bluuebunny/crossref_metadata_2025 huggingface dataset:
Disrupted metabolic signatures in amniotic fluid associated with increased risk of intestinal inflammation in cesarean section offspring
Authors: Liu Yongjie , Zhang Jun , Feng Liping
Published: January 2023

Introduction

Children born by cesarean section (CS) are at a greater risk of inflammatory bowel disease (IBD). However, the mechanisms underlying the association are not yet well understood. Herein, we investigated the impact of CS delivery on colonic inflammation and mechanisms underlying these effects in offspring.

Methods

CS mice model and dextran sulfate sodium (DSS)-induced colitis model were constructed and used to analyze the impact of CS on the development of colitis. Colonic tight junction markers and epithelium differentiation markers were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Levels of zonulin in serum were detected by enzyme-linked immunosorbent assay (ELISA). Immune cells in colon were analyzed by flow cytometry. Metabolic profiling between human vaginal delivery (VD) and CS AF were analyzed by using mass spectrometry. Transcriptome changes between VD AF- and CS AF-treated human intestine epithelial cells were analyzed by RNA-sequencing. A multi-omics approach that integrated transcriptomics with metabolomics to identify the pathways underlying colonic inflammation associated with delivery modes. Then, the identified pathways were confirmed by immunoblotting and ELISA.

Results

Mice pups delivered by CS exhibited a defective intestinal homeostasis manifested by decreased expression of tight junction markers of ZO-1 and Occludin in the colons, increased levels of zonulin in serum and dysregulated expression of intestinal epithelium differentiation markers of Lysozyme, Mucin2, and Dipeptidyl peptidase-4. CS pups were more susceptible to DSS-induced colitis compared to VD pups. The proportion of macrophage, dendritic cells (DCs), and natural killer cells (NKs) in the colons were altered in an age-dependent manner compared with pups born naturally. The metabolites in AF differed between CS and VD cases, and the CS AF-induced differentially expressed genes (DEGs) were significantly enriched in pathways underlying IBD. Signal transducer and activator of transcription 3 (STAT3) signaling was downregulated in NCM460 intestinal epithelial cells by CS AF compared to VD AF and in colon of CS pups compared to VD pups. Deficiency in metabolites like vitamin D2 glucosiduronate in CS AF may attribute to the risk of inflammatory intestine through STAT3 signaling.

Conclusion

Our study provides a novel insight into the underlying mechanisms of CS-associated intestinal inflammation and potential prevention strategies.
Inflammasome activation by Gram-positive bacteria: Mechanisms of activation and regulation
Authors: Keestra-Gounder A. Marijke , Nagao Prescilla Emy
Published: January 2023

The inflammasomes are intracellular multimeric protein complexes consisting of an innate immune sensor, the adapter protein ASC and the inflammatory caspases-1 and/or -11 and are important for the host defense against pathogens. Activaton of the receptor leads to formation of the inflammasomes and subsequent processing and activation of caspase-1 that cleaves the proinflammatory cytokines IL-1β and IL-18. Active caspase-1, and in some instances caspase-11, cleaves gasdermin D that translocates to the cell membrane where it forms pores resulting in the cell death program called pyroptosis. Inflammasomes can detect a range of microbial ligands through direct interaction or indirectly through diverse cellular processes including changes in ion fluxes, production of reactive oxygen species and disruption of various host cell functions. In this review, we will focus on the NLRP3, NLRP6, NLRC4 and AIM2 inflammasomes and how they are activated and regulated during infections with Gram-positive bacteria, including Staphylococcus spp., Streptococcus spp. and Listeria monocytogenes.
Kinetics of SARS-CoV-2 neutralizing antibodies in Omicron breakthrough cases with inactivated vaccination: Role in inferring the history and duration of infection
Authors: Simayi Aidibai , Li Chuchu , Chen Cong , Wang Yin , Dong Chen , Tian Hua , Kong Xiaoxiao , Zhou Lu , Peng Jiefu , Zhang Shihan , Zhu Fengcai , Hu Jianli , Xu Ke , Jin Hui , Fan Huafeng , Bao Changjun , Zhu Liguo
Published: January 2023

Background

The quantitative level and kinetics of neutralizing antibodies (NAbs) in individuals with Omicron breakthrough infections may differ from those of vaccinated individuals without infection. Therefore, we aimed to evaluate the difference in NAb levels to distinguish the breakthrough cases from the post-immunized population to identify early infected person in an outbreak epidemic when nasal and/or pharyngeal swab nucleic acid real-time PCR results were negative.

Methods

We collected 1077 serum samples from 877 individuals, including 189 with Omicron BA.2 breakthrough infection and 688 post-immunized participants. NAb titers were detected using the surrogate virus neutralization test, and were log(2)-transformed to normalize prior to analysis using Student’s unpaired t-tests. Geometric mean titers (GMT) were calculated with 95% confidence intervals (CI). Linear regression models were used to identify factors associated with NAb levels. We further conducted ROC curve analysis to evaluate the NAbs’ ability to identify breakthrough infected individuals in the vaccinated population.

