bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential efficacy of dopaminergic antidepressants in treatment resistant anergic-anhedonic depression results of the chronic anergic-anhedonic depression open trial – CADOT
Authors: Dormegny-Jeanjean Ludovic Christophe , de Billy Clément , Mainberger Olivier , Weibel Sébastien , Schorr Benoit , Obrecht Alexandre , Landré Lionel , Berna Fabrice , Causin Jean-Baptiste , Blanc Frederic , Danila Vlad , Tomsa Mihaela , Pfleger Geraldine , Meyer Camille , Humbert Ilia , Javelot Hervé , Meyer Guillaume , Bertschy Gilles , Foucher Jack Rene
Published: October 2023

Introduction

Among treatment-resistant depression (TRD), we identified anergic-anhedonic clinical presentations (TRAD) as putatively responsive to pro-dopaminergic strategies. Based on the literature, non-selective monoamine oxidase inhibitors (MAOI) and dopamine D2 receptor agonists (D2RAG) were sequentially introduced, frequently under the coverage of a mood stabilizer. This two-step therapeutic strategy will be referred to as the Dopaminergic Antidepressant Therapy Algorithm (DATA). We describe the short and long-term outcomes of TRAD managed according to DATA guidelines.

Method

Out of 52 outpatients with TRAD treated with DATA in a single expert center, 48 were included in the analysis [severity – QIDS (Quick Inventory of Depressive Symptomatology) = 16 ± 3; episode duration = 4.1 ± 2.7 years; Thase and Rush resistance stage = 2.9 ± 0.6; functioning – GAF (Global Assessment of Functioning) = 41 ± 8]. These were followed-up for a median (1st – 3rd quartile) of 4 (1–9) months before being prescribed the first dopaminergic treatment and remitters were followed up 21 (11–33) months after remission.

Results

At the end of DATA step 1, 25 patients were in remission (QIDS <6; 52% [38–66%]). After DATA step 2, 37 patients were in remission (77% [65–89%]) to whom 5 patients with a QIDS score = 6 could be added (88% [78–97%]). Many of these patients felt subjectively remitted (GAF = 74 ± 10). There was a significant benefit to combining MAOI with D2RAG which was maintained for at least 18 months in 30 patients (79% [62–95%]).

Conclusion

These results support TRAD sensitivity to pro-dopaminergic interventions. However, some clinical heterogeneities remain in our sample and suggest some improvement in the description of dopamine-sensitive form(s).
Autism symptoms, functional impairments, and gaze fixation measured using an eye-tracker in 6-year-old children
Authors: Mori Toko , Tsuchiya Kenji J. , Harada Taeko , Nakayasu Chikako , Okumura Akemi , Nishimura Tomoko , Katayama Taiichi , Endo Masayuki
Published: October 2023

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental disorder clinically characterized by abnormalities in eye contact during social exchanges. We aimed to clarify whether the amount of gaze fixation, measured at the age of 6 years using Gazefinder, which is an established eye-tracking device, is associated with ASD symptoms and functioning.

Methods

The current study included 742 participants from the Hamamatsu Birth Cohort Study. Autistic symptoms were evaluated according to the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), and the functioning of the participating children in real life was assessed using the Japanese version of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). The Gazefinder system was used for gaze fixation rates; two areas of interest (eyes and mouth) were defined in a talking movie clip, and eye gaze positions were calculated through corneal reflection techniques.

Results

The participants had an average age of 6.06 ± 0.14 years (males: 384; 52%). According to ADOS, 617 (83%) children were assessed as having none/mild ASD and 51 (7%) as severe. The average VABS-II scores were approximately 100 (standard deviation = 12). A higher gaze fixation rate on the eyes was associated with a significantly lower likelihood of the child being assigned to the severe ADOS group after controlling for covariates (odds ratio [OR], 0.02; 95% confidence interval [CI], 0.002–0.38). The gaze fixation rate on the mouth was not associated with ASD symptoms. A higher gaze fixation rate on the mouth was associated with a significantly lower likelihood of the child being assigned to the low score group in VABS-II socialization after controlling for covariates (OR, 0.18; 95% CI, 0.04–0.85). The gaze fixation rate on the eyes was not associated with functioning.

Conclusion

We found that children with low gaze fixation rates on the eyes were likely to have more ASD symptoms, and children with low gaze fixation rates on the mouth were likely to demonstrate poorer functioning in socialization. Hence, preschool children could be independently assessed in the general population for clinically relevant endophenotypes predictive of ASD symptoms and functional impairments.
Effect of Annual Influenza Vaccination on the Risk of Lung Cancer Among Patients With Hypertension: A Population-Based Cohort Study in Taiwan
Authors: Jong Hung-Chang , Zheng Jing-Quan , Zheng Cai-Mei , Lin Cheng-Hsin , Chiu Chun-Chih , Hsu Min-Huei , Fang Yu-Ann , Hao Wen-Rui , Chen Chun-Chao , Yang Tsung Yeh , Lee Kang-Yun , Liu Ju-Chi
Published: October 2023

Objectives: Lung cancer is a main contributor to all newly diagnosed cancers worldwide. The chemoprotective effect of the influenza vaccine among patients with hypertension remains unclear.

Methods: A total of 37,022 patients with hypertension were retrospectively enrolled from the Taiwan National Health Insurance Research Database. These patients were further divided into a vaccinated group (n = 15,697) and an unvaccinated group (n = 21,325).

