bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive evolution of antioxidase-related genes in hypoxia-tolerant mammals
Authors: Wang Qiu-Ping , Luo Chao-Yang , Xu Xiong-Hui , Hu Wen-Xian , Gai Yu-Lin , Gong You-Jing , Mu Yuan
Published: April 2024

To cope with the damage from oxidative stress caused by hypoxia, mammals have evolved a series of physiological and biochemical traits, including antioxidant ability. Although numerous research studies about the mechanisms of hypoxia evolution have been reported, the molecular mechanisms of antioxidase-related genes in mammals living in different environments are yet to be completely understood. In this study, we constructed a dataset comprising 7 antioxidase-related genes (CAT, SOD1, SOD2, SOD3, GPX1, GPX2, and GPX3) from 43 mammalian species to implement evolutionary analysis. The results showed that six genes (CAT, SOD1, SOD2, SOD3, GPX1, and GPX3) have undergone divergent evolution based on the free-ratio (M1) model. Furthermore, multi-ratio model analyses uncovered the divergent evolution between hypoxic and non-hypoxic lineages, as well as various hypoxic lineages. In addition, the branch-site model identified 9 positively selected branches in 6 genes (CAT, SOD1, SOD2, SOD3, GPX2, and GPX3) that contained 35 positively selected sites, among which 31 positively selected sites were identified in hypoxia-tolerant branches, accounting for 89% of the total number of positively selected sites. Interestingly, 65 parallel/convergent sites were identified in the 7 genes. In summary, antioxidase-related genes are subjected to different selective pressures among hypoxia-tolerant species living in different habitats. This study provides a valuable insight into the molecular evolution of antioxidase-related genes in hypoxia evolution in mammals.
KIF1C and new Huntingtin-interacting protein 1 binding proteins regulate rheumatoid arthritis fibroblast-like synoviocytes’ phenotypes
Authors: Laragione Teresina , Harris Carolyn , Gulko Percio S.
Published: April 2024

Background

Huntingtin-interacting protein-1 (HIP1) is a new arthritis severity gene implicated in the regulation of the invasive properties of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). These invasive properties of FLS strongly correlate with radiographic and histology damage in patients with RA and rodent models of arthritis. While HIP1 has several intracellular functions, little is known about its binding proteins, and identifying them has the potential to expand our understanding of its role in cell invasion and other disease-contributing phenotypes, and potentially identify new targets for therapy.

Methods

FLS cell lines from arthritic DA (highly invasive) and from arthritis-protected congenic rats R6 (minimally invasive), which differ in an amino-acid changing HIP1 SNP, were cultured and lysed, and proteins were immunoprecipitated with an anti-HIP1 antibody. Immunoprecipitates were analyzed by mass spectrometry. Differentially detected (bound) proteins were selected for functional experiments using siRNA knockdown in human RA FLS to examine their effect in cell invasiveness, adhesion, cell migration and proliferation, and immunofluorescence microscopy.

Results

Proteins detected included a few known HIP1-binding proteins and several new ones. Forty-five proteins differed in levels detected in the DA versus R6 congenic mass spectrometry analyses. Thirty-two of these proteins were knocked down and studied in vitro, with 10 inducing significant changes in RA FLS phenotypes. Specifically, knockdown of five HIP1-binding protein genes (CHMP4BL1, COPE, KIF1C, YWHAG, and YWHAH) significantly decreased FLS invasiveness. Knockdown of KIF1C also reduced RA FLS migration. The binding of four selected proteins to human HIP1 was confirmed. KIF1C colocalized with lamellipodia, and its knockdown prevented RA FLS from developing an elongated morphology with thick linearized actin fibers or forming polarized lamellipodia, all required for cell mobility and invasion. Unlike HIP1, KIF1C knockdown did not affect Rac1 signaling.

Conclusion

We have identified new HIP1-binding proteins and demonstrate that 10 of them regulate key FLS phenotypes. These HIP1-binding proteins have the potential to become new therapeutic targets and help better understand the RA FLS pathogenic behavior. KIF1C knockdown recapitulated the morphologic changes previously seen in the absence of HIP1, but did not affect the same cell signaling pathway, suggesting involvement in the regulation of different processes.
EMMPRIN promotes spheroid organization and metastatic formation: comparison between monolayers and spheroids of CT26 colon carcinoma cells
Authors: Feigelman Gabriele , Simanovich Elina , Brockmeyer Phillipp , Rahat Michal A.
Published: April 2024

Background

In vitro studies often use two-dimensional (2D) monolayers, but 3D cell organization, such as in spheroids, better mimics the complexity of solid tumors. To metastasize, cancer cells undergo the process of epithelial-to-mesenchymal transition (EMT) to become more invasive and pro-angiogenic, with expression of both epithelial and mesenchymal markers.

Aims

We asked whether EMMPRIN/CD147 contributes to the formation of the 3D spheroid structure, and whether spheroids, which are often used to study proliferation and drug resistance, could better model the EMT process and the metastatic properties of cells, and improve our understanding of the role of EMMPRIN in them.

Methods

We used the parental mouse CT26 colon carcinoma (CT26-WT) cells, and infected them with a lentivirus vector to knock down EMMPRIN expression (CT26-KD cells), or with an empty lentivirus vector (CT26-NC) that served as a negative control. In some cases, we repeated the experiments with the 4T1 or LLC cell lines. We compared the magnitude of change between CT26-KD and CT26-WT/NC cells in different metastatic properties in cells seeded as monolayers or as spheroids formed by the scaffold-free liquid overlay method.

