bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variants of creating heterotopic and orthotopic PDX models of human colorectal cancer
Authors: Kiblitskaya A. A. , Maksimov A. Y. , Goncharova A. S. , Nepomnyashchaya Ye. M. , Zlatnik Ye. Y. , Yegorov G. Y. , Lukbanova Ye. A. , Zaikina Ye. V. , Volkova A. V. 
Published: October 2022

Aim. To create heterotopic and orthotopic patient-derived xenograft (PDX) models of colorectal cancer (CRC) by transplantation of patient’s tumor samples into immunodeficient BALB / c Nude mice.Materials and methods. The study was performed on 15 female BALB / c Nude mice aged 6–8 weeks weighing 21–25 g. All animals underwent transplantation of the tumor material obtained from CRC patients into the following sites: heterotopic transplantation (under the skin of the thigh and into the omentum), orthotopic transplantation (into the descending and ascending colon and into the cecum). Weight and general condition of the animals and the size of the tumor nodule had been monitored for 80 days. The success of each model was assessed by the degree of engraftment, the dynamics of tumor growth, and the reproducibility of histopathologic characteristics. At the end of the experiment, the animals were euthanized by cervical dislocation.Results. 100% survival of the animals and similar tumor growth dynamics in the xenograft models were observed throughout the experiment. The analysis of histologic specimens obtained from the xenografts and patient’s tumor showed their correspondence to moderately differentiated intestinal adenocarcinoma. The main advantages and disadvantages of different variants of PDX models were described.Conclusion. Heterotopic and orthotopic PDX models reproduce the morpho-histologic characteristics of human tumors and demonstrate stable growth dynamics. Therefore, they are a suitable tool for the development, testing, and validation of potential anticancer drugs.
Features of the functioning of innate immunity in children with chronic idiopathic urticaria
Authors: Maltsev S. V. , Sizyakina L. P. , Lebedenko A. A. 
Published: October 2022

Aim. To study the features of the functioning of innate immunity in children with chronic idiopathic urticaria.Materials and methods. The study included 28 children of both sexes aged 6–16 years with chronic idiopathic urticaria (CIU). The median age of the patients was 8 years (p = 0.045). Clinical research methods included an analysis of complaints and anamnestic data, as well as an objective examination of the child (dynamics of urticaria, severity of itching, the presence of angioedema). Immunological techniques included determination of the number of monocytes expressing CD14+CD282+, CD14+CD284+, CD14+CD289+, the number of peripheral blood lymphocytes expressing CD3+CD16+, the levels of immunoglobulin (Ig) E, lactoferrin, interferon (IFN) γ, interleukin (IL)4, and IL-6, and a nitroblue tetrazolium test.Results. In the course of the study, an increase in the expression of Toll-like receptors TLR2 and TLR4 by monocytes, a decrease in the expression of TLR9 by monocytes, a significant rise in lactoferrin levels, a slight decrease in the number of natural killer (NK) cells, a decrease in microbicidal activity and adaptive reserves, a rise in IgE levels, a decrease in IL-4 levels, and an increase in IFNγ and IL-6 were revealed in children with CIU.Conclusion. The immunological changes revealed during the study indicate multidirectional expression of Toll-like receptors, disturbances in the work of the cellular components of innate immunity, and a launch of a proinflammatory cytokine cascade in children with CIU, which can serve as a mainstay for the development of new schemes for personalized therapy of CIU in children.
sPD-1/sPD-L1 proteins in non-small cell lung cancer and esophageal squamous cell carcinoma
Authors: Stilidi I. S. , Kovaleva O. V. , Gratchev A. N. , Tchevkina E. M. , Podlesnaya P. A. , Tsarapaev P. V. , Suleymanov E. A. , Kushlinskii N. E. 
Published: October 2022

