Classical Type Research Articles

Weak monotonicity property of Korevaar-Schoen norms on nested fractals

In this paper, we study the weak monotonicity property of Korevaar-Schoen (p-energy) norms on nested fractals for 1<p<∞. Such property has many important applications on fractals and other metric measure spaces, such as constructing p-energies (when p=2 this is basically a Dirichlet form), generalizing the classical Sobolev type inequalities and the celebrated Bourgain-Brezis-Mironescu convergence.

Restoration of military courts as a component of state governance of the judicial system of Ukraine

The article highlights the issue of restoration of military courts as a component of public administration of the judiciary of Ukraine. The author examines the activities of military courts on the territory of Ukraine prior to their liquidation, and also studies the works of scholars and legislative initiatives on the restoration of military courts. It is found that the liquidation of military courts had negative consequences and could have been avoided by reforming them in accordance with the existing needs. The author establishes that the current administration of justice in the field of military offenses by courts without appropriate specialization is ineffective, and the reasons for this situation are identified. The author substantiates the urgent need to restore military courts in Ukraine and the ways of such restoration. Based on the analysis of existing legislative initiatives, the author shows that they are progressive, but at the same time points out the need to adopt a significant number of legislative acts and allocate adequate funding for the restoration of military courts. The author proves the need to restore military courts of a “mixed” type and the practical impossibility of restoring the previously existing classical type of military courts. It is stated that the public administration of the judicial system of Ukraine, in particular, in terms of restoring military courts, is not effective enough, and the author suggests ways to improve it, taking into account the realities of today and the experience of other states.

Thymoquinone as an electron transfer mediator to convert Type II photosensitizers to Type I photosensitizers

The development of Type I photosensitizers (PSs) is of great importance due to the inherent hypoxic intolerance of photodynamic therapy (PDT) in the hypoxic microenvironment. Compared to Type II PSs, Type I PSs are less reported due to the absence of a general molecular design strategy. Herein, we report that the combination of typical Type II PS and natural substrate carvacrol (CA) can significantly facilitate the Type I pathway to efficiently generate superoxide radical (O2–•). Detailed mechanism study suggests that CA is activated into thymoquinone (TQ) by local singlet oxygen generated from the PS upon light irradiation. With TQ as an efficient electron transfer mediator, it promotes the conversion of O2 to O2–• by PS via electron transfer-based Type I pathway. Notably, three classical Type II PSs are employed to demonstrate the universality of the proposed approach. The Type I PDT against S. aureus has been demonstrated under hypoxic conditions in vitro. Furthermore, this coupled photodynamic agent exhibits significant bactericidal activity with an antibacterial rate of 99.6% for the bacterial-infection female mice in the in vivo experiments. Here, we show a simple, effective, and universal method to endow traditional Type II PSs with hypoxic tolerance.

Continuous investigation of the nasal cycle over 48 hours.

Previous results on the nasal cycle refer to measurements over up to 24h. The long-term rhinoflowmetry (LRFM) allows continuous observations over a longer period. The aim of the study was to observe the nasal cycle for the first time over 48h under everyday conditions. The LRFM was continuously applied to 30 rhinologically healthy subjects (20 female, 10 male) over 48h. The different types of nasal cycle were classified as follows: "classic", "in concert", "one-sided", "no-cycle" and "mixed". The focus of this study was on the results over the entire 48 hours. The comparison of the two consecutive days was also made. A nasal cycle could be detected in 100% of the subjects over 48h. With 97%, the mixed type most commonly occurred as a combination of classical and in concert components. In all subjects, classical cycle components could be detected at least once. The no-cycle type was not observed. In the awake state, the mixed type dominated (80%), as a combination of classical and in concert parts. In the sleep state, the classical type was the most common type (97%). The average phase duration was 206 +- 83 minutes. In the very first continuous 48-hour study on the nasal cycle, 100% of the subjects presented a nasal cycle. The LRFM method is the only one that offers the possibility to perform continuous measurements over a longer period during daily routine. The results of previous single-stage examination methods should thus be questioned.

