bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and implementation of a low cost, high performance ionizing radiation source detection and source direction finding system
Authors: CUHADAROGLU Burak , İLK H. Gökhan
Published: July 2023

This study shows the design, implementation, and test results of a low-cost portable radiation-detector system relies on a directionally designed multi detector probe that works in Geiger-Müller counting mode with a single chip solution. The proposed system can perform the functions of detecting the ionizing radiation source, counting gamma and showing the direction and angle of the gamma source relative to the position of the device. The radiation direction finding (RDF) system consists of a radiation probe and electronic sections that are mounted in a metal box. The probe has a has a cast housing made of lead material and it has 8 directional slots for placing the optically isolated PIN diode arrays where each array consists of 4 parallelly connected BPW 34 PIN model diode. The lead housing also blocks incident rays from unintended directions and provides a directional sensing for PIN diodes. The metal box contains 8 low noise amplifiers and pulse shaping detector boards that are assigned to each channel of PIN diode arrays, a signal inverter board, a step-up high voltage board, a 12 V battery and a parallel processing FPGA board with an embedded VHDL software that can process all 8 channels simultaneously and execute the direction estimation algorithm. The system also has an adjustable detector bias voltage and the applied voltage can be displayed on a seven-segment display located in front of the unit so that different models of PIN diodes can be used and tested with different bias voltage levels. It also has a HMI touch screen unit and user interface for displaying the Cpm or Cps values of each channel; a 360-degree scale showing the direction of the source with its pointer and an indicator showing the direction of the source numerically in degrees. The system works as a gamma detector and the source direction can also be detected within ±45° interval. The success of system within this interval is 99.22%. The detector was tested with low to high energy gamma sources (241Am, 9.761 μCi, 59.54 keV, 137Cs 661, 3.7 MBq, keV and 60Co, μCi, 1173 and 1332 keV) and showed good sensitivity performance level in gamma ray detection. The major outcome of this study and the major contribution of this work to the literature is therefore is the design and production details of a hand-held detector and source direction locator prototype; which is a light, portable and compact system.
Correction of irregular postkeratoplastic astigmatism in patients with cataract
Authors: Sinitsyn M. V. , Pozdeeva N. A.
Published: July 2023

Introduction. Penetrating keratoplasty (PKP) is known to lead to the occurrence of post-keratoplasty astigmatism (PA) that is often of a high degree and irregular shape. Phacoemulsification (PE) with implantation of toric intraocular lenses (toric IOLs) is able to compensate for regular PA. However, this method is not effective enough with irregular PA.

The aim was to conduct a clinical and functional analysis of the combined method for correcting irregular postkeratoplastic astigmatism (PA) in patients with cataract.

Materials and methods. The study has been conducting from February 2018 to September 2022. We operated on 27 eyes (27 patients) aged 38 to 52 years. Of these, there were 17 men and 10 women. All patients with a history of 4–6 years ago underwent penetrating keratoplasty for stage IV keratoconus and pellucid marginal degeneration of the cornea. In all patients, an irregular form of PA was noted according to keratotopography. Surgical treatment of these patients took place in 2 stages. At the stage I, in order to correct irregular PA and increase sphericity and regularity of the penetrating corneal graft, MyoRing was implanted into the intrastromal pocket having been formed in it using a femtosecond laser. One year after the MyoRing implantation, the stage II was performed – cataract phacoemulsification (CPE) with implantation of an intraocular lens (IOL). The follow-up period after the CPE with the IOL implantation was 1 year.

Results. One year after the MyoRing implantation into the penetrating corneal graft, a slight increase in visual acuity was noted. However, there was a pronounced decrease in corneal astigmatism by an average of 4.9 times, an increase in sphericity and regularity of the penetrating corneal graft according to keratotopography, as well as an increase in its biomechanical properties. One month after the operation, there was an increase in uncorrected visual acuity (UCVA) by 6.8 times and best corrected visual acuity (BCVA) – by 3.9 times, a decrease in the cylindrical component of refraction to –0.65 ± 0.28 D that no longer changed.

Conclusions. The combined method for correcting irregular PA in patients with cataract by MyoRing implantation into a penetrating corneal graft followed by CPE with IOL implantation showed a high refractive result, stability and safety in the late postoperative period.
New detection method of SARS-CoV-2 antibodies toward a point-of-care biosensor
Authors: Nelson-Mora Janikua , Rubio Diana , Ventura-Martínez Amairani , González Luis A. , Del-Rio Diana , Aranda-López Yuli , Jiménez-Díaz Edgar , Zamarrón-Hernández Diego , Ríos-López Diana G. , Aguirre Stephanie , Ruiz-Hernandez Yasab , Cruz-Ramírez Aarón , Barjau Jonás S. , Jáurez Miguel A. , Lopez-Aparicio Jehú , Campa-Higareda Andrea , Fiordelisio Tatiana
Published: July 2023