Results

We show that reduced EMMPRIN expression changed the morphology of cells and their spatial organization in both 2D and 3D models. The 3D models more clearly demonstrated how reduced EMMPRIN expression inhibited proliferation and the angiogenic potential, while it enhanced drug resistance, invasiveness, and EMT status, and moreover it enhanced cell dormancy and prevented CT26-KD cells from forming metastatic-like lesions when seeded on basement membrane extract (BME). Most interestingly, this approach enabled us to identify that EMMPRIN and miR-146a-5p form a negative feedback loop, thus identifying a key mechanism for EMMPRIN activities. These results underline EMMPRIN role as a gatekeeper that prevents dormancy, and suggest that EMMPRIN links EMT characteristics to the process of spheroid formation.

Conclusions

Thus, 3D models can help identify mechanisms by which EMMPRIN facilitates tumor and metastasis progression, which might render EMMPRIN as a promising target for anti-metastatic tumor therapy.
Unveiling the hidden role of extracellular vesicles in brain metastases: a comprehensive review
Authors: Li Ji , Lu Shuangqing , Chen Feihu , Zhu Hui
Published: April 2024

Background

Extracellular vesicles (EVs) are small, transparent vesicles that can be found in various biological fluids and are derived from the amplification of cell membranes. Recent studies have increasingly demonstrated that EVs play a crucial regulatory role in tumorigenesis and development, including the progression of metastatic tumors in distant organs. Brain metastases (BMs) are highly prevalent in patients with lung cancer, breast cancer, and melanoma, and patients often experience serious complications and are often associated with a poor prognosis. The immune microenvironment of brain metastases was different from that of the primary tumor. Nevertheless, the existing review on the role and therapeutic potential of EVs in immune microenvironment of BMs is relatively limited.

Main body

This review provides a comprehensive analysis of the published research literature, summarizing the vital role of EVs in BMs. Studies have demonstrated that EVs participate in the regulation of the BMs immune microenvironment, exemplified by their ability to modify the permeability of the blood-brain barrier, change immune cell infiltration, and activate associated cells for promoting tumor cell survival and proliferation. Furthermore, EVs have the potential to serve as biomarkers for disease surveillance and prediction of BMs.

Conclusion

Overall, EVs play a key role in the regulation of the immune microenvironment of brain metastasis and are expected to make advances in immunotherapy and disease diagnosis. Future studies will help reveal the specific mechanisms of EVs in brain metastases and use them as new therapeutic strategies.
Highlighting the gap on spatial regulatory data in the official MPAs databases
Authors: Lippi Simona , Piroddi Chiara , Graziano Mariagrazia , Di Franco Antonio
Published: April 2024

Marine protected areas (MPAs) are a cornerstone for conserving marine ecosystems. Legal instruments and directives have been put in place to foster conservation of species and habitats; among all, the development and implementation of a coherent network of effective MPAs. Spatial information on management measures and on regulated, forbidden or allowed activities are fundamental to understand the actual role of MPAs and to support/guide policy decisions. The shortage of standardized geospatial information on MPA management, governance features, and human uses hinders policy makers’ ability to make informed decisions regarding the designation, implementation and evaluation of marine associated policies. This policy brief aims to stimulate international actions to enable researchers and decision-makers accessing data for policy development, marine/maritime spatial planning and decision-making processes.
The incidence of surgical site infection and its predictors among women delivered via cesarean sections in Ethiopia: a systematic review and meta-analysis
Authors: Wondmeneh Temesgen Gebeyehu , Mohammed Jemal Abdu
Published: April 2024

Background

Although surgical wound infection remains a serious issue worldwide, the disease burden is greater in developing countries, including Ethiopia. Even though there were primary studies conducted at district levels in Ethiopia, there is little evidence about the pooled incidence of surgical site infections at the national level. Thus, this systematic review and meta-analysis determined the pooled incidence of surgical site infection and its associated factors among cesarean-delivered women in Ethiopia.

Methods

We searched PubMed, CINAHL, African Journals Online, Google Scholar, and higher educational institutional repositories. A random-effects model was used to estimate the pooled effect size with 95% confidence intervals (CIs). Funnel plot and egger tests were computed to determine the existence of publication bias. A subgroup analysis was carried out.

Results

Twenty-three studies were included in the final analysis. The pooled incidence of surgical site infection among women delivered via cesarean section was 12.32% (95% CI: 8.96–16.11%). Rural residence (AOR = 2.51, 95% CI: 1.15–3.87), membrane rupture (AOR = 2.04, 95% CI: 1.24–2.85), chorioammionitis (AOR = 4.13, 95% CI: 1.45–6.8), general anesthesia (AOR = 1.99, 95% CI: 1.22–2.75), post-operative Hgb level less than 11 mg/dL (AOR = 3.25, 95% CI: 1.54–4.96) and membrane rupture greater or equal to 12 h (AOR = 3.93, 95% CI: 1.93–5.92) were independent risk factors for surgical site infections.

