bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase II study on the efficacy of regorafenib in treating patients with c-KIT-mutated metastatic malignant melanoma that progressed after previous treatment (KCSG-UN-14-13)
Authors: Kim Kyoo Hyun , Jung Minkyu , Lee Hyo Jin , Lee Su Jin , Kim Miso , Ahn Mi Sun , Choi Moon Young , Lee Na-Ri , Shin Sang Joon
Published: May 2023

Background c-KIT mutations are found in approximately 15% of the patients with malignant melanoma; agents such as imatinib have previously shown high response rates. Regorafenib, an oral multikinase inhibitor, acts against wild-type and mutant KIT. This multi-institutional phase II single-arm study aimed to evaluate the efficacy of regorafenib against metastatic malignant melanoma harboring the c-KIT mutation.Methods Patients with recurrent/metastatic melanoma positive for c-KIT mutations, whose disease progressed after at least one line of systemic treatment, were eligible. The patients received oral regorafenib 160 mg once daily for 3 weeks (4-week cycle). The primary endpoint was the disease control rate (DCR), and the secondary endpoints were safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).Results In all, 153 patients were screened for c-KIT mutations and 23 patients were enrolled (December 2014–January 2022). c-KIT mutations were frequently reported in exon 11 (14/23, 60.9%), followed by exons 13, 17, and 9 in 5 (21.7%), 5 (21.7%), and 2 (8.7%) patients, respectively. The DCR at 8 weeks was 73.9%, with 2 patients (8.7%) achieving CR, 5 (21.7%) achieving PR, and 10 (43.5%) showing stable disease. The ORR was 30.4% (7/23). The median follow-up period was 15.2 months (95% confidence interval [CI], 10.0–21.5), and median OS and PFS were 21.5 months (95% CI, 15.1–27.9) and 7.1 months (95% CI, 5.0–9.2), respectively. Circulating tumor DNA (ctDNA) analysis in selected patients showed high c-KIT correlation (85.7%) with tissue-based tumor mutational profiles. Skin reactions, including Palmar-plantar erythrodysesthesia (52.2%) and skin rash (30.4%) were the most common adverse events (AEs). Grade 3 AEs, including infection, rash, mucositis, and marrow suppression, occurred in 9 patients (39.1%).Conclusion Regorafenib in second- or later-line settings demonstrated significant activity in patients with metastatic melanoma harboring c-KIT mutations, with an ORR of 30.4% and DCR of 73.9%.Trial registration ClinicalTrials.gov NCT02501551, registered Jul 17, 2015.
STAT3-mediated ferroptosis is involved in α-synuclein pathology
Authors: Zhang Han , Jing Xiuna , Zhang Jieli , Huang Kaixun , Chen Ying , Shen Qingyu , Tao Enxiang , Lin Danyu
Published: May 2023

BackgroundOligomeric α-synuclein (α-syn) can activate microglia to drive the early stages of Parkinson's disease (PD) pathogenesis. Our previous studies have found a significant expression difference between the lncRNA IL6ST-AS and its antisense RNA IL6ST in the cerebrospinal fluid of PD patients. Furthermore, in α-syn-induced HMC3 cells, a decline in IL6ST and its downstream target JAK2/STAT3 were also observed. Accumulating investigations have illustrated that STAT3 regulates the expression of ferroptosis-related genes and further influences the proliferation of cells.MethodsThe role and mechanisms of IL6ST/JAK2/STAT3 axis in α-syn induced HMC3 cells and PD mouse models were explored by Western blot or immunohistochemistry. Transcriptome sequencing of HMC3 cells exposed to α-syn oligomers and PD mouse models were performed. The STAT3 activator and the STAT3 inhibitor were used to regulate the expression of STAT3. qPCR was used to detect the expression of ferroptosis regulation genes (FRG) in HMC3 cells induced by α-syn or STAT3 inhibitor. ROS, lipid peroxidation and iron levels were measured by flow cytometry.ResultsWe found that α-syn could impair cell activity and stalely inhibit the IL6ST/ STAT3/HIF-1α pathway in α-syn-induced HMC3 cells. Besides, we performed transcriptomic analysis for α-syn-induced HMC3 cells and in α-syn-induced PD mouse models and GSEA indicated an association with ferroptosis. The reduction in P-STAT3 resulted in the lower expression of HIF-1α and the transcriptional activation of ferroptosis positive regulation (FPR) genes. P-STAT3 mediated ferroptotic cell death in α-syn-induced HMC3 cells by modulating lipid peroxidation and iron metabolism levels. An in vivo study revealed that the IL6ST/JAK2/STAT3/HIF-1α pathway was upregulated in PD mouse models.ConclusionsSTAT3 was an important factor that regulates ferroptosis in α-syn pathology via the JAK2/STAT3/HIF-1α axis. Our research illustrated the relationship of the JAK2/STAT3/HIF-1α axis and ferroptosis in the pathological process of α-syn both in vitro and in vivo, providing new topics of interest regarding the inflammation damage hypothesis and pathogenesis in PD.
A Fuzzy Colored Petri-Net Approach for Hybrid Intrusion Prediction
Authors: Jemili Farah
Published: May 2023

