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Background: Vaccination is one of the best ways to control the SARS-CoV-2 outbreak. In Taiwan, healthcare workers were prioritized for vaccination, but the effectiveness of these vaccines for them remains unclear. Thus, it's essential to examine their neutralizing antibodies after prime-boost vaccinations.

Methods: In this prospective observational study, 514 healthcare workers from Chang Gung Memorial hospitals in Taiwan were included between 19 March 2021 and 21 August 2021. The two doses of COVID-19 vaccines were either a match or a mixing of AZD1222 and mRNA-1273, e.g. AZD1222 + AZD1222 (n = 406), mRNA-1273 + mRNA-1273 (n = 62), and AZD1222 + mRNA-1273 (n = 46). Blood specimens were drawn after two doses of vaccines, defined as post-vaccine days [median 34.00 days and interquartile range (IQR) 29.00-42.00 days], and examined for the neutralizing antibodies via SARS-CoV-2 neutralization kits. The results were analyzed as a percentage of inhibition based on the negative control.

Results: After 2 vaccination doses, subjects with AZD1222 + mRNA-1273 (median 97.15%, IQR 96.06-98.06%) and mRNA-1273 + mRNA-1273 (median 97.47%, IQR 96.75-97.89%) exhibited higher neutralizing antibodies than those receiving AZD1222 + AZD1222 vaccines (median 71.28%, IQR 49.39-89.70%) (the percentage was referred to inhibition of surrogate virus). The post-vaccination days negatively impacted the neutralizing antibodies, except for the mRNA-1273 + mRNA-1273 group. The presence of fever, headache, and myalgia after the second dosage was reflected in the higher neutralizing antibodies (median of no fever 76.00% vs. fever 97.00%, p < 0.0001; median of no headache 76.00% vs. headache 95.00%, p < 0.0001; median of no myalgia 75.50% vs. myalgia 96.00%, p < 0.0001). The subjects with underlying diseases, including hypertension and cancer showed lower neutralizing antibodies (median of no hypertension 81.00% vs. hypertension 56.00%, p = 0.0029; median of no cancer 81.00% vs. cancer 56.00%, p = 0.0143).

Conclusion: Heterologous prime-boost vaccines (AZD1222 + mRNA-1273) and two doses of mRNA vaccines are recommended. For future directions, we need to investigate the effectiveness of the vaccination against new SARS-CoV-2 variants.

Background: Adjuvant immunotherapy and targeted therapy are now the standard of care for patients with resected stage IIIA-IV melanoma. However, little is known regarding its efficacy in real-world patients who were not represented in these landmark trials.

Methods: This retrospective study included all patients with resected stage IIIA-IV melanoma who received adjuvant systemic therapy between January 1 2018 and December 31 2020, in two Canadian academic cancer. Primary outcome was the proportion of trial non-eligible patients in the real-world setting. Survival and safety analyses were also conducted.

Results: Of the total 113 patient, 99 (88%) were trial non-eligible patients. Most common reasons for trial non-eligible criteria was having no baseline CLND (72%), followed by outside of treatment window >12 weeks (30%), stage IIIA (14%), unknown primary (9%), stage IV (14%), and baseline AD on immunosuppressants (3%). There were no significant RFS (P = 0.731) or OS (P = 0.110) differences in the overall population of trial eligible vs. non-eligible. Safety profiles were similar between the trial eligible vs. non-eligible groups.

Conclusion: Our study suggested a high proportion of real-world patients would have been deemed non-eligible for clinical trials. Regardless, adjuvant systemic therapy delivered similar survival and toxicity outcomes in both groups.

Background: Currently, the pathogenesis of depression remains poorly understood, leading to many patients receiving ineffective treatment. Resveratrol has demonstrated beneficial effects in the prevention and treatment of depression. However, it remains unknown whether resveratrol administration can counteract depression-like behaviors by regulating the SIRT1/NF-κB signaling pathway.

