bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling Novel Avenues in mTOR-Targeted Therapeutics: Advancements in Glioblastoma Treatment
Authors: Singh Shilpi , Barik Debashis , Lawrie Karl , Mohapatra Iteeshree , Prasad Sujata , Naqvi Afsar R. , Singh Amar , Singh Gatikrushna
Published: October 2023

The mTOR signaling pathway plays a pivotal and intricate role in the pathogenesis of glioblastoma, driving tumorigenesis and proliferation. Mutations or deletions in the PTEN gene constitutively activate the mTOR pathway by expressing growth factors EGF and PDGF, which activate their respective receptor pathways (e.g., EGFR and PDGFR). The convergence of signaling pathways, such as the PI3K-AKT pathway, intensifies the effect of mTOR activity. The inhibition of mTOR has the potential to disrupt diverse oncogenic processes and improve patient outcomes. However, the complexity of the mTOR signaling, off-target effects, cytotoxicity, suboptimal pharmacokinetics, and drug resistance of the mTOR inhibitors pose ongoing challenges in effectively targeting glioblastoma. Identifying innovative treatment strategies to address these challenges is vital for advancing the field of glioblastoma therapeutics. This review discusses the potential targets of mTOR signaling and the strategies of target-specific mTOR inhibitor development, optimized drug delivery system, and the implementation of personalized treatment approaches to mitigate the complications of mTOR inhibitors. The exploration of precise mTOR-targeted therapies ultimately offers elevated therapeutic outcomes and the development of more effective strategies to combat the deadliest form of adult brain cancer and transform the landscape of glioblastoma therapy.
Validation of a SARS-CoV-2 Surrogate Neutralization Test Detecting Neutralizing Antibodies against the Major Variants of Concern
Authors: Santos da Silva Eveline , Servais Jean-Yves , Kohnen Michel , Arendt Vic , Staub Therese ,   the CON-VINCE Consortium,   the CoVaLux Consortium, Krüger Rejko , Fagherazzi Guy , Wilmes Paul , Hübschen Judith M. , Ollert Markus , Perez-Bercoff Danielle , Seguin-Devaux Carole
Published: October 2023

SARS-CoV-2 infection and/or vaccination elicit a broad range of neutralizing antibody responses against the different variants of concern (VOC). We established a new variant-adapted surrogate virus neutralization test (sVNT) and assessed the neutralization activity against the ancestral B.1 (WT) and VOC Delta, Omicron BA.1, BA.2, and BA.5. Analytical performances were compared against the respective VOC to the reference virus neutralization test (VNT) and two CE-IVD labeled kits using three different cohorts collected during the COVID-19 waves. Correlation analyses showed moderate to strong correlation for Omicron sub-variants (Spearman’s r = 0.7081 for BA.1, r = 0.7205 for BA.2, and r = 0.6042 for BA.5), and for WT (r = 0.8458) and Delta-sVNT (r = 0.8158), respectively. Comparison of the WT-sVNT performance with two CE-IVD kits, the “Icosagen SARS-CoV-2 Neutralizing Antibody ELISA kit” and the “Genscript cPass, kit” revealed an overall good correlation ranging from 0.8673 to −0.8773 and a midway profile between both commercial kits with 87.76% sensitivity and 90.48% clinical specificity. The BA.2-sVNT performance was similar to the BA.2 Genscript test. Finally, a correlation analysis revealed a strong association (r = 0.8583) between BA.5-sVNT and VNT sVNT using a double-vaccinated cohort (n = 100) and an Omicron-breakthrough infection cohort (n = 91). In conclusion, the sVNT allows for the efficient prediction of immune protection against the various VOCs.
Synthesis and Crystal Structure of the Europium(II) Hydride Oxide Iodide Eu5H2O2I4 Showing Blue-Green Luminescence
Authors: Rudolph Daniel , Wylezich Thomas , Netzsch Philip , Blaschkowski Björn , Höppe Henning A. , Goldner Philippe , Kunkel Nathalie , Hoslauer Jean-Louis , Schleid Thomas
Published: October 2023

As the first europium(II) hydride oxide iodide, dark red single crystals of Eu5H2O2I4 could be synthesized from oxygen-contaminated mixtures of EuH2 and EuI2. Its orthorhombic crystal structure (a = 1636.97(9) pm, b = 1369.54(8) pm, c = 604.36(4) pm, Z = 4) was determined via single-crystal X-ray diffraction in the space group Cmcm. Anion-centred tetrahedra [HEu4]7+ and [OEu4]6+ serve as central building blocks interconnected via common edges to infinite ribbons parallel to the c axis. These ribbons consist of four trans-edge connected (Eu2+)4 tetrahedra as repetition unit, two H−-centred ones in the inner part, and two O2−-centred ones representing the outer sides. They are positively charged, according to ∞1{[Eu5H2O2]4+}, to become interconnected and charge-balanced by iodide anions. Upon excitation with UV light, the compound shows blue–green luminescence with the shortest Eu2+ emission wavelength ever observed for a hydride derivative, peaking at 463 nm. The magnetic susceptibility of Eu5H2O2I4 follows the Curie-Weiss law down to 100 K, and exhibits a ferromagnetic ordering transition at about 10 K.
Dickkopf-Related Protein 1 (DKK-1) as a Possible Link between Bone Erosions and Increased Carotid Intima-Media Thickness in Psoriatic Arthritis: An Ultrasound Study
Authors: Biță Cristina-Elena , Dinescu Ștefan Cristian , Riza Anca-Lelia , Ciurea Paulina Lucia , Mușetescu Anca Emanuela , Marinescu Daniela , Dumitrașcu Roxana Mihaela , Șuiu Larisa Ionela , Ionescu Răzvan Adrian , Popoviciu Horațiu Valeriu , Vreju Florentin Ananu
Published: October 2023

