Difference in Baseline Antimicrobial Prescription Patterns of Hospitals According to Participation in the National Antimicrobial Monitoring and Feedback System in Korea.

This study aimed to evaluate the differences in the baseline characteristics and patterns of antibiotic usage among hospitals based on their participation in the Korea National Antimicrobial Use Analysis System (KONAS). We obtained claims data from the National Health Insurance for inpatients admitted to all secondary- and tertiary-care hospitals between January 2020 and December 2021 in Korea. 15.9% (58/395) of hospitals were KONAS participants, among which the proportion of hospitals with > 900 beds (31.0% vs. 2.6%, P < 0.001) and tertiary care (50.0% vs. 5.2%, P < 0.001) was higher than that among non-participants. The consumption of antibiotics targeting antimicrobial-resistant gram positive bacteria (33.7 vs. 27.1 days of therapy [DOT]/1,000 patient-days, P = 0.019) and antibiotics predominantly used for resistant gram-negative bacteria (4.8 vs. 3.7 DOT/1,000 patient-days, P = 0.034) was higher in KONAS-participating versus -non-participating hospitals. The current KONAS data do not fully represent all secondary- and tertiary-care hospitals in Korea; thus, the KONAS results should be interpreted with caution.

Exploring the Challenges of Distinguishing Punctate Inner Choroidopathy from Multifocal Choroiditis and Panuveitis.

PURPOSE: This retrospective case series aimed to assess the concordance between clinical diagnoses of punctate inner choroidopathy (PIC) and multifocal choroiditis and panuveitis (MCP) using the 2021 Standardization of Uveitis Nomenclature (SUN) Working Group criteria. METHODS: Using the medical records of the patients, we reevaluated 100 eyes of 75 patients with idiopathic multifocal chorioretinal inflammatory lesions based on SUN criteria and compared the result to the clinical diagnosis. RESULTS: Of 100 eyes, 29 eyes (29%) were diagnosed as PIC and 15 eyes (15%) were diagnosed as MCP using SUN criteria, and 56 (56%) eyes could not be diagnosed as either. Clinically diagnosed PIC eyes were significantly more myopic than the clinically diagnosed MCP eyes (mean spherical equivalent -6.65 ± 4.63 vs. -3.85 ± 2.31, P = 0.01). Sixteen eyes with vitreous inflammation were all clinically diagnosed as MCP, but four (25%) could not be diagnosed as MCP using SUN criteria. CONCLUSIONS: The existing diagnostic criteria showed limitations in capturing all clinical cases of PIC or MCP, and adding or revising criteria on features such as vitreous inflammation or myopia, could be considered to enhance diagnostic accuracy.

Living lab modelling as a pilot study assessing the potential psychological health benefits of forest environment for cancer survivors.

OBJECTIVE: To evaluate the physiological and psychological changes in cancer survivors who engage in repeated forest therapy in a living environment. METHODS: This study included stay-based forest therapy for female cancer survivors aged ≥40 years. The program was conducted in two cycles, each spanning 3 weeks and consisting of a 2-night, 3-day stay, followed by daily life integration. The cycles were repeated from July 2, 2022, to August 18, 2022. Participant assessment included standard physical health parameters and a questionnaire on general characteristics, lifestyle habits, stress levels, and health status. RESULTS: Thirty-seven female cancer survivors participated in the forest healing program, 56.8% of whom had a history of breast cancer. The median body mass index (BMI) was 23.80 kg/m2 (range, 21.00-25.60). More than half of the patients reported mild-to-moderate fatigue, chronic pain, and mild-to-moderate depression (81%, 65%, and 73%, respectively). After two cycles of forest therapy, no significant differences were observed in terms of fatigue, pain, or BMI levels. However, significant improvements were found in quality of life measures, particularly the psychological quality of life (mean score 12.54 at baseline vs. 13.48 after cycle 2; P=0.007). Positive improvements were also observed in terms of stress (mean score 17.03 vs. 13.76; P=0.002) and depression (mean score 8.35 vs. 6.11; P=0.002) levels. CONCLUSION: Our forest-healing program demonstrated that nature-based therapies improve the mental health and quality of life of female cancer survivors, suggesting the need for further research on nature-based interventions to better support cancer survivors.

