bluuebunny/crossref_metadata_2025 huggingface dataset:
Double‐digest restriction‐associated DNA sequencing‐based genotyping and its applications in sesame germplasm management
Authors: Ruperao Pradeep , Bajaj Prasad , Yadav Rashmi , Angamuthu Mahalingam , Subramani Rajkumar , Rai Vandana , Tiwari Kapil , Rathore Abhishek , Singh Kuldeep , Singh Gyanendra Pratap , Angadi Ulavappa B. , Mayes Sean , Rangan Parimalan
Published: April 2024

Sesame (Sesamum indicum L.) is an ancient oilseed crop belonging to the family Pedaliaceae and a globally cultivated crop for its use as oil and food. In this study, 2496 sesame accessions, being conserved at the National Genebank of ICAR‐National Bureau of Plant Genetic Resources (NBPGR), were genotyped using genomics‐assisted double‐digest restriction‐associated DNA sequencing (ddRAD‐seq) approach. A total of 64,910 filtered single‐nucleotide polymorphisms (SNPs) were utilized to assess the genome‐scale diversity. Applications of this genome‐scale information (reduced representation using restriction enzymes) are demonstrated through the development of a molecular core collection (CC) representing maximal SNP diversity. This information is also applied in developing a mid‐density panel (MDP) comprising 2515 hyper‐variable SNPs, representing almost equally the genic and non‐genic regions. The sesame CC comprising 384 accessions, a representative set of accessions with maximal diversity, was identified using multiple criteria such as k‐mer (subsequence of length “k” in a sequence read) diversity, observed heterozygosity, CoreHunter3, GenoCore, and genetic differentiation. The coreset constituted around 15% of the total accessions studied, and this small subset had captured >60% SNP diversity of the entire population. In the coreset, the admixture analysis shows reduced genetic complexity, increased nucleotide diversity (π), and is geographically distributed without any repetitiveness in the CC germplasm. Within the CC, India‐originated accessions exhibit higher diversity (as expected based on the center of diversity concept), than those accessions that were procured from various other countries. The identified CC set and the MDP will be a valuable resource for genomics‐assisted accelerated sesame improvement program.
Maternal prepregnancy weight as an independent risk factor for congenital heart defect: systematic review and meta‐analysis stratified by subtype and severity of defect
Authors: Salmeri N. , Seidenari A. , Cavoretto P. I. , Papale M. , Candiani M. , Farina A.
Published: April 2024

Objective

To assess the association between increased maternal prepregnancy body mass index (BMI) and the risk of congenital heart defect (CHD) in offspring.

Methods

This systematic review and meta‐analysis searched PubMed/MEDLINE, Web of Science and Scopus from inception to 20 April 2023. Risk estimates were abstracted or calculated for increased BMI categories (overweight, obesity, moderate obesity and severe obesity) compared with normal weight (reference). Fixed‐effects or random‐effects models were used to combine individual study risk estimates based on the degree of heterogeneity. Sensitivity analyses were conducted to weight pooled estimates for relevant moderators, particularly diabetes before and during pregnancy. Subgroup analyses for specific CHD subtypes were conducted if there were at least two studies with available data. Findings were presented for groups of defects, categorized using severity and topographic–functional criteria, and for individual defects. The certainty of the evidence for each effect estimate was evaluated according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines.

Results

Overall, 31 studies comprising 4 861 693 patients and 86 136 CHD cases were included. The risk of CHD increased progressively from moderate to severe obesity (pooled odds ratio (OR), 1.15 (95% CI, 1.11–1.20) and 1.39 (95% CI, 1.27–1.53), respectively). Sensitivity analysis indicated that this effect persisted independently of maternal diabetes status before or during pregnancy. In the subgroup analysis, obesity was associated with up to a 1.5‐fold increase in the risk of severe CHD (pooled OR, 1.48 (95% CI, 1.03–2.13)). Severe obesity was associated with an even higher risk, with 1.8‐times higher odds compared with the reference group for specific CHD subtypes, including tetralogy of Fallot (pooled OR, 1.72 (95% CI, 1.38–2.16)), pulmonary valve stenosis (pooled OR, 1.79 (95% CI, 1.39–2.30)) and atrial septal defect (pooled OR, 1.71 (95% CI, 1.48–1.97)).