Conclusion

More than one in 10 women delivered via cesarean section developed surgical site infections in Ethiopia. Women living in rural areas and those with a membrane rupture, chorioammionitis, or anemia should be given special attention. General anesthesia should not be a mandatory procedure.
Biochemical characterization of Fsa16295Glu from “Fervidibacter sacchari,” the first hyperthermophilic GH50 with β-1,3-endoglucanase activity and founding member of the subfamily GH50_3
Authors: Covington Jonathan K. , Torosian Nicole , Cook Allison M. , Palmer Marike , Bryan Scott G. , Nou Nancy O. , Mewalal Ritesh , Harmon-Smith Miranda , Blaby Ian K. , Cheng Jan-Fang , Hess Matthias , Brumm Phillip J. , Singh Nitin K. , Venkateswaran Kasthuri , Hedlund Brian P.
Published: April 2024

The aerobic hyperthermophile “Fervidibacter sacchari” catabolizes diverse polysaccharides and is the only cultivated member of the class “Fervidibacteria” within the phylum Armatimonadota. It encodes 117 putative glycoside hydrolases (GHs), including two from GH family 50 (GH50). In this study, we expressed, purified, and functionally characterized one of these GH50 enzymes, Fsa16295Glu. We show that Fsa16295Glu is a β-1,3-endoglucanase with optimal activity on carboxymethyl curdlan (CM-curdlan) and only weak agarase activity, despite most GH50 enzymes being described as β-agarases. The purified enzyme has a wide temperature range of 4–95°C (optimal 80°C), making it the first characterized hyperthermophilic representative of GH50. The enzyme is also active at a broad pH range of at least 5.5–11 (optimal 6.5–10). Fsa16295Glu possesses a relatively high kcat/KM of 1.82 × 107 s−1 M−1 with CM-curdlan and degrades CM-curdlan nearly completely to sugar monomers, indicating preferential hydrolysis of glucans containing β-1,3 linkages. Finally, a phylogenetic analysis of Fsa16295Glu and all other GH50 enzymes revealed that Fsa16295Glu is distant from other characterized enzymes but phylogenetically related to enzymes from thermophilic archaea that were likely acquired horizontally from “Fervidibacteria.” Given its functional and phylogenetic novelty, we propose that Fsa16295Glu represents a new enzyme subfamily, GH50_3.
Whole-plant silage maize to improve fiber digestive characteristics and intestinal microbiota of Hezuo pigs
Authors: Wang Longlong , Wang Pengfei , Yan Zunqiang , Zhang Pengxia , Yin Xitong , Jia Rui , Li Yao , Yang Jiaojiao , Gun Shuangbao , Yang Qiaoli
Published: April 2024

Introduction

Utilizing roughage resources is an effective approach to alleviate the shortage of corn-soybean feed and reducing the costs in the swine industry. Hezuo pig is one group of plateau type local Tibetan pig with strong tolerance to crude feeding. Nevertheless, current research on the roughage tolerance in Hezuo pigs and the microbiological mechanisms behind it is still minimally.This study explored the impact of various ratios of whole-plant silage (WPS) maize on the pH, cellulase activity, short-chain fatty acids (SCFAs), and intestinal microbiota in Hezuo pigs.

Methods

Thirty-two Hezuo pigs were randomly divided into four groups (n = 8). The control group received a basal diet, while experimental groups I, II, and III were given diets with incremental additions of 5%, 10%, and 15% air-dried WPS maize, respectively, for 120 days.

Results

The findings revealed that compared with the control group, in Group II, the pH of cecum and colon were notably decreased (p < 0.05), while acid detergent fiberdigestibility, the concentration of propionic and isobutyric acid in the cecum, and the concentration of isobutyric acid in the colon were significantly increased (p < 0.05). Also, carboxymethyl cellulase activity in the cecum in group II of Hezuo pigs was significantly higher than that in the other three groups (p < 0.05). Furthermore, the cecum microbiota showed a higher diversity in the group II of Hezuo pigs than that in the control group, as shown by the Simpson and Shannon indices. Specifically, 15 and 24 bacterial species showed a significant difference in relative abundance at the family and genus levels, respectively. Correlation analyses revealed significant associations between bacterial genera and SCFAs concentrations in the cecum. The abundance of Bacteroides and NK4A214_group was positively correlated with amounts of valeric and isovaleric acid but negatively with propionic acid (p < 0.05). The abundance of UCG-010 was positively linked with acetic acid and negatively correlated with butyric acid (p < 0.05). Actinobacillus abundance was positively associated with butyric acid levels (p < 0.05).

Discussion

In conclusion, a 10% WPS maize diet improved crude fiber digestibility by lowering cecal and colonic chyme pH, enhancing intestinal cellulase activity, improving SCFA production, and increasing intestinal microbiota diversity.
Integrating systemic immune-inflammation index, fibrinogen, and T-SPOT.TB for precision distinction of active pulmonary tuberculosis in the era of mycobacterial disease research
Authors: Yu Zhikang , Shang Zifang , Huang Qingyan , Wen Feiqiu , Patil Sandip
Published: April 2024

Background

The clinical challenge of differentiating suspected tuberculosis with positive T-SPOT.TB results persist. This study aims to investigate the utility of the Systemic Immune-Inflammation Index (SII), Fibrinogen, and T-SPOT.TB in distinguishing between active pulmonary tuberculosis (PTB) and non-tuberculous lung diseases.

Methods

A retrospective analysis included 1,327 cases of active PTB with positive T-SPOT.TB results and 703 cases of non-tuberculous lung diseases from May 2016 to December 2020 at Meizhou People’s Hospital. These were designated as the case group and the control group, respectively. The detection indicators of T-SPOT.TB: Early Secreted Antigenic Target 6 (ESAT-6), Culture Filtrate Protein 10 (CFP-10), as well as SII and Fibrinogen levels—were compared and analyzed for association and joint diagnostic value between the two groups.

