bluuebunny/crossref_metadata_2025 huggingface dataset:
Study and Design of Privacy-Preserving Range Query Protocol in Sensor Networks Based on the Integration Reversal 0-1 Encoding with Bloom Filter
Authors: Deng Yun , Zheng Zitao , Wang Yu
Published: December 2022

In the current research on data query for two-tiered WSN, the privacy-preservation range query is one of the hotspots. However, there are some problems in the existing researches in two-tiered wireless sensor networks such as high computational and communication costs for security comparison items and high energy consumption of sensing nodes. In this paper, a privacy-preservation range query protocol based on the integration reversal 0-1 encoding with Bloom filter is researched and designed. In the sensing data submission stage, the optimized reversal 0-1 encoding, HMAC algorithm, AES encryption algorithm and variable-length Bloom filter are used for generating the maximum–minimum comparison encoding and constructing a shorter verification index chain to reduce computational and communication costs of sensing nodes; in the private data range query stage, the base station uses the HMAC algorithm to convert the plaintext query range into the ciphertext query range and sends it to the storage node. In the storage node, the bitmap encoding information of the verification index chain is calculated with the comparison rule of the reversal 0-1 encoding and it is returned to the base station together with the verification index chain and the data ciphertext that compliance with the query rule; in the data integrity verification stage, the integrity of the query results using the verification index chain and bitmap encoding is verified at the base station. In the experimental section, the Cortex-M4 development board equipped with the Alios-Things operating system as sensing node and the Cortex-A9 development board equipped with the Linux operating system as storage node are implemented in this protocol, which is compared with the existing protocols in three aspects: the number of data collected in each cycle, the length of data and the number of data dimensions. The experimental results show that the energy consumption of this protocol is lower under the same experimental environment.
A Hierarchical Model for Quality Evaluation of Mixed Source Software Based on ISO/IEC 25010
Authors: Zhang Chunguang , Li Bixin , Wang Lulu , Xu Haixin , Shao Tao
Published: December 2022

With the emergence of mixed source software, the existing quality models are not able to better assess the community quality and autonomy controllability of mixed source software. To fill this gap, we propose a hierarchical model in this paper for quality assessment of mixed source software. In our model, the new attributes are proposed to meet the quality requirements of mixed source software based on the ISO/IEC 25010 standards, and a set of metrics are designed for the new attributes. The model evaluates the quality of mixed source software through quality attributes that have been quantified by the metrics. Applying our quality model to some mixed source software and comparing the model results with the actual situation, we verify whether our proposed two quality attributes, community intensity and autonomy controllability, can effectively assess the quality of mixed source software. The results of the experiments show that our model is indeed effective in assessing the quality of mixed source software. An important feature of our model is that the model has good flexibility, and the set of quality attributes and metrics can be adjusted freely, which provides a flexible and feasible way for various software quality assessment requirements.
COMPARISON BETWEEN FIVE MINLP SOLVERS AND NEW RESULTS RELATED TO TRIGONOMETRIC FUNCTIONS
Authors: ALKHALIFA LOAY
Published: December 2022

Due to the rapid development of algorithms and techniques that are used to deal with mixed integer nonlinear programming (MINLP) problems, many global MINLP solvers were introduced. In this paper, computational experiments were done to compare between the performances of five of these solvers. Some of these solvers do not support trigonometric functions. Therefore, piecewise linear approximation (PLA) is applied to problems having these function so the solvers can deal with these problems. Additional computational tests were performed on to show how PLA can be useful, even to some powerful global solvers.
OPTIMAL INVESTMENT IN INTERRELATED PROJECTS
Authors: NAINDEBAM SHASIKANTA , RAYBAUDI MARZIA , SOLA MARTIN
Published: December 2022

This paper addresses the effects in partial equilibrium models of relaxing one of the critical underlying assumptions of [A. K. Dixit & R. S. Pindyck (1994) Investment Under Uncertainty. Princeton: Princeton University Press] to investment under uncertainty: either the potential investor has access to a single project or can consider competing (or complementary) projects independently. This paper studies the investment decision of a multi-product monopolist where the projects exhibit interdependence between the cash flows of different products. We derive the optimal entry time for each product and show that the choice and investment timing differ from that suggested by the single project approach. It is well known that the decision to produce related goods simultaneously or sequentially crucially depends on their degree of substitutability or complementarity. We derive the optimal timing for the investment under this scenario.
Hybrid Mayfly Lévy Flight Distribution Optimization Algorithm-Tuned Deep Convolutional Neural Network for Indoor–Outdoor Image Classification
Authors: Pakhare Jayamala D. , Uplane Mahadev D.
Published: December 2022

Image classification in the image is the persistent task to be computed in robotics, automobiles, and machine vision for sustainability. Scene categorization remains one of the challenging parts of various multi-media technologies implied in human–computer communication, robotic navigation, video surveillance, medical diagnosing, tourist guidance, and drone targeting. In this research, a Hybrid Mayfly Lévy flight distribution (MLFD) optimization algorithm-tuned deep convolutional neural network is proposed to effectively classify the image. The feature extraction process is a significant task to be executed as it enhances the classifier performance by reducing the execution time and the computational complexity. Further, the classifier is optimally trained by the Hybrid MLFD algorithm which in turn reduces optimization issues. The accuracy of the proposed MLFD-based Deep-CNN using the SCID-2 dataset is 95.2683% at 80% of training and 97.6425% for 10 K-fold. This manifests that the proposed MLFD-based Deep-CNN outperforms all the conventional methods in terms of accuracy, sensitivity, and specificity.
Three-dimensional remodeling of collagen fibers within cervical tissues in pregnancy
Authors: Zhou Lingxi , Jiang Rushan , Meng Jia , Qian Shuhao , Jiang Shenyi , Wang Chuncheng , Yang Chen , Ding Zhihua , Shu Zheyue , Liu Zhiyi
Published: December 2022