Reducing the impact of computer attacks is crucial, and Intrusion Detection Systems (IDS) are an important tool in achieving this goal. However, IDSs have limitations and are unable to detect all attacks or anticipate future ones. To address this issue, we propose a new approach called a hybrid intrusion prediction system (IPS) that not only detects attacks but also predicts potential intrusions. By simulating the behavior of intruders on internal machines, our system provides network administrators with a comprehensive overview, enabling them to identify possible future intrusions and minimize the impact of attacks. Our study aims to predict future attacks based on the behavioral patterns of previously detected intrusions. We describe the architecture and implementation of our proposed system in this paper. Our experiments using real-world datasets demonstrate that the system is highly effective, achieving a high rate of accurate predictions.
Acceptance and use of a clinical decision support system in musculoskeletal pain disorders – The SupportPrim Project
Authors: Granviken Fredrik , Meisingset Ingebrigt , Vasseljen Ottar , Bach Kerstin , Bones Anita Formo , Klevanger Nina Elisabeth
Published: May 2023

Background We have developed a clinical decision support system (CDSS) based on methods from artificial intelligence to support physiotherapists and patients in the decision-making process of managing musculoskeletal (MSK) pain disorders in primary care. The CDSS finds the most similar successful patients from the past to give treatment recommendations for a new patient. Using previous similar patients with successful outcomes to advise treatment moves management of MSK pain patients from one-size fits all recommendations to more individually tailored treatment. This study aimed to describe the development and explore the acceptance and use of the CDSS for MSK pain patients.Methods This mixed-methods study was carried out in the Norwegian physiotherapy primary healthcare sector between October and November 2020, ahead of a randomised controlled trial. We included four physiotherapists and three of their patients, in total 12 patients, with musculoskeletal pain in the neck, shoulder, back, hip, knee or complex pain. We conducted semi-structured telephone interviews with all participants. The interviews were analysed using the Framework Method. In addition, physiotherapists answered the 10-item System Usability Scale.Results Overall, both the physiotherapists and patients found the system acceptable and usable. Important findings from the analysis of the interviews were that the CDSS was valued as a preparatory and exploratory tool, facilitating the therapeutic relationship. However, the physiotherapists used the system mainly to support their previous and current practice rather than involving patients to a greater extent in decisions and learning from previous successful patients.Conclusions The CDSS was acceptable and usable to both the patients and physiotherapists. However, the system appeared not to considerably influence the physiotherapists' clinical reasoning and choice of treatment based on information from most similar successful patients. This could be due to a smaller than optimal number of previous patients in the CDSS or insufficient clinical implementation. Extensive training of physiotherapists should not be underestimated to build understanding and trust in CDSSs.
The Importance of Development and Application of Subtyping Models for Breast Cancer on the Same Platform
Authors: Li Xiangnan , Hu Zixin
Published: May 2023

Background Intrinsic subtypes have played an important role in breast cancer research. The accuracy of breast cancer research findings depends on the accuracy of intrinsic subtype classification of breast cancer samples. Popular intrinsic subtype models, such as PAM50 and AIMS, were mainly developed on Microarray but are widely used in other platforms. The transferability of these models to RNA-seq and other platforms has rarely been studied. We aim to assess the effectiveness of popular intrinsic subtype models on RNA-seq data and improve the accuracy of breast cancer subtyping on this platform.Methods Assuming that one breast cancer sample only belongs to one subtype irrespective of the expression measuring platform, we assessed the consistency of subtype predictions of PAM50 and AIMS for TCGA Microarray and RNA-seq data from the same samples using Kappa statistic. We also built 12 models using common and intrinsic genes on both Microarray and RNA-seq data, and evaluated their performance under the same assumption.Results Both PAM50 and AIMS failed to produce consistent predictions for Microarray and RNA-seq data from the same samples, with Kappa values of 0.33 and 0.21, respectively. Data normalization improved prediction consistency but introduced false classification. Microarray-developed models showed low prediction consistency when applied to both Microarray and RNA-seq profiles of the same samples. However, prediction consistency between predictions of RNA-seq developed model predicting RNA-seq data and Microarray developed model predicting Microarray data was high with most Kappa values above 0.85.Conclusion Great caution should be taken when using PAM50 and AIMS for the subtyping of breast cancer RNA-seq data. Breast cancer subtyping models should be developed and applied on the same platform, using unnormalized expression data for accurate subtype prediction purpose.
Cirrhotic-extracellular matrix attenuates aPD-1 treatment response by initiating immunosuppressive neutrophil extracellular traps formation in hepatocellular carcinoma
Authors: Shen Xiao-Tian , Xie Sun-Zhe , Zou Tian-Tian , Hu Bei-Yuan , Xu Jing , Zhen Xin , Xu Yun-Feng , Wang Xu-Feng , Wang Hao , Wang Shun , Zhu Le , Yu Kang-Kang , Zhu Wen-Wei , Lu Lu , Zhang Ju-Bo , Chen Jin-Hong , Dong Qiong-Zhu , Yang Lu-Yu , Qin Lun-Xiu
Published: May 2023

