bluuebunny/crossref_metadata_2025 huggingface dataset:
CD91 and its ligand heat shock proteins regulate dendritic cell functions during immunosurveillance of emerging tumors
Authors: Nayak Devanshi , Sedlacek Abigail , Cillo Anthony , Watkins Simon , Binder Robert
Published: November 2024

Dendritic cells (DCs) play a pivotal role in initiating and modulating responses against nascent tumors. This study investigates how immunogenic heat shock proteins (HSPs), particularly glycoprotein 96 (gp96), efficiently chaperone minute amounts of peptides during early tumor development to evoke antigen-specific immunity. Tumor-derived gp96 is endocytosed by CD91, a receptor on DCs that is crucial for cross-priming T cells. Here we generated mouse models with DC-specific CD91 deficiency (CD11cCre, XCR1Cre, Mgl2Cre) and a system to track dispersal of tumor-derived gp96. Our data suggests that CD91 expression on type 1 conventional DCs (cDC1) is essential for uptake of gp96 during cancer immunosurveillance. While gp96+ cDC1s contribute to early tumor control, sustained and long-term tumor control is facilitated by other gp96+ cross-priming DCs (CD11b+ cDCs) through intercellular transfer of gp96. Single cell analysis of antigen-presenting cells (APCs) in tumor-draining lymph nodes illustrates that CD91 promotes T cell priming, while downregulating immune regulatory pathways. Engagement of CD91 initiates co-stimulation, cytokine production and cross-presentation of HSP-chaperoned peptides establishing it as a primary mechanism immunosurveillance. Understanding the role of CD91+ DCs in cancer immunosurveillance holds significant implications for cancer prognosis and therapy, revealing the division of labor among APCs in the successful elimination of cancer cells.
Quantifying how TCR sequence influences cell fate commitment in chronic LCMV infection
Authors: Brown Ryan , Cui Weiguo
Published: November 2024

Repetitive T cell receptor (TCR) engagement on CD8 T cells during chronic infection is a critical driver of the dysfunctional state termed exhaustion. These exhausted cells are characterized by additional heterogeneity including a memory-like progenitor cell (Tpro) that continuously gives rise to either non-cytolytic exhausted cells (Texh) or cytotoxic effector cells (Teff). While we and others have shown that TCR avidity influence cell fate commitment to Texh or Teff, it is not certain if TCR sequence features influence this fate choice. In this study, we identify how TCR V(D)J gene recombination influences T cell differentiation at the single-cell resolution. To investigate this, we performed single-cell resolution TCR sequencing (scTCR-seq) on GP33+ tetramer sorted cells within lymphocytic choriomeningitis virus (LCMV) Clone 13 model of chronic infection across 7 different mice. Utilizing TCRdist and Clonotype Neighbor Graph Analysis (CoNGA), we construct correlations between gene expression and TCR features. We find that both chain usage and cdr3 motifs correlate to effector or exhausted cell fate commitment across these different mice. Overall, our results suggest that TCR gene rearrangement is critical not only for antigen specificity, but also determining CD8 T cell phenotypic outcomes during chronic viral infection.
Molecular characterization of post-translational modifications of DUSP12 in T cells
Authors: Yang Chia-Yu
Published: November 2024

Dual-specificity phosphatase 12 (DUSP12) belongs to a family of DUSP protein phosphatases (DUSPs) that are associated with cell cycle regulation, insulin sensitivity, and Toll-like receptor signaling. It has been reported that protein expression and phosphatase activity of DUSPs are regulated by post-translational modifications that may be mediated through phosphorylation, ubiquitination, or methylation. However, the functional roles of post-translational modifications on DUSP12 in T cells remain unclear. Our results showed that DUSP12 expression was increased upon T cell receptor (TCR) signaling. The number of T cells was decreased in DUSP12-deficient mice. To study the upstream regulators of DUSP12 in T cells, we used a proteomics approach to identify the potential post-translational modifications on DUSP12 protein. Our result showed that DUSP12 may be ubiquitinated, and we also identified multiple ubiquitination sites on DUSP12. Using DUSP12 co-immunoprecipitation and liquid chromatography-mass spectrometry experiment, we have identified a novel E3 ligase as a DUSP12-binding protein, which may regulate T-cell activation. Furthermore, the effects of ubiquitination in regulating the activity and expression of DUSP12 in T cells upon T cell receptor signaling were explored. Our study reveals the molecular regulation of DUSP12 in T-cell activation and immune responses.
Understanding the role of TNFR2 signaling in CD8 T cell exhaustion.
Authors: Hoyt-Miggelbrink Alexandra , Waibl Polania Jessica , Wachsmuth Luke , Lorrey Selena , Wilkinson Daniel , Hotchkiss Kelly , Lerner Emily , Cook Quackenbush Sarah , Hemmers Saskia , Ayasoufi Kathy , Fecci Peter
Published: November 2024

Glioblastoma (GBM) is the most common primary brain cancer in adults with a median survival less than 15 months. Approaches harnessing the immune response are hindered by multiple factors, including T cell exhaustion. Exhausted T cells are less capable of limiting tumor progression. As cells progress along the exhaustion pathway, SLAM Family Member 6 (SLAMF6) gets downregulated and T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) and TOX are upregulated. TOX is both necessary and sufficient to initiate the terminal exhaustion program. However, our understanding of the pathways that lead to the upregulation of TOX remains incomplete.

