bluuebunny/crossref_metadata_2025 huggingface dataset:
Transhumeral Arm Reaching Motion Prediction through Deep Reinforcement Learning-Based Synthetic Motion Cloning
Authors: Ahmed Muhammad Hannan , Kutsuzawa Kyo , Hayashibe Mitsuhiro
Published: August 2023

The lack of intuitive controllability remains a primary challenge in enabling transhumeral amputees to control a prosthesis for arm reaching with residual limb kinematics. Recent advancements in prosthetic arm control have focused on leveraging the predictive capabilities of artificial neural networks (ANNs) to automate elbow joint motion and wrist pronation–supination during target reaching tasks. However, large quantities of human motion data collected from different subjects for various activities of daily living (ADL) tasks are required to train these ANNs. For example, the reaching motion can be altered when the height of the desk is changed; however, it is cumbersome to conduct human experiments for all conditions. This paper proposes a framework for cloning motion datasets using deep reinforcement learning (DRL) to cater to training data requirements. DRL algorithms have been demonstrated to create human-like synergistic motion in humanoid agents to handle redundancy and optimize movements. In our study, we collected real motion data from six individuals performing multi-directional arm reaching tasks in the horizontal plane. We generated synthetic motion data that mimicked similar arm reaching tasks by utilizing a physics simulation and DRL-based arm manipulation. We then trained a CNN-LSTM network with different configurations of training motion data, including DRL, real, and hybrid datasets, to test the efficacy of the cloned motion data. The results of our evaluation showcase the effectiveness of the cloned motion data in training the ANN to predict natural elbow motion accurately across multiple subjects. Furthermore, motion data augmentation through combining real and cloned motion datasets has demonstrated the enhanced robustness of the ANN by supplementing and diversifying the limited training data. These findings have significant implications for creating synthetic dataset resources for various arm movements and fostering strategies for automatized prosthetic elbow motion.
Polysilicon-Channel Synaptic Transistors for Implementation of Short- and Long-Term Memory Characteristics
Authors: Baek Myung-Hyun , Kim Hyungjin
Published: August 2023

The rapid progress of artificial neural networks (ANN) is largely attributed to the development of the rectified linear unit (ReLU) activation function. However, the implementation of software-based ANNs, such as convolutional neural networks (CNN), within the von Neumann architecture faces limitations due to its sequential processing mechanism. To overcome this challenge, research on hardware neuromorphic systems based on spiking neural networks (SNN) has gained significant interest. Artificial synapse, a crucial building block in these systems, has predominantly utilized resistive memory-based memristors. However, the two-terminal structure of memristors presents difficulties in processing feedback signals from the post-synaptic neuron, and without an additional rectifying device it is challenging to prevent sneak current paths. In this paper, we propose a four-terminal synaptic transistor with an asymmetric dual-gate structure as a solution to the limitations of two-terminal memristors. Similar to biological synapses, the proposed device multiplies the presynaptic input signal with stored synaptic weight information and transmits the result to the postsynaptic neuron. Weight modulation is explored through both hot carrier injection (HCI) and Fowler–Nordheim (FN) tunneling. Moreover, we investigate the incorporation of short-term memory properties by adopting polysilicon grain boundaries as temporary storage. It is anticipated that the devised synaptic devices, possessing both short-term and long-term memory characteristics, will enable the implementation of various novel ANN algorithms.
Rapid Quantification of Microvessels of Three-Dimensional Blood–Brain Barrier Model Using Optical Coherence Tomography and Deep Learning Algorithm
Authors: Zhang Huiting , Kang Dong-Hee , Piantino Marie , Tominaga Daisuke , Fujimura Takashi , Nakatani Noriyuki , Taylor J. , Furihata Tomomi , Matsusaki Michiya , Fujita Satoshi
Published: August 2023

The blood–brain barrier (BBB) is a selective barrier that controls the transport between the blood and neural tissue features and maintains brain homeostasis to protect the central nervous system (CNS). In vitro models can be useful to understand the role of the BBB in disease and assess the effects of drug delivery. Recently, we reported a 3D BBB model with perfusable microvasculature in a Transwell insert. It replicates several key features of the native BBB, as it showed size-selective permeability of different molecular weights of dextran, activity of the P-glycoprotein efflux pump, and functionality of receptor-mediated transcytosis (RMT), which is the most investigated pathway for the transportation of macromolecules through endothelial cells of the BBB. For quality control and permeability evaluation in commercial use, visualization and quantification of the 3D vascular lumen structures is absolutely crucial. Here, for the first time, we report a rapid, non-invasive optical coherence tomography (OCT)-based approach to quantify the microvessel network in the 3D in vitro BBB model. Briefly, we successfully obtained the 3D OCT images of the BBB model and further processed the images using three strategies: morphological imaging processing (MIP), random forest machine learning using the Trainable Weka Segmentation plugin (RF-TWS), and deep learning using pix2pix cGAN. The performance of these methods was evaluated by comparing their output images with manually selected ground truth images. It suggested that deep learning performed well on object identification of OCT images and its computation results of vessel counts and surface areas were close to the ground truth results. This study not only facilitates the permeability evaluation of the BBB model but also offers a rapid, non-invasive observational and quantitative approach for the increasing number of other 3D in vitro models.
Investigating the Role of Second Chance Schools and COVID-19 Pandemic on the Mental Health and Self-Image of Greek Adult Students
Authors: Karakitsiou Georgia , Plakias Spyridon , Kedraka Katerina , Arvaniti Aikaterini , Kokkotis Christos , Tsiakiri Anna , Samakouri Maria
Published: August 2023

