bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Multi-Scale Approach to Model K+ Permeation Through the KcsA Channel
Authors: Horng T. L. , Chen R. S. , Leonardi M. V. , Franciolini F. , Catacuzzeno L. 
Published: July 2022

K+ channels allow a very efficient passage of K+ ions through the membrane while excluding Na+ ions, and these properties are essential for life. The 3D structure of the KcsA K+ channel, solved more than 20 years ago, allows to address many relevant aspects of K+ permeation and selectivity mechanisms at the molecular level. Recent crystallographic data and molecular dynamics (MD) studies suggest that no water is normally present inside the selectivity filter (SF), which can instead accommodate four adjacent K+ ions. Using a multi-scale approach, whereby information taken from a low-level simulation approach is used to feed a high-level model, we studied the mechanism of K+ permeation through KcsA channels. More specifically, we used MD to find stable ion configurations under physiological conditions. They were characterized by two adjacent K+ ions occupying the more central positions of the SF (sites S2 and S3), while the other two K+ ions could be found at the external and internal entrances to the SF. Sites S1 and S4 were instead not occupied by K+. A continuum Bikerman–Poisson–Boltzmann model that takes into account the volume of the ions and their dehydration when entering the SF fully confirmed the MD results, showing peaks of K+ occupancy at S2, S3, and the external and internal entrances, with S1 and S4 sites being virtually never occupied by K+. Inspired by the newly found ion configuration in the SF at equilibrium, we developed a simple kinetic permeation model which, fed with kinetic rate constants assessed from molecular meta-dynamics, reproduced the main permeation properties of the KcsA channel found experimentally, including sublinear current-voltage and saturating conductance-concentration relationships. This good agreement with the experimental data also implies that the ion configuration in the SF we identified at equilibrium would also be a key configuration during permeation.
Association of Serum Interleukin-8 and Serum Amyloid A With Anxiety Symptoms in Patients With Cerebral Small Vessel Disease
Authors: Shan Li-Li , Wang Yi-Lin , Qiao Tian-Ci , Bian Yue-Feng , Huo Ya-Jing , Guo Cen , Liu Qian-Yun , Yang Zi-Dong , Li Ze-Zhi , Liu Ming-Yuan , Han Yan 
Published: July 2022

ObjectiveCerebral small vessel disease (CSVD) is a clinical syndrome caused by pathological changes in small vessels. Anxiety is a common symptom of CSVD. Previous studies have reported the association between inflammatory factors and anxiety in other diseases, but this association in patients with CSVD remains uncovered. Our study aimed to investigate whether serum inflammatory factors correlated with anxiety in patients with CSVD.MethodsA total of 245 CSVD patients confirmed using brain magnetic resonance imaging (MRI) were recruited from December 2019 to December 2021. Hamilton Anxiety Rating Scale (HAMA) was used to assess the anxiety symptoms of CSVD patients. Patients with HAMA scores ≥7 were considered to have anxiety symptoms. The serum levels of interleukin-1β (IL-1β), IL-2R, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), serum amyloid A (SAA), C-reactive protein (CRP), high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) were detected. We compared levels of inflammatory factors between the anxiety and non-anxiety groups. Logistic regression analyses examined the correlation between inflammatory factors and anxiety symptoms. We further performed a gender subgroup analysis to investigate whether this association differed by gender.ResultsIn the fully adjusted multivariate logistic regression analysis model, we found that lower levels of IL-8 were linked to a higher risk of anxiety symptoms. Moreover, higher levels of SAA were linked to a lower risk of anxiety symptoms. Our study identified sex-specific effects, and the correlation between IL-8 and anxiety symptoms remained significant among males, while the correlation between SAA and anxiety symptoms remained significant among females.ConclusionsIn this study, we found a suggestive association between IL-8, SAA, and anxiety symptoms in CSVD participants. Furthermore, IL-8 and SAA may have a sex-specific relationship with anxiety symptoms.
FOXS1 Promotes Tumor Progression by Upregulating CXCL8 in Colorectal Cancer
Authors: Qiu Junfeng , Li Mingzhou , Su Cailin , Liang Yihao , Ou Ruizhang , Chen Xiaoning , Huang Chengmei , Zhang Yaxin , Ye Yaping , Liao Wenting , Zhang Chao 
Published: July 2022

