Spontaneous Pneumomediastinum in a Patient with Marijuana Use.

The Macklin effect plays an essential role in the pathogenesis of spontaneous pneumomediastinum. It is the process by which is there is a blunt alveolar rupture that leads to air dissection through the bronchopulmonary sheaths and spreads into the mediastinum. Theoretically, marijuana use can cause spontaneous pneumomediastinum indirectly by inducing rigorous vomiting. We report a case of a healthy 22-year-old male with a history of recent marijuana use who presented with pneumomediastinum and rhabdomyolysis concurrently. After a thorough investigation, we concluded that this patient had spontaneous pneumomediastinum due to the Macklin effect from severe vomiting. LEARNING POINTS: Spontaneous pneumomediastinum is the presence of air in the mediastinum that occurs from an unclear aetiology.Marijuana use can trigger severe vomiting in patients, leading to spontaneous pneumomediastinum through the Macklin effect.

Assessment of safety: In vitro reverse mutation and in vivo acute oral toxicity tests of three biomass products from amino acid-producing Corynebacterium glutamicum.

Microbial fermentation has emerged as a pivotal process for sustainable production of essential goods and chemicals. Corynebacterium glutamicum is a proficient platform organism that contributes significantly to amino acid production through microbial fermentation. Despite its recognized safety, challenges persist in efficiently biosynthesizing natural products compared with other organisms. This study evaluated the safety of biomass products from bioengineered C. glutamicum through two different toxicological studies: a bacterial reverse mutation test (AMES test) and an acute oral toxicity test in rats. Three types of dried fermentation biomass products, each engineered for the enhanced production of specific amino acids (L-lysine, L-threonine, and L-tryptophan), were examined. The tests were conducted in compliance with Organization for Economic Co-operation and Development guidelines and revealed no mutagenicity or acute toxicity at the tested doses. These findings suggest the safety of biomass products from bioengineered C. glutamicum as potential feed materials, although further toxicity studies are recommended for comprehensive evaluation. This study underscores the importance of stringent safety assessments for advancing biotechnological applications and provides valuable insights into the potential utilization of microbial fermentation products in various industries. Moreover, this study highlights the significance of regulatory compliance and adherence to international standards to ensure the safety and efficacy of novel biotechnological products.

Oncological outcomes in patients with residual triple-negative breast cancer after preoperative chemotherapy.

PURPOSE: This study aimed to evaluate the clinical outcomes and prognostic implications of regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NAC) in patients with residual triple-negative breast cancer (TNBC). MATERIALS AND METHODS: We analyzed 152 patients with residual TNBC who underwent breast-conserving surgery after NAC between December 2008 and December 2017. Most patients (n = 133; 87.5%) received taxane-based chemotherapy. Adjuvant radiotherapy (RT) was administered at a total dose of 45-65 Gy in 15-30 fractions to the whole breast, with some patients also receiving RT to regional nodes. Survival was calculated using the Kaplan-Meier method, and prognostic factors influencing survival were analyzed using the Cox proportional-hazards model. RESULTS: During a median follow-up of 66 months (range, 9 to 179 months), the 5-year disease-free survival (DFS) rate was 68.0%. The 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 83.6%, 72.6%, and 78.7%, respectively. In the univariate analysis, the cN stage, ypT stage, ypN stage, axillary operation type, and RT field were associated with DFS. Multivariate analysis revealed that higher ypT stage (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.00-3.82; p = 0.049) and ypN stage (HR = 4.7; 95% CI 1.57-14.24; p = 0.006) were associated with inferior DFS. Among clinically node-positive patients, those who received RT to the breast only had a 5-year DFS of 73.7%, whereas those who received RNI achieved a DFS of 59.6% (p = 0.164). There were no differences between the DFS and RNI. CONCLUSION: In patients with residual TNBC, higher ypT and ypN stages were associated with poorer outcomes after NAC. RNI did not appear to improve DFS. More intensive treatments incorporating systemic therapy and RT should be considered for these patients.