Background Hepatocellular carcinoma (HCC) is closely associated with chronic liver diseases, particularly liver cirrhosis, which has an altered extracellular matrix (ECM) composition. The influence and its mechanism of the cirrhotic-ECM on the response of HCC to immune checkpoint inhibitor (ICI) remains less clarified.Methods In silico, proteomic and IHC assessment of alteration of cirrhotic-ECM were applied in clinical cohort. Multiple pre-clinical models with ECM manipulation were used to evaluate cirrhotic-ECM’s effect on ICI treatment. In silico, flow cytometry and IHC were applied to explore how cirrhotic-ECM affect HCC microenvironment. In vitro and in vivo experiments were carried out to identify the mechanism of how cirrhotic-ECM undermined ICI treatment.Results We defined “a pro-tumor cirrhotic-ECM” which was featured as the up-regulation of Col1. Cirrhotic-ECM/Col1 was closely related to impaired T cell function and limited aPD-1 response of HCC patients from the TCGA pan cancer cohort and the authors’ institution, as well as in multiple pre-clinical models. Mechanically, cirrhotic-ECM/Col1 orchestrated an immunosuppressive microenvironment (TME) by triggering Col1-DDR1-NFκB-CXCL8 axis, which initiated neutrophil extracellular traps (NETs) formation to shield HCC cells from attacking T cells and impede approaching T cells. Nilotinib, an inhibitor of DDR1, reversed the neutrophils/NETs dominant TME and efficiently enhanced the response of HCC to aPD-1.Conclusions cirrhotic-ECM modulated a NETs enriched TME in HCC, produced an immune suppressive TME and weakened ICI efficiency. Col1 receptor DDR1 could be a potential target synergically used with ICI to overcome ECM mediated ICI resistance. These provide a mechanical insight and novel strategy to overcome the ICI resistance of HCC.
An Improved DQN Algorithm for Automated Guided Vehicle Pathfinding Problem in Port Environment
Authors: Leibing Xiao , Wei Xinchao , Xu Yuelei , Xu Xin , Li Huafeng
Published: May 2023

This paper introduces the D* Hindsight Deep Q-learning (DH-DQN) algorithm, which combines the D* algorithm and is applied to the port AGV path planning problem. To address the drawbacks of long decision times and large storage space of the D* algorithm, this paper proposes an improved DQN algorithm for a single AGV path planning problem. The Hindsight experience replay algorithm is used to alleviate the problem of slow or non-convergence due to sparse reward space. By selecting the actions planned by the D* algorithm with a certain probability, the DH-DQN algorithm's convergence speed and stability are improved, and its decision time is shorter than the classical D* algorithm. The DH-DQN algorithm is used to control an AGV to perform different tasks in different layouts. Experimental results show that the DH-DQN algorithm not only avoids non-convergence in four different layouts but also converges faster than the classical DQN algorithm. Furthermore, the DH-DQN and DQN algorithms' decision-making process's time comparison under the four layouts reveals that DH-DQN saves 24.91\% of the time in the large-scale environment and 28.08\% in the small-scale environment. Therefore, the DH-DQN algorithm performs well in solving the port AGV path planning problem.
Nature and timing of Sn mineralization in southern Hunan, South China: Constraints from LA-ICP-MS cassiterite U-Pb geochronology and trace element composition
Authors: Ren Tao , Li Huan , Algeo Thomas J. , Girei Musa Bala , Wu Jinghua , Liu Biao
Published: May 2023

Accurately determining the timing and mechanism of metallogenesis of ore deposits is essential for developing a robust genetic model for their exploration. In this paper, we analyze the formation conditions of cassiterite in five major deposits of southern Hunan Province, one of the most important tungsten-tin (W-Sn) provinces in South China, using a combination of cathodoluminescence imaging, in situ U-Pb geochronology, and trace-element concentration data. In situ cassiterite U-Pb geochronology constrains the main period of Sn mineralization to between 155.4 and 142.0 Ma, demonstrating a temporal and genetic relationship to silicic intrusive magmatism in the same area. Three stages of magmatic activity and metallogenic evolution are recognized: (1) Early Paleozoic and Triassic: the initial enrichment stage of tungsten and tin; (2) Jurassic: the metasomatic mineralization stage; and (3) Cretaceous: the magmatic-hydrothermal superposition stage. The cassiterite in these deposits takes four forms, i.e., quartz vein-type, greisen-skarn-type, greisen-type, and granite-type, representing a progression characterized by the increasing content and decreasing range of variation of high field strength elements (HFSEs), and reflecting a general increase in the degree of evolution of the associated granites. Rare earth element (REE) concentrations suggest that precipitation of cassiterite was insensitive to the redox state of the fluid and that precipitation of cassiterite in the southern Hunan Sn deposits did not require a high-fO2 environment. These findings provide new insights into tin mineralization processes and exploration strategies.
The role of albumin replacement therapy in the treat ment of hepatic encephalopathy in patients with liver cirrhosis
Authors: Turkina A. A. , Maevskaya M. V. , Zharkova M. S. , Ivashkin V. T.
Published: May 2023

Introduction. It is often observed that decompensated liver cirrhosis is accompanied by hepatic encephalopathy. The role of violation of the structural and functional properties of albumin in the development of this pathology is currently not defined.

Aim. Was to evaluate the effect of albumin replacement therapy on the clinical manifestations of hepatic encephalopathy and the severity of structural and functional changes in serum albumin.