The outbreak of COVID-19, a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is regarded as the most severe of the documented coronavirus pandemics. The measurement and monitoring of SARS-CoV-2 antibody levels by serological tests are relevant for a better epidemiological and clinical understanding of COVID-19. The aim of this work was to design a method called the SARS-CoV-2 antibody detection method (SARS-CoV-2 AbDM) for fluorescence immunodetection of anti-SARS-CoV-2 IgG and IgM on both plate and microfluidic chip. For this purpose, a system with magnetic beads that immobilize the antigen (S protein and RBD) on its surface was used to determine the presence and quantity of antibodies in a sample in a single reaction. The SARS-CoV-2 AbDM led to several advantages in the performance of the tests, such as reduced cost, possibility of performing isolated or multiple samples, potential of multiplex detection, and capacity to detect whole blood samples without losing resolution. In addition, due to the microfluidic chip in conjunction with the motorized actuated platform, the time, sample quantity, and operator intervention during the process were reduced. All these advantages suggest that the SARS-CoV-2 AbDM has the potential to be developed as a PoC that can be used as a tool for seroprevalence monitoring, allowing a better understanding of the epidemiological and clinical characteristics of COVID-19 and contributing to more effective and ethical decision-making in strategies to fight against the COVID-19 pandemic.
Fence detection in Amsterdam: transparent object segmentation in urban context
Authors: Ypenga Jorrit , Sukel Maarten , Alavi Hamed S.
Published: July 2023

Introduction

Accessibility and safe movement in urban areas entail infrastructure that minimizes the risks for pedestrians and bikers with diverse levels of abilities. Recognizing and mapping unsafe areas can increase awareness among citizens and inform city projects to improve their infrastructure. This contribution presents an example in which the specific objective is to recognize the unprotected areas around the canals in the city of Amsterdam.

Method

This is accomplished through running image processing algorithms on 11K waterside panoramas taken from the city of Amsterdam's open data portal. We created an annotated subset of 2K processed images for training and evaluation. This dataset debuts a novel pixel-level annotation style using multiple lines. To determine the best inference practice, we compared the IoU and robustness of several existing segmentation frameworks.

Results

The best method achieves an IoU of 0.79. The outcome is superimposed on the map of Amsterdam, showing the geospatial distribution of the low, middle, and high fences around the canals.

Discussion

In addition to this specific application, we discuss the broader use of the presented method for the problem of “transparent object detection” in an urban context.
The value of left atrial longitudinal strain in evaluating left atrial appendage spontaneous echo contrast in non-valvular atrial fibrillation
Authors: Ma Chang sheng , Sun Shi kun , Wang Li , Zhou Bing yuan , Dong Feng lin
Published: July 2023

Background

Spontaneous echo contrast (SEC) observed in transesophageal echocardiography (TEE) is a reliable predictor of the risk of future ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Left atrial strain globally reflects atrial function, remodeling and distensibility. The left atrial appendage (LAA) is a myogenic remnant of the left atrium, which can actively relax and contract. The left atrial appendage (LAA) is an important part of releasing the pressure of the left atrium. The key role of the left atrium is to regulate the left ventricular filling pressure, act as a reservoir for pulmonary venous return during ventricular contraction, and act as a conduit, transferring blood to the Left ventricle during early ventricular diastole. The purpose of this study was to explore the relationship between left atrial function and left atrial appendage spontaneous echo contrast (LAASEC).

Methods

A retrospective study of 338 patients with non-valvular AF was conducted. Two-dimensional speckle-tracking echocardiography provided the following metrics of LA strain: LA strain during the reservoir phase (LASr), LA strain during the conduit phase (LAScd). LA or LAA has the dense SEC of more than grade 3, which is defined as mud like change or pre thrombosis.

Results

Patients with level 3 SEC (n = 81) has lower LASr than those with lower grades of SEC (n = 257) (7.20 ± 3.70 vs. 17.48 ± 8.67, P < 0.001). Multivariate logistic regression model showed that the type of atrial fibrillation (persistent∼), increased heart rate, decreased LASr were independently associated with the dense LAASEC (OR (CI 95%), 5.558 (1.618–19.09), 1.016 (1.006–1.026) 0.002, 1.224 (1.085–1.381), both P < 0.01). Venn Diagram showed that lower CHADVASC2 score groups had dense SEC cases. Receiver operating characteristic (ROC) curve was used for analyzing results and selecting cut off values. The cut off point for LASr < 8.85% and CHADVASC2 score was >2 scores with sensitivity and specificity were 79% and 85%.

Conclusion

Lower LASr is independently associated with the dense LAASEC in NVAF and has incremental values superior to clinical scores. The decrease of LASr may be a potential non-invasive parameter for evaluating the higher risk of LAA thrombosis.
Paleopathological characteristics of Neolithic early rice farmers in the lower reaches of the Yangtze river
Authors: Sawada Junmei , Sun Guoping , Huang Weijin , Kubota Shinji , Saeki Fumiko , Okazaki Kenji , Yoneda Minoru , Nakamura Shin’ichi
Published: July 2023

Paleopathological investigations of human remains from the Neolithic Hemudu culture in the lower reaches of the Yangtze River in southern East Asia were conducted to clarify the health status of people in early rice-farming societies. Our results show that the occurrence ratios of cribra orbitalia and enamel hypoplasia did not differ significantly between early rice farmers and hunter-gatherers. By contrast, the occurrence ratios of periosteal reactions, dental caries, and antemortem tooth loss in adults were higher among the early rice farmers. Based on these findings and the results of archaeological research on the Hemudu culture, it was suggested that: 1) the Hemudu culture adopted a diversified livelihood strategy that was not overly dependent on rice as a food resource, which did not lead to an extreme decline in health status, 2) the work in the rice fields or the working environment caused stress to the workers, and 3) the rice-farming society’s dietary habits led to a decline in oral health. Our results provide new paleopathological insights into the health status of early rice farmers in East Asia. However, the sample size of early rice farmers used in this study was small, and more data are needed to verify the validity of the views presented here.
Snow identification from unattended automatic weather stations images using DANet
Authors: Gong Jie , Wang Yonghua , Liu Min , Deng Fan
Published: July 2023