Conclusions

Maternal weight is a crucial modifiable risk factor for CHD, particularly for severe forms of defect. Further research is needed to investigate whether weight management before pregnancy might serve as a preventive measure against CHD. In pregnant women with obesity, fetal echocardiography should be a routine diagnostic procedure. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Recent developments in the use of nanocrystals to improve bioavailability of APIs
Authors: Ding Yidan , Zhao Tongyi , Fang Jianing , Song Jiexin , Dong Haobo , Liu Jiarui , Li Sijin , Zhao Min
Published: April 2024

Nanocrystals refer to materials with at least one dimension smaller than 100 nm, composing of atoms arranged in single crystals or polycrystals. Nanocrystals have significant research value as they offer unique advantages over conventional pharmaceutical formulations, such as high bioavailability, enhanced targeting selectivity and controlled release ability and are therefore suitable for the delivery of a wide range of drugs such as insoluble drugs, antitumor drugs and genetic drugs with broad application prospects. In recent years, research on nanocrystals has been progressively refined and new products have been launched or entered the clinical phase of studies. However, issues such as safety and stability still stand that need to be addressed for further development of nanocrystal formulations, and significant gaps do exist in research in various fields in this pharmaceutical arena. This paper presents a systematic overview of the advanced development of nanocrystals, ranging from the preparation approaches of nanocrystals with which the bioavailability of poorly water‐soluble drugs is improved, critical properties of nanocrystals and associated characterization techniques, the recent development of nanocrystals with different administration routes, the advantages and associated limitations of nanocrystal formulations, the mechanisms of physical instability, and the enhanced dissolution performance, to the future perspectives, with a final view to shed more light on the future development of nanocrystals as a means of optimizing the bioavailability of drug candidates.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Emerging Technologies

Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Permanent Counterrevolution, Technocracy, and World War III
Authors: Hughes David A.
Published: April 2024

An undeclared global class war was initiated in 2020, whose aim is the controlled demolition of liberal democracy and the institution of global technocracy—a novel, biodigital form of totalitarianism that threatens to lead to the irreversible enslavement of humanity. World War III looks nothing like its two predecessors and is waged by the transnational deep state against populations using the novel methods of Omniwar, i.e. war waged in every domain, but clandestinely, so that the public does not recognise it as such. The opening campaign of World War III involved the largest psychological warfare operation in history, which I refer to as the “‘Covid-19’ operation.” This was intended to demoralise, disorientate, and debilitate the public, thus weakening its resistance to the intended transition to technocracy. Historically, psychological warfare has served as the prelude to physical war, raising the alarm concerning what is to come.
Cognitive Attack
Authors: Hughes David A.
Published: April 2024

Menticide attacks the cognitive faculties of victims to break down their mental integrity and render them susceptible to indoctrination. During “Covid-19,” confusion was weaponised in various ways, including a proliferation of nonsensical and ever-changing “rules,” last-minute U-turns on key Government decisions, unpredictability of restrictions easing or tightening, and a fundamental irrationality in Government behaviour. Verbal confusion was deployed against the public through constant mixed messaging. A strategy of continuous questioning by the media caused bewilderment. Words and phrases were twisted to mean their opposites, or were used in an esoteric fashion. The public was made to question its own sanity via means used to make social reality seem surreal. The past was rewritten to deny events that actually took place. The public was gaslighted to think that anything but the “vaccines” were to blame for injuries/deaths to young people. A Soviet-style abuse of psychiatry was used to pathologise dissent.
Legal Design and Visual Law: The Roadmap
Authors: Parola Giulia , Poto Margherita Paola
Published: April 2024

This chapter focuses on illustrating the steps of Legal Design (LD) and Visual Law (VL). Before delving into the process of comic book co-creation, the chapter provides an overview of LD and VL, emphasizing their relative unfamiliarity, even among legal scholars. LD, originating from an initiative at Stanford Law School, aims to simplify legal language by evaluating and designing legal business in a simple, functional, attractive, and usable way. It centers on people’s needs, shifting focus from professionals to recipients, such as citizens, organizations, and communities. LD emphasizes ongoing interactions and feedback from recipients throughout the project, fostering empathy and active listening. While LD focuses on effective communication for the benefit of legal beneficiaries, VL serves as its visual manifestation. VL utilizes various visual elements, such as images, illustrations, videos, infographics, comics, and more, making legal documents more explanatory. LD and VL, initially tools for law firms to aid law firm clients understanding, have evolved for broader applications in legal education, research dissemination, empowering society to advocate for their rights, and supporting the decolonization of legal mindsets. The chapter discusses the interchangeable use of LD and VL in legal research, legal education, and as strategic tools for societal empowerment. Importantly, it highlights their potential role in decolonizing legal mindsets by involving participants outside the dominant Western legal doctrine and supporting knowledge co-creation. The chapter underscores the importance of LD and VL in contributing to the re-emergence of Indigenous perspectives and cosmovisions, ultimately facilitating effective participation in environmental matters.
Toward a Spanish Version of the Escazú Agreement in Comics: Needs, Research Background, and Methodological Steps
Authors: Parola Giulia , Poto Margherita Paola , Porrone Arianna , Koessl Natasha
Published: April 2024