Comparing Diagnostic Accuracy of Radiologists versus GPT-4V and Gemini Pro Vision Using Image Inputs from Diagnosis Please Cases.

Background The diagnostic abilities of multimodal large language models (LLMs) using direct image inputs and the impact of the temperature parameter of LLMs remain unexplored. Purpose To investigate the ability of GPT-4V and Gemini Pro Vision in generating differential diagnoses at different temperatures compared with radiologists using Radiology Diagnosis Please cases. Materials and Methods This retrospective study included Diagnosis Please cases published from January 2008 to October 2023. Input images included original images and captures of the textual patient history and figure legends (without imaging findings) from PDF files of each case. The LLMs were tasked with providing three differential diagnoses, repeated five times at temperatures 0, 0.5, and 1. Eight subspecialty-trained radiologists solved cases. An experienced radiologist compared generated and final diagnoses, considering the result correct if the generated diagnoses included the final diagnosis after five repetitions. Accuracy was assessed across models, temperatures, and radiology subspecialties, with statistical significance set at P < .007 after Bonferroni correction for multiple comparisons across the LLMs at the three temperatures and with radiologists. Results A total of 190 cases were included in neuroradiology (n = 53), multisystem (n = 27), gastrointestinal (n = 25), genitourinary (n = 23), musculoskeletal (n = 17), chest (n = 16), cardiovascular (n = 12), pediatric (n = 12), and breast (n = 5) subspecialties. Overall accuracy improved with increasing temperature settings (0, 0.5, 1) for both GPT-4V (41% [78 of 190 cases], 45% [86 of 190 cases], 49% [93 of 190 cases], respectively) and Gemini Pro Vision (29% [55 of 190 cases], 36% [69 of 190 cases], 39% [74 of 190 cases], respectively), although there was no evidence of a statistically significant difference after Bonferroni adjustment (GPT-4V, P = .12; Gemini Pro Vision, P = .04). The overall accuracy of radiologists (61% [115 of 190 cases]) was higher than that of Gemini Pro Vision at temperature 1 (T1) (P < .001), while no statistically significant difference was observed between radiologists and GPT-4V at T1 after Bonferroni adjustment (P = .02). Radiologists (range, 45%-88%) outperformed the LLMs at T1 (range, 24%-75%) in most subspecialties. Conclusion Using direct radiologic image inputs, GPT-4V and Gemini Pro Vision showed improved diagnostic accuracy with increasing temperature settings. Although GPT-4V slightly underperformed compared with radiologists, it nonetheless demonstrated promising potential as a supportive tool in diagnostic decision-making. © RSNA, 2024 See also the editorial by Nishino and Ballard in this issue.

Computed tomography-based vascular burden index as a predictor of vascular resection and pathological vascular invasion in pancreatic cancer with neo-adjuvant chemotherapy.

BACKGROUND: Determination of vessel resection in patients with pancreatectomy after neo-adjuvant chemotherapy remains controversial. The recently introduced computed tomography-based vascular burden index presents a potential solution to this challenge. This study aimed to evaluate the model performance for the prediction of vascular resection and pathological invasion. METHODS: Patients who underwent surgery after neo-adjuvant chemotherapy were included. Two independent reviewers measured the vascular tumour burden index around the adjacent artery (AVBI), and vein (VVBI). The area under the curve was compared to assess the predictive capacity of vascular burden index values and their changes for vascular resection and pathological vascular invasion. RESULTS: Among 252 patients, 179 and 73 had borderline resectable and locally advanced pancreatic cancer, respectively. Concurrent vessel resection and pathological vascular invasion were observed in 121 (48.0 %) and 42 (16.6 %) patients, respectively. In all patients, the VVBI (area under the curve: 0.872) and AVBI (0.911) after neo-adjuvant therapy significantly predicted vessel resection. In patients with vascular resection, the VVBI after neo-adjuvant chemotherapy (0.752) and delta value of the AVBI (0.706) demonstrated better performance for predicting pathological invasion of the resected vein. The regression of the AVBI and VVBI was an independent prognostic factor for survival (hazard ratio: 0.54, 95 % confidence interval: 0.34-0.85; P = 0.009) CONCLUSIONS: Regressed VVBI on serial computed tomography scans is useful for predicting vein resection and pathological venous invasion before surgery. The delta value of the AVBI may therefore be helpful for predicting pathological arterial invasion after neo-adjuvant chemotherapy.

