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Purpose: To evaluate the efficacy of using a customized xenograft shell with a 1:1 mixture of particulate xenograft and autogenous bone for the reconstruction of horizontally deficient anterior maxillary alveolar ridges. Materials and Methods: CBCT images of the atrophic maxilla of eight patients were acquired and generated into 3D models. The data were transferred to a 3D printer for fabrication. During the surgery, xenograft blocks were manually sliced and customized on the 3D-printed models into bone shells. Then they were fixed to the atrophic site, and the gap was augmented with a 1:1 mixture of particulate xenograft and autogenous bone. Results: Clinical assessment showed no adverse effects; however, one patient exhibited wound dehiscence. The mean difference between the preoperative and 6-month postoperative CBCTs showed a net average bone gain of 4.06 mm at 2 mm from the crest and 4.34 mm at 5 mm from the crest, which was statistically significant. On the other hand, a statistically significant graft resorption of 1.41 mm at 2 mm from the crest and 2.19 mm at 5 mm from the crest was found when the mean difference between the immediate and 6-month postoperative CBCTs was calculated. Conclusions: Within the limitations of the study, the use of xenograft shells as a barrier for maxillary alveolar ridge reconstruction is a predictable technique; however, further investigations regarding the required time for graft consolidation are required. [ABSTRACT FROM AUTHOR]

Purpose: To investigate bone regeneration among three different bone graft materials in a rat calvarum model. Materials and Methods: A total of 24 rats had two 5-mm defects placed per calvarial. Rats were divided into four groups: bovine xenograft (XG), demineralized bone matrix (DBM), mineralized bone graft (MBG), and collagen membrane control (CC). Within each group, samples were collected at two time points: 4 weeks (T4) and 8 weeks (T8). Bone regeneration was assessed by microcomputed tomography (micro-CT) imaging and was analyzed using MATLAB software. Additionally, the fixed samples were subsequently demineralized for immunohistochemistry and histomorphometry. Slides were mounted and stained with hematoxylin and eosin (H&E) stain as well as bone morphogenetic protein 2 (BMP-2) and runt-related transcription factor 2 (RUNX2) markers. The numbers of positive cells/area were calculated for each group and analyzed. Results: At 4 weeks, DBM showed low mineral density (7.7%) compared to the control (25.2%), but increased dramatically at 8 weeks (DBM, T8 = 27.6%; CC, T8 = 27.2%). Xenograft material showed an increase in mineral desnity between T4 and T8 (XG, T4 = 25.0%; XG, T8 = 32.3%). MBG remained consistent over the 8-week trial period (MBG, T4 = 30.4%; MBG, T8 = 30.4%). BMP-2 expression was present in cells adherent to all graft materials. RUNX2 expression was also observed in cells adherent to all graft materials, indicating that during the 4- to 8-week healing period, all materials supported osteogenesis. Conclusions: Compared to other materials, the DBM had high osteoinductive properties during the 4- to 8-week time period based on increased mineral content. All materials were associated with immunohistologic evidence of osteogenesis in the rat calvarial defect model. [ABSTRACT FROM AUTHOR]

We propose a new reaction device for the microdiffusion analysis of CO2 in fluid samples from volcanic areas to improve the conventional analysis procedure, which requires a fixative and good handling skills. To accomplish this, a small resin reaction cell for the sample solution and acid (initiator for CO2 liberation) was devised and placed in a commercially available air-tight glass container with a Petri dish to form a microdiffusion analysis unit. The analysis was based on the principles of the conventional manual titration method that uses Ba(OH)2 as the CO2 absorbent. Using the new device, 99.5% recovery, with a relative standard deviation of 4.5% (n = 8), was achieved in a test analysis for 0.03 mmol of CO2 liberated from a Na2CO3 solution as a simulated sample. The analytical performance of the new device was almost comparable to that of conventional units under the experimental conditions of this study. Applying this new device for analyzing fluid samples from volcanic areas will contribute to enhancing the performance by reducing the possibility of CO2 contamination and by simplifying the process by eliminating the need for preparatory cleaning for fixative application. [ABSTRACT FROM AUTHOR]

Lymph node (LN)‐resident dendritic cells (DCs) are a promising target for vaccination given their professional antigen‐presenting capabilities and proximity to a high concentration of immune cells. Direct intra‐LN injection has been shown to greatly enhance the immune response to vaccine antigens compared to traditional intramuscular injection, but it is infeasible to implement clinically in a vaccination campaign context. Employing the passive lymphatic flow of antigens to target LNs has been shown to increase total antigen uptake by DCs more than inflammatory adjuvants, which recruit peripheral DCs. Herein, we describe a novel vaccination platform in which two complementary multi‐arm poly(ethylene glycol) (PEG) polymers—one covalently bound to the model antigen ovalbumin (OVA)—are injected subcutaneously into two distinct sites. These materials then drain to the same LN through different lymphatic vessels and, upon meeting in the LN, rapidly crosslink. This system improves OVA delivery to, and residence time within, the draining LN compared to all control groups. The crosslinking of the two PEG components also improves humoral immunity without the need for any pathogen‐mimicking adjuvants. Further, we observed a significant increase in non‐B/T lymphocytes in LNs cross‐presenting the OVA peptide SIINFEKL on MHC I over a dose‐matched control containing alum, the most common clinical adjuvant, as well as an increase in DC activation in the LN. These data suggest that this platform can be used to deliver antigens to LN‐resident immune cells to produce a stronger humoral and cellular immune response over materials‐matched controls without the use of traditional adjuvants. [ABSTRACT FROM AUTHOR]

Objective: The objective was to investigate the feasibility of prospectively validating multiple clinical prediction scores (CPSs) for pediatric appendicitis in an Australian pediatric emergency department (ED). Methods: A literature search was conducted to identify potential CPSs and a single‐center prospective observational feasibility study was performed between November 2022 and May 2023 to evaluate the performance of identified CPSs. Children 5–15 years presenting with acute right‐sided or generalized abdominal pain and clinician suspicion of appendicitis were included. CPSs were calculated by the study team from prospectively clinician‐collected data and/or review of medical records. Accuracy of CPSs were assessed by area under the receiver operating characteristic curve (AUC) and proportions correctly identifiable as either low‐risk or high‐risk with the best performing CPS compared to clinician gestalt. Final diagnosis of appendicitis was confirmed on histopathology or by telephone/email follow‐up for those discharged directly from ED. Results: Thirty CPSs were identified in the literature search and 481 patients were enrolled in the study. A total of 150 (31.2%) patients underwent appendectomy with three (2.0%) having a normal appendix on histopathology. All identified CPSs were calculable for at least 50% of the patient cohort. The pediatric Appendicitis Risk Calculator for pediatric EDs (pARC‐ED; n = 317) was the best performing CPS with AUC 0.90 (95% confidence interval [CI] 0.86–0.94) and specificity 99.0% (95% CI 96.4%–99.7%) in diagnosing high‐risk cases and a misclassification rate of 4.5% for low‐risk cases. Conclusions: The study identified 30 CPSs that could be validated in a majority of patients to compare their ability to assess risk of pediatric appendicitis. The pARC‐ED had the highest predictive accuracy and can potentially assist in risk stratification of children with suspected appendicitis in pediatric EDs. A multicenter study is now under way to evaluate the potential of these CPSs in a broader range of EDs to aid clinical decision making in more varied settings. [ABSTRACT FROM AUTHOR]

The text discusses the career and research contributions of Walther Mothes in the field of retrovirology. Mothes transitioned from studying protein secretion to investigating retroviruses, focusing on topics such as virus entry pathways, cell-to-cell transmission, and antiviral immunity. His lab developed innovative tools for live-cell imaging and single molecule studies to understand the structure and dynamics of viral proteins, such as HIV-1 Env and SARS-CoV-2 spike protein. Mothes' research also delves into the interplay between viruses and the immune system, shedding light on virus dissemination and pathogenesis. [Extracted from the article]