We hypothesized that tumor necrosis factor (TNF) could be involved in the upregulation of TOX, as TNF has been shown to induce exhaustion. We observed upregulation of the TNF receptor type II (TNFR2) in tumor-infiltrating T cells, but not in lymphoid organs. Furthermore, TNFR2 expression is correlated with canonical exhaustion markers. Interestingly, TNFR2 knock out (KO) CD8 T cells express TIM3 but exhibit significantly less TOX. These data suggest that TIM3 and TOX are regulated independently. Finally, TNFR2 KO mice have significantly better CD8-mediated tumor control against subcutaneous GBM tumors. Further studies will need to be performed to determine whether TNFR2 expression on CD8 T cells is sufficient to mediate this anti-tumor effect and whether TNFR2 blockade could improve the efficacy of current treatments.
StarBright Dyes — Simplifying Flow Cytometry with 8-color No Compensation Panels
Authors: Sanderson Sharon , Santos Magda , Perike Srikanth , Dreskin Elizabeth , Blundell Michael , Long Tracey
Published: November 2024

Flow cytometry is a powerful technique, allowing a vast amount of information to be obtained from a single sample. A well-designed panel is vital for good quality data. One aspect of panel design is to use fluorophore combinations that avoid close or overlapping spectra. If not, the panel will risk having high spillover, spreading, and reduced population resolution.

We have designed 8-color, no compensation panels for conventional flow cytometry where the fluorophores used have distinct spectra, therefore they have minimal signal into detection filters other than their own. This removes the need for post-acquisition compensation, saving time, as well as ensuring high resolution of cells due to the lack of spread. We show 8-color immunophenotyping panels, acquired on a 5-laser ZE5 Cell Analyzer, for human peripheral blood and mouse splenocytes which require no compensation. B cell, cytotoxic and memory T cell, natural killer cell, and monocyte populations were easily identified. These panels can also be used as a backbone for building larger panels by adding additional markers to detect other cells of interest.

Many antibodies incorporated into these panels, have been conjugated to StarBrightTM Dyes which have narrow excitation and emission profiles, making them ideal for inclusion in no compensation panels. StarBright Dyes also simplify panel design as they work with all buffers and most fixatives making them suitable for use in a wide range of protocols.
Detecting immune activity in human tumors with novel high-throughput whole slide imaging approaches using Imaging Mass Cytometry.
Authors: Motta Vinicius , Raza Qanber , Pfister Thomas , Lim Liang , Howell David , Parsotam Nikesh , King David , Loh Christina
Published: November 2024

Deciphering the spatial biology of the tumor immune microenvironment (TIME) has potential to inform clinical and translational researchers about the likelihood of immunotherapy success. Imaging Mass Cytometry™ (IMC™) is a spatial biology imaging technique that enables deep characterization of the TIME while fully retaining spatial features of tissues using 40-plus markers simultaneously.

We developed two new whole slide imaging methods for IMC. Tissue mode (TM) rapidly acquires an image of the whole tissue that can be used for quantitative analysis of spatial biology. Preview mode (PM) samples the entire tissue at predefined spacing to rapidly capture a low-resolution image of all expressed markers, improving informed identification of areas for high-resolution cell mode (CM) imaging on the same slide.

Tumor tissues were stained using a 40-marker panel comprised of the Maxpar™ Human Immuno-Oncology IMC Panel Kit, designed for tumor and immune cell profiling. TM imaging in combination with pixel-based analysis quantified tissue areas containing high or low abundance of myeloid and lymphoid immune, tumor and stromal cell compartments. PM in combination with CM imaging followed by single-cell analysis on selected tumor regions identified cell populations with varying activation states and expression profiles.

Overall, we highlight the power of IMC to provide quantitative insights into the spatial biology of the TIME.

For Research Use Only. Not for use in diagnostic procedures.
The use of DNAPK inhibitors increases the efficacy of Lentiviral vectors and decreases off-target effects.
Authors: Corbin Seana , Johnson Lauren , Azevedo-Pouly Ana , Burdine Marie , Burdine Lyle
Published: November 2024

Lentiviral vectors are a powerful tool in many models to deliver genetic material to target cells. Many methods of developing gene therapy treatment for multiple human diseases rely on using viral vectors to deliver genetic material into target cells. While viral vectors are a powerful tool, their use is not without its limitations and hurdles. Work must be done to overcome these hurdles to improve the delivery and reliability of vector-based gene therapy mechanisms in a clinically relevant and affordable manner.

The primary objective of this study was to enhance the precision and efficacy of lymphocyte modification while minimizing the systemic spread of the vectors. This was achieved through the strategic inhibition of DNA-PK, a key enzyme in DNA repair, to facilitate effective gene integration into lymphocyte genomes. These vectors were administered through trans-splenic injection, a novel approach aimed at directly targeting the lymphocyte-rich environment of the spleen with concurrent DNA-PK inhibition.

