bluuebunny/crossref_metadata_2025 huggingface dataset:
The functional and molecular impact of triamcinolone acetonide on primary human bone marrow mesenchymal stem cells
Authors: Kumlin Maritha , Ungerstedt Johanna , Cai Huan , Leonard Elory , Felländer-Tsai Li , Qian Hong
Published: December 2023

Traumatic or degenerative joint pain is abundant in the population. Symptom relief by intra- and periarticular glucocorticoid administration is frequently used, however may have potentially devastating effects, changing the normal healing process of the joint. Mesenchymal stem cells (MSCs) are important for wound-healing processes due to their multipotency in regenerating osteoblasts, chondrocytes and adipocytes but also have immunomodulatory properties. The aim of this study was to investigate the impact of triamcinolone acetonide (TA) a common glucocorticoid administrated intra- and periarticularly, on human bone marrow derived MSC viability, functionality, multi-lineage differentiation and transcriptomic output. We found that TA treatment induced apoptosis and promoted adipogenesis while impairing chondrogenesis of MSCs. RNA sequencing indicated that TA modulated the inflammatory response of MSCs, which may have an impact on the immunologic environment where the inflammatory phase is a physiological part of the natural healing process. These data indicate that triamcinolone acetonide should be used with consideration bearing the patient’s outcome in mind, with the intention to optimize joint recovery and homeostasis.
Modulating hierarchical self-assembly in thermoresponsive intrinsically disordered proteins through high-temperature incubation time
Authors: Sethi Vaishali , Cohen-Gerassi Dana , Meir Sagi , Ney Max , Shmidov Yulia , Koren Gil , Adler-Abramovich Lihi , Chilkoti Ashutosh , Beck Roy
Published: December 2023

The cornerstone of structural biology is the unique relationship between protein sequence and the 3D structure at equilibrium. Although intrinsically disordered proteins (IDPs) do not fold into a specific 3D structure, breaking this paradigm, some IDPs exhibit large-scale organization, such as liquid–liquid phase separation. In such cases, the structural plasticity has the potential to form numerous self-assembled structures out of thermal equilibrium. Here, we report that high-temperature incubation time is a defining parameter for micro and nanoscale self-assembly of resilin-like IDPs. Interestingly, high-resolution scanning electron microscopy micrographs reveal that an extended incubation time leads to the formation of micron-size rods and ellipsoids that depend on the amino acid sequence. More surprisingly, a prolonged incubation time also induces amino acid composition-dependent formation of short-range nanoscale order, such as periodic lamellar nanostructures. We, therefore, suggest that regulating the period of high-temperature incubation, in the one-phase regime, can serve as a unique method of controlling the hierarchical self-assembly mechanism of structurally disordered proteins.
Correlation of PD-1 and PD-L1 expression in oral leukoplakia and oral squamous cell carcinoma: an immunohistochemical study
Authors: Greeshma L. R. , Joseph Anna P. , Sivakumar T. T. , Raghavan Pillai Varun , Vijayakumar Gopikrishnan
Published: December 2023

The programmed cell death protein (PD-1)/programmed cell death protein ligand (PD-L1) pathway and cytotoxic T lymphocyte antigen are the most important co-stimulatory molecules that play a key role in the negative regulation of T cells during carcinogenesis. We aimed to evaluate the immunohistochemical expression of PD-1 and PD-L1 in oral leukoplakia and squamous cell carcinoma compared with normal oral mucosa. Twenty-five cases of oral squamous cell carcinoma, oral leukoplakia and normal oral mucosa tissue specimens were immunohistochemically stained to assess PD-1 and PD-L1 expression. The PD-L1 positivity of subepithelial TAFs (p < 0.001) increased with increasing grades of oral leukoplakia. Pearson’s correlation indicated a high positive correlation between the PD-L1 labelling index of epithelial tumour cells and the PD-1 labelling index of tumour infiltrating lymphocytes (p value: 0.005) in OSCC. A high positive correlation was noted between the H-score of PD-L1 positive tumour epithelial cells and the H-score of PD-1 positive tumour infiltrating lymphocytes in OSCC (p value: 0.001). PD-L1 positivity increased in dysplastic epithelial cells from premalignant lesions to malignancy. The sub-epithelial PD-L1 positive TAFs were higher in oral leukoplakia compared to OSCC inferring that PD-L1 positivity in TAFs decreased with malignant transformation. The PD-1 positivity in TILs was higher in oral leukoplakia than in OSCC.
Glycosyltransferase 8 domain-containing protein 1 (GLT8D1) is a UDP-dependent galactosyltransferase
Authors: Vicente João B. , Guerreiro Ana Catarina L. , Felgueiras Beatriz , Chapla Digantkumar , Tehrani Daniel , Moremen Kelley W. , Costa Júlia
Published: December 2023

Glycosyltransferases (GTs) are enzymes that catalyze the formation of glycosidic bonds and hundreds of GTs have been identified so far in humans. Glycosyltransferase 8 domain-containing protein 1 (GLT8D1) has been associated with central nervous system diseases and cancer. However, evidence on its enzymatic properties, including its substrates, has been scarcely described. In this paper, we have produced and purified recombinant secretory GLT8D1. The enzyme was found to be N-glycosylated. Differential scanning fluorimetry was employed to analyze the stabilization of GLT8D1 by Mn2+ and nucleotides, revealing UDP as the most stabilizing nucleotide scaffold. GLT8D1 displayed glycosyltransferase activity from UDP-galactose onto N-acetylgalactosamine but with a low efficiency. Modeling of the structure revealed similarities with other GT-A fold enzymes in CAZy family GT8 and glycosyltransferases in other families with galactosyl-, glucosyl-, and xylosyltransferase activities, each with retaining catalytic mechanisms. Our study provides novel structural and functional insights into the properties of GLT8D1 with implications in pathological processes.
Measurement of solid size in early-stage lung adenocarcinoma by virtual 3D thin-section CT applied artificial intelligence
Authors: Iwano Shingo , Kamiya Shinichiro , Ito Rintaro , Kudo Akira , Kitamura Yoshiro , Nakamura Keigo , Naganawa Shinji
Published: December 2023

