cancer is increasing, but they may be associated with immune-related adverse events (irAEs). Pancreatitis is a rare irAE, mostly responsive to steroid treatment. There are no published data on the management of steroid-refractory ICI-induced pancreatitis. Rituximab has shown efficacy in the setting of relapsing non-ICI-induced autoimmune pancreatitis. However, its use has not been tested for treating immunotherapy-related pancreatitis. Here, we present the case of a patient with steroid-refractory immune-related pancreatitis successfully treated with rituximab as a potential strategy for irAE management.
Molecular residual disease detection in resected, muscle-invasive urothelial cancer with a tissue-based comprehensive genomic profiling–informed personalized monitoring assay
Authors: Powles Thomas , Young Amanda , Nimeiri Halla , Madison Russell W. , Fine Alexander , Zollinger Daniel R. , Huang Yanmei , Xu Chang , Gjoerup Ole V. , Aushev Vasily N. , Wu Hsin-Ta , Aleshin Alexey , Carter Corey , Davarpanah Nicole , Degaonkar Viraj , Gupta Pratyush , Mariathasan Sanjeev , Schleifman Erica , Assaf Zoe June , Oxnard Geoffrey , Hegde Priti S.
Published: July 2023

Introduction

Circulating tumor DNA (ctDNA) detection postoperatively may identify patients with urothelial cancer at a high risk of relapse. Pragmatic tools building off clinical tumor next-generation sequencing (NGS) platforms could have the potential to increase assay accessibility.

Methods

We evaluated the widely available Foundation Medicine comprehensive genomic profiling (CGP) platform as a source of variants for tracking of ctDNA when analyzing residual samples from IMvigor010 (ClinicalTrials.gov identifier NCT02450331), a randomized adjuvant study comparing atezolizumab with observation after bladder cancer surgery. Current methods often involve germline sampling, which is not always feasible or practical. Rather than performing white blood cell sequencing to filter germline and clonal hematopoiesis (CH) variants, we applied a bioinformatic approach to select tumor (non-germline/CH) variants for molecular residual disease detection. Tissue-informed personalized multiplex polymerase chain reaction–NGS assay was used to detect ctDNA postsurgically (Natera).

Results

Across 396 analyzed patients, prevalence of potentially actionable alterations was comparable with the expected prevalence in advanced disease (13% FGFR2/3, 20% PIK3CA, 13% ERBB2, and 37% with elevated tumor mutational burden ≥10 mutations/megabase). In the observation arm, 66 of the 184 (36%) ctDNA-positive patients had shorter disease-free survival [DFS; hazard ratio (HR) = 5.77; 95% confidence interval (CI), 3.84–8.67; P < 0.0001] and overall survival (OS; HR = 5.81; 95% CI, 3.41–9.91; P < 0.0001) compared with ctDNA-negative patients. ctDNA-positive patients had improved DFS and OS with atezolizumab compared with those in observation (DFS HR = 0.56; 95% CI, 0.38–0.83; P = 0.003; OS HR = 0.66; 95% CI, 0.42–1.05). Clinical sensitivity and specificity for detection of postsurgical recurrence were 58% (60/103) and 93% (75/81), respectively.

Conclusion

We present a personalized ctDNA monitoring assay utilizing tissue-based FoundationOne® CDx CGP, which is a pragmatic and potentially clinically scalable method that can detect low levels of residual ctDNA in patients with resected, muscle-invasive bladder cancer without germline sampling.
Efficacy and safety of ‘dropless vitrectomy surgery’ and comparison of outcomes to standard of care topical therapy
Authors: Chalam K. V. , Ahmed Harris
Published: July 2023

Objective/Background

To compare the effectiveness of intravitreal injection of triamcinolone acetonide/moxifloxacin (Tri-Moxi) with the standard eye drop regimen for controlling postoperative inflammation, intraocular pressure, infections, macular thickness, and visual acuity (VA) in patients undergoing pars plana vitrectomy for various retinal disorders.

Subject/Methods

In this retrospective longitudinal study, patients who underwent vitrectomy using intravitreal Tri-Moxi at the end of surgery (Group 1) were compared with those who received standard topical steroid antibiotics (Group 2) in terms of intraocular inflammation, intraocular pressure, macular thickness based on optical coherence tomography, and visual acuity.

Results

In total, 162 consecutive eyes (group 1 [81 eyes]; group 2 [82 eyes]) were included. VA improved by two lines in both groups at 90 days. In Group 1, preoperative VA (logMAR) was 0.92 (0.66) compared to 0.92 (0.75) in Group 2 (p = 1), while at 3 months, it was 0.61 (0.3) and 0.57 (0.3), respectively (p = 0.46). Group 1 showed superior outcomes concerning central foveal thickness. The average central foveal thickness CFT (µm) in group 2 preoperatively was 423 (95) and 348 (63) at 3 months compared to group 1 526 (109) and 306 (108) preoperatively and 3 months, respectively (p = 0.042). There was no statistically significant difference in the rate of elevated intraocular pressure between the two groups or anterior chamber cell reaction severity, and no cases of endophthalmitis were observed in either group.