Psoriatic arthritis (PsA) is a heterogenous systemic inflammatory disorder that affects peripheral joints and skin, but also causes inflammation at entheseal sites, digits (dactylitis) and the axial skeleton. Despite considerable advances, our understanding of the pathogenesis and management of PsA is hampered by its complex clinical expression. We enrolled patients who met the ClASsification for Psoriatic Arthritis (CASPAR) criteria for PsA (n = 17), and healthy controls (n = 13). The lipid profile, C-reactive protein (CRP) and Dickkopf-related protein 1 (DKK-1) circulating levels were measured for all subjects. For the patients with PsA, (1) the erosive character of the articular disease was assessed by a musculoskeletal ultrasound and (2) the cardiovascular risk was evaluated using the Systematic Coronary Risk Evaluation (SCORE) chart and the ultrasound measurement of the carotid intima-media thickness. A higher titer of serum DKK-1 was associated with the presence of erosions (p < 0.005) and the cIMT correlated with DKK-1 levels in patients with PsA (r = 0.6356, p = 0.0061). Additionally, we observed a positive correlation between increased cIMT and CRP (r = 0.5186, p = 0.0329). Our results suggest that DKK-1 could be used as an early biomarker for the erosive character of the articular disease and for the assessment of the cardiovascular risk in PsA patients.
Effects of SKCPT on Osteoarthritis in Beagle Meniscectomy and Cranial Cruciate Ligament Transection Models
Authors: Kim Hye-Min , Kang Minseok , Jung Yoon-Seok , Lee Yoon-Jung , Choi Wonjae , Yoo Hunseung , Kim JeongHoon , An Hyo-Jin
Published: October 2023

Osteoarthritis (OA) affects >500 million people globally, and this number is expected to increase. OA management primarily focuses on symptom alleviation, using non-steroidal anti-inflammatory drugs, including Celecoxib. However, such medication has serious side effects, emphasizing the need for disease-specific treatment. The meniscectomy and cranial cruciate ligament transection (CCLx)-treated beagle dog was used to investigate the efficacy of a modified-release formulation of SKI306X (SKCPT) from Clematis mandshurica, Prunella vulgaris, and Trichosanthes kirilowii in managing arthritis. SKCPT’s anti-inflammatory and analgesic properties have been assessed via stifle circumference, gait, incapacitance, histopathology, and ELISA tests. The different SKCPT concentrations and formulations also affected the outcome. SKCPT improved the gait, histopathological, and ELISA OA assessment parameters compared to the control group. Pro-inflammatory cytokines and matrix metalloproteinases were significantly lower in the SKCPT-treated groups than in the control group. This study found that SKCPT reduces arthritic lesions and improves abnormal gait. The 300 mg modified-release formulation was more efficacious than others, suggesting a promising approach for managing OA symptoms and addressing disease pathogenesis. A high active ingredient level and a release pattern make this formulation effective for twice-daily arthritis treatment.
Changes in Lymphocyte Subpopulations after Remdesivir Therapy for COVID-19: A Brief Report
Authors: Cianci Rossella , Massaro Maria Grazia , De Santis Elisabetta , Totti Beatrice , Gasbarrini Antonio , Gambassi Giovanni , Giambra Vincenzo
Published: October 2023

Remdesivir (RDV) has demonstrated clinical benefit in hospitalized COronaVIrus Disease (COVID)-19 patients. The objective of this brief report was to assess a possible correlation between RDV therapy and the variation in lymphocyte subpopulations. We retrospectively studied 43 hospitalized COVID-19 patients: 30 men and 13 women (mean age 69.3 ± 15 years); 9/43 had received RDV therapy. Six patients had no need for oxygen (severity group 0); 22 were on oxygen treatment with a fraction of inspired oxygen (FiO2) ≤ 50% (group 1); 7 on not-invasive ventilation (group 2); 3 on invasive mechanical ventilation (group 3); and 5 had died (group 4). Cytofluorimetric assessment of lymphocyte subpopulations showed substantial changes after RDV therapy: B lymphocytes and plasmablasts were significantly increased (p = 0.002 and p = 0.08, respectively). Cytotoxic T lymphocytes showed a robust reduction (p = 0.008). No changes were observed in CD4+-T cells and natural killers (NKs). There was a significant reduction in regulatory T cells (Tregs) (p = 0.02) and a significant increase in circulating monocytes (p = 0.03). Stratifying by disease severity, after RDV therapy, patients with severity 0–2 had significantly higher B lymphocyte and monocyte counts and lower memory and effector cytotoxic T cell counts. Instead, patients with severity 3–4 had significantly higher plasmablast and lower memory T cell counts. No significant differences for CD4+-T cells, Tregs, and NKs were observed. Our brief report showed substantial changes in the lymphocyte subpopulations analyzed between patients who did not receive RDV therapy and those after RDV treatment. Despite the small sample size, due to the retrospective nature of this brief report, the substantial changes in lymphocyte subpopulations reported could lead to speculation on the role of RDV treatment both on immune responses against the virus and on the possible downregulation of the cytokine storm observed in patients with more severe disease.
Articular Cartilage—From Basic Science Structural Imaging to Non-Invasive Clinical Quantitative Molecular Functional Information for AI Classification and Prediction
Authors: Kurz Bodo , Lange Thomas , Voelker Marita , Hart Melanie L. , Rolauffs Bernd
Published: October 2023