COVID-19 has globally impacted both physical and mental health. This study aimed to explore the impact of Second Chance Schools (SCS) and the COVID-19 pandemic on the mental health and self-image of Greek SCS students. A total of 251 SCS students from two consecutive study cycles participated, completing the research instruments at the beginning and end of their studies. Participants’ anxiety, depressive symptomatology, well-being, self-esteem and self-efficacy were evaluated by means of the GAD-7, PHQ-8, WHO-5 Well-being Index, Rosenberg Self-Esteem Scale and Generalized Self-Efficacy Scale, respectively. The research spanned three years, including a year of universal lockdown, a year with protective measures and a year without anti-COVID-19 measures. Factor analysis, regression analyses and two two-way repeated measures ANOVAs were applied to the collected data. All five psychological dimensions measured by the study’s instruments were grouped into two factors, namely mental health and self-image. Well-being positively influenced mental health, while anxiety and depression had a negative impact. On the other hand, self-efficacy and self-esteem positively contributed to self-image. Mental health and self-image were moderately correlated. Pre-SCS values of mental health and self-image predicted a higher percentage of variance in post-SCS values compared to anxiety, depression, well-being, self-efficacy and self-esteem. Moreover, mental health improved after the completion of SCS, but only for participants after the lifting of anti-COVID-19 measures. Conversely, self-image improved for all participants regardless of the presence of anti-COVID-19 measures. Overall, the SCS had a considerable impact on the participants’ mental health and self-image, although the effect was influenced by COVID-19.
Pharmacological Treatment of Alcohol Cravings
Authors: Marin Matheus Cheibub David , Pedro Maria Olívia Pozzolo , Perrotte Giuliana , Martins-da-Silva Anderson S. , Lassi Dangela L. S. , Blaas Israel Kanaan , Castaldelli Fernando Ikeda , Brisola dos Santos Maria Beatriz , Kortas Guilherme Trevizan , Campos Marcela Waisman , Torales Julio , Ventriglio Antonio , Périco Cintia de Azevedo-Marques , Negrão André B. , Leopoldo Kae , de Andrade Arthur Guerra , Malbergier André , Castaldelli-Maia João Maurício
Published: August 2023

(1) Background: The treatment of substance addiction is challenging and has persisted for decades, with only a few therapeutic options. Although there are some recommendations for specific treatments for Alcohol Use Disorder (AUD), there is no specific medication used to treat alcohol cravings, which could benefit millions of patients that are suffering from alcoholism. Cravings, or the urge to use drugs, refer to the desire to experience the effects of a previously experienced psychoactive substance. (2) Methods: We included original studies of alcohol abuse or dependence extracted from a controlled, blind, pharmacological treatment study which presented measures and outcomes related to alcohol cravings. (3) Results: Specific drugs used for the treatment of alcoholism, such as Naltrexone and Acamprosate, have had the best results in relieving craving symptoms, as well as promoting abstinence. Baclofen and anticonvulsants such as Gabapentin and Topiramate have shown good results in promoting abstinence and the cessation of cravings. (4) Conclusions: Specific drugs used for the treatment of alcoholism to obtain the best results can be considered the gold standard for promoting abstinence and relieving cravings. Anticonvulsants and Baclofen also had good results, with these medications being considered as second-line ones. Varenicline is an option for alcohol dependents who also concomitantly ingest tobacco.
Association between Reaction Times in the Joint Simon Task and Personality Traits
Authors: Irie Shun , Tachibana Atsumichi , Matsuo Akiko
Published: August 2023

Joint go and no-go effects (joint Simon effects; JSEs) are considered to have a stimulus–response compatibility effect on joint reaction time tasks (joint Simon task) caused by the presence of other people. Additionally, JSEs are known to be associated with various social factors and are therefore a potential clinical marker for communicative function; however, the relationship with the personality that is associated with communication skills remains unclear. In this study, we focused on the association between JSE and personality traits. Thirty Japanese participants (fifteen women) were recruited. First, personality trait scores were obtained using the Japanese version of the ten-item personality inventory before the experiment. Second, we measured reaction times in the joint Simon task and single go and no-go tasks with the go signal presented on the congruent and incongruent sides. At last, we analyzed the association between reaction times and personality traits by using Spearman’s correlation analysis. As a result, we observed two pairs with significant correlations: JSE and neuroticism and short reaction times in the joint condition and agreeableness. In conclusion, we identified potential psychological markers associated with the joint Simon task. These findings may lead to an additional hypothesis regarding the neurobiological mechanisms of JSEs.
Application of Cluster Analysis to Examine the Performance of Low-Cost Volatile Organic Compound Sensors
Authors: Kolarik Jakub , Lyng Nadja Lynge , Bossi Rossana , Li Rongling , Witterseh Thomas , Smith Kevin Michael , Wargocki Pawel
Published: August 2023