Identifying snow phenomena in images from automatic weather station (AWS) is crucial for live weather monitoring. In this paper, we propose a convolutional neural network (CNN) based model for snow identification using images from AWS cameras. The model combines the attention mechanism of the DANet model with the classical residual network ResNet-34 to better extract the features of snow cover in camera images. To improve the generalizability of the model, we also use images from public datasets in addition to images taken by cameras from unmanned weather stations. Our results show that the proposed model achieved a POD of 91.65%, a FAR of 7.34% and a TS score of 85.45%, demonstrating its effectiveness in snow identification. This study has the potential to facilitate more efficient and effective weather monitoring in a variety of locations.
Characteristics of high-quality early childhood education and care: a study from Australia
Authors: Phillips Alicia , Boyd Wendy
Published: July 2023

The early childhood environment influences a young child's growth, wellbeing, and development, and the young child's environment determines lifelong outcomes. The impact of the environment on children's developing brain capacity has been shown to affect the hard wiring that occurs in the 1st years of life. Brain development in the early years is shaped and formed in response to environmental experiences. The learning environment in early childhood education and care (ECEC) services is designed by the early childhood educators—for example, by establishing and implementing routines, deciding on how to resource the environment, and developing and maintaining relationships with children, families, and staff. The Australian Children's Education and Care Quality Authority (ACECQA) has developed and implemented a national quality standard (NQS) that addresses the quality of the learning environment in ECEC services. The NQS comprises seven quality areas that early childhood educators implement. Even though early childhood educators are the key decision-makers in implementing quality learning experience for children, their perspectives on the NQS have not been heard. This study presents the early childhood educators' perspectives on the characteristics of long day care (LDC) centers (for children aged from birth to 5 years) that they perceived to be important for provision of high-quality ECEC. Findings are presented from 15 interviews with early childhood educators regarding their perspectives of what characteristics enabled their LDC center to be assessed as Exceeding the NQS, one of the highest quality ratings possible. Findings indicate that the educator characteristics and their qualities in leadership and teamwork were important in determining high-quality ECEC. However, while the educators' attributes were deemed important, it was clear that there was an interconnectedness of factors including the relationships between children, families, and educators, the financial capacity, the governance, and structure of the LDC center that contributed to the provision of high-quality ECEC. Recommendations are that LDC centers could be incentivised to provide professional learning for staff leadership, teamwork, and capability to provide high-quality ECEC.
Predictive nomogram for central lymph node metastasis in papillary thyroid microcarcinoma based on pathological and ultrasound features
Authors: Wang Denghui , Hu Ji , Deng Chang , Yang Zhixin , Zhu Jiang , Su Xinliang
Published: July 2023

Background

Central lymph node metastases (CLNM) in papillary thyroid microcarcinoma (PTMC) are common, but management through prophylactic central lymph node dissection (pCLND) remains controversial. In this study, the independent predictors of CLNM in PTMC were retrospectively studied based on ultrasound and pathological data, and we aim to establish the prediction model to predict CLNM in PTMC.

Methods

This study included a total of 1,506 patients who underwent thyroid surgery for PTMC at the First Affiliated Hospital of Chongqing Medical University from 2015 to 2018. Ultrasound and clinicopathological features were summarized and analyzed. Univariate and multivariate analyses were performed to determine the risk factors associated with CLNM. The prediction model is established and verified according to the multivariate analysis results. The Kaplan–Meier curve was used to evaluate the effect of CLNM on survival.

Results

The CLNM rate was 44.5% (670/1,506). Multivariate analysis showed that men, younger age, smaller diameter, ETE, microcalcification, without Hashimoto’s thyroiditis, and multifocal were independent risk predictors of CLNM. Nomogram has a good discriminative ability (C-index: 0.755 in the validation group), and the calibration effect is good. In the DCA curve, the CLNM prediction model performed better net benefit given any high-risk thresholds. The median follow-up time was 30 months (12–59 months), 116 cases were lost, and the follow-up rate was 92.8% (1,506/1,622). Of the 1,506 patients included, 12 (0.8%) experienced recurrence.

Conclusion

The likelihood of CLNM can be objectively quantified before surgery by using this reliable and accurate nomogram that combines preoperative ultrasound with clinicopathological features. Clinicians can use this nomogram to assess central lymph node status in patients with PTMC and consider prophylactic CND in patients with high scores.
New potential biomarkers for early chronic kidney disease diagnosis in patients with different glucose tolerance status
Authors: Cassano Velia , Pelaia Corrado , Armentaro Giuseppe , Miceli Sofia , Tallarico Valeria , Perini Daniele Dallimonti , Fiorentino Vanessa T. , Imbalzano Egidio , Maio Raffaele , Succurro Elena , Hribal Marta L. , Andreozzi Francesco , Sesti Giorgio , Sciacqua Angela
Published: July 2023

Background

The purpose of the present study was to investigate the role of oxidative stress, platelet activation, and endocan levels in renal dysfunction in normal glucose tolerance (NGT) patients with 1-h plasma glucose values ≥155 mg/dl (NGT ≥ 155), compared to NGT < 155, impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) newly diagnosed subjects. We enlisted 233 patients subjected to an oral glucose tolerance test (OGTT).