Nationwide Analysis of Antimicrobial Prescription in Korean Hospitals between 2018 and 2021: The 2023 KONAS Report.

BACKGROUND: Data on antimicrobial use at the national level are crucial for establishing domestic antimicrobial stewardship policies and enabling medical institutions to benchmark each other. This study aimed to analyze antimicrobial use in Korean hospitals. MATERIALS AND METHODS: We investigated antimicrobials prescribed in Korean hospitals between 2018 and 2021 using data from the Health Insurance Review and Assessment. Primary care hospitals (PCHs), secondary care hospitals (SCHs), and tertiary care hospitals (TCHs) were included in this analysis. Antimicrobials were categorized according to the Korea National Antimicrobial Use Analysis System (KONAS) classification, which is suitable for measuring antimicrobial use in Korean hospitals. RESULTS: Among over 1,900 hospitals, PCHs constituted the highest proportion, whereas TCHs had the lowest representation. The most frequently prescribed antimicrobials in 2021 were piperacillin/ß-lactamase inhibitor (9.3%) in TCHs, ceftriaxone (11.0%) in SCHs, and cefazedone (18.9%) in PCHs. Between 2018 and 2021, the most used antimicrobial classes according to the KONAS classification were 'broad-spectrum antibacterial agents predominantly used for community-acquired infections' in SCHs and TCHs and 'narrow spectrum beta-lactam agents' in PCHs. Total consumption of antimicrobials decreased from 951.7 to 929.9 days of therapy (DOT)/1,000 patient-days in TCHs and 817.8 to 752.2 DOT/1,000 patient-days in SCHs during study period; however, no reduction was noted in PCHs (from 504.3 to 527.2 DOT/1,000 patient-days). Moreover, in 2021, the use of reserve antimicrobials decreased from 13.6 to 10.7 DOT/1,000 patient-days in TCHs and from 4.6 to 3.3 DOT/1,000 patient-days in SCHs. However, in PCHs, the use increased from 0.7 to 0.8 DOT/1,000 patient-days. CONCLUSION: This study confirmed that antimicrobial use differed according to hospital type in Korea. Recent increases in the use of total and reserve antimicrobials in PCHs reflect the challenges that must be addressed.

Clinical impact and potential utility of non-enhanced computed tomography performed immediately after transarterial chemoembolization for hepatocellular carcinoma.

Background: Intratumoral lipiodol deposition following transarterial chemoembolization (TACE) is associated with the prognosis of hepatocellular carcinoma (HCC) patients. However, there is insufficient evidence regarding the actual clinical significance of the imaging tests conducted to evaluate the lipiodol uptake after TACE. This study evaluates the clinical impact and potential utility of performing immediate post-TACE non-enhanced computed tomography (NECT) on the treatment of HCC. Methods: This retrospective study at a tertiary referral center included patients undergoing their first session of conventional TACE for initial treatment of HCC from November 2021 to December 2022 with available immediate post-TACE NECT. Patients were categorized based on lipiodol uptake into Cohorts A (incomplete uptake with additional treatment before the first follow-up 1 month after TACE), B incomplete uptake without additional treatment before first follow-up), and C (complete uptake). Survival curves for the time to progression (TTP) were estimated using the Kaplan-Meier method and were compared by using the log-rank test. Results: Out of 189 patients, 58 (29.6%) showed incomplete lipiodol uptake; 2 in Cohort A and 56 in Cohort B. Cohort C included 131 patients (69.3%). Cohort B had the highest rate of residual viable tumor (48.2%) 1 month after TACE, compared to the other cohorts (0% in Cohort A and 32.1% in Cohort C). The median TTP of Cohort B was 7.9 months [95% confidence interval (CI): 4.6-15.7 months], significantly shorter than the 15.4 months (95% CI: 10.9-20.9 months) for Cohort C (P=0.03). During follow-up, no progression occurred in Cohort A. Conclusions: Assessment of lipiodol uptake by performing immediate post-TACE NECT can stratify HCC patients and facilitate early prediction of therapeutic response. Identifying suboptimal lipiodol uptake immediately after TACE can aid future treatment adjustments and potentially improving oncologic outcomes.