Results: After adjusting for sex, age, comorbidities, medications, level of urbanization and monthly income, vaccinated patients had a significantly lower risk of lung cancer occurrence than unvaccinated patients (adjusted hazard ratio [aHR]: 0.56, 95% confidence interval [CI]: 0.47–0.67). A potential protective effect was observed for both sexes and in the elderly age group. With a greater total number of vaccinations, a potentially greater protective effect was observed (aHR: 0.75, 95% CI 0.60–0.95; aHR: 0.66, 95% CI: 0.53–0.82; aHR: 0.26, 95% CI: 0.19–0.36, after receiving 1, 2–3 and ≥4 vaccinations, respectively).

Conclusion: Influenza vaccination was associated with a lower risk of lung cancer among patients with hypertension. The potentially chemoprotective effect appeared to be dose dependent.
Excess Mortality in Kidney and Kidney-Pancreas Transplant Recipients in the COVID-19 Pandemic in Portugal—A Cohort Study
Authors: Coimbra Miguel T. , Francisco José A. T. S. , Freitas Joana C. , Carvalho Renata V. , Vilela Sara R. B. , Ribeiro Catarina I. C. D. , Silvano José L. C. S. L. , Pedroso Sofia , Almeida Manuela , Martins La Salete , Malheiro Jorge
Published: October 2023

The COVID-19 pandemic increased morbidity and mortality worldwide, particularly in the Kidney and Kidney-Pancreas Transplant Recipient (KTR/KPTR) population. Aiming at assessing the absolute and relative excess mortality (EM) in a Portuguese KTR/KPTR cohort, we conducted a retrospective observational study of two KTR/KPTRs cohorts: cohort 1 (P1; n = 2,179) between September/2012 and March/2020; cohort 2 (P2; n = 2067) between March/2020, and August/2022. A correlation between relative and absolute EM and age, sex, time from transplantation and cause of death was explored. A total of 145 and 84 deaths by all causes were observed in P1 and P2, respectively. The absolute EM in P2 versus P1 was 19.2 deaths (observed/expected mortality ratio 1.30, p = 0.006), and the relative EM was 1.47/1,000 person-months (95% CI 1.11–1.93, p = 0.006). Compared to the same period in the general population, the standardized mortality rate by age in P2 was 3.86 (95% CI 2.40–5.31), with a peak at 9.00 (95% CI 4.84–13.16) in P2C. The higher EM identified in this population was associated, mainly, with COVID-19 infection, with much higher values during the second seasonal COVID-19 peak when compared to the general population, despite generalized vaccination. These highlight the need for further preventive measures and improved therapies in these patients.
A Novel Transversal-Feed Electron Cyclotron Resonance Plasma Thruster: Design and Plasma Characteristics Analysis
Authors: Han Yajie , Xia Guangqing , Sun Bin , Zhang Junjun , Chen Liuwei , Lu Chang
Published: October 2023

This paper presents the development, analysis, and performance evaluation of a novel transversal-feed Electron Cyclotron Resonance Plasma Thruster (ECRPT). The ECRPT operates based on the transversal-feed principle and incorporates optimized structural design. Through extensive simulation of the S-parameters of the antenna, optimal antenna sizes are determined for both coaxial and transversal-feed configurations. Additionally, the electric field intensity of the antenna is simulated for both feed structures, revealing higher electric field intensity in the transversal structure, thereby promoting discharge. We employ the drift-diffusion model to calculate the number density of electrons in the discharge chamber and ascertain that the number density can reach an order of magnitude of 1018 m−3. Experimental discharge tests are conducted under various microwave power conditions, demonstrating that the thruster can initiate and cease operation with an incident power as low as 5 W, significantly lower than that of traditional coaxial feed structures. At a power level of 20 W, the ion current density can attain 3 A/m2. Moreover, the transversal-feed thruster exhibits exceptional performance when the power exceeds 10 W, and the propellant flow rate ranges from 0.5 SCCM to 5 SCCM. The superior performance characteristics of the proposed thruster configuration make it a promising candidate for applications demanding efficient and low-power plasma propulsion systems.
Multiscale Aeroelastic Optimization Method for Wing Structure and Material
Authors: Li Keyu , Yang Chao , Wang Xiaozhe , Wan Zhiqiang , Li Chang
Published: October 2023

Microstructured materials, characterized by their lower weight and multifunctionality, have great application prospects in the aerospace field. Optimization methods play a pivotal role in enhancing the design efficiency of both macrostructural and microstructural topology (MMT) for aircraft. This paper proposes a multiscale aeroelastic optimization method for wing structure and material considering realistic aerodynamic loads for large aspect ratio wings with significant aeroelastic effects. The aerodynamic forces are calculated by potential flow theory and the aeroelastic equilibrium equations are solved through finite element method. The parallel design of the wing MMT is achieved by utilizing the optimization criterion (OC) method based on sensitivity information. The optimization results indicate that wing elastic effects reinforce the outer section of the wing structure compared with the optimization results obtained under rigid aerodynamic forces. As the optimization constraints become more rigorous, the optimization results show that the components with larger loads are strengthened. Furthermore, the method presented in this paper can effectively optimize the wing structure under complex boundary conditions to achieve a reasonable stiffness distribution in the wing.
Developmental Mapping of Hair Follicles in the Embryonic Stages of Cashmere Goats Using Proteomic and Metabolomic Construction
Authors: Gao Yuan , Duo Lei , Zhe Xiaoshu , Hao Lingyun , Song Weiguo , Gao Lizhong , Cai Jun , Liu Dongjun
Published: October 2023

