Basal cell adenoma and basal cell adenocarcinoma of the parotid gland: clinical findings and surgical outcomes in a single-institution study.

BACKGROUND: Basal cell adenoma (BCA) is a rare benign tumor within the salivary glands. Basal cell adenocarcinoma (BCAC), the malignant counterpart of BCA, is also an exceedingly rare tumor with very limited clinical studies conducted. This study aims to investigate the clinical characteristics, demographics, and surgical outcomes of patients diagnosed with BCA and BCAC within the parotid gland. METHODS: A retrospective analysis from May 2003 to August 2023 was performed for all patients undergoing parotidectomy for masses. Retrospective data on gender, age, tumor characteristics, and outcomes were collected. Surgical approaches, including negative margin attainment, capsule removal, and histological diagnosis, were also detailed. RESULTS: The study included 1268 patients who underwent parotidectomy, resulting in 81 cases of BCA and 7 cases of BCAC. BCA patients, with a mean age of 55.1 years, showed diverse age distribution and predominantly presented in the 50s. In BCAC cases, seven female patients exhibited a predominant location in the deep lobes. FNA revealed BCAC in three out of seven cases, and subsequent parotidectomy was performed, resulting in no observed recurrences or metastases. CONCLUSION: This study reports the largest number of BCA cases from a single institution and provides comprehensive insights into the demographics, tumor characteristics, and clinical outcomes of both BCA and BCAC. Although further research should be conducted, based on clinical follow-up results, appropriately including the capsule in the tumor excision indicates favorable outcomes, especially when the tumor size is not large.

Higher body mass index increases the risk of shoulder adhesive capsulitis in young adults: a nationwide cohort study.

BACKGROUND: The impact of overweight on the incidence of shoulder adhesive capsulitis (AC) has not been clearly proven. This study aimed to investigate the association between overweight and AC by age using a large-scale nationwide population-based cohort in Korea. METHODS: We analyzed clinical data from 3,517,066 individuals older than 20 years who had undergone a National Health Insurance Service health checkup in 2009. Patients who visited a hospital or private clinic to treat shoulder pain at least three times in 1 year and were assigned a diagnostic code for AC (International Classification of Diseases,10th Revision code M75.00) were identified using claims data during a median follow-up duration of 8.3 years. Hazard ratios (HRs) and 95% confidence intervals for AC were calculated using the Cox proportional hazards model. RESULTS: The adjusted HR for AC in the < 40 year group started to increase in overweight status and was associated with the severity of obesity (body mass index (BMI) < 18.5; 0.654 (0.613-0.697), <23; 1, <25; 1.272 (1.231-1.315), <30; 1.322 (1.281-1.364), ≥30; 1.332 (1.253-1.416)). But in the 40-64 year group and the ≥ 65 year group, there was no significant increasing trend of HR for AC according to BMI level. We conducted a subgroup analysis based on the BMI 23 for defining overweight and presence of comorbidities including diabetes and hyperlipidemia. The adjusted HR for AC was highest with overweight and comorbidities of diabetes and hyperlipidemia (diabetes; 1.528 (1.508-1.549), hyperlipidemia; 1.212 (1.199-1.226)). CONCLUSIONS: In the young age group (20-40 years), a higher BMI level increased the HR for AC. Overweight along with diabetes or hyperlipidemia significantly increased the risk of AC.

Comparative In Vivo Study of Solid-Type Pure Hyaluronic Acid in Thread Form: Safety and Efficacy Compared to Hyaluronic Acid Filler and Polydioxanone Threads.

