bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxicity of cannabidiol and its metabolites in TM3 mouse Leydig cells: a comparison with primary human Leydig cells
Authors: Li Yuxi , Wu Qiangen , Li Xilin , Cournoyer Patrick , Choudhuri Supratim , Guo Lei , Chen Si 
Published: April 2024

AbstractCannabidiol (CBD), one of the major components extracted from the plant Cannabis sativa L., has been used as a prescription drug to treat seizures in many countries. CBD-induced male reproductive toxicity has been reported in animal models; however, the underlying mechanisms remain unclear. We previously reported that CBD induced apoptosis in primary human Leydig cells, which constitute the primary steroidogenic cell population in the testicular interstitium. In this study, we investigated the effects of CBD and its metabolites on TM3 mouse Leydig cells. CBD, at concentrations below 30 µM, reduced cell viability, induced G1 cell cycle arrest, and inhibited DNA synthesis. CBD induced apoptosis after exposure to high concentrations (≥ 50 µM) for 24 h or a low concentration (20 µM) for 6 days. 7-Hydroxy-CBD and 7-carboxy-CBD, the main CBD metabolites of CBD, exhibited the similar toxic effects as CBD. In addition, we conducted a time-course mRNA-sequencing analysis in both primary human Leydig cells and TM3 mouse Leydig cells to understand and compare the mechanisms underlying CBD-induced cytotoxicity. mRNA-sequencing analysis of CBD-treated human and mouse Leydig cells over a 5-day time-course indicated similar responses in both cell types. Mitochondria and lysosome dysfunction, oxidative stress, and autophagy were the major enriched pathways in both cell types. Taken together, these findings demonstrate comparable toxic effects and underlying mechanisms in CBD-treated mouse and primary human Leydig cells.
Tautological characteristic classes II: the Witt class
Authors: Dymara Jan , Januszkiewicz Tadeusz 
Published: April 2024

AbstractLet K be an arbitrary infinite field. The cohomology group $$H^{2}(SL(2,K);H_2 SL(2,K))$$

H
2

(
S
L

(
2
,
K
)

;

H
2

S
L

(
2
,
K
)

)

contains the class of the universal central extension. When studying representations of fundamental groups of surfaces in SL(2, K) it is useful to have classes stable under deformations (Fenchel-Nielsen twists) of representations. We identify the maximal quotient of the universal class which is stable under twists as the Witt class of Nekovàř. The Milnor-Wood inequality asserts that an $$SL(2,\textbf{R})$$

S
L
(
2
,
R
)

-bundle over a surface of genus g admits a flat structure if and only if its Euler number is $$\le (g - 1)$$

≤
(
g
-
1
)

. We establish an analog of this inequality, and a saturation result for the Witt class. The result is sharp for the field of rationals, but not sharp in general.
Paper-based fluorescence sensor array with functionalized carbon quantum dots for bacterial discrimination using a machine learning algorithm
Authors: Wang Fangbin , Xiao Minghui , Qi Jing , Zhu Liang 
Published: April 2024

AbstractThe rapid discrimination of bacteria is currently an emerging trend in the fields of food safety, medical detection, and environmental observation. Traditional methods often require lengthy culturing processes, specialized analytical equipment, and bacterial recognition receptors. In response to this need, we have developed a paper-based fluorescence sensor array platform for identifying different bacteria. The sensor array is based on three unique carbon quantum dots (CQDs) as sensing units, each modified with a different antibiotic (polymyxin B, ampicillin, and gentamicin). These antibiotic-modified CQDs can aggregate on the bacterial surface, triggering aggregation-induced fluorescence quenching. The sensor array exhibits varying fluorescent responses to different bacterial species. To achieve low-cost and portable detection, CQDs were formulated into fluorescent ink and used with an inkjet printer to manufacture paper-based sensor arrays. A smartphone was used to collect the responses generated by the bacteria and platform. Diverse machine learning algorithms were utilized to discriminate bacterial types. Our findings showcase the platform's remarkable capability to differentiate among five bacterial strains, within a detection range spanning from 1.0 × 103 CFU/mL to 1.0 × 107 CFU/mL. Its practicality is further validated through the accurate identification of blind bacterial samples. With its cost-effectiveness, ease of fabrication, and high degree of integration, this platform holds significant promise for on-site detection of diverse bacteria.
Graphical abstract
Restrictions on local embeddability into finite semigroups
Authors: Kudryavtsev Dmitry 
Published: April 2024