Methodology/principal findings: Male C57BL/6 mice were randomly assigned to a control group, a depression group, and a resveratrol group. The depression model was established using chronic unpredictable mild stress (CUMS) for 5 weeks. Behavioral tests were conducted to assess depressive-like behaviors. The expression levels of SIRT1 and NF-κB in the hippocampus of mice and BV2 microglial cells were measured. After 5 weeks of modeling, the results indicated that mice in the depression group exhibited significant depressive-like behaviors and inhibited activation of the SIRT1/NF-κB signaling pathway. In contrast, resveratrol administration effectively reversed these changes. Results from in vitro experiments showed that LPS stimulation increased microglial activity and downregulated the SIRT1/NF-κB signaling pathway in microglia; however, resveratrol treatment mitigated these effects.

Conclusions/significance: Our findings suggested that resveratrol can alleviate CUMS-induced depression-like behaviors via the activation of the Sirt1/NF-κB pathway in microglia.

Purpose: The Appraisal of Guidelines for Research and Evaluation II Instrument (AGREE II) was developed to enhance the methodological rigor of clinical practice guidelines (CPGs), aiming to generate trustworthy recommendations for various clinical scenarios. Despite its importance, there exists a gap in the quality of CPGs pertaining to Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS-TEN). The aim of the study was to evaluate SJS-TEN CPGs to shed light on areas for enhancing SJS-TEN guidelines' quality.

Materials and methods: A systematic review was conducted to identify SJS-TEN CPGs from January 2011 to December 2023 across bibliographic and guideline databases, as well as dermatology association websites. Four reviewers employed the AGREE II instrument to appraise the quality of eligible CPGs. Subsequently, AGREE II domain scores were calculated and their recommendations mapped.

Results and conclusions: Seven eligible SJS-TEN CPGs reviewed, originating from Europe, North America, Asia, and an authorship Group. The highest AGREE II domain scores were observed in scope and purpose (mean: 63%, standard deviation [SD]: 23.195%) and clarity of presentation (mean: 70%, SD: 14.5%). Conversely, the lowest score was noted in the applicability domain (mean: 28%, SD: 17.44%). Only two guidelines by the British Association of Dermatologists (28.6%) met the 'recommend' level. Recommendations from all CPGs were compared in tabular form.

Background: Dolutegravir/lamivudine (DTG/3TC) is a recommended therapy regimen for hepatitis B surface antigen (HBsAg)-negative people living with HIV (PLWH) who have achieved HIV virological suppression or are treatment-naïve. However, this may overlook the impact of occult hepatitis B infection on HIV suppression, which mainly present as hepatitis B core antibody (HBcAb) positive but HBsAg negative. We aim to assess the effect of HBcAb positivity on HIV suppression among PLWH who had switched to DTG/3TC.

Methods: A retrospective study was conducted including 127 HBcAb-positive and 474 HBcAb-negative PLWH (all were HBsAg negative) who had switched to DTG/3TC at the Beijing Ditan Hospital in China. HIV-RNA suppression was compared pre-switch (not baseline), at switch, and at 12&24 months post-switch, across three categories: (1) target not detected (TND); (2) HIV RNA < 40 cp/mL; (3) blip. Virological suppression included TND and HIV RNA < 40 cp/mL. Epidemiological (gender, age) and clinical data (CD4 count, HIV viral load, etc.) were extracted from the hospital information system. A p-value < 0.05 was considered statistically significant.

Result: HBcAb-positive PLWH were older at DTG/3TC switch (median age: 41 vs. 36 years old, p < 0.001) and had lower nadir CD4 counts (median nadir CD4 counts: 255 vs. 295, p = 0.011). No difference in TND and HIV RNA < 40 cp/mL was present in the two groups at the switch (HBcAb-positive and -negative: 86.6% vs. 88.8%, 12.6% vs. 10.5%, p = 0.789). Similar HBcAb-positive compared with -negative PLWH resulted in TND at 12&24 months post-switch: 91.4% vs. 91% (p = 0.522) and 88.4% vs. 92.7% (p = 0.249), respectively. Consistent result was observed in HIV RNA < 40 cp/mL.

Conclusion: In the 24-month follow-up after switching to DTG/3TC, HBcAb positivity was not significantly associated with HIV virological suppression.