The results were significant. We observed a markedly high level of gene transduction in splenocytes 30% of T lymphocytes with minimal off-target effects. Notably, there was a substantial reduction in the systemic spread of the vectors, which is a critical factor in mitigating potential side effects. The transduced lymphocytes demonstrated stable gene expression, indicating the success of this method in achieving persistent genetic modification.
Development of NULISAseq™ 250-Plex Inflammation Panel for Immune Profiling of Autoimmune Diseases
Authors: Ma Xiao-Jun , Hao Qinyu , Sun Helena , Murlidhar Vasudha , Lee Anna , Yu Ming , Ariyapala Ishara , Kim Sean , Beer Joanne , Kuo Dwight , Fang Lei , Luo Yuling
Published: November 2024

Comprehensive profiling of cytokines and chemokines in blood can provide deeper insights into the mechanisms underlying this highly complex and heterogeneous group of diseases. However, many of these proteins are present at very low concentrations in plasma, below the limit of detection of current immunoassays. We recently developed a novel automated multiplex immunoassay technology, NULISA™, capable of attomolar-level sensitivity and high levels of multiplexing. Here we report the development of a 250-plex inflammation-focused panel targeting a broad range of cytokines/chemokines and other important inflammation and immune response-related proteins. We conducted a pilot study to assess the utility of this panel for autoimmune disease research. We analyzed plasma samples from patients with rheumatoid arthritis (RA), Sjögren's syndrome (SjS), systemic lupus erythematosus (SLE), and ulcerative colitis (UC), and compared to healthy donors. Linear model analysis identified differentially abundant proteins associated with diseases including many low-abundance targets with important roles in autoimmune diseases, such as IL4, IL5, IL20, IL17A, IL17F, IL33, and IL2RB. In summary, with the ultrahigh sensitivity and the most comprehensive inflammatory cytokine/chemokine panel, the NULISA™ Platform promises to be a powerful discovery tool for autoimmune disease research, which may lead to new diagnostic biomarkers and therapeutic targets.
Combinatorial genome engineering strategy for CAR-Treg antigen-specific immune protection of stem cell-derived cells
Authors: Barra Jessie , Robino Rob , Castro-Gutierrez Roberto , Ferreira Leonardo , Russ Holger
Published: November 2024

Improved methods for generating human pluripotent stem cell (hPSC)-derived cells and tissues have rapidly expanded the field of regenerative medicine. Yet, in most cases, hPSC-derived cells need to be protected, ideally in a localized manner, from an antagonistic host immune response. Chimeric antigen receptor (CAR) technology can confer new antigen specificities to effector T cells and, more recently, regulatory T cells (Tregs), potent immunosuppressive cells. However, one challenge in CAR design is identifying a target molecule uniquely expressed by the cells of interest to prevent unwanted off-target effects. Here, we developed a combinatorial genetic engineering approach to confer CAR-Treg-mediated localized immune protection specifically to transplanted stem cell-derived cells using a humanized type 1 diabetes preclinical mouse model. We engineered hPSCs to express a truncated epidermal growth factor receptor (EGFRt) and differentiated functional stem cell derived beta-like cells (sBCs) from them. In parallel, we generated EGFR CAR-Tregs that were activated by EGFRt-expressing sBCs without disrupting Treg identity. Strikingly, activated CAR-Tregs suppressed innate and adaptive effector immune responses in vitro and prevented effector CAR-T-cell-mediated sBC graft destruction in vivo. These data provide evidence that combinatorial genome engineering of hPSCs and Tregs can be harnessed to protect hPSC-derived tissues from immune attack via immune tolerance induction.
Notch2+ Marginal zone B cell depletion decreases antigen shuttle to Follicular Dendritic cells and reduces alloantibody production
Authors: Benedetti Gassen Rodrigo , de Jesus Borges Thiago , Magee Ciara , Murakami Naoka , Riella Leonardo
Published: November 2024

Chronic antibody-mediated rejection (CAMR) is a major cause of allograft loss. Most anti-rejection therapies target T cells and novel treatments to suppress CAMR are needed. Notch2+ Marginal zone (MZ) B cells have a key role in rapidly generating antibodies and facilitating the shuttle of antigens to follicular dendritic cells (FDCs). The FDC:B cell interaction is crucial to the formation of memory B cells and long-lived plasma cells. To evaluate the role of Notch2+ MZ B cells in transplantation, we utilize a mouse model of kidney transplantation, in which HLA-A2-expressing allografts are transplanted into B6 recipients. Here, we demonstrate that the anti-Notch2 treatment depletes MZ B cells and decreases pathological features of alloantibody-mediated rejection. Mechanistically, the anti-Notch2 treatment decreases plasma cells and the formation of donor-specific antibodies abrogates C4d deposition and reduces graft-infiltrating NK cells. Moreover, the Notch2+ MZ B cell depletion decreases the shuttling of antigens to FDCs as evidenced by the reduction of antigen (HLA.A2+) within FDCs (CD35+) clusters. Thus, Notch2+ MZ B cell depletion reduces alloantibody responses by decreasing alloantigen shutting to FDCs, leading to fewer signs of antibody-mediated graft rejection. Further elucidating the role of the Notch2 pathway will be important to the development of novel therapeutic strategies to prevent alloantibody production.
Activated B cell transcriptome induced by mATG treatment of heart allograft recipients
Authors: Yamamoto Yosuke , Anna Valujskikh , Gorbacheva Victoria , Fan Ran , Nicosia Michael , Fairchild Robert , Gaudette Brian
Published: November 2024