An artificial intelligence (AI) system that reconstructs virtual 3D thin-section CT (TSCT) images from conventional CT images by applying deep learning was developed. The aim of this study was to investigate whether virtual and real TSCT could measure the solid size of early-stage lung adenocarcinoma. The pair of original thin-CT and simulated thick-CT from the training data with TSCT images (thickness, 0.5–1.0 mm) of 2700 pulmonary nodules were used to train the thin-CT generator in the generative adversarial network (GAN) framework and develop a virtual TSCT AI system. For validation, CT images of 93 stage 0–I lung adenocarcinomas were collected, and virtual TSCTs were reconstructed from conventional 5-mm thick-CT images using the AI system. Two radiologists measured and compared the solid size of tumors on conventional CT and virtual and real TSCT. The agreement between the two observers showed an almost perfect agreement on the virtual TSCT for solid size measurements (intraclass correlation coefficient = 0.967, P < 0.001, respectively). The virtual TSCT had a significantly stronger correlation than that of conventional CT (P = 0.003 and P = 0.001, respectively). The degree of agreement between the clinical T stage determined by virtual TSCT and the clinical T stage determined by real TSCT was excellent in both observers (k = 0.882 and k = 0.881, respectively). The AI system developed in this study was able to measure the solid size of early-stage lung adenocarcinoma on virtual TSCT as well as on real TSCT.
The evidential value of dental calculus in the identification process
Authors: Lisman Dagmara , Drath Joanna , Zielińska Grażyna , Zacharczuk Julia , Piątek Jarosław , van de Wetering Thierry , Ossowki Andrzej
Published: December 2023

DNA analysis-based identification is by far the gold standard in forensic genetics and it should be performed in every case involving human remains or unidentified bodies. Bones and teeth are the preferred source of human DNA for genetic analysis. However, there are cases where the nature of the proceedings and historical significance prevent the disruption of skeletal structure. The remains may also be heavily degraded. In such situations, forensic geneticists seek alternative sources of human DNA. Teeth calculus has proven to be a viable source of DNA for identification purposes. The aim of this study was to assess the concentration of human DNA in teeth calculus and evaluate the usefulness of teeth calculus as a DNA source in the identification process. Teeth calculus was collected from skeletons exhumed between 2021 and 2022 by the PBGOT (Polish Genetic Database of Victims of Totalitarianism) team from the former Stalag IID prisoner-of-war camp in Stargard. Genetic analyses included the determination of autosomal and Y-STR markers. The total concentration of human DNA was also evaluated in samples from teeth calculus and teeth taken from the same individuals. The pilot study included 22 skeletons with a sufficient amount of calculus for isolation (specified in the protocol). Samples were taken from the largest areas of calculus deposited on lingual surfaces of mandibular incisors. The prepared samples underwent DNA extraction. Our study demonstrated that teeth calculus is a source of human DNA for remains from the World War II period. The obtained DNA concentration allowed for the determination of STR markers. It was shown that teeth calculus contains human DNA in an amount suitable for preliminary identification analyses.
Assessment of heavy metal accumulation and health risk in three essential edible weeds grown on wastewater irrigated soil
Authors: Abdelgawad Zinab A. , Abd El-Wahed Mona N. , Ahmed Asmaa A. , Madbouly Seliem M. , El-Sayyad Gharieb S. , Khalafallah Ahmed A.
Published: December 2023

The main problem facing Egypt recently is the shortage of available water resources. Therefore, farmers resort to use wastewater for irrigation. So, the present work aims to assess the impacts of wastewater irrigation on the productivity of three edible weeds (Cichorium endivia, Sonchus oleraceous and Beta vulgaris) and its effect on the nutritional value of plants and its risk on human health. This study will focus on Shibin Al Kanater region, and the physicochemical characteristics of drainage water, canal water, drainage water-irrigated soils and canal-irrigated soils were estimated. The vegetative and traits of edible weeds were determined including their photosynthetic pigments, organic and inorganic nutrients content, and heavy metals content. The health risk index (HRI) associated with consumption of polluted plants was created using the estimated exposure factor of a crop to the oral reference dosage of the toxic metal. The main results showed that biomass productivity of S. oleraceous, B. vulgaris and C. endivia increased due to drainage water irrigation with increasing percentage as 27.9, 19.6, and 19.1%, respectively. Irrigation with drainage water significantly increased the photosynthetic pigments of edible weeds. Irrigation with drainage water increased carbohydrate content, crude protein, total soluble sugar, and gross energy in all studied weeds. C. endivia, S. oleraceus and B. vulgaris plants irrigated with canal and drainage water could accumulate Fe, Zn, Cu, and Co in their roots. C. endivia, S. oleraceus and B. vulgaris plants irrigated with canal water indicated HRI more than the unit for Mn, Cu, Pb, and Cd. This research advises that regulation be put in place to prohibit irrigation using untreated drainage and to restrict the discharge of industrial, domestic, and agricultural wastewater into irrigation canals.
Ag nanorod@PEI-Ag nanohybrid as an excellent signal label for sensitive and rapid detection of serum HER2
Authors: Hakimian Fatemeh , Mazloum-Ardakani Mohammad
Published: December 2023

