bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethical implications of COVID-19 management—is freedom a desired aim, or a desired means to an end?
Authors: Košec Andro , Hergešić Filip , Zdilar Boris , Svetina Lucija , Ćurković Marko
Published: April 2024

Most developed societies managed, due to their prosperity and resource abundance, to structure relationships among free individuals in such a way to leave them fundamentally unstructured, according to the free market principle. As the pandemic illustrated well, this lack of structure when facing collective threats makes it impossible to collectively and proportionately assess and manage its implications and consequences. This may be particularly precarious when introducing comprehensive, monitoring and tracking, surveillance systems dependent on the vaccination status of the individual. If our previously shared aims were successfully and collectively enacted with the greatest of costs, is it permissible that the degree of personal freedom is a commodity, and everyone is a compulsory participant? The need to control one’s COVID-19 status allows the individual to become legally free from excessive enactment of sovereignty of the state. Should these rights be regulated by the free market?
Ultrastructure of silk threads of the water spider Argyroneta aquatica (Clerck, 1757) (Araneae, Cybeidae) in comparison with that of some mites
Authors: Shatrov Andrey B. , Soldatenko Elena V.
Published: April 2024

Silk of the water spider Argyroneta aquatica (Clerck, 1757) was obtained in the laboratory in the form of a capturing web irrespective of the formation of a diving bell and egg cocoon. Silk threads were examined by light microscopy, scanning (SEM), and transmission electron microscopy (TEM) as well as by atomic force (AFM) microscopy. Based on the diameter and internal organization, the silk threads have been divided into five types—a-, b-, c-, d-, and e-types interlaced freely in the thread bundles taken for examinations. Threads of all types are infinitely long, non-branched, round in shape, uniform in width through their course, and rarely found to be ruptured. Threads of the a-type are mostly straight, up to 1,000 nm in diameter, and composed of a fibrillary wall enveloping an electron-dense vacuolated core, which may be occasionally absent. The wall may also become lost, leaving a single core substance surrounded by a slightly wrinkled double membrane. Threads of the b-, c-, and d-types are organized nearly identical, being composed of a fine granular electron-light uniform material enveloped by a fine membrane. The diameter of these threads varies from max. 500 nm in the b-type and 120 nm in the c-type to around 50 nm in the d-type. Threads of these types are more convoluted and more numerous than threads of the a-type. Threads of the last kind, the e-type, occur rarely and are significantly larger with a diameter of around 3.5–4.5 µm. They possess the layered membranous wall surrounding a uniformly dense core. The silk of the water mites Limnochares aquatica (L., 1758) and Limnesia maculata (O.F. Müller, 1776) is composed of threads of only one type that closely corresponded to the a-type threads of A. aquatica. Conversely, the silk of the two-spotted spider mite Tetranychus urticae (C.L. Koch, 1836) consists of threads highly correlated with the d-type threads of A. aquatica. This finding shows that in different phylogenetic lineages of arachnids, the mechanisms of silk production are quite similar.
Micronutrient regulation of the DNA methylome
Authors: Leesang Tiffany , Lyon Peter , Pinzone Joey , Cimmino Luisa
Published: April 2024

The formation, inheritance, and removal of DNA methylation in the genome of mammalian cells is directly regulated by two families of enzymes–DNA methyltransferases (DNMTs) and Ten-Eleven Translocation proteins (TETs). DNMTs generate and maintain the inheritance of 5-methylcytosine (5mC), which is the substrate targeted by the TET enzymes for conversion to 5-hydroxymethylcytosine (5hmC) and its downstream oxidized derivatives. The activity of DNMT and TET is dependent on the availability of micronutrients and metabolite co-factors, including essential vitamins, amino acids, and trace metals, highlighting how DNA methylation levels can be directly enhanced, suppressed, or remodeled via metabolic and nutritional perturbations. Dynamic changes in DNA methylation are required during embryonic development, lineage specification, and maintenance of somatic cell function that can be fine-tuned based on the influence of essential micronutrients. As we age, DNA methylation and hydroxymethylation levels drift in patterning, leading to epigenetic dysregulation and genomic instability that underlies the formation and progression of multiple diseases including cancer. Understanding how DNA methylation can be regulated by micronutrients will have important implications for the maintenance of normal tissue function upon aging, and in the prevention and treatment of diseases for improved health and lifespan.
IDO1 correlates with the immune landscape of head and neck squamous cell carcinoma: a study based on bioinformatics analyses
Authors: Gkountana Georgia Vasiliki , Wang Lezhou , Giacomini Martina , Hyytiäinen Aini , Juurikka Krista , Salo Tuula , Al-Samadi Ahmed
Published: April 2024

Background

Head and neck squamous cell carcinoma (HNSCCs) is a common cancer type with a high mortality rate and poor prognosis. Recent studies have focused on the role of immune checkpoints in HNSCC progression and in their potential use as prognostic markers and immunotherapeutic candidates. Some immune checkpoints, such as PD-1 and PD-L1, have been studied thoroughly in HNSCC. Other molecules, such as indoleamine 2,3-dioxygenase 1 (IDO1), have been investigated minimally.

Methods

IDO1 expression, prognostic potential, and association with the immune profile of HNSCC were explored using online databases, including GEPIA, UALCAN, TIMER2.0, cBioPortal, and LinkedOmics, which utilize TCGA datasets and are freely available for use. For validation purposes, seven pairs of primary and metastatic HNSCC were immunostained for IDO1.