After transplant recipient treatment with anti-thymocyte globulin (ATG), B cells recover and drive reconstitution of depletion-resistant memory T cells. This study investigated the effects of ATG depletion on B cells in transplant recipients. Experimental groups were: 1) BALB/c to B6 heart Tx; 2) heart Tx + ATG; 3) ATG alone; 4) naïve B6. Spleen cells were isolated on d. 8 posttransplant and analyzed by single cell RNA-seq. Across all B cell subsets, immune stimulatory genes including lymphotoxin A and B, MHC-related and costimulatory genes were increased in Heart Tx + ATG group. Despite T cell depletion, recipients of heart Tx + ATG had twice as many germinal center (GC) B cells with increased expression of MHC II-associated and costimulatory genes as other groups and uniquely showed signs of early IgG class switching in GC and plasma cells. Heart Tx + ATG treatment induced a robust interferon response signature across B cell subsets, quite strikingly in the marginal zone (MZ) and transitional B cells. Targeting MZ B cells with anti-integrin mAb or the use MZ B cell-deficient recipients delayed recovery of CD8 T lymphocytes compared to controls suggesting that interferon signaling in MZ B cells is driving their proinflammatory functions required for T cell reconstitution. In sum, ATG lymphoablation induce proinflammatory signature in recipient B cells consistent with their role in T cell homeostatic expansion and raising a possibility of enhanced humoral responses.
Coronavirus Immune History Affects Breadth of Anti-SARS-CoV-2 Receptor-Binding Domain Responses.
Authors: Brice David , Lin Chun-Yang , Castellaw Ashley , Allen E , Wehenkel Marie , Lewis Carlessia , Roubidoux Ericka , Wolf Joshua , Thomas Paul , Schultz-Cherry Stacey , Webby Richard , McGargill Maureen
Published: November 2024

As novel SARS-CoV-2 variants continue to emerge, it is essential to gain further insight into the impact of imprinting on the protective antibody response to SARS-CoV-2. Utilizing a longitudinal cohort with samples collected before and after infection or vaccination, we assessed associations between pre-existing humoral immunity to common cold human coronaviruses (hCoVs) and the subsequent antibody response to the Spike Receptor Binding Domain (RBD) of different variants of SARS-CoV-2 following infection and vaccination. We found baseline anti-hCoV Spike IgM levels negatively correlate with anti-RBD breadth after infection, but not vaccination, with binding to the RBDs more antigenically distant to the Wuhan strain most affected. To investigate the effect of prior exposure to Spike proteins of individual coronaviruses, we utilized a mouse model. Unexpectedly, initial vaccination with SARS-CoV-1 Spike generated higher levels of SARS-CoV-2 RBD-specific antibodies compared to initial immunization with SARS-CoV-2 Spike, a phenomenon that continued even after SARS-CoV-2 Spike boosting of both groups. Moreover, SARS-CoV-1 Spike vaccination induced a broader and more durable SARS-CoV-2 RBD antibody response compared to SARS-CoV-2 Spike vaccination. Overall, these data highlight the lasting impact of prior exposure to related coronaviruses and demonstrate how SARS-CoV-1 Spike exposure induces a broader antibody response to the RBD of SARS-CoV-2 variants compared to SARS-CoV-2 Spike.
Characterization of AMEV2, A Multi-Peptide Vaccine Against Acinetobacter baumannii
Authors: Jeffreys Sean , Yu Jieh-Juen , Tompkins Megan , Aki Jadelynn , Guentzel Neal , Chambers James , Hung Chiung-Yu , Arulanandam Bernard
Published: November 2024

Multi-drug resistant (MDR) Acinetobacter baumannii is an opportunistic pathogen associated with hospital-acquired infections. This pathogen’s extensive MDR phenotype offers limited treatment options and requires alternative immunotherapeutic interventions, such as prophylactic vaccination in susceptible populations. In this study, we employed immunoinformatics to identify peptides containing both putative B and T cell epitopes from proteins associated with A. baumannii pathogenesis. An Acinetobacter Multi-Epitope Vaccine (AMEV2) comprising an A. baumannii thioredoxin A leading protein sequence followed by 5 identified peptide antigens was created. Subcutaneous immunization of mice with AMEV2 plus AddaS03 adjuvant demonstrates robust humoral and cellular immunogenicity. AMEV2 immunization results in high antibody titers to the antigen and the constitutional peptide components in addition to high frequencies of antibody-secreting cells in the spleen and bone marrow of the mice. In vitro opsonophagocytosis assays demonstrate anti-AMEV2 serum enhances the killing of opsonized bacteria by bone marrow-derived macrophages. Additionally, AMEV2 immunized mice were protected from both a lethal intraperitoneal and intranasal challenge with hypervirulent strains of A. baumannii, 4 weeks post-final vaccination, and achieved survival rates of 80% and 60%, respectively. AMEV2 vaccination affords antibody-mediated protection against hypervirulent A. baumannii infections.
Call for regulation of social media health content: an initiative of the Italian Association of Hospital Dermatologists (ADOI)
Authors: Cassalia Fortunato , Danese Andrea , D'Acunto Carmine , Russo Antonio , Zengarini Corrado , Stanganelli Ignazio , Cusano Francesco , Fantini Fabrizio , Amato Salvatore , Massone Cesare , Belloni Fortina Anna
Published: November 2024

Social media platforms have become integral to healthcare communication, particularly in dermatology, where visual assessment and patient education are paramount. While platforms like Instagram, Facebook, and Twitter offer significant opportunities to raise awareness about skin health, promote preventive measures, and encourage early detection of dermatological conditions, the unregulated dissemination of health information poses substantial risks due to misinformation. In response to these challenges, the Italian Association of Hospital Dermatologists (ADOI) has launched a nationwide survey titled "Use of Social Media by Dermatology Professionals: Impact on Public Awareness, Appropriateness of Information, and Correctness of Prevention Messages—An Italian Survey".
This initiative aims to analyze social media usage among dermatology professionals, evaluate its impact on public awareness and preventive behaviors, examine the appropriateness and correctness of shared information, identify challenges and opportunities, and assess the need for official guidelines supported by ADOI. The importance of this study lies in its potential to enhance public health outcomes by ensuring that information shared on social media is accurate, evidence-based, and ethically presented.
By collecting data-driven insights, the survey seeks to inform the development of professional guidelines, promote responsible digital engagement, and improve patient education and outcomes. Addressing ethical and privacy concerns is also a key objective. The participation of dermatology professionals is crucial in shaping the future of dermatological care and public health education. This initiative represents a critical step toward improving the quality of dermatological information available on social media and ultimately enhancing patient outcomes through better-informed patients and earlier interventions.
Procedure di indagine prenatale: significato diagnostico e pericolosità
Authors: Loverro G. , Selvaggi L. , Boscia F.M.
Published: November 2024