Airtight energy-efficient buildings of today need efficient ventilation to secure high indoor air quality. There is a need for affordable and reliable sensors to make demand control available in a broad range of ventilation systems. Low-cost metal oxide semiconductor (MOS) volatile organic compound (VOC) sensors offer such a possibility, but they are usually non-selective and react to broad range of compounds. The objective of the present paper was to use cluster analysis to assess the ability of five commercially available MOS VOC sensors to detect pollutants in a residential setting. We studied three scenarios: emissions from people (human bioeffluents), furnishing materials (linoleum), and human activity (surface cleaning with spray detergent). We monitored each scenario with five MOS VOC sensors and a proton-transfer-reaction–time-of-flight mass spectrometer (PTR-ToF-MS). We applied an agglomerative hierarchical clustering algorithm to evaluate the dissimilarity between clusters. Four of the five tested sensors produced signals in agreement with the concentration patterns measured with the PTR-ToF-MS; one sensor underperformed in all cases. Three sensors showed a very similar performance under all emission scenarios. The results showed that the clustering could help in understanding whether a particular sensor matched the intended emission scenario.
Analysis and Evaluation of the Progressive Collapse of Cable Dome Structures Induced by Joint Damage
Authors: Chen Lian-Meng , Huang Kai-Yu , Liu Yi-Jie , Li Ze-Bin , Zeng Yi-Hong , Li Wei , Zhou Yi-Yi , Dong Shi-Lin
Published: August 2023

The current literature lacks an effective progressive collapse analysis of a cable dome structure induced by joint damage. In this study, a dynamic analysis was performed using actual construction cases, an ANSYS LS-DYNA analysis platform, and a fully dynamic equivalent load instantaneous removal method. First, the structure’s dynamic responses and collapse modes induced by different joints with different types of damage were explored. Subsequently, joint importance coefficients were proposed depending on the structure’s displacement before and after joint removal, and the relationships between the joint importance coefficients and the joint properties and collapse modes, respectively, were then identified. Finally, the relationship between the joint damage and the connected component damage was explored. The results revealed that different joints and identical joints with different types induced a variety of dynamic responses. However, the dynamic response induced by the discontinuous joint damage was more apparent than that induced by the continuous joint damage. When a continuous joint model was used, the damage on all joints did not result in the progressive or local progressive collapse of the structure. Thus, all these joints were considered as common joints. However, when a discontinuous joint model was used, the failure of the joints resulted in three distinct collapse modes, namely a progressive collapse, a local progressive collapse, and a nonprogressive collapse, corresponding to the key joints, the important joints, and the common joints, respectively. These three types of joints corresponded to different importance coefficients. When damage occurred in the discontinuous joints separately linked to the key components, the important components, and the common components, the joints resulted in the progressive collapse, local progressive collapse, and nonprogressive collapse, respectively, of the structure.
Re-Analysis of Historical Data and Model Calibration of Duration of Load Effect on Structural Timber
Authors: Zhao Mingyun , Zhao Ernian , Zhang Xin , Yue Qingxia
Published: August 2023

The duration of load (DOL) effect in structure timber refers to the degradation of strength and stiffness that occurs under long-term continuous loading. This paper investigated the DOL effect in structure timber using DOL tests and DOL damage models. Based on the empirical-fitted formulae, the DOL coefficients were derived for three long-term sustained loads in bending, tension perpendicular to grain, and shear parallel to grain, and the results were compared and analyzed with the Madison equation, Gerhards model, Nielsen model, and Foschi and Yao model derivations to verify the applicability of the DOL empirical model and the three DOL damage models. The results show that based on the historical data of the DOL tests, the Madison empirical formula was found to be better applied to the derivation of DOL coefficients under the bending and tension perpendicular to grain long-term sustained loading, and the derivation of DOL coefficients under shear loading is not satisfactory. Among the three DOL damage models, the Foschi and Yao model was better than the Gerhards and Nielsen models for fitting the DOL test results under bending, tension perpendicular to grain, and shear parallel to grain. The DOL coefficients derived based on the Foschi and Yao model are more comparable to test results and resemble those derived from the Madison formula.
Planning CT Identifies Patients at Risk of High Prostate Intrafraction Motion
Authors: Ballhausen Hendrik , Li Minglun , Lombardo Elia , Landry Guillaume , Belka Claus
Published: August 2023

Prostate motion (standard deviation, range of motion, and diffusion coefficient) was calculated from 4D ultrasound data of 1791 fractions of radiation therapy in N = 100 patients. The inner diameter of the lesser pelvis was obtained from transversal slices through the pubic symphysis in planning CTs. On the lateral and craniocaudal axes, motility increases significantly (t-test, p < 0.005) with the inner diameter of the lesser pelvis. A diameter of >106 mm (ca. 6th decile) is a good predictor for high prostate intrafraction motion (ca. 9th decile). The corresponding area under the receiver operator curve (AUROC) is 80% in the lateral direction, 68% to 80% in the craniocaudal direction, and 62% to 70% in the vertical direction. On the lateral x-axis, the proposed test is 100% sensitive and has a 100% negative predictive value for all three characteristics (standard deviation, range of motion, and diffusion coefficient). On the craniocaudal z-axis, the proposed test is 79% to 100% sensitive and reaches 95% to 100% negative predictive value. On the vertical axis, the proposed test still delivers 98% negative predictive value but is not particularly sensitive. Overall, the proposed predictor is able to help identify patients at risk of high prostate motion based on a single planning CT.
Brown Tumour in Chronic Kidney Disease: Revisiting an Old Disease with a New Perspective
Authors: Santoso Djoko , Thaha Mochammad , Empitu Maulana A. , Kadariswantiningsih Ika Nindya , Suryantoro Satriyo Dwi , Haryati Mutiara Rizki , Hertanto Decsa Medika , Pramudya Dana , Bintoro Siprianus Ugroseno Yudho , Nasronudin Nasronudin , Alsagaff Mochamad Yusuf , Susilo Hendri , Wungu Citrawati Dyah Kencono , Budhiparama Nicolaas C. , Hogendoorn Pancras C. W.
Published: August 2023

