UNASSIGNED: Oxidative stress plays a critical role in promoting tumor resistance to hypoxia and chemotherapeutic drugs. However, the prognostic role of oxidative stress-related genes (OSRGs) in hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) has not been fully explored.
UNASSIGNED: We used transcriptome data from the GSE104580 cohort containing patients marked as responders or nonresponders to TACE therapy to identify differentially expressed OSRGs associated with TACE response (TR-OSRGs). We created a TR-OSRG prognostic signature based on TR-OSRGs using least absolute shrinkage and selection operator Cox and stepwise Cox regression analyses in a training cohort of patients with HCC (TCGA-LIHC). We verified this prognostic signature in two external cohorts of patients who received TACE for HCC (GSE14520-TACE and ZS-TACE-37). Finally, we constructed a prognostic nomogram model for predicting survival probability of patients with HCC based on Cox regression analysis.
UNASSIGNED: The TR-OSRG prognostic signature was created and shown to be a robust independent prognostic factor for treatment response and outcomes for HCC after TACE therapy. Risk scores based on this signature correlated with tumor stage and grade. Tumor samples from patients with higher risk scores exhibited more infiltration of immune cells and significantly increased expression of immune checkpoint genes. We also developed a nomogram for patients with HCC based on the TR-OSRG prognostic signature and clinical parameters; this nomogram was a useful quantitative analysis tool for predicting patient survival.
UNASSIGNED: The TR-OSRGs signature exhibited good performance in predicting treatment response and outcomes in patients with HCC treated with TACE.

BACKGROUND: Data on the preoperative factors for bariatric surgery response in patients with morbid obesity are limited, and there are no studies on the relationship between myosteatosis and surgery response.
OBJECTIVE: We investigated the preoperative factors determining bariatric surgery response and the impact of preoperative muscle fat infiltration on bariatric surgery response.
METHODS: This retrospective longitudinal cohort study included 125 individuals (37 men, 88 women) with morbid obesity who underwent bariatric surgery. Muscle fat infiltration (skeletal muscle fat index [SMFI]) was evaluated using computed tomography-based psoas muscle mass and density at the 4th lumbar level. A bariatric surgery response was defined as ≥50% excessive weight loss at one year postoperatively.
RESULTS: Before bariatric surgery, the patient mean body weight and body mass index (BMI) were 107.0 kg and 39.0 kg/m2, respectively. After one year, the mean body weight was 79.6 kg. The mean excessive weight loss at one year was 75.6% and 102 (81.6%) patients were categorized as responders. There were no statistically significant differences in initial BMI, age, sex, or proportion of diabetes between responders and non-responders. Responders were more likely to have lower SMFI and triglyceride and glycated hemoglobin A1c levels than non-responders at baseline (P<0.05). Multiple logistic regression analysis showed that a lower baseline SMFI was associated with bariatric surgery response (odds ratio=0.31, 95% confidence interval=0.14-0.69, P=0.004).
CONCLUSIONS: Preoperative myosteatosis may determine the response to bariatric surgery.

UNASSIGNED: With the increasing application of large language models like ChatGPT in various industries, its potential in the medical domain, especially in standardized examinations, has become a focal point of research.
UNASSIGNED: The aim of this study is to assess the clinical performance of ChatGPT, focusing on its accuracy and reliability in the Chinese National Medical Licensing Examination (CNMLE).
UNASSIGNED: The CNMLE 2022 question set, consisting of 500 single-answer multiple choices questions, were reclassified into 15 medical subspecialties. Each question was tested 8 to 12 times in Chinese on the OpenAI platform from April 24 to May 15, 2023. Three key factors were considered: the version of GPT-3.5 and 4.0, the prompt\'s designation of system roles tailored to medical subspecialties, and repetition for coherence. A passing accuracy threshold was established as 60%. The χ2 tests and κ values were employed to evaluate the model\'s accuracy and consistency.
UNASSIGNED: GPT-4.0 achieved a passing accuracy of 72.7%, which was significantly higher than that of GPT-3.5 (54%; P<.001). The variability rate of repeated responses from GPT-4.0 was lower than that of GPT-3.5 (9% vs 19.5%; P<.001). However, both models showed relatively good response coherence, with κ values of 0.778 and 0.610, respectively. System roles numerically increased accuracy for both GPT-4.0 (0.3%-3.7%) and GPT-3.5 (1.3%-4.5%), and reduced variability by 1.7% and 1.8%, respectively (P>.05). In subgroup analysis, ChatGPT achieved comparable accuracy among different question types (P>.05). GPT-4.0 surpassed the accuracy threshold in 14 of 15 subspecialties, while GPT-3.5 did so in 7 of 15 on the first response.
UNASSIGNED: GPT-4.0 passed the CNMLE and outperformed GPT-3.5 in key areas such as accuracy, consistency, and medical subspecialty expertise. Adding a system role insignificantly enhanced the model\'s reliability and answer coherence. GPT-4.0 showed promising potential in medical education and clinical practice, meriting further study.