AbstractThe efficacy of therapeutics can be enhanced with their off-target effects being minimized through targeted delivery. In vaccination and cancer immunotherapy, targeting dendritic cells (DCs) and macrophages (Mφs) is crucial for the activation of the immune system. To this end, we have developed a set of carbohydrate-based ligands targeting C-type lectins (CTLs) present on the surface of DCs for receptor-mediated uptake. Branched structures functionalized with up to four mannose units were synthesized through CuI-catalysed click chemistry, and the products were further functionalized with the DBCO group to facilitate their conjugation with cargos of interest via Cu-free click chemistry. Thus, the ligands were conjugated with fluorescein azide, and the fluorescent conjugates were assessed for their internalization in CTL expressing immature DCs. The results showed that high-mannose branched structures were efficiently internalized through the endocytic pathway, with a positive qualitative correlation between branching degree of sugar-based ligands and internalization. As evidence for payload delivery, conjugating with a mannotriose ligand quantitatively increased the uptake of a fluorescently labeled oligonucleotide by immature DCs. Our work supports the use of click chemistry to synthesize and conjugate promising ligands for efficient delivery of nucleic acid-based drugs. [ABSTRACT FROM AUTHOR]

RNA modifications play a pivotal role in the regulation of RNA chemistry within cells. Several technologies have been developed with the goal of using RNA modifications to regulate cellular biochemistry selectively, but achieving selective and precise modifications remains a challenge. Here, we show that by using designer organelles, we can modify mRNA with pseudouridine in a highly selective and guide-RNA-dependent manner. We use designer organelles inspired by concepts of phase separation, a central tenet in developing artificial membraneless organelles in living mammalian cells. In addition, we use circular guide RNAs to markedly enhance the effectiveness of targeted pseudouridinylation. Our studies introduce spatial engineering through optimized RNA editing organelles (OREO) as a complementary tool for targeted RNA modification, providing new avenues to enhance RNA modification specificity. Synthetic organelles enable the selective manipulation of cellular biochemistry. Here the authors focus on RNA modifications and use designer organelles in mammalian cells to selectively incorporate pseudouridine into mRNA using circular guide RNAs. [ABSTRACT FROM AUTHOR]

Objectives: Oral mucosal lesions are prevalent and often cause pain, thus impacting patients' quality of life. Platelet-rich fibrin (PRF) has emerged as a promising autologous biomaterial for wound healing, yet comprehensive evidence regarding its efficacy in treating oral mucosal lesions is limited. This study aims to update the current evidence on the effectiveness of PRF in treating various types of oral mucosal lesions. Materials and methods: We conducted a literature search in PubMed, Scopus, Embase, and Web of Science databases until April 2024. The search included studies that investigated the use of PRF in treating oral mucosal lesions. Twelve studies met the inclusion criteria, comprising three case reports, three randomized controlled trials, two animal studies, three split-mouth trials, and one retrospective study. We performed data extraction according to a predefined form. Results: PRF was applied in two forms—membranes and injectable gels—to treat a range of oral mucosal lesions, including ulcerative, red and white, pigmented, and potentially malignant or malignant lesions. Compared to control groups or conventional treatments, PRF generally demonstrated superior outcomes regarding faster healing, lesion size reduction, symptom relief, and lower recurrence rates. Histological and molecular analyses from some studies also indicated PRF's regenerative and anti-inflammatory effects. Conclusion: PRF shows promise as an effective and safe alternative to current treatments for oral mucosal lesions due to its autologous nature, ease of preparation, and wound-healing capabilities. However, further research is needed to standardize PRF preparation protocols and confirm its long-term efficacy across different lesion types. [ABSTRACT FROM AUTHOR]

In recent years, there has been an increased focus on studying light–battery interactions in the context of operando optical studies and integrated photoelectrochemical energy harvesting. However, there has been little insight into identifying suitable "light‐accepting" current collectors for this class of batteries. In this study, fluorine‐doped tin oxide, indium‐tin oxide, and silver nanowire‐graphene films are analyzed along with carbon paper, carbon nanotube paper, and stainless‐steel mesh as current collectors for optical batteries. They are categorized into two classes – transmissive and non‐transmissive, based on the orientation of the light–electrode interaction. Various methods to prepare the electrode are highlighted, including drop casting and the fabrication of free‐standing electrodes. The optical and electrical properties of these current collectors as well as their electrochemical stability are measured using linear sweep voltammetry against zinc and lithium anodes. Finally, the rate performance and long‐term cycling stability of lithium manganese oxide (LiMn2O4) cathodes are measured against lithium anodes with these current collectors and their performance is compared. These results show which current collector to choose depends on the application and cell chemistry. These guidelines will assist in the design of future optical cells for in‐situ measurements and photoelectrochemical energy storage. [ABSTRACT FROM AUTHOR]

Aim: To assess the efficacy of intratesticular injection of autologous platelet‐rich plasma (PRP) in men with non‐obstructive azoospermia (NOA) and a history of failed microdissection‐testicular sperm extraction (mTESE) procedures. Methods: A prospective case series of a cohort study was conducted involving couples diagnosed with NOA. Patients with at least one failed mTESE procedure were included. Intratesticular PRP injection was performed using a standardized protocol. Follow‐up assessments included sperm analysis, hormonal evaluation, and in vitro fertilization (IVF) outcomes. Results: Data from 177 men with NOA were analyzed, with 135 patients meeting eligibility criteria. PRP treatment resulted in positive sperm retrieval rates of 27.5% in patients with one prior failed mTESE procedure and 16.4% in patients with two or more failed attempts. IVF outcomes showed fertilization rates of 86.4% and 100.0% in respective groups, with pregnancy rates of 36.8% and 22.2% per embryo transfer. Histopathological examination post‐mTESE revealed varied patterns, including Sertoli cell‐only syndrome and maturation arrest. Conclusions: Intratesticular PRP injection shows promise as a potential therapeutic approach for NOA patients with prior failed mTESE procedures, demonstrating improved sperm retrieval rates and favorable IVF outcomes. Further randomized controlled trials are warranted to validate these findings and refine the technique's efficacy in male infertility management to answer the question of whether PRP could significantly improve the second attempt retrieval rate. [ABSTRACT FROM AUTHOR]

Granular cell tumors of breast are rare neoplasms, majority of which are benign. Their imaging appearances are often indistinguishable from breast cancer. They may demonstrate a few differentiating features and unlike breast cancer, typically follow a benign course. Histopathology and immunochemistry form the cornerstone of diagnosis of granular cell tumor. In this article, we presented a series of three cases of granular cell tumors with variable presentations. Our goal is to increase familiarity for these neoplasms and for the readers to be able to distinguish them from the more common entity of breast cancer, as their prognosis and management differ. [ABSTRACT FROM AUTHOR]

The 1T-rich MoS 2 @PC materials were rationally constructed and evaluated as an efficient polysulfide promotor for high-performance Li-S batteries. The constructed 1T-rich MoS 2 nanosheets not only have strong adsorption capacity for polysulfide, but also can catalyze the conversion of polysulfide rapidly. [Display omitted] The practical applications of lithium-sulfur (Li-S) batteries have severely been hindered by notorious shuttle effect and sluggish redox kinetics of lithium polysulfide intermediates (LiPSs), which bring about rapid capacity degradation, low coulombic efficiency and poor cycling stability. In this work, 1T-rich MoS 2 nanosheets are in-situ developed onto the conductive porous carbon matrix (1T-rich MoS 2 @PC) as efficient polysulfide promotors for high-performance Li-S batteries. The porous carbon skeleton tightly anchors MoS 2 nanosheets to prevent their reaggregation and ensures accessible electrical channels, and at the same time provides a favorable confined space that promotes the generation of 1T-rich MoS 2 structure. More importantly, the uniformly distributed metallic 1T-rich MoS 2 nanosheets not only affords rich sulfphilic sites and high binding energy for immobilizing LiPSs, but also favors rapid electron transfer and LiPSs conversation kinetics, substantially regulating sulfur chemistry in working cells. Consequently, the Li-S cell assembled with 1T-rich MoS 2 @PC modified separator delivers a remarkable cycling stability with ultralow capacity decay rate of 0.067% over 500 cycles at 1C. Encouragingly, under harsh conditions (high sulfur loading of 4.78 mg cm−2 and low E/S ratio of 8 μL mg−1), a favorable electrochemical performance can still be demonstrated. This study highlights the profitable design of 1T-rich MoS 2 /carbon based electrocatalyst for suppressing shuttle effect and promoting catalytic conversation of LiPSs, and has the potential to be applied to in other energy storage systems. [ABSTRACT FROM AUTHOR]