Osteitis fibrosa cystica (OFC) and Brown Tumours are two related but distinct types of bone lesions that result from the overactivity of osteoclasts and are most often associated with chronic kidney disease (CKD). Despite their potential consequences, these conditions are poorly understood because of their rare prevalence and variability in their clinical manifestation. Canonically, OFC and Brown Tumours are caused by secondary hyperparathyroidism in CKD. Recent literature showed that multiple factors, such as hyperactivation of the renin–angiotensin–aldosterone system and chronic inflammation, may also contribute to the occurrence of these diseases through osteoclast activation. Moreover, hotspot KRAS mutations were identified in these lesions, placing them in the spectrum of RAS–MAPK-driven neoplasms, which were until recently thought to be reactive lesions. Some risk factors contributed to the occurrence of OFC and Brown Tumours, such as age, gender, comorbidities, and certain medications. The diagnosis of OFC and Brown Tumours includes clinical symptoms involving chronic bone pain and laboratory findings of hyperparathyroidism. In radiological imaging, the X-ray and Computed tomography (CT) scan could show lytic or multi-lobular cystic alterations. Histologically, both lesions are characterized by clustered osteoclasts in a fibrotic hemorrhagic background. Based on the latest understanding of the mechanism of OFC, this review elaborates on the manifestation, diagnosis, and available therapies that can be leveraged to prevent the occurrence of OFC and Brown Tumours.
Tumor-Free Resection Margin Distance in the Surgical Treatment of Node-Negative Squamous Cell Cancer of the Vulva Has No Impact on Survival: Analysis of a Large Patient Cohort in a Tertiary Care Center
Authors: Taran Florin Andrei , Pasternak Jana , Staebler Annette , Rohner Annika , Neis Felix , Engler Tobias , Oberlechner Ernst , Schönfisch Birgitt , Juhasz-Böss Ingolf , Hartkopf Andreas Daniel , Brucker Sara , Walter Christina Barbara
Published: August 2023

Background: The aim of this study was to evaluate the impact of pathological tumor-free margin distance on survival in SCC patients treated with surgery alone. Methods: This retrospective study included 128 patients with node-negative disease that received no adjuvant treatment. Disease-free and overall survival were analyzed according to pathological tumor-free margin distance. Results: The patients were subclassified into three resection margin category groups: “1 to 3 mm” (n = 42), “>3 to 8 mm” (n = 47) or “>8 mm” (n = 39). Thirty-nine of the 128 patients (30.5%) developed recurrent disease. Median follow-up for disease-free survival (DFS) was 6.49 years (95% CI 5.16 years; 7.62 years), and median follow-up for overall survival (OS) was 6.29 years (95% CI 5.45 years; 7.33 years). The 5-year DFS rate was 0.70 (95% CI: 0.62–0.79), and the 5-year OS rate was 0.79 (95% CI: 0.71–0.87). Regarding the survival outcome, there were no independent significant differences in either disease-free survival (DFS) (p = 0.300) or overall survival (p = 1.000) among patients within the three tumor-free resection margin categories. Multivariate analyses did not show any statistically significant association between tumor-free resection margin distance and recurrent disease or death, either when analyzed as a categorical variable or when analyzed as a continuous variable. Conclusion: The present study did not show a significant impact of pathological tumor-free resection margin distance following surgery in patients with node-negative SCC of the vulva (that did not receive adjuvant treatment) on disease-free and overall survival.
Hematopoietic Stem Cell Transplantation in Acute Promyelocytic Leukemia in the Era of All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide (ATO)
Authors: Colita Andrei , Tanase Alina Daniela , Tomuleasa Ciprian , Colita Anca
Published: August 2023

Acute promyelocytic leukemia (APL) currently represents one of the malignant hemopathies with the best therapeutic responses, following the introduction of all-trans retinoic acid (ATRA) and subsequently of arsenic trioxide (ATO) treatment. As a result, a large proportion of patients with APL achieve long-term responses after first-line therapy, so performing a hematopoietic stem cell transplant as consolidation of first complete remission (CR) is no longer necessary. Even in the case of relapses, most patients obtain a new remission as a result of therapy with ATO and ATRA, but an effective consolidation treatment is necessary to maintain it. The experience accumulated from studies published in the last two decades shows the effectiveness of hematopoietic stem cell transplantation (HSCT) in improving the outcome of patients who achieve a new CR. Thus, the expert groups recommend transplantation as consolidation therapy in patients with a second CR, with the indication for autologous HSCT in cases with molecular CR and for allogeneic HSCT in patients with the persistence of minimal residual disease (MRD) or with early relapse. However, there is a variety of controversial aspects related to the role of HSCT in APL, ranging from the fact that outcome data are obtained almost exclusively from retrospective studies and historical analyses to questions related to the type of transplantation, the impact of minimal residual disease, conditioning regimens, or the role of other therapeutic options. All these questions justify the need for controlled prospective studies in the following years.
The Present and Future of Neoadjuvant and Adjuvant Therapy for Locally Advanced Gastric Cancer
Authors: Koerner Anna S. , Moy Ryan H. , Ryeom Sandra W. , Yoon Sam S.
Published: August 2023