Real-world data analysis of first-line targeted therapy for patients with non-small cell lung cancer with different EGFR mutation status in a tertiary care hospital.

e20586 Background: Lung cancer is still the malignant tumor with the highest incidence and mortality rate in the world, of which non-small cell lung cancer (NSCLC) accounts for about 85%. The EGFR mutation rate in Asians is 30%-60%, with exon 19 deletion mutations and exon 21 L858R point mutations accounting for about 90% of EGFR mutations, which are the classic EGFR mutation types. The two have significant differences in clinical characteristics, and some clinical trials have shown differences in efficacy between different subgroups, but whether they exist in the real world needs to be further confirmed. Meanwhile, the efficacy of first-line targeted therapy in patients with coexisting mutant NSCLC harboring different EGFR classical mutations and whether there is a difference in different subgroups has not been conclusively determined. Methods: To collect general clinical data and their genetic test reports of NSCLC patients diagnosed with gene mutations who attended the Affiliated Hospital of North Sichuan Medical College from January 2019 to December 2021 for follow-up, with a follow-up date of June 30,2023, as the end date. Kaplan-Meier survival analysis and log-rank test were applied to compare:1)the median PFS in different subgroups of patients with no co-mutation classic EGFR mutation;2)the median PFS in patients with co-mutation classic EGRR mutation and no co-mutation classic EGFR mutation;3)the median PFS in different subgroups of patients with no co-mutation 19-Del/L858R and with co-mutation 19-Del/L858Rpatients;4)median PFS of patients between co-mutated 19-Del and L858R subgroups. Results: The median PFS of 19Del was significantly better than that of L858R in different subgroups of EGFR classical mutations (14.0 months vs. 8.1 months, p = 0.004 &lt; 0.05). The median PFS of EGFR classical mutation was significantly better than that of EGFR classical mutation with co-mutation,11.1months vs. 5.8 months, respectively, p &lt; 0.001. In different subgroups,19Del median PFS was superior to 19Del co-mutation (14.0 months vs. 6.1 months, p = 0.001 &lt; 0.05),and L858R median PFS was superior to L858R co-mutation (8.1 months vs. 5.8 months, p = 0.449 &gt; 0.05). 19Del co-mutation and L858R co-mutation median PFS were not observed in the analysis of the same simple 19del first-line targeted therapy survival benefit was significantly better than the similar survival benefit of L858R, whose median PFS was 6.1 months vs. 5.8 months, respectively, p = 0.449&gt;0.05, the difference was not statistically significant. Conclusions: The survival benefit of first-line targeted therapy for 19Del in the real world is superior to that of L858R, while the clinical benefit of first-line targeted therapy is poor for classical mutations in EGFR with co-mutations, and combinations with other therapeutic modalities should be considered.

Morusin Inhibits RANKL-induced Osteoclastogenesis and Ovariectomized Osteoporosis.

Postmenopausal osteoporosis (PMOP) is a classic type of osteoporosis that has gradually become a significant health problem worldwide. There is an urgent need for a safe alternative therapeutic agent considering the poor therapeutic strategies currently available for this disease. The roots and bark of the Morus australis tree (Moraceae) are used to make a traditional Chinese medicine known as "Morusin", and accumulating evidence has demonstrated its multiple activities, such as anti-inflammatory and anti-tumor effects. In this study, we aim to explore the effect of Morusin on mouse osteoclasts and its mechanism. In this study, we explored the inhibitory effects of Morusin on murine osteoclasts in vitro and its mechanism, and the protective effect of Morusin on an ovariectomy (OVX)-induced osteoporosis model in vivo. The results showed that Morusin prevented OVX-induced bone loss and dramatically decreased RANKL-induced osteoclastogenesis. Morusin interfered with RANKL-activated NF- κB, MAPK, and PI3K/AKT signaling pathways. The expression of three master factors that control osteoclast differentiation, c-Fos, NFATc1, and c-Jun, was reduced by Morusin treatment. Collectively, in vitro results indicated that Morusin has a protective effect on OVX-induced bone loss in a mouse model. Our data provide encouraging evidence that Morusin may be an effective treatment for PMOP.