Not available
In ricordo del Prof. Attilio Romanini
Authors: Galli Guido
Published: November 2024

Not available.
Random walks and contracting elements II: Translation length and quasi-isometric embedding
Authors: Choi Inhyeok
Published: November 2024

Continuing from Choi (2022), we study random walks on metric spaces with contracting elements. We prove that random subgroups of the isometry group of a metric space are quasi-isometrically embedded into the space. We discuss this problem in two ways, namely in the sense of random walks and counting problem. We also establish the genericity of contracting elements and the central limit theorem and its converse for translation length.
Free metabelian groups are permutation stable
Authors: Ishikura Hiroki
Published: November 2024

We prove that all finitely generated free metabelian groups are permutation stable by verifying that all invariant random subgroups of them are co-sofic. This partially answers to the question asked by Levit and Lubotzky whether all finitely generated metabelian groups are permutation stable. Our proof extends the range of application of Levit and Lubotzky’s method, which is used to show permutation stability of permutational wreath products of finitely generated abelian groups, to non-split and non-permutational metabelian groups.
Curtain characterization of sublinearly Morse geodesics in $\mathrm{CAT}(0)$ spaces
Authors: Vest Elliott
Published: November 2024

We show that the sublinear Morse boundary of every

\operatorname{CAT}(0)

space continuously injects into the Gromov boundary of a hyperbolic space, which was not previously known even for all

\operatorname{CAT}(0)

cube complexes. Our work utilizes the curtain machinery introduced by Petyt, Spriano, and Zalloum. Curtains are more general combinatorial analogues of hyperplanes in cube complexes, and we develop multiple curtain characterizations of the sublinear Morse property along the way. Our results answer multiple questions of Petyt, Spriano, and Zalloum.
Global bifurcation for monotone fronts of elliptic equations
Authors: Chen Robin Ming , Walsh Samuel , Wheeler Miles H.
Published: November 2024

We present two results on global continuation of monotone front-type solutions to elliptic PDEs posed on infinite cylinders. This is done under quite general assumptions, and in particular applies even to fully nonlinear equations as well as quasilinear problems with transmission boundary conditions. Our approach is rooted in the analytic global bifurcation theory of Dancer (1973) and Buffoni–Toland (2003), but extending it to unbounded domains requires contending with new potential limiting behavior relating to loss of compactness. We obtain an exhaustive set of alternatives for the global behavior of the solution curve that is sharp, with each possibility having a direct analogue in the bifurcation theory of second-order ODEs.As a major application of the general theory, we construct global families of internal hydrodynamic bores. These are traveling front solutions of the full two-phase Euler equation in two dimensions. The fluids are confined to a channel that is bounded above and below by rigid walls, with incompressible and irrotational flow in each layer. Small-amplitude fronts for this system have been obtained by several authors. We give the first large-amplitude result in the form of continuous curves of elevation and depression bores. Following the elevation curve to its extreme, we find waves whose interfaces either overturn (develop a vertical tangent) or become exceptionally singular in that the flow in both layers degenerates at a single point on the boundary. For the curve of depression waves, we prove that either the interface overturns or it comes into contact with the upper wall.
Невольтерровость одного класса компактных операторов
Authors: Biyarov Bazarkan Nuroldinovich
Published: November 2024

Авторы Мацаев и Могульский выделили широкий класс слабых возмущений положительного компактного оператора $H$, не имеющих ненулевое собственное значение, т.е. являющихся вольтерровыми. Под слабым возмущением положительного оператора $H$ понимаем оператор вида $H(I+S)$, где $S$ - такой компактный оператор, что $I+S$ непрерывно обратим. С другой стороны, такие слабые возмущения обладают полной системой корневых векторов, если самосопряженный оператор $H$ принадлежит классу Неймана-Шаттена. В данной статье мы рассматриваем компактные операторы $A$, представимые как сумма двух компактных операторов $A=C+T$ (т.е. $A$ не обязательно является слабым возмущением), где $C$ - положительный оператор. В настоящей статье доказаны теоремы существования ненулевых собственных значений для таких операторов.
Известно, что задачи Коши для дифференциальных уравнений, как правило, являются корректными вольтерровыми задачами. Но пример Адамара показывает, что задача Коши для уравнения Лапласа некорректна. До сих пор не известно ни одного вольтеррового корректного сужения или расширения для уравнения эллиптического типа. Таким образом, возникает следующий вопрос: "существует ли вольтерровое корректное сужение максимального оператора $\widehat{L}$ или вольтерровое корректное расширение минимального оператора $L_0$, порожденного уравнениями эллиптического типа?" Полученные абстрактные теоремы существования собственных значений дают, что широкий класс корректных сужений максимального оператора $\widehat{L}$ и широкий класс корректных расширений минимального оператора $L_0$, порожденный уравнениями эллиптического типа не может быть вольтерровым. Более того, в двумерном случае доказано, что для оператора Лапласа вовсе нет вольтерровых корректных сужений и расширений.
Библиография: 14 названий.
Проблема суммируемости ряда Паули-Йордана-Дирака в пространстве Минковского
Authors: Karatsuba Ekatherina Anatol'evna
Published: November 2024