This review presents the changes that the imaging of articular cartilage has undergone throughout the last decades. It highlights that the expectation is no longer to image the structure and associated functions of articular cartilage but, instead, to devise methods for generating non-invasive, function-depicting images with quantitative information that is useful for detecting the early, pre-clinical stage of diseases such as primary or post-traumatic osteoarthritis (OA/PTOA). In this context, this review summarizes (a) the structure and function of articular cartilage as a molecular imaging target, (b) quantitative MRI for non-invasive assessment of articular cartilage composition, microstructure, and function with the current state of medical diagnostic imaging, (c), non-destructive imaging methods, (c) non-destructive quantitative articular cartilage live-imaging methods, (d) artificial intelligence (AI) classification of degeneration and prediction of OA progression, and (e) our contribution to this field, which is an AI-supported, non-destructive quantitative optical biopsy for early disease detection that operates on a digital tissue architectural fingerprint. Collectively, this review shows that articular cartilage imaging has undergone profound changes in the purpose and expectations for which cartilage imaging is used; the image is becoming an AI-usable biomarker with non-invasive quantitative functional information. This may aid in the development of translational diagnostic applications and preventive or early therapeutic interventions that are yet beyond our reach.
Na+/H+ Exchangers (NHEs) in Mammalian Sperm: Essential Contributors to Male Fertility
Authors: Gardner Cameron C. , James Paul F.
Published: October 2023

Na+/H+ exchangers (NHEs) are known to be important regulators of pH in multiple intracellular compartments of eukaryotic cells. Sperm function is especially dependent on changes in pH and thus it has been postulated that NHEs play important roles in regulating the intracellular pH of these cells. For example, in order to achieve fertilization, mature sperm must maintain a basal pH in the male reproductive tract and then alkalize in response to specific signals in the female reproductive tract during the capacitation process. Eight NHE isoforms are expressed in mammalian testis/sperm: NHE1, NHE3, NHE5, NHE8, NHA1, NHA2, NHE10, and NHE11. These NHE isoforms are expressed at varying times during spermatogenesis and localize to different subcellular structures in developing and mature sperm where they contribute to multiple aspects of sperm physiology and male fertility including proper sperm development/morphogenesis, motility, capacitation, and the acrosome reaction. Previous work has provided evidence for NHE3, NHE8, NHA1, NHA2, and NHE10 being critical for male fertility in mice and NHE10 has recently been shown to be essential for male fertility in humans. In this article we review what is known about each NHE isoform expressed in mammalian sperm and discuss the physiological significance of each NHE isoform with respect to male fertility.
Carbon Dots—Types, Obtaining and Application in Biotechnology and Food Technology
Authors: Szczepankowska Joanna , Khachatryan Gohar , Khachatryan Karen , Krystyjan Magdalena
Published: October 2023

Materials with a “nano” structure are increasingly used in medicine and biotechnology as drug delivery systems, bioimaging agents or biosensors in the monitoring of toxic substances, heavy metals and environmental variations. Furthermore, in the food industry, they have found applications as detectors of food adulteration, microbial contamination and even in packaging for monitoring product freshness. Carbon dots (CDs) as materials with broad as well as unprecedented possibilities could revolutionize the economy, if only their synthesis was based on low-cost natural sources. So far, a number of studies point to the positive possibilities of obtaining CDs from natural sources. This review describes the types of carbon dots and the most important methods of obtaining them. It also focuses on presenting the potential application of carbon dots in biotechnology and food technology.
Radiomics Analyses to Predict Histopathology in Patients with Metastatic Testicular Germ Cell Tumors before Post-Chemotherapy Retroperitoneal Lymph Node Dissection
Authors: Scavuzzo Anna , Pasini Giovanni , Crescio Elisabetta , Jimenez-Rios Miguel Angel , Figueroa-Rodriguez Pavel , Comelli Albert , Russo Giorgio , Vazquez Ivan Calvo , Araiza Sebastian Muruato , Ortiz David Gomez , Perez Montiel Delia , Lopez Saavedra Alejandro , Stefano Alessandro
Published: October 2023

Background: The identification of histopathology in metastatic non-seminomatous testicular germ cell tumors (TGCT) before post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) holds significant potential to reduce treatment-related morbidity in young patients, addressing an important survivorship concern. Aim: To explore this possibility, we conducted a study investigating the role of computed tomography (CT) radiomics models that integrate clinical predictors, enabling personalized prediction of histopathology in metastatic non-seminomatous TGCT patients prior to PC-RPLND. In this retrospective study, we included a cohort of 122 patients. Methods: Using dedicated radiomics software, we segmented the targets and extracted quantitative features from the CT images. Subsequently, we employed feature selection techniques and developed radiomics-based machine learning models to predict histological subtypes. To ensure the robustness of our procedure, we implemented a 5-fold cross-validation approach. When evaluating the models’ performance, we measured metrics such as the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, precision, and F-score. Result: Our radiomics model based on the Support Vector Machine achieved an optimal average AUC of 0.945. Conclusions: The presented CT-based radiomics model can potentially serve as a non-invasive tool to predict histopathological outcomes, differentiating among fibrosis/necrosis, teratoma, and viable tumor in metastatic non-seminomatous TGCT before PC-RPLND. It has the potential to be considered a promising tool to mitigate the risk of over- or under-treatment in young patients, although multi-center validation is critical to confirm the clinical utility of the proposed radiomics workflow.
Performance Comparison of Classical Methods and Neural Networks for Colour Correction
Authors: Kucuk Abdullah , Finlayson Graham D. , Mantiuk Rafal , Ashraf Maliha
Published: October 2023