The hair follicle (HF) is the fundamental unit for fleece and cashmere production in cashmere goats and is crucial in determining cashmere yield and quality. The mechanisms regulating HF development in cashmere goats during the embryonic period remain unclear. Growing evidence suggests that HF development involves complex developmental stages and critical events, and identifying the underlying factors can improve our understanding of HF development. In this study, samples were collected from embryonic day 75 (E75) to E125, the major HF developmental stages. The embryonic HFs of cashmere goats were subjected to proteomic and metabolomic analyses, which revealed dynamic changes in the key factors and signalling pathways controlling HF development at the protein and metabolic levels. Gene ontology and the Kyoto Encyclopaedia of Genes and Genomes were used to functionally annotate 1784 significantly differentially expressed proteins and 454 significantly differentially expressed metabolites enriched in different HF developmental stages. A joint analysis revealed that the oxytocin signalling pathway plays a sustained role in embryonic HF development by activating the MAPK and Ca2+ signalling pathways, and a related regulatory network map was constructed. This study provides a global perspective on the mechanism of HF development in cashmere goats and enriches our understanding of embryonic HF development.
Effects of Tributyltin-Contaminated Aquatic Environments and Remediated Water on Early Development of Sea Urchin (Hemisentrotus pulcherrimus)
Authors: Choi Hee-Chan , Lee Ju-Wook , Hwang Un-Ki , Jeon Ha-Jeong , Oh Sung-Yong , Kim Chul-Won , Kang Han-Seung
Published: October 2023

In this study, gametotoxicity and embryotoxicity experiments were performed using Hemicentrotus pulcherrimus to investigate the toxic effects of tributyltin (TBT). The effects of TBT on fertilization and embryogenesis were assessed at various concentrations (0, 0.02, 0.05, 0.09, 0.16, 0.43, 0.73, 4.68, and 9.22 ppb). The fertilization rates decreased in a concentration-dependent manner, with significant reduction following treatment with TBT at 0.05 ppb. Embryos exhibited developmental impairment after TBT exposure at each tested concentration. The frequency of developmental inhibition delay that treatment with TBT delayed embryonic development in a dose-dependent manner, with 100% of embryos exhibiting developmental impairment at 4.68 ppb. During developmental recovery tests, embryos cultured in fresh media without TBT showed advanced embryonic development. Although the observed normal development after transferring the developmentally delayed embryos to fresh media without TBT offers prospects for the restoration of contaminated environments, embryonic development remained incomplete. These results suggest that TBT adversely affects the early embryonic development of H. pulcherrimus.
Quasiconformal Homeomorphisms Explicitly Determining the Basic Curve Quasi-Invariants
Authors: Krushkal Samuel L.
Published: October 2023

The classical Belinskii theorem implies that any sufficiently regular function μ(z) on the extended complex plane C^ with a small C1+α norm generates via the two-dimensional Cauchy integral a quasiconformal automorphism w of C^ with the Beltrami coefficient μ˜=μ+O(∥μ∥2). We consider μ supported in arbitrary bounded quasiconformal disks and show that under appropriate assumptions of μ, this automorphism explicitly provides the basic curvelinear quasi-invariants associated with conformal and quasiconformal maps, advancing an old problem of quasiconformal analysis.
Effects of Barefoot and Shod Conditions on the Kinematics and Kinetics of the Lower Extremities in Alternating Jump Rope Skipping—A One-Dimensional Statistical Parameter Mapping Study
Authors: Li Jun , Wu Kaicheng , Ye Dongqiang , Deng Liqin , Wang Jichao , Fu Weijie
Published: October 2023

Purpose: To explore the difference in the biomechanics of the lower extremity during alternating jump rope skipping (AJRS) under barefoot and shod conditions. Methods: Fourteen experienced AJRS participants were randomly assigned to wear jump rope shoes or be barefoot (BF) during the AJRS at a self-selected speed. The Qualisys motion capture system and Kistler force platform were used to synchronously collect the ground reaction forces and trajectory data of the hip, knee, ankle, and metatarsophalangeal (MTP) joints. One-dimensional statistical parameter mapping was used to analyze the kinematics and kinetics of the lower extremity under both conditions using paired t-tests. Results: Wearing shoes resulted in a significant decrease in the ROM (p < 0.001) and peak angular velocity (p < 0.001) of the MTP joint during the landing phase. In addition, the MTP joint power (p < 0.001) was significantly larger under shod condition at 92–100% of the landing phase. Moreover, wearing shoes reduced the peak loading rate (p = 0.002). Conclusion: The findings suggest that wearing shoes during AJRS could provide better propulsion during push-off by increasing the MTP plantarflexion joint power. In addition, our results emphasize the significance of the ankle and MTP joint by controlling the ankle and MTP joint angle.
Prognostic Significance of β-Catenin in Relation to the Tumor Immune Microenvironment in Oral Cancer
Authors: Lequerica-Fernández Paloma , Rodríguez-Santamarta Tania , García-García Eduardo , Blanco-Lorenzo Verónica , Torres-Rivas Héctor E. , Rodrigo Juan P. , Suárez-Sánchez Faustino J. , García-Pedrero Juana M. , De Vicente Juan Carlos
Published: October 2023