The accurate detection of Human epidermal growth factor receptor-2 (HER2) as a critical breast cancer biomarker can be essential for the early selection of therapeutic approaches. HER2 is a prominent component of a signaling network. Overexpression of the HER2 protein due to amplification of its gene leads to the development of an aggressive subtype of breast cancer. Patients with tumors that overexpress HER2 are eligible for treatment that significantly reduces mortality rates. Herein, we present a fast and simple method for detecting serum HER2. A new electrochemical label has been developed using charged Ag nanorod@ polyethylenimine-Ag (Ag NR@ PEI-Ag) nanohybrid. The synthesized Ag NR@PEI-Ag nanohybrid simultaneously has the electroactive property of silver and the large surface area of the PEI, which results in the enhancement of the detection signal. So, using Ag NR@PEI-Ag nanohybrid as the electrochemical label, a simple, fast, and sensitive electrochemical biosensor was designed to detect HER2. This way, after immobilizing HER2 aptamer on the Au electrode surface, HER2 or human serum was exposed to the aptamer. Then, the positively charged Ag NR@PEI-Ag nanohybrid was adsorbed onto the negatively charged aptamer-HER2 complex, and the current that was produced due to the Ag/AgCl reaction was measured as the electrochemical signal. The aptasensor shows a broad linear response from 10–12 to 10–7 g, a low detection limit (LOD) of 10 pg, and a total assay time of ~ 30 min.
Allergic sensitization does not influence advancement or survival in oral cancer
Authors: Kakabas Lara , Piersiala Krzysztof , Kolev Aeneas , Kumlien Georén Susanna , Cardell Lars-Olaf
Published: December 2023

A history of allergies has been said to be associated with a lower risk of head and neck cancer compared to the general population. However, it is not known whether having an allergic sensitization influences the prognosis and advancement of cancer disease. Thus, the aim of the study was to investigate the relationship between allergic sensitization and oral cancer advancement and patient survival. Allergen-specific IgE antibodies were investigated by ImmunoCAP™ Rapid in consecutive 80 patients with oral cancer. ImmunoCAP Rapid system tests a mix of representative inhalant allergens such as birch, timothy grass, mugwort, house dust mite, cat, dog, cockroach, olive (pollen), wall pellitory and mold. Eighty patients met the inclusion criteria for the study. Fifteen patients (19%) had positive ImmunoCAP test. There was no statistically significant difference in primary tumour size (T-stage) between groups (60% in allergy vs 68% in non-allergy had T1–T2 stage and 40% vs 32% T3–T4, respectively, p = 0.570). 27% of patients with allergy had nodal metastases compared with 37% of patients without allergy (p = 0.557). Both groups had comparable short-term survival. In conclusion, allergic sensitization does not seem to influence either the advancement or the short-term survival of patients with oral squamous cell carcinoma.
Serine 937 phosphorylation enhances KCC2 activity and strengthens synaptic inhibition
Authors: Radulovic Tamara , Rajaram Ezhilarasan , Ebbers Lena , Pagella Sara , Winklhofer Michael , Kopp-Scheinpflug Conny , Nothwang Hans Gerd , Milenkovic Ivan , Hartmann Anna-Maria
Published: December 2023

The potassium chloride cotransporter KCC2 is crucial for Cl-extrusion from mature neurons and thus key to hyperpolarizing inhibition. Auditory brainstem circuits contain well-understood inhibitory projections and provide a potent model to study the regulation of synaptic inhibition. Two peculiarities of the auditory brainstem are (i) posttranslational activation of KCC2 during development and (ii) extremely negative reversal potentials in specific circuits. To investigate the role of the potent phospho-site serine 937 therein, we generated a KCC2 Thr934Ala/Ser937Aspdouble mutation, in which Ser937is replaced by aspartate mimicking the phosphorylated state, and the neighbouring Thr934arrested in the dephosphorylated state. This double mutant showed a twofold increased transport activity in HEK293 cells, raising the hypothesis that auditory brainstem neurons show lower [Cl−]i. and increased glycinergic inhibition. This was tested in a mouse model carrying the same KCC2 Thr934Ala/Ser937Aspmutation by the use of the CRISPR/Cas9 technology. Homozygous KCC2 Thr934Ala/Ser937Aspmice showed an earlier developmental onset of hyperpolarisation in the auditory brainstem. Mature neurons displayed stronger glycinergic inhibition due to hyperpolarized ECl−. These data demonstrate that phospho-regulation of KCC2 Ser937is a potent way to interfere with the excitation-inhibition balance in neural circuits.
A novel feature selection algorithm for identifying hub genes in lung cancer
Authors: Mohamed Tehnan I. A. , Ezugwu Absalom E. , Fonou-Dombeu Jean Vincent , Mohammed Mohanad , Greeff Japie , Elbashir Murtada K.
Published: December 2023