Results

The case group showed higher values of ESAT-6, CFP-10, SII, and Fibrinogen compared to the control group (all p < 0.001). In the case group, SII and Fibrinogen did not correlate with ESAT-6 and CFP-10 (∣rs∣ all < 0.3) but were positively correlated with C-reactive protein (CRP; rs all > 0.3). SII and Fibrinogen values in smear-positive pulmonary tuberculosis were higher than in smear-negative cases (all p < 0.05). The optimal diagnostic thresholds for ESAT-6, CFP-10, SII, and Fibrinogen in differentiating between active PTB and non-tuberculous lung diseases were 21.50 SFCs/106 PBMC, 22.50 SFCs/106 PBMC, 2128.32, and 5.02 g/L, respectively. Regression logistic analysis showed that ESAT-6 < 21.5 (OR: 1.637, 95% CI: 1.311–2.043, p < 0.001), CFP-10 < 22.5 (OR: 3.918, 95% CI: 3.138–4.892, p = 0.025), SII < 2128.32 (OR: 0.763, 95% CI: 0.603–0.967, p < 0.001), and FIB < 5.02 (OR: 2.287, 95% CI: 1.865–2.806, p < 0.001) were independent risk factors for active PTB. The specificity for ESAT-6 + CFP-10, ESAT-6 + CFP-10 + SII, ESAT-6 + CFP-10 + FIB, and ESAT-6 + CFP-10 + SII + FIB was 82.5%, 83.2%, 95.8%, and 80.1%, respectively, while sensitivity was 52.6%, 53.0%, 55.8%, and 44.7%, and positive predictive values were 85.0%, 85.6%, 84.1%, and 89.6%, respectively.

Conclusion

SII and Fibrinogen are positively correlated with the degree of tuberculosis inflammation and the bacterial load of Mycobacterium tuberculosis. The combined detection of SII, Fibrinogen, and T-SPOT.TB is significant in distinguishing between active PTB with positive T-SPOT.TB results and non-tuberculous lung diseases.
First insight about the ability of specific glycerophospholipids to discriminate non-small cell lung cancer subtypes
Authors: Sieminska Julia , Miniewska Katarzyna , Mroz Robert , Sierko Ewa , Naumnik Wojciech , Kisluk Joanna , Michalska-Falkowska Anna , Reszec Joanna , Kozlowski Miroslaw , Nowicki Lukasz , Moniuszko Marcin , Kretowski Adam , Niklinski Jacek , Ciborowski Michal , Godzien Joanna
Published: April 2024

Introduction: Discrimination between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) subtypes in non-small cell lung cancer (NSCLC) patients is a significant challenge in oncology. Lipidomics analysis provides a promising approach for this differentiation.

Methods: In an accompanying paper, we explored oxPCs levels in a cohort of 200 NSCLC patients. In this research, we utilized liquid chromatography coupled with mass spectrometry (LC-MS) to analyze the lipidomics profile of matching tissue and plasma samples from 25 NSCLC patients, comprising 11 ADC and 14 SCC cases. This study builds upon our previous findings, which highlighted the elevation of oxidised phosphatidylcholines (oxPCs) in NSCLC patients.

Results: We identified eight lipid biomarkers that effectively differentiate between ADC and SCC subtypes using an untargeted approach. Notably, we observed a significant increase in plasma LPA 20:4, LPA 18:1, and LPA 18:2 levels in the ADC group compared to the SCC group. Conversely, tumour PC 16:0/18:2, PC 16:0/4:0; CHO, and plasma PC 16:0/18:2; OH, PC 18:0/20:4; OH, PC 16:0/20:4; OOH levels were significantly higher in the ADC group.

Discussion: Our study is the first to report that plasma LPA levels can distinguish between ADC and SCC patients in NSCLC, suggesting a potential role for LPAs in NSCLC subtyping. This finding warrants further investigation into the mechanisms underlying these differences and their clinical implications.
Investigation on the relationship between hemoglobin concentration and stroke risk: a bidirectional Mendelian randomization study
Authors: Wu Wenbao , Fan Daofeng , Que Binfu , Chen Yangui , Qiu Rui
Published: April 2024

Background

The relationship between hemoglobin concentration and stroke has garnered significant interest in the research community. However, findings from published observational epidemiological studies on this relationship have been inconclusive. By using publicly available genome-wide association study (GWAS) aggregated statistics, a two-sample Mendelian randomization analysis is conducted to explore the causal relationship between hemoglobin concentration and stroke.

Methods

Summary statistics data from UK Biobank for hemoglobin concentration and from the FinnGen R9 and MEGASTROKE consortium for stroke are used. A series of quality control steps are taken to select eligible instrumental SNPs closely related to exposure. In order to make the conclusion more robust and reliable, several robust analysis methods are employed including inverse variance weighted, weighted median, MR-Egger regression, which are based on different assumptions of two-sample MR Analysis. Meanwhile, sensitivity analyses such as pleiotropy test and MR-Egg regression, are performed to mitigate horizontal pleiotropy and heterogeneity.

Results

The two-sample Mendelian randomized study indicates a negative association between hemoglobin concentration and stroke, suggesting that hemoglobin concentration acts as a protective factor against stroke. From the FinnGen database, there is a negative association between hemoglobin concentration and stroke, with an odds ratio (OR) of 0.82 and a 95% confidence interval (CI) of 0.73–0.92, p = 0.0006. Similarly, the MEGASTROKE database findings reinforce this observation. The negative association between hemoglobin concentration and stroke (OR: 0.91, 95%CI: 0.83–1.00, p = 0.040), ischemic stroke (OR: 0.87, 95%CI: 0.79–0.96, p = 0.004), and cardiogenic stroke (OR: 0.82, 95% CI: 0.69–0.99, p = 0.039) further suggests that higher hemoglobin levels might confer a protective effect against these conditions.