The transition from indirect band gap to direct band gap and effectively separating of electron-hole pairs in h-BC2N / MoSi2N4 heterojunction for photocatalytic water splitting

To improve the photocatalytic efficiency of MoSi2N4, we decided to use the organic material h-BC2N to form a new photocatalytic heterojunction, h-BC2N/MoSi2N4. Firstly, we calculated the phonon spectra of h-BC2N, MoSi2N4, and h-BC2N/MoSi2N4 heterojunction to determine their dynamical stability. Next, using the HSE06 density functional theory method, we calculated the band structures and DOS of h-BC2N, MoSi2N4, and h-BC2N/MoSi2N4 heterojunction to determine their band structures and types. To analyze the electron transfer in the h-BC2N/MoSi2N4 heterojunction, we calculated the work function and differential charge density to determine the direction of the built-in electric field and the electron transfer between h-BC2N and MoSi2N4. Furthermore, we discussed the interaction between h-BC2N and MoSi2N4, and the results showed that the VBM and CBM of h-BC2N and MoSi2N4 changed with the formation of the heterojunction. Then, we analyzed the reaction mechanism of the h-BC2N/MoSi2N4 heterojunction and found that the built-in electric field promotes the electron transition from the CBM of MoSi2N4 to the VBM of h-BC2N, effectively separating the photo-generated electron-hole pairs of MoSi2N4 in space, making h-BC2N/MoSi2N4 heterojunction a classical Type Z heterojunction. These results suggest that h-BC2N/MoSi2N4 heterojunction can improve the photocatalytic efficiency of MoSi2N4.

A modified Green-Naghdi fractional order model for analyzing thermoelectric MHD

PurposeWhereas, the classical Green-Naghdi Type II (GN-II) model struggles to accurately represent the thermo-mechanical behavior of thermoelectric MHD due to its inability to account for the memory effect. A new mathematical model of the GN-II theory incorporates a fractional order of heat transport to address this issue.Design/methodology/approachThe employment of the matrix exponential method, which forms the basis of the state-space approach in contemporary theory, is central to this strategy. The resulting formulation, together with the Laplace transform techniques, is applied to a variety of problems. Solutions to a thermal shock problem and to a problem of a layer media both without heat sources are obtained. Also, a problem with the distribution of heat sources is considered. The numerical technique is used to achieve the Laplace transform inversion.FindingsAccording to the numerical results and its graphs, the influences of the fractional order parameters, figure-of-merit factor, thermoelectric power and Peltier coefficient on the behavior of the field quantities are investigated in the new theory.Originality/valueThe new modeling of thermoelectric MHD has advanced significantly as a result of this work, providing a more thorough and precise tool for forecasting the behavior of these materials under a range of thermal and magnetic conditions.

Kranz anatomical and biochemical characterization of C4 photosynthesis in an aphyllous shrub Calligonum comosum (Polygonaceae)

Calligonum is a shrubby and aphyllous C4 eudicot lineage, employing green cylindrical shoots for carbon acquisition; however, comprehensive assessments of C4 photosynthesis within the genus are limited. One species, C. comosum, grows in Jordan, offering an opportunity for evaluating features of C4 photosynthesis in Calligonum. Light microscopy showed that C. comosum exhibits a variation of the classical salsoloid Kranz type (Calligonum variant). Transmission electron microscopy revealed traits typical of the NAD-malic enzyme (NAD-ME) subtype. Bundle sheath cells had numerous large mitochondria and mitochondria:chloroplast ratios were greater than those of mesophyll cells. Moreover, bundle sheath chloroplasts had developed grana, whereas mesophyll chloroplasts were deficient of grana. Enzyme activity and western blotting further supported NAD-ME as the principal decarboxylase. Immunolocalization of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), phosphoenolpyruvate carboxylase (PEPC) and pyruvate-phosphate dikinase (PPdK) showed strict intercellular compartmentation patterns, with Rubisco confined to bundle sheath and PEPC and PPdK to mesophyll. Labeling for PEPC was observed in both the mesophyll and hypodermis, while PPdK was restricted to the mesophyll. We suggest classifying C. comosum as a NAD-ME subtype C4 species and propose a mechanism of C4 photosynthesis, suggesting a tractable C4 model for further insights and studies on the biochemical intricacy of C4 photosynthesis.