Colour correction is the process of converting RAW RGB pixel values of digital cameras to a standard colour space such as CIE XYZ. A range of regression methods including linear, polynomial and root-polynomial least-squares have been deployed. However, in recent years, various neural network (NN) models have also started to appear in the literature as an alternative to classical methods. In the first part of this paper, a leading neural network approach is compared and contrasted with regression methods. We find that, although the neural network model supports improved colour correction compared with simple least-squares regression, it performs less well than the more advanced root-polynomial regression. Moreover, the relative improvement afforded by NNs, compared to linear least-squares, is diminished when the regression methods are adapted to minimise a perceptual colour error. Problematically, unlike linear and root-polynomial regressions, the NN approach is tied to a fixed exposure (and when exposure changes, the afforded colour correction can be quite poor). We explore two solutions that make NNs more exposure-invariant. First, we use data augmentation to train the NN for a range of typical exposures and second, we propose a new NN architecture which, by construction, is exposure-invariant. Finally, we look into how the performance of these algorithms is influenced when models are trained and tested on different datasets. As expected, the performance of all methods drops when tested with completely different datasets. However, we noticed that the regression methods still outperform the NNs in terms of colour correction, even though the relative performance of the regression methods does change based on the train and test datasets.
Assessment of Diversity of Marine Organisms among Natural and Transplanted Seagrass Meadows
Authors: Titioatchasai Jatdilok , Surachat Komwit , Rattanachot Ekkalak , Tuntiprapas Piyalap , Mayakun Jaruwan
Published: October 2023

Seagrass ecosystems have been declining, and restorations are conducted in many parts of the world to compensate for habitat loss and restore the ecosystem services seagrasses provide. Assessment of transplantation success requires the monitoring of the level of biodiversity between the donor and transplanted sites. In this study, we assessed a seagrass ecosystem after restoration in terms of the diversity of marine organisms using environmental DNA (eDNA) to compare four sites: (1) bare sand, (2) a natural meadow of Cymodocea serrulata, (3) a natural meadow of Halophila ovalis, and (4) a transplanted seagrass meadow. The results showed the presence of 3 domains, 34 phyla, 59 classes, 92 orders, 155 families, 156 genera, and 121 species. Proteobacteria, Actinobacteria, Cyanobacteria, and Bacteroidetes were the dominant bacterial phyla. Among eukaryotes, Phragmoplastophyta/Charophyta (epiphytes), Ascomycota (fungi), Cnidaria (jelly fish), and Arthropoda (Crabs and bivalves) were the dominant phyla. Dugong tails and commercial species (sea cucumber, dog conch, and swimming crab) have been observed in both the natural and transplanted meadows. Relative abundance among the four sites was significantly different. There were no differences in species richness and evenness between the four sites and no differences in species richness and evenness between the natural meadows and the transplanted seagrass meadow. It is possible that transplanted seagrass meadow can be successfully restored and established and can provide habitat for fauna and microbes. Additionally, fauna are not limited in their capacity to move between the natural and transplanted habitats. This study provides an assessment of biodiversity of restored seagrass patches and a better understanding of a seagrass ecosystem after restoration. However, to assess seagrass ecosystem services after restoration and the success of restoration actions, long-term monitoring of marine organism diversity and additional assessments are needed.
Developments in Marine Propulsors
Authors: Koushan Kourosh
Published: October 2023

Marine propulsors are key components of the many thousands of ships operating in oceans, lakes, and rivers globally [...]
Enhanced Ant Colony Algorithm for Discrete Dynamic Berth Allocation in a Case Container Terminal
Authors: Yu Meng , Lv Yaqiong , Wang Yuhang , Ji Xiaojing
Published: October 2023

Berth allocation is a critical concern in container terminal port logistics, involving the precise determination of where and when arriving vessels should dock along a quay. With berth space limitations and a continuous surge in container handling demands, ensuring an effective berth allocation is paramount for the smooth and efficient operation of container ports. However, due to the randomness of vessel arrival times and uncertainties surrounding container ship loading capacities, berth allocation problems (BAP) often present discrete and dynamic challenges. This paper addresses these challenges by considering real-world terminal operational factors, formulating relevant assumptions, and establishing a model for dynamic berth allocation and efficient ship berthing scheduling. The primary motivation stems from the parallels observed between the BAP problem and ant foraging path selection, leading to the proposal of a novel Parallel Search Structure Enhanced Ant Colony Algorithm (PACO). A proper set of parameters of the algorithm are selected based upon sensitivity analyses on the convergence and parallelism efficiency of the algorithm. To validate our method, a real-world case-container terminal operation in Shanghai Port was studied. The experimental comparison results show that the PACO algorithm outperforms other commonly used algorithms, making it more effective and efficient for the Discrete Dynamic Berth Allocation Problem (DDBAP).
Study on the Resistance of a Large Pure Car Truck Carrier with Bulbous Bow and Transom Stern
Authors: Tian Xiaoqing , Xie Tianwei , Liu Zhangming , Lai Xianghua , Pan Huachen , Wang Chizhong , Leng Jianxing , Rahman M. M.
Published: October 2023