Lung cancer, a life-threatening disease primarily affecting lung tissue, remains a significant contributor to mortality in both developed and developing nations. Accurate biomarker identification is imperative for effective cancer diagnosis and therapeutic strategies. This study introduces the Voting-Based Enhanced Binary Ebola Optimization Search Algorithm (VBEOSA), an innovative ensemble-based approach combining binary optimization and the Ebola optimization search algorithm. VBEOSA harnesses the collective power of the state-of-the-art classification models through soft voting. Moreover, our research applies VBEOSA to an extensive lung cancer gene expression dataset obtained from TCGA, following essential preprocessing steps including outlier detection and removal, data normalization, and filtration. VBEOSA aids in feature selection, leading to the discovery of key hub genes closely associated with lung cancer, validated through comprehensive protein–protein interaction analysis. Notably, our investigation reveals ten significant hub genes—ADRB2, ACTB, ARRB2, GNGT2, ADRB1, ACTG1, ACACA, ATP5A1, ADCY9, and ADRA1B—each demonstrating substantial involvement in the domain of lung cancer. Furthermore, our pathway analysis sheds light on the prominence of strategic pathways such as salivary secretion and the calcium signaling pathway, providing invaluable insights into the intricate molecular mechanisms underpinning lung cancer. We also utilize the weighted gene co-expression network analysis (WGCNA) method to identify gene modules exhibiting strong correlations with clinical attributes associated with lung cancer. Our findings underscore the efficacy of VBEOSA in feature selection and offer profound insights into the multifaceted molecular landscape of lung cancer. Finally, we are confident that this research has the potential to improve diagnostic capabilities and further enrich our understanding of the disease, thus setting the stage for future advancements in the clinical management of lung cancer. The VBEOSA source codes is publicly available at https://github.com/TEHNAN/VBEOSA-A-Novel-Feature-Selection-Algorithm-for-Identifying-hub-Genes-in-Lung-Cancer.
Express detection of visual objects by primate superior colliculus neurons
Authors: Bogadhi Amarender R. , Hafed Ziad M.
Published: December 2023

Primate superior colliculus (SC) neurons exhibit visual feature tuning properties and are implicated in a subcortical network hypothesized to mediate fast threat and/or conspecific detection. However, the mechanisms through which SC neurons contribute to peripheral object detection, for supporting rapid orienting responses, remain unclear. Here we explored whether, and how quickly, SC neurons detect real-life object stimuli. We presented experimentally-controlled gray-scale images of seven different object categories, and their corresponding luminance- and spectral-matched image controls, within the extrafoveal response fields of SC neurons. We found that all of our functionally-identified SC neuron types preferentially detected real-life objects even in their very first stimulus-evoked visual bursts. Intriguingly, even visually-responsive motor-related neurons exhibited such robust early object detection. We further identified spatial frequency information in visual images as an important, but not exhaustive, source for the earliest (within 100 ms) but not for the late (after 100 ms) component of object detection by SC neurons. Our results demonstrate rapid and robust detection of extrafoveal visual objects by the SC. Besides supporting recent evidence that even SC saccade-related motor bursts can preferentially represent visual objects, these results reveal a plausible mechanism through which rapid orienting responses to extrafoveal visual objects can be mediated.
Enhancing autism spectrum disorder classification in children through the integration of traditional statistics and classical machine learning techniques in EEG analysis
Authors: Rogala Jacek , Żygierewicz Jarosław , Malinowska Urszula , Cygan Hanna , Stawicka Elżbieta , Kobus Adam , Vanrumste Bart
Published: December 2023

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder hallmarked by challenges in social communication, limited interests, and repetitive, stereotyped movements and behaviors. Numerous research efforts have indicated that individuals with ASD exhibit distinct brain connectivity patterns compared to control groups. However, these investigations, often constrained by small sample sizes, have led to inconsistent results, suggesting both heightened and diminished long-range connectivity within ASD populations. To bolster our analysis and enhance their reliability, we conducted a retrospective study using two different connectivity metrics and employed both traditional statistical methods and machine learning techniques. The concurrent use of statistical analysis and classical machine learning techniques advanced our understanding of model predictions derived from the spectral or connectivity attributes of a subject's EEG signal, while also verifying these predictions. Significantly, the utilization of machine learning methodologies empowered us to identify a unique subgroup of correctly classified children with ASD, defined by the analyzed EEG features. This improved approach is expected to contribute significantly to the existing body of knowledge on ASD and potentially guide personalized treatment strategies.
Trends in hypertension prevalence, awareness, treatment, and control in South Korea, 1998–2021: a nationally representative serial study
Authors: Lee Myeongcheol , Lee Hojae , Park Jaeyu , Kim Hyeon Jin , Kwon Rosie , Lee Seung Won , Kim Sunyoung , Koyanagi Ai , Smith Lee , Kim Min Seo , Fond Guillaume , Boyer Laurent , Rahmati Masoud , Rhee Sang Youl , Yon Dong Keon
Published: December 2023