AbstractWe expand the concept of local embeddability into finite structures (LEF) for the class of semigroups with investigations of non-LEF structures, a closely related generalising property of local wrapping of finite structures (LWF) and inverse semigroups. The established results include a description of a family of non-LEF semigroups unifying the bicyclic monoid and Baumslag–Solitar groups and demonstrating that inverse LWF semigroups with finite number of idempotents are LEF.
Extreme—Super obesity and panniculectomy: bipolar radiofrequency scalpel assisted surgery as a valuable option for the most challenging cases
Authors: Susini Pietro , Pozzi Mirco , Marcaccini Gianluca , di Seclì Davide , Diluiso Giuseppe , Giardino Francesco Ruben , Cuomo Roberto , Grimaldi Luca , Nisi Giuseppe 
Published: April 2024

Abstract

Background
In Italy, with a cohort of 6.3 million morbidly obese patients, panniculectomy is often necessary both in relation to bariatric surgery and as the sole treatment to reduce excess lower abdominal tissues. At first glance, the procedure could be misjudged as technically simple; however, when considering patients with Extreme obesity or worse (BMI > 40 kg/m2), the surgical risks increase significantly, patients are often inoperable, and few studies are available in the literature. Most surgeons actually avoid this job and related risks. Recent research has highlighted a potential role of the Bipolar Radiofrequency Scalpel (BRS) in various fields as a promising tool to reduce surgical complications. With this paper, the authors report their experience in the management of panniculectomy in Extreme (BMI > 40 kg/m2) and Super (BMI > 50 kg/m2) obese patients through the technique of BRS assisted panniculectomy.

Methods
A retrospective study was conducted on Extreme / Super obese patients who underwent BRS assisted panniculectomy between June 2013—June 2022. The panniculectomy involved lower abdomen excess skin and soft tissues removal, assisted by BRS, minimal undermining, and eventual abdominal hernia repair. Surgical procedures, and complications rate are discussed.

Results
Fourteen patients matched the selection criteria and were included in the study. Minor and major complications occurred in 28,6% and 14,3%, respectively. No flap necrosis, infections, cellulitis or decubitus ulcer occurred. Seroma 28,6% (4/14) and hematoma 7,1% (1/14) were the most relevant complications in the study population.

Conclusions
BRS assisted panniculectomy with minimal undermining is a valuable option for patients with extreme or super obesity. At the time of dissection, minimizing undermining and using BRS could make the operation safer and therefore extendable to a larger cohort of patients.
Level of evidence: Level IV, Therapeutic; Risk/Prognostic.
Intratumor injection of BCG Ag85A high-affinity peptides enhanced anti-tumor efficacy in PPD-positive melanoma
Authors: Qin Lanqun , Zhang Guiying , Wu Yirong , Yang Yueling , Zou Zhengyun 
Published: April 2024

AbstractAs one of the scheduled immunization vaccines worldwide, virtually all individuals have been vaccinated with BCG vaccine. In order to verify the hypothesis that delivering BCG high-affinity peptides to tumor areas could activate the existing BCG memory T cells to attack tumor, we firstly predicted the HLA-A*0201 high-affinity peptides of BCG Ag85A protein (KLIANNTRV, GLPVEYLQV), and then, A375 melanoma cells and HLA-A*0201 PBMCs (from PPD-positive adults) were added to co-incubated with the predicted peptides in vitro. We found that the predicted BCG high-affinity peptides could be directly loaded onto the surface of tumor cells, enhancing the tumor-killing efficacy of PBMCs from PPD-positive volunteer. Then, we constructed PPD-positive mice model bearing B16F10 subcutaneous tumors and found that intratumor injection of BCG Ag85A high-affinity peptides (SGGANSPAL, YHPQQFVYAGAMSGLLD) enhanced the anti-tumor efficacy in PPD-positive melanoma mice. Along with the better anti-tumor efficacy, the expression of PDL1 on tumor cell surface was also increased, and stronger antitumor effects occurred when further combined with anti-PD1 antibody. For microenvironment analysis, the proportion of effector memory T cells was increased and the better treatment efficacy may be attributed to the elevated effector memory CD4 + T cells within the tumor. In conclusion, using the existing immune response of BCG vaccine by delivering high-affinity peptides of BCG to tumor area is a safe and promising therapy for cancer.
Military education in extended reality (XR): learning troublesome knowledge through immersive experiential application
Authors: Garcia Estrada Jose , Prasolova-Førland Ekaterina , Kjeksrud Stian , Themelis Chryssa , Lindqvist Petter , Kvam Kristine , Midthun Ole , Sverre Knut , Hokstad Leif Martin , Mohamed Soud Khalifa , Grassini Simone , Ricci Serena 
Published: April 2024