Multiple origins of freshwater invasion and parental care reflecting ancient vicariances in the bivalve family Cyrenidae (Mollusca).

Habitat transitions in living organisms are key innovations often coupled with species diversification after their successful adaptation to new environment. The Cyrenidae is among the most well-known heterodont bivalve groups that have successfully invaded freshwater systems from brackish water environments and display diverse lineage-specific developmental modes. Phylogenetic and molecular clock-based divergence time analyses using 12 complete mitochondrial genome sequences suggest that Cyrenidae species independently colonized freshwater habitats during three distinct spatial and geological periods: one from the American continents approximately in the Early Jurassic and the two others from Australasian/East Asian continents in the Early/Middle Cretaceous and the Paleogene-Neogene boundary, respectively. This study provides significant insight into the temporal and spatial patterns of multiple freshwater invasions, aligning with ancient vicariance events inferred from different geological timelines of plate tectonics. Additionally, mitogenome phylogeny confirms the earlier hypothesis of the repeated parallel evolution of parental care system within this bivalve group.

Effects of a Pre-Conception Care Program in Women with Inflammatory Bowel Disease: A Mixed-Methods Study Including a Randomized Controlled Trial.

PURPOSE: The purpose of this study was to conduct a pre-conception care program for women of childbearing age with inflammatory bowel disease (IBD) in Korea and verify its effects on self-efficacy for IBD management, IBD-related pregnancy knowledge, and IBD-related pregnancy anxiety. It also aimed to explore the changes in participants through the program. METHODS: A convergent mixed-methods study design was adopted. In the quantitative phase, 35 women (17 and 18 in the intervention and control group, respectively) participated. The intervention group attended a program that included small-group sessions and individual tele-coaching. To confirm the effects, data were collected before and one and four weeks after the intervention. In the qualitative stage, focus group interviews and tele-coaching were conducted with the intervention group. RESULTS: After the program ended, significant differences were observed over time between the intervention and control groups for self-efficacy for IBD management (Wald χ² = 4.41, p = .036), IBD-related pregnancy knowledge (Wald χ² = 13.80, p < .001) and IBD-related pregnancy anxiety (Wald χ² = 8.61, p = .003). Qualitative data analysis revealed the following themes: (1) improving confidence in IBD management and awareness for planned pregnancy; (2) improving IBD awareness related to pregnancy and childbirth; and (3) relieving anxiety about and actively facing pregnancy. CONCLUSION: This study is meaningful in that, to the best of our knowledge, it is the first to develop a pre-conception care program for women diagnosed with IBD and confirm its effectiveness. Furthermore, this program is expected to be suitable for patient counseling and education in clinical practice.

Comparative assessment of trough and peak levels and AUC24 for amikacin in nontuberculous mycobacterial infection.

BACKGROUND: Amikacin, an aminoglycoside antibiotic, is widely used for the treatment of nontuberculous mycobacterial (NTM) infections. To date, therapeutic drug monitoring (TDM) of amikacin has primarily relied on the measurement of peak and trough levels as indicators rather than the 24-hr area under the concentration-time curve (AUC24). METHODS: NTM patients referred for amikacin TDM from March 2021 to May 2023 were assessed for the AUC24 values based on administered dose. We investigated re-admission rates, all-cause mortality and AFB smear results to evaluate clinical outcome based on the actual AUC24 values. Ototoxicity and nephrotoxicity were also investigated as adverse effects in correlation with TDM parameters. RESULTS: Among 65 patients, the mean and median values of AUC24 were 234 and 249 mg·hr/L, respectively. In a group of patients with AUC24 values less than 250 mg·hr/L, 42.4 % of patients were re-admitted for pulmonary symptoms. On the contrary, another group with AUC24 values equal to or more than 250 mg·hr/L, had lower re-admission rates (25.0 %). They also showed lower all-cause mortality rates and more improvement on acid-fast bacilli smear results. Moderate to poor correlation between AUC24 values and peak/trough levels were observed. Ototoxicity and nephrotoxicity were revealed to be associated with drug exposure duration rather than AUC24 values. CONCLUSION: In this study, we performed comparative assessment of trough/peak level, traditional clinical marker for amikacin TDM, and AUC24 value. Although AUC24 values showed poor to moderate correlation to trough/peak levels, higher AUC24 correlated with favorable clinical outcomes without additional risk of toxicity.