Results

The breakthrough infection group had a consistently higher NAb levels than the post-immunized group according to time since the last vaccination. NAb titers in the breakthrough infection group were 6.4-fold higher than those in the post-immunized group (GMT: 40.72 AU/mL and 6.38 AU/mL, respectively; p<0.0001). In the breakthrough infection group, the NAbs in the convalescent phase were 10.9-fold higher than in the acute phase (GMT: 200.48 AU/mL and 18.46 AU/mL, respectively; p<0.0001). In addition, the time since infection, booster vaccination, and the time since last vaccination were associated with log(2)-transformed NAb levels in the breakthrough infection group. ROC curve analysis showed that ROC area was largest (0.728) when the cut-off value of log(2)-transformed NAb was 6, which indicated that NAb levels could identify breakthrough infected individuals in the vaccinated population.

Conclusion

Our study demonstrates that the NAb titers of Omicron BA.2 variant breakthrough cases are higher than in the post-immunized group. The difference in NAb levels could be used to identify cases of breakthrough infection from the post-immunized population in an outbreak epidemic.
Platelets derived citrullinated proteins and microparticles are potential autoantibodies ACPA targets in RA patients
Authors: Xu Minjie , Du Rong , Xing Wenping , Chen Xueting , Wan Jian , Wang Shengqing , Xiong Li , Nandakumar Kutty Selva , Holmdahl Rikard , Geng Hui
Published: January 2023

Citrullinated neoepitopes have emerged as key triggers of autoantibodies anti-citrullinated protein antibodies (ACPA) synthesis in rheumatoid arthritis (RA) patients. Apart from their critical role in homeostasis and thrombosis, platelets have a significant contribution to inflammation as well. Although anuclear in nature, platelets have an intricate post-translational modification machinery. Till now, citrullination in platelets and its contribution to trigger autoantibodies ACPA production in RA is an unexplored research direction. Herein, we investigated the expression of peptidylarginine deiminase (PAD) enzymes and citrullinated proteins/peptides in the human platelets and platelet derived microparticles (PDP). Both PAD4 mRNA and protein, but not the other PAD isoforms, are detectable in the human platelets. With a strict filtering criterion,108 citrullination sites present on 76 proteins were identified in the human platelets, and 55 citrullinated modifications present on 37 different proteins were detected in the PDPs. Among them, some are well-known citrullinated autoantigens associated with RA. Citrullinated forms of thrombospondin-1, β-actin, and platelet factor-4 (also known as CXCL4) are highly immunogenic and bound by autoantibodies ACPA. Furthermore, ACPA from RA sera and synovial fluids recognized citrullinated proteins from platelets and significantly activated them as evidenced by P-selectin upregulation and sCD40 L secretion. These results clearly demonstrate the presence of citrullinated autoantigens in platelets and PDPs, thus could serve as potential targets of ACPA in RA.
Heterogeneity on the abyssal plains: A case study in the Bering Sea
Authors: Sigwart Julia D. , Brandt Angelika , Di Franco Davide , Briones Elva Escobar , Gerken Sarah , Gooday Andrew J. , Grimes Candace J. , Głuchowska Kamila , Hoffmann Sven , Jażdżewska Anna Maria , Kamyab Elham , Kelch Andreas , Knauber Henry , Kohlenbach Katharina , Miguez-Salas Olmo , Moreau Camille , Ogawa Akito , Poliseno Angelo , Santín Muriel Andreu , Tandberg Anne Helene S. , Theising Franziska I. , Walter Thomas , Wölfl Anne-Cathrin , Chen Chong
Published: January 2023

The abyssal plains are vast areas without large scale relief that occupy much of the ocean floor. Although long considered relatively featureless, they are now known to display substantial biological heterogeneity across different spatial scales. Ecological research in these regions benefits increasingly from non-destructive visual sampling of epifaunal organisms with imaging technology. We analysed images from ultra-high-definition towed camera transects at depths of around 3500 m across three stations (100–130 km apart) in the Bering Sea, to ask whether the density and distribution of visible epifauna indicated any substantial heterogeneity. We identified 71 different megafaunal taxa, of which 24 occurred at only one station. Measurements of the two most abundant faunal elements, the holothurian Elpidia minutissima and two xenophyophores morphotypes (the more common identifiable as Syringammina limosa), indicated significant differences in local densities and patchy aggregations that were strikingly dissimilar among stations. One station was dominated by xenophyophores, one was relatively depauperate in both target taxa as well as other identified megafauna, and the third station was dominated by Elpidia. This is an unexpected level of variation within comparable transects in a well-mixed oceanic basin, reinforcing the emerging view that abyssal habitats encompass biological heterogeneity at similar spatial scales to terrestrial continental realms.
EBHI-Seg: A novel enteroscope biopsy histopathological hematoxylin and eosin image dataset for image segmentation tasks
Authors: Shi Liyu , Li Xiaoyan , Hu Weiming , Chen Haoyuan , Chen Jing , Fan Zizhen , Gao Minghe , Jing Yujie , Lu Guotao , Ma Deguo , Ma Zhiyu , Meng Qingtao , Tang Dechao , Sun Hongzan , Grzegorzek Marcin , Qi Shouliang , Teng Yueyang , Li Chen
Published: January 2023

Background and purpose

Colorectal cancer is a common fatal malignancy, the fourth most common cancer in men, and the third most common cancer in women worldwide. Timely detection of cancer in its early stages is essential for treating the disease. Currently, there is a lack of datasets for histopathological image segmentation of colorectal cancer, which often hampers the assessment accuracy when computer technology is used to aid in diagnosis.