Conclusion

Hemoglobin concentration serves as a protective factor against stroke, and managing abnormal hemoglobin levels can effectively reduce the incidence of stroke.
Removal of movement artifacts and assessment of mental stress analyzing electroencephalogram of non-driving passengers under whole-body vibration
Authors: Song Byoung-Gyu , Kang Namcheol
Published: April 2024

The discomfort caused by whole-body vibration (WBV) has long been assessed using subjective surveys or objective measurements of body acceleration. However, surveys have the disadvantage that some of participants often express their feelings in a capricious manner, and acceleration data cannot take into account individual preferences and experiences of their emotions. In this study, we investigated vibration-induced mental stress using the electroencephalogram (EEG) of 22 seated occupants excited by random vibrations. Between the acceleration and the EEG signal, which contains electrical noise due to the head shaking caused by random vibrations, we found that there was a strong correlation, which acts as an artifact in the EEG, and therefore we removed it using an adaptive filter. After removing the artifact, we analyzed the characteristics of the brainwaves using topographic maps and observed that the activities detected in the frontal electrodes showed significant differences between the static and vibration conditions. Further, frontal alpha asymmetry (FAA) and relative band power indices in the frontal electrodes were analyzed statistically to assess mental stress under WBV. As the vibration level increased, EEG analysis in the frontal electrodes showed a decrease in FAA and alpha power but an increase in gamma power. These results are in good agreement with the literature in the sense that FAA and alpha band power decreases with increasing stress, thus demonstrating that WBV causes mental stress and that the stress increases with the vibration level. EEG assessment of stress during WBV is expected to be used in the evaluation of ride comfort alongside existing self-report and acceleration methods.
Impacts of dioxin exposure on brain connectivity estimated by DTI analysis of MRI images in men residing in contaminated areas of Vietnam
Authors: Thao Pham Ngoc , Nishijo Muneko , Tai Pham The , Nghi Tran Ngoc , Yokawa Takashi , Hoa Vu Thi , Tien Tran Viet , Kien Nguyen Xuan , Anh Tran Hai , Nishino Yoshikazu , Nishijo Hisao
Published: April 2024

Introduction

Effects of dioxin exposure on gray matter volume have been reported in previous studies, but a few studies reported effects of dioxin exposure on white matter structure. Therefore, this study was undertaken to investigate the impact of dioxin exposure on white matter microstructure in men living in the most severely dioxin-contaminated areas in Vietnam.

Methods

In 2019 brain MRI scans from 28 men living near Bien Hoa airbase were obtained at Dong Nai General Hospital, Vietnam, on a 3 T scanner using a conventional diffusion tensor imaging sequence. Two exposure markers were indicated by perinatal exposure estimated by assessment of maternal residency in a dioxin-contaminated area during pregnancy and by measurement of blood dioxin levels. A general linear model was used to compare fractional anisotropy (FA) values in 11 white matter tracts in both hemispheres between groups with and without perinatal dioxin exposure and groups with high and low blood dioxin levels after adjusting for covariates.

Results

The adjusted mean FA value in the left cingulum hippocampal part (CGH) was significantly lower in the perinatal dioxin exposure group compared with the group without perinatal dioxin exposure. The high blood TCDD group showed significantly reduced FA values in the left and right CGH and right uncinate fasciculus (UNC). Moreover, the high blood TEQ-PCDDs group showed significantly lower FA values in the left and right CGH and the left UNC. There were no significant differences in FA values between the groups with high and low TEQ-PCDFs levels or between the groups with high and low TEQ-PCDD/Fs levels.

Discussion

It was concluded that dioxin exposure during the perinatal period and adulthood may alter the microstructure of white matter tracts in individuals with neurodevelopmental disorders.
BRCA testing and management of BRCA-mutated early-stage breast cancer: a comprehensive statement by expert group from GCC region
Authors: Al-Shamsi Humaid O. , Alwbari Ahmed , Azribi Fathi , Calaud Francois , Thuruthel Sanjay , Tirmazy Syed Hammad Hassan , Kullab Sharif , Ostomane Sonia , Abulkhair Omalkhair
Published: April 2024

BReast CAncer (BRCA)1 and BRCA2 gene pathogenic variants account for most hereditary breast cancers (BC). Identification of BRCA mutations can significantly influence both prognosis and treatment outcomes. Furthermore, it enables the identification of individuals who are at heightened risk of developing BC due to inherited genetic mutations. Many developing countries rely on western guidelines for BRCA testing and BC management; however, there exist wide disparities in the prevalence of risk factors, availability of medical resources, and practice patterns. Guidelines tailored to specific regions can help mitigate healthcare variations, promote consistency in treatment, and aid healthcare providers in identifying effective therapies for improving patient outcomes. Hence, oncologists from the Gulf Cooperation Council (GCC) congregated virtually in March 2023 and reviewed existing data on the epidemiology of BC, BRCA mutations, practices and challenges associated with BRCA testing and management of BRCA mutated early-stage BC in the GCC region. They also provided insights on the real-world diagnostic and treatment practices and challenges in the GCC region in the BRCA-mutated early-stage BC domain and suggested some variations to international guidelines to aid their uptake in this region.
Prognostic analysis of stage IIIC1p cervical cancer patients
Authors: Gao Ting , Yang Zixuan , Wei Liqun , Tang Xiaobi , Ma Shanshan , Jiang Li , Zhang Yong , Wu Fang
Published: April 2024

Background

Stage IIIC1p cervical cancer is characterized by marked heterogeneity and considerable variability in the postoperative prognosis. This study aimed to identify the clinical and pathological characteristics affecting the survival of patients diagnosed with stage IIIC1p cervical cancer.