Serous borderline tumors of the ovary fall in between the benign and malignant category. These tumors are often diagnosed early, and the prognosis is usually favorable. However, there are variations in the histopathological findings of borderline ovarian tumors. Xanthomatous change is one such rare change in which deposition of lipid-rich material is seen morphologically as xanthoma cells within tumor tissue and reports of this are sparse. There is postulated literature on xanthomatous change being a contributing factor for progression of cancer. We present a case of a 75-year-old postmenopausal female with complaint of pain abdomen since 3 days, diagnosed radiologically as right ovarian mucinous cystadenoma/cystadenocarcinoma. Histopathology revealed a serous borderline tumor with extensive xanthomatous change. This case presents important thoughts on exploring the connection of xanthomatous change with borderline ovarian tumors, which till date is a matter of debate. [ABSTRACT FROM AUTHOR]

Gardner's syndrome has been recognized as a hereditary affliction that is autosomal in nature. This disorder is known to exhibit characteristics of familial adenomatous polyposis, of which it is also considered a variation. The features of this syndrome include the gradual development of osteomas and epidermoid cysts, including a characteristic feature that is the noted presence of intestinal polyps, which are generally multiple in number. Additionally, dental anomalies have been observed and recorded in a sizeable ratio of cases encompassing an increased frequency of multiple odontomas that are benign tumors linked to the development of a tooth and tooth agenesis/hypodontia that refers to developmental absence of one or more teeth. The other dental ascertainment includes abnormal morphology of the tooth/teeth as well as the presence of supernumerary teeth and impacted or unerupted teeth. This case report outlines the case of a 59-year-old male patient who had reported to the clinic, and was then diagnosed with Gardner's syndrome post a thorough examination. On radiographic examination, the manifestation of multiple osteomas in the frontal bone was revealed. The presence of a motley of diffused benign lesions of the bone in both the upper and lower jaw as well as the presence of an epidermoid cyst on the scalp was suggestive of an exemplar presentation of Gardner's syndrome. [ABSTRACT FROM AUTHOR]

Background: Xuefu Zhuyu decoction (XFZYD) has been extensively utilized to treat traumatic brain injury (TBI). However, the bioactive compounds and the underlying mechanisms have not yet been elucidated. Objectives: This study aimed to investigate the bioactive constituents of XFYZD that are absorbed in the blood and the mechanisms in treating TBI. Methods: The study presents an integrated strategy in three steps to investigate the material basis and pharmacological mechanisms of XFZYD. The first step involves: (1) performing metabolomics analysis of XFZYD to obtain the main functions and targets; (2) screening the blood-entry ingredients and targets of XFZYD from databases; (3) obtaining the potential components targeting the key functions by integrated analysis of metabolomics and network pharmacology. The second step involves screening pharmacological effects with active ingredients in vitro. In the third step, the effects of the top active compound were validated in vivo, and the mechanisms were explored by protein antagonist experiments. Results: Metabolomics analysis revealed that XFZYD treated TBI mice mainly through affecting the functions of blood vessels. We screened 62 blood-entry ingredients of XFZYD by network pharmacology. Then, we focused on 39 blood-entry ingredients related to vascular genes enriched by XFZYD-responsive metabolites. Performing the natural products library, we verified that hydroxysafflor yellow A (HSYA), vanillin, ligustilide, paeoniflorin, and other substances promoted endothelial cell proliferation significantly compared to the control group. Among them, the efficacy of HSYA was superior. Further animal studies demonstrated that HSYA treatment alleviated neurological dysfunction in TBI mice by mNSS and foot fault test, and decreased neuronal damage by HE, nissl, and TUNEL staining. HSYA increased the density of cerebral microvessels, raised the expression of angiogenesis marker proteins VEGFA and CD34, and activated the PI3K/Akt/mTOR signaling pathway significantly. The angiogenic effects disappeared after the intervention of PI3K antagonist LY294002. Conclusion: By applying a novel strategy of integrating network pharmacology of constituents absorbed in blood with metabolomics, the research screened HSYA as one of the top bioactive constituents of XFZYD, which stimulates angiogenesis by activating the PI3K/Akt/mTOR signaling pathway after TBI. [ABSTRACT FROM AUTHOR]

Simple Summary: Raman spectroscopy is a label-free optical method that has proven its suitability for the discrimination between cancerous and noncancerous tissue. Bladder cancer diagnosis typically relies on excisional biopsies and histopathology, which are considered the gold standard. Here, we want to use an endoscopic setup to demonstrate the applicability of Raman spectroscopy in a clinical in vivo setting. In the European Union, the regulatory framework is given by the Medical Device Regulation. We describe the path and the necessary effort to be able to conduct a clinical investigation within this framework. The aim of this clinical examination was to perform Raman spectroscopy in the living bladder and to record Raman spectra of normal and tumorous bladder tissue and to determine the degree of bladder tumor in a post-processing step. The open prospective study includes 21 patients and presents preliminary results for the diagnostic abilities of our approach. This work reports on an in vivo Raman-based endoscopy system, invaScope, enabling Raman measurements of healthy and tumor bladder tissue during an endoscopic procedure in the operating theatre. The presented study outlines the progression from the initial concept (validated through previously performed ex vivo studies) to the approval and implementation of a clinical investigational device according to the requirement within the framework of the European Medical Device Regulation (MDR2017/745). The study's primary objective was to employ the invaScope Raman system within the bladder, capturing in vivo spectroscopic Raman data followed by standard histo- and cytopathological examinations of urological tissue (considered the gold standard). The collected data were analyzed and correlated with histopathological findings post-procedure. Additionally, the study aimed to assess the feasibility of using diagnostic equipment, probes, and software for application in a clinical setting, evaluating usability aspects that are important during surgical procedures. This research represents a pivotal step toward advancing Raman spectroscopy for routine clinical use in characterizing bladder lesions. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancers of the lip and oral cavity are common cancers worldwide. Up to 46% of oral cancers are preventable if risk factors are avoided and if precancerous lesions are detected at an early stage. To reduce the incidence of oral cancer and its mortality rate, there is ongoing research studying new diagnostic and treatment methods. This review aims to present a novel glance at oral cancer—its current classification and epidemiology—and will provide new insights into the development of new diagnostic methods and therapies of oral cancer. Oral cavity and lip cancers are the 16th most common cancer in the world. It is widely known that a lack of public knowledge about precancerous lesions, oral cancer symptoms, and risk factors leads to diagnostic delay and therefore a lower survival rate. Risk factors, which include drinking alcohol, smoking, HPV infection, a pro-inflammatory factor-rich diet, and poor oral hygiene, must be known and avoided by the general population. Regular clinical oral examinations should be enriched in an oral cancer search protocol for the most common symptoms, which are summarized in this review. Moreover, new diagnostic methods, some of which are already available (vital tissue staining, optical imaging, oral cytology, salivary biomarkers, artificial intelligence, colposcopy, and spectroscopy), and newly researched techniques increase the likelihood of stopping the pathological process at a precancerous stage. Well-established oral cancer treatments (surgery, radiotherapy, chemotherapy, and immunotherapy) are continuously being developed using novel technologies, increasing their success rate. Additionally, new techniques are being researched. This review presents a novel glance at oral cancer—its current classification and epidemiology—and will provide new insights into the development of new diagnostic methods and therapies. [ABSTRACT FROM AUTHOR]

Primary breast lymphoma (PBL) is a rare malignant lymphoid neoplasm limited to the breast, accounting for about 0.15% of all malignant breast tumors and 1.7% to 2.2% of extra-nodal lymphomas. PBL must be distinguished from conventional breast carcinomas due to different therapeutic approaches. A 25-year-old female presented with a left breast mass. Histopathology and immunohistochemical tests confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL). She had no similar lesions elsewhere in the body. She received 1 cycle of R-CHOP chemotherapy but absconded from the treatment and succumbed afterward while at home. Recent developments in DLBCL treatment have greatly improved patient outcomes by incorporating targeted medicines like rituximab, increased chemotherapy regimens, new drugs, and individualized treatment techniques. PBL appears to have a worse prognosis; thus, delay or abscondment from treatment is of serious concern when it comes to improving the prognosis of patients with PBL. [ABSTRACT FROM AUTHOR]