Results

Our analysis revealed significantly higher expression of IDO1 in HNSCC, especially in HPV+ SCCs compared with healthy control tissue. However, IDO1 expression showed weak to no prognostic potential for overall and disease-free survival in HNSCC. IDO1 expression in HNSCC was positively correlated with several immune-related molecules, including most of the immune checkpoints. Additionally, GO enrichment analysis revealed that several immune-related pathways are positively correlated with IDO1 expression in HNSCC, such as response to type I interferon and lymphocyte-mediated immunity pathways. Finally, IDO1 expression positively correlated with infiltration of most of the immune cells in HNSCC, such as CD4+ T cells, CD8+ T cells, M1 and M2 macrophages, dendritic cells, and B cells.

Conclusion

IDO1 expression is closely correlated with the immune profile of the HNSCC. This observation should be explored further to elucidate the potential of targeting IDO1 as a novel immunotherapeutic approach for HNSCC.
Development of the pediatric narcolepsy patient-reported outcomes scale (PN-PROs)
Authors: Wang Grace Y. , Worhach Jennifer , Zhou Eric S. , Strunc Michael , Morse Anne M. , Owens Judith A. , Flygare Julie , Revette Anna , Meltzer Lisa J. , Maski Kiran
Published: April 2024

Background

Pediatric narcolepsy is a chronic neurological disorder that impacts the health and overall wellbeing of children and adolescents with the disease. Meaningful and regular assessment of symptom frequency and severity is important for the long-term management of narcolepsy and for optimizing quality of life. However, there is currently no patient-reported outcomes (PROs) measure developed from both patient and expert input that is designed specifically to assess the impact of pediatric narcolepsy on daily life and overall disease burden.

Methods

We conducted a qualitative mixed-methods study to develop a novel patient-reported outcomes measure for pediatric narcolepsy patients. We created and refined a conceptual framework through literature review, semi-structured interviews with narcolepsy experts, and focus groups of children and adolescents with narcolepsy and their parents. Guided by the domains and facets identified in our conceptual framework and further literature review, we developed a PROs item bank. Our team further refined the item bank and classified items through team discussions and expert guidance. Content validity of the item pool was evaluated with expert review, readability analysis, and cognitive interviews with narcolepsy patients.

Results

Through our processes, we developed a PROs item bank comprising two domains (narcolepsy symptoms and functional impairment) that contains 10 facets. The final item bank consists of 55 items, with 27 items representing five facets of narcolepsy symptoms (behavior, cataplexy, cognitive difficulties, sleep quality, and sleepiness) and 28 items representing five facets of functional impairment (bothered by/worried about symptom, cognitive/academic, global functioning, safety, and social).

Conclusion

We developed items for the Pediatric Narcolepsy Patient-Reported Outcomes (PN-PROs) measure that incorporates expert insight, published literature, and testimony from children/adolescents living with narcolepsy and their families. Upon completion of the psychometric testing and content validation process, we believe the PN-PROs will provide a useful longitudinal measure of disease control and standardize outcome assessments in clinical practice and research studies.
Electrocardiographic manifestations in female team handball players: analyzing ECG changes in athletes
Authors: Malmgren A. , Trägårdh E. , Gudmundsson P. , Kjellström B. , Stagmo M. , Dencker M.
Published: April 2024

Introduction

Long-term intense training leads to structural, functional, and electrical remodeling of the heart. How different sports affect the heart has not been fully investigated, particularly for female athletes. The aim of the present study was to investigate the morphology of 12-lead resting electrocardiogram (ECG) in elite female handball players compared to non-athlete female subjects. Potential changes will be explored to see if they could be explained by differences in cardiac dimensions and exercise hours.

Materials and methods

A cross-sectional study of 33 elite female team handball players compared to 33 sex and age-matched, non-athletic controls (age range 18–26 years) was performed. All participants underwent a resting 12-lead ECG and an echocardiographic examination. ECG variables for left ventricular hypertrophy and durations were evaluated and adjusted for cardiac dimensions and exercise hours using ANCOVA analysis. A linear regression analysis was used to describe relation between echocardiographic and ECG measures and exercise hours.

Results

The female handball players had larger cardiac dimensions and significantly lower heart rate and QTc duration (Bazett's formula) as well as increased QRS and QT durations compared to controls. The 12-lead sum of voltage and the 12-lead sum of voltage ∗ QRS were significantly higher among handball players. Changes in ECG variables reflecting the left ventricle could in part be explained by left ventricular size and exercise hours. Correlation with exercise hours were moderately strong in most of the echocardiographic measures reflecting left ventricular (LV), left ventricular mass (LVM), left atrium (LA) and right atrium (RA) size. Poor to fair correlations were seen in the majority of ECG measures.

Conclusions

Female team handball players had altered ECGs, longer QRS and QT durations, higher 12-lead sum of voltage and 12-lead sum of voltage ∗ QRS as well as shorter QTc (Bazett's formula) duration compared to non-athletic controls. These findings could only partly be explained by differences in left ventricular size. Despite larger atrial size in the athletes, no differences in P-wave amplitude and duration were found on ECG. This suggest that both structural, and to some degree electrical remodeling, occur in the female team handball players' heart and highlight that a normal ECG does not rule out structural adaptations. The present study adds knowledge to the field of sports cardiology regarding how the heart in female team handball players adapts to this type of sport.
Impact of a varied set of stimuli on a suite of immunological parameters within peripheral blood mononuclear cells: toward a non-animal approach for assessing immune modulation by materials intended for human use
Authors: Cochrane Stella , Rajagopal Ramya , Sheffield David , Stewart Fay , Hathaway Lindsay , Barnes Nicholas M. , Qureshi Omar , Gordon John
Published: April 2024

Introduction: In toxicology, steps are being taken towards more mechanism-focused and human relevant approaches to risk assessment, requiring new approaches and methods. Additionally, there is increasing emphasis by regulators on risk assessment of immunotoxicity.