The cervix is a collagen-rich connective tissue that must remain closed during pregnancy while undergoing progressive remodeling in preparation for delivery, which begins before the onset of the preterm labor process. Therefore, it is important to resolve the changes of collagen fibers during cervical remodeling for the prevention of preterm labor. Herein, we assessed the spatial organization of collagen fibers in a three-dimensional (3D) context within cervical tissues of mice on day 3, 9, 12, 15 and 18 of gestation. We found that the 3D directional variance, a novel metric of alignment, was higher on day 9 than that on day 3 and then gradually decreased from day 9 to day 18. Compared with two-dimensional (2D) approach, a higher sensitivity was achieved from 3D analysis, highlighting the importance of truly 3D quantification. Moreover, the depth-dependent variation of 3D directional variance was investigated. By combining multiple 3D directional variance-derived metrics, a high level of classification accuracy was acquired in distinguishing different periods of pregnancy. These results demonstrate that 3D directional variance is sensitive to remodeling of collagen fibers within cervical tissues, shedding new light on highly-sensitive, early detection of preterm birth (PTB).
The Sparse Synchronous Model on Real Hardware
Authors: Hui John , Edwards Stephen A.
Published: December 2022

We present the Sparse Synchronous model (SSM) of computation, which allows a programmer to specify software timing more precisely than the traditional “heartbeat” of mainstream operating systems or the synchronous languages. SSM is a mix of semantics inspired by discrete event simulators and the synchronous languages designed to operate in resource-constrained environments such as microcontrollers. SSM provides precise timing prescriptions, concurrency, and determinism. We implement SSM in SSML, a toy language along with a runtime system that includes a scheduler, memory manager, and an interface that works with a real-time operating system to keep the model synchronized with the real world. Experimentally, we find our implementation is able to perform jitter-free I/O in the 10s of kHz on a microcontroller.
Cancers Attributable to Modifiable Risk Factors: A Road Map for Prevention
Authors: Collatuzzo Giulia , Boffetta Paolo
Published: December 2022

The implementation of primary and secondary preventive strategies is based on the evidence generated by cancer epidemiology, where the identification of risk factors and the description of their prevalence are fundamental to derive estimates on the burden of cancer from different etiologies, typically expressed as the population attributable fraction, which corresponds to the proportion of a cancer that may be prevented by controlling a given risk factor. However, even when cancer finds its etiology in modifiable factors, its prevention through the control of those factors is not always feasible, or it remains suboptimal despite the possibility of reducing the burden. We reviewed selected associations between modifiable risk factors and cancer, including tobacco smoking, occupational exposures, infections, air pollution, alcohol, and diet and obesity, and illustrated examples of both successes and failures in cancer control, underlying how current understanding of the avoidable causes of cancer is incomplete.
17α-estradiol, a lifespan-extending compound, attenuates liver fibrosis by modulating collagen turnover rates in male mice
Authors: Ali Mondal Samim , Sathiaseelan Roshini , Mann Shivani N. , Kamal Maria , Luo Wenyi , Saccon Tatiana D. , Isola José V. V. , Peelor Frederick F. , Li Tiangang , Freeman Willard M. , Miller Benjamin F. , Stout Michael B.
Published: December 2022

Estrogen signaling is protective against chronic liver diseases, although men and a subset of women are contraindicated for chronic treatment with 17β-estradiol (17β-E2) or combination hormone replacement therapies. We sought to determine if 17α-estradiol (17α-E2), a naturally occurring diastereomer of 17β-E2, could attenuate liver fibrosis. We evaluated the effects of 17α-E2 treatment on collagen synthesis and degradation rates using tracer-based labeling approaches in male mice subjected to carbon tetrachloride (CCl4)-induced liver fibrosis. We also assessed the effects of 17α-E2 on markers of hepatic stellate cell (HSC) activation, collagen cross-linking, collagen degradation, and liver macrophage content and polarity. We found that 17α-E2 significantly reduced collagen synthesis rates and increased collagen degradation rates, which was mirrored by declines in transforming growth factor β1 (TGF-β1) and lysyl oxidase-like 2 (LOXL2) protein content in liver. These improvements were associated with increased matrix metalloproteinase 2 (MMP2) activity and suppressed stearoyl-coenzyme A desaturase 1 (SCD1) protein levels, the latter of which has been linked to the resolution of liver fibrosis. We also found that 17α-E2 increased liver fetuin-A protein, a strong inhibitor of TGF-β1 signaling, and reduced proinflammatory macrophage activation and cytokines expression in the liver. We conclude that 17α-E2 reduces fibrotic burden by suppressing HSC activation and enhancing collagen degradation mechanisms. Future studies will be needed to determine if 17α-E2 acts directly in hepatocytes, HSCs, and/or immune cells to elicit these benefits.
Untargeted metabolomic profiling identifies serum metabolites associated with type 2 diabetes in a cross-sectional study of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study
Authors: Liu Yuzhao , Gan Lu , Zhao Bin , Yu Kai , Wang Yangang , Männistö Satu , Weinstein Stephanie J. , Huang Jiaqi , Albanes Demetrius
Published: December 2022