This chapter delves into the project’s evolution after the successful publication of books on the Escazú Agreement in English and Portuguese. The initiative shifted focus towards disseminating the knowledge contained in these works to the Chiquitano communities in Mato Grosso and sharing project results in academic fora and international conferences. The reception of these books was enthusiastic among both indigenous and scientific communities, garnering positive feedback. One notable suggestion emerged prominently: the urgent need to develop a Spanish version. This recommendation was driven by the widespread prevalence of Spanish as a major language in Latin American and Caribbean countries, including Bolivia, where the majority of Chiquitano communities reside. Therefore, this chapter explores the process of expanding the initiative to include a Spanish version, emphasizing its significance and implications for promoting indigenous rights and environmental protection. Adapting the project to this crucial language aims to ensure broader and more effective access to information about the Escazú Agreement, thereby strengthening indigenous community participation and fostering environmental protection in the region.
Dark showers from Z-dark Z′ mixing
Authors: Cheng Hsin-Chia , Jiang Xu-Hui , Li Lingfeng , Salvioni Ennio
Published: April 2024

Abstract

We discuss dark shower signals at the LHC from a dark QCD sector, containing GeV-scale dark pions. The portal with the Standard Model is given by the mixing of the Z boson with a dark Z′ coupled to the dark quarks. Both mass and kinetic mixings are included, but the mass mixing is the essential ingredient, as it is the one mediating visible decays of the long-lived dark pions. We focus especially on the possibility that the dark Z′ is lighter than the Z. Indirect constraints are dominated by electroweak precision tests, which we thoroughly discuss, showing that both Z-pole and low-energy observables are important. We then recast CMS and LHCb searches for displaced dimuon resonances to dark shower signals initiated by the production of on-shell Z or Z′, where the visible signature is left by a dark pion decaying to μ+μ−. We demonstrate how dark shower topologies have already tested new parameter space in Run 2, reaching better sensitivity on a light dark Z′ compared to the flavor-changing decays of B mesons, which can produce a single dark pion at a time, and the electroweak precision tests.
Rational numbers with small denominators in short intervals
Authors: Shparlinski Igor E.
Published: April 2024

We use bounds on bilinear forms with Kloosterman fractions and improve the error term in the asymptotic formula of Balazard and Martin (Bull Sci Math 187:Art. 103305, 2023) on the average value of the smallest denominators of rational numbers in short intervals.
RUNX transcription factors are essential in maintaining epididymal epithelial differentiation
Authors: Toriseva Mervi , Björkgren Ida , Junnila Arttu , Mehmood Arfa , Mattsson Jesse , Raimoranta Inka , Kim Bongki , Laiho Asta , Nees Matthias , Elo Laura , Poutanen Matti , Breton Sylvie , Sipilä Petra
Published: April 2024

Apart from the androgen receptor, transcription factors (TFs) that are required for the development and formation of the different segments of the epididymis have remained unknown. We identified TF families expressed in the developing epididymides, of which many showed segment specificity. From these TFs, down-regulation of runt related transcription factors (RUNXs) 1 and 2 expression coincides with epithelial regression in Dicer1 cKO mice. Concomitant deletion of both Runx1 and Runx2 in a mouse epididymal epithelial cell line affected cell morphology, adhesion and mobility in vitro. Furthermore, lack of functional RUNXs severely disturbed the formation of 3D epididymal organoid-like structures. Transcriptomic analysis of the epididymal cell organoid-like structures indicated that RUNX1 and RUNX2 are involved in the regulation of MAPK signaling, NOTCH pathway activity, and EMT-related gene expression. This suggests that RUNXs are master regulators of several essential signaling pathways, and necessary for the maintenance of proper differentiation of the epididymal epithelium.
When DNA-damage responses meet innate and adaptive immunity
Authors: Tong Jie , Song Jiangwei , Zhang Wuchao , Zhai Jingbo , Guan Qingli , Wang Huiqing , Liu Gentao , Zheng Chunfu
Published: April 2024