Materials and methods. The study included 28 adult patients with decompensated cirrhosis and hepatic encephalopathy divided into two comparable groups. In addition to the standard examination, the properties of the albumin molecule were evaluated using the EPR test. The dynamics of indicators was assessed in the groups of standard treatment and standard treatment + albumin. Mathematical processing was carried out in the StatTech v. 3.1.4 (developer Stattech LLC, Russia).

Results and discussion. It was revealed that patients with decompensated liver cirrhosis have serious disturbances in the albumin configuration, which lead to a decrease in its functional activity. The ability to bind, transport and detoxify were impaired in the vast majority of patients. The native conformation of the molecule was abnormal in all patients. Against the background of albumin replacement therapy, these disorders are able to recover to normal values. Along with this, we found that albumin replacement therapy reduced the severity of hepatic encephalopathy to a greater extent than standard treatment.

Conclusion. Violation of the structural and functional albumin properties is associated with the progression of hepatic encephalopathy in patients with liver cirrhosis. Transfusions of highly concentrated human albumin lead to the normalization of the molecule properties and the encephalopathy regression.
Two-stage Minimum Cost Spanning Tree Game under Fuzzy Optimistic Coalition
Authors:   St. Petersburg State University, Guo Zhao , Wang Dan ,   St. Petersburg State University, Chen Min ,   St. Petersburg State University, Li Yin ,   St. Petersburg State University,   Harbin Institute of Technology
Published: May 2023

This paper discusses the problem of cost allocation when players have different levels of optimism based on the two-stage minimum spanning tree game, and uses Choquet integral to calculate the characteristic function of fuzzy optimistic coalition and fuzzy pessimistic coalition. It is proved that the subgame of the two-stage clear optimistic coalition minimum cost spanning tree game is also a convex game. Finally, an example is used to prove that the two-stage fuzzy pessimistic coalition minimum cost spanning tree game has a dynamical instability solution.
Coordination in Supply Networks with Combined Topology
Authors:   St. Petersburg State University, Zenkevich Nikolay A. , Nikolchenko Natalia K. ,   St. Petersburg State University, Berezinets Irina V. ,   HSE University, Ivanova Margarita V. ,   St. Petersburg State University
Published: May 2023

The paper considers the problem of supply chain coordination in supply networks using the revenue-sharing contract. The supply network has a combined topology and consists of three levels of participants: manufacturers, a distributor, and retailers. The authors consider the companies' performance improvement as the motivation of companies to operate in coordinating conditions. Simulation of contract conditions is implemented for different types of supply networks: from a simple case to a more complex one. The contract procedure is modeled as a game between two companies. The game solution is a set of contract parameters, providing Nash equilibrium, achieving the maximum of the supply network profit and Pareto-optimality of the obtained solution. The results show the application of revenue-sharing contracts in such networks has several peculiarities: the role of a coordinator in the supply network should be performed by a distributor; the distributor, by setting unified revenue shares for all retailers and manufacturers, gets a share of the expected profit of the supply network, each retailer gets a share of the supply network profit for its sales channel, and each manufacturer gets a share of the supply network profit for its product.
Metabolic Reprogramming of Immune Cells Following Vaccination:
From Metabolites to Personalized Vaccinology
Authors: Mussap Michele , Puddu Melania , Fanos Vassilios
Published: May 2023

Identifying metabolic signatures induced by the immune response to vaccines
allows one to discriminate vaccinated from non-vaccinated subjects and decipher the
molecular mechanisms associated with the host immune response. This review illustrates
and discusses the results of metabolomics-based studies on the innate and adaptive immune
response to vaccines, long-term functional reprogramming (immune memory), and
adverse reactions. Glycolysis is not overexpressed by vaccines, suggesting that the immune
cell response to vaccinations does not require rapid energy availability as necessary
during an infection. Vaccines strongly impact lipids metabolism, including saturated
or unsaturated fatty acids, inositol phosphate, and cholesterol. Cholesterol is strategic for
synthesizing 25-hydroxycholesterol in activated macrophages and dendritic cells and stimulates
the conversion of macrophages and T cells in M2 macrophage and Treg, respectively.
In conclusion, the large-scale application of metabolomics enables the identification
of candidate predictive biomarkers of vaccine efficacy/tolerability.
Physiologically Based Pharmacokinetic Model for Older Adults and Its Application in Geriatric Drug Research
Authors: Wu Xinyi , Sia Jie En Valerie , Hai Min , Lai Xuan , Li Haiyan , Cui Cheng , Liu Dongyang
Published: May 2023

Drug-related adverse events are higher in older patients than in non-older patients, increasing the risk of medication and reducing compliance. Aging is accompanied by a decline in physiological functions and metabolic weakening. Most tissues and organs undergo anatomical and physiological changes that may affect the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of drugs. Clinical trials are the gold standard for selecting appropriate dosing regimens. However, older patients are generally underrepresented in clinical trials, resulting in a lack of evidence for establishing an optimal dosing regimen for older adults. The physiologically based pharmacokinetic (PBPK) model is an effective approach to quantitatively describe the absorption, distribution, metabolism, and excretion of drugs in older adults by integrating physiological parameters, drug physicochemical properties, and preclinical or clinical PK data. The PBPK model can simulate the PK/PD characteristics of clinical drugs in different scenarios, ultimately compensating for inadequate clinical trial data in older adults, and is recommended by the Food and Drug Administration for clinical pharmacology studies in older adults. This review describes the effects of physiological changes on the PK/PD process in older adults and summarises the research progress of PBPK models. Future developments of PBPK models are also discussed, together with the application of PBPK models in older adults, aiming to assist the development of clinical study strategies in older adults.
Effects of Advanced Glycation End Products via Oxidative Stress on Beta
Cells: Insights from in vitro and in vivo Studies and Update on Emerging
Therapies
Authors: Anastasiou Ioanna A. , Tentolouris Konstantinos N. , Lambadiari Vaia , Eleftheriadou Ioanna , Tektonidou Maria , Tentolouris Nikolaos
Published: May 2023