Materials and methods

The serum levels of platelet activation (glycoprotein VI and sP-selectin), oxidative stress biomarkers (8-isoprostane and Nox-2), and endocan were evaluated using an ELISA test.

Results

Among NGT < 155 patients and the T2DM group, there was a statistically significant increase in 8-isoprostane (p < 0.0001), Nox-2 (p < 0.0001), glycoprotein VI (p < 0.0001), and sP-selectin (p < 0.0001) serum levels. Higher serum endocan levels were found with the worsening of metabolic profile (p < 0.0001); specifically, NGT ≥ 155 patients presented higher serum endocan values when compared to NGT < 155 patients (p < 0.0001). From the multivariate linear regression analysis, 1-h glucose resulted in the major predictor of estimated glomerular filtration rate (e-GFR) justifying 23.6% of its variation (p < 0.0001); 8-isoprostane and Nox-2 added respectively another 6.0% (p < 0.0001) and 3.2% (p = 0.001).

Conclusion

Our study confirmed the link between 1-h post-load glucose ≥155 mg/dl during OGTT and the possible increased risk for chronic kidney disease (CKD) in newly diagnosed patients. The novelty is that we demonstrated a progressive increase in oxidative stress, platelet activation, and serum endocan levels with the worsening of metabolic profile, which becomes evident early during the progression of CKD.
Optimal glycated hemoglobin A1c value for prediabetes and diabetes in patients with pancreatic diseases
Authors: Chen Guanhua , Zhang Rui , Tan Chunlu , Liu Xubao , Yu Lei , Chen Yonghua
Published: July 2023

Background

Some articles suggest that using HbA1c alone for diabetes diagnosis is inappropriate. It requires considerable researches to explore the efficacy of HbA1c for diagnosing hyperglycemia in patients with pancreatic disease.

Methods

This study analyzed 732 patients, comprising of 331 without pancreatic disease and 401 patients diagnosed with pancreatic diseases. All participants underwent the HbA1c assay and oral glucose tolerance test. Kappa coefficients were calculated to assess agreement between the HbA1c and glucose criteria. The receiver operating characteristic curve (ROC) was used to calculate the optimal HbA1c value. DeLong test was analyzed to compared the aera under curves (AUCs).

Results

There were 203 (61.3%) patients with NGT, 78 (23.6%) with prediabetes, and 50 (15.1%) with diabetes in patients without pancreatic diseases. In patients with pancreatic disease, 106 participants were diagnosed with NGT (36.4%), 125 with prediabetes (31.2%), and 130 with diabetes (32.4%). Patients with pancreatic disease exhibited elevated levels of bilirubin, transaminase enzymes, aspartate transaminase, high density lipoprotein cholesterol and total bile acid. The sensitivity and specificity of the HbA1c (6.5%) for diagnosing pancreatic diabetes were 60.8% (95% CI 52.3, 69.3) and 92.6% (95% CI 89.5, 95.7). In prediabetes, the sensitivity and specificity of HbA1c (5.7%) is 53.2% (44.3, 62.0) and 59.6 (51.5, 67.6). The optimal HbA1c value for diagnosing diabetes was 6.0% (AUC = 0.876, 95% CI 0.839, 0.906), with the sensitivity of 83.8% and the specificity of 76.8%. The optimal HbA1c value for the diagnosis of prediabetes was 5.8% (AUC = 0.617, 95% CI: 0.556, 0.675), with the corresponding sensitivity and specificity of 48.0% and 72.6% respectively. The combined tests (HbA1c, 6.0% or FPG, 7.0mmol/L) presented the sensitivity of 85.7% (95% CI 79.1, 91.3)and the specificity of 92.6% (95% CI 87.6, 97.3) in pancreatic diabetes.

Conclusion

From our results, the recommended HbA1c by ADA criterion may not be sufficiently sensitive to diagnose hyperglycemia in pancreatic disease. The optimal value of 5.8% and 6.0% improved the accuracy for diagnosing prediabetes and diabetes and should be considered to be applied. Besides, we advocate the combination of HbA1c and FPG test for the diagnosis of diabetes in patients with pancreatic diseases.
Improving solar radiation source efficiency using adaptive dynamic squirrel search optimization algorithm and long short-term memory
Authors: Khafaga Doaa Sami , Alhussan Amel Ali , Eid Marwa M. , El-kenawy El-Sayed M.
Published: July 2023

Artificial intelligence and machine learning are used to optimize the design parameters of renewable energy sources, which are now regarded as vital components in current clean energy sources. As a result, system requirements can be reduced, and a well-designed system can improve performance. Artificial intelligence approaches in renewable energy sources and system design would significantly cut optimization time while maintaining high modeling accuracy and optimum performance. This study examines machine learning in depth, emphasizing how it can be used in developing renewable energy sources because of the vast range of technologies it can use. This paper approximates the hourly tilted solar irradiation using climate factors. The irradiance is estimated using a hybrid ensemble-learning approach. This approach combines a proposed adaptive dynamic squirrel search optimization algorithm (ADSSOA) with long short-term memory (LSTM) methods. To the best of our knowledge, this combination has not been used for solar radiation. The results are analyzed and contrasted with the outcomes of several recent swarm intelligence algorithms, such as the genetic algorithm, particle swarm optimization, and gray wolf optimizer. The binary ADSSOA approach performed as expected, with an average error of 0.1801 and a standard deviation of 0.0656. The ADSSOA–LSTM model had the lowest root mean square error (0.000388) compared to LSTM’s (0.001221). In addition, the statistical analysis uses 10 iterations of each presented and evaluated method to provide accurate comparisons and reliable results.
A method review of the climate change impact on crop yield
Authors: Feng Xinyao , Tian Haoliang , Cong Jiahui , Zhao Chuang
Published: July 2023