Beyond the Classical Type I Error: Bayesian Metrics for Bayesian Designs Using Informative Priors

There is growing interest in Bayesian clinical trial designs with informative prior distributions, for example for extrapolation of adult data to pediatrics, or use of external controls. While the classical Type I error is commonly used to evaluate such designs, it cannot be strictly controlled and it is acknowledged that other metrics may be more appropriate. We focus on two common situations—borrowing control data or information on the treatment contrast—and discuss several fully probabilistic metrics to evaluate the risk of false positive conclusions. Each metric requires specification of a design prior, which can differ from the analysis prior and permits understanding of the behavior of a Bayesian design under scenarios where the analysis prior differs from the true data generation process. The metrics include the average Type I error and the pre-posterior probability of a false positive result. When borrowing control data, our empirical cases demonstrate that the average Type I error is asymptotically controlled (in certain cases strictly) when the analysis and design prior coincide. We illustrate use of these Bayesian metrics with real applications, and discuss how they could facilitate discussions between sponsors, regulators and other stakeholders about the appropriateness of Bayesian borrowing designs for pivotal studies.

TIMP-1 is an activator of MHC-I expression in myeloid dendritic cells with implications for tumor immunogenicity

Immune checkpoint therapies (ICT) for advanced solid tumors mark a new milestone in cancer therapy. Yet their efficacy is often limited by poor immunogenicity, attributed to inadequate priming and generation of antitumor T cells by dendritic cells (DCs). Identifying biomarkers to enhance DC functions in such tumors is thus crucial. Tissue Inhibitor of Metalloproteinases-1 (TIMP-1), recognized for its influence on immune cells, has an underexplored relationship with DCs. Our research reveals a correlation between high TIMP1 levels in metastatic melanoma and increased CD8 + T cell infiltration and survival. Network studies indicate a functional connection with HLA genes. Spatial transcriptomic analysis of a national melanoma cohort revealed that TIMP1 expression in immune compartments associates with an HLA-A/MHC-I peptide loading signature in lymph nodes. Primary human and bone-marrow-derived DCs secrete TIMP-1, which notably increases MHC-I expression in classical type 1 dendritic cells (cDC1), especially under melanoma antigen exposure. TIMP-1 affects the immunoproteasome/TAP complex, as seen by upregulated PSMB8 and TAP-1 levels of myeloid DCs. This study uncovers the role of TIMP-1 in DC-mediated immunogenicity with insights into CD8 + T cell activation, providing a foundation for mechanistic exploration and highlighting its potential as a new target for combinatorial immunotherapy to enhance ICT effectiveness.

Rigidity properties of holomorphic isometries into homogeneous Kähler manifolds

We prove two rigidity results on holomorphic isometries into homogeneous Kähler manifolds. The first shows that a Kähler-Ricci soliton induced by the homogeneous metric of the Kähler product of a special generalized flag manifold (i.e. a flag of classical type or integral type) with a bounded homogeneous domain is trivial, i.e. Kähler-Einstein. In the second one we prove that: (i) a flat space is not relative to the Kähler product of a special generalized flag manifold with a homogeneous bounded domain, (ii) a special generalized flag manifold is not relative to the Kähler product of a flat space with a homogeneous bounded domain and (iii) a homogeneous bounded domain is not relative to the Kähler product of a flat space with a special generalized flag manifold. Our theorems strongly extend the results of Cheng and Hao [Ann. Global Anal. Geom. 60 (2021), pp. 167–180], Cheng, Di Scala, and Yuan [Internat. J. Math. 28 (2017), p. 1750027], Loi and Mossa [Proc. Amer. Math. Soc. 149 (2021), pp. 4931–4941], Loi and Mossa [Proc. Amer. Math. Soc. 151 (2023), pp. 3975–3984] and Umehara [Tokyo J. Math. 10 (1987), pp. 203–214].