Background:

Protein, lipid, and nucleic acid glycation reactions begin and continue as a
result of persistent hyperglycemia in patients with diabetes mellitus. Advanced glycated end products
(AGEs) are a complex group of chemical moieties that are formed as a result of the glycation process
and play an important role in the pathogenesis of diabetes mellitus. When AGEs interact with their
cellular receptor (RAGE), numerous signaling pathways, including nuclear factor kappa-light-chainenhancer
of activated B cells (NF-κB), c-Jun N-terminal kinase (JNK), and mitogen-activated protein
kinase/extracellular signal-regulated kinase (MAPK/ERK), are activated, increasing oxidative stress.

Objective:

The aim of this review was to summarize in vitro and in vivo studies underlining the involvement
of AGEs on beta cell dysfunction and death via oxidative stress.

Methods:

A literature search of publications published between 1912 and December 2022 was conducted
using MEDLINE, EMBASE, and the Cochrane Library, with restrictions on articles written in
English.

Results:

Recent insights have revealed that oxidative stress has a crucial role in the development of
beta cell dysfunction and insulin resistance, the major hallmarks of type 2 diabetes mellitus. Studies
also revealed that AGEs decrease insulin synthesis and secretion in the pancreatic beta cells and induce
cell apoptosis.

Conclusion:

Experimental data have shown that both AGEs and oxidative stress contribute to beta
cell dysfunction and development as well as to the progression of diabetic complications. Many anti-
AGE therapies are being developed; however, it remains to be seen whether these therapies can help
maintain beta cell function and prevent diabetes complications.
The mTOR Signaling Pathway and mTOR Inhibitors in Cancer:
Next-generation Inhibitors and Approaches
Authors: Ihlamur Murat , Akgul Busra , Zengin Yağmur , Korkut Şenay Vural , Kelleci Kübra , Abamor Emrah Şefik
Published: May 2023

mTOR is a serine/threonine kinase that plays various roles in cell growth,
proliferation, and metabolism. mTOR signaling in cancer becomes irregular. Therefore,
drugs targeting mTOR have been developed. Although mTOR inhibitors rapamycin and
rapamycin rapalogs (everolimus, rapamycin, temsirolimus, deforolimus, etc.) and new
generation mTOR inhibitors (Rapalink, Dual PI3K/mTOR inhibitors, etc.) are used in
cancer treatments, mTOR resistance mechanisms may inhibit the efficacy of these
drugs. Therefore, new inhibition approaches are developed. Although these new
inhibition approaches have not been widely investigated in cancer treatment, the use of
nanoparticles has been evaluated as a new treatment option in a few types of cancer.

:

This review outlines the functions of mTOR in the cancer process, its resistance
mechanisms, and the efficiency of mTOR inhibitors in cancer treatment. Furthermore, it
discusses the next-generation mTOR inhibitors and inhibition strategies created using
nanoparticles.

:

Since mTOR resistance mechanisms prevent the effects of mTOR inhibitors used in
cancer treatments, new inhibition strategies should be developed. Inhibition approaches
are created using nanoparticles, and one of them offers a promising treatment option
with evidence supporting its effectiveness.
An Up-to-date Review on Protein-based Nanocarriers in the Management
of Cancer
Authors: Almalki Waleed H.
Published: May 2023

Background:

A big health issue facing the world's population is cancer. An alarming increase
in cancer patients was anticipated by worldwide demographic statistics, which showed that the
number of patients with different malignancies was rapidly increasing. By 2025, probably 420 million
cases were projected to be achieved. The most common cancers diagnosed are breast, colorectal, prostate,
and lung. Conventional treatments, such as surgery, chemotherapy, and radiation therapy, have
been practiced.

Objective:

In recent years, the area of cancer therapy has changed dramatically with expanded studies
on the molecular-level detection and treatment of cancer. Recent advances in cancer research have seen
significant advances in therapies such as chemotherapy and immunotherapy, although both have limitations
in effectiveness and toxicity.

Methods:

The development of nanotechnology for anticancer drug delivery has developed several potentials
as nanocarriers, which may boost the pharmacokinetic and pharmacodynamic effects of the drug
product and substantially reduce the side effects.

Results:

The advancement in non-viral to viral-based protein-based nanocarriers for treating cancer has
earned further recognition in this respect. Many scientific breakthroughs have relied on protein-based
nanocarriers, and proteins are essential organic macromolecules for life. It allows targeted delivery of
passive or active tumors using non-viral-based protein-based nanocarriers to viral-based protein
nanocarriers. When targeting cancer cells, both animal and plant proteins may be used in a formulation
process to create self-assembled viruses and platforms that can successfully eradicate metastatic cancer
cells.