AbstractExtended reality (XR) applications for education are usually associated with motivation, engagement, knowledge and experiences that are difficult to achieve in the real world. One example of such knowledge in military education is the threat-based approach to protection of civilians in armed conflicts. The Norwegian Defence University College (NDUC) educates officers on the threat-based approach. This approach challenges conventional military practice, introducing new ways of thinking about what military forces can and cannot do to protect civilians from violence. Today, militaries are expected to protect civilians from perpetrators that target them as part of their warfare, expanding their responsibilities under International Humanitarian Law. This expansion of tasks represents “troublesome knowledge” for many military officers and demands a deeper understanding of the rationales and strategies driving perpetrators’ targeting of civilians. To overcome this pedagogical challenge, we developed an XR-supported educational program combining immersive experiences and pedagogical approaches, including combined 360°-videos and embodiment, dialogue with virtual humans and collaborative VR-landscapes to encourage immersive peer-to-peer learning. The results are encouraging, suggesting high levels of acceptance by learners of the threat-based concept, an effect on stimulating critical discussion and a positive reaction to XR-supported learning.
Orthobiologics in knee osteoarthritis, dream or reality?
Authors: Budhiparama Nicolaas Cyrillus , Putramega Dananjaya , Lumban-Gaol Imelda 
Published: April 2024

AbstractCartilage restoration or repair, also known as orthobiologic therapy, is indicated after the failure of conservative or supportive treatment. However, there is paucity in evidence supporting the efficacy of orthobiologic therapy. The blood-derived products, such as platelet-rich plasma (PRP), is one of the commonly used orthobiologic therapy for knee osteoarthritis. Several studies have shown that PRP is superior to other treatments, but the anatomic changes are scarce. Treatment with mesenchymal stem cells (MSCs) offers the greatest potential for curing degenerative disease due to their self-renewal ability, ability to migrate towards injured tissues (homing/trafficking), and ability to promote repair and regeneration of osteochondral defects. However, ethical concerns and high costs remain major challenges associated with MSC therapy. Gene therapy, another promising orthobiologic therapy, is currently in phase II clinical trial and has shown promising results. The key factors for successful orthobiologic therapy include patient selection, appropriate dosing, treatment of underlying mechanical problems, age, severity, and cost-effectiveness.
Effect of siponimod on lymphocyte subsets in active secondary progressive multiple sclerosis and clinical implications
Authors: Spiezia Antonio Luca , Scalia Giulia , Petracca Maria , Caliendo Daniele , Moccia Marcello , Fiore Antonia , Cerbone Vincenza , Lanzillo Roberta , Brescia Morra Vincenzo , Carotenuto Antonio 
Published: April 2024

Abstract
Background
Circulating immune cells play a pathogenic role in multiple sclerosis (MS). However, the role of specific lymphocyte subpopulations is not unveiled yet, especially in progressive stages. We aimed to investigate lymphocyte changes during siponimod treatment in active secondary progressive MS (aSPMS) and their associations with clinical outcomes.

Methods
We enrolled 46 aSPMS patients starting on siponimod treatment with at least 6 months of follow-up and two visits within the scheduled timeframes and 14 sex- and age-matched healthy controls (HCs). Clinical and laboratory data were collected retrospectively at baseline, 3rd, 6th, 12th, and 24th month for MS patients, and at baseline for HCs.

Results
At baseline SPMS patients presented with increased naïve regulatory T lymphocytes (p = 0.02) vs. HCs. Over time, SPMS patients showed decreased T CD4+ (coeff. range = −24/−17, 95% CI range = −31.60 to −10.40), B lymphocyte (coeff. range = −3.77/−2.54, 95% CI range = −6.02 to −0.35), memory regulatory B cells (coeff. range = −0.78/−0.57, 95% CI range = −1.24 to −0.17) and CD4/CD8 ratio (coeff. range = −4.44/−0.67, 95% CI range = −1.61 to −0.17) from month 3 thereafter vs. baseline, and reduced CD3+CD20+ lymphocytes from month 12 thereafter (coeff. range = −0.32/−0.24, 95% CI range = −0.59 to −0.03). Patients not experiencing disability progression while on siponimod treatment showed B lymphocyte reduction from month 3 (coeff. range = −4.23/−2.32, 95% CI range = −7.53 to −0.15) and CD3+CD20+ lymphocyte reduction from month 12 (coeff. range = −0.32/−0.24, 95% CI range = −0.59 to −0.03) vs. patients experiencing progression.