Methods

This present study provided a new publicly available Enteroscope Biopsy Histopathological Hematoxylin and Eosin Image Dataset for Image Segmentation Tasks (EBHI-Seg). To demonstrate the validity and extensiveness of EBHI-Seg, the experimental results for EBHI-Seg are evaluated using classical machine learning methods and deep learning methods.

Results

The experimental results showed that deep learning methods had a better image segmentation performance when utilizing EBHI-Seg. The maximum accuracy of the Dice evaluation metric for the classical machine learning method is 0.948, while the Dice evaluation metric for the deep learning method is 0.965.

Conclusion

This publicly available dataset contained 4,456 images of six types of tumor differentiation stages and the corresponding ground truth images. The dataset can provide researchers with new segmentation algorithms for medical diagnosis of colorectal cancer, which can be used in the clinical setting to help doctors and patients. EBHI-Seg is publicly available at: https://figshare.com/articles/dataset/EBHI-SEG/21540159/1.
Probiotic mediated intestinal microbiota and improved performance, egg quality and ovarian immune function of laying hens at different laying stage
Authors: Xu Hengyong , Lu Yuxiang , Li Dan , Yan Chaoyang , Jiang Yuru , Hu Zhi , Zhang Zhipeng , Du Ranran , Zhao Xiaoling , Zhang Yao , Tian Yaofu , Zhu Qing , Liu Yiping , Wang Yan
Published: January 2023

In order to investigate the effects of dietary probiotics supplementation on laying performance, egg quality, serum hormone levels, immunity, antioxidant, and gut microbiota of layers at different laying stages, a total of 168 Tianfu green shell laying hens (28-day-old) were randomly divided into 2 treatments: a non-supplemented control diet (NC), and diet supplemented with 10 g/kg of probiotics, respectively. Each treatment had 6 replicates with 14 hens per replicate. The feeding trial lasted for 54 weeks. The results showed that the supplementation of probiotics significantly increased the average egg weight, improved egg quality (p < 0.05) and ovarian development. Meanwhile, probiotics increased the serum hormone levels of E2 and FSH, and antioxidant indices T-AOC and T-SOD (p < 0.05) of laying hens at different laying stages (p < 0.05), decreased the expression of proinflammatory factors including IL-1, IL-6 and TNF-α (p < 0.05). Furthermore, using 16S rRNA sequencing, we observed that the addition of probiotics increased the distribution of Firmicutes, Bacteroidota and Synergistota at early laying period. Meanwhile, Bacteroidota, Actinobacteriota, Verrucomicrobiota and Deferribacterota showed an increasing trend at the peak of egg production. The relative abundance of Firmicutes, Desulfobacterota and Actinobacteriota were significantly increased at the late laying period. Moreover, PICRUSt2 and BugBase analysis revealed that at the late laying period, the probiotics supplementation not only enriched many significant gene clusters of the metabolism of terpenoids and polyketide, genetic information processing, enzyme families, translation, transcription, replication and repair, and nucleotide metabolism, but also decreased the proportion of potential pathogenic bacteria. To sum up, these data show that the addition of probiotics not only improves the performance, egg quality, ovarian development and immune function of laying hens at different laying period, but also improves the gut microbiota of layers, thus enhances production efficiency.
Comparison of gut microbiota between immigrant and native populations of the Silver-eared Mesia (Leiothrix argentauris) living in mining area
Authors: Zhou Tianlong , Liu Shilong , Jiang Aiwu
Published: January 2023

The complex gut bacterial communities have a major impact on organismal health. However, knowledge of the effects of habitat change on the gut microbiota of wild birds is limited. In this study, we characterized the gut microbiota of two different subspecies of the Silver-eared Mesia (Leiothrix argentauris), the native subspecies (L. a. rubrogularis) and immigrant subspecies (L. a. vernayi), using 16S rRNA gene high-throughput sequencing. These two subspecies live in a trace metal-contaminated area, and L. a. vernayi was trafficked. They are an excellent system for studying how the gut microbiome of wild animal changes when they move to new habitats. We hypothesized that the immigrant subspecies would develop the same adaptations as the native subspecies in response to habitat changes. The results showed that there were no significant differences in the composition, diversity, or functional metabolism of gut microbiota between native and immigrant subspecies under the combined action of similar influencing factors (the p values of all analyses of variance >0.05). In addition, the composition and functional metabolism of gut microbiota in two subspecies showed adaptation against trace metal damage. Linear discriminant analysis effect size (LEfSe) analysis revealed that Massilia in the intestinal microbiota of immigrant subspecies was significantly higher than that of native subspecies, suggesting that immigrant subspecies suffered habitat change. Finally, we found that these two subspecies living in the mining area had an extremely high proportion of pathogenic bacteria in their gut microbiota (about 90%), much higher than in other species (about 50%) living in wild environment. Our results revealed the adaptation of intestinal microbiota of immigrant Silver-eared Mesias under heavy metals stress, which would provide guidance for biodiversity conservation and pollution management in mining area.
Evaluation of computational phage detection tools for metagenomic datasets
Authors: Schackart Kenneth E. , Graham Jessica B. , Ponsero Alise J. , Hurwitz Bonnie L.
Published: January 2023

Introduction

As new computational tools for detecting phage in metagenomes are being rapidly developed, a critical need has emerged to develop systematic benchmarks.