Gastric cancer is a highly prevalent and lethal disease worldwide. Given the insidious nature of the presenting symptoms, patients are frequently diagnosed with advanced, unresectable disease. However, many patients will present with locally advanced gastric cancer (LAGC), which is often defined as the primary tumor extending beyond the muscularis propria (cT3-T4) or having nodal metastases (cN+) disease and without distant metastases (cM0). LAGC is typically treated with surgical resection and perioperative chemotherapy. The treatment of LAGC remains a challenge, given the heterogeneity of this disease, and the optimal multimodal treatment regimen may be different for different LAGC subtypes. However, many promising treatments are on the horizon based on knowledge of molecular subtypes and key biomarkers of LAGC, such as microsatellite instability, HER2, Claudin 18.2, FGFR2, and PD-L1. This review will expand upon the discussion of current standard neoadjuvant and adjuvant therapies for LAGC and explore the ongoing and future clinical trials for novel therapies, with information obtained from searches in PubMed and ClinicalTrials.gov.
Zoledronic Acid Prevents Bone Resorption Caused by the Combination of Radium-223, Abiraterone Acetate, and Prednisone in an Intratibial Prostate Cancer Mouse Model
Authors: Suominen Mari I. , Knuuttila Matias , Sjöholm Birgitta , Wilson Timothy , Alhoniemi Esa , Mumberg Dominik , Käkönen Sanna-Maria , Scholz Arne
Published: August 2023

An increased risk of non-pathological fractures in patients with prostate cancer and bone metastases has been associated with combination treatment with radium-223, abiraterone, and prednisone/prednisolone in the absence of bone-protecting agents. Here, we investigated possible mechanisms leading to this outcome using an intratibial LNCaP model mimicking prostate cancer bone metastases. Male NOD.scid mice were inoculated intratibially with LNCaP prostate cancer cells and treated with vehicle, radium-223, abiraterone, prednisone, zoledronic acid, or their combinations for 28 days. Serum TRACP 5b and PSA levels were measured. Bone structure, quality, and formation rate of non-tumor-bearing and tumor-bearing tibiae were analyzed by microCT, 3-point bending assay, and dynamic histomorphometry, respectively. Radium-223 incorporation into bone was also measured. Radium-223/abiraterone/prednisone combination treatment induced a transient increase in bone resorption indicated by elevated TRACP 5b levels, which was inhibited by concurrent treatment with zoledronic acid. Furthermore, radium-223/abiraterone/prednisone combination reduced periosteal and trabecular new bone formation and the number of osteoblasts, but bone structure or biomechanical quality were not affected. The abiraterone/prednisone treatment decreased radium-223 incorporation into tumor-bearing bone, possibly explaining the lack of additional antitumor efficacy. In conclusion, radium-223/abiraterone/prednisone combination increased bone resorption, which may have been one of the mechanisms leading to an increased fracture risk in patients with mCRPC.
Association of Metabolic Syndrome with the Risk of Head and Neck Cancer: A 10-Year Follow-Up Study of 10 Million Initially Healthy Individuals
Authors: Kim Geun-Jeon , Han Kyung-Do , Joo Young-Hoon
Published: August 2023

The aim of this national population-based retrospective study was to analyze the relationship between MetS and the incidence of HNC. In this Korean population-based cohort study, 9,598,085 subjects above the age of 20 were monitored from 1 January 2009 to 31 December 2018. In the study population, a total of 10,732 individuals were newly diagnosed with HNC during the 10-year follow-up. The hazard ratio (HR), after adjusting for age, gender, smoking status, alcohol intake, and exercise, indicated that participants with MetS were at a 1.06-fold (95% CI: 1.01–1.10) higher risk of having HNC than those without MetS. Participants with MetS showed an increased risk of developing oral cavity cancer (HR, 1.12; 95% CI, 1.03–1.23) and laryngeal cancer (HR, 1.18; 95% CI, 1.09–1.27). Among the components of MetS, elevated fasting glucose (HR = 1.04, 95% CI: 1.00–1.08) and elevated blood pressure (HR = 1.08, 95% CI: 1.04–1.13) were significantly associated with an increased HR for HNC in an adjusted multivariable model. The association between HNC and MetS remained significant even among individuals who had never smoked or were ex-smokers (HR: 1.09; 95% CI: 1.04–1.15), as well as those who did not drink or were mild drinkers (HR: 1.07; 95% CI: 1.02–1.12). The findings of this cohort study suggest MetS was associated with an increased risk for some types of HNCs. The results of this study could assist with etiological investigations and prevention strategies.
Photocatalytic Degradation of 1,4-Dioxane by Heterostructured Bi2O3/Cu-MOF Composites
Authors: Wang Wen-Min , Zhang Lu , Wang Wen-Long , Huang Jin-Yi , Wu Qian-Yuan , Wu Jerry J.
Published: August 2023