Background. Implementation of immunotherapy in clinical oncological practice has significantly improved the results of cancer treatment. It resulted in the need for seeking new markers to assess the effectiveness of therapy and the disease prognosis.Aim. To analyze the content of soluble forms of PD-1 and PD-L1 immune checkpoint proteins in the blood serum of patients with non-small cell lung cancer and esophageal squamous cell carcinoma and their association with clinical and morphological characteristics of the disease and the disease prognosis.Materials and methods. The study included tumor samples obtained from 43 patients with non-small cell lung cancer and 21 patients with esophageal squamous cell carcinoma. The concentration of sPD-L1 and sPD-1 in the blood serum was determined using enzyme-linked immunosorbent assay (ELISA). The Mann – Whitney test was used to determine statistically significant differences in independent groups. A correlation analysis was performed using the Spearman’s rank correlation coefficient. Overall survival was analyzed by constructing survival curves using the Kaplan – Meier method and a Cox proportional hazards model. The differences were considered statistically significant at p < 0.05.Results. The study showed that sPD-1 and sPD-L1 were found in the blood serum of both cancer patients and healthy donors, and their concentrations did not differ significantly. It was shown that the high concentration of sPD-L1 in the blood serum of patients with non-small cell lung cancer was significantly associated with the late stage of the disease and was an independent unfavorable prognostic factor. It should be noted that for patients with esophageal cancer, an unfavorable prognostic marker was the high concentration of the soluble form of PD-1 protein, and not PD-L1 ligand, as in case of lung cancer.Conclusion. The content of sPD-1 and sPD-L1 in the blood serum can have different prognostic significance for various types of cancer, and further studies are required to confirm their clinical usability.
Spatial-temporal distribution of incidence, mortality, and case-fatality ratios of coronavirus disease 2019 and its social determinants in Brazilian municipalities
Authors: Raymundo Carlos Eduardo , Oliveira Marcella Cini , Eleuterio Tatiana Araujo , Junior Édnei César de Arruda Santos , Silva Marcele Gonçalves , André Suzana Rosa , Sousa Ana Inês , Medronho Roberto de Andrade 
Published: October 2022

Abstract

The COVID-19 pandemic caused impact on public health worldwide. Brazil gained prominence during the pandemic due to the magnitude of disease. This study aimed to evaluate the spatial-temporal dynamics of incidence, mortality, and case fatality of COVID-19 and its associations with social determinants in Brazilian municipalities and epidemiological week. We modelled incidence, mortality, and case fatality rates using spatial-temporal Bayesian model. The rates were standardised using the indirect method. “Bolsa Família Programme” (BOLSAFAM) and “proportional mortality ratio” (PMR) were inversely associated with the standardised incidence ratio (SIR), while “health insurance coverage” (HEALTHINSUR) and “Gini index” were directly associated with the SIR. BOLSAFAM and PMR were inversely associated with the standardised mortality ratio (SMR) and standardised case fatality ratio (SCFR), while HEALTHINSUR and “proportion of black andpardopopulation” were directly associated with the SMR and SCFR. The highest proportion of excess risk for SIR and the SMR started in the North, expanding to the Midwest, Southeast, and South regions. However, this excess risk was detected predominantly in the North region in all periods. The highest proportion of excess risk for the SCFR outcome was observed in some municipalities in the North region and in the other Brazilian regions. The COVID-19 incidence and mortality in municipalities that most benefited from the cash transfer programme and with better social development decreased. The municipalities with a higher proportion of non-white people were at greater risk of having their population becoming ill and dying from the disease.
Evidence for validity, reliability and measurement invariance of the Emotion Regulation Questionnaire for Children and Adolescents (ERQ-CA) in secondary students from Chile
Authors: Villacura-Herrera C. , Gaete J. , Andaur J. , Meza D. , Robinson J. , Nuñez D. 
Published: October 2022

Abstract

Emotion regulation (ER) is associated with both healthy and unhealthy behavioral and affective responses, especially in adolescents. It is frequently assessed by self-report measures such as the Emotion Regulation Questionnaire for Children and Adolescents (ERQ-CA), which has shown mixed psychometric properties when used in Spanish-speaking adolescents. The present study provides evidence for its validity and reliability in a sample of secondary students in Chile. Six-hundred and thirty-four students were recruited from ten educational institutions to complete the ERQ-CA, along with the Cognitive Behavioral Therapy Skills Questionnaire (CBTSQ), the Suicide Ideation Questionnaire Junior (SIQ-JR), the Multidimensional Adolescent Functioning Scale (MAFS) and the Patient Health Questionnaire-9 (PHQ-9). Confirmatory factor analysis (CFA) was performed on the ERQ-CA for two- and single-factor models. Convergent and discriminant validity as well as measurement invariance were also tested. The original ERQ-CA two-factor structure showed the best model fit and parsimony along with high internal consistency. It also demonstrated high convergent and discriminant validity, with reappraisal strategies positively correlating with cognitive-behavioral skills and psychosocial functioning and negatively with suicide ideation and depressive symptoms, while the opposite was true for suppression strategies. Partial scalar invariance was established when testing by biological sex (male/female) and psychiatric treatment history (past/current/no). We conclude that the ERQ-CA was found to be a valid and reliable self-report instrument for the assessment of ER strategies in secondary students, proving its utility as a research and clinical tool.
A five year descriptive analysis of potentially preventable hospitalisations for Ear, Nose, and Throat conditions in regional Victoria, Australia, from 2015 to 2020
Authors: O'Neill Susan , Begg Stephen , Spelten Evelien 
Published: October 2022