These metabolomic patterns may provide new additional evidence and potential insights relevant to the molecular basis of insulin resistance and the etiology of T2D.
Hierarchizing the Product Characteristics of Industrial Plain Sewing Machine for Making Best Purchase Decision
Authors: Shahriar M. M. , Parvez M. S. , Talapatra S.
Published: December 2022

Thousands of readymade garment industries are available in Bangladesh, where thousands of sewing machines are being used. The productivity of these sewing machines mostly depends on workers but more or less depends on the machine too. Suitable machines should be sourced to increase worker efficiency and production. Purchasing these machines needs some information or criteria ranking for choosing the best or most suitable machine. This study focuses on identifying and prioritizing those characteristics that fulfil the workers’ (users’) requirements and benefit the industry’s overall income. This study intends to investigate the application of the fuzzy Kano model and AHP (analytical hierarchy process) to translate consumer expectations and design into quality products. Customer needs and technical attributes are assessed and prioritized using the AHP. Then, the optional attributes were prioritized by using the Kano model. RMG industries and their purchasing departments can use these prioritized qualities charts to help them choose a sewing machine. Manufacturers of sewing machines can utilize this information to improve their sewing machine qualities, such as if they need to add or remove any attributes that the consumer requires or does not require.
Autophagy Modulates the Migration of Retinal Pericytes Induced by Advanced Glycation End Products
Authors: Lin Wen-Jian , Ma Xue-Fei , Zhou Huan-Ran , Xu Cheng-Ye , Yu Xin-Yang , Hu Yu-Xin , Hao Ming , Xu Qian , Li Hong-Xue , Kuang Hong-Yu
Published: December 2022

Retinal pericyte migration occurs in the early stage of diabetic retinopathy (DR), which is one of the important causes of pericyte loss. Autophagy has been found to play essential roles in the regulation of many types of cell migration. In this study, we explored the relationship between autophagy and retinal pericyte migration. In diabetic rats, the retinas became thinner, and the level of autophagy in each cell layer increased. In the primary culture of bovine retinal pericytes, we found that advanced glycation end products (AGEs) increased the migratory cell ability without influencing cell viability, which also increased the phosphorylation of focal adhesion kinase (FAK) and the expression of matrix metalloproteinase (MMP)-2 and decreased the expression of vinculin. AGEs-induced retinal pericyte autophagy and the inhibition of autophagy with chloroquine significantly inhibited cell migration, reversed AGEs-induced FAK phosphorylation, and changed vinculin and MMP-2 protein expression. These results provide a new insight into the migration mechanism of retinal pericytes. The early control of autophagy has a potential effect on regulating pericyte migration, which may contribute to keeping the integrity of retinal vessels in DR.
Research Progress of Rehabilitation Orthoses Based on 3D Printing Technology
Authors: Li Junqi , Chen Shenggui , Shang Xin , Li Nan , Aiyiti Wurikaixi , Gao Fei
Published: December 2022

Rehabilitation orthoses is currently a research hotspot in the field of 3D printing. Compared with traditional manufacturing methods, orthoses manufactured by 3D printing can meet the needs of patients in terms of structure and performance. This paper mainly introduces the research progress, main problems, and challenges of 3D printing rehabilitation orthoses in the medical field. At the same time, different 3D printing processes, types of medical materials, and contour extraction methods of the body surface area are compared. Its purpose is to provide a reference for the additive manufacturing of rehabilitation orthoses and their printing methods in medical research.
Image Super-Resolution Network Based on Feature Fusion Attention
Authors: Zou Changjun , Ye Lintao
Published: December 2022

The residual structure may learn the entire input region indiscriminately because the residual connection can still learn well as the network depth grows. To a certain extent, the attention mechanism can focus the network’s attention to the interesting area, enhancing the learning performance of essential areas while decreasing the computational load for the system. As a result, the combination of these two advantages could have substantial research significance, for both improve the efficiency and reduce the computational load. A dense residual connection network that combine feature fusion attention approach in image super resolution process is proposed. The dense residual block is enhanced with pixel and channel attention blocks, and a dual-channel path design incorporating global maximum pooling and global average pooling is utilized. A hybrid loss function is also proposed in order to increase the network’s sensitivity to the maximum error between individual pixels. The PSNR/SSIM/

L

∞

performance metrics increased after applying the hybrid loss function and our attention techniques. The experimental results demonstrated that our novel approach has several advantages over some recent approaches, as well as showing good outcomes on many testing datasets.
The Cytokine and Bone Protein Expression by Ellagic Acid-Hydroxyapatite in Bone Remodelling Model
Authors: Primasari Dyah Noviana , Nirwana Intan , Budi Hendrik Setia , Wardhana Agung Satria , Sari Annisa Fitria , Novita Novita , Setyawan Andika Putri , Surboyo Meircurius Dwi Condro , Shariff Khairul Anuar
Published: December 2022