Methods

In this study, we surveyed 19 metagenomic phage detection tools, 9 of which could be installed and run at scale. Those 9 tools were assessed on several benchmark challenges. Fragmented reference genomes are used to assess the effects of fragment length, low viral content, phage taxonomy, robustness to eukaryotic contamination, and computational resource usage. Simulated metagenomes are used to assess the effects of sequencing and assembly quality on the tool performances. Finally, real human gut metagenomes and viromes are used to assess the differences and similarities in the phage communities predicted by the tools.

Results

We find that the various tools yield strikingly different results. Generally, tools that use a homology approach (VirSorter, MARVEL, viralVerify, VIBRANT, and VirSorter2) demonstrate low false positive rates and robustness to eukaryotic contamination. Conversely, tools that use a sequence composition approach (VirFinder, DeepVirFinder, Seeker), and MetaPhinder, have higher sensitivity, including to phages with less representation in reference databases. These differences led to widely differing predicted phage communities in human gut metagenomes, with nearly 80% of contigs being marked as phage by at least one tool and a maximum overlap of 38.8% between any two tools. While the results were more consistent among the tools on viromes, the differences in results were still significant, with a maximum overlap of 60.65%. Discussion: Importantly, the benchmark datasets developed in this study are publicly available and reusable to enable the future comparability of new tools developed.
Approximations of algorithmic and structural complexity validate cognitive-behavioral experimental results
Authors: Zenil Hector , Marshall James A. R. , Tegnér Jesper
Published: January 2023

Being able to objectively characterize the intrinsic complexity of behavioral patterns resulting from human or animal decisions is fundamental for deconvolving cognition and designing autonomous artificial intelligence systems. Yet complexity is difficult in practice, particularly when strings are short. By numerically approximating algorithmic (Kolmogorov) complexity (K), we establish an objective tool to characterize behavioral complexity. Next, we approximate structural (Bennett’s Logical Depth) complexity (LD) to assess the amount of computation required for generating a behavioral string. We apply our toolbox to three landmark studies of animal behavior of increasing sophistication and degree of environmental influence, including studies of foraging communication by ants, flight patterns of fruit flies, and tactical deception and competition (e.g., predator-prey) strategies. We find that ants harness the environmental condition in their internal decision process, modulating their behavioral complexity accordingly. Our analysis of flight (fruit flies) invalidated the common hypothesis that animals navigating in an environment devoid of stimuli adopt a random strategy. Fruit flies exposed to a featureless environment deviated the most from Levy flight, suggesting an algorithmic bias in their attempt to devise a useful (navigation) strategy. Similarly, a logical depth analysis of rats revealed that the structural complexity of the rat always ends up matching the structural complexity of the competitor, with the rats’ behavior simulating algorithmic randomness. Finally, we discuss how experiments on how humans perceive randomness suggest the existence of an algorithmic bias in our reasoning and decision processes, in line with our analysis of the animal experiments. This contrasts with the view of the mind as performing faulty computations when presented with randomized items. In summary, our formal toolbox objectively characterizes external constraints on putative models of the “internal” decision process in humans and animals.
The protective role of breastfeeding in multiple sclerosis: Latest evidence and practical considerations
Authors: Collorone Sara , Kodali Srikirti , Toosy Ahmed T.
Published: January 2023

The immunoprotective role of pregnancy in multiple sclerosis (MS) has been known for decades. Conversely, there has been rich debate on the topic of breastfeeding and disease activity in MS. In clinical practice, women are often offered to restart their disease-modifying drug (DMD) soon after delivery to maintain their relapse risk protection. Limited available information about peri-partum DMD safety can discourage women to choose breastfeeding, despite the World Health Organization's recommendation to breastfeed children for the first 6 months of life exclusively. New evidence is emerging about the protective role of exclusive breastfeeding on relapse rate. Research studies shed light on the hormonal and immunological mechanisms driving the risk of relapses during pregnancy and postpartum. Finally, case reports, real-world data, and clinical trials are increasing our knowledge of the safety of DMDs for the fetus and infant. While some DMDs must be avoided, others may be considered in highly active pregnant or lactating women with MS. This mini-review conveys recent evidence regarding the protective role of exclusive breastfeeding in MS and offers clinicians practical considerations for a patient-tailored approach.
Case report: Physical findings, physical therapy practice, and characteristics of disability of activities of daily living caused by obturator nerve palsy after neurotmesis
Authors: Shima Daichi , Kinoshita Tokio , Umemoto Yasunori , Yasuoka Yoshinori , Hashizaki Takamasa , Asaeda Makoto , Nishimura Yukihide , Yahata Tamaki , Shimoe Takashi , Tajima Fumihiro
Published: January 2023