Methods: Here we present data from a peripheral blood mononuclear cell (PBMC) system whereby a varied set of stimuli, including those against the TCR and Toll-like receptors, enable readouts of cytokine and prostaglandin E2 (PGE2) production with monocyte, T cell and B cell viability, proliferation, and associated activation markers. In addition to results on the impact of the stimuli used, initial profiling data for a case study chemical, curcumin, is presented, illustrating how the system can be used to generate information on the impact of exogenous materials on three major constituent immune cell subsets for use in risk assessment and to direct follow-on studies.

Results: The different stimuli drove distinct responses, not only in relation to the “quantity” of the response but also the “quality”. Curcumin had a limited impact on the B cell parameters measured, with the stimuli used, and it was noted that in contrast to T cells where there was either no impact or a reduction in viability and proliferation with increasing concentration, for B cells there was a small but significant increase in both measurements at curcumin concentrations below 20 µM. Similarly, whilst expression of activation markers by T cells was reduced by the highest concentration of curcumin, they were increased in B cells. Curcumin only impacted the viability of stimulated monocytes at the highest concentration and had differential impact on different activation markers. Levels of all cytokines and PGE2 were reduced at higher concentrations.

Discussion: Although the platform has certain limitations, it nevertheless enables assessment of healthy baseline monocyte, T-, and B-cell responses, and scrutiny of the impact of different stimuli to detect potential immune suppression or enhancement from exogenous materials. In the case of curcumin, a pattern of responses indicative of immune suppressive / anti-inflammatory effects was detected. It is an accessible, highly modifiable system that can be used to screen materials and guide further studies, providing a holistic, integrated picture of effects.
Management Efficacy and Response to Post-Application Precipitation of Fungicides for Southern Stem Rot of Peanut and Evaluation of Co-Application with Micronized Sulfur
Authors: Anco Daniel J. , Hiers Justin , Zurweller Brendan
Published: April 2024

Southern stem rot (SSR) is caused by Athelia rolfsii and is an economically important disease of peanut (Arachis hypogaea L.). Application of protectant fungicides is an effective management component for reducing levels of this soil-borne disease. The majority of peanut hectarage in South Carolina and Mississippi is rainfed. Timely precipitation has the potential to aid the movement of foliar-applied fungicides through the canopy and into contact with soil interfaces where SSR infections occur. Questions have arisen as to the quantitative relationship of post-application precipitation and fungicide-active ingredient efficacy in managing SSR and protecting associated pod yield potentials. To examine this, fungicide efficacy experiments were screened for inclusion in a meta-analysis, from which eleven experiments conducted from 2015 to 2023 were selected and paired with environmental data from nearby weather stations. Precipitation during the two days following fungicide application was associated with significant reduction in SSR incidence (logit rate of −0.0039/mm) and increased pod yield (log slope of 0.0028/mm). Active ingredient interactions with precipitation among pod yield but not SSR incidence data were present for benzovindiflupyr plus azoxystrobin, flutolanil, and tebuconazole. Fungicides with the greatest levels of control per application at maximum label rates were inpyrfluxam (18.8%), benzovindiflupyr plus azoxystrobin (15.4%), flutolanil (12.3%), and prothioconazole plus tebuconazole (10.5%). Micronized sulfur neither contributed to SSR control nor pod yield increase. Tebuconazole was associated with the greatest % SSR control per fungicide product cost (0.47%/$/ha/application) but was also the treatment with the least amount of control (3.5%) at its maximum label rate. Maximum label rates of benzovindiflupyr plus azoxystrobin (USD 637) and inpyrfluxam (USD 548) were estimated as conferring the greatest returns over the chlorothalonil-only control. Results serve as a helpful reference for farmers and practitioners in selecting fungicide management options and targeting application times, as feasible, to utilize natural precipitation to improve management outcomes.
Enhancing Soil Aggregate Stability and Organic Carbon in Northwestern China through Straw, Biochar, and Nitrogen Supplementation
Authors: Wu Jun , Teng Binqing , Zhong Yuan , Duan Xuejiao , Gong Lijuan , Guo Wanli , Qi Peng , Haider Fasih Ullah , Cai Liqun
Published: April 2024