INTRODUCTION: Although various products are commonly used for skin rejuvenation, solid-type hyaluronic acid (HA) as an injectable form has not been researched or utilized. This study aimed to demonstrate the safety and efficacy of solid-type HA in thread form, which differs from the conventional gel-type HA commonly used. METHOD: Solid-type HA threads, conventional HA fillers, and polydioxanone (PDO) threads were inserted into the dorsal subcutaneous layer of mice. Photographs were taken on days 0, 1, 3, and 7, and on day 7, the samples were harvested for histological analysis. Inflammatory reactions and detection of collagen were confirmed through tissue staining, and real-time PCR was conducted to quantify collagen synthesis. RESULTS: In the histological analysis, the PDO threads exhibited a greater inflammatory response compared to the HA threads. Masson's trichrome staining revealed a higher degree of collagen synthesis in the HA thread group compared to the HA filler group. While collagen type 1 expression was significantly higher in the PDO thread group than in the HA thread group, the HA thread group showed higher expression levels of collagen type 3. Furthermore, the PDO thread group demonstrated a statistically significant increase in TGF-ß1 compared to the HA group. CONCLUSION: This in vivo study demonstrated the stable application of solid-type pure HA threads and their potential for inducing collagen production, while also yielding a low inflammatory response. The findings highlight the promising applications of solid-type HA in the field of cosmetic dermatology. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Air- and Moisture Robust Surface Modification for Ni-Rich Layered Cathode Materials for Li-Ion Batteries.

The mainstream of high-energy cathode development is focused on increasing the Ni-ratio in layered structured cathode materials. The increment of the Ni portion in the layered cathode material escalates not only the deliverable capacity but also the structural degradation. High-Ni layered cathodes are highly vulnerable to exposure to air that contains CO2 and H2 O, forming problematic residual lithium compounds at the surface. In this work, a novel air- and moisture robust surface modification is reported for LiNi0.8 Co0.1 Mn0.1 O2 (NCM811) via the sol-gel coating method that selectively coats the internal surface area of the polycrystalline morphology secondary particles. Bare-, Li2 SnO3 -coated and LiCoO2 -coated NCM811 are exposed to different ambient environments (air, hot-air, and moisture-air) to systematically investigate the correlation between the internal/external coating morphology and performance degradations. The LiCoO2 -coated NCM811s exhibit high-capacity retention after exposure to all environments, due to the internal surface coating that prevents the penetration of harmful compounds into the polycrystalline NCM811. On the other hand, the Li2 SnO3 -coated NCM811s exposed to the ambient environments show gradual capacity fading, implying the occurrence of internal degradation. This paper highlights the impact of the internal degradation of polycrystalline NCM811 after environmental exposure and the correct coating mechanisms required to successfully prevent it.

Effect of dexamethasone and ramosetron on the prevention of postoperative nausea and vomiting in low-risk patients: a randomized, double-blind, placebo-controlled, multicenter trial.

BACKGROUND: Several studies have investigated the effect of antiemetics on postoperative nausea and vomiting (PONV) in high-risk groups. However, few studies have investigated the effect of antiemetics in patients at low risk of developing PONV. METHODS: In this prospective, randomized, double-blinded trial, 177 patients undergoing surgery under general anesthesia were randomly allocated to three groups. Patients allocated to group C (control group) received 2 mL of intravenous 0.9% saline, those allocated to group R (ramosetron group) received 0.3 mg of intravenous ramosetron, and those allocated to group DR (ramosetron plus dexamethasone group) received 5 mg of intravenous dexamethasone and 0.3 mg of intravenous ramosetron. RESULTS: Finally, 174 patients completed the study, and the types of surgeries were orthopedic (n = 80), rhinologic (n = 47), urologic (n = 29), and others (n = 18). The incidence of PONV up to 48 h postoperatively was significantly lower in group DR than in group C. The incidence of PONV up to 0-1 h postoperatively was significantly lower in groups R and DR than in group C. The usage pattern of rescue antiemetics was consistent with the incidence of PONV. The percentage of patients requiring rescue analgesics 0-1 h postoperatively was significantly lower in groups R and DR than in group C. CONCLUSIONS: The combination of dexamethasone and ramosetron demonstrated a superior effect in preventing PONV for 48 h after surgery under general anesthesia than saline in patients at low risk of developing PONV. Compared with saline injections, ramosetron injections yielded better outcomes for the incidence of PONV and the use of rescue antiemetics and rescue analgesics 0-1 h postoperatively. TRIAL REGISTRATION: Clinical trial registration number: criskorea@korea.kr, KCT0006749.