Исследуются свойства антикоммутатора Паули-Йордана-Дирака квантовой теории поля свободных электронов Дирака в дискретном представлении в пространственно трехмерном случае. Устанавливаются условия сходимости ряда Паули-Йордана-Дирака.
Библиография: 23 названия.
О множителях Вейля для безусловной сходимости рядов по системам Чисельского
Authors: Gevorkyan Gegham Grigor'evich
Published: November 2024

Доказывается, что неубывающая последовательность положительных чисел $\omega_n$ является множителем Вейля для безусловной сходимости п.в. рядов по системам Чисельского тогда и только тогда, когда выполняется неравенство $\sum_{n=1}^{\infty}(n\omega_n)^{-1}<\infty$.
Библиография: 15 названий.
Estimating prognosis of gastric neuroendocrine neoplasms using machine learning: A step towards precision medicine
Authors: Wang Hong-Niu , An Jia-Hao , Zong Liang
Published: November 2024

Survival rates following radical surgery for gastric neuroendocrine neoplasms (g-NENs) are low, with high recurrence rates. This fact impacts patient prognosis and complicates postoperative management. Traditional prognostic models, including the Cox proportional hazards (CoxPH) model, have shown limited predictive power for postoperative survival in gastrointestinal neuroectodermal tumor patients. Machine learning methods offer a unique opportunity to analyze complex relationships within datasets, providing tools and methodologies to assess large volumes of high-dimensional, multimodal data generated by biological sciences. These methods show promise in predicting outcomes across various medical disciplines. In the context of g-NENs, utilizing machine learning to predict survival outcomes holds potential for personalized postoperative management strategies. This editorial reviews a study exploring the advantages and effectiveness of the random survival forest (RSF) model, using the lymph node ratio (LNR), in predicting disease-specific survival (DSS) in postoperative g-NEN patients stratified into low-risk and high-risk groups. The findings demonstrate that the RSF model, incorporating LNR, outperformed the CoxPH model in predicting DSS and constitutes an important step towards precision medicine.
Unraveling the role of cancer-associated fibroblasts in colorectal cancer
Authors: Cui Jia-Yu , Ma Jing , Gao Xin-Xin , Sheng Zhi-Mei , Pan Zi-Xin , Shi Li-Hong , Zhang Bao-Gang
Published: November 2024

Within the intricate milieu of colorectal cancer (CRC) tissues, cancer-associated fibroblasts (CAFs) act as pivotal orchestrators, wielding considerable influence over tumor progression. This review endeavors to dissect the multifaceted functions of CAFs within the realm of CRC, thereby highlighting their indispensability in fostering CRC malignant microenvironment and indicating the development of CAFs-targeted therapeutic interventions. Through a comprehensive synthesis of current knowledge, this review delineates insights into CAFs-mediated modulation of cancer cell proliferation, invasiveness, immune evasion, and neovascularization, elucidating the intricate web of interactions that sustain the pro-tumor metabolism and secretion of multiple factors. Additionally, recognizing the high level of heterogeneity within CAFs is crucial, as they encompass a range of subtypes, including myofibroblastic CAFs, inflammatory CAFs, antigen-presenting CAFs, and vessel-associated CAFs. Innovatively, the symbiotic relationship between CAFs and the intestinal microbiota is explored, shedding light on a novel dimension of CRC pathogenesis. Despite remarkable progress, the orchestrated dynamic functions of CAFs remain incompletely deciphered, underscoring the need for continued research endeavors for therapeutic advancements in CRC management.
Risk factors for hepatocellular carcinoma in cirrhosis: A comprehensive analysis from a decade-long study
Authors: Zhou Da-Qiong , Liu Jiang-Yu , Zhao Feng , Zhang Jing , Liu Li-Li , Jia Jian-Ru , Cao Zhen-Huan
Published: November 2024

BACKGROUND

Cirrhosis is a significant risk factor for the development of hepatocellular carcinoma (HCC). Variability in HCC risk among patients with cirrhosis is notable, particularly when considering the diverse etiologies of cirrhosis.

AIM

To identify specific risk factors contributing to HCC development in patients with cirrhosis.

METHODS

This retrospective study analyzed data from cirrhotic patients at Beijing Youan Hospital from January 1, 2012 to September 30, 2022 with at least 6 mo of follow-up. Patient demographics, medical histories, etiologies, and clinical characteristics were examined. Cox regression analysis was used to analyze correlations of the above parameters with hepatocarcinogenesis, while competing risk regression was used to estimate their adjusted hazard ratios accounting for death. The cumulative incidence was plotted over time.

RESULTS

Overall, 5417 patients with cirrhosis (median age: 54 years; 65.8% males) were analyzed. Hepatitis B virus (HBV) was the most common etiology (23.3%), with 25% (n = 1352) developing HCC over a 2.9-year follow-up period. Patients with multiple etiologies had the HCC highest incidence (30.3%), followed by those with HBV-related cirrhosis (29.5%). Significant risk factors included male sex, advanced age, hepatitis C virus (HCV) infection, elevated blood ammonia, and low platelet count. Men had a higher 5-year HCC risk than women (37.0% vs 31.5%). HBV, HCV, and HBV/HCV co-infected patients had 5-year risks of HCC of 45.8%, 42.9%, and 48.1%, respectively, compared to 29.5% in nonviral hepatitis cases, highlighting the significant HCC risk from viral hepatitis, especially HBV, and underscores the importance of monitoring these high-risk groups.