Enhancing soil stability through the incorporation of straw and biochar is well documented. Nevertheless, the combined impact of straw, biochar, and nitrogen supplementation on soil aggregates and organic carbon still needs to be explored, with limited attention given to various sieving methods in the existing literature. Therefore, the current experiment used four sieving methods—routine wet sieving (RoutW), fast-wetting sieving (FastW), slow-wetting sieving (SlowW), and wetting–stirring sieving (WetS)—to investigate the effects of adding straw (0 or 4.5 t ha−1), biochar (from maize straw, 0 or 15 t ha−1), and N (0 or 100 kg ha−1) on soil aggregate stability and soil organic C in silt–loam soil of rainfed farmland in northwest China. The field experiment was started in 2014; soil samples were collected in 2021. The results revealed that straw returned, biochar, and N addition significantly increased soil mean weight diameter (MWD) and soil organic C (SOC). Compared to CN0 (zero-amendment) plots, straw returned with nitrogen addition (SN100) significantly increased the MWD of aggregates by 130.3% (RoutW), 121.66% (FastW), 73.94% (SlowW), and 91.78% (WetS) in the 0–30 cm soil layer. The addition of biochar and nitrogen (BN100) treatment showed the most significant effects on the relative slaking index (RSI), relative mechanical breakdown index (RMI), and SOC; compared with CN0 treatment, BN100 plots can reduce RSI and RMI by 42.90% and 54.66% and increase SOC by 53.27% for all soil layers. Therefore, adding organic materials with N can enhance the stability of soil aggregates and SOC of silt–loam soils in northwest China. Integrating biochar as an organic soil amendment in the agricultural practices of northwest China presents a multifaceted solution that addresses soil health, crop productivity, and environmental sustainability. The current study provides valuable insights that support adopting this innovative approach, paving the way for future sustainable agricultural practices that can benefit both the region and the global community.
Strategic Challenges to the Eradication of African Swine Fever Genotype II in Domestic Pigs in North Italy
Authors: Pavone Silvia , Bellini Silvia , Iscaro Carmen , Farioli Marco , Chiari Mario , Lavazza Antonio , Ruocco Luigi , Lelli Davide , Pintus Giorgia , Prati Paola , Feliziani Francesco
Published: April 2024

African swine fever (ASF) is a severe viral disease characterized by high lethality in suids and caused by the African Swine Fever Virus (ASFV). The ASF genotype I virus was introduced to Europe in 1957, marking the onset of the first European epidemic wave. In 2007, ASFV genotype II was detected in Georgia, affecting domestic pigs and wild boars before spreading to various European and extra-European countries, including Italy. The first case of ASFV in Italy was documented on 7 January 2022, in a wild boar in the Piedmont region. Since then, several ASFV-positive wild boar carcasses have been identified in the Piedmont and Liguria regions. By June 2023, ASFV had spread to Lombardy, one of the major pig-producing regions in northern Italy; the virus was first detected in early summer in wild boar carcasses. Two months later, it was diagnosed in a commercial pig farm as a consequence of the disease’s spread amongst wild boars and an increase in the viral environmental load. This report aims to describe the features of ASFV domestic pig outbreaks that occurred in the Zinasco municipality (Lombardy) and the joint efforts to mitigate potential direct and indirect economic impacts on the Italian and global pig industry. The epidemiological investigation and the measures implemented, which were all performed according to national and European regulations, as well as exceptional ad hoc measures aimed at protecting the pig industry, are described in order to provide a practical and effective approach to combating ASF.
Hepatic Epithelioid Hemangioendothelioma in a Dog
Authors: Muscatello Luisa Vera , Massari Federico , Roccabianca Paola , Sarli Giuseppe , Benazzi Cinzia , Bianchi Marco Luigi
Published: April 2024

A 5-year-old spayed female Breton dog was referred for a thyroid nodule. A total body CT scan evidenced multifocal hepatic nodules. Cytological liver samples were hemodiluted and non-diagnostic. Following a thyroidectomy, the histology was consistent with a follicular-compact thyroid carcinoma. On laparoscopy, most hepatic lobes had multifocal dark-red nodules that were biopsied for histology. Microscopically, the hepatic parenchyma in the nodules was substituted by blood channels lined by bland spindle cells but adjacent to epithelioid neoplastic cells, single or in clusters, embedded in a moderate amount of edematous collagen matrix. These cells had optically empty cytoplasmic space, occasionally containing erythrocytes (microlumina). Spindle and epithelioid cells expressed membranous-to-cytoplasmic CD31 and FVIII-RA consistent with endothelial origin. Based on morphology and immunolabelling, a hemangioendothelioma with epithelioid differentiation was diagnosed. Lesions in the liver were initially stable, showing progression with time. The dog was alive with no systemic clinical signs 36 months after laparoscopy.
A Retrospective Descriptive Study of Staphylococcus Species Isolated from Canine Specimens Submitted to a Diagnostic Laboratory in South Africa, 2012–2017
Authors: Sigudu Themba , Qekwana Daniel , Oguttu James
Published: April 2024

There is a scarcity of published studies on the occurrence of Staphylococcus spp. Among dogs in South Africa. The objective of the study was to characterise the Staphylococcus spp. Isolated from dog samples submitted to a veterinary diagnostic laboratory in South Africa in terms of time, place, and person. This study utilised a dataset of 1627 positive Staphylococcus isolates obtained from a veterinary diagnostic laboratory in South Africa from 2012 to 2017. Out of the 1627 confirmed isolates, 10 different species of Staphylococcus were identified. Among these, 92.0% were classified as coagulase-positive staphylococci (CoPS), 6.0% were coagulase-negative staphylococci (CoNS), and 3.0% were coagulase-variable. Male dogs contributed just over half (53.2%) of the Staphylococcus isolates, while female dogs contributed the remaining 46.8%. The largest proportion of isolates (23.2%) were obtained from dogs aged ≥ 9 years, with the highest number of isolates originating from KwaZulu-Natal Province (45.0%) and the least from Northern Cape Province (0.1%). Out of the total samples included in the records, the majority (46.0%) were skin specimens. The number of Staphylococcus isolates recorded showed limited variation between the seasons (24.3% in autumn, 26.3% in winter, 26.0% in spring, and 24.0% in summer). This study highlighted the diversity of Staphylococcus spp. isolated from dogs, and the burden of staphylococcal carriage among dogs in South Africa. Further research is required to examine the factors that contribute to the observed discrepancies in the proportions of Staphylococcus spp. between the provinces.
Validation of Bos taurus SNPs for Milk Productivity of Sahiwal Breed (Bos indicus), Pakistan
Authors: Younis Asma , Hussain Imtiaz , Ahmad Syeda Nadia , Shah Amin , Inayat Iram , Kanwal Muhammad Ali , Suleman Sadia , Kamran Muhammad Atif , Matloob Saima , Ahmad Khawaja Raees
Published: April 2024