Peripheral Artery Bypass Graft for the Treatment of Ischemic Ulcer or Severe Pain of Hand in Connective Tissue Diseases.

ABSTRACT: Chronic ischemia of the hands and feet is a rare medical condition that requires surgical revascularization. In particular, digital ischemia resulting from connective tissue diseases (CTDs) is among the most important manifestations that negatively affect patients' quality of life. Here, we describe a bypass graft technique for treating digital ischemia. This study aimed to share the considerable benefits of surgical intervention for CTD and present a treatment algorithm. From 2009 to 2020, bypass graft surgery was performed on 10 patients with CTD to relieve their ischemic symptoms or ulceration. Preoperative angiography was performed, and blood distribution patterns were analyzed in detail. Based on the angiographic 4-level analysis, bypass graft surgeries were performed accordingly. The postoperative follow-up was 15 to 72 months. Pain in the hands that underwent the bypass graft surgery improved immediately after surgery. All ulcerations healed and the mean time recorded for ulceration healing was 45.7 days. Here, we propose an appropriate surgical treatment algorithm for managing CTD using arterial bypass graft surgery, and its positive long-term results demonstrate that it is an appropriate option for treating digital ischemia. In conclusion, strict measures with precise preoperative planning can provide satisfactory long-term results in patients with CTD.

Attention-Based Bi-Prediction Network for Versatile Video Coding (VVC) over 5G Network.

As the demands of various network-dependent services such as Internet of things (IoT) applications, autonomous driving, and augmented and virtual reality (AR/VR) increase, the fifthgeneration (5G) network is expected to become a key communication technology. The latest video coding standard, versatile video coding (VVC), can contribute to providing high-quality services by achieving superior compression performance. In video coding, inter bi-prediction serves to improve the coding efficiency significantly by producing a precise fused prediction block. Although block-wise methods, such as bi-prediction with CU-level weight (BCW), are applied in VVC, it is still difficult for the linear fusion-based strategy to represent diverse pixel variations inside a block. In addition, a pixel-wise method called bi-directional optical flow (BDOF) has been proposed to refine bi-prediction block. However, the non-linear optical flow equation in BDOF mode is applied under assumptions, so this method is still unable to accurately compensate various kinds of bi-prediction blocks. In this paper, we propose an attention-based bi-prediction network (ABPN) to substitute for the whole existing bi-prediction methods. The proposed ABPN is designed to learn efficient representations of the fused features by utilizing an attention mechanism. Furthermore, the knowledge distillation (KD)- based approach is employed to compress the size of the proposed network while keeping comparable output as the large model. The proposed ABPN is integrated into the VTM-11.0 NNVC-1.0 standard reference software. When compared with VTM anchor, it is verified that the BD-rate reduction of the lightweighted ABPN can be up to 5.89% and 4.91% on Y component under random access (RA) and low delay B (LDB), respectively.

Retrospective study using biosensor data of a milking Holstein cow with jejunal haemorrhage syndrome.

Jejunal haemorrhage syndrome (JHS) is a sporadic and fatal enterotoxaemic disease in dairy cows associated with acute development and poor prognosis despite treatment. A 5-year-old Holstein cow with no reported pregnancy, three calving numbers, and 303 days in milk presented with hypothermia, discomfort, and inappetence. Anaemia, dehydration, faeces with blood clots, and absence of rumen and bowel movements were observed. We identified the presence of neutrophilia, hyperglycaemia, hypoproteinaemia, azotaemia, hyperlactatemia, hypocalcaemia, hypermagnesemia, hypokalaemia, and hypochloraemia through blood analyses. Necropsy and histopathologic examination revealed a dilated bluish-purple jejunum, blood clots within the jejunum, neutrophil infiltration into the submucosa of the jejunum, and vascular necrosis. Retrospective examination revealed extraordinary patterns of rumination time, activity, rumen mobility, and rumen temperature using biosensors and decreased milk yield. The abnormalities in the affected cow were detected before recognition by farm workers. To the best of our knowledge, this is the first report to examine data from biosensors in a cow with JHS. Our findings suggest that using biometric data may help understand the development of JHS.