Conclusions

Tri-Moxi is effective after vitrectomy and is not inferior to standard postoperative topical therapy.
An investigation of the use of ethyl chloride and meloxicam to decrease the pain associated with a single or double incision method of castration in piglets
Authors: Garcia Arlene , Sutherland Mhairi , Vasquez Gizell , Quintana Adrian , Thompson Garrett , Willis Jemma , Chandler Shelbie , Niure Kiran , McGlone John
Published: July 2023

Castration is a stressful and painful procedure that can impact swine welfare negatively. The objectives of this study were to (1) evaluate the effect of one incision compared to two incisions and the use of a topical vapocoolant (VAPO; ethyl chloride; a topical anesthetic) applied before castration and (2) evaluate the most effective combination in reducing pain in objective 1 and the use of Metacam®; meloxicam before castration on measures of performance, behavior, and physiology. Study 1 consisted of six treatment groups (N = 27 pigs per treatment) and included: nothing (NO); sham castrated (SH); one incision castration (C1); one incision castration plus VAPO (C1V); two incision castration (C2); two incision castration plus VAPO (C2V). Body weights and blood samples were taken at baseline and other time points after castration. Behavior measures were collected for 24 h after castration. Wound scores were collected daily for 10 days. The C1 pigs and C1V pigs were significantly heavier than the other castrated treatment groups but not different from NO and SH pigs. Vocalizations were louder for C1 and C1V pigs (P = 0.0015). Study 2 (N = 40 pigs per treatment) included: nothing (NO); one incision castration (C1); and one incision castration plus meloxicam administered 15 min before castration (C1M). The same measures (performance, behavior, and physiology) were collected as in Study 1. Performance measures and behavior did not differ among treatment groups. Physiological measures were only different for red blood cells (RBC;P = 0.0304). Pigs in C1 and C1M treatment groups had cortisol concentrations that were greater than the NO treatment group at 15 min post-castration (P < 0.05). The data collected give insight into the benefits of one-incision castration compared to 2-incision castration. However, the data only support a lower-level relief from acute pain associated with castration, as it is evident that pigs still experience stress at 15 min post-castration with or without the use of meloxicam. Further research could potentially identify the correct timing, route and dose for the administration of meloxicam.
Have we got the optimal treatment for refractory Kawasaki disease in very young infants? A case report and literature review
Authors: Lersch Robert , Mandilaras Guido , Schrader Meike , Anselmino Felicitas , Haas Nikolaus A. , Jakob André
Published: July 2023

A small group of patients with Kawasaki disease (KD) demonstrates resistance to standard therapy, putting them at high risk for an unfavorable prognosis, especially regarding coronary artery aneurysms. Although adding corticosteroids to first-line i.v. immunoglobulins (IVIGs) is considered beneficial, and despite timely treatment initiation, very young infants, in particular, can present an unfavorable clinical course. We report on a 3-month-old boy with a clinically severe KD phenotype involving the early development of giant coronary artery aneurysms. Because of his poor response to the first course of IVIG and prednisolone, we administered infliximab. His clinical condition improved after that, and his temperature dropped. Inflammatory markers however did not recover completely, and he remained subfebrile. In addition, as the coronary artery dimensions deteriorated, a second IVIG course was administered and prednisolone continued at the initial dosage. Although fever and routine inflammatory parameters normalized, close follow-up investigations revealed both still increasing coronary artery dimensions and renewed rise in inflammatory parameters, necessitating two more infliximab administrations in addition to continuous prednisolone. Because of the coronary artery dimensions (left anterior descending artery, 4.9 mm, Z-score 11.1; right coronary artery 5.8 mm, Z-score 15.5), dual platelet inhibitory therapy with ASA and later clopidogrel combined with low-molecular heparin was indicated. Four weeks after his initial KD diagnosis, we detected no renewed increase in inflammatory markers; at that time, we observed a slight reduction in coronary dimensions. In summary, despite timely guideline-fulfilling therapy, the prolonged clinical course of this very young infant with KD entailing the development of giant coronary artery aneurysms makes us question whether this age group may benefit from early, even more intense therapy.
How did Bursaphelenchus nematodes acquire a specific relationship with their beetle vectors, Monochamus?
Authors: Kirino Haru , Maehara Noritoshi , Shinya Ryoji
Published: July 2023

For insect-borne pathogens, phoretic ability is important not only to spread more widely and efficiently but also to evolve virulence. Bursaphelenchus xylophilus, the causal agent of pine wilt disease, is transmitted by the cerambycid beetle Monochamus alternatus, which is associated with pine tree host. Their specific phoretic ability to appropriate vectors depending on their life cycle is critical for efficient transfer to the correct host and is expected to enhance virulence. We evaluated how B. xylophilus acquired a specific relationship with M. alternatus with a focus on Bursaphelenchus okinawaensis, a close relative of B. xylophilus that has evolved a relationship with a cerambycid beetle vector. Bursaphelenchus okinawaensis has a single dispersal stage (dauer) larva (third-stage dispersal [DIII] larva), whereas B. xylophilus has two distinct dispersal stages (DIII and fourth-stage dispersal [DIV] larva). Also, the dauer formation in B. okinawaensis is not completely dependent on its beetle vector, whereas DIV larvae of B. xylophilus are induced by volatile from the beetle vector. We investigated the induction conditions of dauer larvae in B. okinawaensis and compared to with B. xylophilus. The dauer percentages of B. okinawaensis significantly increased when the nematode population on the plate increased or when we propagated the nematodes with a crude extract of cultured nematodes, which likely contained dauer-inducing pheromones. In addition, dauer formation tended to be enhanced by the crude extract at high temperatures. Furthermore, when we propagated the nematodes with M. alternatus pupae until the beetles eclosed, B. okinawaensis significantly developed into dauer larvae. However, only 1.3% of dauer larvae were successfully transferred to M. alternatus, the rate lower than that of B. xylophilus. DIII and DIV of B. xylophilus were induced by increasing the nematode population and the presence of the beetle vector, respectively. These results suggest that B. okinawaensis has acquired specificity for the cerambycid beetle through dauer formation, which is efficiently induced in the presence of the beetle, and the DIV larval stage, exclusive to the xylophilus group, may be crucial for high transfer ability to the beetle vector.