Abstract
Background

Potentially preventable hospitalisations (PPH) of ear, nose, and throat (ENT) conditions in the Murray Primary Health Network (PHN) region have been found to be higher than the state average of Victoria, Australia. This study aimed to examine the association between patient characteristics and PPH for ENT conditions from 2015 to 2020 in the Murray PHN region

Methods

Unit record hospital separation data were obtained from the Victorian Admitted Episodes Dataset. Differences between patients from ‘higher than expected’ postcodes and ‘other’ postcodes (with respect to the distribution of demographic and other patient characteristics) were determined using chi-squared tests for each ENT subgroup. The results were confirmed by logistic regression analyses using resident of a postcode with higher than expected hospitalisations as the outcome variable.

Results

There were 4816 hospital separations in the Murray PHN with a primary diagnosis of ENT as defined by the PPH framework in the National Health Agreement. Of the 169 postcodes located in the catchment area, 15 were identified as having higher than expected numbers of upper respiratory tract infection hospitalisations, 14 were identified for acute tonsillitis, and 12 were identified for otitis media.

Conclusion

Of the identified postcodes, differential patient factors included 0–9 year old’s, the Indigenous population, and those from culturally and linguistically diverse backgrounds (patients requiring an interpreter and language other than English patients). Further investigation of the identified postcodes is warranted to determine access to and utilisation of primary healthcare services in the management of PPH ENT conditions in the region.
Receiving or not Deemed Necessary Healthcare Services
Authors: Sulku Seher Nur , Tokatlioglu Yagmur , Cosar Kubra 
Published: October 2022

Abstract
Background
Avoiding deemed necessary healthcare needs may worsen prognosis and treatment options, and damage people’s ability to perform their roles in society. Our study investigates why people avoid healthcare services in an upper-middle-income country, Turkey.
Methods
We apply TurkStat’s 2012 Health Survey Data that includes a comprehensive health and social-demographic information of 28,055 survey participants who were 15 + aged. We prefer to use bivariate probit model to analyze the avoiding behaviour in inpatient level in accordance with outpatient level because of the observed significant correlation between people’s avoiding behaviour under tertiary and lower level of health care.
Results
According to our descriptive analysis, we see that 2.6% of 15 + aged population were avoiding deemed necessary hospital services. Furthermore, it is found that high cost (31%), organizational factors (21%) and fear (12%) are prominent reasons of avoiding tertiary care. Thereafter, in our bivariate probit model findings, we figure out that being covered by social security schemes decreases the probability of avoiding both outpatient and inpatient health services by 6.9%. Moreover, being female, living in rural area, having lower income increase the chance of being avoider in both stages of healthcare.
Conclusions
We conclude that social inequalities were main underlying determinants of the avoiding behavior. As health and effective provision of health care are vital for the smooth functioning of society, we suggest that improve health care protection of people from disadvantaged social groups and develop better organizational factors to prevent difficulty of having treatment at policlinics.
U-Pb age of the oldest achondrite points to 26Al heterogeneity in the early Solar System
Authors: Krestianinov Evgenii , Amelin Yuri , Yin Qing-Zhu , Cary Paige , Huyskens Magdalena , Miller Audrey , Dey Supratim , Hibiya Yuki , Tang Haolan , Young Edward , Pack Andreas , Rocco Tommaso Di 
Published: October 2022

Abstract
The homogeneity of distribution of radioisotope 26Al in the early solar nebula, a major heat source for early planetary differentiation and foundational assumption to high resolution cosmochronology, remains debatable. Here we report a precise Pb-isotopic age of 4565.56±0.12 million years (Ma) for the recently discovered andesitic achondrite Erg Chech 002. Combining this age with published high-precision 26Al-26Mg data, we demonstrate that the initial 26Al/27Al in the source material of this achondrite was distinctly higher than in several well preserved and precisely dated achondrites. We argue that the current data clearly indicate spatial heterogeneity of 26Al in the precursor molecular cloud or the protoplanetary disk of the Solar System, likely associated with the late infall of stellar materials with freshly synthesized radionuclides.
Denervation Aggravates Renal Ischemia Reperfusion Injury via BMAL1-mediated Nrf2/ARE pathway
Authors: sun qian , WANG YIFEI , TANG QIAO , ZENG CHENG , DU LI , DONG CHONG 
Published: October 2022