Recombinant Human IL-32θ Induces Polarization Into M1-like Macrophage in Human Monocytic Cells.

The tumor microenvironment (TME) is formed by several immune cells. Notably, tumor-associated macrophages (TAMs) are existed in the TME that induce angiogenesis, metastasis, and proliferation of cancer cells. Recently, a point-mutated variant of IL-32θ was discovered in breast cancer tissues, which suppressed migration and proliferation through intracellular pathways. Although the relationship between cancer and IL-32 has been previously studied, the effects of IL-32θ on TAMs remain elusive. Recombinant human IL-32θ (rhIL-32θ) was generated using an Escherichia coli expression system. To induce M0 macrophage polarization, THP-1 cells were stimulated with PMA. After PMA treatment, the cells were cultured with IL-4 and IL-13, or rhIL-32θ. The mRNA level of M1 macrophage markers (IL-1ß, TNFα, inducible nitric oxide synthase) were increased by rhIL-32θ in M0 macrophages. On the other hand, the M2 macrophage markers (CCL17, CCL22, TGFß, CD206) were decreased by rhIL-32θ in M2 macrophages. rhIL-32θ induced nuclear translocation of the NF-κB via regulation of the MAPK (p38) pathway. In conclusion, point-mutated rhIL-32θ induced the polarization to M1-like macrophages through the MAPK (p38) and NF-κB (p65/p50) pathways.

Is Hooke's law applicable to an orthodontic cantilever?

INTRODUCTION: This study aimed to analyze the load-deflection characteristics of an orthodontic cantilever by using the large deflection elastic model. METHODS: We experimentally measured the vertical deflections of a cantilever with round or rectangular cross-sections, with lengths of 20 mm and 30 mm, and made of either stainless steel or titanium molybdenum alloy. The measurements were obtained under clinically relevant loading ranges (20-60 g of force for round and 20-140 g of force for rectangular wires) and compared with theoretical predictions derived from small and large deflection elastic models. Load-deflection and tangent stiffness curves were subsequently plotted. RESULTS: The impact of a permanent deformation was clinically insignificant. The stiffness of the cantilever increased with the load or deflection rather than remaining constant. Within the clinical loading range, we identified stiffness reversal loading values at which the stiffness of titanium molybdenum alloy surpassed that of stainless steel. The textbook guidelines on cantilevers can apply only when the vertical deflection remains within 16% of its length. CONCLUSIONS: Within the typical clinical loading range, the load-deflection relationship of a cantilever deviates from Hooke's law because of the prominent deflection trait. The conventional model remains effective when the vertical deflection is within 16% of the cantilever length. Otherwise, it is advisable to determine the load and stiffness on the basis of actual measurements rather than relying on theoretical predictions.

Multifaceted roles of trained immunity in diverse pathological contexts.

Trained immunity, an innate immune response characterized by enhanced cellular responsiveness, exhibits a profound memory akin to adaptive immunity. This phenomenon involves intricate metabolic and epigenetic reprogramming triggered by stimuli such as ß-glucan and BCG, shaping innate immune memory. Following elucidation of the background on trained immunity, it is important to explore its multifaceted roles in various pathological contexts. In this review, we delve into the specific contributions of trained immunity in the intricate landscape of viral infections, tumorigenesis, and diverse inflammatory diseases, shedding light on its potential as a therapeutic target, and offering comprehensive understanding of its broader immunological implications.

HPK1 Dysregulation-Associated NK Cell Dysfunction and Defective Expansion Promotes Metastatic Melanoma Progression.

Distant metastasis, the leading cause of cancer death, is efficiently kept in check by immune surveillance. Studies have uncovered peripheral natural killer (NK) cells as key antimetastatic effectors and their dysregulation during metastasis. However, the molecular mechanism governing NK cell dysfunction links to metastasis remains elusive. Herein, MAP4K1 encoding HPK1 is aberrantly overexpressed in dysfunctional NK cells in the periphery and the metastatic site. Conditional HPK1 overexpression in NK cells suffices to exacerbate melanoma lung metastasis but not primary tumor growth. Conversely, MAP4K1-deficient mice are resistant to metastasis and further protected by combined immune-checkpoint inhibitors. Mechanistically, HPK1 restrains NK cell cytotoxicity and expansion via activating receptors. Likewise, HPK1 limits human NK cell activation and associates with melanoma NK cell dysfunction couples to TGF-ß1 and patient response to immune checkpoint therapy. Thus, HPK1 is an intracellular checkpoint controlling NK-target cell responses, which is dysregulated and hijacked by tumors during metastatic progression.