Photocatalysts exhibiting high activity for the degradation of 1,4-dioxane (1,4-D) have been a subject of intense focus due to their high toxicity and challenging degradability. Bismuth oxide (Bi2O3) is recognized as an ideal photocatalyst; however, there have been limited studies on its effectiveness in 1,4-D degradation. It is crucial to address the issue of low photocatalytic efficiency attributed to the instability and easy recombination of photogenerated electrons and holes in Bi2O3 upon photoexcitation. In this study, Cu-MOF and oxygen vacancy were utilized to improve the 1,4-D photocatalytic degradation efficiency of Bi2O3 by preparing Bi2O3, Bi2O3/Cu-MOF, Bi2O3−x, and Bi2O3−x/Cu-MOF. The results revealed that the incorporation of Cu-MOF induced a larger specific surface area, a well-developed pore structure, and a smaller particle size in Bi2O3, facilitating enhanced visible light utilization and an improved photoelectron transfer rate, leading to the highest photocatalytic activity observed in Bi2O3/Cu-MOF. In addition, oxygen vacancies were found to negatively affect the photocatalytic activity of Bi2O3, mainly due to the transformation of the β-Bi2O3 crystalline phase into α-Bi2O3 caused by oxygen vacancies. Further, the synergistic effect of MOF and oxygen vacancies did not positively affect the photocatalytic activity of Bi2O3. Therefore, the construction of heterojunctions using Cu-MOF can significantly enhance the efficiency of degradation of 1,4-D, and Bi2O3/Cu-MOF appears to be a promising photocatalyst for 1,4-D degradation. This study opens new avenues for the design and optimization of advanced photocatalytic materials with improved efficiency for the treatment of recalcitrant organic pollutants.
Recent Progress in Pd-Catalyzed Tandem Processes
Authors: Nikoshvili Linda Z. , Matveeva Valentina G.
Published: August 2023

In recent years, Pd-containing catalytic systems for tandem processes have gained special attention due to their enhanced catalytic properties and their possibility of performing several reactions without the necessity of separating the intermediates. In this review, recent progress in Pd-catalyzed tandem processes is considered. Three types of catalytic systems are described: homogeneous catalysts (including immobilized Pd complexes); heterogeneous catalysts supported on oxides, MOFs, COFs, etc., with particular attention to the supports containing acid/base sites; and metal-enzyme catalysts for chemoenzymatic tandem processes applied in fine organic synthesis and biotechnology. For homogeneous Pd-catalyzed reactions, different tandem reactions were considered, i.e., cross-coupling, cyclization, carbonylation, isomerization, alkylation, arylation, etc.
Metabolic Disruption Induced by mTOR Signaling Pathway Inhibition in Regulatory T-Cell Expansion for Clinical Application
Authors: Gedaly Roberto , Orozco Gabriel , Ancheta Alexandre P. , Donoho Mackenzie , Desai Siddharth N. , Chapelin Fanny , Khurana Aman , Lewis Lillie J. , Zhang Cuiping , Marti Francesc
Published: August 2023

Background: Regulatory T cell (Treg) therapy is considered an alternative approach to induce tolerance in transplantation. If successful, this therapy may have implications on immunosuppression minimization/withdrawal to reduce drug-induced toxicity in patients. The aim of this study was to assess the efficacy of the mTORC1/C2 inhibitor, AZD8055, in the manufacturing of clinically competent Treg cells and compare the effects with those induced by rapamycin (RAPA), another mTOR inhibitor commonly used in Treg expansion protocols. Methods: Primary human Treg cells were isolated from leukapheresis product. Cell viability, expansion rates, suppressive function, autophagy, mitochondrial unfolded protein response (mitoUPR), and cell metabolic profile were assessed. Results: We observed a stronger inhibition of the mTORC2 signaling pathway and downstream events triggered by Interleukin 2 (IL2)-receptor in AZD8055-treated cells compared with those treated with RAPA. AZD8055 induced progressive metabolic changes in mitochondrial respiration and glycolytic pathways that disrupted the long-term expansion and suppressive function of Tregs. Unlike RAPA, AZD8055 treatment impaired autophagy and enhanced the mitoUPR cell stress response pathway. Conclusions: A distinct pattern of mTOR inhibition by AZD, compared with RAPA, induced mitochondrial stress response and dysfunction, impaired autophagy, and disrupted cellular bioenergetics, resulting in the loss of proliferative potential and suppressive function of Treg cells.
Human Lung Organoids—A Novel Experimental and Precision Medicine Approach
Authors: Kühl Laura , Graichen Pauline , von Daacke Nele , Mende Anne , Wygrecka Malgorzata , Potaczek Daniel P. , Miethe Sarah , Garn Holger
Published: August 2023

The global burden of respiratory diseases is very high and still on the rise, prompting the need for accurate models for basic and translational research. Several model systems are currently available ranging from simple airway cell cultures to complex tissue-engineered lungs. In recent years, human lung organoids have been established as highly transferrable three-dimensional in vitro model systems for lung research. For acute infectious and chronic inflammatory diseases as well as lung cancer, human lung organoids have opened possibilities for precise in vitro research and a deeper understanding of mechanisms underlying lung injury and regeneration. Human lung organoids from induced pluripotent stem cells or from adult stem cells of patients’ samples introduce tools for understanding developmental processes and personalized medicine approaches. When further state-of-the-art technologies and protocols come into use, the full potential of human lung organoids can be harnessed. High-throughput assays in drug development, gene therapy, and organoid transplantation are current applications of organoids in translational research. In this review, we emphasize novel approaches in translational and personalized medicine in lung research focusing on the use of human lung organoids.
An Improved Protocol for Targeted Differentiation of Primed Human Induced Pluripotent Stem Cells into HLA-G-Expressing Trophoblasts to Enable the Modeling of Placenta-Related Disorders
Authors: Shum Ian O. , Merkert Sylvia , Malysheva Svitlana , Jahn Kirsten , Lachmann Nico , Verboom Murielle , Frieling Helge , Hallensleben Michael , Martin Ulrich
Published: August 2023