Abstract
Background Denervation is an inevitable pathological situation of renal graft. This study was to explore the change of clock gene rhythm under renal denervation (RDN) and its effect on renal function and oxidative stress during renal ischemia-reperfusion (IR) injury.
Method C57/BL6 mice were randomly divided into 4 groups at daytime 7AM (zeitgeber time [ZT] 0) or at nighttime 7PM (ZT12) in respectively: Sham (S) group, RDN group, IR group and RDN+ IR (DIR) group. Renal pathological and functional changes were assessed by H&E staining, and serum creatinine, urea nitrogen and neutrophil gelatinase-associated lipocalin levels. Renal oxidative stress was detected by SOD and MDA levels, and renal inflammation was measured by IL-6, IL-17AF and TNF-ɑ levels. BMAL1, CLOCK, Nrf2 and HO-1 mRNA and protein expressions were tested by qPCR and Western Blot.
Result Compared with S groups, the rhythm of BMAL1 and CLOCK genes in the kidney was disordered in RDN groups, while renal pathological and functional indexes did not change significantly. Compared with IR groups, renal pathological and functional indexes were significantly higher in the DIR groups, as well as oxidative stress and inflammation in renal tissues. The protein expressions of BMAL1 and Nrf2 were upregulated by RDN at ZT12 timepoint. In DIR groups, renal injury was aggravated after the Brusatol treatment, but there was no significant improvement after the t-BHQ treatment, which might be consistent with the changes of Nrf2 and HO-1 protein expressions. Knockdown BMAL1 gene alone didn’t reverse the aggravation of renal IR injury at nighttime caused by RDN, but it could recover the protective effect of activating Nrf2/ARE pathway by t-BHQ.
Conclusion RDN lead to the disruption of BMAL1-mediatedNrf2 rhythm accumulation in the kidney, which reduced the renal ability to resist oxidative stress and inflammation, due to the impaired effect of activating Nrf2/ARE pathway in renal IR injury at nighttime.
Fucosylation of HLA-DRB1 regulates CD4+T cell-mediated anti-melanoma immunity and enhances immunotherapy efficacy
Authors: Lau Eric , Lester Daniel , Burton Chase , Gardner Alycia , Innamarato Patrick , Kodumudi Krithika , Liu Qian , Adhikari Emma , Ming Qianqian , Williamson Daniel , Frederick Dennie , Sharova Tatyana , White Michael , Markowitz Joseph , Cao Biwei , Nguyen Jonathan , Johnson Joseph , Beatty Matthew , Mockabee-Macias Andrea , Mercurio Matthew , Watson Gregory , Chen Pei-Ling , McCarthy Susan , Moran Carlos , Messina Jane , Thomas Kerry , Darville Lancia , Izuma Victoria , Koomen John , Pilon-Thomas Shari , Ruffell Brian , Luca Vince , Haltiwanger Robert S , Wang Xuefeng , Wargo Jennifer , Boland Genevieve 
Published: October 2022

Abstract
Despite reports of striking outcomes, immunotherapy efficacy in melanoma is limited to subsets of patients 1, 2. Combining immunotherapies with other modalities has yielded limited improvements but also adverse events requiring cessation of treatment 1. In addition to ineffective patient stratification, efficacy can be impaired by paucity of tumor-infiltrating lymphocytes (TILs). Thus, effective strategies to safely increase TILs are urgently needed to improve immunotherapies 3. Here, we report that dietary administration of the sugar L-fucose triggers CD4+T cell-mediated increases in TILs, anti-tumor immunity, and enhanced immune checkpoint blockade responses. This is induced by the fucosylation and cell surface enrichment of the MHC-II protein HLA-DRB1 in melanoma. Single-cell immunofluorescent staining analysis of patient melanoma specimens demonstrates that fucosylation and fucosylated HLA-DRB1 is associated with intratumoral T cell abundance and anti-PD1 responder status. Our findings demonstrate that fucosylation is a key mediator of anti-tumor immunity, via regulation of melanoma cell surface HLA-DRB1 and induction of anti-tumor immunity, suggesting use of melanoma fucosylation as a novel strategy to stratify patients for immunotherapies. Importantly, our study suggests that L-fucose represents a powerful, non-toxic agent for safely increasing anti-tumor immunity and immunotherapy efficacy in melanoma.
Blunt Liver Trauma: Spectrum of injuries and outcomes, managed At Level – I Trauma Center
Authors: Javed Sidra , Shahid Muhammad Hasaan , Naqvi Syed Waqas Aslam , Khan Anwar Zeb , Javed Amna , Kaiser Adeel , Aslam Samana , Javed Amna 
Published: October 2022