Aim: Neoadjuvant chemotherapy (NAC) has transitioned from a treatment modality used solely for inoperable and locally advanced breast cancer to a therapeutic approach for early-stage breast cancer. High-risk patients, such as those with HER2-positive and triple- negative breast cancer, particularly benefit from NAC. This study aimed to evaluate the factors affecting pathological complete response (pCR) in primary breast tumors and axillary lymph nodes in patients with breast cancer. Methods: The study included female patients with breast cancer who received NAC at a training and research hospital between 2020 and 2024. Patients were categorized based on age, tumor stage, and tumor biology: luminal A, HER2-positive luminal B, HER2- negative luminal B, HER2-positive alone, or triple-negative. The presence or absence of E-cadherin in tumor cells and Ki-67 levels were also examined. Data were obtained from medical records to assess the impact of these factors on complete response in patients with breast cancer and axillary metastatic lymph nodes following NAC. Results: Univariate analysis revealed that histopathological subtypes, estrogen receptor and progesterone receptor (PR) status, HER2 status, perineural invasion, lymphovascular invasion (LVI), Ki-67 index, and carcinoma in situ (CIS) component significantly influenced pCR. Multivariate analysis confirmed that PR status [Odds ratio (OR): 3.33, 95% confidence interval (CI): 1.57-7.08, p=0.002], HER2 status (OR: 3.56, 95% CI: 1.71-7.44, p=0.001), LVI (OR: 3.91, 95% CI: 1.84-8.30, p<0.001), Ki-67 index (OR: 1.03, 95% CI: 1.01-1.05, p<0.001), and CIS component (OR: 7.01, 95% CI: 2.44-20.11, p<0.001) were independent predictors of complete response. Conclusion: Our findings underscore the multifaceted nature of NAC response in breast cancer, which is influenced by histopathological and molecular characteristics. [ABSTRACT FROM AUTHOR]

Background: Lung cancer (LC) is one of the leading causes of cancer-related deaths worldwide. In Iran, it is the second most common cause of cancer-related deaths for men and the third most common for women. This study aimed to examine the clinicopathological characteristics of Iranian patients with LC. Methods: Clinicopathological data of 1382 patients with primary LC diagnosed over 11 years (2012-2023) at the "National Institute of Tuberculosis and Lung Disease" (NRITLD), Tehran, Iran, were retrospectively reviewed. Results: Adenocarcinoma was the most common type of cancer found in the patients (42.44%). The median age was 59.69 years (mean: 60.41 years) ranging 24-88 years. The mean male-to-female ratio was 3.65. Additionally, 65.84% of patients were smokers. The majority of patients (82.69%) were diagnosed at an advanced stage (stage IV) of cancer. Conclusion: Although some of our findings are consistent with those of previous LC studies, there are some discrepancies, especially concerning the smoking status and median age of the Iranian patients. Therefore, additional clinical and epidemiological studies are needed to determine the impact of non-smoking factors, such as environmental exposure and genetic predisposition, on the development of LC. [ABSTRACT FROM AUTHOR]

Background: Posttraumatic osteoarthritis (PTOA) arises secondarily to joint trauma and is driven by catabolic inflammatory pathways. Alpha-2-macroglobulin (α2M) is a naturally occurring proteinase inhibitor found in human serum and synovial fluid that binds proteases as well as proinflammatory cytokines involved in the pathogenesis of PTOA. Purpose: (1) To investigate the therapeutic potential of intra-articular α2M injections during the acute stages of PTOA by inhibiting inflammatory pathways driven by the cytokines expressed by the synovium in a large preclinical Yucatan minipig model and (2) to determine if 3 intra-articular α2M injections have greater chondroprotective effects compared with 1 intra-articular injection. Study Design: Controlled laboratory study. Methods: A total of 48 Yucatan minipigs were randomized into 4 groups (n = 12 each): (1) modified intra-articular drilling (mIAD) and saline (mIAD + saline), (2) mIAD and 1 intra-articular α2M injection (mIAD +α2M-1), (3) mIAD and 3 α2M injections (mIAD +α2M-3), and (4) sham control. Surgical hindlimbs were harvested at 15 weeks after surgery. Cartilage degeneration, synovial changes, inflammatory gene expression, and matrix metalloproteinase levels were evaluated. Gait asymmetry was measured before and after surgery using a pressure-sensing walkway system. Results: Macroscopic lesion areas and microscopic cartilage degeneration scores were lower in the mIAD +α2M-1 and mIAD +α2M-3 groups compared with the mIAD + saline group (P <.05) and similar to those in the sham group (P >.05). Synovial membrane scores of the mIAD +α2M-1 and mIAD +α2M-3 groups were lower than that of the mIAD + saline group (P <.05) and higher than that of the sham group (P <.05). Interleukin-1 beta, nuclear factor kappa B, and tumor necrosis factor alpha mRNA expression in the synovium and matrix metalloproteinase-1 levels in synovial fluid were significantly lower in the mIAD +α2M-1 and mIAD +α2M-3 groups compared with the mIAD + saline group (P <.05). No significant differences were observed between the mIAD +α2M-1 and mIAD +α2M-3 groups for all measured outcomes. There were early changes in gait (P <.05) between preoperative and postoperative time points for the mIAD + saline, mIAD +α2M-1, and mIAD +α2M-3 groups that normalized by 15 weeks. Conclusion: Animals receiving early α2M treatment exhibited less cartilage damage, milder synovitis, and lower inflammation compared with animals with no α2M treatment. These results exemplify the early anti-inflammatory effects of α2M and provide evidence that intra-articular α2M injections may slow the progression of PTOA. Clinical Relevance: In patients presenting with an acute joint injury, an early intervention with α2M may have the potential to reduce cartilage degeneration from catabolic pathways and delay the development of PTOA. [ABSTRACT FROM AUTHOR]

Objective: We evaluated patients who underwent excisional peripheral lymph node biopsy in terms of histopathologic findings, palpability of lymph nodes, incision depth, and surgery duration, together with demographic and clinical characteristics of the patients. Methods: This prospective study was conducted over an 18-month period at a university research hospital. The total number of 42 patients who attended the oncologic surgery outpatient clinic for excisional lymph biopsy was included in the study. Results: Reactive lymph nodes were found in most benign cases (n=15/25), but the most common malignancy in the malignant group was B-cell lymphoma (n=5/17). When the lymph node was clinically non-palpable and had a size of up to 3.5 cm, the incision was deeper (p<0.05). Conclusion: It would be a useful approach to add the depth of peripheral lymph nodes to the ultrasound reports together with other necessary data to assist the surgeon so that the exact location of the node can be more precisely predicted, and unnecessary incision size, depth, elongation of the duration of the surgery, and complications can be avoided. Collaboration between the surgeon, radiologist, and pathologist is a very important corner stone not to underdiagnose a malignancy and to avoid complications. [ABSTRACT FROM AUTHOR]

Oligonucleotide drugs are shining in clinical therapeutics, but efficient and safe delivery systems severely limit their widespread use. A disulfide unit technology platform based on dynamic thiol exchange chemistry at the cell membrane has the potential for drug delivery. However, the alteration of the disulfide unit CSSC dihedral angle induced by different substituents directly affects the effectiveness of this technology and its stability. Previously, we constructed a trivalent low dihedral angle disulfide unit that can effectively promote the cellular uptake of small molecules. Here, we constructed a novel disulfide unit-masked oligonucleotide hybrid based on a low dihedral angle disulfide unit, motivated by prodrug design. Cellular imaging results showed that such a system exhibited superior cellular delivery efficiency than the commercial Lipo2000 without cytotoxicity. The thiol reagents significantly reduced its cellular uptake (57–74%), which proved to be endocytosis-independent. In addition, in vivo distribution experiments in mice showed that such systems can be rapidly distributed in liver tissues with a duration of action of more than 24 h, representing a potential means of silencing genes involved in the pathogenesis of liver-like diseases. In conclusion, this trivalent disulfide unit-masked system we constructed can effectively deliver large oligonucleotide drugs. [ABSTRACT FROM AUTHOR]

Lithium-ion batteries (LIBs) are employed in a range of devices due to their high energy and power density. However, the increased power density of LIBs raises concerns regarding their safety when subjected to external abuse. The thermal behavior is influenced by a number of factors, i.e., the state of charge (SoC), the cell chemistry and the abuse conditions. In this study, three distinct cylindrical Li-ion cells, i.e., lithium nickel cobalt aluminum oxide (NCA), lithium titanate oxide (LTO), and lithium iron phosphate (LFP), were subjected to thermal abuse (heating rate of 5 °C/min) in an air flow reactor, with 100% SoC. Venting and thermal runaway (TR) were recorded in terms of temperature and pressure, while the emitted products (gas, solid, and liquid) were subjected to analysis by FT-IR and ICP-OES. The concentrations of the toxic gases (HF, CO) are significantly in excess of the Immediate Danger to Life or Health Limit (IDLH). Furthermore, it is observed that the solid particles are the result of electrode degradation (metallic nature), whereas the liquid aerosol is derived from the electrolyte solvent. It is therefore evident that in the event of a LIB fire, in order to enhance the safety of the emergency responders, it is necessary to use appropriate personal protective equipment (PPE) in order to minimize exposure to toxic substances, i.e., particles and aerosol. [ABSTRACT FROM AUTHOR]