Objective. Ellagic acid, a phenolic compound with anti-inflammatory potential, can be used to accelerate the bone healing process and affect human health, while hydroxyapatite is the most commonly used bone graft material. Using a combination of the two materials results in reduced inflammation and increased osteogenesis. This study aimed to determine the effects of combining ellagic acid and hydroxyapatite in bone marker remodelling by analysing the expression of tumour necrosis factor-α (TNF-α), interleukin 10 (IL-10), bone morphogenetic 4 protein (BMP-4), and osteopontin (OPN). Methods. Thirty Wistar rats were used in the study. A defect was created in each animal’s femur using a low-speed diamond bur. In the control group, the bone was then treated with polyethylene glycol (PEG). In one of the other groups, the bone was treated with hydroxyapatite, and in the other, with ellagic acid-hydroxyapatite. The femur was biopsied 7 days after the procedure and again 14 days after the procedure, and an indirect immunohistochemical (IHC) examination was performed for TNF-α, IL-10, BMP-4, and OPN expression. Results. The ellagic acid-hydroxyapatite decreased TNF-α expression in the bone tissue after 7 days and again after 14 days (

p

 < 0.05). On the other hand, it increased IL-10, BMP-4, and OPN expression (

p

 < 0.05) during the same time periods. Conclusion. Ellagic acid-hydroxyapatite plays a role in bone marker remodelling by decreasing the expression of TNF-α and increasing the expression of IL-10, BMP-4, and OPN. This hydroxyapatite combination can therefore be recommended for use as bone graft material.
Hydrogel Derived from Glucomannan-Chitosan to Improve the Survival of Lactobacillus acidophilus FNCC 0051 in Simulated Gastrointestinal Fluid
Authors: Aprilia Veriani , Murdiati Agnes , Hastuti Pudji , Harmayani Eni
Published: December 2022

The probiotic encapsulating hydrogel derived from porang (Amorphophallus oncophyllus) glucomannan and chitosan was investigated with regard to its encapsulation efficiency, physical properties, prebiotic activity, and survival under simulated gastrointestinal conditions. The hydrogel’s encapsulation efficiency was improved by varying the number of the Lactobacillus acidophilus FNCC 0051, which also served to increase the diameter (2-3 mm), polydispersity index (1.23–1.65), positive zeta potential, whiteness, and brightness of the hydrogel. Moreover, the hydrogel’s prebiotic activity score was higher than that of inulin after 24 h of incubation, reflecting its role as a cell encapsulant, particularly when it comes to maintaining cells during exposure to simulated gastrointestinal fluid. The cell viability increased from 86% to 100% when immersed in intestinal juice, which is comparable to the increase achieved using alginate and konjac glucomannan hydrogels. Future animal studies are required to determine the cell viability in actual gastrointestinal conditions and assess the health effects of the hydrogel.
Risk Factors for Nonalcoholic Fatty Liver Disease with Different Insulin Resistance in a Nonobese Chinese Population
Authors: Wu Xiaojuan , Wang Ying , Jia Yumei , Liu Jia , Wang Guang
Published: December 2022

Purposes. The aim of this study is to identify the risk factors of nonobese nonalcoholic fatty liver disease (NAFLD) individuals under different insulin resistance status. Methods. This cross-sectional study was conducted at the Medical Center of Beijing Chaoyang Hospital affiliated with Capital Medical University. NAFLD was diagnosed based upon ultrasonographic findings consistent with fatty liver disease. Results. A total of 1257 nonobese adults (625 non-NAFLD and 632 nonobese NAFLD) with body mass index (BMI) 18.5-24.9 kg/m2 were enrolled in the study. And all patients were divided into homeostasis model assessment of insulin resistance

HOMA
−
IR

>
1

group and

HOMA
−
IR
≤
1

group. When all the variables were adjusted in both the

HOMA
−
IR
>
1

group and

HOMA
−
IR
≤
1

group, older age (>50 years), higher BMI (23.0-24.9 kg/m2), higher AST (>18 U/L), higher TG (>0.9 mmol/L), higher GLU (>5.25 mmol/L), and higher HbA1C (>5.5%) were associated with higher risks of nonobese NAFLD. In patients with

HOMA
−
IR
>
1

, lower homeostatic model assessment of β-cell function (HOMA-β) (<47.1%) (OR, 7.460, 95% CI, 3.051-18.238,

P
<
0.001

) was associated with higher risks of nonobese NAFLD. Conclusions. Metabolic profiles (i.e., higher BMI, hyperglycemia, hypertriglyceridemia, and higher glycosylated hemoglobin) are risk factors of nonobese NAFLD, regardless of insulin resistance status. Decreased function of pancreatic β-cells may be the risk factor of nonobese NAFLD with insulin resistance, who should pay attention to further development of pancreatic β-cell dysfunction.
Modelling the Long-Term Health Outcome and Costs of Thrombectomy in Treating Stroke Patients with Large Ischaemic Core: Comparison between Clinical Trials and Real-World Data
Authors: Gao Lan , Moodie Marj , Levi Christopher , Lin Longting , Cheng Xin , Kleinig Timothy , Butcher Ken , Yan Bernard , Bivard Andrew , Parsons Mark
Published: December 2022

