bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of a prediction model for the prolonged length of stay in Chinese patients with lower extremity atherosclerotic disease: a retrospective study
Authors: Wang Xue , Yang Yu , Zhang Jian , Zang Shuang
Published: February 2023

Objectives

This study aims to develop and internally validate a prediction model, which takes account of multivariable and comprehensive factors to predict the prolonged length of stay (LOS) in patients with lower extremity atherosclerotic disease (LEAD).

Design

This is a retrospective study.

Setting

China.

Participants, primary and secondary outcomes

Data of 1694 patients with LEAD from a retrospective cohort study between January 2014 and November 2021 were analysed. We selected nine variables and created the prediction model using the least absolute shrinkage and selection operator (LASSO) regression model after dividing the dataset into training and test sets in a 7:3 ratio. Prediction model performance was evaluated by calibration, discrimination and Hosmer-Lemeshow test. The effectiveness of clinical utility was estimated using decision curve analysis.

Results

LASSO regression analysis identified age, gender, systolic blood pressure, Fontaine classification, lesion site, surgery, C reactive protein, prothrombin time international normalised ratio and fibrinogen as significant predictors for predicting prolonged LOS in patients with LEAD. In the training set, the prediction model showed good discrimination using a 500-bootstrap analysis and good calibration with an area under the receiver operating characteristic of 0.750. The Hosmer-Lemeshow goodness of fit test for the training set had a p value of 0.354. The decision curve analysis showed that using the prediction model both in training and tests contributes to clinical value.

Conclusion

Our prediction model is a valuable tool using easily and routinely obtained clinical variables that could be used to predict prolonged LOS in patients with LEAD and help to better manage these patients in routine clinical practice.
Optimising diagnosis and treatment of tuberculosis infection in community and primary care settings in two urban provinces of Viet Nam: a cohort study
Authors: Vo Luan Nguyen Quang , Nguyen Viet Nhung , Nguyen Nga Thi Thuy , Dong Thuy Thi Thu , Codlin Andrew , Forse Rachel , Truong Huyen Thanh , Nguyen Hoa Binh , Dang Ha Thi Minh , Truong Vinh Van , Nguyen Lan Huu , Mac Tuan Huy , Le Phong Thanh , Tran Khoa Tu , Ndunda Nduku , Caws Maxine , Creswell Jacob
Published: February 2023

Objectives

To end tuberculosis (TB), the vast reservoir of 1.7–2.3 billion TB infections (TBIs) must be addressed, but achieving global TB preventive therapy (TPT) targets seems unlikely. This study assessed the feasibility of using interferon-γ release assays (IGRAs) at lower healthcare levels and the comparative performance of 3-month and 9-month daily TPT regimens (3HR/9H).

Design, setting, participants and intervention

This cohort study was implemented in two provinces of Viet Nam from May 2019 to September 2020. Participants included household contacts (HHCs), vulnerable community members and healthcare workers (HCWs) recruited at community-based TB screening events or HHC investigations at primary care centres, who were followed up throughout TPT.

Primary and secondary outcomes

We constructed TBI care cascades describing indeterminate and positivity rates to assess feasibility, and initiation and completion rates to assess performance. We fitted mixed-effects logistic and stratified Cox models to identify factors associated with IGRA positivity and loss to follow-up (LTFU).

Results

Among 5837 participants, the indeterminate rate was 0.8%, and 30.7% were IGRA positive. TPT initiation and completion rates were 63.3% (3HR=61.2% vs 9H=63.6%; p=0.147) and 80.6% (3HR=85.7% vs 9H=80.0%; p=0.522), respectively. Being male (adjusted OR=1.51; 95% CI: 1.28 to 1.78; p<0.001), aged 45–59 years (1.30; 1.05 to 1.60; p=0.018) and exhibiting TB-related abnormalities on X-ray (2.23; 1.38 to 3.61; p=0.001) were associated with positive IGRA results. Risk of IGRA positivity was lower in periurban districts (0.55; 0.36 to 0.85; p=0.007), aged <15 years (0.18; 0.13 to 0.26; p<0.001), aged 15–29 years (0.56; 0.42 to 0.75; p<0.001) and HCWs (0.34; 0.24 to 0.48; p<0.001). The 3HR regimen (adjusted HR=3.83; 1.49 to 9.84; p=0.005) and HCWs (1.38; 1.25 to 1.53; p<0.001) showed higher hazards of LTFU.

Conclusion

Providing IGRAs at lower healthcare levels is feasible and along with shorter regimens may expand access and uptake towards meeting TPT targets, but scale-up may require complementary advocacy and education for beneficiaries and providers.
Pharmacological tumor PDL1 depletion with chlorambucil treats ovarian cancer and melanoma: improves antitumor immunity and renders anti-PDL1-resistant tumors anti-PDL1-sensitive through NK cell effects
Authors: Bai Haiyan , Padron Alvaro S , Deng Yilun , Liao Yiji J , Murray Clare J , Ontiveros Carlos , Kari Suresh J , Kancharla Aravind , Kornepati Anand V R , Garcia Myrna , Reyes Ryan Michael , Gupta Harshita B , Conejo-Garcia Jose R , Curiel Tyler
Published: February 2023

Background

Tumor intracellular programmed cell death ligand-1 (PDL1) mediates pathologic signals that regulate clinical treatment responses distinctly from surface-expressed PDL1 targeted by αPDL1 immune checkpoint blockade antibodies.

Methods

We performed a drug screen for tumor cell PDL1 depleting drugs that identified Food and Drug Administration (FDA)-approved chlorambucil and also 9-[2-(phosphonomethoxy)ethyl] guanine. We used in vitro and in vivo assays to evaluate treatment and signaling effects of pharmacological tumor PDL1 depletion focused on chlorambucil as FDA approved, alone or plus αPDL1.