The aim of this study was to investigate the prognostic relevance of β-catenin expression in oral squamous cell carcinoma (OSCC) and to explore relationships with the tumor immune microenvironment. Expression of β-catenin and PD-L1, as well as lymphocyte and macrophage densities, were evaluated by immunohistochemistry in 125 OSCC patient specimens. Membranous β-catenin expression was detected in 102 (81.6%) and nuclear β-catenin in 2 (1.6%) tumors. There was an association between β-catenin expression, tumoral, and stromal CD8+ T-cell infiltration (TIL) and also the type of tumor immune microenvironment (TIME). Tumors harboring nuclear β-catenin were associated with a type II TIME (i.e., immune ignorance defined by a negative PD-L1 expression and low CD8+ TIL density), whereas tumors with membranous β-catenin expression were predominantly type IV (i.e., immune tolerance defined by negative PD-L1 and high CD8+ TIL density). Combined, but not individual, high stromal CD8+ TILs and membranous β-catenin expression was independently associated with better disease-specific survival (HR = 0.48, p = 0.019). Taken together, a combination of high stromal CD8+ T-cell infiltration and membranous β-catenin in the tumor emerges as an independent predictor of better survival in OSCC patients.
Evaluation of the Kinetics of Pancreatic Stone Protein as a Predictor of Ventilator-Associated Pneumonia
Authors: Ceccato Adrian , Camprubí-Rimblas Marta , Bos Lieuwe D. J. , Povoa Pedro , Martin-Loeches Ignacio , Forné Carles , Areny-Balagueró Aina , Campaña-Duel Elena , Morales-Quinteros Luis , Quero Sara , Ramirez Paula , Esperatti Mariano , Torres Antoni , Blanch Lluis , Artigas Antonio
Published: October 2023

BACKGROUND: Ventilator-associated pneumonia (VAP) is a severe condition. Early and adequate antibiotic treatment is the most important strategy for improving prognosis. Pancreatic Stone Protein (PSP) has been described as a biomarker that increases values 3–4 days before the clinical diagnosis of nosocomial sepsis in different clinical settings. We hypothesized that serial measures of PSP and its kinetics allow for an early diagnosis of VAP. METHODS: The BioVAP study was a prospective observational study designed to evaluate the role of biomarker dynamics in the diagnosis of VAP. To determine the association between repeatedly measured PSP and the risk of VAP, we used joint models for longitudinal and time-to-event data. RESULTS: Of 209 patients, 43 (20.6%) patients developed VAP, with a median time of 4 days. Multivariate joint models with PSP, CRP, and PCT did not show an association between biomarkers and VAP for the daily absolute value, with a hazard ratio (HR) for PSP of 1.01 (95% credible interval: 0.97 to 1.05), for CRP of 1.00 (0.83 to 1.22), and for PCT of 0.95 (0.82 to 1.08). The daily change of biomarkers provided similar results, with an HR for PSP of 1.15 (0.94 to 1.41), for CRP of 0.76 (0.35 to 1.58), and for PCT of 0.77 (0.40 to 1.45). CONCLUSION: Neither absolute PSP values nor PSP kinetics alone nor in combination with other biomarkers were useful in improving the prediction diagnosis accuracy in patients with VAP. Clinical Trial Registration: Registered retrospectively on August 3rd, 2012. NCT02078999.
Perspectives on the Current State of Bioprinted Skin Substitutes for Wound Healing
Authors: Sörgel Celena A. , Cai Aijia , Schmid Rafael , Horch Raymund E.
Published: October 2023

Human skin is particularly vulnerable to external damaging influences such as irradiation, extreme temperatures, chemical trauma, and certain systemic diseases, which reduce the skin’s capacity for regeneration and restoration and can possibly lead to large-scale skin defects. To restore skin continuity in severe cases, surgical interventions such as the transplantation of autologous tissue are needed. Nevertheless, the coverage of larger skin defects caused by severe third-grade burns or extensive irradiation therapy is limited due to the depletion of uninjured autologous tissue. In such cases, many of the patient’s epidermal cells can become available using biofabricated skin grafts, thereby restoring the skin’s vital functions. Given the limited availability of autologous skin grafts for restoring integrity in large-scale defects, using bioprinted constructs as skin graft substitutes could offer an encouraging therapeutic alternative to conventional therapies for large-scale wounds, such as the transplantation of autologous tissue. Using layer-by-layer aggregation or volumetric bioprinting, inkjet bioprinting, laser-assisted bioprinting, or extrusion-based bioprinting, skin cells are deposited in a desired pattern. The resulting constructs may be used as skin graft substitutes to accelerate wound healing and reconstitute the physiological functions of the skin. In this review, we aimed to elucidate the current state of bioprinting within the context of skin tissue engineering and introduce and discuss different bioprinting techniques, possible approaches and materials, commonly used cell types, and strategies for graft vascularization for the production of bioprinted constructs for use as skin graft substitutes.
Trophoblast Cell Function in the Antiphospholipid Syndrome
Authors: Vrzić Petronijević Svetlana , Vilotić Aleksandra , Bojić-Trbojević Žanka , Kostić Sanja , Petronijević Miloš , Vićovac Ljiljana , Jovanović Krivokuća Milica
Published: October 2023

Antiphospholipid syndrome (APS) is a complex thrombo-inflammatory autoimmune disease characterized by the presence of antiphospholipid antibodies (aPL). Women with APS are at high risk of recurrent early pregnancy loss as well as late obstetrical complications—premature birth due to placental insufficiency or severe preeclampsia. Accumulating evidence implies that vascular thrombosis is not the only pathogenic mechanism in obstetric APS, and that the direct negative effect of aPL on the placental cells, trophoblast, plays a major role. In this review, we summarize the current findings regarding the potential mechanisms involved in aPL-induced trophoblast dysfunction. Introduction on the APS and aPL is followed by an overview of the effects of aPL on trophoblast—survival, cell function and aPL internalization. Finally, the implication of several non-coding RNAs in pathogenesis of obstetric APS is discussed, with special emphasis of their possible role in trophoblast dysfunction and the associated mechanisms.
Bioprospecting of Sea Anemones (Cnidaria, Anthozoa, Actiniaria) for β-Defensin-like α-Amylase Inhibitors
Authors: Popkova Daria , Otstavnykh Nadezhda , Sintsova Oksana , Baldaev Sergey , Kalina Rimma , Gladkikh Irina , Isaeva Marina , Leychenko Elena
Published: October 2023