The aim of the present study was the validation of the already reported Bos taurus SNPs in the Sahiwal breed. A total of nine SNPs of the casein gene were studied. Out of nine, seven Bos taurus SNPs of casein protein genes were found to be significantly associated with milk productivity traits. The genomic DNA was extracted from the mammary alveolar endothelial cells of a flock of 80 purebred Sahiwal lactating dams available at Khizrabad Farm near Sargodha. New allele-specific primers were designed from the NCBI annotated sequence database of Bos taurus to obtain 100 nt-long PCR products. Each dam was tested separately for all the SNPs investigated. Animals with genotype GG for the SNPs rs43703010, rs10500451, and 110323127, respectively, exhibited high milk yield. Similarly, animals with genotype AA for the SNPs rs11079521, rs43703016, and rs43703017 showed high milk yield consistently. For the SNP rs43703015, animals with genotype CC showed high milk productivity. These above-mentioned SNPs have previously been reported to significantly up-regulate casein protein contents in Bos taurus. Our results indicated SNPs that significantly affect the milk protein contents may also significantly increase per capita milk yield. These finding suggest that the above-mentioned reported SNPs can also be used as genetic markers of milk productivity in Sahiwal cattle.
Studying the Changes in Physical Functioning and Oxidative Stress-Related Molecules in People Living with HIV after Switching from Triple to Dual Therapy
Authors: Cusato Jessica , Mulasso Anna , Ferrara Micol , Manca Alessandra , Antonucci Miriam , Accardo Guido , Palermiti Alice , Bianco Gianluca , Chiara Francesco , Mula Jacopo , Maddalone Maria Grazia , Tettoni Maria Cristina , Cuomo Simone , Trevisan Giulia , Bonora Stefano , Di Perri Giovanni , Lupo Corrado , Rainoldi Alberto , D’Avolio Antonio
Published: April 2024

Background: Physical activity could increase the production of oxidative stress biomarkers, affecting the metabolism and excretion of antiretroviral drugs and, consequently, the clinical outcome. Nowadays, people living with HIV (PLWH) are mostly switching from triple to dual therapy, but no data are available in terms of physical functioning and oxidative stress. The aim of this study was to evaluate if some antioxidant biomarkers and physical functioning tests could be different according to triple or dual antiretroviral therapy. Methods: PLWH were evaluated at baseline (BL), while treated with three drugs, and six months after the switch to dual therapy. Physical functioning was quantified using validated tools. Mitochondrial and cytosol antioxidant molecules were evaluated through liquid chromatography. Results: Twenty-five patients were analyzed. A statistically significant difference between triple and dual therapy was found for mitochondrial glutathione, but not for physical tests. Evaluating differences between physically active and inactive individuals, the following statistically significant differences were suggested, considering triple therapy (mitochondrial n-formyl-methionine p = 0.022, triglycerides p = 0.023) and double therapy (mitochondrial glycine p = 0.035, cytosol glutamic acid p = 0.007, cytosol s-adenosylmethionine p = 0.021). Conclusions: For the first time, this study suggests possible differences in terms of antioxidant molecules and physical functioning in PLWH switching from triple to dual therapy.
Lysyl Oxidase in Ectopic Cardiovascular Calcification: Role of Oxidative Stress
Authors: Ballester-Servera Carme , Alonso Judith , Cañes Laia , Vázquez-Sufuentes Paula , García-Redondo Ana B. , Rodríguez Cristina , Martínez-González José
Published: April 2024

Lysyl oxidase (LOX)-mediated extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease; however, this enzyme also induces oxidative stress. We addressed the contribution of LOX-dependent oxidative stress to cardiovascular calcification. LOX is upregulated in human-calcified atherosclerotic lesions and atheromas from atherosclerosis-challenged LOX transgenic mice (TgLOXVSMC) and colocalized with a marker of oxidative stress (8-oxo-deoxyguanosine) in vascular smooth muscle cells (VSMCs). Similarly, in calcific aortic valves, high LOX expression was detected in valvular interstitial cells (VICs) positive for 8-oxo-deoxyguanosine, while LOX and LOXL2 expression correlated with osteogenic markers (SPP1 and RUNX2) and NOX2. In human VICs, mito-TEMPO and TEMPOL attenuated the increase in superoxide anion levels and the mineralization induced by osteogenic media (OM). Likewise, in OM-exposed VICs, β-aminopropionitrile (a LOX inhibitor) ameliorated both oxidative stress and calcification. Gain- and loss-of-function approaches in VICs demonstrated that while LOX silencing negatively modulates oxidative stress and calcification induced by OM, lentiviral LOX overexpression exacerbated oxidative stress and VIC calcification, effects that were prevented by mito-TEMPO, TEMPOL, and β-aminopropionitrile. Our data indicate that LOX-induced oxidative stress participates in the procalcifying effects of LOX activity in ectopic cardiovascular calcification, and highlight the multifaceted role played by LOX isoenzymes in cardiovascular diseases.
Profiling of Metabolites in Organically Grown Plums from Norway: Does Location or Cultivar Matter?
Authors: Meland Mekjell , Dabić Zagorac Dragana , Jakanovski Mihajlo , Sredojević Milica , Natić Maja , Kitanović Marko , Fotirić Akšić Milica
Published: April 2024