Real-time assessment of relative mitochondrial ATP synthesis response against inhibiting and stimulating substrates (MitoRAISE).

BACKGROUND: Mitochondria are known to synthesize adenosine triphosphate (ATP) through oxidative phosphorylation. Understanding and accurately measuring mitochondrial ATP synthesis rate can provide insights into the functional status of mitochondria and how it contributes to overall cellular energy homeostasis. Traditional methods only estimate mitochondrial function by measuring ATP levels at a single point in time or through oxygen consumption rates. This study introduced the relative mitochondrial ATP synthesis response against inhibiting and stimulating substrates (MitoRAISE), designed to detect real-time changes in ATP levels as the cells respond to substrates. METHODS: The sensitivity and specificity of the MitoRAISE assay were verified under various conditions, including the isolation of mitochondria, variations in cell numbers, cells exhibiting mitochondrial damage, and heterogeneous mixtures. Using peripheral blood mononuclear cells (PBMCs), we analyzed MitoRAISE data from 19 patients with breast cancer and 23 healthy women. RESULTS: The parameters observed in the MitoRAISE data increased depending on the quantity of isolated mitochondria and cell count, whereas it remained unmeasured in mitochondrial-damaged cell lines. Basal ATP, rotenone response, malonate response, and mitochondrial DNA copy numbers were lower in PBMCs from patients with breast cancer than in those from healthy women. CONCLUSIONS: The MitoRAISE assay has demonstrated its sensitivity and specificity by measuring relative ATP synthesis rates under various conditions. We propose MitoRAISE assay as a potential tool for monitoring changes in the mitochondrial metabolic status associated with various diseases.

Development and Psychometric Evaluation of the End-of-Life Nursing Competency Scale for Clinical Nurses.

This study aimed to develop and establish psychometric properties of the End-of-Life Nursing Competency Scale for Clinical Nurses. The initial items were derived from an in-depth literature review and field interviews. The content validation of these items was assessed over three rounds by experts in end-of-life nursing care. The study included 437 clinical nurses from four hospitals in S, E, and D cities in South Korea. The final exploratory factor analysis resulted in a scale consisting of 21 items with the following five factors that explained 68.44% of the total variance: Physical care-imminent end-of-life, legal and administrative processes, psychological care-patient and family, psychological care-nurses' self, and ethical nursing. The final model with these five subscales was validated through confirmatory factor analysis. Both item convergent-discriminant validity and known-group validity, which compared two groups based on clinical experience (p < 0.008) and working department (p < 0.008), were satisfactory. The internal consistency, as measured by Cronbach's α, ranged from 0.62 to 0.89 for the subscales and was 0.91 for the total scale. This scale has been validated as a reliable and effective instrument for clinical nurses to self-assess their end-of-life nursing competencies in a clinical setting.

Path to Suicidality in Korean Adolescents: Mediating Role of Self-Esteem, Somatic Symptoms, and Self-Harm Amid Depressive Symptoms.