Peripheral Osteoma of the Zygoma.

ABSTRACT: Osteoma is a benign, slow growing lesion that consists of compact or cancellous bone. Three types of osteomas could be classified: the central osteoma arising from the endosteum, the peripheral osteoma from the periosteum, and the extraskeletal soft tissue osteoma. in the craniofacial region, peripheral osteomas of the zygoma are quite rare. A literature review identified 7 cases of zygomatic arch and 3 cases of zygomatic body. This is the first report of zygomatic osteoma that was endoscopically removed. This report presents a rare case of osteoma of the zygoma and its endoscopic approach. The authors were able to confirm that endo-scopic approach of this zygomatic osteoma was safe and effective surgical choice.

Core Extirpation and Zygoma Reduction: A New Surgical Approach for Fibrous Dysplasia of Zygomaticomaxillary Region.

INTRODUCTION: In case of zygomaticomaxillary fibrous dysplasia (FD), surgical treatment is often required due to visual disturbance, exophthalmos, and also necessary for cosmetic reasons. However, it is not easy to determine the timing and method of operation. The objective of our study is to define a new surgical option, for the treatment of FD of zygomaticomaxillary area. MATERIALS AND METHODS: Five patients affected by FD of their zygomaticomaxillary area who underwent surgery with a core extirpation were included in this study. A retrospective chart review and pre- and post-operative analysis of computed tomography scan were performed. RESULTS: All patients underwent core extirpation surgery and zygoma reduction was combined in 2 patients. All patients showed the cessation of the increase of external size postoperatively and results of the operation were well maintained over the follow-up period of 1 year. CONCLUSIONS: In this article, we present our experiences in the management of FD using the core extirpation with or without zygoma reduction, focusing on surgical indication, techniques, and results. Although there are limitations due to selective operative indication, the procedure can be usefully performed to prevent external growth and avoid repetitive surgery.

Development of a Robot Arm Link System Embedded with a Three-Axis Sensor with a Simple Structure Capable of Excellent External Collision Detection.

In order to effectively detect the contact state between the operator and the collaborative robot, a sensor with excellent external force detection performance is needed. The existing force/torque sensor and joint torque sensor, which are the two main external force sensors methods in cooperative robots, have limitations; only the force exerted at the end effector is detected, and it induces a low stiffness in the overall structure which affects the control performance. In the case of sensorless collision detection methods that utilize the current sensor that is used for motor control, the estimation of the performance of external force is sensitive to the sensor noise and dynamic model accuracy only to the extent that it can be used for collision detection. In this paper, we propose a strain gauge-based three-axis sensor of a cylindrical shape, which is often used as a link in a robot. By integrating sensors with robot links, the external force can be precisely measured without compromising the stiffness and is decoupled with joint disturbances, such as motor friction. Sensor calibration is conducted using static load evaluation equipment, and the reliability of collision detection is confirmed by comparing the theoretical/structural analysis results. Through the weight test and sensor characteristic evaluation, the performance and output stability are validated.

Light-Activated Monomethyl Auristatin E Prodrug Nanoparticles for Combinational Photo-Chemotherapy of Pancreatic Cancer.

Pancreatic cancer is a highly fatal disease that is becoming an increasingly leading cause of cancer-related deaths. In clinic, the most effective approach to treat pancreatic cancers is the combination treatment of several chemotherapeutic drugs, including fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), but this approach is not adequate to manage patients due to their severe toxic side effects. Herein, we proposed light-activated monomethyl auristatin E (MMAE) prodrug nanoparticles for combinational photo-chemotherapy and optimized its applications for pancreatic cancer treatment. The photosensitizer (Ce6) and chemotherapeutic drug (MMAE) were conjugated through caspase-3-specific cleavable peptide (KGDEVD). The resulting CDM efficiently promoted the reactive oxygen species (ROS) under visible light irradiation and thereby induced caspase-3 overexpression in pacreatic cancers, which subsequently released the MMAE from the system. Importantly, MMAE released from CDM further amplified the activation of CDM into MMAE by inducing extensive apoptotic cell death in tumor microenvironment for treatment of tumor cells in deep in the tumor tissues as far visible light cannot reach. In addition, CDM formed prodrug nanoparticles via intermolecular π-π stacking and hydrophobic interactions, allowing durable and reliable treatment by preventing fast leakage from the pancreatic cancers via the lymphatic vessels. The CDM directly (intratumoral) injected into pancreatic cancers in orthotopic models through an invasive approach significantly delayed the tumor progression by combinational photo-chemotherapy with less toxic side effects. This study offers a promising and alternative approach for safe and more effective pancreatic cancer treatment via prodrug nanoparticles that combine photodynamic therapy and chemotherapy.