Climate change significantly impacts global agricultural production, giving rise to considerable uncertainties. To explore these climate impacts, three independent methods have been employed: manipulated experiments, process-based crop models, and empirical statistical models. However, the uncertainty stemming from the use of different methods has received insufficient attention, and its implications remain unclear, necessitating a systematic review. In this study, we conducted a comprehensive review of numerous previous studies to summarize the historic development and current status of each method. Through a method comparison, we identified their respective strengths, limitations, and ideal areas of application. Additionally, we outlined potential prospects and suggested directions for future improvements, including clarifying the response mechanisms, updating simulation technologies, and developing multi-method ensembles. By addressing the knowledge gap regarding method differences, this review could contribute to a more accurate assessment of climate impacts on agriculture.
Effect of antiviral and immunomodulatory treatment on a cytokine profile in patients with COVID-19
Authors: Martonik Diana , Parfieniuk-Kowerda Anna , Starosz Aleksandra , Grubczak Kamil , Moniuszko Marcin , Flisiak Robert
Published: July 2023

Background

The severity of COVID-19 is associated with an elevated level of a variety of inflammatory mediators. Increasing evidence suggests that the Th17 response contributes to the severity of COVID-19 pneumonia, whereas Th22 response plays a regulatory role in SARS-CoV-2 infection. Two main types of available COVID-19 treatments are antivirals and immunomodulatory drugs; however, their effect on a cytokine profile is yet to be determined.

Methods

This study aim to analyse a cytokine profile in peripheral blood from patients with COVID-19 (n=44) undergoing antiviral or/and immunomodulatory treatment and healthy controls (n=20). Circulating CD4+ and CD8+ T cells and their intracellular expression of IL-17A and IL-22 were assessed by flow cytometry.

Results

Initial results showed an overexpression of IL-17F, IL-17A, CCL5/RANTES, GM-CSF, IL-4, IL-10, CXCL-10/IP-10 and IL-6 in COVID-19 patients compared to healthy controls. Treatment with remdesivir resulted in a significant decline in concentrations of IL-6, IL-10, IFN-alpha and CXCL10/IP-10. Immunomodulatory treatment contributed to a significant downregulation of IL-10, IFN-alpha, CXCL10/IP-10 and B7-H3 as well as upregulation of IL-22 and IL-1 beta. A combination of an antiviral and immunomodulatory treatment resulted in a significant decrease in IL-17F, IL-10, IFN-alpha, CXCL10/IP-10 and B7-H3 levels as well as an increase in IL-17A and IL-1 beta. We found significantly higher percentage of both CD4+ and CD8+ T cells producing IL-17A and CD4+ T cells producing IL-22 in patients with COVID-19.

Conclusion

Administration of antiviral or/and immunomodulatory treatment resulted in a significant downregulation of pro-inflammatory cytokine expression and an upregulation of T cell absolute counts in most cases, thus showing effectiveness of treatment in COVID-19. SARS-CoV-2 infection induced cytokine overexpression in hospitalized patients with COVID-19 as well as lymphopenia, particularly a decrease in CD4+ and CD8+ T cell counts. Moreover, despite the reduced counts of CD4+ and CD8+ T cells, both subsets showed overactivation and increased expression of IL-17A and IL-22, thus targeting Th17 response might alleviate inflammatory response in severe disease.
External control arms: COVID-19 reveals the merits of using real world evidence in real-time for clinical and public health investigations
Authors: Silva Patrick , Janjan Nora , Ramos Kenneth S. , Udeani George , Zhong Lixian , Ory Marcia G. , Smith Matthew Lee
Published: July 2023

Randomized controlled trials are considered the ‘gold standard’ to reduce bias by randomizing patients to an experimental intervention, versus placebo or standard of care cohort. There are inherent challenges to enrolling a standard of care or cohorts: costs, site engagement logistics, socioeconomic variability, patient willingness, ethics of placebo interventions, cannibalizing the treatment arm population, and extending study duration. The COVID-19 pandemic has magnified aspects of constraints in trial recruitment and logistics, spurring innovative approaches to reducing trial sizes, accelerating trial accrual while preserving statistical rigor. Using data from medical records and databases allows for construction of external control arms that reduce the costs of an external control arm (ECA) randomized to standard of care. Simultaneously examining covariates of the clinical outcomes in ECAs that are being measured in the interventional arm can be particularly useful in phase 2 trials to better understand social and genetic determinants of clinical outcomes that might inform pivotal trial design. The FDA and EMA have promulgated a number of publicly available guidance documents and qualification reports that inform the use of this regulatory science tool to streamline clinical development, of phase 4 surveillance, and policy aspects of clinical outcomes research. Availability and quality of real-world data (RWD) are a prevalent impediment to the use of ECAs given such data is not collected with the rigor and deliberateness that characterizes prospective interventional control arm data. Conversely, in the case of contemporary control arms, a clinical trial outcome can be compared to a contemporary standard of care in cases where the standard of care is evolving at a fast pace, such as the use of checkpoint inhibitors in cancer care. Innovative statistical methods are an essential aspect of an ECA strategy and regulatory paths for these innovative approaches have been navigated, qualified, and in some cases published.
Cognition in older adults with healthy aging: analysis of the Mexican Health and Aging Study 2012–2015
Authors: Yeverino-Castro Sara G. , Garza-Guerra José D. , Aguilar-Díaz Gabriela E. , González-Galván Célica R. , Salinas-Martínez Ricardo , Morales-Delgado Rocío
Published: July 2023

Introduction

Maintaining older adults’ health and well-being can be achieved through the optimization of physical and mental health, while preserving independence, social participation, and quality of life. Cognitive change has been described as a normal process of aging and it involves domains such as processing speed, attention, memory, language, visuospatial abilities, and executive functioning, among others.