Conclusion:

This review, therefore, explores in depth the applications of non-viral to viral proteinbased
noncarriers with a specific focus on intracellular drug delivery and anti-cancer drug targeting
ability.
The Experiences of Families Raising an Autistic Child: A Rapid Review
Authors: Phetoe Boitumelo K. , Coetzee Heleen K. , Erasmus Petro , Tsabedze Wandile F.
Published: May 2023

Background:

Autism is becoming more prominent in South Africa and in the rest of the world. A family raising an autistic child plays a key role in the treatment and lifelong management. This responsibility goes with demanding challenges, which are unique to every child and situation. A deeper understanding of the psychosocial experiences and impact of autism and its symptoms on the involved families is ultimately essential in the development of relevant and scientifically based interventions and support programmes.

Objectives:

The aim of this review was to conduct a rapid review to explore, synthesise, and integrate existing scientific literature on the pre- and post-diagnostic psychosocial experiences of families that raise an autistic child.

Methods:

A comprehensive and systematic keywords search were conducted, and 142 relevant studies were found. These studies were then screened for relevance with regard to inclusion and exclusion criteria. Nine articles, published between 2008 and 2018, were identified for final inclusion in the study. Data were analysed using a thematic synthesis approach.

Results:

The thematic synthesis revealed three main themes and ten sub-themes that were anchored on families’ psychosocial experiences of raising an autistic child, both pre- and post-diagnosis. The themes include psychological experiences (emotions experienced, grieving process, parenting, and family dynamics), social experiences (lack of support services, and social awareness), and psychosocial coping strategies (isolation, information seeking, meaning-making, and support system).

Conclusion:

The analyses and synthesis of the identified articles indicated that the identified psychosocial experiences of families raising an autistic child were multidimensional and fit well within a contextual and systemic perspective. The family quality of life (FQOL) framework provides a positive approach that seeks to improve and optimise the quality of life of families that raise a child with a disability. It is recommended that families need to be informed of services available for autism and psychosocially supported so that they feel empowered to deal with the challenges at hand.
Development and Characterization of a Gel Formulation Containing
Golden Cherry Exosomes (Physalis minima) as a Potential Anti-Photoaging
Authors: Setiadi Vincent Evan , Adlia Amirah , Barlian Anggraini , Ayuningtyas Fitria Dwi , Rachmawati Heni
Published: May 2023

Aim:

The present study aims to produce a novel therapeutic approach for the treatment of
photoaging.

Background:

Plant-derived exosome-like nanoparticles (PDENs) are nano-sized vesicles containing biomolecules
released by multivesicular bodies. Recently, studies have shown the efficacy of exosomes in
treating photoaging through increasing collagen synthesis and decreasing collagen degradation. In addition,
some PDENs were also proven to contain bioactive metabolites, which also have potential antioxidant
activity to mitigate the risk of photoaging.

Objective:

Formulating and developing a gel and incorporating it with exosomes derived from golden
cherry (Physalis minima).

Methods:

The formulation was developed by first preparing various base formulations with different
compositions and selecting the best through evaluation tests. The results showed that only polymer base
natrosol with a concentration of 0.25% was suitable for incorporating exosomes. The selected base was
then incorporated with various concentrations of golden cherry exosomes and was evaluated regarding
its physical and stability profile.

Result:

The result demonstrates that the incorporated gel displayed pleasant organoleptic properties
and a pH compatible with the skin, with pseudoplastic flow and a suitable viscosity for topical application.
The stability study also only revealed minor changes in viscosity and pH without affecting the
general stability of the formulation. Formulation incorporating 0.25% golden cherry exosomes had
shown the best stability profile compared to other concentrations. On characterization, although the incorporated
exosomes showed heterogeneous particle size distribution (PI > 0.3), they still maintained
their structural integrity. In addition, the incorporated exosomes showed antioxidant activity with
IC50 of 372.435 μg/mL, which can help mitigate the risk of photoaging.

Conclusion:

Golden cherry exosomes have been successfully incorporated into gel and, thus, can be potentially
utilized as a novel therapeutic approach for the treatment of photoaging.
The Effectiveness of Digital Apps Providing Personalized Exercise Videos: Systematic Review With Meta-Analysis
Authors: Davergne Thomas , Meidinger Philippe , Dechartres Agnès , Gossec Laure
Published: May 2023

Background

Among available digital apps, those providing personalized video exercises may be helpful for individuals undergoing functional rehabilitation.

Objective

We aimed to assess the effectiveness of apps providing personalized video exercises to support rehabilitation for people with short- and long-term disabling conditions, on functional capacity, confidence in exercise performance, health care consumption, health-related quality of life, adherence, and adverse events.

Methods

In this systematic review, we searched MEDLINE, CENTRAL, and Embase databases up to March 2022. All randomized controlled trials evaluating the effect of apps providing personalized video exercises to support rehabilitation for any condition requiring physical rehabilitation were included. Selection, extraction, and risk of bias assessment were performed by 2 independent reviewers. The primary outcome was functional capacity at the end of the intervention. The secondary outcomes included confidence in exercise performance, care consumption, health-related quality of life, adherence, and adverse events. A meta-analysis was performed where possible; the magnitude of the effect was assessed with the standardized mean difference (SMD).