Results

PDL1-expressing mouse and human ovarian cancer lines and mouse melanoma were more sensitive to chlorambucil-mediated proliferation inhibition in vitro versus corresponding genetically PDL1-depleted lines. Orthotopic peritoneal PDL1-expressing ID8agg ovarian cancer and subcutaneous B16 melanoma tumors were more chlorambucil-sensitive in vivo versus corresponding genetically PDL1-depleted tumors. Chlorambucil enhanced αPDL1 efficacy in tumors otherwise αPDL1-refractory, and improved antitumor immunity and treatment efficacy in a natural killer cell-dependent manner alone and plus αPDL1. Chlorambucil-mediated PDL1 depletion was relatively tumor-cell selective in vivo, and treatment efficacy was preserved in PDL1KO hosts, demonstrating tumor PDL1-specific treatment effects. Chlorambucil induced PDL1-dependent immunogenic tumor cell death which could help explain immune contributions. Chlorambucil-mediated PDL1 reduction mechanisms were tumor cell-type-specific and involved transcriptional or post-translational mechanisms, including promoting PDL1 ubiquitination through the GSK3β/β-TRCP pathway. Chlorambucil-mediated tumor cell PDL1 depletion also phenocopied genetic PDL1 depletion in reducing tumor cell mTORC1 activation and tumor initiating cell content, and in augmenting autophagy, suggesting additional treatment potential.

Conclusions

Pharmacological tumor PDL1 depletion with chlorambucil targets tumor-intrinsic PDL1 signaling that mediates treatment resistance, especially in αPDL1-resistant tumors, generates PDL1-dependent tumor immunogenicity and inhibits tumor growth in immune-dependent and independent manners. It could improve treatment efficacy of selected agents in otherwise treatment-refractory, including αPDL1-refractory cancers, and is rapidly clinically translatable.
Localization and density of tertiary lymphoid structures associate with molecular subtype and clinical outcome in colorectal cancer liver metastases
Authors: Zhang Chong , Wang Xiang-Yu , Zuo Jie-Liang , Wang Xue-Fu , Feng Xiao-Wen , Zhang Bo , Li Yi-Tong , Yi Chen-He , Zhang Peng , Ma Xiao-Chen , Chen Zhen-Mei , Ma Yue , Han Jia-Hao , Tao Bao-Rui , Zhang Rui , Wang Tian-Qi , Tong Li , Gu Wang , Wang Si-Yu , Zheng Xiao-Fei , Yuan Wen-Kang , Kan Zi-Jie , Fan Jie , Hu Xiang-Yang , Li Jun , Zhang Chao , Chen Jin-Hong
Published: February 2023

Background

Tertiary lymphoid structures (TLSs) have been proposed to assess the prognosis of patients with cancer. Here, we investigated the prognostic value and relevant mechanisms of TLSs in colorectal cancer liver metastases (CRCLM).

Methods

603 patients with CRCLM treated by surgical resection from three cancer centers were included. The TLSs were categorized according to their anatomic subregions and quantified, and a TLS scoring system was established for intratumor region (T score) and peritumor region (P score). Differences in relapse-free survival (RFS) and overall survival (OS) between groups were determined. Multiplex immunohistochemical staining (mIHC) was used to determine the cellular composition of TLSs in 40 CRCLM patients.

Results

T score positively correlated with superior prognosis, while P score negatively associated with poor survival (all p<0.05). Meanwhile, T score was positively associated with specific mutation subtype of KRAS. Furthermore, TLSs enrichment gene expression was significantly associated with survival and transcriptomic subtypes of CRCLM. Subsequently, mIHC showed that the densities of Treg cells, M2 macrophages and Tfh cells were significantly higher in intratumor TLSs than in peritumor TLSs (p=0.029, p=0.047 and p=0.041, respectively), and the frequencies of Treg cells and M2 macrophages were positively correlated with P score, while the frequencies of Tfh cells were positively associated with T scores in intratumor TLSs (all p<0.05). Next, based on the distribution and abundance of TLSs, an Immune Score combining T score and P score was established which categorized CRCLM patients into four immune classes with different prognosis (all p<0.05). Among them, patients with higher immune class have more favorable prognoses. The C-index of Immune Class for RFS and OS was higher than Clinical Risk Score statistically. These results were also confirmed by the other two validation cohorts.

Conclusions

The distribution and abundance of TLSs is significantly associated with RFS and OS of CRCLM patients, and a novel immune class was proposed for predicting the prognosis of CRCLM patients.
Deployment of whole genome next-generation sequencing of SARS-CoV-2 in a military maritime setting
Authors: Bosworth Andrew , Robson J , Lawrence B , Casey A L , Fair A , Khanam S , Hudson C , O'Shea M K
Published: February 2023

Background

SARS-CoV-2 can spread rapidly on maritime platforms. Several outbreaks of SARS-CoV-2 have been reported on warships at sea, where transmission is facilitated by living and working in close quarters. Core components of infection control measures such as social distancing, patient isolation and quarantine of exposed persons are extremely difficult to implement. Whole genome sequencing (WGS) of SARS-CoV-2 has facilitated epidemiological investigations of outbreaks, impacting on outbreak management in real time by identifying transmission patterns, clusters of infection and guiding control measures. We suggest such a capability could mitigate against the impact of SARS-CoV-2 in maritime settings.

Methods

We set out to establish SARS-CoV-2 WGS using miniaturised nanopore sequencing technology aboard the Royal Fleet Auxiliary ARGUS while at sea. Objectives included designing a simplified protocol requiring minimal reagents and processing steps, the use of miniaturised equipment compatible for use in limited space, and a streamlined and standalone data analysis capability to allow rapid in situ data acquisition and interpretation.