Objective To evaluate the risk of end-stage kidney disease (ESKD) in LN patients using tubulointerstitial lesion scores. Methods Clinical profiles and histopathological presentations of 151 biopsy-proven LN patients were retrospectively examined. Risk factors of ESKD based on characteristics and scoring of their tubulointerstitial lesions [e.g. interstitial inflammation (II), tubular atrophy (TA) and interstitial fibrosis (IF)] were analysed. Results The mean age of 151 LN patients was 36 years old, and 136 (90.1%) were female. The LN cases examined included: class I/II (n  = 3, 2%), class III/IV (n  = 119, 78.8%), class V (n  = 23, 15.2%) and class VI (n  = 6, 4.0%). The mean serum creatinine level was 1.4 mg/dl. Tubulointerstitial lesions were recorded in 120 (79.5%) patients. Prior to receiving renal biopsy, nine (6.0%) patients developed ESKD. During the follow-up period (mean, 58 months), an additional 47 patients (31.1%) progressed to ESKD. Multivariate analyses identified serum creatinine [hazard ratio (HR): 1.7, 95% CI: 1.42–2.03, P   <  0.001] and IF (HR: 3.2, 95% CI: 1.58–6.49, P   =  0.001) as independent risk factors of ESKD. Kaplan–Meier analysis further confirmed a heightened risk of ESKD associated with IF. Conclusion Tubulointerstitial involvement is commonly observed in the histopathological presentation of LN. However, IF, rather than II or TA, was found to increase the risk of ESKD in our cohort. Therefore, to predict renal outcome in LN patients prior to adjusting immunosuppressive treatment, the degree of IF should be reviewed. [ABSTRACT FROM AUTHOR]

Rapid advancements in lithium-ion battery (LIB) technology have paved the way for the electrification of diverse applications, with continuous improvements in performance, substantial cost reductions, and the emergence of new manufacturers, formats, and cell chemistries. However, this diversity poses challenges in identifying the most suitable battery cells for specific applications. Here, we present a high-level techno-economic framework for cell selection, leveraging an extensive database of over 500 real-world cells, techno-economic analyses of emerging applications, and a Python-based modeling approach. We apply this method to three electrifiable mobile applications with distinct characteristics: battery electric cars, industrial forklifts, and regional passenger trains. Our results emphasize substantial variations in technical requirements, from power capability to energy density or longevity. We observe no particular differentiation according to cell formats, but tendencies for most suitable chemistries per application. No cell is suitable for all applications, particularly regarding the required maximum cell costs to ensure profitability, ranging from a few to several hundred Euros per kWh to achieve cost parity with a state-of-the-art reference technology. These findings highlight the importance of tailored cell selection strategies for decision makers to optimize performance and cost-effectiveness across different applications. [ABSTRACT FROM AUTHOR]

Lipid remodeling, the modification of cell membrane chemistry via structural rearrangements within the lipid pool of an organism, is a common physiological response amongst all domains of life to alleviate environmental stress and maintain cellular homeostasis. Whereas culture experiments and environmental studies of phytoplankton have demonstrated the plasticity of lipids in response to specific abiotic stressors, few analyses have explored the impacts of multi-environmental stressors at the community-level scale. Here, we study changes in the pool of intact polar lipids (IPLs) of a phytoplanktonic community exposed to multi-environmental stressors during a ∼ 2-month-long mesocosm experiment deployed in the eastern tropical South Pacific off the coast of Callao, Peru. We investigate lipid remodeling of IPLs in response to changing nutrient stoichiometries, temperature, pH, and light availability in surface and subsurface water masses with contrasting redox potentials, using multiple linear regressions, classification and regression trees, and random forest analyses. We observe proportional increases in certain glycolipids (namely mono- and diglycosyldiacylglycerol – MGDG and DGDG, respectively) associated with higher temperatures and oxic conditions, consistent with previous observations of their utility to compensate for thermal stress and their degradation under oxygen stress. N-bearing (i.e., betaine lipids and phosphatidylethanolamine – BLs and PE) and non-N-bearing (i.e., MGDG; phosphatidylglycerol, PG; and sulfoquinovosyldiacylglycerol, SQDG) IPLs are anti-correlated and have strong positive correlations with nitrogen-replete and nitrogen-depleted conditions, respectively, which suggests a substitution mechanism for N-bearing IPLs under nitrogen limitation. Reduced CO 2 (aq) availability and increased pH levels are associated with greater proportions of DGDG and SQDG IPLs, possibly in response to the lower concentration of CO 2 (aq) and the overall lower availability of inorganic carbon for fixation. A higher production of MGDG in surface waters corresponds well with its established photoprotective and antioxidant mechanisms in thylakoid membranes. The observed statistical relationships between IPL distributions, physicochemical parameters, and the composition of the phytoplankton community suggest evidence of lipid remodeling in response to environmental stressors. These physiological responses may allow phytoplankton to reallocate resources from structural or extrachloroplastic membrane lipids (i.e., phospholipids and betaine lipids) under high-growth conditions to thylakoid and/or plastid membrane lipids (i.e., glycolipids and certain phosphatidylglycerols) under growth-limiting conditions. Further investigation of the exact mechanisms controlling the observed trends in lipid distributions is necessary to better understand how membrane reorganization under multi-environmental stressors can affect the pools of cellular C, N, P, and S, as well as their fluxes to higher trophic levels in marine environments subjected to increasing environmental pressure. Our results suggest that future studies addressing the biogeochemical consequences of climate change in the eastern tropical South Pacific Ocean must take into consideration the impacts of lipid remodeling in phytoplankton. [ABSTRACT FROM AUTHOR]

Cell phones, tablets, laptop computers, and many other consumer technology gadgets use lithium-ion batteries (LIBs). The characteristics of lithium batteries include a high specific energy, great efficiency, and a long life. Owing to their distinctive qualities, lithium batteries are now the preferred power source for the electronics industry, with annual production in billions of units. This paper discusses several safety hazards introduced by mechanical, thermal, and electrical abuse as well as cutting-edge fixes for these difficulties. This review sought to achieve a deeper understanding of the safety risks of lithium-ion batteries depending on materials chemistry together with a positive response to these problems. This review discusses different methods for enhancing cell safety, including cooling, balancing, and cell chemistry. It then examines current safety regulations and associated testing procedures. Finally, it concludes with observations on potential future advancements and the prospects for safer lithium-ion batteries (LIBs). [ABSTRACT FROM AUTHOR]

Simple Summary: Adenoid cystic carcinoma is a rare but devastating disease. Currently, treatment options are very poor, and ACC does not respond well to conventional chemotherapy or radiation therapy and has a high rate of recurrence or metastasis. The molecular drivers that govern disease pathology are currently poorly understood. We conducted a molecular analysis of adenoid cystic carcinoma of the salivary and lacrimal glands in order to better understand these mechanisms and pave the way for the development of future therapeutics. Adenoid cystic carcinoma (ACC) of head and neck origin is associated with slow but relentless progression and systemic metastasis, resulting in poor long-term survival rates. ACC does not respond to conventional chemotherapy. Determination of molecular drivers may provide a rational basis for personalized therapy. Herein, we investigate the clinical and detailed molecular genomic features of a cohort of patients treated in Ireland and correlate the site of origin, molecular features, and outcomes. Clinical and genomic landscapes of all patients diagnosed with ACC over a twenty-year period (2002–2022) in a single unit in Ireland were examined and analyzed using fluorescence in situ hybridization, DNA sequencing, and bioinformatic analysis. Fourteen patients were included for analysis. Eleven patients had primary salivary gland ACC and three primary lacrimal gland ACC; 76.9% of the analyzed tumors displayed evidence of NFIB-MYB rearrangement at the 6q23.3 locus; 35% had mutations in NOTCH pathway genes; 7% of patients had a NOTCH1 mutation, 14.3% NOTCH2 mutation, and 14.3% NOTCH3 mutation. The presence of epigenetic modifications in ACC patients significantly correlated with worse overall survival. Our study identifies genetic mutations and signaling pathways that drive ACC pathogenesis, representing potential molecular and therapeutic targets. [ABSTRACT FROM AUTHOR]