BackgroundForkhead box S1 (FOXS1) is a member of the forkhead box (FOX) transcriptional factor superfamily. The biological roles and underlying regulatory mechanism of FOXS1 in CRC remain unclear.MethodsBioinformatics analysis, Western blotting, real-time PCR, and immunohistochemistry (IHC) were used to detect the expression FOXS1 in CRC. MTT assay, transwell assay, human umbilical vein endothelial cell tube formation assay, and chicken chorioallantoic membrane assay were performed to investigate the effects of FOXS1 on proliferation, invasion, and angiogenesis. Additionally, tumor formation assay and orthotopic implantation assay were used to investigate the effects of FOXS1 on tumor growth and metastasis in vivo. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the correlation between FOXS1 and EMT or angiogenesis. The correlation between FOXS1 and CXCL8 expression was analyzed in clinical CRC samples using IHC.ResultsThe results showed that FOXS1 expression was upregulated in CRC tissues compared with adjacent normal intestine tissues. A high FOXS1 expression is positively correlated with poor survival. FOXS1 promoted the malignant behavior of CRC cancer cells in vitro, including proliferation, invasion, and angiogenesis. In addition, FOXS1 promoted tumor growth and metastasis in nude mice. Mechanistically, FOXS1 upregulated the expression of C–X–C motif chemokine ligand 8 (CXCL8) at the transcriptional level. Knockdown of CXCL8 blocked FOXS1 induced the enhancement of the EMT and angiogenesis. GSEAs in public CRC datasets revealed strong correlations between FOXS1 expression and EMT marker and angiogenesis markers. IHC showed that FOXS1 expression was positively correlated with CXCL8 expression and CD31 expression in clinical CRC samples.ConclusionThe results suggest that FOXS1 promotes angiogenesis and metastasis by upregulating CXCL8 in CRC. Interference with the FOXS1/CXCL8 axis may serve as a potential therapeutic target for the treatment of metastatic CRC.
Feasibility and Short-Term Toxicity of a Consecutively Delivered Five Fraction Stereotactic Body Radiation Therapy Regimen in Early-Stage Breast Cancer Patients Receiving Partial Breast Irradiation
Authors: Liu Yilan , Veale Christopher , Hablitz Diana , Krontiras Helen , Dalton Allison , Meyers Korie , Dobelbower Michael , Lancaster Rachael , Bredel Markus , Parker Catherine , Keene Kimberly , Thomas Evan , Boggs Drexell 
Published: July 2022

BackgroundFor appropriately selected patients with early-stage breast cancer (ESBC), accelerated partial breast irradiation (APBI) yields equivalent rates of ipsilateral breast tumor recurrence with mixed results in patient-rated cosmesis compared with whole-breast radiotherapy depending on the technique utilized. When utilizing external beam radiotherapy for APBI, techniques to reduce target margins and overall treatment volume are potentially important to decrease rates of long-term adverse cosmesis. Stereotactic body radiotherapy (SBRT) is a promising technique to deliver APBI because of its increased accuracy and sparing of uninvolved breast tissue. We report the initial results of a prospective clinical trial investigating feasibility, safety, and cosmetic outcomes of a daily five-fraction SBRT regimen for APBI.MethodsTwenty-three patients with ESBC after lumpectomy who met APBI suitability were enrolled. During lumpectomy, a bioabsorbable three-dimensional fixed array tissue marker (BioZorb™, Hologic, Marlborough, MA) was placed for enhanced visualization of the cavity boundaries. Clinical target volume (CTV) was defined as the delineable cavity plus a 1-cm isotropic expansion followed by a 3-mm isotropic planning target volume (PTV) expansion. Patients received 30 Gy delivered in five planned consecutive daily fractions in either prone or supine positioning depending on individual anatomy. Two patients completed the five-fraction treatments in 9-day interval and 11-day interval due to external circumstances. A maximum PTV of 124cc was allowed to minimize incidence of fat necrosis. Plans utilized 10-MV flattening filter–free beams delivered on a Varian Edge linear accelerator. Local control, toxicity, and nurse/patient-scored cosmesis at pre-treatment baseline, 1 month post-treatment, and at subsequent 6-month intervals were recorded.ResultsTwenty-three patients were accrued at the time of submission with median follow-up of 6 months. No patients experienced grade ≥3 acute toxicity. Of the 10 events reported probably related to SBRT, nine were grade 1 (n = 9/10, 90%). There was no evidence of difference, deterioration, or change in patient or nurse-scored cosmesis from baseline to 1 and 6 months post-treatment. One patient developed nodal failure shortly after APBI.ConclusionsAlthough longer follow-up is needed to assess long-term toxicity and local control, this study demonstrated a five-fraction SBRT regimen delivered over consecutive days is a safe, efficient, well-tolerated, and cosmetically favorable means of delivering APBI in suitable women.Clinical Trial Registrationhttps://www.clinicaltrials.gov/ct2/show/NCT03643861, NCT03643861.
Association Between ABO Blood Group and Venous Thromboembolism Risk in Patients With Peripherally Inserted Central Catheters: A Meta-analysis and Systematic Review
Authors: Zhang Qiang , Peng Hong , Hu Lu , Ren Ran , Peng Xingqiao , Song Jifang 
Published: July 2022