This study explored the relationship between depressive symptoms and suicidality among community-dwelling adolescents aged 10-18 years, examining whether self-esteem, somatic symptoms, and self-harm mediate this relationship. Utilizing a pre-existing dataset from a nationwide adolescent mental health survey conducted in Korea in 2021, data were collected using several standardized self-administered instruments: the Korean version of Rosenberg's self-esteem scale, Korean Children's Somatization Inventory, Korean version of the Self-Harm Inventory, Mental Health Screening for Depressive Disorders, and Mental Health Screening for Suicide Risk. A path model was constructed and validated, followed by path analysis to assess the effects. Data from 6689 adolescents, including 5937 students and 752 out-of-school adolescents, revealed that 18.7% were in the suicidality group, 11.8% experienced depressive symptoms, 57.9% exhibited somatic symptoms, and 27.4% engaged in self-harm. Depressive symptoms had a positive direct effect on suicidality (ß = 0.166, p < 0.001, 95% confidence interval = 0.159-0.172). Bootstrapping tests showed a statistically significant indirect effect of self-esteem, somatic symptoms, and self-harm on the relationship between depressive symptoms and suicidality (ß = 0.021, 95% confidence interval = 0.013-0.029). Our findings suggest that self-esteem, somatic symptoms, and self-harm mediate the relationship between depressive symptoms and suicidality, and comprehensive mental health management strategies addressing these factors are recommended.

Protective effect of Phyllostachys edulis (Carrière) J. Houz against chronic ethanol-induced cognitive impairment in vivo.

BACKGROUND/OBJECTIVES: Chronic alcohol consumption causes oxidative stress in the body, which may accumulate excessively and cause a decline in memory; problem-solving, learning, and exercise abilities; and permanent damage to brain structure and function. Consequently, chronic alcohol consumption can cause alcohol-related diseases. MATERIALS/METHODS: In this study, the protective effects of Phyllostachys edulis (Carrière) J. Houz (PE) against alcohol-induced neuroinflammation and cognitive impairment were evaluated using a mouse model. Alcohol (16%, 5 g/kg/day for 6 weeks) and PE (100, 250, and 500 mg/kg/day for 21 days) were administered intragastrically to mice. RESULTS: PE showed a protective effect against memory deficits and cognitive dysfunction caused by alcohol consumption, confirmed through behavioral tests such as the T-maze, object recognition, and Morris water maze tests. Additionally, PE attenuated oxidative stress by reducing lipid oxidation, nitric oxide, and reactive oxygen species levels in the mice's brains, livers, and kidneys. Improvement of neurotrophic factors and downregulation of apoptosis-related proteins were confirmed in the brains of mice fed low and medium concentrations of PE. Additionally, expression of antioxidant enzyme-related proteins GPx-1 and SOD-1 was enhanced in the liver of PE-treated mice, related to their inhibitory effect on oxidative stress. CONCLUSION: This suggests that PE has both neuroregenerative and antioxidant effects. Collectively, these behavioral and histological results confirmed that PE could improve alcohol-induced cognitive deficits through brain neurotrophic and apoptosis protection and modulation of oxidative stress.

A Rare Presentation of a Large Left Atrial Myxoma with Gastrointestinal Symptoms.

Atrial myxoma is a rare primary tumour of the heart that typically arises from the left atrium. Patients typically present with obstructive symptoms such as dyspnoea, but constitutional and embolic symptoms can be seen as well. Gastrointestinal symptoms in the absence of embolisation are rarely reported in the literature. Our case presents a 55-year-old female who was found to have a large left atrial myxoma after presenting with gastrointestinal symptoms, which resolved upon resection of the tumour. This case illustrates that atrial myxomas can have an atypical presentation with gastrointestinal symptoms, which could be related to inflammation of gastric mucosa from interleukin-6 produced by the tumour cells. Careful history-taking followed by early detection and prompt treatment is important as atrial myxomas can lead to potentially devastating complications. LEARNING POINTS: Atrial myxomas are primary tumours of the heart that can present with a wide spectrum of symptoms.Early consideration and recognition of atypical presentations of atrial myxomas can be crucial in preventing serious consequences such as cardiac arrest.

Evolution of blaKPC Under the Pressure of Carbapenems and Ceftazidime/Avibactam in a Patient With Persistent Bacteremia Caused by Klebsiella pneumoniae.