Methods

We retrospectively analyzed patients diagnosed with stage IIIC1p cervical cancer who underwent radical hysterectomy and lymph node dissection between March 2012 and March 2022. Overall survival (OS) was estimated using Kaplan-Meier survival curves. Univariate and multivariate Cox proportional hazards models were used to evaluate prognostic factors for OS and forest plots were used to visualize these findings. Nomogram charts were created to forecast survival rates at 3 and 5 years, and the accuracy of predictions was evaluated using Harrell’s concordance index (C-index) and calibration curves.

Results

The study cohort comprised 186 women diagnosed with stage IIIC1p cervical cancer. The median follow-up duration was 51.1 months (range, 30-91 months), and the estimated 5-year OS rate was 71.5%. Multivariate analysis revealed that concurrent chemoradiotherapy plus adjuvant chemotherapy (CCRT + AC), monocyte-lymphocyte ratio (MLR), ratio of lymph node metastasis (LNM), and squamous cell carcinoma antigen (SCCA) levels independently predicted OS.

Conclusions

Significant prognostic disparities exist among patients diagnosed with stage IIIC1p cervical cancer. MLR, ratio of LNM, and SCCA were associated with poor OS. In contrast, the CCRT + AC treatment regimen appeared to confer a survival advantage.
Construction and verification of an endoplasmic reticulum stress-related prognostic model for endometrial cancer based on WGCNA and machine learning algorithms
Authors: Lin Shanshan , Wei Changqiang , Wei Yiyun , Fan Jiangtao
Published: April 2024

Background

Endoplasmic reticulum (ER) stress arises from the accumulation of misfolded or unfolded proteins within the cell and is intricately linked to the initiation and progression of various tumors and their therapeutic strategies. However, the precise role of ER stress in uterine corpus endometrial cancer (UCEC) remains unclear.

Methods

Data on patients with UCEC and control subjects were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Using differential expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA), we identified pivotal differentially expressed ER stress-related genes (DEERGs). Further validation of the significance of these genes in UCEC was achieved through consensus clustering and bioinformatic analyses. Using Cox regression analysis and several machine learning algorithms (least absolute shrinkage and selection operator [LASSO], eXtreme Gradient Boosting [XGBoost], support vector machine recursive feature elimination [SVM-RFE], and Random Forest), hub DEERGs associated with patient prognosis were effectively identified. Based on the four identified hub genes, a prognostic model and nomogram were constructed. Additionally, a drug sensitivity analysis and in vitro validation experiments were performed.

Results

A total of 94 DEERGs were identified in patients with UCEC and healthy controls. Consensus clustering analysis revealed significant differences in prognosis, typical immune checkpoints, and tumor microenvironments between the subtypes. Using Cox regression analysis and machine learning, four hub DEERGs, MYBL2, RADX, RUSC2, and CYP46A1, were identified to construct a prognostic model. The reliability of the model was validated using receiver operating characteristic (ROC) curves. Decision curve analysis (DCA) demonstrated the superior predictive ability of the nomogram in terms of 3- and 5-year survival, compared with that of other clinical indicators. Drug sensitivity analysis revealed increased sensitivity to dactinomycin, docetaxel, selumetinib, and trametinib in the low-risk group. The expressions of RADX, RUSC2, and CYP46A1 were downregulated, whereas that of MYBL2 was upregulated in UCEC tissues, as demonstrated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence assays.

Conclusion

This study developed a stable and accurate prognostic model based on multiple bioinformatics analyses, which can be used to assess the prognosis of UCEC. This model may contribute to future research on the risk stratification of patients with UCEC and the formulation of novel treatment strategies.
Research progress in endometriosis-associated ovarian cancer
Authors: Tang Ling , Bian Ce
Published: April 2024

Endometriosis-associated ovarian cancer (EAOC) is a unique subtype of ovarian malignant tumor originating from endometriosis (EMS) malignant transformation, which has gradually become one of the hot topics in clinical and basic research in recent years. According to clinicopathological and epidemiological findings, precancerous lesions of ovarian clear cell carcinoma (OCCC) and ovarian endometrioid carcinoma (OEC) are considered as EMS. Given the large number of patients with endometriosis and its long time window for malignant transformation, sufficient attention should be paid to EAOC. At present, the pathogenesis of EAOC has not been clarified, no reliable biomarkers have been found in the diagnosis, and there is still a lack of basis and targets for stratified management and precise treatment in the treatment. At the same time, due to the long medical history of patients, the fast growth rate of cancer cells, and the possibility of eliminating the earliest endometriosis-associated ovarian cancer, it is difficult to find the corresponding histological evidence. As a result, few patients are finally diagnosed with EAOC, which increases the difficulty of in-depth study of EAOC. This article reviews the epidemiology, pathogenesis, risk factors, clinical diagnosis, new treatment strategies and prognosis of endometriosis-associated ovarian cancer, and prospects the future direction of basic research and clinical transformation, in order to achieve stratified management and personalized treatment of ovarian cancer patients.
Treatment with (chemo)-radiation in old patients (≥76 years of age) with newly diagnosed non-metastatic squamous cell cancer of the head and neck region: real-world data from a tertiary referral center
Authors: Winkler Leah-Sophie , Haderlein Marlen , Semrau Sabine , Putz Florian , Höfler Daniel , Müller Sarina K. , Iro Heinrich , Kesting Marco , Fietkau Rainer , Schubert Philipp
Published: April 2024

Purpose

Treatment of patients with cancer of the head and neck region is in focus in a multitude of studies. Of these patients, one patient group, those aged 76 and more, is mostly underrepresented despite requiring thorough and well-reasoned treatment decisions to offer curative treatment. This study investigates real-world data on curative treatment of old (≥76 years) patients with newly diagnosed squamous cell carcinoma of the head and neck region (HNSCC).