Results

Eleven clinical samples with blinded SARS-CoV-2 status were tested at sea. Following viral RNA extraction and ARTIC sequencing library preparation, reverse transcription and ARTIC PCR-tiling were performed. Samples were subsequently barcoded and sequenced using the Oxford Nanopore MinION Mk1B. An offline version of the MinKNOW software was used followed by CLC Genomics Workbench for downstream analysis for variant identification and phylogenetic tree construction. All samples were correctly classified, and relatedness identified.

Conclusions

It is feasible to establish a small footprint sequencing capability to conduct SARS-CoV-2 WGS in a military maritime environment at sea with limited access to reach-back support. This proof-of-concept study has highlighted the potential of deploying such technology in the future to military environments, both maritime and land-based, to provide meaningful clinical data to aid outbreak investigations.
Lipid management in systemic lupus erythematosus according to risk classifiers suggested by the European Society of Cardiology and disease-related risk factors reported by the EULAR recommendations
Authors: Drosos George C , Konstantonis George , Sfikakis Petros P , Tektonidou Maria G
Published: February 2023

Background

The European Alliance of Associations for Rheumatology recommended that lipid-lowering therapy (LLT) in systemic lupus erythematosus (SLE) should follow general population guidelines. We examined the eligibility for LLT in SLE according to Systematic Coronary Risk Evaluation (SCORE), with and without the addition of vascular ultrasound (VUS) and disease-related features.

Methods

210 patients with SLE without prior cardiovascular events, diabetes or antiphospholipid syndrome underwent cardiovascular risk assessment with SCORE. LLT eligibility was evaluated in low-risk and moderate-risk patients following European Society of Cardiology (ESC) guidelines. Atherosclerotic plaques on carotid ultrasound (cUS)) and carotid and femoral ultrasound (cfUS), prolonged disease duration (PDD, ≥10 years), failure to achieve lupus low disease activity state (LLDASno), cumulative glucocorticoid ‘cardiovascular harm’ dose (GCCVH, optimal cut-off to predict ultrasound-detected plaques) and antiphospholipid antibody positivity (aPLpos) were tested as SCORE risk enhancers for classification ability (phi coefficient) and agreement (Cohen’s kappa) using SCORE plus cfUS as a reference modality for LLT eligibility.

Results

Plaques were detected in 9.9% of low-risk cases and 54.6% of moderate-risk cases. SCORE alone would indicate 0% of low-risk patients and 3% of moderate-risk patients for LLT eligibility. According to SCORE+cfUS, 9.9% of low-risk patients and 57.6% of moderate-risk patients, respectively, would be eligible for LLT based on ESC guidelines. Ιn low-risk/moderate-risk patients, phi values for SCORE+PDD, GCCVH(cut-off ≥11 g), LLDASnoand aPLposin antiplatelet-naïve antiphospholipid antibody-positive (aPLpos/APT−) cases were 0.06/0.13, 0.23/0.20, 0.07/0.16 and 0.06/0.33, respectively. Agreement for LLT eligibility to SCORE+cfUS was better for SCORE+PDD in moderate-risk patients and for SCORE+cUS in both groups of patients. SCORE+GCCVH and SCORE+aPLposshowed at least fair agreement (kappa ≥0.20) to SCORE+cfUS in low-risk or moderate-risk and in aPLpos/APT− moderate-risk patients, respectively.

Conclusion

Disease-related and VUS features, in addition to SCORE, may help to improve LLT decision making in SLE. GCCVHand aPLposimprove LLT eligibility similarly and to a greater degree than PDD or LLDASno.
A Cooperative Attack Detection Framework for MANET-IoT Network Using Optimized Gradient Boosting Convolutional Neural Network
Authors: Sathyaraj P. , Rukmani Devi S. , Kannan K.
Published: February 2023

The implementation of large-scale Internet of Things (IoT) devices results in smart cities. Using standard mobile ad-hoc networks and IoT, developers establish the communication model for a smart city. The rapid growth of IoT devices based on smart cities poses different Quality of Service (QoS) and security problems. This research presents a novel Modified Elephant Herd Optimization (MEHO) method and a Gradient Boosting Convolutional Neural Network (CNN) strategy to address these issues. The cooperative attacks with varied disruption probabilities are initially assessed at the edge nodes of the IoT network. The MEHO-based Gradient Boosting CNN (MEHO-CNN) approach effectively detects cooperative attacks, ensuring the identification of malicious entities. For traditional cloud access, both bandwidth utilization as well as expected latency are minimized in edge computing. By using the IoT network, the proposed MEHO-CNN model identifies and eliminates malicious nodes. To establish the claimed trustworthy background, the legitimate accusations are based on an examination of trust-based allegations. When compared to existing methodologies, the proposed approach lowers the impact of cooperative attacks, resulting in increased throughput, reduced attack detection rates, lower packet loss ratio, lower packet delivery ratio, and other benefits.
Infinitely many solutions for Schrödinger–Newton equations
Authors: Hu Yeyao , Jevnikar Aleks , Xie Weihong
Published: February 2023

We prove the existence of infinitely many non-radial positive solutions for the Schrödinger–Newton system [Formula: see text] provided that [Formula: see text] has the following behavior at infinity: [Formula: see text] where [Formula: see text] and [Formula: see text] are some positive constants. In particular, for any [Formula: see text] large we use a reduction method to construct [Formula: see text]-bump solutions lying on a circle of radius [Formula: see text].
OFC-Delaunay triangulation: A new efficient algorithm for merging two adjacent Delaunay triangulations
Authors: An Phan Thanh , Duc Trinh Minh , Oanh Dang Thi
Published: February 2023