A 30-year-old Korean man with myelodysplastic syndrome admitted hospital due to undifferentiated fever and recurrent skin lesions. He received combination therapy with high doses of meropenem, tigecycline and amikacin, yielding carbapenem resistant Klebsiella pneumoniae (CRKP) harboring K. pneumoniae carbapenemase (KPC)-2 from blood cultures on hospital day (HD) 23. Ceftazidime/avibactam was started at HD 37 and CRKP was eradicated from blood cultures after 5 days. However, ceftazidime/avibactam-resistant CRKP carrying KPC-44 emerged after 26 days of ceftazidime/avibactam treatment and then ceftazidime/avibactam-resistant, carbapenem-susceptible K. pneumoniae carrying KPC-135 was isolated on HD 65. The 3-D homology of KPC protein showed that hot spot changes in the omega loop could be attributed to ceftazidime/avibactam resistance and loss of carbapenem resistance. Whole genome sequencing of serial isolates supported that phenotypic variation was due to clonal evolution than clonal replacement. The treatment regimen was changed from CAZ/AVI to meropenem-based therapy (meropenem 1 g iv q 8 hours and amikacin 600 mg iv per day) starting with HD 72. CAZ/AVI-susceptible CRKP was presented again from blood cultures on HD 84, and the patient expired on HD 85. This is the first Korean report on the acquisition of ceftazidime/avibactam resistance through the emergence of blaKPC variants.

Prognostic value of structural variants in early breast cancer patients.

Genomic analysis of structural variants(SVs) in breast cancer (BC) patients has been conducted, but the relationship between genomic alterations and BC prognosis remains unclear. We performed RNA sequencing of 297 early BC fresh-frozen tissues. We identified SVs using three tools (STAR.Arriba, STAR.fusion, and STAR.SEQR) with the COSMIC and Mitelman databases as guide references. We found a median of five to eight fusions per sample. In BC intrinsic subtypes, normal subtype had the fewest fusions (median: 1, interquartile range [IQR]: 0, 3) followed by luminal A (median: 5.5, IQR: 2.75, 10.25), luminal B (median: 9, IQR: 6, 16.5), HER2-enriched (median: 9, IQR: 6, 16.5) and basal (median 10, IQR: 6, 15.5) subtypes (p < 0.05). Intrachromosomal fusion was more frequent observed rather than interchromosomal fusion. In location, chromosome 17 had the most fusions followed by chromosome 1 and 11. When samples were divided into high and low fusion groups based on a cut-off value of 11 fusions, five-year event-free survival (5Y-EFS) was 68.1% in the high fusion group (n = 72) and 80.1% in the low fusion group (n = 125) (p = 0.024) while 75.6% among all patients (95% confidence interval: 0.699, 0.819). Among BC subtype, TNBCs with more fusions had shorter EFS compared to those with fewer fusions (5Y-EFS rate: 65.1% vs. 85.7%; p = 0.013) but no EFS differences were observed in other BC subtypes. ESTIMATE ImmuneScore was also associated with the number of fusions in TNBC (p < 0.005) and TNBCs with high ImmuneScore had better 5Y-EFS compared to those with low ImmuneScore (p = 0.041). In conclusion, diverse fusions were observed by BC subtype, and the number of fusions was associated with BC survival outcome and immune status in TNBC.

NRF2 is a spatiotemporal metabolic hub essential for the polyfunctionality of Th2 cells.