Holoprosencephaly: The Disease and Its Related Disabilities

AbstractHoloprosencephaly (HPE), the most prevalent developmental anomaly affecting the forebrain in humans, occurs in ∼1 in 16,000 liveborn neonates, with an incidence reaching 1 in 250 in conceptuses. This condition is distributed worldwide. HPE is etiologically heterogeneous, and its pathogenesis is variable. Environmental, teratogenic, genetic, or metabolic factors can contribute to the development of HPE. Notably, maternal insulin-dependent diabetes mellitus and maternal alcoholism are among the primary causative factors. HPE may be linked to various well-defined multiple malformation syndromes characterized by a normal karyotype, such as Smith–Lemli–Opitz's, Pallister–Hall's, or velocardiofacial syndrome. Alternatively, it can be associated with chromosomal abnormalities. (i.e., Patau's syndrome and, less frequently, Edwards' syndrome or Down's syndrome). The major genes implicated in HPE are SHH, ZIC2, SIX3, and TGIF. The range of HPE is extensive, covering diverse neuropathological phenotypes of varying severity. Three classical types of HPE can be distinguished in increasing order of severity: lobar HPE, characterized by separated right and left ventricles with some continuity across the frontal cortex; semilobar HPE, featuring a partial separation; and the most severe form, alobar HPE, where there is a single brain ventricle and the absence of an interhemispheric fissure. Additionally, there are other variations of HPE, ranging in severity, including the less severe interhemispheric median HPE (also known as middle interhemispheric variant). The phenotypic spectrum of HPE is highly extensive, encompassing severe cerebral malformations to microforms. Children with HPE often encounter numerous medical challenges; among them neurological disorders, craniofacial malformations, endocrine disorders, oral and motor dysfunction, and dysfunction of the autonomic nervous system. Neurologic problems, such as cerebral palsy and seizures, are common. The diagnosis of HPE is typically made prenatally, relying primarily on ultrasound and magnetic resonance imaging examinations. The prognosis for individuals with HPE is largely dependent on its underlying causes. Those with cytogenetic abnormalities, in particular, face a significantly poorer prognosis, with only 2% surviving beyond 1 year.

Proteomic Analysis of Idiopathic Nephrotic Syndrome Triggered by Primary Podocytopathies in Adults: Regulatory Mechanisms and Diagnostic Implications.

Idiopathic nephrotic syndrome (NS) is a heterogeneous group of glomerular disorders which includes two major phenotypes: minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). MCD and FSGS are classic types of primary podocytopathies. We aimed to explore the molecular mechanisms in NS triggered by primary podocytopathies and evaluate diagnostic value of the selected proteomic signatures by analyzing blood proteome profiling. Totally, we recruited 90 participants in two cohorts. The first cohort was analyzed using label-free quantitative (LFQ) proteomics to discover differential expressed proteins and identify enriched biological process in NS which were further studied in relation to clinical markers of kidney injury. The second cohort was analyzed using parallel reaction monitoring-based quantitative proteomics to verify the data of LFQ proteomics and assess the diagnostic performance of the selected proteins using receiver-operating characteristic curve analysis. Several biological processes (such as immune response, cell adhesion, and response to hypoxia) were found to be associated with kidney injury during MCD and FSGS. Moreover, three proteins (CSF1, APOC3, and LDLR) had over 90% sensitivity and specificity in detecting adult NS triggered by primary podocytopathies. The identified biological processes may play a crucial role in MCD and FSGS pathogenesis. The three blood protein markers are promising for diagnosing adult NS triggered by primary podocytopathies.