In this paper, we present an efficient algorithm, namely Orienting and Final Circles (OFC)-Delaunay Triangulation, for constructing the Delaunay triangulation of a finite planar point set using the idea of the Method of Orienting Curves (introduced by Phu in Zur Lösung einer regulären Aufgabenklasse der optimalen Steuerung im Groen mittels Orientierungskurven, Optimization 18(1) (1987) 65–81 and Ein konstruktives Lösungsverfahren für das Problem des Inpolygons kleinsten Umfangs von J. Steiner, Optimization 18(3) (1987) 349–359). The concepts of orienting and final circles are introduced. The Delaunay edges are determined by orienting circles and a final circle. Our algorithm has [Formula: see text]([Formula: see text]) worst-case running time. The algorithm is implemented in Python and some numerical examples are presented.
Edge-vertex domination on interval graphs
Authors: Samanta Adhya Amita , Mondal Sukumar , Charan Barman Sambhu
Published: February 2023

For an undirected as well as connected graph [Formula: see text], a node point [Formula: see text] is edge-vertex dominated by an edge [Formula: see text] if [Formula: see text] is incident to [Formula: see text] or [Formula: see text] is incident to an adjacent edge of [Formula: see text]. A set [Formula: see text] is called an edge-vertex dominating set of [Formula: see text] if every node point of [Formula: see text] is edge-vertex dominated by at least one edge of [Formula: see text]. The minimum cardinality among all edge-vertex dominating sets is the edge-vertex domination number, symbolled by [Formula: see text]. Here, we propose an algorithm that runs in [Formula: see text]-time for determining a minimum-cardinality [Formula: see text] of interval graph with [Formula: see text] nodes. We also study some properties relating to the edge-vertex dominating set of interval graphs.
Transfer Learning for Human Activity Recognition Using Representational Analysis of Neural Networks
Authors: An Sizhe , Bhat Ganapati , Gumussoy Suat , Ogras Umit
Published: February 2023

Human activity recognition (HAR) has increased in recent years due to its applications in mobile health monitoring, activity recognition, and patient rehabilitation. The typical approach is training a HAR classifier offline with known users and then using the same classifier for new users. However, the accuracy for new users can be low with this approach if their activity patterns are different than those in the training data. At the same time, training from scratch for new users is not feasible for mobile applications due to the high computational cost and training time. To address this issue, we propose a HAR transfer learning framework with two components. First, a representational analysis reveals common features that can transfer across users and user-specific features that need to be customized. Using this insight, we transfer the reusable portion of the offline classifier to new users and fine-tune only the rest. Our experiments with five datasets show up to 43% accuracy improvement and 66% training time reduction when compared to the baseline without using transfer learning. Furthermore, measurements on the hardware platform reveal that the power and energy consumption decreased by 43% and 68%, respectively, while achieving the same or higher accuracy as training from scratch. Our code is released for reproducibility.

1
Hybrid Quantum Annealing for Larger-than-QPU Lattice-structured Problems
Authors: Raymond Jack , Stevanovic Radomir , Bernoudy William , Boothby Kelly , McGeoch Catherine C. , Berkley Andrew J. , Farré Pau , Pasvolsky Joel , King Andrew D.
Published: February 2023

Quantum processing units (QPUs) executing annealing algorithms have shown promise in optimization and simulation applications. Hybrid algorithms are a natural bridge to larger applications. We present a simple greedy method for solving larger-than-QPU lattice-structured Ising optimization problems. The method, implemented in the open source D-Wave Hybrid framework, uses a QPU coprocessor operating with generic parameters. Performance is evaluated for standard spin-glass problems on two lattice types with up to 11,616 spin variables, double the size that is directly programmable on any available QPU. The proposed method is shown to converge to low-energy solutions faster than an open source simulated annealing method that is either directly employed or substituted as a coprocessor in the hybrid method. Using newer Advantage QPUs in place of D-Wave 2000Q QPUs is shown to enhance convergence of the hybrid method to low energies and to achieve a lower final energy.
Novel Prognostic Biomarkers for Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) Patients via Analysis of Competing Endogenous RNA (ceRNA) Network
Authors: Dong Yanru , Wen Weibo , Yuan Tiezheng , Liu Lan , Li Xiangdan
Published: February 2023

Background. Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is a common malignant gynecological cancer. The ceRNA networks play important roles in many tumors, while RILPL2-related ceRNA network has been seldom studied in CESC. Methods. All CESC data was obtained from TCGA database. Differentially expressed RNAs and predicted target RNAs were cross analyzed to construct ceRNA network. RNA and clinicopathological characteristics’ influence on overall survival (OS) were determined by univariate and multivariate Cox regression analyses. Lasso regression was used to construct the prediction model. Coexpression analysis was performed to explore the association of gene expression with CESC. This was followed by an experimental validation based on these results. Results. Between high and low RILPL2 expression CESC patients, totally 1227 DEmRNAs, 39 DEmiRNAs, and 1544 DElncRNAs were identified. After multiple cross analyses, 1 miRNA hsa-miR-1293, 20 mRNAs, and 43 lncRNAs were maintained to construct ceRNA network. CADM3-AS1, LINC00092, and ZNF667-AS1 in ceRNA network were significantly associated with the OS of CESC patients, and patients with low expression of these lncRNAs had worse prognosis. Significant lower expressions of these lncRNAs were also observed in CESC cell line compared with normal cell line. Conclusion. Low expressions of CADM3-AS1, LINC00092, and ZNF667-AS1 in ceRNA network were probably promising poor prognostic biomarkers for CESC patients. The genes show a prospective research area for CESC-targeted treatment in the future.
Study on the Compaction Performance and Its Key Influencing Factors of Asphalt Mixture Based on Intelligent Sensing Techniques
Authors: Ma Rong , Wang Zhijun
Published: February 2023