The impact of the pandemic on hypertension management is unknown, particularly regarding changes in demographic risk factors. We conducted a comprehensive study between 1998 and 2021 on the long-term trends in hypertension prevalence in South Korea, including a comparison of the pre-pandemic and pandemic eras. Data from 1998 to 2021 of 108,687 Korean adults were obtained through a nationwide, large-scale, and serial study. We conducted a weighted complex sampling analysis on the estimates of national prevalence and compared the slope of hypertension prevalence before and during the pandemic to determine the trend dynamics. We included 108,687 participants over 24 years, 1998–2021. While the prevalence of patients with hypertension consistently increased before the pandemic from 25.51% [95% CI: 24.27–26.75] in 1998–2005 to 27.81% [95% CI: 26.97–28.66] in 2016–2019, the increasing slope in hypertension prevalence slowed during the pandemic period (28.07% [95% CI: 26.16–29.98] for 2021; βdiff, −0.012 [−0.023 to 0.000]). Hypertension awareness, treatment, control, and control rates among patients receiving treatment followed similar trends. Compared to the pre-pandemic era, individuals aged 19–59 years or male had significantly increased control rates among the treated patients during the pandemic. This study investigated long-term trends in hypertension prevalence, awareness, treatment, and control among Korean adults. The absence of a reduction in the health indicators associated with hypertension during the pandemic implies that medical services for individuals with hypertension remain unaffected.
Investigating the value of balance and proprioception scores to predict lower limb injuries in professional judokas
Authors: Darbandi Shirzad Mian , Zarei Mostafa , Mohammadi Haniyeh , Hosseinzadeh Mahdi
Published: December 2023

We investigated the ability of balance and proprioception screening tests to predict lower limb injuries in professional male judokas. Fifty-three male judokas of the national teams (Mean ± SD, age 18.68 ± 3.08 years, weight 75.34 ± 11.62 kg, height 175.28 ± 7.24 cm) participated in this study. Limits of stability (LOS), single leg stability (SLS), and knee joint position sense (JPS) was recorded as the screening tests before starting the 10 month follow up. Lower limb injury was recorded all through the follow up. Fifteen lower limb sport injuries were recorded for 53 judokas during the follow-up recordings. Significant accuracy of SLS, overall bilateral ratio (AUC 0.646, 95% CI 0.452–0.839, p = 0.046), as well as JPS 60° bilateral ratio (AUC 0.657, 95% CI 0.480–0.834, p = 0.044), and LOS overall (AUC 0.696, 95% CI 0.551–0.840, p = 0.031) were revealed discriminating between injured and uninjured judokas. The optimum cut-off of SLS, overall bilateral ratio, JPS 60° bilateral ratio, and LOS overall associated with belonging to uninjured judokas group was ≤ 1.15%, ≤ 1.09%, and ≤ 1.09 respectively (sensitivity, 0.763, 0.711, 0.789 respectively; specificity, 0.600). Although the absolute unilateral balance and proprioception scores were almost the same between injured and non-injured judokas, the bilateral ratio of both these indices were different between the two groups. Lower limbs bilateral balance and proprioception asymmetries is a more important risk factor than the absolute unilateral balance and proprioception scores for sustaining lower limb injuries in professional male judokas. Medical professionals and coaches are suggested to use these findings as pre-participation screening tools identify injury-prone athletes.
Dynamics of major environmental disasters involving fire in the Brazilian Pantanal
Authors: Pelissari Tatiane Deoti , Teodoro Paulo Eduardo , Teodoro Larissa Pereira Ribeiro , Lima Mendelson , Santana Dthenifer Cordeiro , Rossi Fernando Saragosa , dos Santos Daniel Henrique , De Almeida Silva Renan , Lourençoni Thaís , da Silva Junior Carlos Antonio
Published: December 2023

The 2020 environmental catastrophe in Pantanal has highlighted the fragility of environmental policies and practices for managing and fighting fires in this biome. Therefore, it is essential to know the causes and circumstances that potentiate these fires. This study aimed to: (I) assess the relationship between fire foci and carbon absorption (GPP), precipitation, and carbon dioxide (CO2) flux; (ii) analyze vegetation recovery using the differenced normalized burn ratio (ΔNBR) in Brazilian Pantanal between 2001 and 2022; and (iii) identify priority areas, where the highest intensities of fire foci have occurred, in order to guide public policies in Brazil to maintain local conservation. To this purpose, fire foci were detected using data from the MODIS MOD14/MYD14 algorithm, annual precipitation with CHIRPS (Climate Hazards Group InfraRed Precipitation with Station data), and CO2 flux using the MODIS/MODO9A1 product, and Gross Primary Production (GPP) with the MODIS/MOD17A2 product. The severity of the burned area was also assessed using the ΔNBR index and the risk areas were determined using the averages of these images. During the time series studied, a total of 300,127 fire foci were detected throughout the Pantanal, where 2020 had the highest number of foci and the lowest accumulated precipitation. The years with the highest precipitation were 2014 and 2018. The year 2018 was also the second year with the highest GPP value. The Pettit test showed a trend for 2008 and 2011 as the points of change in the CO2 flux and GPP variables. Principal component analysis clustered fire foci and precipitation on opposite sides, as well as GPP and CO2 flux, while ΔNBR clustered HS, MHS and MLS classes with the years 2020, 2019, 2002 and 2021. There was a high negative correlation between fire foci × rainfall and GPP × CO2 flux. The years with the largest areas of High severity (HS), Moderate-high severity (MHS) and Moderate-low severity (MLS) classes were 2020 and 2019, respectively. The most vulnerable areas for severe fires were the municipalities of Cáceres, Poconé, and Corumbá. The major fire catastrophe in 2020 is correlated with the low precipitation in 2019, the high precipitation in 2018, and the increased GPP, as well government policies unfavorable to the environment.
Load-induced deformation of the tibia and its effect on implant loosening detection
Authors: ter Wee M. A. , Dobbe J. G. G. , Buijs G. S. , Kievit A. J. , Schafroth M. U. , Maas M. , Blankevoort L. , Streekstra G. J.
Published: December 2023