The resistance of a large Pure Car Truck Carrier (PCTC) with a bulbous bow and a transom stern is evaluated in the present paper. Several cases at nine different ship speeds in calm water are simulated and results are compared with the experimental measurements. The maximum relative error is 0.93% at a Froude number (Fr) of 0.209. The total resistance coefficient of the ship in calm water shows a parabolic trend with increasing Fr, and it reaches a minimum value at Fr = 0.1794. Furthermore, the cases of the ship in regular waves with six different wavelengths and three wave heights are simulated. It is observed that the total resistance exhibits a quadratic relationship with the wavelength when the wave height is fixed. The wave-making resistance increases with the increase in wave height at any fixed wavelength, and it reaches a maximum value when the wave-length is 1.2 times the ship length (Lpp). Additionally, we also investigated the resistance in three different sea states at four different speeds. When the significant wave height of irregular waves is the same as regular waves, the wave-making resistance under irregular waves is much smaller than that of the regular waves. All of these results indicate that the bulbous bow and transom stern can reduce the wave-making and residuary resistances, which can provide a useful reference for the subsequent design and manufacturing of related ships.
An Unorthodox Arrangement of Boussinesq-Type Wave Equations for Accurate and Robust Numerical Treatment
Authors: Beji Serdar
Published: October 2023

A set of Boussinesq-type wave equations with enhanced dispersion characteristics is presented for accurate, efficient, and robust numerical treatment. New arrangement uses three different velocity variables simultaneously in order to keep continuity and momentum equations in simplest conservation forms while improving the dispersion characteristics. This approach allows us to retain all the nonlinear contributions with minimum number of terms. Spatial and time-dependent variations of the seabed are fully accounted for and the effect of external free surface pressure is included. A numerical scheme based on finite differences is developed, and various well-known experimental cases are simulated for testing the performance of the proposed set of equations. Comparisons of simulations with measurements reveal quite satisfactory agreements and, hence, bolster confidence in the wave model.
Researching Tourism Space in China’s Great Bay Area: Spatial Pattern, Driving Forces and Its Coupling with Economy and Population
Authors: Li Lingfeng , Gao Quan
Published: October 2023

Analysis of the spatial patterns and dynamics of tourism services and facilities is crucial for tourism and land use planning. However, most studies in the spatial analysis of tourism rely on the city- or regional-level data; limited research has used POI (point of interest) data to accurately uncover the spatial distribution of tourism, especially its interactive and coupling relationship with the local economy and population. Based on POI data, this paper, therefore, investigates the spatial patterns and driving forces of tourism services distribution and how tourism space is coupled with the local economy and population in the Guangdong–Hong Kong–Macao Greater Bay Area (GBA) of China. The results show the following: (1) Different categories of tourism services (catering, shopping, scenic spots, leisure, and sports) exhibit diverse spatial patterns and agglomerations, but they tend to align with the variables of economic level and population in a grid of 1 km2. (2) The spatial econometric models further reveal that population density, transportation, and hospitality facilities are positively correlated with the spatial distribution of tourism services, but GDP in a grid of 1 km2 shows a weak negative correlation with the POI of tourism services, which may be attributed to the incoordination between GDP and tourism in some areas. (3) The analysis of coupling degree further identifies the areas where tourism services have good interaction/coupling with the local GDP and population density, such that these areas can be viewed as hotspots suitable for tourism promotion. This paper thus offers meaningful policy implications by calling for an optimization of the coupling of tourism services with local social–economic factors in the GBA.
One Hundred Priority Questions for the Development of Sustainable Food Systems in Sub-Saharan Africa
Authors: Devenish Adam J. M. , Schmitter Petra , Jellason Nugun. P. , Esmail Nafeesa , Abdi Nur M. , Adanu Selase K. , Adolph Barbara , Al-Zu’bi Maha , Amali Amali A. , Barron Jennie , Chapman Abbie S. A. , Chausson Alexandre M. , Chibesa Moses , Davies Joanne , Dugan Emmanuel , Edwards Glory I. , Egeru Anthony , Gebrehiwot Tagel , Griffiths Geoffrey H. , Haile Amleset , Hunga Henry G. , Igbine Lizzy , Jarju Ousman M. , Keya Francis , Khalifa Muhammad , Ledoux Wamba A. , Lejissa Lemlem T. , Loupa Pius , Lwanga Jonathan , Mapedza Everisto D. , Marchant Robert , McLoud Tess , Mukuyu Patience , Musah Labram M. , Mwanza Morton , Mwitwa Jacob , Neina Dora , Newbold Tim , Njogo Samuel , Robinson Elizabeth J. Z. , Singini Wales , Umar Bridget B. , Wesonga Frank , Willcock Simon , Yang Jingyi , Tobias Joseph A.
Published: October 2023