Real‐time and accurate compaction quality monitoring is one of the key steps in the pavement construction. In this study, the effect of roller passes and temperature on the compactness of asphalt mixtures and its uniformity is discussed using the semivariance function. Further, the indoor asphalt mixture gyratory compaction test was carried out based on the embedded SmartRock sensor, with the aim of monitoring the changes in rotation and contact forces between aggregates. In addition, the effect of temperature on the dynamic response of SmartRock is discussed, and the compaction mechanism of asphalt mixtures is investigated from a microscopic scale. It is found that compaction degree and uniformity are not always positively correlated with the number of roller passes and that excessive compaction leads to a decrease in compaction effect; meanwhile, the variation in the compactness of asphalt mixtures can be characterized by the dynamic response of SmartRock, which providing a feasible method for real‐time monitoring of the compaction process and optimization of the construction plan.
Restenosis of Coronary Arteries in Patients with Coronavirus Infection: Case Series
Authors: Batenova Gulnara , Pivina Lyudmila , Dedov Evgeny , Dyussupov Altay , Zhumanbayeva Zhanar , Smail Yerbol , Belikhina Tatyana , Pak Laura , Ygiyeva Diana
Published: February 2023

Introduction. Coronavirus infection is a risk factor for vascular thrombosis. This is of particular importance for patients undergoing myocardial revascularization since this infection can be a trigger for the formation of restenosis in the area of a previously implanted coronary stent. Understanding the risk factors for stent thrombosis and restenosis is of particular importance in individuals at risk for adverse outcomes. The rarity of such situations makes the present study unique. Objective. Studying the peculiarities of restenosis and thrombosis of the coronary arteries in patients after coronavirus infection. Methods. The study was performed in the Department of Cardiovascular Surgery of Emergency Hospital, Semey City, in 2021. We have examined the medical records of 10 consecutive patients with restenosis of coronary arteries after coronavirus infection and 10 matched-by-age patients with similar restenosis of coronary arteries who did not have coronavirus infection as a comparison group. To determine statistically significant differences between independent samples, we calculated the Mann–Whitney U test. Results. The average age of patients was 65.7 years. Only one case was classified as early restenosis (within 8 days of previous revascularization), two cases represented late restenosis, and seven cases were very late restenoses. In 70% of cases, restenosis was localized in the left anterior descending artery, in 30% of cases, it was in the right coronary artery, and in 40% of cases, it was in the left circumflex artery. In comparison with patients who did not have a coronavirus infection, there were statistically significant differences regarding IgG (

P
<
0.001

) and fibrinogen (

P
=
0.019

). Conclusion. Patients with myocardial revascularization in the past have a higher risk of stent restenosis against the background of coronavirus infection due to excessive neointimal hyperplasia, hypercoagulability, increased inflammatory response, and endothelial dysfunction.
An Enriched Environment Promotes Motor Function through Neuroprotection after Cerebral Ischemia
Authors: Shi Liang-Feng , Wang Chuan-Jie , Yu Ke-Wei , Wu Jun-Fa , Zhang Qi-Qi
Published: February 2023

Stroke seriously affects human health. Many studies have shown that enriched environment (EE) can promote functional recovery after stroke, but the intrinsic mechanisms remain unclear. In order to study the internal mechanisms of EE involved in functional recovery after ischemic stroke and which mechanism plays a leading role in the recovery of limb function after cerebral infarction, key proteins potentially involved in neuronal protection and synaptic remodeling in the ischemic penumbra have been investigated. In this study, adult C57BL/6 mice after permanent middle cerebral artery occlusion (pMCAO) were assigned to the EE and standard housing (SH) groups 3 days after operation. The EE house was spacious that contained a large variety of small toys; the SH was a normal sized cage. Sham‐operated mice without artery occlusion were housed under standard conditions and were fed a normal diet. On days 3, 7, 14, and 21, postoperative motor functional recovery was tested using the modified neurological severity score (mNSS) and the Rotarod test. The expression of B‐cell lymphoma‐2 (Bcl‐2), Bcl‐2‐associated X protein (Bax), growth‐associated protein‐43 (GAP‐43), and synaptophysin (SYN) was examined by western blotting and immunofluorescence staining. The motor functional recovery (based on the mNSS and Rotarod test 3, 7, 14, and 21 days post operation) of mice in the EE group improved significantly compared to the SH group. The expression of GAP‐43 and SYN and the ratio of Bcl‐2/Bax were all upregulated in the EE group compared to the SH group. In addition, we also explored the relationship between neuronal protection and synaptic remodeling in the EE‐mediated recovery of limb function after cerebral infarction by correlation analysis. Correlation analysis showed that compared with the increase of Bcl‐2/Bax ratio, the increased expression of GAP‐43 and SYN was more closely related to the recovery of limb function in ischemic mice. These data support the hypothesis that EE can promote the process of improvement of limb dysfunction induced by ischemic stroke, and this behavior restoration may, via promoting neuroprotection in the ischemic penumbra, be dependent on the regulation of the expression of GAP‐43, SYN, Bcl‐2, and Bax. A limitation of the study was that we only observed several representative key indicators of synaptic remodeling and neuronal apoptosis, without an in‐depth study of the potential mechanisms involved.
Enriched Environment Attenuates Ferroptosis after Cerebral Ischemia/Reperfusion Injury via the HIF-1α-ACSL4 Pathway
Authors: Liu Jingying , Luo Qihang , Ke Jie , Zhang DongDong , Xu Yang , Liao Weijing , Chen Xiuping , Zhang Xin
Published: February 2023