RNA is a promising nucleic acid-based biomolecule for various treatments because of its high efficacy, low toxicity, and the tremendous availability of targeting sequences. Nevertheless, RNA shows instability and has a short half-life in physiological environments such as the bloodstream in the presence of RNAase. Therefore, developing reliable delivery strategies is important for targeting disease sites and maximizing the therapeutic effect of RNA drugs, particularly in the field of immunotherapy. In this mini-review, we highlight two major approaches: (1) delivery vehicles and (2) chemical modifications. Recent advances in delivery vehicles employ nanotechnologies such as lipid-based nanoparticles, viral vectors, and inorganic nanocarriers to precisely target specific cell types to facilitate RNA cellular entry. On the other hand, chemical modification utilizes the alteration of RNA structures via the addition of covalent bonds such as N-acetylgalactosamine or antibodies (antibody–oligonucleotide conjugates) to target specific receptors of cells. The pros and cons of these technologies are enlisted in this review. We aim to review nucleic acid drugs, their delivery systems, targeting strategies, and related chemical modifications. Finally, we express our perspective on the potential combination of RNA-based click chemistry with adoptive cell therapy (e.g., B cells or T cells) to address the issues of short duration and short half-life associated with antibody–oligonucleotide conjugate drugs. [ABSTRACT FROM AUTHOR]

Power loss is a limiting factor for batteries and individual cells. The resulting heat generation due to the power loss leads to reduced battery performance and, thus, lower efficiency. These losses are largely due to the internal resistance of the cells. Therefore, it is important to accurately determine the value of the internal resistance of lithium–ion cells. From the literature, it was found that there are three widely used internal resistance-measurement methods (current step method, direct-energy-loss method, and calorimeter measurement), with negligible research on their comparison demonstrating the most efficient method. Henceforth, to find the most optimal method, this research adopts all three methods on a variety of cell chemistries, including Lithium-ion Manganese Oxide (LMO), Lithium Iron Phosphate (LFP), Nickel Manganese Cobalt (NMC), and Lithium Titanium-Oxide (LTO) for different c-rates (1 C, 2 C, and 3 C), with a wide temperature range (from 0 °C to 40 °C). [ABSTRACT FROM AUTHOR]

Background: Invasive lobular cancer is the second most common subtype of invasive breast cancer. Due to the wide diversity of histopathological, clinical, and radiological presentations, it can provide diagnostic and therapeutic challenges. Magnetic resonance imaging (MRI) has the highest sensitivity for its detection and the most accurate determination of invasive lobular cancer extent. The aim of our pictorial review was to demonstrate the different presentations of invasive lobular cancer on MRI and thus facilitate the interpretation of imaging findings for radiologists. The pictorial essay carefully extracted six different MRI presentations of an invasive lobular cancer with brief histopathological and clinical patient data. We showed that invasive lobular cancer presentation on MRI varied, ranged from a single focus to single and multiple lesions, non-mass enhancements of various distributions, and in some cases with nonspecific enhancement curves. Conclusions: This pictorial essay presented a spectrum of MRI findings of invasive lobular cancer, showing the variety of their appearances. Considering the variety of MRI imaging, the radiologist sometimes has to look for other diagnostic methods for the final interpretation of the imaging findings. We believe that the presentation of different cases will educate radiologists and help in making appropriate diagnostic and therapeutic decisions. [ABSTRACT FROM AUTHOR]

Rehmannia glutinosa is widely recognized as a prominent medicinal herb employed by practitioners across various generations for the purpose of fortifying kidney yin. Within Rehmannia glutinosa, the compound known as catalpol (CAT) holds significant importance as a bioactive constituent. However, the protective effects of CAT on kidneys, including ameliorative effects on chronic kidney disease — most prominently renal anemia and renal fibrosis — have not been clearly defined. In this study, the kidney injury model of NRK-52E cells and C57BL/6N male mice was prepared by exposure to aristolochic acid I (AA-I), and it was discovered that CAT could ameliorate oxidative stress injury, inflammatory injury, apoptosis, renal anemia, renal fibrosis, and other renal injuries both in vivo and in vitro. Further treatment of NRK-52E cells with Nrf2 inhibitors (ML385) and activators (ML334), as well as NF-κB inhibitors (PDTC), validated CAT's ability to target Nrf2 activation. Furthermore, the expression of phosphorylated NF-κB p65, IL-6, and Cleaved-Caspase3 protein was inhibited. CAT also inhibited NF-κB, and then inhibited the expression of IL-6, p-STAS3, TGF-β1 protein. Therefore, CAT can regulate Nrf2/NF-κB signaling pathway, significantly correct renal anemia and renal fibrosis, and is conducive to the preservation of renal structure and function, thus achieving a protective effect on the kidneys. [ABSTRACT FROM AUTHOR]

Organophosphorus pesticide poisoning can lead to severe brain damage, but the specific mechanisms involved are not fully understood. Our research aims to elucidate the function of the TRPV4 ion channel in the development of brain injury induced by paraoxon (POX). In vivo, we examined the survival rate, behavioral seizures, histopathological alterations, NMDA receptor phosphorylation, as well as the expression of the NLRP3-ASC-caspase-1 complex and downstream inflammatory factors in the POX poisoning model following intervention with the TRPV4 antagonist GSK2193874. In vitro, we investigated the effects of GSK2193874 on NMDA-induced inward current, cell viability, cell death rate, and Ca2+ accumulation in primary hippocampal neurons. The treatment with the TRPV4 antagonist increased the survival rate, suppressed the status epilepticus, improved pathological damage, and reduced the phosphorylation level of NMDA receptors after POX exposure. Additionally, it inhibited the upregulation of NLRP3 inflammasome and inflammatory cytokines expression after POX exposure. Moreover, the TRPV4 antagonist corrected the NMDA-induced increase in inward current and cell death rate, decrease in cell viability, and Ca2+ accumulation. TRPV4 participates in the mechanisms of brain injury induced by POX exposure through NMDA-mediated excitotoxicity and NLRP3-mediated inflammatory response. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Cancer Biotherapy is the property of Editorial Office of Chinese Journal of Cancer Biotherapy and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cell spheroids are an important three-dimensional (3D) model for in vitro testing and are gaining interest for their use in clinical applications. More natural 3D cell culture environments that support cell–cell interactions have been created for cancer drug discovery and therapy applications, such as the scaffold-free 3D Petri Dish® technology. This technology uses reusable and autoclavable silicone micro-molds with different topographies, and it conventionally uses gelled agarose for hydrogel formation to preserve the topography of the selected micro-mold. The present study investigated the feasibility of using a patterned Poly(vinyl alcohol) hydrogel using the circular topography 12–81 (9 × 9 wells) micro-mold to form HeLa cancer cell spheroids and compare them with the formed spheroids using agarose hydrogels. PVA hydrogels showed a slightly softer, springier, and stickier texture than agarose hydrogels. After preparation, Fourier transform infrared (FTIR) spectra showed chemical interactions through hydrogen bonding in the PVA and agarose hydrogels. Both types of hydrogels favor the formation of large HeLa spheroids with an average diameter of around 700–800 µm after 72 h. However, the PVA spheroids are more compact than those from agarose, suggesting a potential influence of micro-mold surface chemistry on cell behavior and spheroid formation. This was additionally confirmed by evaluating the spheroid size, morphology, integrity, as well as E-cadherin and Ki67 expression. The results suggest that PVA promotes stronger cell-to-cell interactions in the spheroids. Even the integrity of PVA spheroids was maintained after exposure to the drug cisplatin. In conclusion, the patterned PVA hydrogels were successfully prepared using the 3D Petri Dish® micro-molds, and they could be used as suitable platforms for studying cell–cell interactions in cancer drug therapy. [ABSTRACT FROM AUTHOR]