Sub-Saharan Africa is facing an expected doubling of human population and tripling of food demand over the next quarter century, posing a range of severe environmental, political, and socio-economic challenges. In some cases, key Sustainable Development Goals (SDGs) are in direct conflict, raising difficult policy and funding decisions, particularly in relation to trade-offs between food production, social inequality, and ecosystem health. In this study, we used a horizon-scanning approach to identify 100 practical or research-focused questions that, if answered, would have the greatest positive impact on addressing these trade-offs and ensuring future productivity and resilience of food-production systems across sub-Saharan Africa. Through direct canvassing of opinions, we obtained 1339 questions from 331 experts based in 55 countries. We then used online voting and participatory workshops to produce a final list of 100 questions divided into 12 thematic sections spanning topics from gender inequality to technological adoption and climate change. Using data on the background of respondents, we show that perspectives and priorities can vary, but they are largely consistent across different professional and geographical contexts. We hope these questions provide a template for establishing new research directions and prioritising funding decisions in sub-Saharan Africa.
Transformation of Soils and Mire Community Reestablishment Potential in Disturbed Abandoned Peatland: A Case Study from the Kaliningrad Region, Russia
Authors: Antsiferova Olga , Napreenko Maxim , Napreenko-Dorokhova Tatiana
Published: October 2023

Degrading organic soils usually become a source of increased greenhouse gas emissions and fire frequency in disturbed peatlands. As a solution, the rewetting concept should consider not only the detailed hydrological characteristics of the peatland, but should also appraise the properties of the soils. Here, we provide the results of a detailed soil study carried out on an abandoned peatland in the Kaliningrad Region, Russia. The study aims to integrate data on soil properties, hydrology, and the degree of transformation of the current soil cover in terms of how this affects spontaneous revegetation and the potential for further mire community reestablishment. The paper contributes to a greater understanding of rehabilitation patterns of disturbed peatlands depending on the soil’s physical and hydrological properties in the humid climate of the southeastern Baltic region. The present-day soils of the peatland refer to two World Reference Base (WRB) groups: Gleisols and Histosols; the latter change successively from the periphery to the centre of the peatland as follows: Eutric/Sapric → Hemic → Dystric → Fibric. Most Histosols are characterised by hydrothermal degradation in the upper layers with patches of pyrogenic degradation. Some local inundated areas show environmental conditions favourable for Sphagnum growth and the formation of mire communities. We have identified six groups of sites with different ecological and time-span potentials for mire community restoration during the implementation of rewetting activities. The rewetting feasibility of the peatland’s sites does not coincide with the degree of transformation of their soil profile, but is rather determined by the hydrological regime.
Early Hominin Dispersal across the Qinling Mountains, China, during the Mid-Pleistocene Transition
Authors: Guo Xiaoqi , Sun Xuefeng , Lu Huayu , Wang Shejiang , Lu Chengqiu
Published: October 2023

The Qinling Mountain Range (QMR), where more than 500 hominin fossils and Paleolithic sites have been preserved, was a major center of hominin evolution and settlement and an important link for the hominin migration and dispersal between the north and the south during the Pleistocene in China. The rich culture remains and the related data make it possible and meaningful to study the characteristics and mechanisms of hominin occupation and dispersal in the region. This paper has summarized and analyzed the geographical distributions and chronologies of 55 dated hominin fossils and Paleolithic sites in the QMR to date. By combining them with the evidence from the loess–paleosol sequence, a relatively continuous and chronological sequence of hominin occupation and dispersal has been established, in which we have identified five stages, viz. ~before 1.2 Ma, the sporadic occurrence stage of early hominin occupation; ~1.2–0.7 Ma, the initial expansion stage; ~0.7–0.3 Ma, the stability and maintenance stage; ~0.3–0.05 Ma, the large-scale expansion stage; ~0.05–0.01 Ma, the sharp decline stage of the record of hominin occupation. We conclude that the environmental and ecosystem changes associated with the MPT drove early hominins to disperse southwards across the QMR. In addition, the evidence suggests that the hominin occupation and dispersal here was broadly continuous during both glacial and interglacial scales from early to late Pleistocene, and that the southern QMR provided a glacial refuge.
Research on the Preference of Public Art Design in Urban Landscapes: Evidence from an Event-Related Potential Study
Authors: Cheng Yue , Chen Jiayin , Li Jiahua , Li Lin , Hou Guanhua , Xiao Xuan
Published: October 2023

As urbanization quickens, the role of public art in urban landscape design gains prominence. Nevertheless, how stylistic characteristics of landscape public art affect aesthetic preferences remains insufficiently discussed, particularly with objective assessment methods. The use of event-related potential (ERP) can offer neurophysiological evidence to support research and practice in landscape art design. We employed a 2 (artistic features) × 2 (professional proficiency) repeated-measures design, involving abstract and figurative experimental stimuli; both experts and non-experts participated, with their aesthetic reactions and relevant electroencephalographic data recorded. Behavioral findings show a preference for figurative public artworks regardless of professional background. From neurophysiological outcomes, stimuli elicit an elevated N100 during early perceptual processing, signifying increased attentional resources. During aesthetic processing, figurative stimuli more effectively evoke positive emotions, particularly among professionals, yielding a heightened P200 response. Conversely, abstract stimuli may evoke a higher N200 amplitude, reflecting augmented negative biases. Nevertheless, non-experts exhibit no marked differences in their stimulus responses during aesthetic processing. Research indicates that low-level physical attributes of public artworks are initially noted, while the visual processing of artistic traits lies at a higher perceptual level, necessitating specialized expertise involvement. Furthermore, the complexity of visual perceptual processing plays a significant role in the assessment of landscape art preferences. This study not only offers crucial reference indices for designing urban landscapes that satisfy diverse public aesthetic needs but also lays the foundation for neural techniques to assess landscape design preferences and expands the field of landscape design research.
The Successful Management of Primary Amenorrhea in Woodhouse–Sakati Syndrome: A Case Report and a Literature Review
Authors: Bakhsh Hanadi , Alqntash Norah , Almajed Ebtesam
Published: October 2023