Introduction: We aimed to assess the long-term health outcomes and costs of endovascular thrombectomy (EVT) using clinical trials and real-world evidence in patients with large ischaemic core. Methods: Both clinical trials and the INternational Stroke Perfusion Imaging REgistry (INSPIRE) were used. Patients with acute computed tomography perfusion scan with an ischaemic core of ≥70 mL were included. A Markov model was constructed to simulate the long-term costs and health outcomes (quality-adjusted life year) post-index stroke. Effectiveness of EVT (modified Rankin scale score at 3 months) was derived from the trials and INSPIRE registry (compared to matched patients not treated with EVT), respectively. Results: Based on the trial and real-world data, the overall results revealed varied health benefits and costs due to EVT, with reduced health benefits and increased costs from EVT treatment in everyday practice. The long-term simulation estimated that offering EVT to large vessel occlusion stroke patients with large ischaemic core was associated with greater benefits (1.12 vs. 0.25 quality-adjusted life year gains) and lower (−A$19,320) or higher costs (A$11,278), using trial and real-world data, respectively. The incremental cost of the EVT procedure (i.e., A$14,356) could be primarily offset to a different extent by the reduction in costs related to the nursing home care (−$31,986 vs. −A$1,874) in the clinical trial and real-world practice. Conclusions: Our results highlight the potential gaps when implementing an effective intervention in the real world and the importance of the rigorous selection of large infarct core patients for EVT.
Transcatheter Occlusion of Left-To-Right Shunts in Premature Infants with Bronchopulmonary Dysplasia
Authors: Haregu Firezer , McCulloch Michael , Vergales Brooke , Garrod Andrea , Conaway Mark , Hainstock Michael
Published: December 2022

Introduction: Patent ductus arteriosus (PDA) and atrial septal defects (ASDs) cause pulmonary overcirculation, potentially worsening bronchopulmonary dysplasia (BPD) in premature infants. Transcatheter device occlusion of these defects is feasible and safe, though no case-controlled studies have assessed respiratory outcomes in infants with BPD. We hypothesized infants with BPD and ASDs or PDAs would experience improved respiratory outcomes following device occlusion of these lesions as compared to those who did not. Methods: We conducted a single-center, retrospective case-control study of premature infants diagnosed with BPD and either a small to large ASD or a small to moderate PDA from 2015 to 2021. The intervention group underwent transcatheter device occlusion of their defects and the control group did not. We compared changes in BPD severity over time between these two groups. Results: The control and intervention groups demonstrated comparable baseline demographics. Of the 15 patients in the intervention group, 9 underwent PDA device occlusion and 6 underwent ASD device occlusion at median postmenstrual age of 42 weeks (IQR 41–45 weeks). Despite having higher severity BPD at baseline, there was a more pronounced improvement in BPD severity in the intervention group as compared to the control group. Discussion: Premature infants with BPD and an ASD or PDA who underwent transcatheter occlusion of their lesion demonstrated a faster rate of improvement of their BPD severity as compared to a control cohort with similar lesions who did not undergo device occlusion of their lesion.
Profiles of Successful Aging and Their Association with All-Cause Mortality Risk among the Oldest-Old Chinese in Singapore
Authors: Cheng Grand H.-L. , Feng QiuShi , Chong Yap-Seng , Koh Woon-Puay
Published: December 2022

Introduction: Although successful aging (SA) studies have examined objective indicators such as disease and disability, physical and cognitive function, and social and productive engagement, as well as subjective indicators such as self-rated health, function, and well-being, the interplay among these indicators is rarely studied. We studied SA profiles that captured this interplay and evaluated the association of these profiles with mortality in the oldest-old. Methods: Respondents were 1,000 Chinese Singaporeans aged ≥85 years during interview visits from 2017 to 2018. Latent class analysis examined 12 objective and subjective indicators to identify SA profiles. Multivariable Cox regression assessed the relationship between these profiles and all-cause mortality risk through 2020. Results: Four distinct SA profiles were identified: “frail and dejected” (poor performance in nearly all objective and subjective indicators), “frail but resilient” (poor in objective but good in subjective indicators), “fairly fit and neutral” (good in about half of the indicators), and “fit and positive” (good in nearly all indicators). Compared with “frail and dejected,” the adjusted hazard ratio (95% confidence interval) for mortality risk was 0.63 (0.40–0.97) in “frail but resilient,” 0.56 (0.34–0.93) in “fairly fit and neutral,” and 0.31 (0.19–0.49) in “fit and positive.” Discussion: SA in the oldest-old could take different profiles based on objective and subjective indicators, and these profiles have implications for mortality risk. Individuals with good subjective indicators have advantage in survival despite poor objective indicators.
High-Volume Hemodiafiltration with Step-Down Approach versus Standard-of-Care Continuous Renal Replacement Therapy Approach in Critically Ill Burn Patients
Authors: Khandelwal Anjay , Yerigeri Keval , Lou Richard , Raina Rupesh
Published: December 2022

Introduction: Acute kidney injury (AKI) is a common complication of severe burn injuries and contributes to morbidity and mortality. It is exacerbated in burn patients by elevated serum creatinine and pro-inflammatory cytokines, leading to immune dysregulation. Chronic renal replacement therapy is standard of care and removes cytokines to return the body to homeostasis. Continuous veno-venous hemodiafiltration (CVVHDF) is a high-filtration method to enhance cytokine clearance; we analyze a step-down approach for improved outcomes in burn patients. Methods: This study reviewed 15 burn patients at Akron Children’s Hospital stratified into 2 groups: high-flow CVVHDF with step-down approach versus standard CVVHDF. A normocarbia bicarbonate-based dialysate solution and citrate anticoagulation was applied, and blood flow rate was maintained greater than 200 mL/min. Results: Fifteen burn patients at Akron Children’s Hospital were separated into groups managed with high-flow CVVHDF (n = 9) and standard-flow CVVHDF (n = 6). All 15 developed AKI symptoms and diuretic-resistant fluid overload, with 4/15 displaying fluid overload greater than 40%. The most common indication for hemofiltration was acute tubular necrosis (11/15). Average time on CVVHDF was 20.2 days and length of admission was 58.6 days. Vasodepressor dependency index was significantly reduced in the high-flow group at 48 h, but no significant difference in mortality was identified. No significant difference was identified in adverse reactions, notably electrolyte imbalances. Conclusion: The literature on the efficacy of high-flow CVVHDF is limited. This study suggests improved mortality rates and length of stay with high flow compared to the literature. Further studies with multicenter involvement are necessary.
How to Avoid Misdiagnosing Spontaneous Cervical Spinal Epidural Hematoma as Ischemic Stroke: 3 Case Reports and Literature Review
Authors: Hu Yaowen , Su Junhui , Cui Xinxin , Pan Lizhen , Jin Lingjing , Teng Fei
Published: December 2022