A case of carboxyatractyloside intoxication by ingestion of the cocklebur (Xanthium strumarium) in a Korean native cow.

A 19-month-old Korean native cow died the following day after consuming new silage. Grossly, the liver showed enlargement, redness, and haemorrhages in all the lobes. Additionally, many of the bur-shaped fruits of the cocklebur (Xanthium strumarium) were found in the gastric contents. The histological evaluation confirmed centrilobular hepatic necrosis. Additionally, carboxyatractyloside (CATR), a material fatal to animals found in the cocklebur, was detected in the gastric contents using high-performance liquid chromatography-quadrupole-time of flight mass spectrometry (HPLC-Q-TOF-MS). Based on the pathological findings and analytical confirmation, CATR intoxication was diagnosed. Therefore, careful feeding and elimination of the cocklebur is essential for minimising economic loss.

Clinical cases of zoonotic Cryptosporidium parvum (subtype IIdA15G1) infections in Korean goats.

Cryptosporidium parvum is an enteric protozoan, which causes severe diarrhoea in a wide range of vertebrate hosts including ruminants and humans. C. parvum infections are responsible for immense economic losses to the livestock industry; furthermore, the zoonotic spread of the infection may lead to mortality in immunosuppressed humans. In the present study, we report two cases of severe cryptosporidiosis in goat kids in the Republic of Korea. Both cases were afflicted with severe diarrhoea upon presentation; the histopathological examinations revealed atrophied and fused intestinal villi and numerous circular basophilic organisms in the jejunum and ileum. Both cases were diagnosed with cryptosporidiosis based on the results of the histopathological analysis, amplification of the C. parvum gp60 gene, modified Ziehl-Neelsen staining, and C. parvum antigen ELISA. According to the phylogenetic analysis using the C. parvum gp60 gene for the genetic subtypes, the C. parvum isolates were identified as subtype IIdA15G1 with zoonotic potential. This is the first pathological report of caprine cryptosporidiosis induced by C. parvum subtype IId in the Republic of Korea. Considering the clinical manifestations associated with the pathological lesions and the zoonotic significance of these findings, the continuous monitoring and prevention of C. parvum infections in goats are essential for minimising the economic losses in ruminant farms and in maintaining public health safety standards.

The Relationship between Perioperative Blood Transfusion and Postoperative Delirium in Patients Undergoing Spinal Fusion Surgery: Clinical Data Warehouse Analysis.

Background and Objectives: For preventing postoperative delirium (POD), identifying the risk factors is important. However, the relationship between blood transfusion and POD is still controversial. The aim of this study was to identify the risk factors of POD, to evaluate the impact of blood transfusion in developing POD among people undergoing spinal fusion surgery, and to show the effectiveness of big data analytics using a clinical data warehouse (CDW). Materials and Methods: The medical data of patients who underwent spinal fusion surgery were obtained from the CDW of the five hospitals of Hallym University Medical Center. Clinical features, laboratory findings, perioperative variables, and medication history were compared between patients without POD and with POD. Results: 234 of 3967 patients (5.9%) developed POD. In multivariate logistic regression analysis, the risk factors of POD were as follows: Parkinson's disease (OR 5.54, 95% CI 2.15-14.27; p < 0.001), intensive care unit (OR 3.45 95% CI 2.42-4.91; p < 0.001), anti-psychotics drug (OR 3.35 95% CI 1.91-5.89; p < 0.001), old age (≥70 years) (OR 3.08, 95% CI 2.14-4.43; p < 0.001), depression (OR 2.8 95% CI 1.27-6.2; p < 0.001). The intraoperative transfusion (OR 1.1, 95% CI 0.91-1.34; p = 0.582), and the postoperative transfusion (OR 0.91, 95% CI 0.74-1.12; p = 0.379) had no statistically significant effect on the incidence of POD. Conclusions: There was no relationship between perioperative blood transfusion and the incidence of POD in spinal fusion surgery. Big data analytics using a CDW could be helpful for the comprehensive understanding of the risk factors of POD, and for preventing POD in spinal fusion surgery.