Background: Woodhouse–Sakati syndrome (WSS) is a rare multisystemic disease resulting from an autosomal recessive gene mutation characterized by distinctive facial appearance, alopecia, impaired HbA1c, and hypogonadism. Purpose: To present the successful management of primary amenorrhea in a WSS patient. Case Presentation: We report a 19-year-old Saudi female referred to the gynecology clinic at the age of 16 as a case of primary amenorrhea. The patient underwent a genetic analysis, which revealed mutations in the DCAF17 gene, confirming the diagnosis of WSS. Treatment includes hormonal replacement therapy for the induction of puberty. Conclusions: Careful and detailed medical and physical examination led to appropriate testing confirming the WSS diagnosis. Genetic tests for family members and the offspring of the patient are strongly recommended. Treatment timing and dosage are determined by the patient’s individual needs, which take into consideration the patient’s potential for growth, the family’s readiness, and any comorbidities.
On Generalized Dominance Structures for Multi-Objective Optimization
Authors: Deb Kalyanmoy , Ehrgott Matthias
Published: October 2023

Various dominance structures have been proposed in the multi-objective optimization literature. However, a systematic procedure to understand their effect in determining the resulting optimal set for generic domination principles, besides the standard Pareto-dominance principle, is lacking. In this paper, we analyze and lay out properties of generalized dominance structures which help provide insights for resulting optimal solutions. We introduce the concept of the anti-dominance structure, derived from the chosen dominance structure, to explain how the resulting non-dominated or optimal set can be identified easily compared to using the dominance structure directly. The concept allows a unified explanation of optimal solutions for both single- and multi-objective optimization problems. The anti-dominance structure is applied to analyze respective optimal solutions for most popularly used static and spatially changing dominance structures. The theoretical and deductive results of this study can be utilized to create more meaningful dominance structures for practical problems, understand and identify resulting optimal solutions, and help develop better test problems and algorithms for multi-objective optimization.
Ciprofloxacin-Induced Anaphylactic Reaction Followed by Negative Provocation Test in Response to Levofloxacin: A Case Report
Authors: Kurtov Marija , Kilić Paula , Ikić Lucija , Kurtov Karlo , Dorčić Gordan , Vodanović Marko , Artuković Marinko , Ikić Matijašević Marina
Published: October 2023

Fluoroquinolones are a commonly prescribed class of antibiotics due to their broad spectrum of antimicrobial activity, favorable pharmacokinetic properties, ability to switch from parenteral to oral administration, and global availability. After beta-lactams, they are the second most common antibiotic class associated with drug allergies. The mechanism of fluoroquinolone-induced hypersensitivity reactions has not yet been fully understood, so the true incidence of hypersensitivity reactions remains unknown. Cross-reactivity between fluoroquinolones has been the subject of conflicting and limited clinical research. Due to their similar chemical structure, some argue for close cross-reactivity within the group. However, recent studies have produced contradictory results. We present the case of a young patient who had an anaphylactic reaction to ciprofloxacin but was tolerant to levofloxacin, as determined via a skin prick test followed by a drug provocation test. Our findings support the notion that there is little cross-reactivity between fluoroquinolones. Consequently, exposure to another fluoroquinolone in a hospital setting may be beneficial, particularly for patients who lack adequate antibiotic alternatives. However, additional research on this subject is required.
Milestones in the History of Esophagectomy: From Torek to Minimally Invasive Approaches
Authors: Thomas Pascal Alexandre
Published: October 2023

The history of esophagectomy reflects a journey of dedication, collaboration, and technical innovation, with ongoing endeavors aimed at optimizing outcomes and reducing complications. From its early attempts to modern minimally invasive approaches, the journey has been marked by perseverance and innovation. Franz J. A. Torek’s 1913 successful esophageal resection marked a milestone, demonstrating the feasibility of transthoracic esophagectomy and the potential for esophageal cancer cure. However, its high mortality rate posed challenges, and it took almost two decades for similar successes to emerge. Surgical techniques evolved with the left thoracotomy, right thoracotomy, and transhiatal approaches, expanding the indications for resection. Mechanical staplers introduced in the early 20th century transformed anastomosis, reducing complications. The advent of minimally invasive techniques in the 1990s aimed to minimize complications while maintaining oncological efficacy. Robot-assisted esophagectomy further pushed the boundaries of minimally invasive surgery. Collaborative efforts, particularly from the Worldwide Esophageal Cancer Collaboration and the Esophageal Complications Consensus Group, standardized reporting and advanced the understanding of outcomes. The introduction of risk prediction models aids in making informed decisions. Despite significant improvements in survival rates and postoperative mortality, anastomotic leaks remain a concern, with recent rates showing an increase. Prevention strategies include microvascular anastomosis and ischemic preconditioning, yet challenges persist.
Effect of Laser Welding Parameters with Different Fillers on Solidification Cracking and Mechanical Properties of AA7075
Authors: Alkhabbat Mohammed , Nadeau François , Mirakhorli Fatemeh , Dao Thien-My , Pham Xuan-Tan
Published: October 2023