The obturator nerve originates from the lumbar plexus and innervates sensation in the thigh and movement of the adductor muscle group of the hip. Reports on physical therapy for patients with obturator nerve injuries have been limited due to insufficient injuries, and there have been no reports on rehabilitation after neurotmesis. Furthermore, there are no reports on the status of activities of daily living (ADL) and details of physical therapy in patients with paralysis of the adductor muscle group. In this study, we reported on a patient with adductor paralysis due to obturator neurotmesis, including the clinical symptoms, characteristics of ADL impairment, and effective movement instruction. The patient is a woman in her 40's who underwent laparoscopic total hysterectomy, bilateral adnexectomy, and pelvic lymph node dissection for uterine cancer (grade-2 endometrial carcinoma). During pelvic lymph node dissection, she developed an obturator nerve injury. She underwent nerve grafting during the same surgery by the microsurgeon. Donor nerve was the ipsilateral sural nerve with a 3-cm graft length. Due to obturator nerve palsy, postoperative manual muscle test results were as follows: adductor magnus muscle, 1; pectineus muscle, 1; adductor longs muscle, 0; adductor brevis muscle, 0; and gracilis muscle, 0. On postoperative day 6, the patient could independently perform ADL; however, she was at risk of falling toward the affected side when putting on and taking off her shoes while standing on the affected leg. The patient was discharged on postoperative day 8. Through this case, we clarified the ADL impairment of a patient with adductor muscle palsy following obturator neurotmesis, and motion instruction was effective as physical therapy for this disability. This case suggests that movement instruction is important for acute rehabilitation therapy for patients with hip adductor muscle group with obturator neurotmesis.
Ultra-processed foods consumption is associated with multiple sclerosis severity
Authors: Guglielmetti Monica , Grosso Giuseppe , Ferraris Cinzia , Bergamaschi Roberto , Tavazzi Eleonora , La Malfa Alessandro , Wahidah H. Al-Qahtani , Tagliabue Anna
Published: January 2023

Background

MS is a chronic inflammatory neurological and immune-mediated disease of multifactorial etiology. Ultra-processed foods (UPFs) have been generally considered unhealthy due to their poor nutritional value. Emerging evidence suggests that factors other than their nutritional content may play an additional role toward chronic inflammation.

Aim

To investigate the potential association of UPF consumption and MS severity in a group of MS Italian consecutive patients.

Methods

Demographic (age, sex, marital status, educational level), neurological (EDSS, MSSS), and nutritional (anthropometric measures, dietary habits) information were collected. Physical activity and smoking habits were also investigated. Food items were grouped according to the NOVA classification. Patients were classified in two groups based on MS severity (“mild” and “moderate to high”).

Results

Higher UPF consumption was associated with moderate-to-high MS severity compared to lower consumption in both the unadjusted model (OR = 2.28, 95% CI: 1.04–5.01) and after adjustment for potential background (OR = 2.46, 95% CI: 1.04–5.83) and clinical confounding factors (OR = 2.97, 95% CI: 1.13–7.77).

Conclusions

Although these results are only preliminary and hypothesis generating, it is important to explore how various aspects of the diet may relate to MS severity in order to identify the best strategy to support MS patients over the disease course.
Association between urinary levels of 8-hydroxy-2-deoxyguanosine and F2a-isoprostane in male football players and healthy non-athlete controls with dietary inflammatory and antioxidant indices
Authors: Zare Mahsa , Shateri Zainab , Nouri Mehran , Sarbakhsh Parvin , Eftekhari Mohammad Hasan , Pourghassem Gargari Bahram
Published: January 2023

Purpose

The relationship between the inflammatory and antioxidant potential of an athlete's diet and their oxidative biomarkers is an important area of investigation. Therefore, this study aimed to assess the excretion of 8-hydroxy-2-deoxyguanosine (8-OHdG) and F2alpha-isoprostane (F2a-IP) in the urine of male football players and healthy non-athlete controls. This study also aimed to examine the associations among the dietary inflammatory index (DII), the dietary total antioxidant capacity (DTAC), and the dietary phytochemical index (PI) with 8-OHdG and F2a-IP.

Methods

In this descriptive-analytical study, 45 male football players and 45 healthy non-athletes, who were individually matched based on age and body mass index (BMI), were recruited from Shiraz City, Iran. Fasted urine samples were analyzed for 8-OHdG and F2a-IP levels. Anthropometric measurements were performed, and body composition was assessed using a body composition analyzer. A valid food frequency questionnaire (FFQ) was used to calculate DII, DTAC, and PI scores. Data analysis was conducted using a generalized estimating equation (GEE) model.

Results

We found that 8-OHdG (β = −6.96), F2a-IP (β = −82.58), and DII (β = −2.06) were significantly lower, while DTAC (β = 2.37) and PI (β = 0.084) were significantly higher in the football player group compared with the non-athlete group (P < 0.001 for all variables). In all participants, dietary indices were significantly associated with oxidative biomarkers. DII was positively associated with 8-OHdG (β = 2.25; P < 0.001) and F2a-IP (β = 38.34; P < 0.001). Furthermore, negative associations between DTAC (β = −1.42; P < 0.001) and PI (β = −35.37; P < 0.001) with 8-OHdG were found. Moreover, DTAC (β = −17.34; P < 0.001) and PI (β = −428.11; P = 0.003) were negatively associated with F2a-IP.

Conclusion

The results of this study highlighted the importance of a healthy diet in reducing oxidative stress among football athletes. The levels of urinary biomarkers for DNA and lipid oxidation were found to be lower in football players compared to non-athletes. This suggests that following an anti-inflammatory and antioxidant-rich diet may help reduce oxidative stress in these individuals.
Psidium guajava L.: From byproduct and use in traditional Mexican medicine to antimicrobial agent
Authors: Gutierrez-Montiel Daniela , Guerrero-Barrera Alma L. , Chávez-Vela Norma A. , Avelar-Gonzalez Francisco J. , Ornelas-García Ingrid G.
Published: January 2023