M6A-methylated Lonp1 drives mitochondrial proteostasis stress to induce testicular pyroptosis upon environmental cadmium exposure

Cadmium (Cd) is a widely distributed typical environmental pollutant and one of the most toxic heavy metals. It is well-known that environmental Cd causes testicular damage by inducing classic types of cell death such as cell apoptosis and necrosis. However, as a new type of cell death, the role and mechanism of pyroptosis in Cd-induced testicular injury remain unclear. In the current study, we used environmental Cd to generate a murine model with testicular injury and AIM2-dependent pyroptosis. Based on the model, we found that increased cytoplasmic mitochondrial DNA (mtDNA), activated mitochondrial proteostasis stress occurred in Cd-exposed testes. We used ethidium bromide to generate mtDNA-deficient testicular germ cells and further confirmed that increased cytoplasmic mtDNA promoted AIM2-dependent pyroptosis in Cd-exposed cells. Uracil-DNA glycosylase UNG1 overexpression indicated that environmental Cd blocked UNG-dependent repairment of damaged mtDNA to drive the process in which mtDNA releases to cytoplasm in the cells. Interestingly, we found that environmental Cd activated mitochondrial proteostasis stress by up-regulating protein expression of LONP1 in testes. Testicular specific LONP1-knockdown significantly reversed Cd-induced UNG1 protein degradation and AIM2-dependent pyroptosis in mouse testes. In addition, environmental Cd significantly enhanced the m6A modification of Lonp1 mRNA and its stability in testicular germ cells. Knockdown of IGF2BP1, a reader of m6A modification, reversed Cd-induced upregulation of LONP1 protein expression and pyroptosis activation in testicular germ cells. Collectively, environmental Cd induces m6A modification of Lonp1 mRNA to activate mitochondrial proteostasis stress, increase cytoplasmic mtDNA content, and trigger AIM2-dependent pyroptosis in mouse testes. These findings suggest that mitochondrial proteostasis stress is a potential target for the prevention of testicular injury.

Abstract PO3-08-11: Association between Histologic Variants and the Results of Multigene Testing in Patients with Hormone Receptor-positive, HER2-negative Invasive Lobular Cancer

Abstract Invasive lobular carcinoma (ILC), which accounts for approximately 5-15% of all breast cancers, can be divided into classic type and various other variants. Multigene testing (MGT) has prognostic value in hormone receptor (HR)-positive, HER2-negative breast cancer. We aimed to investigate the association between the results of MGT and histological variation of ILC. 1582 HR-positive, HER2-negative breast cancer patients treated between January 2014 and December 2022 were reviewed. Patients were divided into three groups; ILC-favorable group, ILC-unfavorable group and invasive ductal carcinoma (IDC) group. The ILC-favorable group consisted of classic and tubulolobular types, while the ILC-unfavorable group included pleomorphic, solid, signet ring cell, florid, and alveolar types according to the reported prognosis of each ILC variant. Among the various types of MGT, the 21-gene assay (OncotypeDX), the 70-gene assay (Mammaprint), and the 12-gene assay (Endopredict) assay were used in clinical setting. The median age of patients was 50 years (range 20-85 years). 75.5% of patients received the 21-gene assay, 12.8% received the 70-gene assay, and 11.6% received the 12-gene assay. The high-risk results in MGT were showed in 7.7% of 155 patients in ILC-favorable group, 26.1% of 23 patients in ILC-unfavorable group, and 20.9% of 1404 patients in IDC group (p-value &amp;lt; 0.001). In the multivariate logistic regression analysis, ILC-favorable group showed significantly lower odds of high-risk results compared to IDC group (OR=0.284, 95% CI; 0.147-0.548), while ILC-unfavorable group did not show any significant difference compared to IDC group (OR=0.797, 95% CI; 0.263-2.411). In comparison to IDC, the variants of ILC with favorable prognosis show lower rates of high-risk results in MGT, while the variants of ILC with poor prognosis do not differ significantly from IDC. For patients who diagnosed the variants of ILC with poor prognosis, MGT could be useful for prognosis prediction or treatment decision-making. Citation Format: Jee Hyun Ahn, Suk Jun Lee, Seung Hye Yang, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Byeong Woo Park, Seho Park. Association between Histologic Variants and the Results of Multigene Testing in Patients with Hormone Receptor-positive, HER2-negative Invasive Lobular Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-11.