Diabetes mellitus is one of the most serious diseases of our century. The drugs used are limited or have serious side effects. The search for new sources of compounds for effective treatment is relevant. Magnificamide, a peptide inhibitor of mammalian α-amylases, isolated from the venom of sea anemone Heteractis magnifica, can be used for the control of postprandial hyperglycemia in diabetes mellitus. Using the RACE approach, seven isoforms of magnificamide were detected in H. magnifica tentacles. The exon–intron structure of magnificamide genes was first established, and intron retention in the mature peptide-encoding region was revealed. Additionally, an α-amylase inhibitory domain was discovered in the mucins of some sea anemones. According to phylogenetics, sea anemones diverge into two groups depending on the presence of β-defensin-like α-amylase inhibitors and/or mucin-inhibitory domains. It is assumed that the intron retention phenomenon leads to additional diversity in the isoforms of inhibitors and allows for its neofunctionalization in sea anemone tentacles. Bioprospecting of sea anemones of the order Actiniaria for β-defensin-like α-amylase inhibitors revealed a diversity of inhibitory sequences that represents a starting point for the design of effective glucose-lowering drugs.
Novel Para-Aminobenzoic Acid Analogs and Their Potential Therapeutic Applications
Authors: Haroon Faisal , Farwa Umme , Arif Maimoona , Raza Muhammad Asam , Sandhu Zeshan Ali , El Oirdi Mohamed , Farhan Mohd , Alhasawi Mohammed Ahmed Ismail
Published: October 2023

A “building block” is a key component that plays a substantial and critical function in the pharmaceutical research and development industry. Given its structural versatility and ability to undergo substitutions at both the amino and carboxyl groups, para-aminobenzoic acid (PABA) is a commonly used building block in pharmaceuticals. Therefore, it is great for the development of a wide range of novel molecules with potential medical applications. Anticancer, anti-Alzheimer’s, antibacterial, antiviral, antioxidant, and anti-inflammatory properties have been observed in PABA compounds, suggesting their potential as therapeutic agents in future clinical trials. PABA-based therapeutic chemicals as molecular targets and their usage in biological processes are the primary focus of this review study. PABA’s unique features make it a strong candidate for inclusion in a massive chemical database of molecules having drug-like effects. Based on the current literature, further investigation is needed to evaluate the safety and efficacy of PABA derivatives in clinical investigations and better understand the specific mechanism of action revealed by these compounds.
Mu-Net a Light Architecture for Small Dataset Segmentation of Brain Organoid Bright-Field Images
Authors: Brémond Martin Clara , Simon Chane Camille , Clouchoux Cédric , Histace Aymeric
Published: October 2023

To characterize the growth of brain organoids (BOs), cultures that replicate some early physiological or pathological developments of the human brain are usually manually extracted. Due to their novelty, only small datasets of these images are available, but segmenting the organoid shape automatically with deep learning (DL) tools requires a larger number of images. Light U-Net segmentation architectures, which reduce the training time while increasing the sensitivity under small input datasets, have recently emerged. We further reduce the U-Net architecture and compare the proposed architecture (MU-Net) with U-Net and UNet-Mini on bright-field images of BOs using several data augmentation strategies. In each case, we perform leave-one-out cross-validation on 40 original and 40 synthesized images with an optimized adversarial autoencoder (AAE) or on 40 transformed images. The best results are achieved with U-Net segmentation trained on optimized augmentation. However, our novel method, MU-Net, is more robust: it achieves nearly as accurate segmentation results regardless of the dataset used for training (various AAEs or a transformation augmentation). In this study, we confirm that small datasets of BOs can be segmented with a light U-Net method almost as accurately as with the original method.
Regulation of Protein-Induced Apoptosis and Autophagy in Human Hepatocytes Treated with Metformin and Paclitaxel In Silico and In Vitro
Authors: Al-Zahrani Norah Saeed , Zamzami Mazin Abdulaziz , Baghdadi Mohammed A. , El-Gowily Afnan H. , Ali Ehab M. M.
Published: October 2023

Metformin and paclitaxel therapy offer promising outcomes in the treatment of liver cancer. Combining paclitaxel with metformin enhances treatment effectiveness and mitigates the adverse effects associated with paclitaxel alone. This study explored the anticancer properties of metformin and paclitaxel in HepG2 liver cancer cells, MCF-7 breast cancer cells, and HCT116 colon cancer cells. The results demonstrated that the combination of these agents exhibited a lower IC50 in the tested cell lines compared to paclitaxel monotherapy. Notably, treating the HepG2 cell line with this combination led to a reduction in the G0/G1 phase and an increase in the S and G2/M phases, ultimately triggering early apoptosis. To further investigate the interaction between the cellular proteins with paclitaxel and metformin, an in silico study was conducted using proteins chosen from a protein data bank (PDB). Among the proteins studied, AMPK-α, EGFRK, and FKBP12-mTOR exhibited the highest binding free energy, with values of −11.01, −10.59, and −15.63 kcal/mol, respectively, indicating strong inhibitory or enhancing effects on these proteins. When HepG2 cells were exposed to both paclitaxel and metformin, there was an upregulation in the gene expression of AMPK-α, a key regulator of the energy balance in cancer growth, as well as apoptotic markers such as p53 and caspase-3, along with autophagic markers including beclin1 and ATG4A. This combination therapy of metformin and paclitaxel exhibited significant potential as a treatment option for HepG2 liver cancer. In summary, the combination of metformin and paclitaxel not only enhances treatment efficacy but also reduces side effects. It induces cell cycle alterations and apoptosis and modulates key cellular proteins involved in cancer growth, making it a promising therapy for HepG2 liver cancer.
CAR T-Cells in Acute Lymphoblastic Leukemia: Current Status and Future Prospects
Authors: Almaeen Abdulrahman H. , Abouelkheir Mohamed
Published: October 2023