A protocolized five strategies in open repair for ruptured abdominal aortic aneurysm.

OBJECTIVES: Although the medical field has made significant progress, there has been little improvement in the survival rate of patients with ruptured abdominal aortic aneurysms (rAAAs). We implemented a protocol consisting of five strategies in the management of rAAA patients who underwent open repair surgery. METHODS: The protocol comprised the following strategies: intentional hypotension <70 mmHg, lung first and kidney last policy (restricted fluid resuscitation and permissive oligoanuria), immediate postoperative extubation, free-water intake with active ambulation, and open abdomen with the routine second-look operation. The study included 13 patients (11 male) with a mean age of 75.5 ± 7.4 (range: 58-87) years who underwent the procedure from 2016 to 2018, with a mean follow-up of 40.1 ± 9.04 months. Five deteriorating to hemodynamic shock and decreased consciousness requiring intubation and ventilation prior to surgery were observed. Two of these patients required preoperative cardiopulmonary resuscitation (CPR). RESULTS: All patients regained consciousness after surgery, including the two patients who required cardiopulmonary resuscitation. Immediate postoperative extubation was performed in nine patients, but two (22.2%) of them needed re-intubation due to ventilation/perfusion mismatch. Four patients underwent continuous renal replacement therapy, with three of them having anuria for up to 48 h after surgery. Two of these patients made a full recovery. Daily ambulation was carried out for a mean of 4.77 ± 3.5 (range 1-13) days with an open abdomen, during which no significant events were reported. Four cases of colon ischemia/necrosis were identified in the second-look operation, with two patients requiring Hartman's procedure and the other two undergoing left colon partial resection. There were two in-hospital mortalities (15.4%). CONCLUSIONS: A protocol-based approach, through multidisciplinary team consensus and the development of optimal surgical strategies, could improve clinical outcomes for patients undergoing emergency surgery for rAAA. Further studies with larger sample sizes are needed to refine the protocols.

The Impact of an Antimicrobial Stewardship Program on Days of Therapy in the Pediatric Center: An Interrupted Time-Series Analysis of a 19-Year Study.

BACKGROUND: We aimed to analyze the effects of an antimicrobial stewardship program (ASP) on the proportion of antimicrobial-resistant pathogens in bacteremia, antimicrobial use, and mortality in pediatric patients. METHODS: A retrospective single-center study was performed on pediatric inpatients under 19 years old who received systemic antimicrobial treatment from 2001 to 2019. A pediatric infectious disease attending physician started ASP in January 2008. The study period was divided into the pre-intervention (2001-2008) and the post-intervention (2009-2019) periods. The amount of antimicrobial use was defined as days of therapy per 1,000 patient-days, and the differences were compared using delta slope (= changes in slopes) between the two study periods by an interrupted time-series analysis. The proportion of resistant pathogens and the 30-day overall mortality rate were analyzed by the χ². RESULTS: The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia increased from 17% (39 of 235) in the pre-intervention period to 35% (189 of 533) in the post-intervention period (P < 0.001). The total amount of antimicrobial use significantly decreased after the introduction of ASP (delta slope value = -16.5; 95% confidence interval [CI], -30.6 to -2.3; P = 0.049). The 30-day overall mortality rate in patients with bacteremia did not increase, being 10% (55 of 564) in the pre-intervention and 10% (94 of 941) in the post-intervention period (P = 0.881). CONCLUSION: The introduction of ASP for pediatric patients reduced the delta slope of the total antimicrobial use without increasing the mortality rate despite an increased incidence of ESBL-producing gram-negative bacteremia.

Clinical Efficacy and Safety of an Automatic Closed-Suction System in Mechanically Ventilated Patients with Pneumonia: A Multicenter, Prospective, Randomized, Non-Inferiority, Investigator-Initiated Trial.