Abstract PO3-20-11: Among the &amp;lt; 0.1 percent of breast cancers: A case of adenoid cystic carcinoma

Abstract Among the &amp;lt; 0.1 percent of breast cancers: A case of adenoid cystic carcinoma Sera Choi, B.A., Sarah Keshwani, M.D., Andrea Madrigrano, M.D. Introduction: Adenoid cystic carcinoma in the breast (ACCB) is a rare subtype of breast cancer that accounts for &amp;lt; 0.1% of all breast-related malignancies. The majority of ACCB cases in existing literature are comprised of estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 negative, abbreviated as triple-negative breast cancer. Although most triple negative breast cancers are aggressive in nature and prognosis, ACCB is reported to be more indolent with a favorable outcome. This disparity raises the question of whether the treatment approach for ACCB should follow the well-established treatment plan for other triple negative breast cancers given its atypical characteristics. Furthermore, while adenoid cystic carcinoma of the salivary glands is a well-known type of head and neck cancer with established treatment guidelines, there is limited data for recommendations regarding treatment for ACCB. We report a pathologically confirmed case of ACCB and review the existing literature regarding treatment strategy and prognosis. Case: This case is of a 69-year-old female who presented with an abnormal screening mammogram with a core needle biopsy confirming ACCB in the left lower outer quadrant. The patient was asymptomatic with no palpable masses, nipple discharge, or skin changes of the breast. Biopsy revealed adenoid cystic carcinoma grade 2, classic type, with immunochemistry confirming estrogen-receptor negative, progesterone-receptor negative, and human epidermal growth factor-receptor negative. After a thorough discussion of the options, the patient elected for breast conserving therapy and sentinel lymph node biopsy. Tumor was resected with negative margins and two out of two lymph nodes were negative for metastasis. The patient was recommended whole breast adjuvant radiation therapy given the large tumor size of 4.8cm. Chemotherapy was not recommended due to data that largely supports local targeted therapy over systemic treatment in patients without metastatic ACCB. The patient is continuing with routine follow-up evaluations. Discussion: Currently, mainstay treatment comprises of surgical resection with lumpectomy or mastectomy, with or without nodal evaluation. Radiation therapy is seen as beneficial in reducing recurrence and prolonging disease-free survival in ACCB. There is ongoing debate regarding the role of chemotherapy in ACCB patients, as triple-negative breast cancers are typically treated with a systemic chemotherapy regimen. However, since ACCB has a more favorable prognosis, the role of chemotherapy remains uncertain. With lack of data on ACCB, treatment modalities should be evaluated on a case-by-case basis. Moreover, considering the scarcity of information concerning this particular subtype of breast cancer, it is advisable to discuss these patients within a multi-disciplinary tumor board setting to ensure patients receive the maximum benefit. Citation Format: Sera Choi, Sarah Keshwani, Andrea Madrigrano. Among the &amp;lt; 0.1 percent of breast cancers: A case of adenoid cystic carcinoma [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-20-11.

Intranasal PAMAM-G3 scavenges cell-free DNA attenuating the allergic airway inflammation