Mexico is one of the largest guava producers in the world, so it has access to a huge amount of waste and byproducts obtained after the industrial processing of the fruit. This review discusses the potential recovery of this residue for its application as an antimicrobial agent, considering the phytochemical composition, the bioactivity reported in-vivo and in-vitro, and the toxicology of the plant. Nowadays there is a growing demand for more natural and safer products, so the use of guava extracts is an interesting initiative, especially due to its availability in the country, its wide variety of traditional uses, and its phytochemical profile. This review highlights the importance and potential antimicrobial use of this plant in today's world.
Development and validation of a nomogram to predict overall survival in patients with incidental gallbladder cancer: A retrospective cohort study
Authors: Xie Zhi-Hua , Shi Xuebing , Liu Ming-Qi , Wang Jinghan , Yu Yong , Zhang Ji-Xiang , Chu Kai-Jian , Li Wei , Ge Rui-Liang , Cheng Qing-Bao , Jiang Xiao-Qing
Published: January 2023

Objective

The aim of this study was to develop and validate a nomogram to predict the overall survival of incidental gallbladder cancer.

Methods

A total of 383 eligible patients with incidental gallbladder cancer diagnosed in Shanghai Eastern Hepatobiliary Surgery Hospital from 2011 to 2021 were retrospectively included. They were randomly divided into a training cohort (70%) and a validation cohort (30%). Univariate and multivariate analyses and the Akaike information criterion were used to identify variables independently associated with overall survival. A Cox proportional hazards model was used to construct the nomogram. The C-index, area under time-dependent receiver operating characteristic curves and calibration curves were used to evaluate the discrimination and calibration of the nomogram.

Results

T stage, N metastasis, peritoneal metastasis, reresection and histology were independent prognostic factors for overall survival. Based on these predictors, a nomogram was successfully established. The C-index of the nomogram in the training cohort and validation cohort was 0.76 and 0.814, respectively. The AUCs of the nomogram in the training cohort were 0.8, 0.819 and 0.815 for predicting OS at 1, 3 and 5 years, respectively, while the AUCs of the nomogram in the validation cohort were 0.846, 0.845 and 0.902 for predicting OS at 1, 3 and 5 years, respectively. Compared with the 8th AJCC staging system, the AUCs of the nomogram in the present study showed a better discriminative ability. Calibration curves for the training and validation cohorts showed excellent agreement between the predicted and observed outcomes at 1, 3 and 5 years.

Conclusions

The nomogram in this study showed excellent discrimination and calibration in predicting overall survival in patients with incidental gallbladder cancer. It is useful for physicians to obtain accurate long-term survival information and to help them make optimal treatment and follow-up decisions.
Targeting the cMET pathway to enhance immunotherapeutic approaches for mUM patients
Authors: Machiraju Devayani , Hassel Jessica C.
Published: January 2023

The liver is the most preferential initial site of metastasis for uveal melanoma (mUM), and this preference is associated with rapid mortality in mUM patients. Despite the significant clinical benefits of Immune checkpoint inhibitors (ICIs) in metastatic cutaneous melanoma patients, ICIs have shown little to no benefit in mUM patients. A potential reason for this inefficiency of ICI could be partly devoted to the involvement of the liver itself, thanks to its rich source of growth factors and immunosuppressive microenvironment. Uveal melanoma cells show increased expression of a transmembrane protein called cMET, which is known as the sole receptor for the Hepatocyte growth factor (HGF). Hyperactivation of cMET by HGF contributes to mUM development, and the liver, being the major source of HGF, may partially explain the metastasis of uveal melanoma cells to the liver. In addition, cMET/HGF signaling has also been shown to mediate resistance to ICI treatment, directly and indirectly, involving tumor and immune cell populations. Therefore, targeting the cMET/HGF interaction may enhance the efficacy of immunotherapeutic regimes for mUM patients. Hence in this minireview, we will discuss the rationale for combining cMET inhibitors/antibodies with leading immune checkpoint inhibitors for treating mUM. We will also briefly highlight the challenges and opportunities in targeting cMET in mUM.
Stomach and duodenum dose–volume constraints for locally advanced pancreatic cancer patients treated in 15 fractions in combination with chemotherapy
Authors: Broggi Sara , Passoni Paolo , Tiberio Paolo , Cicchetti Alessandro , Cattaneo Giovanni Mauro , Longobardi Barbara , Mori Martina , Reni Michele , Slim Najla , Del Vecchio Antonella , Di Muzio Nadia G. , Fiorino Claudio
Published: January 2023

Purpose

To assess dosimetry predictors of gastric and duodenal toxicities for locally advanced pancreatic cancer (LAPC) patients treated with chemo-radiotherapy in 15 fractions.

Methods

Data from 204 LAPC patients treated with induction+concurrent chemotherapy and radiotherapy (44.25 Gy in 15 fractions) were available. Forty-three patients received a simultaneous integrated boost of 48–58 Gy. Gastric/duodenal Common Terminology Criteria for Adverse Events v. 5 (CTCAEv5) Grade ≥2 toxicities were analyzed. Absolute/% duodenal and stomach dose–volume histograms (DVHs) of patients with/without toxicities were compared: the most predictive DVH points were identified, and their association with toxicity was tested in univariate and multivariate logistic regressions together with near-maximum dose (D0.03) and selected clinical variables.