Abnormalities at any stage of trophoblast development may result in pregnancy-related complications. Many of these adverse outcomes are discovered later in pregnancy, but the underlying pathomechanisms are constituted during the first trimester. Acquiring developmentally relevant material to elucidate the disease mechanisms is difficult. Human pluripotent stem cell (hPSC) technology can provide a renewable source of relevant cells. BMP4, A83-01, and PD173074 (BAP) treatment drives trophoblast commitment of hPSCs toward syncytiotrophoblast (STB), but lacks extravillous trophoblast (EVT) cells. EVTs mediate key functions during placentation, remodeling of uterine spiral arteries, and maintenance of immunological tolerance. We optimized the protocol for a more efficient generation of HLA-Gpos EVT-like trophoblasts from primed hiPSCs. Increasing the concentrations of A83-01 and PD173074, while decreasing bulk cell density resulted in an increase in HLA-G of up to 71%. Gene expression profiling supports the advancements of our treatment regarding the generation of trophoblast cells. The reported differentiation protocol will allow for an on-demand access to human trophoblast cells enriched for HLA-Gpos EVT-like cells, allowing for the elucidation of placenta-related disorders and investigating the immunological tolerance toward the fetus, overcoming the difficulties in obtaining primary EVTs without the need for a complex differentiation pathway via naïve pluripotent or trophoblast stem cells.
An Update on Nucleolar Stress: The Transcriptional Control of Autophagy
Authors: Pfister Astrid S.
Published: August 2023

Nucleolar stress reflects a misfunction of the nucleolus caused by a failure in ribosome biogenesis and defective nucleolar architecture. Various causes have been reported, most commonly mutation of ribosomal proteins and ribosome processing factors, as well as interference with these processes by intracellular or ectopic stress, such as RNA polymerase I inhibition, ROS, UV and others. The nucleolus represents the place for ribosome biogenesis and serves as a crucial hub in the cellular stress response. It has been shown to stimulate multiple downstream consequences, interfering with cell growth and survival. Nucleolar stress induction is most classically known to stimulate p53-dependent cell cycle arrest and apoptosis. Nucleolar stress represents a friend and enemy at the same time: From a pathophysiological perspective, inactivation of the nucleolar function by mutation or stress conditions is connected to multiple diseases, such as neurodegeneration, cancer and ribosomopathy syndromes. However, triggering the nucleolar stress response via specific chemotherapeutics, which interfere with nucleolar function, has beneficial effects for anti-cancer therapy. Interestingly, since the nucleolar stress response also triggers p53-independent mechanisms, it possesses the potential to specifically target p53-mutated tumors, which reflects the most common aberration in human cancer. More recent data have shown that the nucleolar stress response can activate autophagy and diverse signaling cascades that might allow initial pro-survival mechanisms. Nevertheless, it depends on the situation whether the cells undergo autophagy-mediated apoptosis or survive, as seen for autophagy-dependent drug resistance of chemotherapy-exposed tumor cells. Given the relatively young age of the research field, precise mechanisms that underly the involvement of autophagy in nucleolar stress are still under investigation. This review gives an update on the emerging contribution of nucleolar stress in the regulation of autophagy at a transcriptional level. It also appears that in autophagy p53-dependent as well as -independent responses are induced. Those could be exploited in future therapies against diseases connected to nucleolar stress.
Indian Ornamental Tarantula (Poecilotheria regalis) Venom Affects Myoblast Function and Causes Skeletal Muscle Damage
Authors: Richards Nicholas J. , Alqallaf Ali , Mitchell Robert D. , Parnell Andrew , Haidar Husain Bin , Almeida José R. , Williams Jarred , Vijayakumar Pradeep , Balogun Adedoyin , Matsakas Antonios , Trim Steven A. , Patel Ketan , Vaiyapuri Sakthivel
Published: August 2023

Envenomation by the Indian ornamental tarantula (Poecilotheria regalis) is medically relevant to humans, both in its native India and worldwide, where they are kept as pets. Muscle-related symptoms such as cramps and pain are commonly reported in humans following envenomation by this species. There is no specific treatment, including antivenom, for its envenomation. Moreover, the scientific knowledge of the impact of this venom on skeletal muscle function is highly limited. Therefore, we carried out this study to better understand the myotoxic properties of Poecilotheria regalis venom by determining its effects in cultured myoblasts and in the tibialis anterior muscle in mice. While there was no effect found on undifferentiated myoblasts, the venom affected differentiated multinucleated myotubes resulting in the reduction of fusion and atrophy of myotubes. Similarly, intramuscular administration of this venom in the tibialis anterior muscle in mice resulted in extensive muscle damage on day 5. However, by day 10, the regeneration was evident, and the regeneration process continued until day 20. Nevertheless, some tissue abnormalities including reduced dystrophin expression and microthrombi presence were observed on day 20. Overall, this study demonstrates the ability of this venom to induce significant muscle damage and affect its regeneration in the early stages. These data provide novel mechanistic insights into this venom-induced muscle damage and guide future studies to isolate and characterise individual toxic component(s) that induce muscle damage and their significance in developing better therapeutics.
Disparities in Neonatal Mortalities in the United States
Authors: Qattea Ibrahim , Burdjalov Maria , Quatei Amani , Agha Khalil Tamr , Kteish Rayan , Aly Hany
Published: August 2023