Conclusions
Patients treated with siponimod showed a T and B lymphocyte reduction, especially CD4+, CD3+CD20+ and naïve regulatory T cells and memory regulatory B cells. Disability progression while on siponimod treatment was associated with a less pronounced effect on B and CD3+CD20+ lymphocytes.
Artesunate attenuates the tumorigenesis of choroidal melanoma via inhibiting EFNA3 through Stat3/Akt signaling pathway
Authors: Yao Ningning , Ma Qingyue , Yi Wendan , Zhu Yuanzhang , Liu Yichong , Gao Xiaodi , Zhang Qian , Luo Wenjuan 
Published: April 2024

Abstract
Purpose
Choroidal melanoma (CM), a kind of malignant tumor, is the main type of Uveal melanoma and one half of CM patients develop metastases. As a member of Eph/ephrin pathway that plays vital role in tumors, EphrinA3 (EFNA3) has been proved to promote tumorigenesis in many tumors. But the effect of EFNA3 in CM has not been studied yet. Through inhibiting angiogenesis, inducing apoptosis and autophagy and so on, Artesunate (ART) plays a key anti-tumor role in many tumors, including CM. However, the exact mechanisms of anti-tumor in CM remain unclear.

Methods
The UALCAN and TIMER v2.0 database analyzed the role of EFNA3 in CM patients. Quantitative real time polymerase chain reaction (qPCR) and Western blot were used to detect the expression of EFNA3 in CM. The growth ability of CM was tested by clonogenic assay and Cell counting kit-8 assay, and the migration ability using Transwell assay.

Results
Our results found EFNA3 boosted CM cells’ growth and migration through activating Stat3/Akt signaling pathway, while ART inhibited the tumor promoting effect of CM via downregulating EFNA3. In xenograft tumor model, EFNA3 knockdown and ART significantly inhibited tumor growth.

Conclusion
EFNA3 could be a valuable prognostic factor in CM.

Graphical abstract
Responses of stem growth and canopy greenness of temperate conifers to dry spells
Authors: Mašek Jiří , Dorado-Liñán Isabel , Treml Václav 
Published: April 2024

AbstractDry spells strongly influence biomass production in forest ecosystems. Their effects may last several years following a drought event, prolonging growth reduction and therefore restricting carbon sequestration. Yet, our understanding of the impact of dry spells on the vitality of trees' above-ground biomass components (e.g., stems and leaves) at a landscape level remains limited. We analyzed the responses of Pinus sylvestris and Picea abies to the four most severe drought years in topographically complex sites. To represent stem growth and canopy greenness, we used chronologies of tree-ring width and time series of the Normalized Difference Vegetation Index (NDVI). We analyzed the responses of radial tree growth and NDVI to dry spells using superposed epoch analysis and further explored this relationship using mixed-effect models. Our results show a stronger and more persistent response of radial growth to dry spells and faster recovery of canopy greenness. Canopy greenness started to recover the year after the dry spell, whereas radial tree growth remained reduced for the two subsequent years and did not recover the pre-drought level until the fourth year after the event. Stem growth and canopy greenness were influenced by climatic conditions during and after drought events, while the effect of topography was marginal. The opposite responses of stem growth and canopy greenness following drought events suggest a different impact of dry spells on trees´ sink and source compartments. These results underscore the crucial importance of understanding the complexities of tree growth as a major sink of atmospheric carbon.
Hierarchical fuzzy regression functions for mixed predictors and an application to real estate price prediction
Authors: Demirhan Haydar , Baser Furkan 
Published: April 2024