When spontaneous cervical spinal epidural hematoma (SCEH) presents with hemiparesis, it can be misdiagnosed with ischemic stroke (IS), and the treatment of IS such as thrombolysis may deteriorate the symptoms of patients with SCEH, leading to worse sequelae or even death. We reported 3 SCEH patients who were initially suspected as IS in our center between Jun 2020 and April 2022 and analyzed their clinical characteristics together with 48 patients reported in the literature from Jan 1995 to April 2022. Two of the 3 SCEH patients had neck symptoms, while none of them presented cranial nerve symptoms. Cranial computed tomography (CT) scans were negative; however, abnormal signals in the cervical spinal canal were observed during cranial computed tomography angiography (CTA) and subsequent cervical CT confirmed the diagnosis of SCEH. All of them avoid mistreatment with recombinant tissue plasminogen activator (rt-PA). Subsequently, we analyzed the clinical characteristics of a total of 51 patients. Thirteen of them developed symptoms during activity. Neck pain was an important sign of SCEH because 35 patients had neck pain or neck discomfort. Sensory impairment was reported in a small proportion of patients (11/51), which varied a lot in the patients. Some special manifestations highly suggested spinal cord lesions and provided evidence for the early differential diagnosis of SCEH and stroke, but the incidence of which was quite low: ipsilateral Horner syndrome in 2 patients, Brown-Séquard syndrome in 2 cases, and Lhermitte’s sign in 1 case. Only a minority (8/51) of the patients were correctly diagnosed at the emergency unit using cervical CT. Six patients were correctly diagnosed when performing CTA. A large portion of the cases (21/51) were first misdiagnosed as IS, but no responsible lesions were found on cranial magnetic resonance imaging (MRI), and subsequent cervical MRI confirmed the diagnosis. Sixteen patients were diagnosed with SCEH after the deterioration of symptoms. A total of 13 patients received rt-PA, and 10 of them had symptoms aggravation after thrombolysis. For patients with acute onset of hemiparesis but without cranial nerve symptoms, especially those accompanied by clinical features such as neck pain, ipsilateral Horner syndrome, Brown-Séquard syndrome, and Lhermitte’s sign, SCEH should be highly suspected rather than stroke. Careful differential diagnosis should be performed with a comprehensive medical history and thorough physical examination. Cervical CT scan is a reasonable choice for quick differential diagnosis prior to administering potentially harmful therapy, especially rt-PA.
Effects of Hyperferritinemia on Functional Outcome in Acute Ischemic Stroke Patients with Admission Hyperglycemia
Authors: Wu Qian , Wei Chenchen , Liu Junfeng , Wang Yanan , Liu Ming
Published: December 2022

Introduction: Hyperferritinemia, presented as elevated serum ferritin level, is an indicator of high iron status which plays roles in secondary brain injury after acute ischemic stroke (AIS). However, the effects of hyperferritinemia and poor outcomes remain uncertain. Additionally, admission hyperglycemia quite frequently accompanies AIS patients, which is associated with unfavorable outcome. Thus, we aimed to investigate the effects of hyperferritinemia on 3-month and 1-year functional outcomes in AIS patients and especially those with admission hyperglycemia. Methods: AIS patients within 24 h of onset were enrolled at West China Hospital from October 2016 to December 2019. Serum ferritin and blood glucose levels were tested on admission. Poor functional outcome at 3 months and 1 year was defined as modified Rankin Scale score ≥3. Multivariable analysis was used to investigate the associations between hyperferritinemia and 3-month and 1-year outcomes. Subgroup analysis was performed in patients with and without hyperglycemia. Results: Of 723 patients (mean age 68.11 years, 60.6% males) finally included, 347 (48.0%) had hyperferritinemia. The incidence of poor outcome was 45.2% at 3 months and 41.2% at 1 year. Patients with hyperferritinemia had a higher frequency of poor 3-month outcome (51.8% vs. 39.2%, p = 0.001) and poor 1-year outcome (46.8% vs. 36.1%, p = 0.004). In all AIS patients, hyperferritinemia was not independently associated with poor functional outcome at 3 months or 1 year after adjusting for confounders (all p > 0.05). In AIS patients with hyperglycemia, hyperferritinemia was an independent factor correlated with poor 3-month outcome (OR = 1.711, 95% CI 1.093–2.681, p = 0.019) but not with poor 1-year outcome (p > 0.05). Conclusions: High iron status, presented as hyperferritinemia, is associated with poor 3-month functional outcome in AIS patients with hyperglycemia. Evaluating serum ferritin level may be conducive to assess the risk of short-term poor outcome in AIS patients with hyperglycemia. Further studies will be required to confirm our findings.
Neurotensin-Binding Immunoglobulin G in Patients with Parkinson’s Disease
Authors: Muruzheva Zamira M. , Egorov Daniil S. , Absalyamova Margarita T. , Traktirov Dmitrii S. , Karpenko Marina N. , Fetissov Serguei O.
Published: December 2022