Allergic airway inflammation (AAI), including allergic rhinitis (AR) and allergic asthma, is driven by epithelial barrier dysfunction and type 2 inflammation. However, the underlying mechanism remains uncertain and available treatments are constrained. Consequently, we aim to explore the role of cell-free DNA (cfDNA) in AAI and assess the potential alleviating effects of cationic polymers (CPs) through cfDNA elimination. Levels of cfDNA were evaluated in AR patients, allergen-stimulated human bronchial epithelium (BEAS-2B cells) and primary human nasal epithelium from both AR and healthy control (HC), and AAI murine model. Polyamidoamine dendrimers-generation 3 (PAMAM-G3), a classic type of cationic polymers, were applied to investigate whether the clearance of cfDNA could ameliorate airway epithelial dysfunction and inhibit AAI. The levels of cfDNA in the plasma and nasal secretion from AR were higher than those from HC (P < 0.05). Additionally, cfDNA levels in the exhaled breath condensate (EBC) were positively correlated with Interleukin (IL)-5 levels in EBC (R = 0.4191, P = 0.0001). Plasma cfDNA levels negatively correlated with the duration of allergen immunotherapy treatment (R = −0.4297, P = 0.006). Allergen stimulated cfDNA secretion in vitro (P < 0.001) and in vivo (P < 0.0001), which could be effectively scavenged with PAMAM-G3. The application of PAMAM-G3 inhibited epithelial barrier dysfunction in vitro and attenuated the development of AAI in vivo. This study elucidates that cfDNA, a promising biomarker for monitoring disease severity, aggravates AAI and the application of intranasal PAMAM-G3 could potentially be a novel therapeutic intervention for AAI.Allergen stimulates the secretion of cell-free DNA (cfDNA) in both human and mouse airway. Intranasal polyamidoamine dendrimers-generation 3 (PAMAM-G3) scavenges cfDNA and alleviates allergic airway inflammation.

Comparative genomic analysis provides insights into the genetic diversity and pathogenicity of the genus Brucella.

Some Brucella spp. are important pathogens. According to the latest prokaryotic taxonomy, the Brucella genus consists of facultative intracellular parasitic Brucella species and extracellular opportunistic or environmental Brucella species. Intracellular Brucella species include classical and nonclassical types, with different species generally exhibiting host preferences. Some classical intracellular Brucella species can cause zoonotic brucellosis, including B. melitensis, B. abortus, B. suis, and B. canis. Extracellular Brucella species comprise opportunistic or environmental species which belonged formerly to the genus Ochrobactrum and thus nowadays renamed as for example Brucella intermedia or Brucella anthropi, which are the most frequent opportunistic human pathogens within the recently expanded genus Brucella. The cause of the diverse phenotypic characteristics of different Brucella species is still unclear. To further investigate the genetic evolutionary characteristics of the Brucella genus and elucidate the relationship between its genomic composition and prediction of phenotypic traits, we collected the genomic data of Brucella from the NCBI Genome database and conducted a comparative genomics study. We found that classical and nonclassical intracellular Brucella species and extracellular Brucella species exhibited differences in phylogenetic relationships, horizontal gene transfer and distribution patterns of mobile genetic elements, virulence factor genes, and antibiotic resistance genes, showing the close relationship between the genetic variations and prediction of phenotypic traits of different Brucella species. Furthermore, we found significant differences in horizontal gene transfer and the distribution patterns of mobile genetic elements, virulence factor genes, and antibiotic resistance genes between the two chromosomes of Brucella, indicating that the two chromosomes had distinct dynamics and plasticity and played different roles in the survival and evolution of Brucella. These findings provide new directions for exploring the genetic evolutionary characteristics of the Brucella genus and could offer new clues to elucidate the factors influencing the phenotypic diversity of the Brucella genus.

Insight into Impacts of π-π Assembly on Phthalocyanine Based Heterogeneous Molecular Electrocatalysis.

Electrochemical CO2 reduction (CO2R) to feedstocks competes with the hydrogen evolution reaction (HER). Cobalt phthalocyanine (CoPc) immobilized onto carbon driven by π-π interaction represents a classical type of heterogeneous molecular catalyst for CO2R. However, the impacts of π conjugation on the electrocatalysis have not been clarified. Herein, the electrochemical properties of CoPc were investigated by comparison of its analogue to 2,3-naphthalocyanine cobalt (NapCo) having extended π conjugation. It is found that CoPc is redox-active on carbon to provide low oxidized Co sites for improving the CO2R activity and selectivity, while NapCo on carbon turned out to be redox-inert leading to lower performance. In addition, the redox-mediated mechanism for CO2R on CoPc tends to operate with increasing electrolyte alkalinity, which further enhances the reaction selectivity. We speculated that moderate π conjugation allows the redox-mediated mechanism on CoPc, which is critical to promote CO2R performance while depressing the competing HER.