UNASSIGNED: The COVID-19 pandemic devastated many countries worldwide by causing large numbers of fatalities. In our research, we wanted to answer the question: Why was there such a large difference in the mortality rate between South Korea and the United States? This is because many East Asian countries, such as Korea, had a lower mortality rate than many countries, including developed ones, across the world - the mortality rate of South Korea was about five times lower than the United States.
UNASSIGNED: This study comprehensively compares strategies used to address the COVID-19 pandemic in two different countries: South Korea and the United States. The various aspects of these two countries\' responses are examined, including initial response, information dissemination and public compliance, mitigation strategies, and vaccine rollout and their impacts.
UNASSIGNED: Early and widespread testing, rigorous contact tracing, the clear release of government information, and an organized vaccine rollout powered a proactive approach in South Korea. The United States had a contrasting response consisting of delayed and more decentralized measures, where testing lagged due to varying policies and the political controversies facing vaccine distribution.
UNASSIGNED: We signify the gravity of rapid response and testing, clear communication, and efficient vaccine distribution, as we believe this could correlate with a lower mortality rate. In addition, we discuss future directions, including the need for a specific health infrastructure and protocol against highly infectious outbreaks.
Main findings: The study suggests strategies that may be effective ways to reduce fatalities during a pandemic through a comparative analysis of COVID-19 responses in South Korea and the United States.Added knowledge: This review further consolidates the importance of an effective defense strategy involving testing, contact tracing, information dissemination, and vaccine rollouts.Global health impact for policy and action: There is a need for the development of a specific pandemic response infrastructure against fast-spreading and fatal viruses involving effective policies that take into account both the freedom and health of citizens.

UNASSIGNED: Although omalizumab has shown success in treating chronic spontaneous urticaria (CSU) patients unresponsive to antihistamines, the exact mechanism of action and predictive markers of response remain unclear.
UNASSIGNED: The aim of this study was to examine the correlation between baseline levels of biomarkers and clinical parameters with omalizumab response and response rate in patients with CSU.
UNASSIGNED: This retrospective study included 82 adult CSU patients who received omalizumab 300mg every 4 weeks for 16 weeks between January 2022 and December 2023. Treatment response was assessed using UAS7 and DLQI scores at baseline and weeks 4, 8, 12, and 16. Responders were defined as patients achieving UAS7 < 7, with early and late responders categorized based on response within or after 4 weeks, respectively. Baseline clinical features and laboratory biomarkers were compared between responders and non-responders.
UNASSIGNED: The overall response rate was 71.95% (59/82), with 23 early responders and 36 late responders. Responders had significantly lower baseline UAS7 (median: 28 vs 35, P < 0.01), DLQI (median: 8 vs 15, P < 0.001), and IL-17 levels (median: 0.53 vs 1.26 pg/mL, P < 0.001) compared to non-responders. Baseline UAS7 > 31, DLQI > 9.5, and IL-17 > 0.775 pg/mL predicted non-response with sensitivities of 78.26%, 100%, and 78.26%, and specificities of 67.8%, 59.32%, and 72.88%, respectively. ASST positivity and comorbid allergic diseases were associated with early response (P < 0.05). Adverse events were reported in 6.09% of patients, including mild injection site reactions and transient urticaria exacerbation, not requiring treatment discontinuation.
UNASSIGNED: This study suggests that omalizumab is an effective and safe treatment option for antihistamine-refractory CSU. Baseline UAS7, DLQI, ASST status, serum total IgE levels, and IL-17 may serve as potential predictors of omalizumab response. Notably, ASST positivity and comorbid allergic diseases were associated with an early response to treatment. These findings highlight the importance of considering individual patient characteristics when predicting the likelihood and timing of response to omalizumab in CSU.