Upon encountering allergens, CD4+ T cells differentiate into IL-4-producing Th2 cells in lymph nodes, which later transform into polyfunctional Th2 cells producing IL-5 and IL-13 in inflamed tissues. However, the precise mechanism underlying their polyfunctionality remains elusive. In this study, we elucidate the pivotal role of NRF2 in polyfunctional Th2 cells in murine models of allergic asthma and in human Th2 cells. We found that an increase in reactive oxygen species (ROS) in immune cells infiltrating the lungs is necessary for the development of eosinophilic asthma and polyfunctional Th2 cells in vivo. Deletion of the ROS sensor NRF2 specifically in T cells, but not in dendritic cells, significantly abolished eosinophilia and polyfunctional Th2 cells in the airway. Mechanistically, NRF2 intrinsic to T cells is essential for inducing optimal oxidative phosphorylation and glycolysis capacity, thereby driving Th2 cell polyfunctionality independently of IL-33, partially by inducing PPARγ. Treatment with an NRF2 inhibitor leads to a substantial decrease in polyfunctional Th2 cells and subsequent eosinophilia in mice and a reduction in the production of Th2 cytokines from peripheral blood mononuclear cells in asthmatic patients. These findings highlight the critical role of Nrf2 as a spatial and temporal metabolic hub that is essential for polyfunctional Th2 cells, suggesting potential therapeutic implications for allergic diseases.

Neoadjuvant Chemotherapy Response in Triple-Negative Apocrine Carcinoma: Comparing Apocrine Morphology, Androgen Receptor, and Immune Phenotypes.

CONTEXT.­: Apocrine differentiation and androgen receptor (AR) positivity represent a specific subset of triple-negative breast cancer (TNBC) and are often considered potential prognostic or predictive factors. OBJECTIVE.­: To evaluate the response of TNBC to neoadjuvant chemotherapy (NAC) and to assess the impact of apocrine morphology, AR status, Ki-67 labeling index (Ki-67LI), and tumor-infiltrating lymphocytes (TILs). DESIGN.­: A total of 232 TNBC patients who underwent NAC followed by surgical resection in a single institute were analyzed. The study evaluated apocrine morphology and AR and Ki-67LI expression via immunohistochemistry from pre-NAC biopsy samples. Additionally, pre-NAC intratumoral TILs and stromal TILs (sTILs) were quantified from biopsies using a deep learning model. The response to NAC after surgery was assessed based on residual cancer burden. RESULTS.­: Both apocrine morphology and high AR expression correlated with lower Ki-67LI (P < .001 for both). Apocrine morphology was associated with lower postoperative pathologic complete response (pCR) rates after NAC (P = .02), but the difference in TILs between TNBC cases with and without apocrine morphology was not statistically significant (P = .09 for sTILs). In contrast, AR expression did not significantly affect pCR (P = .13). Pre-NAC TILs strongly correlated with postoperative pCR in TNBCs without apocrine morphology (P < .001 for sTILs), whereas TNBC with apocrine morphology demonstrated an indeterminate trend (P = .82 for sTILs). CONCLUSIONS.­: Although TIL counts did not vary significantly based on apocrine morphology, apocrine morphology itself was a more reliable predictor of NAC response than AR expression. Consequently, although apocrine morphology is a rare subtype of TNBC, its identification is clinically important.

Artificial intelligence-enhanced automation of left ventricular diastolic assessment: a pilot study for feasibility, diagnostic validation, and outcome prediction.