Enriched environment (EE) has been proven to be an effective intervention strategy which can improve neurofunctional recovery following cerebral ischemia/reperfusion (I/R) injury. However, it still needs further investigation for the underlying mechanisms. Recently, it has been shown that ferroptosis played an essential role in the pathophysiological development of ischemic stroke (IS). This study is aimed at investigating whether EE plays a neuroprotective role by attenuating ferroptosis after cerebral I/R injury. We used middle cerebral artery occlusion/reperfusion (MCAO/R) to build a model of cerebral I/R injury. To evaluate the effect of EE on neurological recovery, we used the modified neurological severity score (mNSS) and the Morris water maze (MWM). We used the western blot to detect the protein levels of glutathione peroxidase 4 (GPX4), hypoxia-inducible factor-1α (HIF-1α), and acyl-CoA synthetase long-chain family member 4 (ACSL4). We used the quantitative real-time PCR (qRT-PCR) to measure the mRNA levels of ACSL4 and inflammatory cytokines including tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and interleukin 1 beta (IL-1β). The occurrence of ferroptosis was detected by TdT-mediated dUTP nick-end labeling (TUNEL) assay, diaminobenzidine- (DAB-) enhanced Perls’ staining, iron level assays, and malondialdehyde (MDA) level assays. The results verified that EE enhanced functional recovery and attenuated ferroptosis and neuroinflammation after cerebral I/R injury. EE increased the expression of HIF-1α while inhibited the expression of ACSL4. Our research indicated that EE improved functional recovery after cerebral I/R injury through attenuating ferroptosis, and this might be related to its regulation of the neuroinflammation and HIF-1α-ACSL4 pathway.
An Optimization Method Combining RSSI and PDR Data to Estimate Distance between Smart Devices for COVID‐19 Contact Tracing
Authors: Zhao Bo , Zheng Chao , Ren Xinxin , Dai Jianrong
Published: February 2023

Distance estimation methods arise in many applications, such as indoor positioning and COVID‐19 contact tracing. The received signal strength indicator (RSSI) is favored in distance estimation. However, the accuracy is not satisfactory due to the signal fluctuation. Besides, the RSSI‐only method has a large‐ranging error because it uses fixed parameters of the path loss model. Here, we propose an optimization method combining RSSI and pedestrian dead reckoning (PDR) data to estimate the distance between smart devices. The PDR may provide high accuracy of walking distance and direction. Moreover, the parameters of the path loss model are optimized to dynamically fit the complex electromagnetic environment. The proposed method is evaluated in outdoor and indoor environments and compared with the RSSI‐only method. The results show that the mean absolute error is reduced up to 0.51 m and 1.02 m, with an improvement of 10.60% and 64.55% for outdoor and indoor environments, respectively, compared with the RSSI‐only method. Consequently, the proposed optimization method has better accuracy of distance estimation than the RSSI‐only method, and its feasibility is demonstrated through real‐world evaluations.
IL18 Receptor Signaling Regulates Tumor-Reactive CD8+ T-cell Exhaustion via Activation of the IL2/STAT5/mTOR Pathway in a Pancreatic Cancer Model
Authors: Lutz Veronika , Hellmund Veronique M. , Picard Felix S.R. , Raifer Hartmann , Ruckenbrod Teresa , Klein Matthias , Bopp Tobias , Savai Rajkumar , Duewell Peter , Keber Corinna U. , Weigert Andreas , Chung Ho-Ryun , Buchholz Malte , Menke André , Gress Thomas M. , Huber Magdalena , Bauer Christian
Published: February 2023

Intratumoral cytotoxic CD8+ T cells (CTL) enter a dysfunctional state characterized by expression of coinhibitory receptors, loss of effector function, and changes in the transcriptional landscape. Even though several regulators of T-cell exhaustion have been identified, the molecular mechanisms inducing T-cell exhaustion remain unclear. Here, we show that IL18 receptor (IL18R) signaling induces CD8+ T-cell exhaustion in a murine pancreatic cancer model. Adoptive transfer of Il18r−/− OT-1 CD8+ CTLs resulted in enhanced rejection of subcutaneous tumors expressing ovalbumin (OVA) as a model antigen (PancOVA), compared with wild-type OT-1 CTLs. Transferred intratumoral IL18R-deficient CTLs expressed higher levels of effector cytokines TNF and IFNγ and had reduced expression of coinhibitory receptors (PD-1, TIM-3, 2B4, LAG-3) and the transcription factors Eomes and TOX. Lower expression of coinhibitory receptors and TOX on IL18R-deficient versus IL18R-sufficient CD8+ T cells were confirmed in an orthotopic KPC model. IL18R-induced T-cell exhaustion was regulated by IL2/STAT5 and AKT/mTOR pathways, as demonstrated in an in vitro exhaustion assay. Concordantly, mice deficient in NLRP3, the molecular complex activating IL18, had decreased expression of coinhibitory receptors on intratumoral T cells and similar changes in signaling pathways at the transcriptome level. Thus, molecular pathways promoting T-cell exhaustion indicate an involvement of an NLRP3-expressing tumor microenvironment, which mediates IL18 release. The Cancer Genome Atlas analysis of patients with pancreatic carcinoma showed an association between NLRP3-mediated IL18 signaling and shorter survival. These findings indicate NLRP3-mediated IL18R signaling as a regulator of intratumoral T-cell exhaustion and a possible target for immunotherapy.

See related Spotlight by Stromnes, p. 400
Embryonal Sarcoma of the Liver in the Adult: Challenges in the Diagnosis of a Rare Entity
Authors: Fontinha Guilherme Nogueira , Gama João Martins , Caetano Oliveira Rui , Cipriano Augusta
Published: February 2023