AbstractCategorical features appear in datasets from almost every practice area, including real estate datasets. One of the most critical handicaps of machine learning algorithms is that they are not designed to capture the qualitative nature of the categorical features, leading to sub-optimal predictions for the datasets with categorical observations. This study focuses on a new fuzzy regression functions framework, namely hierarchical fuzzy regression functions, that can handle categorical features properly for the regression task. The proposed framework is benchmarked with linear regression, support vector machines, deep neural networks, and adaptive neuro-fuzzy inference systems with real estate data having categorical features from six markets. It is observed that the proposed method produces better prediction performance for real estate price prediction than the benchmark methods in a wide variety of real estate markets. Since we provide all the required software codes to implement the proposed hierarchical fuzzy regression functions framework, our approach offers practitioners a readily applicable, high-performing tool for real estate price prediction and other regression problems involving categorical independent features.
Extension of convex functions from a hyperplane to a half-space
Authors: Ball John M. , Horner Christopher L. 
Published: April 2024

AbstractIt is shown that a possibly infinite-valued proper lower semicontinuous convex function on $$\mathbb {R}^n$$

R

n

has an extension to a convex function on the half-space $$\mathbb {R}^n\times [0,\infty )$$

R

n

×

[
0
,
∞
)

which is finite and smooth on the open half-space $$\mathbb {R}^n\times (0,\infty )$$

R

n

×

(
0
,
∞
)

. The result is applied to nonlinear elasticity, where it clarifies how the condition of polyconvexity of the free-energy density $$\psi (Dy)$$

ψ
(
D
y
)

is best expressed when $$\psi (A)\rightarrow \infty $$

ψ
(
A
)
→
∞

as $$\det A\rightarrow 0+$$

det
A
→
0
+

.
Ubiquitous arbuscular mycorrhizal fungi in the roots of herbaceous understory plants with hyphal degeneration in Colchicaceae and Gentianaceae
Authors: Kusakabe Ryota , Sasuga Moe , Yamato Masahide 
Published: April 2024

AbstractDue to the loss of photosynthetic ability during evolution, some plant species rely on mycorrhizal fungi for their carbon source, and this nutritional strategy is known as mycoheterotrophy. Mycoheterotrophic plants forming Paris-type arbuscular mycorrhizas (AM) exhibit two distinctive mycorrhizal features: degeneration of fungal materials and specialization towards particular fungal lineages. To explore the possibility that some understory AM plants show partial mycoheterotrophy, i.e., both photosynthetic and mycoheterotrophic nutritional strategies, we investigated 13 green herbaceous plant species collected from five Japanese temperate forests. Following microscopic observation, degenerated hyphal coils were observed in four species: two Colchicaceae species, Disporum sessile and Disporum smilacinum, and two Gentianaceae species, Gentiana scabra and Swertia japonica. Through amplicon sequencing, however, we found that all examined plant species exhibited no specificity toward AM fungi. Several AM fungi were consistently found across most sites and all plant species studied. Because previous studies reported the detection of these AM fungi from various tree species in Japanese temperate forests, our findings suggest the presence of ubiquitous AM fungi in forest ecosystems. If the understory plants showing fungal degeneration exhibit partial mycoheterotrophy, they may obtain carbon compounds indirectly from a wide range of surrounding plants utilizing such ubiquitous AM fungi.
Graphene quantum dots on TiO2 nanotubes as a light-assisted peroxidase nanozyme
Authors: Çakıroğlu Bekir 
Published: April 2024

AbstractHybrid nanozyme graphene quantum dots (GQDs) deposited TiO2 nanotubes (NTs) on titanium foil (Ti/TiO2 NTs-GQDs) were manufactured by bestowing the hybrid with the advantageous porous morphology, surface valence states, high surface area, and copious active sites. The peroxidase-like activity was investigated through the catalytic oxidation of chromogenic substrate 3,3′,5,5′-tetramethylbenzidine (TMB) in the presence of H2O2, which can be visualized by the eyes. TiO2 NTs and GQDs comprising oxygen-containing functional groups can oxidize TMB in the presence of H2O2 by mimicking peroxidase enzymes. The peroxidase-mimicking activity of hybrid nanozyme was significantly escalated by introducing light illumination due to the photosensitive features of the hybrid material. The peroxidase-like activity of Ti/TiO2 NTs-GQDs enabled H2O2 determination over the linear range of 7 to 250 μM, with a LOD of 2.1 µM. The satisfying peroxidase activity is possibly due to the unimpeded access of H2O2 to the catalyst’s active sites. The porous morphology provides the easy channeling of reactants and products. The periodic structure of the material also gave rise to acceptable reproducibility. Without material functionalization, the Ti/TiO2 NTs-GQDs can be a promising substitute for peroxidases for H2O2 detection.
Graphical abstract