Comparison of the Effect of Sugammadex and Pyridostigmine on Postoperative Catheter-Related Bladder Discomfort: A Retrospective Matched Cohort Analysis.

Background and Objectives: As the use of sugammadex for reversing neuromuscular blockade during general anesthesia increases, additional effects of sugammadex have been reported compared to cholinesterase inhibitors. Here, we compare the incidence of postoperative catheter-related bladder discomfort (CRBD) between sugammadex and pyridostigmine/glycopyrrolate treatments for reversing neuromuscular blockade. Materials and Methods: We retrospectively analyzed patients aged ≥ 18 years who underwent surgery under general anesthesia, received sugammadex or pyridostigmine with glycopyrrolate to reverse neuromuscular blockade, and had a urinary catheter in the post-anesthesia care unit between March 2019 and February 2021. After applying the exclusion criteria, 1179 patients were included in the final analysis. The incidence and severity of CRBD were collected from post-anesthesia recovery records. Results: The incidence was 13.7% in the sugammadex group (n = 211) and 24.7% in the pyridostigmine group (n = 968). Following propensity score matching, 211 patients each were included in the pyridostigmine and sugammadex matched group (absolute standardized difference (ASD), 0.01-0.05). Compared to the pyridostigmine group, the odds ratio for CRBD occurring in the sugammadex group was 0.568 (95% confidential interval, 0.316-1.021, p = 0.059). Conclusions: Sugammadex has a similar effect on the occurrence of postoperative CRBD compared with pyridostigmine.

Transition-Metal Dichalcogenide Artificial Antibodies with Multivalent Polymeric Recognition Phases for Rapid Detection and Inactivation of Pathogens.

Antibodies are recognition molecules that can bind to diverse targets ranging from pathogens to small analytes with high binding affinity and specificity, making them widely employed for sensing and therapy. However, antibodies have limitations of low stability, long production time, short shelf life, and high cost. Here, we report a facile approach for the design of luminescent artificial antibodies with nonbiological polymeric recognition phases for the sensitive detection, rapid identification, and effective inactivation of pathogenic bacteria. Transition-metal dichalcogenide (TMD) nanosheets with a neutral dextran phase at the interfaces selectively recognized S. aureus, whereas the nanosheets bearing a carboxymethylated dextran phase selectively recognized E. coli O157:H7 with high binding affinity. The bacterial binding sites recognized by the artificial antibodies were thoroughly identified by experiments and molecular dynamics simulations, revealing the significance of their multivalent interactions with the bacterial membrane components for selective recognition. The luminescent WS2 artificial antibodies could rapidly detect the bacteria at a single copy from human serum without any purification and amplification. Moreover, the MoSe2 artificial antibodies selectively killed the pathogenic bacteria in the wounds of infected mice under light irradiation, leading to effective wound healing. This work demonstrates the potential of TMD artificial antibodies as an alternative to antibodies for sensing and therapy.

Bakuchiol, main component of root bark of Ulmus davidiana var. japonica, inhibits TGF-ß-induced in vitro EMT and in vivo metastasis.