Results

From 1641 identified references, 10 papers (n=1050 participants, 93% adults) were included: 7 papers (n=906 participants) concerned musculoskeletal disorders and 3 (n=144 participants) concerned neurological disorders. Two (n=332 participants) were employee based. The apps were mostly commercial (7/10); the videos were mostly elaborated on by a physiotherapist (8/10). The duration of app use was 3-48 weeks. All included studies had a high overall risk of bias. Low-quality evidence suggested that the use of apps providing personalized video exercises led to a significant small to moderate improvement in physical function (SMD 0.35, 95% CI 0.19-0.51; Phet=.86; I2=0%) and confidence in exercise performance (SMD 0.67; 95% CI 0.37-0.96; Phet=.22; I2=33%). Because of the very low quality of the evidence, the effects on quality of life and exercise adherence were uncertain. Apps did not influence the rate of adverse events.

Conclusions

Apps providing personalized video exercises to support exercise performance significantly improved physical function and confidence in exercise performance. However, the level of evidence was low; more robust studies are needed to confirm these results.

Trial Registration

PROSPERO CRD42022323670; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=323670
Forecasting Artificial Intelligence Trends in Health Care: Systematic International Patent Analysis
Authors: Benjamens Stan , Dhunnoo Pranavsingh , Görög Márton , Mesko Bertalan
Published: May 2023

Background

Artificial intelligence (AI)– and machine learning (ML)–based medical devices and algorithms are rapidly changing the medical field. To provide an insight into the trends in AI and ML in health care, we conducted an international patent analysis.

Objective

It is pivotal to obtain a clear overview on upcoming AI and MLtrends in health care to provide regulators with a better position to foresee what technologies they will have to create regulations for, which are not yet available on the market. Therefore, in this study, we provide insights and forecasts into the trends in AI and ML in health care by conducting an international patent analysis.

Methods

A systematic patent analysis, focusing on AI- and ML-based patents in health care, was performed using the Espacenet database (from January 2012 until July 2022). This database includes patents from the China National Intellectual Property Administration, European Patent Office, Japan Patent Office, Korean Intellectual Property Office, and the United States Patent and Trademark Office.

Results

We identified 10,967 patents: 7332 (66.9%) from the China National Intellectual Property Administration, 191 (1.7%) from the European Patent Office, 163 (1.5%) from the Japan Patent Office, 513 (4.7%) from the Korean Intellectual Property Office, and 2768 (25.2%) from the United States Patent and Trademark Office. The number of published patents showed a yearly doubling from 2015 until 2021. Five international companies that had the greatest impact on this increase were Ping An Medical and Healthcare Management Co Ltd with 568 (5.2%) patents, Siemens Healthineers with 273 (2.5%) patents, IBM Corp with 226 (2.1%) patents, Philips Healthcare with 150 (1.4%) patents, and Shanghai United Imaging Healthcare Co Ltd with 144 (1.3%) patents.

Conclusions

This international patent analysis showed a linear increase in patents published by the 5 largest patent offices. An open access database with interactive search options was launched for AI- and ML-based patents in health care.
Assessing SARS-CoV-2 Testing Adherence in a University Town: Recurrent Event Modeling Analysis (Preprint)
Authors: García Yury E , Schmidt Alec J , Solis Leslie , Daza-Torres María L , Montesinos-López J Cricelio , Pollock Brad H , Nuño Miriam
Published: May 2023

BACKGROUND

Healthy Davis Together was a program launched in September 2020 in the city of Davis, California, to mitigate the spread of COVID-19 and facilitate the return to normalcy. The program involved multiple interventions, including free saliva-based asymptomatic testing, targeted communication campaigns, education efforts, and distribution of personal protective equipment, community partnerships, and investments in the local economy.

OBJECTIVE

This study identified demographic characteristics of individuals that underwent testing and assessed adherence to testing over time in a community pandemic-response program launched in a college town in California, United States.

METHODS

This study outlines overall testing engagement, identifies demographic characteristics of participants, and evaluates testing participation changes over 4 periods of the COVID-19 pandemic, distinguished by the dominant variants Delta and Omicron. Additionally, a recurrent model is employed to explore testing patterns based on the participants’ frequency, timing, and demographic characteristics.

RESULTS

A total of 770,165 tests were performed between November 18, 2020, and June 30, 2022, among 89,924 (41.1% of total population) residents of Yolo County, with significant participation from racially or ethnically diverse participants and across age groups. Most positive cases (6351 of total) and highest daily participation (895 per 100,000 population) were during the Omicron period. There were some gender and age-related differences in the pattern of recurrent COVID-19 testing. Men were slightly less likely (hazard ratio [HR] 0.969, 95% CI 0.943-0.996) to be retested and more likely (HR 1.104, 95% CI 1.075-1.134) to stop testing altogether than women. People aged between 20 and 34 years were less likely to be retested (HR 0.861, 95% CI 0.828-0.895) and more likely to stop testing altogether (HR 2.617, 95% CI 2.538-2.699). However, older age groups were less likely to stop testing, especially those aged between 65-74 years and 75-84 years, than those aged between 0 and 19 years. The likelihood of stopping testing was lower (HR 0.93, 95% CI 0.889-0.976) for the Asian group and higher for the Hispanic or Latino (HR 1.185, 95% CI 1.148-1.223) and Black or African American (HR 1.198, 95% CI 1.054-1.350) groups than the White group.