When cells proliferate, stress on DNA replication or exposure to endogenous or external insults frequently results in DNA damage. DNA-Damage Response (DDR) networks are complex signaling pathways used by multicellular organisms to prevent DNA damage. Depending on the type of broken DNA, the various pathways, Base-Excision Repair (BER), Nucleotide Excision Repair (NER), Mismatch Repair (MMR), Homologous Recombination (HR), Non-Homologous End-Joining (NHEJ), Interstrand Crosslink (ICL) repair, and other direct repair pathways, can be activated separately or in combination to repair DNA damage. To preserve homeostasis, innate and adaptive immune responses are effective defenses against endogenous mutation or invasion by external pathogens. It is interesting to note that new research keeps showing how closely DDR components and the immune system are related. DDR and immunological response are linked by immune effectors such as the cyclic GMP-AMP synthase (cGAS)–Stimulator of Interferon Genes (STING) pathway. These effectors act as sensors of DNA damage-caused immune response. Furthermore, DDR components themselves function in immune responses to trigger the generation of inflammatory cytokines in a cascade or even trigger programmed cell death. Defective DDR components are known to disrupt genomic stability and compromise immunological responses, aggravating immune imbalance and leading to serious diseases such as cancer and autoimmune disorders. This study examines the most recent developments in the interaction between DDR elements and immunological responses. The DDR network’s immune modulators’ dual roles may offer new perspectives on treating infectious disorders linked to DNA damage, including cancer, and on the development of target immunotherapy.
Ritueller sexueller Missbrauch
Authors: Fegert Jörg M. , Urbaniok Frank
Published: April 2024

Hintergrund

Hintergrund des Beitrags bildet die polarisierte mediale Debatte um rituelle sexuelle Gewalt gegen Kinder. Es haben sich zwei Lager gebildet, die sich gegenüberstehen und denen ein sachlicher Austausch miteinander nicht möglich ist.

Ziel

Der Artikel verfolgt daher das Ziel, einen klinischen Beitrag zur Überbrückung der Differenzen zu leisten und argumentiert vor allem im Sinne des Wohls von Patient:innen dafür, sich auf eine Evidenzbasierung sowohl in der Krankenbehandlung als auch im wissenschaftlichen Diskurs zu besinnen.

Material und Methoden

Der Beitrag basiert auf der kritischen Auseinandersetzung mit exemplarischer Fachliteratur, öffentlichen Untersuchungsberichten zu Fehlbehandlungen vor allem in der Schweiz sowie auf die Medienberichterstattung.

Ergebnisse

In bestimmten psychotraumatologischen Kreisen sowie in den Medien (gerade auch in sozialen Medien auf Plattformen wie Telegram) ist ein Verschwörungsnarrativ über ein großes Täter:innennetzwerk, welches im rituellen Kontext Kindern schwerste Gewalt antue, präsent. Ein unkritischer Glaube z. B. an Konzepte wie „mind control“ (Vorstellung eines absichtlichen und planvollen Herbeiführens einer dissoziativen Identitätsstörung) hat zu Fehlbehandlungen von Patient:innen sowie im Gegenzug zu einem grundlegenden Misstrauen gegenüber deren Aussagen geführt. Dadurch droht diesen ohnehin vulnerablen Patient:innen weiterer Schaden, was den basalen Prinzipien medizinischer Ethik widerspricht.
A 3D atlas of the human developing pancreas to explore progenitor proliferation and differentiation
Authors: Villalba Adrian , Gitton Yorick , Inoue Megumi , Aiello Virginie , Blain Raphaël , Toupin Maryne , Mazaud-Guittot Séverine , Rachdi Latif , Semb Henrik , Chédotal Alain , Scharfmann Raphaël
Published: April 2024

Aims/hypothesis

Rodent pancreas development has been described in great detail. On the other hand, there are still gaps in our understanding of the developmental trajectories of pancreatic cells during human ontogenesis. Here, our aim was to map the spatial and chronological dynamics of human pancreatic cell differentiation and proliferation by using 3D imaging of cleared human embryonic and fetal pancreases.

Methods

We combined tissue clearing with light-sheet fluorescence imaging in human embryonic and fetal pancreases during the first trimester of pregnancy. In addition, we validated an explant culture system enabling in vitro proliferation of pancreatic progenitors to determine the mitogenic effect of candidate molecules.