The aim of this work was to investigate the influence of two locations and seven cultivars on the profiling of metabolites in organically grown plums (Prunus domestica L.) fruit in Norway. P, K, and Ca were most abundant in the studied fruits, while Ba and Sr formed a clear line between the locations. The most abundant sugars were glucose, fructose, sucrose, and sorbitol, which together accounted for up to 97.00%. Quinic acid and malic acid were the predominant organic acids, while chlorogenic acid, rutin, and kaempferol-3-O-glucoside were the most abundant polyphenols. Plums from Ullensvang were characterized by a higher content of minerals, sugars, organic acids, total polyphenol content (TPC), and radical scavenging activity (RSA), while plums from Telemark had a higher content of quantified polyphenols. The cultivar ‘Mallard’ had the highest mineral and radical scavenging activity, ‘Opal’ had the sweetest fruit, ‘Jubileum’ had the highest acidity, ‘Excalibur’ had the highest TPC content, and ‘Valor’ stored the highest content of quantified polyphenols, especially chlorogenic acid. These results provide comprehensive information on the chemical profiles of selected plum cultivars, suggesting that organic plums are a rich source of beneficial compounds that can have a positive impact on human health.
Satellite Time-Series Analysis for Thermal Anomaly Detection in the Naples Urban Area, Italy
Authors: Scalabrini Alessia , Musacchio Massimo , Silvestri Malvina , Rabuffi Federico , Buongiorno Maria Fabrizia , Salvini Francesco
Published: April 2024

Naples is the most densely populated Italian city (7744 inhabitants per km2). It is located in a particular geological context: the presence of Mt Vesuvius characterizes the eastern part, and the western part is characterized by the presence of the Phlegrean Fields, making Naples a high-geothermal-gradient region. This endogenous heat, combined with the anthropogenic heat due to intense urbanization, has defined Naples as an ideal location for Surface Urban Heat Island (SUHI) analysis. SUHI analysis was effectuated by acquiring the Land Surface Temperature (LST) over Naples municipality by processing Landsat 8 (L8) Thermal Infrared Sensor (TIRS) images in the 2013–2023 time series by employing Google Earth Engine (GEE). In GEE, two different approaches have been followed to analyze thermal images, starting from the Statistical Mono Window (SMW) algorithm, which computes the LST based on the brightness temperature (Tb), the emissivity value, and the atmospheric correction coefficients. The first one is used for the LST retrieval from daytime images; here, the emissivity component is derived using, firstly, the Normalized Difference Vegetation Index (NDVI) and then the Vegetation Cover Method (VCM), defining the Land Surface Emissivity (LSɛ), which considers solar radiation as the main source of energy. The second approach is used for the LST retrieval from nighttime images, where the emissivity is directly estimated from the Advance Spaceborne Thermal Emission Radiometer database (ASTER-GED), as, during nighttime without solar radiation, the main source of energy is the energy emitted by the Earth’s surface. From these two different algorithms, 123 usable daytime and nighttime LST images were downloaded from GEE and analyzed in Quantum GIS (QGIS). The results show that the SUHI is more concentrated in the eastern part, characterized by intense urbanization, as shown by the Corine Land Cover (CLC). At the same time, lower SUHI intensity is detected in the western part, defined by the Land Cover (LC) vegetated class. Also, in the analysis, we highlighted 40 spots (10 hotspots and 10 coldspots, both for daytime and nighttime collection) that present positive or negative temperature peaks for all the time series. Due to the huge amount of data, this work considered only the five representative spots that were most representative for SUHI analysis and determination of thermal anomalies in the urban environment.
Determination of Transport Pathways and Mutual Exchanges of Atmospheric Moisture between Source Regions of Yangtze and Yellow River Basins
Authors: Kang Beiming , Wei Jiahua , Ayantobo Olusola O. , Yang Haijiao
Published: April 2024

Knowledge of the quantitative importance of the moisture transport pathways and mutual moisture exchange of the source regions of the Yangtze (SYZR) and Yellow (SYR) rivers’ basins, the adjacent origins of China’s two longest rivers, can provide insights into the regional atmospheric branch of the hydrological cycle over the source regions. The method with the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model and a Lagrangian moisture source diagnostic to identify the major moisture transport pathways quantifies their importance to two types of daily precipitation events—daily precipitation more than 10 mm (PM) events and daily precipitation less than 10 mm (PL) events—for the two rivers’ regions during the summer (June–August, 1986–2015) and finds the characteristics of mutual moisture exchange. The results indicated that both the Bay of Bengal group pathway and the northwest China group pathway play significant roles in PM and PL events over the SYZR, contributing 41.87% and 39.12% to PM events and 41.33% and 33.16% to PL events, respectively. The SYR has five main moisture path groups; the Bay of Bengal group pathway, the northwest China group pathway, and the southeast China group pathway play significant roles in PM and PL events over the SYR, contributing 32.34%, 23.28%, and 34.36% to PM events and 34.84%, 36.18%, and 19.83% to PL events, respectively. The volume of moisture passing from the SYZR to the SYR is approximately 60 times that of the reverse, constituting about 6.9% of the total moisture released in SYR precipitation. It is worth noting that the moisture release was concentrated in the nearer west group pathway, and the main moisture uptake locations were beyond the source region of the two rivers (remote sources) in the PM events. The aggregate moisture release high-frequency moisture transport path groups are found in the southeastern parts of Zhiduo County and the southeast of Zaduo County.
Modern In Vitro Techniques for Modeling Hearing Loss
Authors: Shah Jamie J. , Jimenez-Jaramillo Couger A. , Lybrand Zane R. , Yuan Tony T. , Erbele Isaac D.
Published: April 2024