Objective: We aimed to look for the mortality of Black and White Neonates and compare the Black and White neonates’ mortalities after stratifying the population by many significant epidemiologic and hospital factors. Design/Method: We utilized the National Inpatient Sample (NIS) dataset over seven years from 2012 through 2018 for all neonates ≤ 28 days of age in all hospitals in the USA. Neonatal characteristics used in the analysis included ethnicity, sex, household income, and type of healthcare insurance. Hospital characteristics were urban teaching, urban non-teaching, and rural. Hospital location was classified according to the nine U.S. Census Division regions. Results: Neonatal mortality continues to be higher in Black populations: 21,975 (0.63%) than in White populations: 35,495 (0.28%). Government-supported health insurance was significantly more among Black populations when compared to White (68.8% vs. 35.3% p < 0.001). Household income differed significantly; almost half (49.8%) of the Black population has income ≤ 25th percentile vs. 22.1% in White. There was a significant variation in mortality in different U.S. locations. In the Black population, the highest mortality was in the West North Central division (0.72%), and the lower mortality was in the New England division (0.51%), whereas in the White population, the highest mortality was in the East South-Central division (0.36%), and the lowest mortality was in the New England division (0.21%). Trend analysis showed a significant decrease in mortality in Black and White populations over the years, but when stratifying the population by sex, type of insurance, household income, and type of hospital, the mortality was consistently higher in Black groups throughout the study years. Conclusions: Disparities in neonatal mortality continue to be higher in Black populations; there was a significant variation in mortality in different U.S. locations. In the Black population, the highest mortality was in the West North Central division, and the lower mortality was in the New England division, whereas in the White population, the highest mortality was in the East South Central division, and the lowest mortality was in the New England division. There has been a significant decrease in mortality in Black and White populations over the years, but when stratifying the population by many significant epidemiologic and hospital factors, the mortality was consistently higher in Black groups throughout the study years.
Risk-Adapted Treatment Strategies with Pre-Irradiation Chemotherapy in Pediatric Medulloblastoma: Outcomes from the Polish Pediatric Neuro-Oncology Group
Authors: Perek-Polnik Marta , Cochrane Anne , Wang Jinli , Chojnacka Marzanna , Drogosiewicz Monika , Filipek Iwona , Swieszkowska Ewa , Tarasinska Magdalena , Grajkowska Wiesława , Trubicka Joanna , Kowalczyk Paweł , Dembowska-Bagińskai Bożenna , Abdelbaki Mohamed
Published: August 2023

Craniospinal irradiation (CSI) has been a major component of the standard of care treatment backbone for childhood medulloblastoma. However, chemotherapy regimens have varied based on protocol, patient age, and molecular subtyping. In one of the largest studies to date, we analyzed treatment outcomes in children with newly-diagnosed medulloblastoma treated with pre-irradiation chemotherapy followed by risk-adapted radiotherapy and maintenance chemotherapy. A total of 153 patients from the Polish Pediatric Neuro-Oncology Group were included in the analysis. The median age at diagnosis was 8.0 years, and median follow-up time was 6.4 years. Sixty-seven patients were classified as standard-risk and eighty-six as high-risk. Overall survival (OS) and event-free survival (EFS) for standard-risk patients at 5 years (±standard error) were 87 ± 4.3% and 84 ± 4.6%, respectively, while 5-year OS and EFS for high-risk patients were 81 ± 4.3% and 79 ± 4.5%, respectively. Only one patient had disease progression prior to radiotherapy. This study demonstrates promising survival outcomes in patients treated with pre-irradiation chemotherapy followed by risk-adapted CSI and adjuvant chemotherapy. Such an approach may be useful in cases where the initiation of radiotherapy may need to be delayed, a common occurrence in many institutions globally.
Mixed Medicinal Mushroom Mycelia Attenuates Alzheimer’s Disease Pathologies In Vitro and In Vivo
Authors: Jeong Ji Heun , Hong Geum-Lan , Jeong Young Gil , Lee Nam Seob , Kim Do Kyung , Park Jong Yea , Park Mina , Kim Hyun Min , Kim Ya El , Yoo Yung Choon , Han Seung Yun
Published: August 2023

Alzheimer’s disease (AD) is characterized by memory impairment and existence of amyloid-β (Aβ) plaques and neuroinflammation. Due to the pivotal role of oxidative damage in AD, natural antioxidative agents, such as polyphenol-rich fungi, have garnered scientific scrutiny. Here, the aqueous extract of mixed medicinal mushroom mycelia (MMMM)—Phellinus linteus, Ganoderma lucidum, and Inonotus obliquus—cultivated on a barley medium was assessed for its anti-AD effects. Neuron-like PC12 cells, which were subjected to Zn2+, an Aβ aggregator, were employed as an in vitro AD model. The cells pretreated with or without MMMM were assayed for Aβ immunofluorescence, cell viability, reactive oxygen species (ROS), apoptosis, and antioxidant enzyme activity. Then, 5XFAD mice were administered with 30 mg/kg/day MMMM for 8 weeks and underwent memory function tests and histologic analyses. In vitro results demonstrated that the cells pretreated with MMMM exhibited attenuation in Aβ immunofluorescence, ROS accumulation, and apoptosis, and incrementation in cell viability and antioxidant enzyme activity. In vivo results revealed that 5XFAD mice administered with MMMM showed attenuation in memory impairment and histologic deterioration such as Aβ plaque accumulation and neuroinflammation. MMMM might mitigate AD-associated memory impairment and cerebral pathologies, including Aβ plaque accumulation and neuroinflammation, by impeding Aβ-induced neurotoxicity.