Patients and methods

Between January 2010 and December 2021, we identified 71 patients older than 76 years with newly diagnosed HNSCC and cM0 at the Department of Radiation Oncology of the University Hospital of Erlangen-Nuremberg. Using electronic medical records, we analyzed treatment patterns and outcomes in terms of overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) rate. Additionally, we performed univariate risk analysis and Cox regression in order to identify predictive factors associated with the abovementioned treatment outcomes.

Results

The median follow-up was 18 months. OS was 83%, 79%, and 72% after 1 year, 2 years, and 3 years, respectively. PFS was 69%, 54%, and 46% after 1 year, 2 years, and 3 years, respectively. A total of 34 (48%) patients were treated with standard therapy according to current guidelines. The reasons for deviation from standard therapy before or during treatment were as follows: unfitness for cisplatin-based chemotherapy (n = 37), reduction of chemotherapy (n = 3), and dose reduction/interruption of radiotherapy (n = 8). Carboplatin-based systemic therapy showed improved PFS compared to cisplatin or cetuximab (60 vs. 28 vs. 15 months, p = 0.037) but without impact on OS (83 vs. 52 vs. 38 months, p = 0.807). Oropharyngeal tumor localization (p = 0.026) and combined treatment (surgery and postoperative treatment) (p = 0.008) were significant predictors for a better OS. In multivariate analysis, oropharyngeal tumor localization (p = 0.011) and combined treatment (p = 0.041) showed significantly increased PFS. After 1 year, 2 years, and 3 years, the cumulative incidence of locoregional recurrences (LRRs) was 13%, 24%, and 27%, respectively, and was significantly decreased in patients with oropharyngeal tumor localization (p = 0.037).

Conclusions

Adherence to treatment protocols for radiotherapy alone in old patients with HNSCC is good, whereas the application of concurrent chemotherapy often deviates from guidelines in terms of de-escalation. An important risk factor for decreased OS, PFS, and a higher rate of LRR appears to be non-oropharyngeal tumor location in old patients.
Glare prediction and mechanism of adaptation following implantation of hydrophilic and hydrophobic intraocular lenses
Authors: Bhogal-Bhamra Gurpreet K. , Aujla Maana , Kolli Sai , Sheppard Amy L. , Wolffsohn James S.
Published: April 2024

Purpose

Glare is a known side effect of intraocular lens (IOL) implantation, affected principally by IOL material and optics, although it is reported subjectively to decrease in impact with time. However, little objective data have been published on changes over time, how these relate to subjective reports, and whether those who will report greater glare symptoms can be predicted prior to IOL implantation.

Methods

A total of 32 patients (aged 72.4 ± 8.0 years) with healthy eyes were implanted bilaterally with hydrophilic 600s (Rayner, Worthing, UK) or hydrophobic Acrysof (Alcon, Texas, USA) acrylic IOLs (n = 16 each, randomly assigned). Each patient reported their dysphotopsia symptoms subjectively using the validated forced choice photographic questionnaire for photic phenomena, and halo size resulting from a bright light in a dark environment was quantified objectively in eight orientations using the Aston Halometer. Assessment was performed binocularly pre-operatively and at 1, 2, 3, and 4 weeks after IOL implantation.

Setting

The study was carried out at the National Health Service Ophthalmology Department, Queen Elizabeth Hospital, Birmingham, UK.

Results

Visual acuity (average 0.37 ± 0.26 logMAR) did not correlate with subjective glare (r = 0.184, p = 0.494) or objective glare (r = 0.294, p = 0.270) pre-surgery. Objective halo size (F = 112.781, p < 0.001) decreased with cataract removal and IOL implantation and continued to decreased over the month after surgery. Subjective dysphotopsia complaints (p < 0.001) were also greater pre-surgery, but did not change thereafter (p = 0.228). In neither case was there a difference with IOL material (p > 0.05). It was not possible to predict post-surgery dysphotopsia from symptoms or a ratio of symptoms to halo size pre-surgery (p > 0.05).

Conclusions

Subjective dysphotopsia and objective halos caused by cataracts are greatly reduced by implantation of IOL after cataract removal causing few perceivable symptoms. However, objective measures are able to quantify a further reduction in light scatter over the first month post-IOL implantation, suggesting that any subjective effects over this period are due to the healing process and not due to neuroadaptation.
Successes and lessons learned from a mobile health behavior intervention to reduce pain and improve health in older adults with obesity and chronic pain: a qualitative study
Authors: Brooks Amber K. , Athawale Abha , Rush Virginia , Yearout Abigail , Ford Sherri , Rejeski W. Jack , Strahley Ashley , Fanning Jason
Published: April 2024

Introduction

Chronic pain is a prevalent issue among older adults in the United States that impairs quality of life. Physical activity has emerged as a cost-effective and non-pharmacological treatment for chronic pain, offering benefits such as improved physical functioning, weight loss, and enhanced mood. However, promoting physical activity in older individuals with chronic pain is challenging, given the cyclical relationship between pain and sedentary behavior. The Mobile Intervention to Reduce Pain and Improve Health (MORPH) trial was designed as an innovative, mobile health (mHealth) supported intervention to address this issue by targeting daylong movement, weight loss, and mindfulness to manage pain in older adults with chronic multisite pain. The objective of this paper is to provide the result of a qualitative analysis conducted on post-intervention interviews with MORPH participants.