CONCLUSIONS

The unique features of a pandemic response program that supported community-wide access to free asymptomatic testing provide a unique opportunity to evaluate adherence to testing recommendations and testing trends over time. Identification of individual and group-level factors associated with testing behaviors can provide insights for identifying potential areas of improvement in future testing initiatives.

CLINICALTRIAL
Conceptualization of an artificial intelligence (AI) conversational agent to follow up anal fistula patients; a technical note (Preprint)
Authors: Teymouri Alireza , Erfani Zahra
Published: May 2023

UNSTRUCTURED

With the advent of artificial intelligence with its new identity and recent developments in natural language processing techniques we will be able to track the disease progression and follow up the patients with more accuracy and effectiveness. The results of this approach is more noticeable in diseases with high rate of complications and treatment failure like anal fistula. Thus, we prepared the following technical note in which the specifications of an artificial intelligence conversational agent or a chatbot is summarized. It seems that narrowing the target population will enhance the efficacy and makes it easier to evaluate the chatbot. We conjecture that three datasets are needed to develop this tool: 1. Institutional information, 2. Follow-up questions, and 3. Patients’ questions and concerns.
A Discussion about the Impact of ChatGPT in Education: Benefits and Concerns
Authors: Alves de Castro Charles
Published: May 2023

The advent of advanced machine learning models such as ChatGPT has led to significant advancements in various fields, including education. The purpose of this article is to explore the impact of ChatGPT in higher education, covering both positive and negative nuances. A critical literature review analysis was conducted, which included references from reliable sources. The methodology used in this article was based on a critical literature review method. The results of the analysis indicate that ChatGPT might have several benefits in education, including improved student engagement, personalized learning experiences, and enhanced teaching practices. However, there are also some negative implications, such as concerns over privacy, academic integrity, and the potential for bias. The article concludes by highlighting the need for further research in this area and providing recommendations for educators and policymakers.
High Phenolic Extra Virgin Olive Oil Influences the Gut-brain Axis in Individuals Diagnosed with Autism Spectrum Disorder
Authors: Thoma Constantinos , Papachristou Anastasia Ioannis , Wozniak Greta
Published: May 2023

Autism Spectrum Disorder (ASD) is an umbrella term that incorporates a range of neurodevelopmental disorders which affect behaviour, emotion, and communication. In recent years, the effects of dietary habits in individuals with ASD have been mentioned and a distinct correlation has been observed between ASD and gastrointestinal (GI) disorders. We used the Autism Treatment Evaluation Checklist (ATEC) to evaluate whether we can observe differences in behaviour by administering High Phenolic Extra Virgin Olive Oil (HP EVOO) in combination with a special diet to reduce inflammation and consequently improve behaviour. We hypothesise that ASD symptoms will soothe at a proportional rate relative to their severity. Individuals that followed the protocol showed a decrease in severity of their symptoms. Regarding data analysis, we calculated the p-values to evaluate the significance of our results. Our objective is to establish the beneficial influence that HP EVOO has on the gut-brain axis by soothing ASD symptoms.
Women Safety Enhancement Application
Authors: E Aarthi. , K Ramya. , M Srilekha. , Mageshwari R.
Published: May 2023

Abstract: The usage of smart phones equipped with GPS navigation unit have increased rapidly from 3% to more than 20% in the past five years. Hence, a smart phone can be used efficiently for personal safety or various other protection purposes especially for women. This app can be activated by a single click when the user feels she is in danger. This application communiqués the user’s location to the registered contacts for every few seconds in the form of message. Thus, it acts like a sentinel following behind the person till the user feels she is safe. This paper presents analysis a unique feature of this application to send the message to the registered contacts continuously till they are pressing ‘HELP’ button. Continuous location tracking information via SMS helps to find the location of the victim quickly and can be rescued safely. This application aims to ensure women safety. This is achieved by addressing the circumstances that compromise the safety of women in today’s day and age. This app ensures women are not put into such situations through various features offered by our system.
Bringing the Garden Online: An Exploration of Best Practices for E-Commerce Plant Sales
Authors: Chaudhary Abhinav , Sharma Ayush , Kumar Manoj , Kaushik Harshit
Published: May 2023

Abstract: As we've learned from reading many research papers and other sources, many people want to acquire plants andgo right to the nursery, but occasionally they don't know all there is to know about a certain plant or the seller is not technically skilled. Customers don't compare plant prices between different retailers, and there is no online payment option available in nurseries. The e-nursery in this instance is a platform where customers can quickly compare plant prices and make online payments. Excellent customer service is crucial. Our staff intends to provide knowledgeable answers to inquiries and advise when we feel it is necessary since we want every customer to have a positive shopping experience.This study investigates the user experience and best practises for a website that sells plants online. An analysis of the functionality and design elements of an existing online plant marketplace is included in the study, along with user comments and evaluations. The study also looks at the difficulties and possibilities brought on by e-commerce plant sales, such as problems with shipping and handling, plant quality control, and customer service. Through this investigation, the paper pinpoints crucial tactics for profitable online plant sales, such as persuasive product descriptions, simple website navigation, and helpful customer service. In the end, this study emphasizes the potential of online plant sales as a successful and long-lasting business model for the green sector while offering advice and suggestions to business owners and developers.