Introduction: Neurotensin (NTS) is a 13-amino acid neuropeptide functionally linked with the brain dopaminergic system via expression of the NTS peptide or its receptor in dopamine neurons. Neuropeptide-binding immunoglobulins (Igs) are present in humans and can be involved in both physiological and pathological processes. Considering the functional link between NTS and dopamine neurons, we studied the occurrence of NTS-binding IgG autoantibodies in patients with Parkinson’s disease (PD). Methods: Plasma levels of NTS-binding IgG were analyzed using enzyme-linked immunosorbent assay in both male and female PD patents and in age-matched healthy controls. Possible microbial origin of NTS cross-reactive IgG was analyzed by sequence alignment of the 6-amino acid C-terminal NTS pharmacophore with bacterial and viral proteins from the public NCBI database. Results: NTS-binding IgG were detected in the plasma of all study subjects, while their levels were consistently lower in PD patients versus controls (p = 0.0001), independently from age or sex of the study participants. Moreover, PD patients with a more severe stage (2.5–3.0) of the disease had lower levels of NTS-binding IgG (p = 0.0004) than those with a milder stage (1.0–2.0). Furthermore, PD patients taking amantadine or high doses of levodopa had higher levels of NTS-binding IgG than those without medication. Contiguous sequence homology for the NTS pharmacophore was present in several microbial proteins occurring in human gut microbiota. Discussion: The study revealed that NTS-binding IgG occur naturally in humans and that PD patients display their low plasma levels accentuated by disease severity. The functional significance of this finding and its relevance to the pathophysiology of PD, including putative link to gut microbiota, remain to be studied.
The Use of IL-17 and IL-23 Inhibitors in Swedish Clinical Practice: A Register-Based Analysis
Authors: Norlin Jenny M , Löfvendahl Sofia , Schmitt-Egenolf Marcus
Published: December 2022

Background: Interleukin (IL) inhibitors have made completely cleared skin achievable for many patients with moderate to severe psoriasis in clinical trial settings. Few observational studies assess treatment response in accordance with treatment goals in guidelines. Objectives: The aim of the study was to analyze the treatment response of IL-17/IL-23 inhibitors in clinical practice and the proportions of patients that reach the treatment target of the Psoriasis Area and Severity Index (PASI) < 3 and the Dermatology Life Quality Index (DLQI) ≤5. Methods: A longitudinal, observational study based on the Swedish National Registry for Systemic Treatment of Psoriasis, PsoReg. Patients using IL-17/IL-23 inhibitors with assessments of PASI, DLQI, and EQ-5D before (maximum 6 months) and after (3–12 months) initiation of IL-17/IL-23 were included. Results: In total, 333 patients using IL-17/IL-23 inhibitors were included. Eighty percent (n = 266) received IL-17 inhibitors, and 20% (n = 67) received IL-23 inhibitors. Sixty-six percent of patients reached both PASI <3 and DLQI ≤5, 23% reached one target, and 11% reached none. The mean (SD) PASI, DLQI, and EQ-5D improvements were 6.75 (6.99), 7.14 (7.97), and 0.126 (0.296), respectively. There was no statistically significant difference in outcomes between IL-17 and IL-23 inhibitor treatment groups. Conclusions: IL-17/IL-23 inhibitors are effective in clinical practice, but there is still an unmet therapeutic need in moderate to severe psoriasis.
Basal Cell Adenocarcinoma Arising from the Parotid Gland
Authors: Vitorino Marina , Tinoco Joaquim , Chaves Andreia Filipa
Published: December 2022

Basal cell adenocarcinoma (BCAC) is a rare malignant tumor of the salivary glands, representing 1–2% of salivary gland neoplasms. It is considered a low-grade tumor, often associated with a good prognosis. We report a case of a 60-year-old man with 3-month history of a growing, painless mass in the right ascending ramus of the mandible. Ultrasound and CT scan showed an asymmetry between parotid glands, depicting a nodular structure on the right side. A parotid fine needle aspiration cytology revealed neoplastic cells suggestive of adenoid cystic carcinoma. The patient underwent a total parotidectomy with lymph node dissection. Histopathology result was reported as BCAC. The patient concluded adjuvant radiotherapy and continued follow-up surveillance without evidence of relapse. The adjuvant approach in this case was decided by a multidisciplinary team given the absence of classically known risk factors. We highlight the importance of considering BCAC in the differential diagnosis in salivary gland tumors.
Indications for the Use of Therapeutic Plasma in Adult Patients
Authors: von Heymann Christian , Lier Heiko , Rosenthal Christoph , Kaufner Lutz
Published: December 2022