AA7075 is considered a ‘non-weldable’ alloy using fusion welding methods. In this study, laser welding is applied in pulse mode to weld 2 mm thick AA7075 aluminum alloy plates using different fillers. The aim is to identify the influence of welding parameters and fillers on solidification cracking susceptibility during laser welding using the circular patch test (CPT). X-ray radiography was used to detect and measure cracks in the CPT samples. Furthermore, the effects of the laser welding process and chemical composition of fillers on the accumulated crack length (CCL), microstructure, and mechanical properties were investigated. Moreover, the mechanical behavior and local deformation of the fusion zone (FZ) were investigated using micro-flat tensile tests with digital image correlation. The mechanical properties of the FZ were correlated with the CCL as well as with the microstructure of the FZ, which was investigated experimentally. The results show that the chemical composition of fillers and welding speed affect the CCL of solidification cracks. Changes in the microstructure were observed within the fusion zone, and the structure became uniform and finer with the formation of Mg2Si and magnesium-rich, copper, and zinc (η-phase) particles.
The Influence of Homogenisation Parameters on the Microstructure and Hardness of AlMnFeMgSi(Zr) Wrought Alloys
Authors: Broer Jette , Mallow Sina , Oldenburg Kevin , Milkereit Benjamin , Kessler Olaf
Published: October 2023

The purpose of this investigation is to improve the mechanical properties of AlMnFeMgSi wrought alloys by forming a high number density of nano-scaled strengthening dispersoids during homogenisation annealing. The process chain for AlMnFeMgSi wrought alloys includes homogenisation annealing after continuous casting. In this step, inhomogeneities and segregations are dissolved and dispersoids are precipitated. The formed dispersoids hinder grain growth, but usually cannot increase the strength due to their coarse size of some 100 nm. Lower homogenisation temperatures should result in the precipitation of smaller dispersoids during homogenisation. The addition of Zr was investigated to increase this effect. Zr should form further dispersoids from the Al3Zr phase. This requires a fundamental understanding of the temperature-dependent kinetics and the nature of precipitation formation during homogenisation. For this purpose, the as-cast state is first characterised via differential scanning calorimetry. Subsequently, a large number of homogenisation parameters are investigated and quantified via hardness testing. The micro- and nanostructure are investigated for promising parameters and a particle analysis is performed. In the present study, it was possible to precipitate fine dispersoids of few 10 nm by reducing the homogenisation temperature, which resulted in a significant increase in hardness. Alloying with Zr enabled the precipitation of further dispersoids with a size of a few nm in a high number density, which further increased the strength.
Implications of Tioguanine Dosing in IBD Patients with a TPMT Deficiency
Authors: Deben Debbie S. , Derijks Luc J. J. , van den Bosch Bianca J. C. , Creemers Rob H. , van Nunen Annick , van Bodegraven Adriaan A. , Wong Dennis R.
Published: October 2023

Tioguanine is metabolised by fewer enzymatic steps compared to azathioprine and mercaptopurine, without generating 6-methylmercaptopurine ribonucleotides. However, thiopurine S-methyl transferase (TPMT) plays a role in early toxicity in all thiopurines. We aimed to describe the hazards and opportunities of tioguanine use in inflammatory bowel disease (IBD) patients with aberrant TPMT metabolism and propose preventative measures to safely prescribe tioguanine in these patients. In this retrospective cohort study, all determined TPMT genotypes (2016–2021) were evaluated for aberrant metabolism (i.e., intermediate and poor TPMT metabolisers). Subsequently, all IBD patients on tioguanine with aberrant TPMT genotypes were evaluated for tioguanine dosages, adverse drug events, lab abnormalities, treatment duration and effectiveness. TPMT genotypes were determined in 485 patients, of whom, 50 (10.3%) and 4 patients (0.8%) were intermediate and poor metabolisers, respectively. Of these patients, 12 intermediate and 4 poor TPMT metabolisers had been prescribed tioguanine in varying doses. In one poor TPMT metaboliser, tioguanine 10 mg/day induced delayed pancytopenia. In general, reduced tioguanine dosages of 5 mg/day for intermediate TPMT metabolisers, and 10 mg two-weekly for poor TPMT metabolisers, resulted in a safe, long-term treatment strategy. Diminished or absent TPMT enzyme activity was related with a pharmacokinetic shift of tioguanine metabolism which is associated with relatively late-occurring myelotoxicity in patients on standard tioguanine dose. However, in strongly reduced dose regimens with strict therapeutic drug and safety monitoring, tioguanine treatment remained a safe and effective option in IBD patients with dysfunctional TPMT.
Two-Stage Deep-Learning Classifier for Diagnostics of Lung Cancer Using Metabolites
Authors: Choudhary Ashvin , Yu Jianpeng , Kouznetsova Valentina L. , Kesari Santosh , Tsigelny Igor F.
Published: October 2023

We developed a machine-learning system for the selective diagnostics of adenocarcinoma (AD), squamous cell carcinoma (SQ), and small-cell carcinoma lung (SC) cancers based on their metabolomic profiles. The system is organized as two-stage binary classifiers. The best accuracy for classification is 92%. We used the biomarkers sets that contain mostly metabolites related to cancer development. Compared to traditional methods, which exclude hierarchical classification, our method splits a challenging multiclass task into smaller tasks. This allows a two-stage classifier, which is more accurate in the scenario of lung cancer classification. Compared to traditional methods, such a “divide and conquer strategy” gives much more accurate and explainable results. Such methods, including our algorithm, allow for the systematic tracking of each computational step.