Objective

To describe cognitive changes in older adults with healthy aging.

Methods

This is a study that involved data from 14,893 and 14,154 individuals aged >60 years or older from the 2012 and 2015 waves, respectively, who participated in the Mexican Health and Aging Study (MHAS). Participants with healthy aging were identified and described in the MHAS-2012 wave and followed to 2015. Eight cognitive domains evaluated in the Cross-Cultural Cognitive Evaluation (CCCE,) as well as sociodemographic and health characteristics, were described. Criteria for healthy aging involved the following: CCCE ≥ −1.5 standard deviations above the mean on reference norms, independence on basic and instrumental activities of daily living, self-reported “life close to ideal,” and preserved functional and social performance.

Results

From a total of n = 9,160 older adults from the MHAS-2012 wave, n = 1,080 (11.8%) had healthy aging. In the healthy aging group, the median age was 67 years (IQR: 63–73), 58.1% were female and the median for education was 6 (IQR: 3–8) years. The mean CCCE score was 57 (SD: 16.9) points. In the MHAS-2012 cross-sectional analysis, except for orientation, visuospatial abilities, and verbal fluency, all cognitive domain scores were lower with passing age. When comparing cognitive domain scores in the 225 older adults identified with healthy aging between the 2012 and 2015 MHAS waves, there were almost no observable differences.

Conclusion

In the cross-sectional analysis, Mexican adults with healthy aging had lower scores in the verbal learning memory, visual scanning, numeracy, visual memory, and verbal recall domains’, as well as lower global cognitive scores in the higher age groups. There were no cognitive changes in the 3 year follow-up, except for a lower gradient of scores in the verbal recall memory domain. Longer prospective studies are needed to characterize greater cognitive changes.
Mining of key genes for cold adaptation from Pseudomonas fragi D12 and analysis of its cold-adaptation mechanism
Authors: Bao Changjie , Li Muzi , Zhao Xuhui , Shi Jia , Liu Yehui , Zhang Na , Zhou Yuqi , Ma Jie , Chen Guang , Zhang Sitong , Chen Huan
Published: July 2023

The psychrotroph Pseudomonas fragi D12, which grew strongly under low temperatures, was screened from tundra soil collected from the permanent alpine zone on Changbai Mountain. To mine the genes critical for cold tolerance and to investigate the cold-adaptation mechanism, whole-genome sequencing, comparative genomic analysis, and transcriptome analysis were performed with P. fragi. A total of 124 potential cold adaptation genes were identified, including nineteen unique cold-adaptive genes were detected in the genome of P. fragi D12. Three unique genes associated with pili protein were significantly upregulated at different degrees of low temperature, which may be the key to the strong low-temperature adaptability of P. fragi D12. Meanwhile, we were pleasantly surprised to find that Pseudomonas fragi D12 exhibited different cold-adaptation mechanisms under different temperature changes. When the temperature declined from 30°C to 15°C, the response included maintenance of the fluidity of cell membranes, increased production of extracellular polymers, elevation in the content of compatibility solutes, and reduction in the content of reactive oxygen species, thereby providing a stable metabolic environment. When the temperature decreased from 15°C to 4°C, the response mainly included increases in the expression of molecular chaperones and transcription factors, enabling the bacteria to restore normal transcription and translation. The response mechanism of P. fragi D12 to low-temperature exposure is discussed. The results provide new ideas for the cold-adaptation mechanism of cold-tolerant microorganisms.
Characteristics and influencing factors of 11C-CFT PET imaging in patients with early and late onset Parkinson’s disease
Authors: Kangli Fan , Hongguang Zhao , Yinghua Li , Xiaoxiao Du , Yuyin Dai , Lulu Gao , Yi Li , Zhihui Sun , Ying Zhang
Published: July 2023

Objective

This study aims to explore the difference between 11C-methyl-N-2β-carbomethoxy-3β-(4-fluorophenyl)-tropanel (11C-CFT) positron emission tomography (PET) imaging in the early-onset Parkinson’s disease (EOPD) and late-onset Parkinson’s disease (LOPD), and to analyze the correlation between 11C-CFT PET imaging and disease duration, Hoehn & Yahr (H&Y) stage, motor symptoms, and non-motor symptoms in patients with idiopathic Parkinson’s disease (PD), so as to explore its application value in assessing the severity of Parkinson’s disease.