Endotracheal suctioning is an essential but labor-intensive procedure, with the risk of serious complications. A brand new automatic closed-suction device was developed to alleviate the workload of healthcare providers and minimize those complications. We evaluated the clinical efficacy and safety of the automatic suction system in mechanically ventilated patients with pneumonia. In this multicenter, randomized, non-inferiority, investigator-initiated trial, mechanically ventilated patients with pneumonia were randomized to the automatic device (intervention) or conventional manual suctioning (control). The primary efficacy outcome was the change in the modified clinical pulmonary infection score (CPIS) in 3 days. Secondary outcomes were the frequency of additional suctioning and the amount of secretion. Safety outcomes included adverse events or complications. A total of 54 participants, less than the pre-determined number of 102, were enrolled. There was no significant difference in the change in the CPIS over 72 h (-0.13 ± 1.58 in the intervention group, -0.58 ± 1.18 in the control group, p = 0.866), but the non-inferiority margin was not satisfied. There were no significant differences in the secondary outcomes and safety outcomes, with a tendency for more patients with improved tracheal mucosal injury in the intervention group. The novel automatic closed-suction system showed comparable efficacy and safety compared with conventional manual suctioning in mechanically ventilated patients with pneumonia.

Effect of transcranial direct current stimulation on supernumerary phantom limb pain in spinal cord injured patient: A case report.

BACKGROUND: Supernumerary phantom limb (SPL) sensation is the experience of additional limbs, either single or a pair of limbs. Unique to traumatic spinal cord injuries, we report effect of transcranial direct current stimulation (tDCS) on SPL pain in a patient with cervical cord injury. CASE SUMMARY: The subject was a 57-year-old man who was diagnosed with complete spinal cord injury (C6/C5, motor level; C5/C5, sensory level; AIS-A) approximately three months ago. After a period of 2 wk, we administered anodal tDCS over the motor cortex for 15 minutes at an intensity of 1.5 mA. Following that treatment, the patient experienced a decrease of SPL pain intensity and frequency, which lasted for 1 week after the end of treatment. CONCLUSION: Targeting the motor cortex through neuromodulation appears to be a promising option for the management of SPL pain.

Investigating Factors Influencing the National Cancer Screening Program among Older Individuals in Republic of Korea-Data from the Korea National Health and Nutrition Examination Survey VIII.

This study aims to determine the influencing factors of the participation of older individuals aged 65 years and above in South Korea's National Cancer Screening Program (NCSP) using data from the eighth wave (2019-2021) of the Korea National Health and Nutrition Examination Survey (KNHANES VIII), and discuss potential problems and coping strategies. Variables were selected based on Andersen's healthcare utilization model. "Participation in the NSCP" was considered the dependent variable, with independent variables including sociodemographic characteristics (sex, marital status, residence, education level, income level, economic activity, medical coverage type, and private insurance), health conditions (subjective health status, hypertension, and diabetes), and health behaviors (physical activity, monthly alcohol consumption, and current smoking status). The analysis revealed that higher participation rates correlated with being married, having an education level beyond elementary school, being employed, subscribing to private insurance, perceiving oneself as having average or poor health, engaging in physical activity, and not smoking. Sex, residence, income, medical coverage type, hypertension, diabetes, and monthly alcohol consumption were found to be insignificantly correlated. These findings underscore the importance of tailored promotion and health education for older individuals to boost NCSP participation rates, which could ultimately elevate public health standards.

Radiologic tumor border can further stratify prognosis in patients with pancreatic neuroendocrine tumor.

BACKGROUND AND OBJECTIVES: Pancreatic neuroendocrine tumor (PanNET), although rare in incidence, is increasing in recent years. Several clinicopathologic and molecular factors have been suggested for patient stratification due to the extensive heterogeneity of PanNETs. We aimed to discover the prognostic role of assessing the tumor border of PanNETs with pre-operative computed tomography (CT) images and correlate them with other clinicopathologic factors. METHODS: The radiologic, macroscopic, and microscopic tumor border of 183 surgically resected PanNET cases was evaluated using preoperative CT images (well defined vs. poorly defined), gross images (expansile vs. infiltrative), and hematoxylin and eosin-stained slides (pushing vs. infiltrative). The clinicopathologic and prognostic significance of the tumor border status was compared with other clinicopathologic factors. RESULTS: A poorly defined radiologic tumor border was observed in 65 PanNET cases (35.5 %), and were more frequent in male patients (P = 0.031), and tumor with larger size, infiltrative macroscopic growth pattern, infiltrative microscopic tumor border, higher tumor grade, higher pT category, lymph node metastasis, lymphovascular and perineural invasions (all, P < 0.001). Patients with PanNET with a poorly defined radiologic tumor border had significantly worse overall survival (OS) and recurrence-free survival (RFS; both, P < 0.001). Multivariable analysis revealed that PanNET with a poorly defined radiologic border is an independent poor prognostic factor for both OS (P = 0.049) and RFS (P = 0.027). CONCLUSION: Pre-operative CT-based tumor border evaluation can provide additional information regarding survival and recurrence in patients with PanNET.