Abstract
Introduction: The liver and spleen sustain the greatest intra-abdominal injuries, followed by the intestine and mesentery in blunt abdominal trauma. Overlooked intra-abdominal injuries and surgical management delays are linked to a significant risk of morbidity. Accurate diagnostic investigations, including eFAST and MSCT, are of the highest significance. Patients who are hemodynamically stable (HDS) can often be managed without surgery due to advances in imaging technology, the expansion of minimally invasive techniques, and improved monitoring adjuncts. This study aims to look into the incidence, clinical manifestations, treatment, and consequences of traumatic blunt liver injuries in level – I trauma center in Pakistan.
Materials & Methods: This retrospective cohort analysis included all blunt abdominal trauma patients with liver injuries who were admitted and treated at the Lahore general hospital, Lahore, between January 2020 and January 2022. Data collected included demographic characteristics, mode of injury, vital signs, CT findings when accessible, the intensity of the liver trauma, management approach, and outcomes such as duration of hospital admission & mortality. Patients who remained hemodynamically stable were managed conservatively.
Results: A total of 124 patients presented with blunt abdominal trauma in the emergency department, out of which 39 reported liver injury. Among them, 33 were male, and the mean age was 31.56 ± 11.04 years. The most frequent mode of injury was motor vehicle collision in 34 patients. Conservative management was done in 16 patients and failed in 3 patients who eventually required operative management. Operative management was done on 23 patients. Most frequently performed procedure was peri-hepatic packing 20 (76.9%). The mortality rate was 3 (7.7%), and all were grade V liver injury patients.
Discussion: Liver trauma is among the most common injury after blunt abdominal trauma, constituting a life threat and a reason for emergency department admission. The treatment of liver injuries is multidisciplinary. Patients with severe hepatic trauma whose successful recovery is complicated by hemodynamic instability must undergo surgery.
Conclusion: To prevent and minimize the significant consequences, emergency physicians must rapidly assess the severity of the injury and select the most suitable treatment option (surgical or non-surgical).
Long-term follow-up results of nonemergent EC-IC bypass surgery for symptomatic, hemodynamically compromised chronic large- vessel occlusion or stenosis: quantitative radiologic analysis and clinical outcomes
Authors: Jo Hyunjun , Lee Si Un , Jeong Han-Gil , Kim Young-Deok , Kim Tackeun , Sunwoo Leonard , Ban Seung Pil , Bang Jae Seung , Kwon Oki , Oh Chang Wan 
Published: October 2022

Abstract
Objective:This study aimed to demonstrate the effectiveness of nonemergent extracranial-to-intracranial bypass (EIB) in symptomatic chronic large artery atherosclerotic stenosis or occlusive disease (LAA) through quantitative analysis of computed tomography perfusion (CTP) parameters using RAPID software.
Methods: We retrospectively analyzed 86 patients who underwent nonemergent EIB due to symptomatic chronic LAA. CTP data obtained preoperatively, immediately postoperatively (PostOp0), and 6 months postoperatively (PostOp6M) after EIB were quantitatively analyzed through RAPID software, and their association with intraoperative bypass flow was assessed. The clinical outcomes, including neurologic state, incidence of recurrent infarction and complications, were also analyzed.
Results: The time-to-maximum (Tmax) >8 s, >6 s and >4 s volumes decreased significantly at PostOp0 and up through PostOp6M (preoperative, 5, 51, and 223 ml (median), respectively; PostOp0, 0, 20.25, and 143 ml, respectively; PostOp6M, 0, 7.5, and 148.5 ml, respectively; p<0.001, p<0.001, and p<0.001, respectively). The postoperative improvement in the Tmax >6 s and >4 s volumes was significantly correlated with the bypass flow at PostOp0 and PostOp6M (PostOp0, r=0.367 (p=0.001) and r=0.275 (p=0.015), respectively; PostOp6M r=0.511 (p<0.001) and r=0.391 (p=0.001), respectively). The incidence of recurrent cerebral infarction was 4.7%, and there were no major complications that produced permanent neurological impairment.
Conclusion: Nonemergent EIB under strict operation indications can be a feasible treatment for symptomatic, hemodynamically compromised LAA patients.