Materials and methods

A total of 113 patients with idiopathic PD were included in this study. The patients were divided into EOPD and LOPD groups according to the age of 60 years, of which 58 were early-onset and 55 were late-onset. All patients underwent 11C-CFT PET imaging and manually sketched regions of interest (ROI) to delineate the caudate nucleus, anterior putamen, and posterior putamen ROI layer-by-layer, and the corresponding values were recorded. Clinical data [age of onset, disease duration, H&Y stage, total Unified Parkinson’s Disease Rating Scale (UPDRS) score, UPDRS III score, tremor score, postural instability/gait difficulty (PIGD) score, rigidity score, bradykinesia score, and Montreal Cognitive Assessment (MoCA) score] were collected from all patients. The differences in striatal 11C-CFT uptake between patients with EOPD and LOPD were compared, and the correlation between striatal 11C-CFT uptake and the clinical data of patients with idiopathic PD was evaluated.

Results

The caudate nucleus 11C-CFT uptake was higher in EOPD than in the LOPD group (t = 3.002, p = 0.003). 11C-CFT uptake in the caudate nucleus in patients with PD was negatively correlated with the age of onset, H&Y stage, disease duration, total UPDRS score, UPDRS III score, rigidity score, and bradykinesia score (p < 0.05). The anterior and posterior putamen 11C-CFT uptake was negatively correlated with H&Y stage, disease duration, total UPDRS score, UPDRS III score, PIGD score, rigidity score, and bradykinesia score (p < 0.05).

Conclusion

11C-CFT PET provides an objective molecular imaging basis for the difference in disease progression rates between patients with EOPD and LOPD. Secondly, 11C-CFT PET can be used as an important objective indicator to assess disease severity and monitor disease progression.
Peptide receptor radionuclide therapy in advanced Pheochromocytomas and Paragangliomas: a systematic review and meta-analysis
Authors: Su Dan , Yang Hongyu , Qiu Chen , Chen Yue
Published: July 2023

Objective

Peptide receptor radionuclide therapy (PRRT) for advanced pheochromocytomas and paragangliomas (PPGLs) has received increasing attention. The purpose of this article is to evaluate the efficacy and safety of PRRT in patients with metastatic or inoperable PPGLs by meta-analysis.

Methods

A literature search was conducted in PubMed, Embase, Scopus, and Cochrane Library databases up to November 2022. All articles on PRRT for PPGLs were searched, and appropriate data were included for analysis. The measures evaluated included objective response rate (ORR), disease control rate (DCR), clinical response rate, biochemical response rate, progression-free survival (PFS), overall survival (OS), and adverse events. Statistical analysis was performed using Stata 16.0 and the R programming language, data were combined using a random-effects model, and the results were presented using forest plots.

Results

A total of 20 studies with 330 patients were included in the analysis. The results showed that ORR and DCR were 20.0% (95% CI: 12.0%-28.0%) and 90.0% (95% CI: 85.0%-95.0%), respectively. Clinical and biochemical responses were 74.9% (95% CI: 56.3%-90.2%) and 69.5% (95%CI: 40.2%-92.9%). Median PFS and median OS were 31.79 (95% CI:21.25-42.33) months and 74.30 (95% CI: 0.75-147.84) months, respectively. Any grade of hematotoxicity and nephrotoxicity occurred in 22.3% (95% CI:12.5%-33.5%) and 4.3% (95% CI:0.2%-11.4%) patients. Grade 3-4 hemotoxicity occurred in 4.3% (95% CI:0.2%-11.4%) and grade 3-4 nephrotoxicity in 4/212 patients. Additionally, Treatment was discontinued in 9.0% (95% CI: 0.5%-23.3%) patients and one patient died as a result of a toxicity.

Conclusion

Patients with metastatic or inoperable PPGLs can be effectively treated with PRRT, and it has a favorable safety profile.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022359232.
Diagnostic value of Kaiser score combined with breast vascular assessment from breast MRI for the characterization of breast lesions
Authors: Zhou Xin-zhu , Liu Lian-hua , He Shuang , Yao Hui-fang , Chen Li-ping , Deng Chen , Li Shuang-Ling , Zhang Xiao-yong , Lai Hua
Published: July 2023

Objectives

The Kaiser scoring system for breast magnetic resonance imaging is a clinical decision-making tool for diagnosing breast lesions. However, the Kaiser score (KS) did not include the evaluation of breast vascularity. Therefore, this study aimed to use KS combined with breast vascular assessment, defined as KS*, and investigate the effectiveness of KS* in differentiating benign from malignant breast lesions.

Methods

This retrospective study included 223 patients with suspicious breast lesions and pathologically verified results. The histopathological diagnostic criteria were according to the fifth edition of the WHO classification of breast tumors. The KS* was obtained after a joint evaluation combining the original KS and breast vasculature assessment. The receiver operating characteristic (ROC) curve was used for comparing differences in the diagnostic performance between KS* and KS, and the area under the receiver operating characteristic (AUC) was compared.

Results

There were 119 (53.4%) benign and 104 (46.6%) malignant lesions in total. The overall sensitivity, specificity, and accuracy of increased ipsilateral breast vascularity were 69.2%, 76.5%, and 73.1%, respectively. The overall sensitivity, specificity, and accuracy of AVS were 82.7%, 76.5%, and 79.4%, respectively. For all lesions included the AUC of KS* was greater than that of KS (0.877 vs. 0.858, P = 0.016). The largest difference in AUC was observed in the non-mass subgroup (0.793 vs. 0.725, P = 0.029).