Introduction: Embryonal sarcoma of the liver (ESL) is a rare neoplasm of the liver occurring mainly in paediatric ages. Making the correct diagnosis can be challenging as the laboratory and radiological findings that are often nonspecific, and the tumour immunophenotype is poorly defined and even somewhat variable. Case Presentation: A large epigastric mass was detected in a computerized tomography scan of a 43-year-old woman presenting with abdominal pain and bloating. The mass was biopsied and submitted to histopathological study. Microscopically the tumour had sarcomatoid features and showed multinucleated cells with periodic acid-Schiff (PAS)-positive globules. Immunostaining revealed positivity for vimentin, CD10, glypican-3, and α1-antitrypsin and negativity for keratins, muscle, adipocytic, and melanocytic differentiation markers. The patient was then submitted to a left hepatectomy with similar histological findings. Discussion: ESL in adults is a rarity and its diagnosis requires the exclusion of other entities. While some microscopic features are very common, they remain nonspecific. The main feature is the presence of multinucleated cells with PAS-positive hyaline globules. While ancillary testing is key, the immunophenotype also lacks specificity and ESL may have variable staining for glypican-3 and epithelial or muscle differentiation markers. Although it has been described for more than 3 decades, the prognosis and optimal treatment are still not well defined, but surgery has yielded favourable results.
SIN3A Defects Associated with Syndromic Congenital Hypogonadotropic Hypogonadism: An Overlap with Witteveen-Kolk Syndrome
Authors: Schnöll Caroline , Krepischi Ana Cristina Victorino , Renck Alessandra Covallero , Amato Lorena Guimaraes Lima , Kulikowski Leslie Domenici , Dantas Naiara Castelo Branco , Costa Elaine Maria Frade , Mendonca Berenice Bilharinho , Latronico Ana Claudia , Jorge Alexander Augusto de Lima , Silveira Leticia Ferreira Gontijo
Published: February 2023

Introduction: Congenital hypogonadotropic hypogonadism (CHH) is a rare condition caused by GnRH deficiency. More than 40 genes have been associated with the pathogenesis of CHH, but most cases still remain without a molecular diagnosis. Mutations involving the same gene (e.g., FGFR1, PROK2/PROKR2, CHD7) were found to cause normosmic CHH and Kallmann syndrome (KS), with and without associated phenotypes, illustrating the coexistence of CHH with signs of other complex syndromes. The Witteveen-Kolk syndrome (WITKOS), caused by defects of the SIN3A gene, is a heterogeneous disorder characterized by distinctive facial features, microcephaly, short stature, delayed cognitive, and motor development. Although micropenis and cryptorchidism have been reported in this syndrome, WITKOS has not been formally associated with CHH so far. Patients and Methods: A man with KS associated with mild syndromic features (S1) and a boy with global developmental delay, syndromic short stature, micropenis and cryptorchidism (S2), in whom common genetic defects associated with CHH and short stature had been previously excluded, were studied by either chromosomal microarray analysis or whole exome sequencing. Results: Rare SIN3A pathogenic variants were identified in these 2 unrelated patients with CHH phenotypic features. A 550 kb deletion at 15q24.1, including the whole SIN3A gene, was identified in S1, and a SIN3A nonsense rare variant (p.Arg471*) was detected in S2. Conclusion: These findings lead us to propose a link between SIN3A defects and CHH, especially in syndromic cases, based on these 2 patients with overlapping phenotypes of WITKOS and CHH.
ОСОБЛИВОСТІ ПЕРЕБІГУ COVID-19 У ХВОРИХ НА ХРОНІЧНІ ГЕПАТИТИ В І С
Authors: Андрейчин М. А. , Копча В. С.
Published: February 2023

Коронавірусна хвороба 2019 (COVID-19) поширилася по всьому світу. Оскільки у пацієнтів з COVID-19 ураження печінки зазвичай має змішаний генез, особливості перебігу коронавірусної хвороби при фонових хронічних гепатитах B (ХГВ) і С (ХГС) остаточно не з’ясовані.

У цьому огляді наведено відомості про порівняння демографічної характеристики, результатів фізикальних і лабораторних обстежень, у т. ч. госпітальної летальності хворих на COVID-19 із супутніми ХГВ і ХГС та без цих коморбідних захворювань.

Для вивчення факторів ризику тяжкості захворювання та летальності були використані одно- та багатозмінні логістичні та регресійні моделі Кокса.

У більшості хворих на ХГВ COVID-19 перебігав тяжко. Крім традиційних печінкових проб (рівні аланін­амінотрансферази – АлАТ, аспартатамінотрансферази – АсАТ, лужної фосфатази – ЛФ, загального білірубіну), дослідники вивчали такі фактори, як активність лактатдегідрогенази – ЛДГ (≥245 ОД/л, коефіцієнт ризику (HR) = 8,639, 95 % достовірний інтервал (ДІ) = 2,528-29,523, р<0,001) та рівень біомаркера коагуляції крові – D-димеру (≥0,5 мкг/мл, HR = 4,321, 95 % ДІ = 1,443-12,939; р<0,005), зниження показника альбуміну (<35 г/л, HR = 0,131, 95 % ДІ = 0,048-0,361; р<0,001), а також альбуміно-глобуліновий коефіцієнт (<1,5, HR = 0,123, 95 % ДІ = 0,017-0,918; р<0,05).

Встановлено, що у хворих на COVID-19 на фоні ХГВ значно вища ймовірність тяжкого перебігу хвороби, а також смерті. ХГС призводить до посилення вірулентності SARS-CoV-2, незалежно від початкових супутніх захворювань, лабораторних показників при госпіталізації чи ураження печінки, спричиненого SARS-CoV-2. Це може бути пов’язано з позапечінковими ефектами ХГС, що призводить до цитокін-опосередкованого запалення та ендотеліальної дисфункції. Таке поєднання захворювань є сильним предиктором внут­рішньолікарняної летальності.
СВІТЛІЙ ПАМ’ЯТІ АНДРІЯ МИКОЛАЙОВИЧА СОКОЛА
Authors: Avtoriv Kolektyv
Published: February 2023

Стисло висвітлено основні біографічні віхи й творчий доробок відомого вченого-інфекціоніста, доктора медичних наук, професора, Заслуженого лікаря України Андрія Миколайовича Сокола.
SWOT-АНАЛІЗ ПРОЦЕСУ НАДАННЯ ОНКОГЕМАТОЛОГІЧНОЇ ДОПОМОГИ В УМОВАХ РОСІЙСЬКОЇ АГРЕСІЇ В УКРАЇНІ
Authors: Рингач Н. О. , Мельник У. І. , Примак С. В.
Published: February 2023

Мета: проаналізувати процес надання онкогематологічної допомоги в умовах російської агресії в Україні (на прикладі гематологічного відділення Київської міської клінічної лікарні № 9).