BackgroundPrevious studies have evaluated the association between ABO blood group and venous thromboembolism (VTE) risk in patients with peripherally inserted central catheters (PICCs). However, it remains unclear whether ABO blood groups are associated with PICC-associated VTE risk. Therefore, we conducted a meta-analysis of related studies to elucidate the potential role of ABO blood group as a risk factor for PICC-associated VTE.MethodsAll detectable case–control and cohort studies comparing the role of ABO blood group as a risk factor for PICC-associated VTE were collected for this analysis by searching PubMed, Embase, CNKI, Web of Science, and Wanfang. We conducted a meta-analysis of the eligible studies and computed the summary risk estimates with random or fixed effects models.ResultsA total of four studies involving 7,804 patients were included. Meta-analysis of the studies showed that the risk of PICC-associated VTE was significantly higher in blood types A [odds ratio (OR)=1.54, 95% CI=1.17–2.03), p=0.002], B (OR=2.35, 95% CI=1.71–3.23, p&lt;0.0001), and AB (OR=2.55, 95% CI=1.68–3.88, p&lt;0.0001) and lower in blood types O (OR=0.58, 95% CI=0.45–0.74, p&lt;0.0001). Subgroup analysis based on ethnicity demonstrated that blood type O may be a genetic protective factor for PICC-associated VTE in Asians. Among Caucasians, individuals with blood types B and AB have a higher risk of PICC-associated VTE. Blood types A, B, and AB are risk factors for PICC-associated VTE in Asians.ConclusionsBlood type O is associated with a decreased risk of PICC-associated VTE, especially in Asian populations. Moreover, blood types A, B, and AB are risk factors for PICC-associated VTE.
Exploration of the Immunotyping Landscape and Immune Infiltration-Related Prognostic Markers in Ovarian Cancer Patients
Authors: Zhao Na , Xing Yujuan , Hu Yanfang , Chang Hao 
Published: July 2022

BackgroundIncreasing evidence indicates that immune cell infiltration (ICI) affects the prognosis of multiple cancers. This study aims to explore the immunotypes and ICI-related biomarkers in ovarian cancer.MethodsThe ICI levels were quantified with the CIBERSORT and ESTIMATE algorithms. The unsupervised consensus clustering method determined immunotypes based on the ICI profiles. Characteristic genes were identified with the Boruta algorithm. Then, the ICI score, a novel prognostic marker, was generated with the principal component analysis of the characteristic genes. The relationships between the ICI scores and clinical features were revealed. Further, an ICI signature was integrated after the univariate Cox, lasso, and stepwise regression analyses. The accuracy and robustness of the model were tested by three independent cohorts. The roles of the model in the immunophenoscores (IPS), tumor immune dysfunction and exclusion (TIDE) scores, and immunotherapy responses were also explored. Finally, risk genes (GBP1P1, TGFBI, PLA2G2D) and immune cell marker genes (CD11B, NOS2, CD206, CD8A) were tested by qRT-PCR in clinical tissues.ResultsThree immunotypes were identified, and ICI scores were generated based on the 75 characteristic genes. CD8 TCR pathways, chemokine-related pathways, and lymphocyte activation were critical to immunophenotyping. Higher ICI scores contributed to better prognoses. An independent prognostic factor, a three-gene signature, was integrated to calculate patients’ risk scores. Higher TIDE scores, lower ICI scores, lower IPS, lower immunotherapy responses, and worse prognoses were revealed in high-risk patients. Macrophage polarization and CD8 T cell infiltration were indicated to play potentially important roles in the development of ovarian cancer in the clinical validation cohort.ConclusionsOur study characterized the immunotyping landscape and provided novel immune infiltration-related prognostic markers in ovarian cancer.
Targeting AKT-Dependent Regulation of Antioxidant Defense Sensitizes AKT-E17K Expressing Cancer Cells to Ionizing Radiation
Authors: Goetting Isabell , Larafa Safa , Eul Katharina , Kunin Mikhail , Jakob Burkhard , Matschke Johann , Jendrossek Verena 
Published: July 2022