Conclusion

Ipsilaterally increased breast vascularity and a positive AVS sign were significantly associated with malignancy. KS combined with breast vascular assessment can effectively improve the diagnostic ability of KS for breast lesions, especially for non-mass lesions.
Detection of KRAS mutation using plasma samples in non-small-cell lung cancer: a systematic review and meta-analysis
Authors: Cai Peiling , Yang Bofan , Zhao Jiahui , Ye Peng , Yang Dongmei
Published: July 2023

Background

The aim of this study was to investigate the diagnostic accuracy of KRAS mutation detection using plasma sample of patients with non-small cell lung cancer (NSCLC).

Methods

Databases of Pubmed, Embase, Cochrane Library, and Web of Science were searched for studies detecting KRAS mutation in paired tissue and plasma samples of patients with NSCLC. Data were extracted from each eligible study and analyzed using MetaDiSc and STATA.

Results

After database searching and screening of the studies with pre-defined criteria, 43 eligible studies were identified and relevant data were extracted. After pooling the accuracy data from 3341 patients, the pooled sensitivity, specificity and diagnostic odds ratio were 71%, 94%, and 59.28, respectively. Area under curve of summary receiver operating characteristic curve was 0.8883. Subgroup analysis revealed that next-generation sequencing outperformed PCR-based techniques in detecting KRAS mutation using plasma sample of patients with NSCLC, with sensitivity, specificity, and diagnostic odds ratio of 73%, 94%, and 82.60, respectively.

Conclusion

Compared to paired tumor tissue sample, plasma sample showed overall good performance in detecting KRAS mutation in patients with NSCLC, which could serve as good surrogate when tissue samples are not available.
Extracellular volume fraction using contrast-enhanced CT is useful in differentiating intrahepatic cholangiocellular carcinoma from hepatocellular carcinoma
Authors: Honda T. , Onishi H. , Fukui H. , Yano K. , Kiso K. , Nakamoto A. , Tsuboyama T. , Ota T. , Tatsumi M. , Tahara S. , Kobayashi S. , Eguchi H. , Tomiyama N.
Published: July 2023

Objectives

To evaluate whether tumor extracellular volume fraction (fECV) on contrast-enhanced computed tomography (CT) aids in the differentiation between intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC).

Methods

In this retrospective study, 113 patients with pathologically confirmed ICC (n = 39) or HCC (n = 74) who had undergone preoperative contrast-enhanced CT were enrolled. Enhancement values of the tumor (Etumor) and aorta (Eaorta) were obtained in the precontrast and equilibrium phase CT images. fECV was calculated using the following equation: fECV [%] = Etumor/Eaorta × (100 – hematocrit [%]). fECV values were compared between the ICC and HCC groups using Welch’s t-test. The diagnostic performance of fECV for differentiating ICC and HCC was assessed using receiver-operating characteristic (ROC) analysis. fECV and the CT imaging features of tumors were evaluated by two radiologists. Multivariate logistic regression analysis was performed to identify factors predicting a diagnosis of ICC.

Results

Mean fECV was significantly higher in ICCs (43.8% ± 13.2%) than that in HCCs (31.6% ± 9.0%, p < 0.001). The area under the curve for differentiating ICC from HCC was 0.763 when the cutoff value of fECV was 41.5%. The multivariate analysis identified fECV (unit OR: 1.10; 95% CI: 1.01–1.21; p < 0.05), peripheral rim enhancement during the arterial phase (OR: 17.0; 95% CI: 1.29–225; p < 0.05), and absence of washout pattern (OR: 235; 95% CI: 14.03–3933; p < 0.001) as independent CT features for differentiating between the two tumor types.

Conclusions

A high value of fECV, peripheral rim enhancement during the arterial phase, and absence of washout pattern were independent factors in the differentiation of ICC from HCC.
Therapeutic drug monitoring of lacosamide among children: is it helpful?
Authors: Kohn Elkana , Lezinger Mirit , Daniel Sharon , Masarwi Majdi , Brandriss Nurit , Bar-Chaim Adina , Berkovitch Matitiahu , Heyman Eli , Komargodski Rinat
Published: July 2023

Objective: This study aimed to investigate the efficacy and tolerability of Lacosamide (LCM) in a pediatric population with epilepsy using LCM serum concentration and its correlation to the age of the participants and the dosage of the drug.

Methods: Demographic and clinical data were collected from the medical records of children with epilepsy treated with LCM at Shamir Medical Center between February 2019 to September 2021, in whom medication blood levels were measured. Trough serum LCM concentration was measured in the biochemical laboratory using High-Performance Liquid Chromatography (HPLC) and correlated with the administered weight-based medication dosing and clinical report.

Results: Forty-two children aged 10.43 ± 5.13 years (range: 1–18) were included in the study. The average daily dose of LCM was 306.62 ± 133.20 mg (range: 100–600). The average number of seizures per day was 3.53 ± 7.25 compared to 0.87 ± 1.40 before and after LCM treatment, respectively. The mean LCM serum concentration was 6.74 ± 3.27 mg/L. No statistically significant association was found between LCM serum levels and the clinical response (p = 0.58), as well as the correlation between LCM dosage and the change in seizure rate (p = 0.30). Our study did not find a correlation between LCM serum concentration and LCM dosage and the gender of the participants: males (n = 17) females (n = 23) (p = 0.31 and p = 0.94, respectively). A positive trend was found between age and LCM serum concentrations (r = 0.26, p = 0.09).

Conclusion: Based on the data that has been obtained from our study, it appears that therapeutic drug monitoring for LCM may not be necessary. Nonetheless, further research in this area is needed in the light of the relatively small sample size of the study.