The currently available treatment for acute lymphoblastic leukemia (ALL) is mainly dependent on the combination of chemotherapy, steroids, and allogeneic stem cell transplantation. However, refractoriness and relapse (R/R) after initial complete remission may reach up to 20% in pediatrics. This percentage may even reach 60% in adults. To overcome R/R, a new therapeutic approach was developed using what is called chimeric antigen receptor-modified (CAR) T-cell therapy. The Food and Drug Administration (FDA) in the United States has so far approved four CAR T-cells for the treatment of ALL. Using this new therapeutic strategy has shown a remarkable success in treating R/R ALL. However, the use of CAR T-cells is expensive, has many imitations, and is associated with some adverse effects. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are two common examples of these adverse effects. Moreover, R/R to CAR T-cell therapy can take place during treatment. Continuous development of this therapeutic strategy is ongoing to overcome these limitations and adverse effects. The present article overviews the use of CAR T-cell in the treatment of ALL, summarizing the results of relevant clinical trials and discussing future prospects intended to improve the efficacy of this therapeutic strategy and overcome its limitations.
The RELT Family of Proteins: An Increasing Awareness of Their Importance for Cancer, the Immune System, and Development
Authors: Cusick John K. , Alcaide Jessa , Shi Yihui
Published: October 2023

This review highlights Receptor Expressed in Lymphoid Tissues (RELT), a Tumor Necrosis Factor Superfamily member, and its two paralogs, RELL1 and RELL2. Collectively, these three proteins are referred to as RELTfms and have gained much interest in recent years due to their association with cancer and other human diseases. A thorough knowledge of their physiological functions, including the ligand for RELT, is lacking, yet emerging evidence implicates RELTfms in a variety of processes including cytokine signaling and pathways that either promote cell death or survival. T cells from mice lacking RELT exhibit increased responses against tumors and increased inflammatory cytokine production, and multiple lines of evidence indicate that RELT may promote an immunosuppressive environment for tumors. The relationship of individual RELTfms in different cancers is not universal however, as evidence indicates that individual RELTfms may be risk factors in certain cancers yet appear to be protective in other cancers. RELTfms are important for a variety of additional processes related to human health including microbial pathogenesis, inflammation, behavior, reproduction, and development. All three proteins have been strongly conserved in all vertebrates, and this review aims to provide a clearer understanding of the current knowledge regarding these interesting proteins.
YOLO-DRS: A Bioinspired Object Detection Algorithm for Remote Sensing Images Incorporating a Multi-Scale Efficient Lightweight Attention Mechanism
Authors: Liao Huan , Zhu Wenqiu
Published: October 2023

Bioinspired object detection in remotely sensed images plays an important role in a variety of fields. Due to the small size of the target, complex background information, and multi-scale remote sensing images, the generalized YOLOv5 detection framework is unable to obtain good detection results. In order to deal with this issue, we proposed YOLO-DRS, a bioinspired object detection algorithm for remote sensing images incorporating a multi-scale efficient lightweight attention mechanism. First, we proposed LEC, a lightweight multi-scale module for efficient attention mechanisms. The fusion of multi-scale feature information allows the LEC module to completely improve the model’s ability to extract multi-scale targets and recognize more targets. Then, we propose a transposed convolutional upsampling alternative to the original nearest-neighbor interpolation algorithm. Transposed convolutional upsampling has the potential to greatly reduce the loss of feature information by learning the feature information dynamically, thereby reducing problems such as missed detections and false detections of small targets by the model. Our proposed YOLO-DRS algorithm exhibits significant improvements over the original YOLOv5s. Specifically, it achieves a 2.3% increase in precision (P), a 3.2% increase in recall (R), and a 2.5% increase in mAP@0.5. Notably, the introduction of the LEC module and transposed convolutional results in a respective improvement of 2.2% and 2.1% in mAP@0.5. In addition, YOLO-DRS only increased the GFLOPs by 0.2. In comparison to the state-of-the-art algorithms, namely YOLOv8s and YOLOv7-tiny, YOLO-DRS demonstrates significant improvements in the mAP@0.5 metrics, with enhancements ranging from 1.8% to 7.3%. It is fully proved that our YOLO-DRS can reduce the missed and false detection problems of remote sensing target detection.
Effect of Bacterial Amyloid Protein Phenol−Soluble Modulin Alpha 3 on the Aggregation of Amyloid Beta Protein Associated with Alzheimer’s Disease
Authors: Peng Bushu , Xu Shaoying , Liang Yue , Dong Xiaoyan , Sun Yan
Published: October 2023