Methods

At the conclusion of the MORPH study, 14 participants were interviewed regarding their experience with the program. All interviews were conducted by phone before being transcribed and verified. A codebook of significant takeaways was created based on these accounts. Summaries were further synthesized into themes using the principles of thematic analysis.

Results

Three key themes of the MORPH intervention emerged from the qualitative interviews: MORPH technology (smart scales, Fitbit, MORPH Companion App) facilitated program adherence and accountability; MORPH intervention components (food tracking and mindfulness activities) facilitated program adherence and awareness, respectively; and, group meetings provided motivational support and accountability. Mobile health technologies, including a dedicated MORPH app, facilitated self-monitoring strategies, helped to break the cycle of old habits, and provided participants with immediate feedback on successes; however, technical issues required timely support to maintain engagement. Food tracking contributed to adherence and accountability for weight loss. Mindfulness activities increased participants’ awareness of anxiety provoking thoughts and pain triggers. Finally, social support via group meetings and connection, played a crucial role in behavior change, but participants noted consistency in the delivery medium was essential to fostering genuine connections.

Conclusion

Overall, the study results highlight the key considerations related to program technology, intervention components, and the value of social support that can help to guide the development of future interventions similar to MORPH.
Efficacy and safety of esketamine for pediatric gastrointestinal endoscopy: a meta-analysis and trial sequential analysis
Authors: Yu Yunfeng , Deng Juan , Tong Keke , Yin Yuman , Yu Rong , Tan Chuanchuan
Published: April 2024

Objective:

The role of esketamine in pediatric gastrointestinal endoscopy is still unclear. This study aims to evaluate the efficacy and safety of esketamine for pediatric gastrointestinal endoscopy.

Methods:

Clinical trials of esketamine for pediatric gastrointestinal endoscopy were searched in eight common databases, up to October 2023. These clinical trials were included in the meta-analysis and trial sequential analysis (TSA). The risk ratio (RR) and weighted mean difference (WMD) were used as the effect sizes for dichotomous variables and continuity variables, respectively. When the heterogeneity test showed I2 < 50%, the fixed effects model was used for the meta-analysis and TSA; Otherwise, the random effects model was used for them.

Results:

In terms of efficacy endpoints, the meta-analysis showed that compared with placebo or blank, esketamine significantly decreased recovery time by 2.34 min (WMD −2.34; 95% Confidence interval [CI] −3.65, −1.02; p = 0.0005) and propofol consumption by 0.70 mg/kg (WMD −0.70; 95% CI −0.98, −0.43; p < 0.00001), and increased mean heart rate by 4.77 beats/min (WMD 4.77; 95% CI 2.67, 6.87; p < 0.00001) and mean arterial pressure by 3.10 mmHg (WMD 3.10; 95% CI 1.52, 4.67; p = 0.0001), while induction time and mean blood oxygen remained comparable. TSA indicated conclusive evidence for these benefits. In terms of safety endpoints, the meta-analysis revealed that esketamine significantly reduced involuntary movements by 59% (RR 0.41; 95% CI 0.22, 0.76; p = 0.005) and choking by 51% (RR 0.49; 95% CI 0.26, 0.92; p = 0.03), while significantly increasing dizziness by 98% (RR 1.98; 95% CI 1.11, 3.56; p = 0.02) and there were no significant differences in total adverse events, respiratory depression, and vomiting. TSA demonstrated conclusive evidence for involuntary movements and dizziness. Low-dose analysis showed that esketamine at ≤0.3 mg/kg significantly reduced recovery time, propofol consumption and involuntary movements, and significantly increasing mean heart rate, with no increase in dizziness. The Begg’s test (p = 0.327) and the Egger’s test (p = 0.413) indicated no significant publication bias, yet the funnel plot suggested potential publication bias.

Conclusion:

Esketamine is an effective adjuvant anesthesia for children undergoing gastrointestinal endoscopy. However, the general dose of esketamine may increase the risk of dizziness, which can be avoided by administering a low dose (≤0.3 mg/kg).
Voluntary wheel running reduces tumor growth and increases capillarity in the heart during doxorubicin chemotherapy in a murine model of breast cancer
Authors: Uurasmaa Tytti-Maria , Ricardo Chloé , Autio Anu , Heinonen Ilkka H. A. , Rundqvist Helene , Anttila Katja
Published: April 2024

Introduction: The possible beneficial effects of physical activity during doxorubicin treatment of breast cancer need further investigation as many of the existing studies have been done on non-tumor-bearing models. Therefore, in this study, we aim to assess whether short-term voluntary wheel-running exercise during doxorubicin treatment of breast cancer-bearing mice could induce beneficial cardiac effects and enhance chemotherapy efficacy.

Methods: Murine breast cancer I3TC cells were inoculated subcutaneously to the flank of female FVB mice (n = 16) that were divided into exercised and non-exercised groups. Two weeks later, doxorubicin treatment was started via intraperitoneal administration (5 mg/kg weekly for 3 weeks). Organs were harvested a day after the last dose.

Results: The tumor volume over time was significantly different between the groups, with the exercising group having lower tumor volumes. The exercised group had increased body weight gain, tumor apoptosis, capillaries per cardiomyocytes, and cardiac lactate dehydrogenase activity compared to the unexercised group, but tumor blood vessel density and maturation and tumor and cardiac HIF1-α and VEGF-A levels did not differ from those of the non-exercised group.

Discussion: We conclude that even short-term light exercise such as voluntary wheel running exercise can decrease the subcutaneous mammary tumor growth, possibly via increased tumor apoptosis. The increase in cardiac capillaries per cardiomyocytes may also have positive effects on cancer treatment outcomes.