CT imaging under external valgus and varus loading conditions and consecutive image analysis can be used to detect tibial implant loosening after total knee arthroplasty. However, the applied load causes the tibia to deform, which could result in an overestimation of implant displacement. This research evaluates the extent of tibia deformation and its effect on measuring implant displacement. Ten cadaver specimen with TKA were CT-scanned under valgus/varus loading (20 Nm), first implanted without bone cement fixation (mimicking a loose implant) and subsequently with bone cement fixation (mimicking a fixed implant). By means of image analysis, three relative displacements were assessed: (1) between the proximal and distal tibia (measure of deformation), (2) between the implant and the whole tibia (including potential deformation effect) and (3) between the implant and the proximal tibia (reduced deformation effect). Relative displacements were quantified in terms of translations along, and rotations about the axes of a local coordinate system. As a measure of deformation, the proximal tibia moved relative to the distal tibia by, on average 1.27 mm (± 0.50 mm) and 0.64° (± 0.25°). Deformation caused an overestimation of implant displacement in the cemented implant. The implant displaced with respect to the whole tibia by 0.45 mm (± 0.22 mm) and 0.79° (± 0.38°). Relative to the proximal tibia, the implant moved by 0.23 mm (± 0.10 mm) and 0.62° (± 0.34°). The differentiation between loose and fixed implants improved when tibia deformation was compensated for by using the proximal tibia rather than the whole tibia.
Effect of lipotoxicity on mitochondrial function and epigenetic programming during bovine in vitro embryo production
Authors: Meulders Ben , Marei Waleed F. A. , Xhonneux Inne , Bols Peter E. J. , Leroy Jo L. M. R.
Published: December 2023

Maternal metabolic disorders may cause lipotoxic effects on the developing oocyte. Understanding the timing at which this might disrupt embryo epigenetic programming and how this is linked with mitochondrial dysfunction is crucial for improving assisted reproductive treatments, but has not been investigated before. Therefore, we used a bovine in vitro model to investigate if pathophysiological palmitic acid (PA) concentrations during in vitro oocyte maturation and in vitro embryo culture alter embryo epigenetic patterns (DNA methylation (5mC) and histone acetylation/methylation (H3K9ac/H3K9me2)) compared to control (CONT) and solvent control (SCONT), at the zygote and morula stage. Secondly, we investigated if these epigenetic alterations are associated with mitochondrial dysfunction and changes in ATP production rate, or altered expression of epigenetic regulatory genes. Compared to SCONT, H3K9ac and H3K9me2 levels were increased in PA-derived zygotes. Also, 5mC and H3K9me2 levels were increased in PA-exposed morulae compared to SCONT. This was associated with complete inhibition of glycolytic ATP production in oocytes, increased mitochondrial membrane potential and complete inhibition of glycolytic ATP production in 4-cell embryos and reduced SOD2 expression in PA-exposed zygotes and morulae. For the first time, epigenetic alterations in metabolically compromised zygotes and morulae have been observed in parallel with mitochondrial dysfunction in the same study.
Behavioral and physiological fatigue-related factors influencing timing and force control learning in pianists
Authors: Takemi Mitsuaki , Akahoshi Mai , Ushiba Junichi , Furuya Shinichi
Published: December 2023

Optimizing the training regimen depending on neuromuscular fatigue is crucial for the well-being of professionals intensively practicing motor skills, such as athletes and musicians, as persistent fatigue can hinder learning and cause neuromuscular injuries. However, accurate assessment of fatigue is challenging because of the dissociation between subjective perception and its impact on motor and cognitive performance. To address this issue, we investigated the interplay between fatigue and learning development in 28 pianists during three hours of auditory-motor training, dividing them into two groups subjected to different resting conditions. Changes in behavior and muscle activity during training were measured to identify potential indicators capable of detecting fatigue before subjective awareness. Our results indicate that motor learning and fatigue development are independent of resting frequency and timing. Learning indices, such as reduction in force and timing errors throughout training, did not differ between the groups. No discernible distinctions emerged in fatigue-related behavioral and physiological indicators between the groups. Regression analysis revealed that several fatigue-related indicators, such as tapping speed variability and electromyogram amplitude per unit force, could explain the learning of timing and force control. Our findings suggest the absence of a universal resting schedule for optimizing auditory-motor learning.
Anti-Bordetella bronchiseptica effects of targeted bacteriophages via microbiome and metabolic mediated mechanisms
Authors: Hosseindoust Abdolreza , Choi YoHan , Ha SangHun , Tajudeen Habeeb , Mun JunYoung , Kinara Elick , Kim YoungIn , Kim JinSoo
Published: December 2023

Bordetella bronchiseptica poses a significant challenge in the context of respiratory infections, particularly in weanling pigs. In this study, we investigated the impact of a novel targeted bacteriophage in controlling B. bronchiseptica challenge (BBC) in an experimental design involving five distinct treatment groups: NC (no challenge), PC (BBC challenge), BF (108 pfu bacteriophage/kg diet + BBC), BN (2 × 107 pfu/day bacteriophage by nasal spray + BBC), and AT (antibiotic + BBC). The experiment was conducted for 2 weeks. The highest turbinate score was observed in the PC. The BF treatment showed higher plasma IL (interleukine)-1β and IL-6 compared with the BN and AT treatments. Plasma concentrations of IL-1β were increased in the BF pigs compared with the BN, AT, and NC. Among the BBC groups, the PC treatment exhibited a higher abundance of Staphylococcus. aureus and B. bronchiseptica in the lung. A lower S. aureus, Streptococcus. suis, and B. bronchiseptica colonization was detected in the AT compared with the BF and BN treatments. The BF showed lower plasma zonulin compared with the BN and AT. A higher plasma concentration of superoxide dismutase was observed in the BF and AT compared with PC and BN. The BN influenced the glycine, serine-threonine metabolism; glycerolipid metabolism; glyoxylate-dicarboxylate metabolism; and arachidonic acid metabolism compared with the NC. In conclusion, nasal-sprayed bacteriophage effectively controlled B. bronchiseptica infection, however, their efficiency was lower than the antibiotic.
Analysis of spatial variation of street landscape greening and influencing factors: an example from Fuzhou city, China
Authors: Jin Bowen , Geng Jianwei , Ke Shan , Pan Hui
Published: December 2023