Results

Toxicity occurred in 18 patients: 3 duodenal (ulcer and duodenitis) and 10 gastric (ulcer and stomatitis); 5/18 experienced both. At univariate analysis, V44cc (duodenum: p = 0.02, OR = 1.07; stomach: p = 0.01, OR = 1.12) and D0.03 (p = 0.07, OR = 1.19; p = 0.008, OR = 1.12) were found to be the most predictive parameters. Stomach/duodenum V44Gy and stomach D0.03 were confirmed at multivariate analysis and found to be sufficiently robust at internal, bootstrap-based validation; the results regarding duodenum D0.03 were less robust. No clinical variables or %DVH was significantly associated with toxicity. The best duodenum cutoff values were V44Gy < 9.1 cc (and D0.03 < 47.6 Gy); concerning the stomach, they were V44Gy < 2 cc and D0.03 < 45 Gy. The identified predictors showed a high negative predictive value (>94%).

Conclusion

In a large cohort treated with hypofractionated radiotherapy for LAPC, the risk of duodenal/gastric toxicities was associated with duodenum/stomach DVH. Constraining duodenum V44Gy < 9.1 cc, stomach V44Gy < 2 cc, and stomach D0.03 < 45 Gy should keep the toxicity rate at approximately or below 5%. The association with duodenum D0.03 was not sufficiently robust due to the limited number of events, although results suggest that a limit of 45–46 Gy should be safe.
Pilot study for generating and assessing nomograms and decision curves analysis to predict clinically significant prostate cancer using only spatially registered multi-parametric MRI
Authors: Mayer Rulon , Turkbey Baris , Choyke Peter , Simone Charles B.
Published: January 2023

Background

Current prostate cancer evaluation can be inaccurate and burdensome. To help non-invasive prostate tumor assessment, recent algorithms applied to spatially registered multi-parametric (SRMP) MRI extracted novel clinically relevant metrics, namely the tumor’s eccentricity (shape), signal-to-clutter ratio (SCR), and volume.

Purpose

Conduct a pilot study to predict the risk of developing clinically significant prostate cancer using nomograms and employing Decision Curves Analysis (DCA) from the SRMP MRI-based features to help clinicians non-invasively manage prostate cancer.

Methods

This study retrospectively analyzed 25 prostate cancer patients. MP-MRI (T1, T2, diffusion, dynamic contrast-enhanced) were resized, translated, and stitched to form SRMP MRI. Target detection algorithm [adaptive cosine estimator (ACE)] applied to SRMP MRI determines tumor’s eccentricity, noise reduced SCR (by regularizing or eliminating principal components (PC) from the covariance matrix), and volume. Pathology assessed wholemount prostatectomy for Gleason score (GS). Tumors with GS >=4+3 (<=3+4) were judged as “Clinically Significant” (“Insignificant”). Logistic regression combined eccentricity, SCR, volume to generate probability distribution. Nomograms, DCA used all patients plus training (13 patients) and test (12 patients) sets. Area Under the Curves for (AUC) for Receiver Operator Curves (ROC) and p-values evaluated the performance.

Results

Combining eccentricity (0.45 ACE threshold), SCR (3, 4 PCs), SCR (regularized, modified regularization) with tumor volume (0.65 ACE threshold) improved AUC (>0.70) for ROC curves and p-values (<0.05) for logistic fit. DCA showed greater net benefit from model fit than univariate analysis, treating “all,” or “none.” Training/test sets achieved comparable AUC but with higher p-values.

Conclusions

Performance of nomograms and DCA based on metrics derived from SRMP-MRI in this pilot study were comparable to those using prostate serum antigen, age, and PI-RADS.
Pan-cancer analysis of chromothripsis-related gene expression patterns indicates an association with tumor immune and therapeutic agent responses
Authors: Zhang Qin , Yang Lujie , Xiao He , Dang Zhaoqian , Kuang Xunjie , Xiong Yanli , Zhu Jianwu , Huang Zhou , Li Mengxia
Published: January 2023

Chromothripsis is a catastrophic event involving numerous chromosomal rearrangements in confined genomic regions of one or a few chromosomes, causing complex effects on cells via the extensive structural variation. The development of whole-genome sequencing (WGS) has promoted great progress in exploring the mechanism and effect of chromothripsis. However, the gene expression characteristics of tumors undergone chromothripsis have not been well characterized. In this study, we found that the transcriptional profile of five tumor types experiencing chromothripsis is associated with an immune evasion phenotype. A gene set variation analysis (GSVA) was used to develop a CHP score, which is based on differentially expressed gene sets in the TCGA database, revealing that chromothripsis status in multiple cancers is consistent with an abnormal tumor immune microenvironment and immune cell cytotoxicity. Evaluation using four immunotherapy datasets uncovered the ability of the CHP score to predict immunotherapy response in diverse tumor types. In addition, the CHP score was found to be related to resistance against a variety of anti-tumor drugs, including anti-angiogenesis inhibitors and platinum genotoxins, while EGFR pathway inhibitors were found to possibly be sensitizers for high CHP score tumors. Univariate COX regression analysis indicated that the CHP score can be prognostic for several types of tumors. Our study has defined gene expression characteristics of tumors with chromothripsis, supporting the controversial link between chromothripsis and tumor immunity. We also describe the potential value of the CHP score in predicting the efficacy of immunotherapy and other treatments, elevating chromothripsis as a tool in clinical practice.
A model for predicting degree of malignancy in patients with intraductal papillary mucinous neoplasm
Authors: He Xiangyi , Fan Rong , Sun Jing , Ren Yanhao , Zhao Xuesong , Rui Weiwei , Yuan Yaozong , Zou Duowu
Published: January 2023

Background/Objectives

There is no predictive model available to address early stage malignant intraductal papillary mucinous neoplasm (IPMN) including high grade dysplasia (HGD) and pT1a (invasive component≤0.5 cm). The aim of this study was to establish an objective and sufficient model to predict the degree of malignancy in patients with IPMN, which can be easily applied in daily practice and adopted for any type of lesion.