BACKGROUND: The prevalence of metastatic melanoma is increasing, necessitating the identification of patients who do not benefit from immunotherapy. This study aimed to develop a radiomic biomarker based on the segmentation of all metastases at baseline and the first follow-up CT for the endpoints best overall response (BOR), progression-free survival (PFS), and overall survival (OS), encompassing various immunotherapies. Additionally, this study investigated whether reducing the number of segmented metastases per patient affects predictive capacity.
METHODS: The total tumour load, excluding cerebral metastases, from 146 baseline and 146 first follow-up CTs of melanoma patients treated with first-line immunotherapy was volumetrically segmented. Twenty-one random forest models were trained and compared for the endpoints BOR; PFS at 6, 9, and 12 months; and OS at 6, 9, and 12 months, using as input either only clinical parameters, whole-tumour-load delta radiomics plus clinical parameters, or delta radiomics from the largest ten metastases plus clinical parameters.
RESULTS: The whole-tumour-load delta radiomics model performed best for BOR (AUC 0.81); PFS at 6, 9, and 12 months (AUC 0.82, 0.80, and 0.77); and OS at 6 months (AUC 0.74). The model using delta radiomics from the largest ten metastases performed best for OS at 9 and 12 months (AUC 0.71 and 0.75). Although the radiomic models were numerically superior to the clinical model, statistical significance was not reached.
CONCLUSIONS: The findings indicate that delta radiomics may offer additional value for predicting BOR, PFS, and OS in metastatic melanoma patients undergoing first-line immunotherapy. Despite its complexity, volumetric whole-tumour-load segmentation could be advantageous.

BACKGROUND: Lebrikizumab is a novel monoclonal antibody with established efficacy in patients with moderate-to-severe atopic dermatitis (AD) in multiple Phase 3 trials. One of the ultimate treatment goals for patients with moderate-to-severe AD is to achieve stable disease control without concern for planning future life events.
METHODS: In ADvocate1 and ADvocate2, lebrikizumab-treated patients meeting the protocol-defined response criteria at Week 16 were re-randomized 2:2:1 to receive lebrikizumab every 2 weeks (Q2W), lebrikizumab every 4 weeks (Q4W), or placebo Q2W (lebrikizumab withdrawal) for 36 additional weeks. In this post hoc analysis, we evaluated the proportions of patients with no or minimal fluctuations of efficacy during the 36-week maintenance period and plotted individual patient trajectories. We defined no or minimal fluctuations as achieving and maintaining the defined endpoint (≥ 75% improvement in the Eczema Area and Severity Index [EASI 75], ≥ 90% improvement in EASI, Pruritus Numeric Rating Scale [NRS] ≥ 4-point improvement, or Pruritus NRS ≥ 3-point improvement) for ≥ 80% of the study visits. If patients used rescue medication, discontinued treatment, or transferred to the escape arm, data collected at or after the event were imputed as non-response.
RESULTS: The proportions of lebrikizumab responders who maintained EASI 75 with no or minimal fluctuations were 70.8% (lebrikizumab Q2W), 71.2% (lebrikizumab Q4W), and 60.0% (lebrikizumab withdrawal). Of the patients with baseline Pruritus NRS ≥ 4 and who achieved ≥ 4-point improvement at Week 16, 66.1% (lebrikizumab Q2W), 62.7% (lebrikizumab Q4W), and 55.2% (lebrikizumab withdrawal) maintained ≥ 4-point Pruritus NRS improvement with no or minimal fluctuations.
CONCLUSIONS: Patients who met the response criteria at Week 16 and continued treatment with lebrikizumab Q2W or Q4W demonstrated a stable response with no or minimal fluctuations of efficacy in measures of skin and itch up to Week 52.
BACKGROUND: NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).
Atopic dermatitis, also known as atopic eczema (or just eczema), is a common skin disease that causes itchy, dry skin. Patients with eczema are often unsure of when disease flares will happen, even while receiving treatment. In two global studies, ADvocate1 and ADvocate2, lebrikizumab improved the signs and symptoms of moderate-to-severe eczema after 16 weeks of treatment. Most of these patients also saw improvement up to 52 weeks. We wanted to know if patients continued to feel better between Week 16 and Week 52. Patients who responded to lebrikizumab after 16 weeks were given lebrikizumab every 2 weeks, lebrikizumab every 4 weeks, or placebo every 2 weeks. We tested how many patients experienced stable response to therapy, which we said was maintaining the same level of improvement on skin signs and itch symptoms for at least 80% of study visits from Week 16 to Week 52. In patients treated with lebrikizumab every 2 weeks or every 4 weeks, we saw that about seven of every ten patients maintained a stable response in skin improvement and about six of every ten patients maintained stable response in itch symptoms. In patients who stopped lebrikizumab therapy, six out of every ten patients maintained a stable skin improvement and more than five of every ten patients maintained a stable improvement in itch symptoms. In ADvocate1 and ADvocate2, most lebrikizumab-treated patients showed a stable response over time on skin and itch with dosing every 2 weeks or every 4 weeks.