Copyright of Balikesir Health Sciences Journal / Balıkesir Sağlık Bilimleri Dergisi is the property of Balikesir Health Sciences Journal (BAUN Health Sci J) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: The purpose was to study the indicators of physical development of primary-school-aged children with intellectual disability by observing the type of autonomic nervous regulation and their levels of catecholamines and serotonin. Methods: A total of 168 primary school age children were examined, of which 54 had intellectual disability. The autonomic nervous system was assessed using cardiointervalography; anthropometric parameters were applied in accordance with recommendations. The contents of serotonin and catecholamines in blood plasma and lymphocytes were assessed using enzyme immunoassay and luminescent histochemical methods. Results and conclusions: Delayed physical and mental development in children with intellectual disability were associated with low serotonin levels in this group of children. The optimal option for the physical development of children with intellectual disability is a sympathetic type of autonomic nervous regulation, while negative-type vagotonic nervous regulation was associated with the maximum delay in physical development. The hypersympathetic type of nervous regulation was accompanied by minimal changes in physical development, despite the hormonal imbalance in the ratio of catecholamines and serotonin. The level of the neurotransmitter serotonin is a prognostic marker of the physical development of children of primary school age. The total amount of catecholamines and serotonin in blood plasma has a direct relationship with the amount of these neurotransmitters in blood lymphocytes; the more hormones in plasma, the more of them in lymphocytes. Therefore, the determination of the contents of catecholamines and serotonin in lymphocytes can be used as a model for studying neurotransmitters in humans. [ABSTRACT FROM AUTHOR]

The clinical significance of lung tumor spread through air spaces (STAS) has been extensively studied, and is recognized as a unique pattern of invasion. Previous studies of STAS have focused primarily on STAS in alveolar spaces, whereas STAS in the bronchiolar spaces (bronchiolar STAS) has been described in only a few case reports only. Here, we examined 306 cases of primary lung adenocarcinoma and found that bronchiolar STAS was present in 18%. Bronchiolar STAS was associated with an inferior prognosis, more advanced stage, and higher histologic grade. No significant difference in clinicopathological factors or prognosis was observed between cases with bronchiolar STAS and those with alveolar STAS alone. Notably, bronchiolar STAS often occurred simultaneously with alveolar STAS and endobronchial spread of adenocarcinoma, particularly when bronchiolar STAS was present outside the main tumor. We also identified cases where bronchiolar STAS and endobronchial spread of adenocarcinoma occurred simultaneously in the same bronchi or bronchioles located outside the main tumor, as well as cases with bronchiolar STAS adjacent to intrapulmonary metastatic nodules. Our results highlight the significant role of bronchiolar STAS in the aerogenous spread of adenocarcinoma cells. Bronchiolar STAS can be regarded as a histologic variant of alveolar STAS. This study also supports the idea that STAS is not a tissue processing artifact, but a true biological process with clinical implications, offering histologic evidence of aerogenous spread in lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe hypersensitivity reaction characterized by cutaneous rash, lymphadenopathy, fever, eosinophilia, leukocytosis, and life-threatening organ dysfunctions. We describe the case of a 26 year old patient admitted to the Emergency Department for DRESS syndrome after sulfasalazine treatment for rheumatoid arthritis in the right knee. Whole body computer tomography showed multiple neck, chest, and abdominal lymphadenopathy with splenomegaly, massive ascites and severe hepatic cytolysis. Serology results for Epstein-Barr Virus (EBV), influenza, measles, rubella, hepatitis A and B were negative. The histologic analysis of skin, lymph node and bone marrow biopsies could not indicate a classical Hodgkin's Disease or iatrogenic immunodeficiency/EBV-associated lymphoproliferative disorder (LPD), Hodgkin type. The relatively small caliber of the CD30 + immunoreactive blastoid cells in the lymph nodes suggested reactive immunoblasts rather than Hodgkin cells. The morphologic aspects of the lymph node biopsies with predominance of T-cells were compatible with the diagnosis of a sulfasalazine-induced DRESS syndrome as the patient had a high RegiSCAR score for DRESS. [DRESS Syndrome Foundation: Diagnosis and Treatment. (2023)] The patient's complex clinical course, marked by two hospital admissions, highlights the challenges in diagnosing and managing DRESS. This case underscores the need for individualized care, close patient monitoring, and further research to better understand DRESS's underlying mechanisms and optimal therapeutic strategies. [ABSTRACT FROM AUTHOR]

Defects in planar cell polarity (PCP) have been implicated in diverse human pathologies. Vangl2 is one of the core PCP components crucial for PCP signaling. Dysregulation of Vangl2 has been associated with severe neural tube defects and cancers. However, how Vangl2 protein is regulated at the posttranslational level has not been well understood. Using chemical reporters of fatty acylation and biochemical validation, here we present that Vangl2 subcellular localization is regulated by a reversible S-stearoylation cycle. The dynamic process is mainly regulated by acyltransferase ZDHHC9 and deacylase acyl-protein thioesterase 1 (APT1). The stearoylation-deficient mutant of Vangl2 shows decreased plasma membrane localization, resulting in disruption of PCP establishment during cell migration. Genetically or pharmacologically inhibiting ZDHHC9 phenocopies the effects of the stearoylation loss of Vangl2. In addition, loss of Vangl2 stearoylation enhances the activation of oncogenic Yes-associated protein 1 (YAP), serine-threonine kinase AKT, and extracellular signal-regulated protein kinase (ERK) signaling and promotes breast cancer cell growth and HRas G12V mutant (HRasV12)-induced oncogenic transformation. Our results reveal a regulation mechanism of Vangl2, and provide mechanistic insight into how fatty acid metabolism and protein fatty acylation regulate PCP signaling and tumorigenesis by core PCP protein lipidation. [ABSTRACT FROM AUTHOR]

Simple Summary: This study analyzes 61 rare tumors and lesions mimicking peripheral nerve tumors using data from the German Peripheral Nerve Tumor Registry. These cases exhibit significant heterogeneity with various morphological features and biological potentials, including malignant peripheral nerve tumors, perineuriomas, and hybrid nerve sheath tumors. This study underscores the challenges in preoperatively differentiating these rare entities from benign tumors using clinical and radiological methods alone. It highlights the importance of a multidisciplinary approach involving radiologists, neurologists, neuropathologists, and neurosurgeons for accurate diagnosis and effective treatment. The supplementary material offers valuable insights to help clinicians recognize these rare tumors early, improving patient outcomes. The most common peripheral nerve tumors are of a benign nature and include schwannoma or neurofibroma. In rare cases, other tumors or non-tumorous lesions can mimic peripheral nerve tumors clinically or radiologically. Based on data from the multicentric German Peripheral Nerve Tumor Registry (PNTR), which encompasses current information on 315 surgically treated patients from three high-volume centers, we present 61 cases of rare tumors and lesions that mimic tumors associated with peripheral nerves. This cohort displays considerable heterogeneity, featuring a broad spectrum of morphological features and biological potentials. Histopathological diagnoses include various intrinsic peripheral nerve tumors such as malignant peripheral nerve tumors (MPNSTs) (n = 13), perineurioma (n = 17), and hybrid nerve sheath tumors (HPNSTs, comprising schwannoma/perineurioma and schwannoma/neurofibroma) (n = 14), as well as atypical neurofibromatous neoplasm with unknown biological potential (ANNUBP) (n = 1). Additionally, the cohort encompasses extrinsic tumorous lesions like lymphoma (n = 3), lymphangioma (n = 2), hemangioma (n = 2), solitary fibrous tumor (n = 2), metastatic disease (n = 1), and single cases of other rare tumor entities (n = 6). An overview of the underlying pathology, imaging features, and clinical presentation is provided, with a brief description of each entity. A definitive preoperative differentiation between benign peripheral nerve tumors and rare intrinsic and extrinsic tumors is often not possible. Clinical examination and subtle imaging clues can at least indicate the possibility of a rare entity. The basic requirement is close cooperation between radiologists, neurologists, neuropathologists, and neurosurgeons at a specialized center to develop a multidisciplinary concept and offer the patient the best therapeutic approaches. [ABSTRACT FROM AUTHOR]

A small molecule disulfide unit technology platform based on dynamic thiol exchange chemistry at the cell membrane has the potential for drug delivery. However, the alteration of the CSSC dihedral angle of the disulfide unit caused by diverse substituents directly affects the effectiveness of this technology platform as well as its own chemical stability. The highly stable open-loop relaxed type disulfide unit plays a limited role in drug delivery due to its low dihedral angle. Here, we have built a novel disulfide unit starship based on the 3,4,5-trihydroxyphenyl skeleton through trigonometric bundling. The intracellular delivery results showed that the trigonometric bundling of the disulfide unit starship effectively promoted cellular uptake without any toxicity, which is far more than 100 times more active than that of equipment with a single disulfide unit in particular. Then, the significant reduction in cell uptake capacity (73–93%) using thiol erasers proves that the trigonometric bundling of the disulfide starship is an endocytosis-independent internalization mechanism via a dynamic covalent disulfide exchange mediated by thiols on the cell surface. Furthermore, analysis of the molecular dynamics simulations demonstrated that trigonometric bundling of the disulfide starship can significantly change the membrane curvature while pushing lipid molecules in multiple directions, resulting in a significant distortion in the membrane structure and excellent membrane permeation performance. In conclusion, the starship system we built fully compensates for the inefficiency deficiencies induced by poor dihedral angles. [ABSTRACT FROM AUTHOR]