Cancer is a second leading cause of death worldwide, and metastasis is the major cause of cancer-related mortality. The epithelial-mesenchymal transition (EMT), known as phenotypic change from epithelial cells to mesenchymal cells, is a crucial biological process during development. However, inappropriate activation of EMT contributes to tumor progression and promoting metastasis; therefore, inhibiting EMT is considered a promising strategy for developing drugs that can treat or prevent cancer. In the present study, we investigated the anti-cancer effect of bakuchiol (BC), a main component of Ulmus davidiana var. japonica, in human cancer cells using A549, HT29 and MCF7 cells. In MTT and colony forming assay, BC exerted cytotoxicity activity against cancer cells and inhibited proliferation of these cells. Anti-metastatic effects by BC were further confirmed by observing decreased migration and invasion in TGF-ß-induced cancer cells after BC treatment. Furthermore, BC treatment resulted in increase of E-cadherin expression and decrease of Snail level in Western blotting and immunofluorescence analysis, supporting its anti-metastatic activity. In addition, BC inhibited lung metastasis of tail vein injected human cancer cells in animal model. These findings suggest that BC inhibits migration and invasion of cancers by suppressing EMT and in vivo metastasis, thereby may be a potential therapeutic agent for treating cancers.

Prognostic value of baseline metabolic tumor volume in children and adolescents with intermediate-risk Hodgkin lymphoma treated with chemo-radiation therapy: FDG-PET parameter analysis in a subgroup from COG AHOD0031.

BACKGROUND: Positron emission tomography (PET)-based measures of baseline total-body tumor burden may improve risk stratification in intermediate-risk Hodgkin lymphoma (HL). MATERIALS AND METHODS: Evaluable patients were identified from a cohort treated homogeneously with the same combined modality regimen on the Children's Oncology Group AHOD0031 study. Eligible patients had high-quality baseline PET scans. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were each measured based on 15 thresholds for every patient. Univariate and multivariable Cox regression and Kaplan-Meier survival analyses assessed for an association of MTV and TLG with event-free survival (EFS). RESULTS: From the AHOD0031 cohort (n = 1712), 86 patients were identified who (i) were treated with four cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC) chemotherapy followed by involved field radiotherapy, and (ii) had a baseline PET scan that was amenable to quantitative analysis. Based on univariate Cox regression analysis, six PET-derived parameters were significantly associated with EFS. For each of these, Kaplan-Meier analyses and the log-rank test were used to compare patients with highest tumor burden (i.e., highest 15%) to the remainder of the cohort. EFS was significantly associated with all six PET parameters (all p < .029). In a multivariable model controlling for important covariates including disease bulk and response to chemotherapy, MTV2BP was significantly associated with EFS (p = .012). CONCLUSION: Multiple baseline PET-derived volumetric parameters were associated with EFS. MTV2BP was highly associated with EFS when controlling for disease bulk and response to chemotherapy. Incorporation of baseline MTV into risk-based treatment algorithms may improve outcomes in intermediate-risk HL.

Identification of ortho catechol-containing isoflavone as a privileged scaffold that directly prevents the aggregation of both amyloid ß plaques and tau-mediated neurofibrillary tangles and its in vivo evaluation.

In this study, polyhydroxyisoflavones that directly prevent the aggregation of both amyloid ß (Aß) and tau were expediently synthesized via divergent Pd(0)-catalyzed Suzuki-Miyaura coupling and then biologically evaluated. By preliminary structure-activity relationship studies using thioflavin T (ThT) assays, an ortho-catechol containing isoflavone scaffold was proven to be crucial for preventing both Aß aggregation and tau-mediated neurofibrillary tangle formation. Additional TEM experiment confirmed that ortho-catechol containing isoflavone 4d significantly prevented the aggregation of both Aß and tau. To investigate the mode of action (MOA) of 4d, which possesses an ortho-catechol moiety, 1H-15N HSQC NMR analysis was thoroughly performed and the result indicated that 4d could directly inhibit both the formation of Aß42 fibrils and the formation of tau-derived neurofibrils, probably through the catechol-mediated nucleation of tau. Finally, 4d was demonstrated to alleviate cognitive impairment and pathologies related to Alzheimer's disease in a 5XFAD transgenic mouse model.