Aberrant activation of the phosphatidyl-inositol-3-kinase/protein kinase B (AKT) pathway has clinical relevance to radiation resistance, but the underlying mechanisms are incompletely understood. Protection against reactive oxygen species (ROS) plays an emerging role in the regulation of cell survival upon irradiation. AKT-dependent signaling participates in the regulation of cellular antioxidant defense. Here, we were interested to explore a yet unknown role of aberrant activation of AKT in regulating antioxidant defense in response to IR and associated radiation resistance.We combined genetic and pharmacologic approaches to study how aberrant activation of AKT impacts cell metabolism, antioxidant defense, and radiosensitivity. Therefore, we used TRAMPC1 (TrC1) prostate cancer cells overexpressing the clinically relevant AKT-variant AKT-E17K with increased AKT activity or wildtype AKT (AKT-WT) and analyzed the consequences of direct AKT inhibition (MK2206) and inhibition of AKT-dependent metabolic enzymes on the levels of cellular ROS, antioxidant capacity, metabolic state, short-term and long-term survival without and with irradiation.TrC1 cells expressing the clinically relevant AKT1-E17K variant were characterized by improved antioxidant defense compared to TrC1 AKT-WT cells and this was associated with increased radiation resistance. The underlying mechanisms involved AKT-dependent direct and indirect regulation of cellular levels of reduced glutathione (GSH). Pharmacologic inhibition of specific AKT-dependent metabolic enzymes supporting defense against oxidative stress, e.g., inhibition of glutathione synthase and glutathione reductase, improved eradication of clonogenic tumor cells, particularly of TrC1 cells overexpressing AKT-E17K.We conclude that improved capacity of TrC1 AKT-E17K cells to balance antioxidant defense with provision of energy and other metabolites upon irradiation compared to TrC1 AKT-WT cells contributes to their increased radiation resistance. Our findings on the importance of glutathione de novo synthesis and glutathione regeneration for radiation resistance of TrC1 AKT-E17K cells offer novel perspectives for improving radiosensitivity in cancer cells with aberrant AKT activity by combining IR with inhibitors targeting AKT-dependent regulation of GSH provision.
Development and External Validation of a Preoperative Nomogram for Predicting Lateral Pelvic Lymph Node Metastasis in Patients With Advanced Lower Rectal Cancer
Authors: Zhang Lei , Shi Feiyu , Hu Chenhao , Zhang Zhe , Liu Junguang , Liu Ruihan , She Junjun , Tang Jianqiang 
Published: July 2022

BackgroundThe preoperative prediction of lateral pelvic lymph node (LPLN) metastasis is crucial in determining further treatment strategies for advanced lower rectal cancer patients. In this study, we established a nomogram model to preoperatively predict LPLN metastasis and then externally validated the accuracy of this model.MethodsA total of 287 rectal cancer patients who underwent LPLN dissection were included in this study. Among them, 200 patients from the Peking University First Hospital were included in the development set, and 87 patients from the First Affiliated Hospital of Xi’an Jiaotong University were included in the independent external validation set. Multivariate logistic regression analysis was used to develop the nomogram. The performance of the nomogram was assessed based on its calibration, discrimination, and clinical utility.ResultsFive factors (differentiation grade, extramural vascular invasion, distance of the tumor from the anal verge, perirectal lymph node status, and largest short-axis diameter of LPLN) were identified and included in the nomogram. The nomogram developed based on the analysis showed robust discrimination with an area under the receiver operating characteristic curve (AUC) of 0.878 (95% CI, 0.824–0.932). The validation set showed good discrimination with an AUC of 0.863 (95% CI, 0.779–0.948). Decision curve analysis showed that the nomogram was clinically useful.ConclusionsThe present study proposed a clinical-imaging nomogram with a combination of clinicopathological risk factors and imaging features. After external verification, the predictive power of the nomogram model was satisfactory, and it is expected to be a convenient, visual, and personalized clinical tool for assessing the risk of LPLN metastasis in advanced lower rectal cancer patients.
Effect of Oropharyngeal Administration of Colostrum in Premature Newborns ≤32 Weeks of Gestation on the Immune Response and Neonatal Morbidity: A Double-Blind Randomized Clinical Trial
Authors: Romero-Maldonado Silvia , Soriano-Becerril Diana Mercedes , García-May Perla Karina , Reyes-Muñoz Enrique , Muñoz-Ortíz Eudoxia Georgina , Carrera-Muiños Sandra , Granados-Cepeda Martha Lucía , Cardona-Pérez Jorge Arturo , Castro-Millán Elsa , Segura-Cervantes Enrique , Ceballos Guillermo , Montoya-Estrada Araceli 
Published: July 2022