Матеріали і методи. Статистичний аналіз за даними Державної служби статистики та Національного канцер-реєстру України (2020, 2021), SWOT-аналіз.

Результати. Військова агресія Російської Федерації проти України спричинила порушення процесу надання медичної допомоги та ланцюжків поставок, що негативно відбилося на ситуації з онкогематологічними захворюваннями.

Визначено та класифіковано фактори впливу на  процес надання стаціонарної онкогематологічної допомоги в умовах російської агресії в Україні. Показано сильні (висококваліфікована та мотивована команда; досвід зарубіжних стажувань і участі у міжнародних клінічних дослідженнях; практика взаємодії та налагоджені професійні контакти тощо) і слабкі (функціонування меншим числом співробітників, збільшення навантаження; зниження участі у міжнародних клінічних дослідженнях; ускладнення пошуку неродинних донорів та обмеження функціонування реєстру) сторони. Висвітлено можливості (безперервність фінансування, сприяння муніципальної влади; добровільне донорство та діяльність Київського міського центру крові; волонтерська допомога; доступність он-лайн тренінгів) і перешкоди (надання допомоги в небезпечних для життя умовах; брак ліків, реактивів та обладнання; обмеження лабораторної діагностики; несприятливі чинники довкілля, стрес).

Висновок. Усвідомлення низки сильних та слабких сторін, можливостей і перешкод є необхідним для організації адекватного потребам надання медичної допомоги при складному воєнному стані в складних умовах воєнного положення й оперативного управління в часи невизначеності та змін.
ОСОБЛИВОСТІ ПРОВЕДЕННЯ КОМУНІКАЦІЙНИХ КАМПАНІЙ, СПРЯМОВАНИХ НА ВРАЗЛИВІ ГРУПИ НАСЕЛЕННЯ
Authors: Лінніков С. В. , Миронюк І. С.
Published: February 2023

Мета: огляд та аналіз ефективності сучасних підходів та інструментів інформаційно-комунікаційних кампаній у громадському здоров’ї, спрямованих на вразливі категорії населення.

Матеріали і методи. Використано бібліосемантичний метод, методи контент і структурно-логічного аналізу та узагальнення. Матеріалами дослідження є теоретичні положення, результати досліджень і методичних напра­цю­вань зарубіжних та вітчизняних учених.

Результати. Проаналізовано еволюцію підходів до оцінки ефективності інформаційно-комунікаційних кампаній, сформульовано принципи ефективного інформування про ризики для вразливих категорій населення. Визначено, що використання досвіду бізнес-сфери в PR-кампаніях, комбінація різних підходів до їх реалізації для різних ці­льо­вих груп впливу дозволяють ефективно реалізувати інформаційно-комунікаційні кампанії у сфері здоров’я на­се­лення. При цьому важливо чітко розуміти основні особливості ключових цільових груп таких інформаційно-комунікаційних кампаній, правильно визначати канали комунікації та змістовне наповнення й оформлення базового повідомлення. Точне розповсюдження інформації серед окремих груп вимагає спеціальних комунікаційних стратегій.

Висновок. Важливою при плануванні інформаційно-комунікаційних кампаній у сфері громадського здоров’я є необхідність враховувати всі особливості ключової цільової групи такої кампанії, серед яких чільне місце займають групи підвищеного ризику (уразливі групи населення) з особливими поведінковими моделями, що і зумовлюють їх уразливість.
ФАКТОРИ РИЗИКУ ТА ПРОФІЛАКТИКА ГЕСТАЦІЙНОГО ЦУКРОВОГО ДІАБЕТУ
Authors: Теренда Н. О. , Подільська Т. І. , Котяш Н. О. , Денефіль О. В.
Published: February 2023

Мета: оцінити основні фактори ризику розвитку гестаційного цукрового діабету (ГЦД) та напрямки його профілактики.

Матеріали і методи. Проведено аналіз наукових джерел інформації (електронна база PubMed) щодо медико-соціальної проблеми ГЦД. Використано бібліосемантичний, аналітичний методи дослідження.

Результати. ГЦД викликає короткострокові та довгострокові негативні наслідки для здоров’я як жінок, так і їхніх дітей, такі, як прееклампсія під час вагітності, значно підвищений ризик розвитку діабету 2 типу, серцево-судинних захворювань, макросомія, аутизм, дитяче ожиріння, порушення толерантності до глюкози та судинні розлади.

Епідеміологічні дослідження вказують на генетичні (обтяжений сімейний анамнез), екологічні (вплив перфтороктанової кислоти), поведінкові (підвищена маса тіла або ожиріння, тютюнокуріння) фактори ризику розвитку ГЦД. Тому корекція останніх, а саме популяризація в жінок до та під час вагітності середземноморської дієти, використання дозованої фізичної активності сприяють профілактиці ГЦД. Серед усіх опублікованих на сьогодні досліджень заходів щодо фізичної активності із модифікацією дієти для профілактики ГЦД результати більшості досліджень вказують на сприятливий ефект, але лише за тієї умови, що втручання розпочато на початку першого триместру.

Висновки. ГЦД не тільки підвищує ризик ускладнень під час вагітності у матері та плода, але й значно підвищує ризик діабету 2 типу, метаболічного синдрому і серцево-судинних захворювань після вагітності. Тому так важливо вживати заходів щодо корекції вищеописаних факторів ризику розвитку ГЦД для адекватної профілактики цього захворювання.