Results

We detected the first insulin-positive cells as early as five post-conceptional weeks, two weeks earlier than previously observed. We observed few insulin-positive clusters at five post-conceptional weeks (mean ± SD 9.25±5.65) with a sharp increase to 11 post-conceptional weeks (4307±152.34). We identified a central niche as the location of onset of the earliest insulin cell production and detected extra-pancreatic loci within the adjacent developing gut. Conversely, proliferating pancreatic progenitors were located in the periphery of the epithelium, suggesting the existence of two separated pancreatic niches for differentiation and proliferation. Additionally, we observed that the proliferation ratio of progenitors ranged between 20% and 30%, while for insulin-positive cells it was 1%. We next unveiled a mitogenic effect of the platelet-derived growth factor AA isoform (PDGFAA) in progenitors acting through the pancreatic mesenchyme by increasing threefold the number of proliferating progenitors.

Conclusions/interpretation

This work presents a first 3D atlas of the human developing pancreas, charting both endocrine and proliferating cells across early development.

Graphical Abstract
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

Cannabidiol (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

Let 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

The 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

We 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

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

As 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

Extended 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

Cartilage 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

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

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

Dry 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

Categorical 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

It 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

Due 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

Hybrid 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
A comparative study of electropolymerization and photopolymerization for the determination of molnupiravir and their application in an electrochemical sensor via computationally designed molecularly imprinted polymers
Authors: Cetinkaya Ahmet , Unal M. Altay , Nazır Hasan , Çorman M. Emin , Uzun Lokman , Ozkan Sibel A.
Published: April 2024

A comparative analysis of molecularly imprinted polymers based on different synthesis techniques was performed for the recognition of molnupiravir (MOL). The polymerizations were performed with 3-thienyl boronic acid (3-TBA) as a functional monomer by electropolymerization (EP) and with guanine methacrylate (GuaM) as a functional monomer by photopolymerization (PP). Morphological and electrochemical characterizations of the developed sensors were investigated to verify the constructed sensors. Moreover, quantum chemical calculations were used to evaluate changes on the electrode surface at the molecular and electronic levels. The dynamic linear range of both designed sensors under optimized experimental conditions was found to be 7.5 × 10−12–2.5 × 10−10 M and 7.5 × 10−13–2.5 × 10−11 M for EP and PP, respectively. The effect of various interfering agents on MOL peak current was assessed for the selectivity of the study. In the presence of 100 times more interfering agents, the RSD and recovery values were determined. The RSD values of GuaM/MOL@MIP/GCE and poly(Py-co-3-PBA)/MOL@MIP/GCE sensors were found to be 1.99% and 1.72%, respectively. Furthermore, the recovery values of the MIP-based sensors were 98.18–102.69% and 98.05–103.72%, respectively. In addition, the relative selectivity coefficient (k′) of the proposed sensor was evaluated, and it exhibited good selectivity for MOL with respect to the NIP sensor. The prepared sensor was successfully applied to determine MOL in commercial serum samples and capsule form. In conclusion, the developed sensors provided excellent reproducibility, repeatability, high sensitivity, and selectivity against the MOL molecule.

Graphical Abstract
Detection and complete genome characterization of a genogroup X (GX) sapovirus (family Caliciviridae) from a golden jackal (Canis aureus) in Hungary
Authors: Balázs Benigna , Boros Ákos , Pankovics Péter , Nagy Gábor , Szekeres Sándor , Urbán Péter , Reuter Gábor
Published: April 2024

In this study, a novel genotype of genogroup X (GX) sapovirus (family Caliciviridae) was detected in the small intestinal contents of a golden jackal (Canis aureus) in Hungary and characterised by viral metagenomics and next-generation sequencing techniques. The complete genome of the detected strain, GX/Dömsöd/DOCA-11/2020/HUN (PP105600), is 7,128 nt in length. The ORF1- and ORF2-encoded viral proteins (NSP, VP1, and VP2) have 98%, 95%, and 88% amino acid sequence identity to the corresponding proteins of genogroup GX sapoviruses from domestic pigs, but the nucleic acid sequence identity values for their genes are significantly lower (83%, 77%, and 68%). During an RT-PCR-based epidemiological investigation of additional jackal and swine samples, no other GX strains were detected, but a GXI sapovirus strain, GXI/Tótfalu/WBTF-10/2012/HUN (PP105601), was identified in a faecal sample from a wild boar (Sus scrofa). We report the detection of members of two likely underdiagnosed groups of sapoviruses (GX and GXI) in a golden jackal and, serendipitously, in a wild boar in Europe.