Background: Evaluating left ventricular diastolic function (LVDF) is crucial in echocardiography; however, the complexity and time demands of current guidelines challenge clinical use. This study aimed to develop an artificial intelligence (AI)-based framework for automatic LVDF assessment to reduce subjectivity and improve accuracy and outcome prediction. Methods: We developed an AI-based LVDF assessment framework using a nationwide echocardiographic dataset from five tertiary hospitals. This framework automatically identifies views, calculates diastolic parameters, including mitral inflow and annular velocities (E/A ratio, e' velocity, and E/e' ratio), maximal tricuspid regurgitation velocity, left atrial (LA) volume index, and left atrial reservoir strain (LARS). Subsequently, it grades LVDF according to guidelines. The AI-framework was validated on an external dataset composed of randomly screened 173 outpatients who underwent transthoracic echocardiography with suspicion for diastolic dysfunction and 33 individuals from medical check-ups with normal echocardiograms at Seoul National University Bundang Hospital, tertiary medical center in Korea, between May 2012 and June 2022. Additionally, we assessed the predictive value of AI-derived diastolic parameters and LVDF grades for a clinical endpoint, defined as a composite of all-cause death and hospitalization for heart failure, using Cox-regression risk modelling. Results: In an evaluation with 200 echocardiographic examinations (167 suspected diastolic dysfunction patients, 33 controls), it achieves an overall accuracy of 99.1% in identifying necessary views. Strong correlations (Pearson coefficient 0.901-0.959) were observed between AI-derived and manually-derived measurements of diastolic parameters, including LARS as well as conventional parameters. When following the guidelines, whether utilizing AI-derived or manually-derived parameters, the evaluation of LVDF consistently showed high concordance rates (94%). However, both methods exhibited lower concordance rates with the clinician's prior assessments (77.5% and 78.5%, respectively). Importantly, both AI-derived and manually-derived LVDF grades independently demonstrated significant prognostic value [adjusted hazard ratio (HR) =3.03; P=0.03 and adjusted HR =2.75; P=0.04, respectively] for predicting clinical outcome. In contrast, the clinician's prior grading lost its significance as a prognostic indicator after adjusting for clinical risk factors (adjusted HR =1.63; P=0.36). AI-derived LARS values significantly decreased with worsening LVDF (P for trend <0.001), and low LARS (<17%) was associated with increased risk for the clinical outcome (Log-rank P=0.04) relative to that for preserved LARS (≥17%). Conclusions: Our AI-based approach for automatic LVDF assessment on echocardiography is feasible, potentially enhancing clinical diagnosis and outcome prediction.

The level of evidence in prosthodontics in relation to author's characteristics: An analysis of three leading prosthodontics journals.

Purpose: The purpose of this study was to examine the level of evidence (LOE) characteristics and associated factors that change over time in three leading prosthodontics journals. Materials and methods: Articles published in The Journal of Prosthetic Dentistry (JPD), International Journal of Prosthodontics (IJP), and Journal of Prosthodontics (JP) in 2013 and 2020 were reviewed by eight independent reviewers. After applying exclusion and inclusion criteria, the number of authors, the corresponding author's educational degree, corresponding author's origin in each clinical research article were recorded. The included articles were rated by reviewers according to the level of evidence criteria and proposed level of evidence-associated factors. Descriptive statistics, univariable, and binary logistic regression analysis were performed to investigate dependent variables and potentially associated factors. All independent variables with a significant effect were analyzed by using a multivariable test. The entry and exit alpha level were set at αE = 0.15. The statistical significance was set at α = 0.05. Results: A total of 439 articles from 3 selected journals for the years studied met the inclusion criteria. The percentages of level 1, 2, 3, 4, and 5 articles were 2.7 %, 11.4 %, 9.6 %, 13.4 % and 62.9 %, respectively. Univariable analysis results demonstrated significant associations related to the number of authors (P = 0.005), the corresponding author's educational degree (P = 0.022), and the corresponding author's geographic origin (P = 0.042). Multivariable analysis results demonstrated significant associations related to the number of authors (P = 0.002), and the corresponding author's geographic origin (P = 0.014). Conclusions: The number of authors, CA degree, and CA origin had a significant association with the LOE of included prosthodontic studies. Although there was an increase in the number of publications from 2013 to 2020, the level of evidence trend shows no improvement over the years.

Tonic type 2 immunity is a critical tissue checkpoint controlling autoimmunity in the skin.