Uncovering associations between interest in One Health and pre-existing conditions and behaviours: Evidence from a UK survey.

This paper endeavours to unveil individual characteristics associated with an interest in One Health. Through the distribution of an online survey randomly distributed among the United Kingdom population, we discovered significant correlations between pre-existing attitudes towards and relationships with nature and animals and interest in One Health, which is quantified by the number of additional pages of One Health information participants agreed to view at the survey's conclusion. Additionally, individuals with poorer mental health demonstrated a higher level of interest in One Health. The findings suggest that interest in One Health and people's connections with nature and animals are driven by the same personal preferences. These insights point towards the potential for more targeted communication strategies to specific groups, facilitating more effective promotion of the One Health concept.

Analysis on efficacy of magnetic resonance lymphangiography using INV-001 in healthy beagle dogs.

We aimed to conduct a proof-of-concept study of INV-001 in visualizing lymphatic vessels and nodes without venous contamination and to determine the optimal dose condition of INV-001 for magnetic resonance lymphangiography (MRL) in healthy beagles. MRL was performed using a 3.0-Tesla (T) whole body clinical magnetic resonance imaging (MRI) scanner. A dose-finding study of INV-001 for MRL in beagles (N = 6) was carried out according to an adaptive optimal dose finding design. For the reproducibility study (N = 6), MRL was conducted at selected INV-001 doses (0.056 and 0.112 mg Fe/kg) with a 15 mM concentration. Additionally, an excretion study (N = 3) of INV-001 was conducted by analyzing T1, T2, and T2* maps of the liver and kidney 48 h post-administration. INV-001 administration at doses of 0.056 and 0.112 mg Fe/kg (concentration: 15 mM) consistently demonstrated the visualization of contrast-enhanced lymphatic vessels and nodes without venous contamination in the beagles. The contrast enhancement effect was highest at 30 min after INV-001 administration, then gradually decreasing. No toxicity-related issues were identified during the study. After 48 h, the T1, T2, and T2* values in the liver and both kidneys were found to be comparable to the pre-administration values, indicating thorough INV-001 excretion. The optimal dosing conditions of INV-001 for MRL for contrast-enhanced visualization of lymphatic vessels and nodes exclusively with no venous contamination in beagles was determined to be 0.056 mg Fe/kg with a 15 mM concentration.

A Mutation in Tmem135 Causes Progressive Sensorineural Hearing Loss.

Transmembrane protein 135 (TMEM135) is a 52 kDa protein with five predicted transmembrane domains that is highly conserved across species. Previous studies have shown that TMEM135 is involved in mitochondrial dynamics, thermogenesis, and lipid metabolism in multiple tissues; however, its role in the inner ear or the auditory system is unknown. We investigated the function of TMEM135 in hearing using wild-type (WT) and Tmem135 FUN025/FUN025 ( FUN025 ) mutant mice on a CBA/CaJ background, a normal-hearing mouse strain. Although FUN025 mice displayed normal auditory brainstem response (ABR) at 1 month, we observed significantly elevated ABR thresholds at 8, 16, and 64 kHz by 3 months, which progressed to profound hearing loss by 12 months. Consistent with our auditory testing, 13-month-old FUN025 mice exhibited a severe loss of outer hair cells and spiral ganglion neurons in the cochlea. Our results using BaseScope in situ hybridization indicate that TMEM135 is expressed in the inner hair cells, outer hair cells, and supporting cells. Together, these results demonstrate that the FUN025 mutation in Tmem135 causes progressive sensorineural hearing loss, and suggest that TMEM135 is crucial for maintaining key cochlear cell types and normal sensory function in the aging cochlea.