Orbital inflammatory disease (OID) comprises approximately 6% of orbital conditions, affecting individuals across all ages. The range of the primary orbital inflammation's differential diagnosis is extensive, encompassing autoimmune disorders such as thyroid diseases, vasculitis, sarcoidosis, connective tissue diseases, immunoglobulin G4-related disease (IgG4-RD), and giant cell myositis, whereas secondary causes span from infections to drug-induced causes. Analyzing histopathological aspects and cell populations could enhance our comprehension of the etiology of orbital inflammatory involvement in systemic diseases such as IgG4-RD. We present a series of four patients from our Rheumatology clinic, each with distinct systemic diseases, illustrating diverse manifestations of OID. This series was conducted to facilitate discussions and diagnoses of challenging cases of OID in a rheumatologic setting. The difficulty in the differential diagnosis arises from the extensive range of structures involved, resulting in a significant variation of clinical manifestations. Furthermore, the lack of definitive diagnostic laboratory tests and, often, histological findings add to the complexity. OID poses diagnostic challenges with variable clinical manifestations and overlapping imaging findings. As a diagnosis of exclusion, a comprehensive evaluation is crucial, often necessitating an orbital biopsy for confirmation. Collaborative efforts among specialists are essential for managing these intricate cases. [ABSTRACT FROM AUTHOR]

Background: Bacterial meningoencephalitis presents significant diagnostic and therapeutic challenges with high morbidity and mortality in pediatric populations worldwide. The early and precise identification of the etiology of these infections is essential for effective treatment and better patient results. Traditional diagnostic methods, while effective, can be time-consuming. This manuscript aims to evaluate the accuracy of serum procalcitonin (PCT), cerebrospinal fluid (CSF) neutrophil-to-lymphocyte ratio (NLR), and CSF lactate as biomarkers in pediatric bacterial meningoencephalitis. Methods: From March 2021 to November 2023, a cross-sectional study was conducted at Dr. Sardjito General Hospital, a tertiary referral hospital in Yogyakarta, Indonesia. One hundred ninety-seven patients underwent complete clinical and laboratory examinations before being divided into bacterial and non-bacterial groups based on CSF culture results and cytochemical profiles. The diagnostic accuracy was evaluated by the receiver operating characteristic curve using Statistical Package for the Social Sciences. Results: Serum PCT, CSF NLR, and CSF lactate levels showed a notable increase in the bacterial meningoencephalitis group (mean = 4.63 ± 5.52 ng/ml, 4.39 ± 6.68, and 3.59 ± 2.38 mmol/l, respectively) compared to the viral/aseptic group (mean = 0.51 ± 0.88 ng/ml, 0.33 ± 0.95, and 2.25 ± 2.33 mmol/l, respectively) (P < 0.001). Serum PCT and CSF NLR combined measurement had high sensitivity (86.4%) and specificity (88.6%), with an area under the curve of 0.929 (95% confidence interval, 0.873--0.985), surpassing other tested biomarkers. Conclusion: The findings suggest that combining serum PCT and CSF NLR could be beneficial for early diagnosis, potentially allowing timely, targeted treatment and differentiating between bacterial and non-bacterial infections, ultimately improving patient outcomes. [ABSTRACT FROM AUTHOR]

Self‐improving dystrophic epidermolysis bullosa (DEB) is a genodermatosis that is inherited autosomal dominantly or recessively, and its clinical symptoms may improve or subside spontaneously. Herein, we report a case of self‐improving DEB with COL7A1 p.Gly2025Asp variant. The diagnosis was made through histopathological, electron microscopic examination, and genetic testing. The same variant is also noted on his father, who presents with dystrophic toenails without any blisters. This study highlights that idiopathic nail dystrophy could be linked to congenital or hereditary disease. Furthermore, we conducted a review of the literature on the characteristics of reported cases of self‐improving DEB with a personal or family history of nail dystrophy. The results supported our findings that nail dystrophy may be the sole manifestation in some family members. We suggest that individuals suffering from idiopathic nail dystrophy may seek genetic counselling when planning pregnancy to early evaluate the potential risk of hereditary diseases. [ABSTRACT FROM AUTHOR]

Background: The incidence of Barrett's esophageal adenocarcinoma (BEA) is increasing, and endoscopic submucosal dissection (ESD) has been frequently performed for its treatment. However, the differences between the characteristics and ESD outcomes between short- and long-segment BEA (SSBEA and LSBEA, respectively) are unclear. We compared the clinicopathological characteristics and short- and long-term outcomes of ESD between both groups. Methods: We retrospectively reviewed 155 superficial BEAs (106 SSBEAs and 49 LSBEAs) treated with ESD in 139 patients and examined their clinicopathological features and ESD outcomes. SSBEA and LSBEA were classified based on whether the maximum length of the background mucosa of BEA was < 3 cm or ≥ 3 cm, respectively. Results: Compared with SSBEA, LSBEA showed significantly higher proportions of cases with the macroscopically flat type (36.7% vs. 5.7%, p < 0.001), left wall location (38.8% vs. 11.3%, p < 0.001), over half of the tumor circumference (20.4% vs. 1.9%, p < 0.001), and synchronous lesions (17.6% vs. 0%, p < 0.001). Compared with SSBEA, regarding ESD outcomes, LSBEA showed significantly longer resection duration (91.0 min vs. 60.5 min, p < 0.001); a lower proportion of submucosal invasion (14.3% vs. 29.2%, p = 0.047), horizontal margin negativity (79.6% vs. 94.3%, p = 0.0089), and R0 resection (69.4% vs. 86.8%, p = 0.024); and a higher proportion of post-procedural stenosis cases (10.9% vs. 1.9%, p = 0.027). The 5-year cumulative incidence of metachronous cancer in patients without additional treatment was significantly higher for LSBEA than for SSBEA (25.0% vs. 0%, p < 0.001). Conclusions: The clinicopathological features of LSBEA and SSBEA and their treatment outcomes differed in many aspects. As LSBEAs are difficult to diagnose and treat and show a high risk of metachronous cancer development, careful ESD and follow-up or eradication of the remaining BE may be required. [ABSTRACT FROM AUTHOR]

Objective: Test the efficacy of the selective orexin 1 receptor (OX1R) antagonist (SO1RA) nivasorexant in an animal model of binge‐eating disorder (BED) and study its dose–response relationship considering free brain concentrations and calculated OX1R occupancy. Compare nivasorexant's profile to that of other, structurally diverse SO1RAs. Gain understanding of potential changes in orexin‐A (OXA) neuropeptide and deltaFosB (ΔFosB) protein expression possibly underlying the development of the binge‐eating phenotype in the rat model used. Method: Binge‐like eating of highly palatable food (HPF) in rats was induced through priming by intermittent, repeated periods of dieting and access to HPF, followed by an additional challenge with acute stress. Effects of nivasorexant were compared to the SO1RAs ACT‐335827 and IDOR‐1104‐2408. OXA expression in neurons and neuronal fibers as well as ΔFosB and OXA‐ΔFosB co‐expression was studied in relevant brain regions using immuno‐ or immunofluorescent histochemistry. Results: All SO1RAs dose‐dependently reduced binge‐like eating with effect sizes comparable to the positive control topiramate, at unbound drug concentrations selectively blocking brain OX1Rs. Nivasorexant's efficacy was maintained upon chronic dosing and under conditions involving more frequent stress exposure. Priming for binge‐like eating or nivasorexant treatment resulted in only minor changes in OXA or ΔFosB expression in few brain areas. Discussion: Selective OX1R blockade reduced binge‐like eating in rats. Neither ΔFosB nor OXA expression proved to be a useful classifier for their binge‐eating phenotype. The current results formed the basis for a clinical phase II trial in BED, in which nivasorexant was unfortunately not efficacious compared with placebo. Public Significance: Nivasorexant is a new investigational drug for the treatment of binge‐eating disorder (BED). It underwent clinical testing in a phase II proof of concept trial in humans but was not efficacious compared with placebo. The current manuscript investigated the drug's efficacy in reducing binge‐like eating behavior of a highly palatable sweet and fat diet in a rat model of BED, which initially laid the foundation for the clinical trial. [ABSTRACT FROM AUTHOR]