Immunoregulatory mechanisms established in the lymphoid organs are vital for preventing autoimmunity. However, the presence of similar mechanisms in non-lymphoid tissues remains unclear. Through transcriptomic and lipidomic analyses, we find a negative association between psoriasis and fatty acid metabolism, as well as Th2 signature. Homeostatic expression of liver X receptor (LXR) and peroxisome proliferator-activated receptor gamma (PPARγ) is essential for maintaining fatty acid metabolism and for conferring resistance to psoriasis in mice. Perturbation of signal transducer and activator of transcription 6 (STAT6) diminishes the homeostatic levels of LXR and PPARγ. Furthermore, mice lacking STAT6, interleukin 4 receptor alpha (IL-4Rα), or IL-13, but not IL-4, exhibit increased susceptibility to psoriasis. Under steady state, innate lymphoid cells (ILCs) are the primary producers of IL-13. In human skin, inhibiting tonic type 2 immunity exacerbates psoriasis-like inflammation and IL-17A, while activating LXR or PPARγ inhibits them. Hence, we propose that tonic type 2 immunity, driven by IL-13-producing ILCs, represents a crucial tissue checkpoint that represses autoimmunity and maintains lipid homeostasis in the skin.

Scalp Cooling in Preventing Persistent Chemotherapy-Induced Alopecia: A Randomized Controlled Trial.

PURPOSE: Current studies of the efficacy of scalp cooling are limited by short-term duration. Therefore, we conducted a randomized controlled trial to evaluate the efficacy of scalp cooling in reducing persistent chemotherapy-induced alopecia (PCIA) 6 months after chemotherapy. METHODS: We conducted an open-label randomized controlled trial comparing scalp cooling versus control in newly diagnosed patients with breast cancer stages I-III scheduled to receive neoadjuvant or adjuvant chemotherapy with curative intent between December 2020 and August 2021. Patients were randomly assigned (2:1 ratio) to scalp cooling or usual clinical practice. The primary outcome was PCIA 6 months after chemotherapy. Hair thickness and density were measured using Folliscope 5.0. CIA-related distress was assessed using the CIA distress scale (CADS), with a higher score reflecting higher stress. RESULTS: The proportion of patients with PCIA at 6 months was 13.5% (12/89) in the scalp-cooling group and 52.0% (26/50) in the control group. The average difference in the change in hair thickness from baseline between the scalp-cooling and control groups was 9.0 µm in favor of the intervention group. The average difference in the change in hair density between intervention and control at the end of the study was -3.3 hairs/cm2. At 6 months after chemotherapy, the average difference in the change in CADS score between the intervention and control groups was -3.2 points, reflecting reduced CIA-related stress in the intervention group. CONCLUSION: Scalp cooling reduced the incidence of PCIA, primarily by increasing hair thickness compared with control. Scalp cooling is helpful in promoting qualitative hair regrowth. Yet, further research is necessary to observe longer-term benefits of scalp cooling.

Concurrent loss of LKB1 and KEAP1 enhances SHMT-mediated antioxidant defence in KRAS-mutant lung cancer.

Non-small-cell lung cancer (NSCLC) with concurrent mutations in KRAS and the tumour suppressor LKB1 (KL NSCLC) is refractory to most therapies and has one of the worst predicted outcomes. Here we describe a KL-induced metabolic vulnerability associated with serine-glycine-one-carbon (SGOC) metabolism. Using RNA-seq and metabolomics data from human NSCLC, we uncovered that LKB1 loss enhanced SGOC metabolism via serine hydroxymethyltransferase (SHMT). LKB1 loss, in collaboration with KEAP1 loss, activated SHMT through inactivation of the salt-induced kinase (SIK)-NRF2 axis and satisfied the increased demand for one-carbon units necessary for antioxidant defence. Chemical and genetic SHMT suppression increased cellular sensitivity to oxidative stress and cell death. Further, the SHMT inhibitor enhanced the in vivo therapeutic efficacy of paclitaxel (first-line NSCLC therapy inducing oxidative stress) in KEAP1-mutant KL tumours. The data reveal how this highly aggressive molecular subtype of NSCLC fulfills their metabolic requirements and provides insight into therapeutic strategies.