Background: Desmopressin (1-deamino-8-D-arginine vasopressin [DDAVP]) has demonstrated efficacy as a treatment option for patients with inherited bleeding disorders. Because of individuals\' variable response to the medication, it is recommended to complete a challenge to document appropriate hemostatic response to the medication before recommending its use prior to surgical procedures or treatment of bleeding symptoms. The project aimed to reduce the errors in hemostatic response assessments for patients with bleeding disorders undergoing a DDAVP challenge (process outcome), particularly timing and number of blood samples drawn, from an error rate baseline of 36% to 0% by December 2021 and sustained for one year. Method: Plan-Do-Study-Act methodology was employed for this qualitative improvement initiative. Interventions designed and implemented included: an order set with medication doses and corresponding laboratory orders as clinically indicated for the bleeding disorder indication, clinical procedure guidelines for infusion nurses to follow, hemostasis nurse coordination of appointments with patients, and family education. Results: Baseline data on 22 patients who completed a DDAVP challenge demonstrated a 36% error rate not involving doses of medication administered. Errors encountered included improper timing of laboratory draw after DDAVP administration, incomplete laboratory evaluation, laboratory results displayed incorrectly due to testing orders released at once instead of in a sequential manner. These interventions resulted in a reduction of DDAVP challenge errors to 0% that were sustained for one year. Conclusion: Improvement in procedural medication administration and appropriate laboratory evaluation of patients undergoing a DDAVP challenge leads to a complete and reliable assessment of hemostatic response following medication administration.

The Preparedness and Resilience for Emerging Threats (PRET) initiative takes an innovative mode-of-transmission approach to pandemic planning by advocating for integrated preparedness and response systems and capacities for groups of pathogens with common transmission pathways. The World Health Organization (WHO) launched this initiative in 2023 with the publication of PRET Module 1 addressing respiratory pathogens. Exercise PanPRET-1 is a customizable tabletop simulation exercise (TTX) package developed to complement PRET Module 1. The exercise scenario focuses on strengthening capacities for multisectoral coordination, risk communication and community engagement, and the triggers for operational decision-making. This article reports on the experiences of the first four countries to implement Exercise PanPRET-1: Cook Islands, Costa Rica, Lebanon and Mongolia. Exercise outcomes demonstrated that PanPRET-1 can be an effective tool for testing pandemic plans in a multisectoral forum and identifying opportunities to improve preparedness and response in key domains. In quantitative evaluations in Cook Islands, Costa Rica and Mongolia, high proportions of exercise participants indicated that multiple aspects of the exercise were well-designed and were beneficial for improving health emergency preparedness. Exercise participants in Lebanon provided qualitative feedback indicating that they found the exercise to be beneficial. Conducting a TTX and monitoring the implementation of action plans based on exercise findings facilitates a country-owned whole-of-society vision for pandemic planning. Countries are encouraged to incorporate TTX such as Exercise PanPRET-1 into a continuous cycle of activity to improve pandemic preparedness.

The potential benefit of probiotics in small ruminant production systems has largely been unexplored. We evaluated the effect of a goat commercial probiotic on health and performance indicators in pastured goats from birth until 10 months. We randomly allocated 26 newborn nursing goat kids to two groups: a control group that received saline and a treatment group that received a commercial probiotic paste orally. We evaluated select observable health indicators (inappetence, diarrhea, coughing), weight, immunity (IgA, IgG, and innate immune response), total protein, hematocrit (HCT), total lactic acid bacteria (LAB), total coliforms, and prevalence of Escherichia coli (E. coli) primary virulence genes (stx1, stx2, and eae) during the experimental period. The results revealed no significant differences in the health indicators, LAB count, and total E. coli count. Prevalence of stx1 at 1 week of age and both stx1 and stx2 genes 4 months post-weaning was significantly (P < 0.05) higher in probiotic-supplemented goats. Probiotic supplementation significantly (P < 0.05) increased the total protein and IgA 1 month post-supplementation during the pre-weaning period and innate immune markers 2 days post-weaning. The HCT in probiotic-supplemented goats was significantly (P < 0.05) higher at 1 and 2 months post-weaning. The growth rate was not affected by probiotic supplementation in pre- and peri-weaned goats but was significantly (P < 0.05) lowered in goats older than 4 months in the supplemented group. In this pastured goat production study, there were mixed responses to a commercial probiotic in healthy goats based on age. The study suggests that early daily probiotic supplementation in pre-weaned pastured goats may have immune stimulation benefits, but in older healthy animals, post-weaning net benefits are unclear and further research is recommended.