Since the proposal of the brainstem axis theory, increasing research attention has been paid to the interactions between bacterial amyloids produced by intestinal flora and the amyloid β−protein (Aβ) related to Alzheimer’s disease (AD), and it has been considered as the possible cause of AD. Therefore, phenol−soluble modulin (PSM) α3, the most virulent protein secreted by Staphylococcus aureus, has attracted much attention. In this work, the effect of PSMα3 with a unique cross−α fibril architecture on the aggregation of pathogenic Aβ40 of AD was studied by extensive biophysical characterizations. The results proposed that the PSMα3 monomer inhibited the aggregation of Aβ40 in a concentration−dependent manner and changed the aggregation pathway to form granular aggregates. However, PSMα3 oligomers promoted the generation of the β−sheet structure, thus shortening the lag phase of Aβ40 aggregation. Moreover, the higher the cross−α content of PSMα3, the stronger the effect of the promotion, indicating that the cross−α structure of PSMα3 plays a crucial role in the aggregation of Aβ40. Further molecular dynamics (MD) simulations have shown that the Met1−Gly20 region in the PSMα3 monomer can be combined with the Asp1−Ala2 and His13−Val36 regions in the Aβ40 monomer by hydrophobic and electrostatic interactions, which prevents the conformational conversion of Aβ40 from the α−helix to β−sheet structure. By contrast, PSMα3 oligomers mainly combined with the central hydrophobic core (CHC) and the C−terminal region of the Aβ40 monomer by weak H−bonding and hydrophobic interactions, which could not inhibit the transition to the β−sheet structure in the aggregation pathway. Thus, the research has unraveled molecular interactions between Aβ40 and PSMα3 of different structures and provided a deeper understanding of the complex interactions between bacterial amyloids and AD−related pathogenic Aβ.
Comparison of Prophylactic Effects between Localized Biomimetic Minocycline and Systematic Amoxicillin on Implants Placed Immediately in Infected Sockets
Authors: Lee Won-Woo , Seo Jin-Won , Jang Il-Seok , Kwon Young-Joong , Joung Won-Jun , Jun Jong-Hun , Kim Jiyeong , Son Donghee , Lim Seung-Weon , Yun Seo-Hyoung , Tallarico Marco , Park Chang-Joo
Published: October 2023

This study evaluated the prophylactic effect of localized biomimetic minocycline and systemic amoxicillin on immediate implant placement at infected extraction sites. Twelve mongrels with six implants each were randomly assigned to five groups: uninfected negative control (Group N); infected with oral complex bacteria (Group P); infected and treated with amoxicillin one hour before implant placement (Group A); infected and treated with minocycline during implant placement (Group B); and infected and treated with amoxicillin one hour before implant placement and with minocycline during implant placement (Group C). Radiographic bone level, gingival index (GI), probing depth (PD), papillary bleeding index (PBI), and removal torque (RT) were recorded. There was no significant difference between Groups A, B, and C for bone loss. Group A showed the highest RT, the lowest PBI, and significantly lower GI and PD values than Group P. Group B exhibited significantly higher RT value than Group N and significantly smaller PD value than Group P at 6 w postoperatively. Localized minocycline could improve implant success by reducing bone loss and increasing RT and systemic amoxicillin could maintain the stability of the peri-implant soft tissue. However, combined use of these two antibiotics did not augment the prophylactic effect.
Interfacial Dynamics in Dual Channels: Inspired by Cuttlebone
Authors: Huang Matthew , Frohlich Karl , Esmaili Ehsan , Yang Ting , Li Ling , Jung Sunghwan
Published: October 2023

The cuttlebone, a chambered gas-filled structure found in cuttlefish, serves a crucial role in buoyancy control for the animal. This study investigates the motion of liquid-gas interfaces within cuttlebone-inspired artificial channels. The cuttlebone’s unique microstructure, characterized by chambers divided by vertical pillars, exhibits interesting fluid dynamics at small scales while pumping water in and out. Various channels were fabricated with distinct geometries, mimicking cuttlebone features, and subjected to different pressure drops. The behavior of the liquid-gas interface was explored, revealing that channels with pronounced waviness facilitated more non-uniform air-water interfaces. Here, Lyapunov exponents were employed to characterize interface separation, and they indicated more differential motions with increased pressure drops. Channels with greater waviness and amplitude exhibited higher Lyapunov exponents, while straighter channels exhibited slower separation. This is potentially aligned with cuttlefish’s natural adaptation to efficient water transport near the membrane, where more straight channels are observed in real cuttlebone.
Reduced Sodium Portions Favor Osteogenic Properties and Cytocompatibility of 45S5-Based Bioactive Glass Particles
Authors: Tsitlakidis Stefanos , Hohenbild Frederike , Saur Merve , Moghaddam Arash , Kunisch Elke , Renkawitz Tobias , Gonzalo de Juan Isabel , Westhauser Fabian
Published: October 2023

Besides its favorable biological properties, the release of sodium (Na) from the well-known 45S5-bioactive glass (BG) composition (in mol%: 46.1, SiO2, 24.5 CaO, 24.5 Na2O, 6.0 P2O5) can hamper its cytocompatibility. In this study, particles of Na-reduced variants of 45S5-BG were produced in exchange for CaO and P2O5 via the sol-gel-route resulting in Na contents of 75%, 50%, 25% or 0% of the original composition. The release of ions from the BGs as well as their impact on the cell environment (pH values), viability and osteogenic differentiation (activity of alkaline phosphatase (ALP)), the expression of osteopontin and osteocalcin in human bone-marrow-derived mesenchymal stromal cells in correlation to the Na-content and ion release of the BGs was assessed. The release of Na-ions increased with increasing Na-content in the BGs. With decreasing Na content, the viability of cells incubated with the BGs increased. The Na-reduced BGs showed elevated ALP activity and a pro-osteogenic stimulation with accelerated osteopontin induction and a pronounced upregulation of osteocalcin. In conclusion, the reduction in Na-content enhances the cytocompatibility and improves the osteogenic properties of 45S5-BG, making the Na-reduced variants of 45S5-BG promising candidates for further experimental consideration.
Penile-Sparing Surgery for Tumour Recurrence after Previous Glansectomy/Partial Penectomy: Treatment Feasibility and Oncological Outcomes
Authors: Musi Gennaro , Molinari Filippo , Mistretta Francesco A. , Piccinelli Mattia Luca , Guzzo Sonia , Tozzi Marco , Lievore Elena , Blezien Oskar , Fontana Matteo , Cioffi Antonio , Cullurà Daniela , Verri Elena , Cossu Rocca Maria , Nolè Franco , Ferro Matteo , de Cobelli Ottavio , Luzzago Stefano
Published: October 2023