IntroductionThe mother's colostrum carries immunological components, such as cytokines and immunoglobulins (Igs), derived from the maternal circulation with bacteriostatic properties.ObjectiveThe objective of this study was to evaluate the effect of oropharyngeal administration of colostrum (OPAC) vs. placebo in the first 4 days of life in premature newborns ≤32 weeks of gestation on serum Ig concentration, neonatal morbidity, and total days of hospitalization.HypothesisThe OPAC increases serum Igs and decreases morbidity and total days of hospitalization.Materials and MethodsA double-blind randomized controlled trial was carried out. Participants were randomly assigned to one of the two groups, namely, group 1: placebo (P) (n = 50) and group 2: colostrum (C) (n = 46). A blood sample was obtained at baseline and 7 and 28 days of life to quantify immunoglobulin G (IgG), immunoglobulin A (IgA), and IgM. Results: The C group showed an increase in serum IgA on day 28 expressed as median and [interquartile range]; C: 25 [12–35] vs. P: 11 [8–18], p &lt; 0.001. There were no significant differences in neonatal morbidity. Newborns in the colostrum group showed the completed enteral feeding earlier (days), C: 13.9 ± 7 vs. P: 17.4 ± 8.4, p &lt; 0.04; they reached the birth weight earlier, C: 10.9 ± 2.8 vs. P: 12.9 ± 4, p &lt; 0.01, and had less days of hospitalization, C: 60.2 ± 33.8 vs. P: 77.2 ± 47.3, p &lt; 0.04. Neonatal mortality was lower in the colostrum group than the placebo group 0% vs. 12%, respectively, without a statistical difference (p = 0.06).ConclusionIn premature newborns ≤32 weeks of gestation, the OPAC within 4 days after birth increases serum IgA concentration at day 28 compared to placebo. Similarly, OPAC decreased the days to complete enteral feeding and reach the birth weight and total days of hospitalization.Clinical Trial Registration[https://clinicaltrials.gov/ct2/show/NCT03578341], identifier: [NCT03578341].
Undernutrition and Associated Factors Among Children Aged 6–23 Months in Dessie Town, Northeastern Ethiopia, 2021: A Community Based Cross-Sectional Study
Authors: Sewenet Tesfamaryam , W/Selassie Mulugeta , Zenebe Yosef , Yimam Wondwossen , Woretaw Lebasie 
Published: July 2022

BackgroundGlobally about 159, 101, and 52 million children are stunted, underweight, and wasted, respectively. According to the 2016 Ethiopian Demographic and Health Survey, about 38% of Ethiopian children are stunted and 46, 28.4, and 9.8% of children in Amhara Region are stunted, underweight and wasted, respectively. This study aimed to assess undernutrition and associated factors among children aged 6-23 months old at Dessie town, 2021.MethodA community-based cross-sectional study was conducted from October – November 2021 in Dessie Town. A total of 421 Mothers/caregivers with children aged 6-23 months old were selected by a systematic sampling method from the health extension registration book. Epi-data 3.01 was used for data entry, SPSS version 20 for statistical analysis, and WHO Anthro version 3.2.2 software for calculating the z scores. Binary logistic regression and multivariate logistic regression were used to analyze the data. AOR with 95% CI and P-values less than 0.05 were considered to see the statistical significance.ResultsA total of 421 mothers or care givers paired with 6-23 months old children participated in the study. The prevalence of stunting, underweight, wasting were 36.8% (95% CI: 32%, 41.6%), 27.6% (95% CI: 23.6%, 32.2%), and 11.5% (95% CI: 8.4%, 14.7%) respectively. Sex of the child (AOR = 1.55; 95% CI: 1.02, 2.34), handwashing practice (AOR = 2.32; 95% CI: 1.05, 5.11) and maternal family planning use (AOR = 0.39; 95% CI: 0.19, 0.77) were significantly associated with stunting. Age of child 12-17 months (AOR = 4.62; 95% CI: 2.65, 8.06) and sex of the child (AOR = 1.93; 95% CI: 1.21, 3.07) were associated with underweight. Age of child 12-17 months (AOR = 2.25; 95% CI: 1.06, 4.78) and treatment of drinking water (AOR = 0.21; 95% CI: 0.07, 0.59) were associated with wasting.Conclusion and RecommendationIn this study, the prevalence of undernutrition among children aged 6-23 months was higher for stunting (36.8%), underweight (27.6%) and wasting (11.5%) compared to WHO classification. Improved access to water, hygiene and sanitation, family planning services, avoiding gender discrimination during child feeding, and age-appropriate feeding practices are recommended. Moreover, implementation of public policies on food and nutrition is required for children 6-23 months of age.