Sensorineural hearing loss (SNHL) is a prevalent and growing global health concern, especially within operational medicine, with limited therapeutic options available. This review article explores the emerging field of in vitro otic organoids as a promising platform for modeling hearing loss and developing novel therapeutic strategies. SNHL primarily results from the irreversible loss or dysfunction of cochlear mechanosensory hair cells (HCs) and spiral ganglion neurons (SGNs), emphasizing the need for innovative solutions. Current interventions offer symptomatic relief but do not address the root causes. Otic organoids, three-dimensional multicellular constructs that mimic the inner ear’s architecture, have shown immense potential in several critical areas. They enable the testing of gene therapies, drug discovery for sensory cell regeneration, and the study of inner ear development and pathology. Unlike traditional animal models, otic organoids closely replicate human inner ear pathophysiology, making them invaluable for translational research. This review discusses methodological advances in otic organoid generation, emphasizing the use of human pluripotent stem cells (hPSCs) to replicate inner ear development. Cellular and molecular characterization efforts have identified key markers and pathways essential for otic organoid development, shedding light on their potential in modeling inner ear disorders. Technological innovations, such as 3D bioprinting and microfluidics, have further enhanced the fidelity of these models. Despite challenges and limitations, including the need for standardized protocols and ethical considerations, otic organoids offer a transformative approach to understanding and treating auditory dysfunctions. As this field matures, it holds the potential to revolutionize the treatment landscape for hearing and balance disorders, moving us closer to personalized medicine for inner ear conditions.
A Novel Mis-Seg-Focus Loss Function Based on a Two-Stage nnU-Net Framework for Accurate Brain Tissue Segmentation
Authors: He Keyi , Peng Bo , Yu Weibo , Liu Yan , Liu Surui , Cheng Jian , Dai Yakang
Published: April 2024

Brain tissue segmentation plays a critical role in the diagnosis, treatment, and study of brain diseases. Accurately identifying these boundaries is essential for improving segmentation accuracy. However, distinguishing boundaries between different brain tissues can be challenging, as they often overlap. Existing deep learning methods primarily calculate the overall segmentation results without adequately addressing local regions, leading to error propagation and mis-segmentation along boundaries. In this study, we propose a novel mis-segmentation-focused loss function based on a two-stage nnU-Net framework. Our approach aims to enhance the model’s ability to handle ambiguous boundaries and overlapping anatomical structures, thereby achieving more accurate brain tissue segmentation results. Specifically, the first stage targets the identification of mis-segmentation regions using a global loss function, while the second stage involves defining a mis-segmentation loss function to adaptively adjust the model, thus improving its capability to handle ambiguous boundaries and overlapping anatomical structures. Experimental evaluations on two datasets demonstrate that our proposed method outperforms existing approaches both quantitatively and qualitatively.
Hypomethylation of ATP1A1 Is Associated with Poor Prognosis and Cancer Progression in Triple-Negative Breast Cancer
Authors: Kim Yesol , Ko Je Yeong , Kong Hyun Kyung , Lee Minyoung , Chung Woosung , Lim Sera , Son Dasom , Oh Sumin , Park Jee Won , Kim Do Yeon , Lee Minju , Han Wonshik , Park Woong-Yang , Yoo Kyung Hyun , Park Jong Hoon
Published: April 2024

Dysregulated DNA methylation in cancer is critical in the transcription machinery associated with cancer progression. Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, but no treatment targeting TNBC biomarkers has yet been developed. To identify specific DNA methylation patterns in TNBC, methyl-binding domain protein 2 (MBD) sequencing data were compared in TNBC and the three other major breast cancer subtypes. Integrated analysis of DNA methylation and gene expression identified a gene set showing a correlation between DNA methylation and gene expression. ATPase Na+/K+-transporting subunit alpha 1 (ATP1A1) was found to be specifically hypomethylated in the coding sequence (CDS) region and to show increased expression in TNBC. The Cancer Genome Atlas (TCGA) database also showed that hypomethylation and high expression of ATP1A1 were strongly associated with poor survival in patients with TNBC. Furthermore, ATP1A1 knockdown significantly reduced the viability and tumor-sphere formation of TNBC cells. These results suggest that the hypomethylation and overexpression of ATP1A1 could be a prognostic marker in TNBC and that the manipulation of ATP1A1 expression could be a therapeutic target in this disease.
Identifying Candidate Gene Drivers Associated with Relapse in Pediatric T-Cell Acute Lymphoblastic Leukemia Using a Gene Co-Expression Network Approach
Authors: Kypraios Anthony , Bennour Juba , Imbert Véronique , David Léa , Calvo Julien , Pflumio Françoise , Bonnet Raphaël , Couralet Marie , Magnone Virginie , Lebrigand Kevin , Barbry Pascal , Rohrlich Pierre S. , Peyron Jean-François
Published: April 2024