CONCLUSION

In conclusion, HBV-related cirrhosis strongly correlates with HCC, with male sex, older age, viral hepatitis, elevated blood ammonia, and lower albumin and platelet levels increasing the risk of HCC.
Vitamin D 1,25-Dihydroxyvitamin D3 reduces lipid accumulation in hepatocytes by inhibiting M1 macrophage polarization
Authors: Luo Wen-Jing , Dong Xian-Wen , Ye Hua , Zhao Qiao-Su , Zhang Qiu-Bo , Guo Wen-Ying , Liu Hui-Wei , Xu Feng
Published: November 2024

BACKGROUND

Non-alcoholic fatty liver disease (NAFLD), which is a significant liver condition associated with metabolic syndrome, is the leading cause of liver diseases globally and its prevalence is on the rise in most nations. The protective impact of vitamin D on NAFLD and its specific mechanism remains unclear.

AIM

To examine the role of vitamin D in NAFLD and how vitamin D affects the polarization of hepatic macrophages in NAFLD through the vitamin D receptor (VDR)-peroxisome proliferator activated receptor (PPAR)γ pathway.

METHODS

Wild-type C57BL/6 mice were provided with a high-fat diet to trigger NAFLD model and administered 1,25-dihydroxy-vitamin D [1,25(OH)2D3] supplementation. 1,25(OH)2D3 was given to RAW264.7 macrophages that had been treated with lipid, and a co-culture with AML12 hepatocytes was set up. Lipid accumulation, lipid metabolism enzymes, M1/M2 phenotype markers, proinflammatory cytokines and VDR-PPARγ pathway were determined.

RESULTS

Supplementation with 1,25(OH)2D3 relieved hepatic steatosis and decreased the proinflammatory M1 polarization of hepatic macrophages in NAFLD. Administration of 1,25(OH)2D3 suppressed the proinflammatory M1 polarization of macrophages induced by fatty acids, thereby directly relieving lipid accumulation and metabolism in hepatocytes. The VDR-PPARγ pathway had a notable impact on reversing lipid-induced proinflammatory M1 polarization of macrophages regulated by the administration of 1,25(OH)2D3.

CONCLUSION

Supplementation with 1,25(OH)2D3 improved hepatic steatosis and lipid metabolism in NAFLD, linked to its capacity to reverse the proinflammatory M1 polarization of hepatic macrophages, partially by regulating the VDR-PPARγ pathway. The involvement of 1,25(OH)2D3 in inhibiting fatty-acid-induced proinflammatory M1 polarization of macrophages played a direct role in relieving lipid accumulation and metabolism in hepatocytes.
Wire, Electric, Polyvinyl Chloride Insulated, Copper or Copper Alloy
Authors:   AE-8D Wire and Cable Committee
Published: November 2024

This specification covers polyvinyl chloride insulated single conductor electric wires made with tin-coated copper conductors or silver-coated copper alloy conductors. The polyvinyl chloride insulation of these wires may be used alone or in combination with other insulating or protective materials.
Hydraulic Power Pump Test Procedure
Authors:   CTTC C1, Hydraulic Systems
Published: November 2024

This test code describes tests for determining characteristics of hydraulic positive displacement pumps used on off-road self-propelled work machines as referenced in SAE J1116.
Gustav Mahler: perilegomena k izvajanju njegovih simfonij št. 1–7
Authors: Lajovic Uroš
Published: November 2024

Edinstvenost pričujočega dela je v pri­stopu, ki na svojevrsten način odstira vpogled na eni strani v Mahlerjevo de­lavnico, v kontekst njegovega ustvarja­nja, na drugi strani pa v razumevanje in interpretiranje njegovih del skupaj s poglavitnimi potezami interpretacijske zgodovine, ki opredeljujejo tudi naše današnje sprejemanje in razumevanje skladateljevega samosvojega ustvar­jalnega pristopa. Branje tega dela je namenjeno intenzivne­mu soočenju s Mahlerjevimi simfoni­jami, detajliranemu uvidu v posamezne vsebinske in strukturne poudarke, raz­odeva navzkrižne reference, opozarja na skrite poudarke in zanke ter se lo­teva njihove natančne večplastne raz­člembe. V knjigi najdemo razlago Ma­hlerjevih artikulacijskih znakov, cezur, lokov pod vezajem ipd.
Nutritional assay and growth performance of West African dwarf goats fed with fresh, wilted and ensiled cassava leaves-based diet
Authors: Olalere G.C. , Iriso B.V. , Ejimevwo J.R. , Etela I.
Published: November 2024