Background: Different preparations for therapeutic plasma are available on the market. The German hemotherapy guideline has been completely updated in 2020 and, for this purpose, has reviewed the evidence for the most frequent clinical indications for the use of therapeutic plasma in adult patients. Summary: The German hemotherapy guideline has reviewed the evidence for the following indications for the use of therapeutic plasma in the adult patient: massive transfusion and bleeding, severe chronic liver disease, disseminated intravascular coagulation, plasma exchange for TTP, and the rare hereditary FV and FXI deficiencies. The updated recommendations for each indication are discussed on the background of existing guidelines and new evidence. For most indications, the quality of evidence is low due to missing prospective randomized trials or rare diseases. However, due to the “balanced” content of coagulation factors and inhibitors therapeutic plasma remains an important pharmacological treatment option in clinical situations with an already activated coagulation system. Unfortunately, the “physiological” content of coagulation factors and inhibitors limits the efficacy in clinical scenarios with high blood losses. Key Messages: The evidence for the use of therapeutic plasma for the replacement of coagulation factors due to massive bleeding is poor. Coagulation factor concentrates seem to be more appropriate for this indication, although the quality of evidence is also low. However, for diseases with an activated coagulation or endothelial system (e.g., disseminated intravascular coagulation, TTP) the balanced replacement of coagulation factors, inhibitors, and proteases may be of advantage.
Role of C-Reactive Protein in Kidney Diseases
Authors: Li Jiaxiao , Chen Junzhe , Lan Hui-yao , Tang Ying
Published: December 2022

Background: C-reactive protein (CRP) is an acute-phase protein and has been found to be a risk factor for acute kidney injury (AKI) and chronic kidney diseases (CKD). However, the role and mechanisms of CRP in AKI and CKD remain largely unclear. Summary: Clinically, elevated serum CRP is a risk factor or biomarker for patients with AKI and CKD. Interestingly, in critically ill COVID-19 patients, increased serum CRP is also associated with the development of AKI. Functionally, studies using human CRP transgenic mouse models find that CRP is pathogenic and can function as a mediator for AKI and CKD as mice overexpressing human CRP promote AKI and CKD. Mechanistically, CRP can promote AKI and CKD via NF-κB and Smad3-dependent mechanisms. We found that CRP can activate Smad3 signaling directly and cause AKI via the Smad3-p27-dependent G1 cell cycle arrest mechanism. Thus, targeting CRP-Smad3 signaling with a neutralizing antibody or Smad3 inhibitor can inhibit AKI. Key Messages: CRP acts not only as a biomarker but also as a mediator for AKI and CKD. CRP can activate Smad3 to induce cell death and cause progressive renal fibrosis. Thus, targeting CRP-Smad3 signaling may represent a promising therapy for AKI and CKD.
Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression
Authors: Born Emmanuelle , Lipskaia Larissa , Breau Marielle , Houssaini Amal , Beaulieu Delphine , Marcos Elisabeth , Pierre Remi , Do Cruzeiro Marcio , Lefevre Marine , Derumeaux Genevieve , Bulavin Dmitry V. , Delcroix Marion , Quarck Rozenn , Reen Virinder , Gil Jesus , Bernard David , Flaman Jean-Michel , Adnot Serge , Abid Shariq
Published: December 2022

Background:

Senescent cells (SCs) are involved in proliferative disorders, but their role in pulmonary hypertension remains undefined. We investigated SCs in patients with pulmonary arterial hypertension and the role of SCs in animal pulmonary hypertension models.

Methods:

We investigated senescence (p16, p21) and DNA damage (γ-H2AX, 53BP1) markers in patients with pulmonary arterial hypertension and murine models. We monitored p16 activation by luminescence imaging in p16-luciferase (p16
LUC/+
) knock-in mice. SC clearance was obtained by a suicide gene (p16 promoter–driven killer gene construct in p16-ATTAC mice), senolytic drugs (ABT263 and cell-permeable FOXO4-p53 interfering peptide [FOXO4-DRI]), and p16 inactivation in p16
LUC/LUC
mice. We investigated pulmonary hypertension in mice exposed to normoxia, chronic hypoxia, or hypoxia+Sugen, mice overexpressing the serotonin transporter (SM22-5-HTT
+
), and rats given monocrotaline.

Results:

Patients with pulmonary arterial hypertension compared with controls exhibited high lung p16, p21, and γ-H2AX protein levels, with abundant vascular cells costained for p16, γ-H2AX, and 53BP1. Hypoxia increased thoracic bioluminescence in p16
LUC/+
mice. In wild-type mice, hypoxia increased lung levels of senescence and DNA-damage markers, senescence-associated secretory phenotype components, and p16 staining of pulmonary endothelial cells (P-ECs, 30% of lung SCs in normoxia), and pulmonary artery smooth muscle cells. SC elimination by suicide gene or ABT263 increased the right ventricular systolic pressure and hypertrophy index, increased vessel remodeling (higher dividing proliferating cell nuclear antigen–stained vascular cell counts during both normoxia and hypoxia), and markedly decreased lung P-ECs. Pulmonary hemodynamic alterations and lung P-EC loss occurred in older p16
LUC/LUC
mice, wild-type mice exposed to Sugen or hypoxia+Sugen, and SM22-5-HTT
+
mice given either ABT263 or FOXO4-DRI, compared with relevant controls. The severity of monocrotaline-induced pulmonary hypertension in rats was decreased slightly by ABT263 for 1 week but was aggravated at 3 weeks, with loss of P-ECs.

Conclusions:

Elimination of senescent P-ECs by senolytic interventions may worsen pulmonary hemodynamics. These results invite consideration of the potential impact on pulmonary vessels of strategies aimed at controlling cell senescence in various contexts.