Pediatric T-cell Acute Lymphoblastic Leukemia (T-ALL) relapses are still associated with a dismal outcome, justifying the search for new therapeutic targets and relapse biomarkers. Using single-cell RNA sequencing (scRNAseq) data from three paired samples of pediatric T-ALL at diagnosis and relapse, we first conducted a high-dimensional weighted gene co-expression network analysis (hdWGCNA). This analysis highlighted several gene co-expression networks (GCNs) and identified relapse-associated hub genes, which are considered potential driver genes. Shared relapse-expressed genes were found to be related to antigen presentation (HLA, B2M), cytoskeleton remodeling (TUBB, TUBA1B), translation (ribosomal proteins, EIF1, EEF1B2), immune responses (MIF, EMP3), stress responses (UBC, HSP90AB1/AA1), metabolism (FTH1, NME1/2, ARCL4C), and transcriptional remodeling (NF-κB family genes, FOS-JUN, KLF2, or KLF6). We then utilized sparse partial least squares discriminant analysis to select from a pool of 481 unique leukemic hub genes, which are the genes most discriminant between diagnosis and relapse states (comprising 44, 35, and 31 genes, respectively, for each patient). Applying a Cox regression method to these patient-specific genes, along with transcriptomic and clinical data from the TARGET-ALL AALL0434 cohort, we generated three model gene signatures that efficiently identified relapsed patients within the cohort. Overall, our approach identified new potential relapse-associated genes and proposed three model gene signatures associated with lower survival rates for high-score patients.
Deciphering the Role of BCAR3 in Cancer Progression: Gene Regulation, Signal Transduction, and Therapeutic Implications
Authors: Moon Dong Oh
Published: April 2024

This review comprehensively explores the gene BCAR3, detailing its regulation at the gene, mRNA, and protein structure levels, and delineating its multifunctional roles in cellular signaling within cancer contexts. The discussion covers BCAR3’s involvement in integrin signaling and its impact on cancer cell migration, its capability to induce anti-estrogen resistance, and its significant functions in cell cycle regulation. Further highlighted is BCAR3’s modulation of immune responses within the tumor microenvironment, a novel area of interest that holds potential for innovative cancer therapies. Looking forward, this review outlines essential future research directions focusing on transcription factor binding studies, isoform-specific expression profiling, therapeutic targeting of BCAR3, and its role in immune cell function. Each segment builds towards a holistic understanding of BCAR3′s operational mechanisms, presenting a critical evaluation of its therapeutic potential in oncology. This synthesis aims to not only extend current knowledge but also catalyze further research that could pivotally influence the development of targeted cancer treatments.
A Re-Examination of Neoadjuvant Therapy for Thymic Tumors: A Long and Winding Road
Authors: Yu Fenghao , Gu Zhitao , Zhang Xuefei , Xu Ning , Hao Xiuxiu , Wang Changlu , Zhao Yizhuo , Mao Teng , Fang Wentao
Published: April 2024

For most patients with advanced thymic epithelial tumors (TETs), a complete resection is a strong indicator of a better prognosis. But sometimes, primary surgery is unsatisfactory, and preoperative therapy is needed to facilitate complete resection. Neoadjuvant chemotherapy is the most used form of preoperative therapy. But studies on neoadjuvant chemotherapy have included mainly patients with thymoma; its efficacy in patients with thymic carcinoma is less known. Neoadjuvant chemoradiation has also been explored in a few studies. Novel therapies such as immunotherapy and targeted therapy have shown efficacy in patients with recurrent/metastatic TETs as a second-line option; their role as preoperative therapy is still under investigation. In this review, we discuss the existing evidence on preoperative therapy and the insight it provides for current clinical practice and future studies.
BRCA1/2 Testing Landscape in Ovarian Cancer: A Nationwide, Real-World Data Study
Authors: Lanjouw Lieke , Bart Joost , Mourits Marian J. E. , Willems Stefan M. , van der Hout Annemieke H. , ter Elst Arja , de Bock Geertruida H.
Published: April 2024

Analyzing BRCA1/2 tumor pathogenic variants (TPVs) in epithelial tubal/ovarian cancers (EOCs) has become an essential part of the diagnostic workflow in many centers to guide treatment options and genetic cascade testing. However, there is no standardization of testing procedures, including techniques, gene assays, or sequencers used, and data on the execution of tumor tests remains scarce. Therefore, we evaluated characteristics of BRCA1/2 tumor testing in advanced-stage EOC with real-world national data. Pathology reports of patients diagnosed with EOC in 2019 in the Netherlands were obtained from the Dutch Pathology Registry (PALGA), and data regarding histological subtype and BRCA1/2 tumor tests were extracted. A total of 999 patients with advanced-stage EOC were included. Tumor tests were performed for 502 patients (50.2%) and BRCA1/2 TPVs were detected in 14.7%. Of all tests, 48.6% used hybrid capture techniques and 26.5% used PCR-based techniques. More than half of the tests (55.0%) analyzed other genes in addition to BRCA1/2. Overall, this study highlights the heterogeneity in the execution of BRCA1/2 tumor tests. Despite a lack of evidence of quality differences, we emphasize that adequate reporting and internal and external quality monitors are essential for the high-quality implementation and execution of reliable BRCA1/2 tumor testing, which is crucial for identifying all patients with BRCA1/2 TPVs.