Methods

A retrospective cohort study of 309 patients who underwent surgical resection for IPMN was performed. Members of the cohort were randomly allocated to the training or testing set. A detection tree model and random forest model were used for a 3-class classification to distinguish low grade dysplasia (LGD), HGD/pT1a IPMN, and invasive intraductal papillary mucinous cancer (I-IPMC) beyond pT1a.

Results

Of the 309 patients, 54 (17.4%) had early stage malignancy (19 HGD, 35 pT1a), 49 (15.9%) had I-IPMC beyond pT1a, and 206 (66.7%) had LGD IPMN. We proposed a 3-class classification model using a random forest algorithm, and the model had an accuracy of 99.5% with the training set, and displayed an accuracy of 96.0% with the testing set. We used SHAP for interpretation of the model and showed the top five factors (mural nodule size, main pancreatic duct diameter, CA19-9 levels, lesion edge and common bile duct dilation) were most likely to influence the 3-class classification results in terms of interpretation of the random forest model.

Conclusions

This predictive model will help assess an individual’s risk for different stages of IPMN malignancy and may help identify patients with IPMN who require surgery.
Comprehensive growth index monitoring of desert steppe grassland vegetation based on UAV hyperspectral
Authors: Liu Xiaomin , Wang Haichao , Cao Yanwei , Yang Yaotian , Sun Xiaotian , Sun Kai , Li Ying , Zhang Junyao , Pei Zhiyong
Published: January 2023

The goal of this study was to establish a comprehensive growth index (CGI) of grassland vegetation for monitor the overall condition of the grassland. Taking the desert grassland in Otuoke Banner, Ordos City, Inner Mongolia as the research object, this study integrates five indicators. First, the optimal band of the unmanned aerial vehicle hyperspectral data is optimized using the correlation analysis, successive projection algorithm (SPA), optimum index factor method, and band combination index method. A dual-band spectral index in good correlation with the CGI is then constructed in the optimal band. Afterwards, a CGI characterization model is established in accordance with the partial least squares regression (PLSR) algorithm and its accuracy is analyzed. Finally, the CGI of the study area is estimated. The experimental results are as follows. 1) The R2 of models built using the training samples of the spectral indices corresponding to the optimal spectra screened by the SPA method was 0.7835, RMSE was 0.0712, and RE was 6.89%, less than 10%. The R2 of the Validation samples was 0.7698, RMSE was 0.0471, and RE was 6.36%, less than 10%, highest precision. 2) Models were built using the spectral indices corresponding to the optimal spectra screened by the SPA method, and the CGI mean values were inverted. A comparison of the mean measured CGI values of the sample quadrat of the test area showed that the mean relative error was 3.82%. The results show that the vegetation growth of desert-steppe grasslands can be adequately monitored, providing technical support for the rapid and accurate diagnosis of grassland conditions. However, there are still shortcomings in this study. 1) The research area for this study was mainly in the desert steppe in Otuoke Banner, Ordos, hence the relevance and universality of the findings need to be verified, and subsequent experiments need to be carried out on desert steppes in other regions or even other types of grasslands to test the universality of the model. 2) In this study, the influence of soil background and litter on the spectral reflectance is not considered in depth. In addition, the influence of sensor observation angle and solar elevation angle on the inversion model demands further investigation efforts.
Combining ability and testcross performance of multi-nutrient maize under stress and non-stress environments
Authors: Matongera Nakai , Ndhlela Thokozile , van Biljon Angeline , Kamutando Casper N. , Labuschagne Maryke
Published: January 2023

While significant progress has been made by several international breeding institutions in improving maize nutritional quality, stacking of nutritional traits like zinc (Zn), quality protein, and provitamin A has not received much attention. In this study, 11 newly introduced Zn-enhanced inbred lines were inter-mated with seven testers from normal, provitamin A and quality protein maize (QPM) nutritional backgrounds in order to estimate the general combining ability (GCA) and specific combining ability (SCA) for grain yield (GY) and secondary traits under stress conditions [(combined heat and drought stress (HMDS) and managed low nitrogen (LN)] and non-stress conditions [(summer rainfed; OPT) and well-watered (irrigated winter; WW)] in Zimbabwe. Lines L6 and L7 had positive GCA effects for GY and secondary traits under OPT and LN conditions, and L8 and L9 were good general combiners for GY under HMDS conditions. Superior hybrids with high GY and desirable secondary traits were identified as L10/T7 and L9/T7 (Zn x normal), L2/T4, L4/T4, L3/T5 (Zn x provitamin A), and L8/T6 and L11/T3 (Zn x QPM), suggesting the possibility of developing Zn-enhanced hybrids with high yield potential using different nutritional backgrounds. Both additive and dominance gene effects were important in controlling most of the measured traits. This suggests that selecting for desirable traits during inbred line development followed by hybridization and testing of specific crosses under different management conditions could optimize the breeding strategy for stacked nutritionally-enhanced maize genotypes.