Urban street greening is an important part of urban green infrastructure, and Green View Index (GVI) is widely used to assess urban street quality and ecosystem service value as an important indicator to quantify the perception of green street landscape from a pedestrian perspective. However, the distribution of street greenery is imbalanced. Therefore, to explore the differences in street greening levels within urban cities, we crawled streetscape data using the Internet to assess the spatial distribution patterns of urban street GVI using deep learning and spatial autocorrelation, and combined 11 surrounding environmental features with multi-source geographic data to further analyze the key factors influencing the spatial variation of block GVI using ordinary least squares, geographically weighted regression (GWR) models, and multi-scale geographically weighted regression (MGWR) models. The results show that the mean value of GVI in Fuzhou city is low (23.08%), with large differences among neighborhoods and a significant spatial autocorrelation. Among the regression models, MGWR has the best fit with an R2 of 0.702, where the variables of NDVI, house price, accessibility of water bodies and parks, and the proportion of built-up land have a greater impact on GVI, and the factors do not have the same spatial effect size. The results can provide a scientific basis for promoting green visual equity in different blocks.
Accelerated soil drying linked to increasing evaporative demand in wet regions
Authors: Qing Yamin , Wang Shuo , Yang Zong-Liang , Gentine Pierre , Zhang Boen , Alexander Jagger
Published: December 2023

The rapid decline in soil water affects water resources, plant physiology, and agricultural development. However, the changes in soil drying rate and associated climatic mechanisms behind such changes remain poorly understood. Here, we find that wet regions have witnessed a significant increasing trend in the soil drying rate during 1980−2020, with an average increase of 6.01 − 9.90% per decade, whereas there is no consistent trend in dry regions. We also identify a near-linear relationship between the annual soil drying rate and its influencing factors associated with atmospheric aridity and high temperatures. Further, enhanced evapotranspiration by atmospheric aridity and high temperatures is the dominant factor increasing the soil drying rate in wet regions. Our results highlight the accelerated soil drying in the recent four decades in wet regions, which implies an increased risk of rapidly developing droughts, posing a serious challenge for the adaptability of ecosystems and agriculture to rapid drying.
Home-run trials for rare cancers: giving the right drug(s) to the right patients at the right time and in the right place
Authors: Adashek Jacob J. , Kurzrock Razelle
Published: December 2023

In oncology clinical trials, many patients spend their final months at a central clinical trial facility far from home for “mandatory” protocol visits/diagnostic testing. Studies suggest that the travel strain may be greatest among patients living in low‐income areas and/or participating in early-phase studies. In this regard, rare cancers constitute a special unmet need with limited therapeutic options and few trials. Though individually uncommon, rare cancers as a group constitute ~22% of the cancer burden; the portion of cancer burden may even be greater if biomarker-defined rare subsets of either a single cancer type or a tissue-agnostic subgroup are included. Exacerbating the access issue is the fact that, in addition to the paucity of trials, many centers will not activate existing single-arm trials, often due to accrual concerns, which may further disadvantage this patient group and also jeopardize trial completion. Decentralized clinical trials may resolve some of these challenges by allowing patients to participate from close to home. Decentralized clinical trials can take the form of being site-less, with the coordinating body working remotely and care provided by the home oncologist, or by taking the tack of National Cancer Institute/cooperative groups (e.g., NCI-MATCH genomics matching trial or SWOG1609 [NCI] DART immunotherapy rare cancer trial) using a platform design with multiple cohorts and opening at >1000 sites. Decentralized trials now also have supportive FDA guidance. Importantly, home-run trials permit clinical trial access to underserved groups, including those in rural areas and patients financially unable to travel to a central facility.
Downregulation of mitochondrial metabolism is a driver for fast skeletal muscle loss during mouse aging
Authors: Fernando Raquel , Shindyapina Anastasia V. , Ost Mario , Santesmasses Didac , Hu Yan , Tyshkovskiy Alexander , Yim Sun Hee , Weiss Jürgen , Gladyshev Vadim N. , Grune Tilman , Castro José Pedro
Published: December 2023