We tested the feasibility and oncological outcomes after penile-sparing surgery (PSS) for local recurrent penile cancer after a previous glansectomy/partial penectomy. We retrospectively analysed 13 patients (1997–2022) with local recurrence of penile cancer after a previous glansectomy or partial penectomy. All patients underwent PSS: circumcision, excision, or laser ablation. First, technical feasibility, treatment setting, and complications (Clavien–Dindo) were recorded. Second, Kaplan–Meier plots depicted overall and local recurrences over time. Overall, 11 (84.5%) vs. 2 (15.5%) patients were previously treated with glansectomy vs. partial penectomy. The median (IQR) time to disease recurrence was 56 (13–88) months. Six (46%) vs. two (15.5%) vs. five (38.5%) patients were treated with, respectively, local excision vs. local excision + circumcision vs. laser ablation. All procedures, except one, were performed in an outpatient setting. Only one Clavien–Dindo 2 complication was recorded. The median follow-up time was 41 months. Overall, three (23%) vs. four (30.5%) patients experienced local vs. overall recurrence, respectively. All local recurrences were safely treated with salvage surgery. In conclusion, we reported the results of a preliminary analysis testing safety, feasibility, and early oncological outcomes of PSS procedures for patients with local recurrence after previous glansectomy or partial penectomy. Stronger oncological outcomes should be tested in other series to optimise patient selection.
MiR-199a-5p Decreases Esophageal Cancer Cell Proliferation Partially through Repression of Jun-B
Authors: Phatak Pornima , Tulapurkar Mohan E. , Burrows Whitney M. , Donahue James M.
Published: October 2023

MicroRNA (miR)-199a-5p has been shown to function as a tumor suppressor in some malignancies but its role in esophageal cancer is poorly understood. To further explore its role in esophageal cancer, we sought to investigate the interaction between miR-199a-5p and Jun-B, an important component of the AP1 transcription factor, which contains a potential binding site for miR-199a-5p in its mRNA. We found that levels of miR-199a-5p are reduced in both human esophageal cancer specimens and in multiple esophageal cancer cell lines compared to esophageal epithelial cells. Jun-B expression is correspondingly elevated in these tumor specimens and in several cell lines compared to esophageal epithelial cells. Jun-B mRNA expression and stability, as well as protein expression, are markedly decreased following miR-199a-5p overexpression. A direct interaction between miR-199a-5p and Jun-B mRNA was confirmed by a biotinylated RNA-pull down assay and luciferase reporter constructs. Either forced expression of miR-199a-5p or Jun-B silencing led to a significant decrease in cellular proliferation as well as in AP-1 promoter activity. Our results provide evidence that miR-199a-5p functions as a tumor suppressor in esophageal cancer cells by regulating cellular proliferation, partially through repression of Jun B.
Exploring Possible Diagnostic Precancerous Biomarkers for Oral Submucous Fibrosis: A Narrative Review
Authors: You Jie-Ru , Chen Ya-Ting , Hsieh Chia-Yu , Chen Sin-Yu , Lin Tzu-Yao , Shih Jing-Syuan , Chen Guan-Ting , Feng Sheng-Wei , Peng Tzu-Yu , Wu Chia-Yu , Lee I-Ta
Published: October 2023

Oral submucous fibrosis (OSF) stands as a progressive oral ailment, designated as a potentially malignant disorder. OSF has gained widespread recognition as a significant precursor to malignant transformation. In the pursuit of dependable, straightforward, and non-invasive diagnostic measures for the early detection of oral malignant progression, research has delved into potential diagnostic biomarkers of OSF. This comprehensive review delves into current investigations that explore the correlation between various biomarkers and OSF. The molecular biomarkers of OSF are categorized based on cytology and sampling methods. Moreover, this review encompasses pertinent studies detailing how these biomarkers are acquired and processed. Within this scope, we scrutinize four potential biomarkers that hold the promise of facilitating the development of diagnostic tools for detecting early-stage OSF.
Radiation Therapy for Gestational Trophoblastic Neoplasia: Forward-Looking Lessons Learnt
Authors: Barcellini Amelia , Fodor Andrei , Charalampopoulou Alexandra , Cassani Chiara , Locati Laura Deborah , Cioffi Raffaella , Bergamini Alice , Pignata Sandro , Orlandi Ester , Mangili Giorgia
Published: October 2023

Gestational trophoblastic neoplasia (GTN) includes several rare malignant diseases occurring after pregnancy: invasive moles, choriocarcinoma, placental site trophoblastic tumours, and epithelioid trophoblastic tumours. Multidisciplinary protocols including multi-agent chemotherapy, surgery, and occasionally radiotherapy achieve good outcomes for some high-risk metastatic patients. In this narrative review of the published studies on the topic, we have tried to identify the role of radiotherapy. The available studies are mainly small, old, and retrospective, with incomplete data regarding radiotherapy protocols delivering low doses (which can make this disease appear radioresistant in some cases despite high response rates with palliative doses) to wide fields (whole-brain, whole-liver, etc.), which can increase toxicity. Studies considering modern techniques are needed to overcome these limitations and determine the full potential of radiotherapy beyond its antihemorrhagic and palliative roles.