The study was carried out to evaluate the in vitro digestibility and growth performance of West African dwarf goats fed with fresh cassava leaves + concentrate mixture, wilted cassava leaves + concentrate mixture and ensiled cassava leaves + concentrate mixture. Six goats were allotted to three treatment groups with two goats per treatment for eight weeks in a completely randomized design. Ensiling of the cassava leaves was done for 21 days and wilting of the leaves was done for 2 days on a concrete floor. There were significant differences (p < 0.05) amongst the values of the chemical composition of cassava leaves. Macro and micro mineral profile differed significantly across treatments (p < 0.05) and values were within the normal range for cassava leaves. The results obtained showed significant (p < 0.05) differences on total weight gain across the treatments. Goats fed wilted cassava leaves + concentrate mixture had the highest weight gain. The values for the post in vitro gas production parameters were significantly different (p < 0.05). Ensiled cassava leaves produced the highest methane gas volume (14.67±2.2 ml) during 24 h of incubation, while, wilted cassava leaves recorded the least gas volume (10.00±2.2 ml). Reduction in methane was highest in wilted cassava leaves (20.00±12.8%) and lowest in fresh cassava leaves (20.00±12.8%). The results showed that wilted and ensiled cassava leaves can promote growth performance and will ameliorate the negative impact of methane emission from West African dwarf goats for sustainable livestock production.
Studies on the taxonomic characteristics of Cythula prostrata (L.) Blume (Amaranthaceae)
Authors: Wahua C. , Durukwuaku A.
Published: November 2024

Cythula prostrata (L.) Blume is used in tradomedicine for calming and treating heart palpitation, and as animal feeds in Nigeria. It is a potential vegetable for health needs. This report highlights the morphological and anatomical properties, and phytochemical analysis of C. prostrata which belongs to the family Amaranthaceae. It is an annual trailing to semi erect, severally branched weed attaining up to a height of 55 ± 35 cm. The samples were fixed in standard fixative (Formaldehyde Glacial Acetic acid Alcohol in the ratio of 1:1:18) and standard methods were used for the epidermal, anatomical and phytochemical properties. The results revealed presence of anomocytic stomata which are amphistomatic, numerous specs of calcium oxalate crystals in epidermal cells, glandular and uniseriate trichomes. Alkaloids, tannins, saponins, flavonoids, Cardiac glycosides and steroids are observed present, except that flavonoid was absent in the crude extract but present in the ethanol extract. This information would assist in improving already existing knowledge of the plant.
Agricultural entrepreneurship education and youth development: a case study of graduates of higher institutions in South-East, Nigeria
Authors: Chah J.M , Okoronkwo C.D. , Obazi S.A. , Dimelu M.U.
Published: November 2024

This study assessed agricultural entrepreneurship education and youth development among graduates of higher institutions in Southeast Nigeria. Data were collected from 123 corps members proportionately selected in a multistage procedure. The tool used for data collection was questionnaire and the data were presented in percentage, mean score, and bar charts. Some corps members favourably perceived that there are good opportunities in Nigeria to start up own agricultural business enterprise while others perceived agriculture as a high-risk enterprise. Skills acquired from the programme include communication, team work, and interpersonal skills. Respondents showed dissatisfaction in the proportion of theory to practical exposure, feedback mechanism employed by resource persons and learning environment. Only 52% of the corps members indicated intention for agricultural entrepreneurship. Respondents’ intention varied with the personal, demographic and institutional factors. Government should provide and support follow-up trainings for graduates with interest and strong aspiration for entrepreneurship in agriculture.
Farmer’s willingness to adopt bamboo (Bambusa vulgaris) in agroforestry along selected areas in Ido Local Government Area, Oyo State, Nigeria
Authors: Okanlawon F.B. , Olaoye K.O. , Badmus M.O. , Ogunbamowo P.O. , Areo O.S. , Adelusi F.T.
Published: November 2024

This study was carried out to investigate the adoption of Bambusa vulgaris in agro-forestry practices along  some selected farms in Ido Local Government Area of Ibadan, Oyo State, Nigeria. A simple random sampling method was used, while 50 pieces of semi-structured interview schedule were randomly administered among agro-forestry farmers in the local government area. The data collected was analysed using SPSS version 20 and was presented using Tables, Pie charts, and Bar charts. The results indicate that farming practices in the study area are predominantly male-dominated (90.0%) and at their prime and active age (86.0%) with little or no formal education (54.0%) coupled with marital responsibility (100.0%). The majority (86.0%) of the access to land ownership for the agro- forestry farmers was mostly communal and owned showing family attributes still exist. The regular farming method adopted there is basically to feed their family (60.0%) and to generate income from sale of products (40.0%) and this has been on for between 0-21 years but their willingness to adopt agro-forestry was observed (100.0%), while citing access to fertilizer was seen as a major problem. But adoption of agro-forestry farming was made to be seen as a means in this study as indicative of soil fertility. There is an indication that most of the farmers (83.0%) have either planted Bamboo before or seen people use it for several other purposes apart from agroforestry hence the adoption of Bamboo for agroforestry farming must be given an urgent attention so as to provide income and ecological stability.
The place of literature review in environmental management research
Authors: Yusuf Farouk Idi
Published: November 2024

Environment management is a multifaced field that encompasses a wide range of issues, from pollution control to sustainability. To effectively manage the environment, a comprehensive understanding of relevant scientific literature is essential for researchers and professionals to explore, assess and consolidate the existing information related to the subject; without which researchers may end of repeating same studies over and over again. Literature review serves as a foundational tool for achieving this goal. It helps to gain a thorough understanding of the current state of knowledge and build on previous research to advance scientific understanding in environmental management. This paper, reviewed many articles from reliable secondary data and explore the importance of literature review in Environmental Management research. The result discusses several applications of types of literature review in Environmental management, the purpose and qualities of literature review in Environmental Management, and the steps in outlining and drafting literature review including selecting appropriate sources, evaluating the quality of the sources, synthesizing the information. The study further explores ways of finding research gap and some important online assisted tools such as Mendeley, Zotero, Scite, PaperPal and Litmap among others.