Skeletal muscle aging is characterized by the loss of muscle mass, strength and function, mainly attributed to the atrophy of glycolytic fibers. Underlying mechanisms driving the skeletal muscle functional impairment are yet to be elucidated. To unbiasedly uncover its molecular mechanisms, we recurred to gene expression and metabolite profiling in a glycolytic muscle, Extensor digitorum longus (EDL), from young and aged C57BL/6JRj mice. Employing multi-omics approaches we found that the main age-related changes are connected to mitochondria, exhibiting a downregulation in mitochondrial processes. Consistent is the altered mitochondrial morphology. We further compared our mouse EDL aging signature with human data from the GTEx database, reinforcing the idea that our model may recapitulate muscle loss in humans. We are able to show that age-related mitochondrial downregulation is likely to be detrimental, as gene expression signatures from commonly used lifespan extending interventions displayed the opposite direction compared to our EDL aging signature.
Reconstructing the post-glacial spread of the sand fly Phlebotomus mascittii Grassi, 1908 (Diptera: Psychodidae) in Europe
Authors: Kniha Edwin , Dvořák Vít , Koblmüller Stephan , Prudhomme Jorian , Ivović Vladimir , Hoxha Ina , Oerther Sandra , Heitmann Anna , Lühken Renke , Bañuls Anne-Laure , Sereno Denis , Michelutti Alice , Toniolo Federica , Alarcón-Elbal Pedro M. , Bravo-Barriga Daniel , González Mikel A. , Lucientes Javier , Colella Vito , Otranto Domenico , Bezerra-Santos Marcos Antônio , Kunz Gernot , Obwaller Adelheid G. , Depaquit Jerome , Alić Amer , Kasap Ozge Erisoz , Alten Bulent , Omeragic Jasmin , Volf Petr , Walochnik Julia , Sebestyén Viktor , Trájer Attila J.
Published: December 2023

Phlebotomine sand flies (Diptera: Phlebotominae) are the principal vectors of Leishmania spp. (Kinetoplastida: Trypanosomatidae). In Central Europe, Phlebotomus mascittii is the predominant species, but largely understudied. To better understand factors driving its current distribution, we infer patterns of genetic diversity by testing for signals of population expansion based on two mitochondrial genes and model current and past climate and habitat suitability for seven post-glacial maximum periods, taking 19 climatic variables into account. Consequently, we elucidate their connections by environmental-geographical network analysis. Most analyzed populations share a main haplotype tracing back to a single glacial maximum refuge area on the Mediterranean coasts of South France, which is supported by network analysis. The rapid range expansion of Ph. mascittii likely started in the early mid-Holocene epoch until today and its spread possibly followed two routes. The first one was through northern France to Germany and then Belgium, and the second across the Ligurian coast through present-day Slovenia to Austria, toward the northern Balkans. Here we present a combined approach to reveal glacial refugia and post-glacial spread of Ph. mascittii and observed discrepancies between the modelled and the current known distribution might reveal yet overlooked populations and potential further spread.
Cooling of hydrothermal fluids rich in carbon dioxide can create large karst cave systems in carbonate rocks
Authors: Roded Roi , Aharonov Einat , Frumkin Amos , Weber Nurit , Lazar Boaz , Szymczak Piotr
Published: December 2023

Karst systems, comprising interconnected voids and caves, are ubiquitous in carbonate formations and play a pivotal role in the global water supply. Accumulating evidence suggests that a significant portion of the global karst is hypogenic, formed via rock dissolution by groundwater ascending from depth (rather than by infiltration from the surface), yet the exact formation mechanism remains unclear. Here we show that cooling of carbon dioxide-rich geothermal fluids, which turns them into highly corrosive agents due to their retrograde solubility, can dissolve and sculpt large caves on short geological timescales. A conceptual hydro-thermo-geochemical scenario is numerically simulated, showing cave formation by rising hot water discharging into a confined layer. Our models predict field observations characteristic of hypogenic caves, including enigmatic locations of the largest passages and intricate maze-like networks. Finally, we suggest that deep-seated carbon dioxide consumption during karst formation may constitute a link to the global carbon cycle.
High nitrous oxide emissions from temporary flooded depressions within croplands
Authors: Elberling By Bo , Kovács Gyula M. , Hansen Hans Frederik E. , Fensholt Rasmus , Ambus Per , Tong Xiaoye , Gominski Dimitri , Mueller Carsten W. , Poultney Daniel M. N. , Oehmcke Stefan
Published: December 2023

Nitrous oxide is an important greenhouse gas and emissions from managed ecosystems are directly correlated to anthropogenic nitrogen input. Here we have measured nitrous oxide emissions from flooded depressions within croplands and from incubated soil samples. We scaled emissions to >20,000 comparable flooded depressions across Zealand in Denmark using a deep-learning approach based on aerial photos and satellite images. We show that flooded depressions within cultivated fields, representing less than 1% of the total cultivated area, can release 80 times more nitrous oxide compared to rest of the fields. Fluxes can remain high for more than two months after fertilisation and can account for 30 ± 1% of the nitrous oxide budget during that period. This highlights the urgent need for assessment of nitrous oxide hotspots, as managing these hotspots appear to represent an important part of the overall greenhouse gas emissions from managed croplands and an efficient mitigation action.
Global inequities in population exposure to urban greenspaces increased amidst tree and nontree vegetation cover expansion
Authors: Leng Song , Sun Ranhao , Yang Xiaojun , Chen Liding
Published: December 2023

Cities worldwide are expanding greenspaces, including parks, urban forests, and grasslands. However, population exposure to tree and nontree vegetation is less well understood. Here, we use multiple satellite-derived datasets on vegetation, climate, and socioeconomic factors to examine the variations of urban tree and nontree vegetation cover, drivers of changes, and the impacts on global urban population exposure between 2000 to 2020. We find that approximately 90% of cities experienced an ascending trend in tree cover, and 49% of cities showed growth in nontree vegetation (p < 0.05). The increase in urban tree cover is most evident in high-latitude areas, such as Eastern Russia and Northern Europe. Human exposure to urban tree vegetation considerably declined in the Global South, widening the disparity between the North and South. Our study underscores persistent inequalities in human exposure to green space in cities and calls for evidence-based strategies that reduce increasing disparities.