Drought-induced osmotic stress is a significant constraint to soybean growth and yield, necessitating the development of effective mitigation strategies. Silicon acts as an important strategy to mitigate the negative stress effects of drought stress. The study was aimed to evaluate the potential of soil-applied silicon in alleviating drought stress in soybean. Two field capacities were tested: control (85% FC) and drought (50% FC), with four silicon application rates (0, 100, 200, and 300 kg ha^-1) applied at sowing. Drought stress significantly affected the morphological parameters in soybean as plant height, leaf area, and water potential were reduced by 25%, 20%, and 36%, respectively, while root length increased as compared to control-85% FC. However, drought stress reduced root density, surface area, and biomass as compared to control-85% FC. Additionally, drought reduced photosynthetic rates, chlorophyll a and b levels, and stomatal conductance, while increasing malondialdehyde and hydrogen peroxide. The natural plant defense system was upregulated, with increased activity of phenolics, soluble proteins, and antioxidant enzymes like catalase, superoxide dismutase, and peroxidase. However, silicon applications, especially at 200 kg ha^-1, significantly alleviated the negative effects of drought stress by improving morphophysiological and biochemical traits in soybeans. Compared to the control, Si₂₀₀ increased plant height, root length, photosynthetic rate, and water potential by 22%, 39%, 23%, and 17%, respectively, as compared to control. Furthermore, silicon reduced malondialdehyde and hydrogen peroxide levels by 21% and 10%, enhancing plant resilience. Silicon supplementation also boosted biochemical attributes, with total soluble proteins, phenolics, and antioxidant enzyme activities increasing by 30%, 55%, 19%, 24%, and 31%, respectively, under drought conditions. In crux, silicon at 200 kg ha^-1 effectively mitigated the effects of drought stress in soybean, becoming a more sustainable approach to sustain crop yield and food security.

Migraine is a common condition that can cause intense headaches, often on one side of the head, along with symptoms like nausea and sensitivity to light and sound. These headaches can be triggered by various factors, including stress, changes in hormones, sleep disturbances, diet, and even gut health. Migraines are more frequent in women, particularly those under 45, and this may be linked to hormones. After age 45, this difference between men and women becomes less noticeable. Women tend to experience migraines that are more severe and last longer than men, with menstrual migraines affecting about 22% of women during nearly half of their menstrual cycles, and 7.6% of women with migraines. Treatments for migraines include medications, lifestyle changes, and alternative therapies, all of which aim to address the different ways migraines can affect people. This review explores these aspects in detail.

Starch metabolism in plants involves a complex network of interacting proteins that work together to ensure the efficient synthesis and degradation of starch. These interactions are crucial for regulating the balance between energy storage and release, adapting to the plant's developmental stage and environmental conditions. Several studies have been performed to investigate protein-protein interactions (PPIs) in starch metabolism complexes, yet it remains impossible to unveil all of the PPIs in this highly regulated process. This study uses yeast-two-hybrid (Y2H) screening against the Arabidopsis leaf cDNA library to explore PPIs, focusing on the starch-granule-initiating protein named Protein Targeting to Starch 2 (PTST2, At1g27070) and the protein involved in starch and maltodextrin metabolism, namely, plastidial phosphorylase 1 (PHS1, EC 2.4.1.1). More than 100 positive interactions were sequenced, and we found chloroplastidial proteins to be putative interacting partners of PTST2 and PHS1. Among them, photosynthetic proteins were discovered. These novel interactions could reveal new roles of PTST2 and PHS1 in the connection between starch metabolism and photosynthesis. This dynamic interplay between starch metabolism and other chloroplast functions highlights the importance of starch as both an energy reservoir and a regulatory component in the broader context of plant physiology and adaptation.

Background: Type A aortic dissection (TAAD) is a severe cardiovascular condition associated with high risks for postoperative complications, particularly renal dysfunction. This study investigated whether intraoperative hypotension and venous congestion are important predictors of postoperative kidney injury and major adverse events.

Methods: We retrospectively analyzed 543 adults undergoing TAAD surgery (2016-2023). Primary outcomes were acute kidney injury (AKI) and acute kidney disease (AKD). Secondary outcomes included death, stroke and composite outcome. Patients were divided into four groups: AKI only, AKD only, AKI and AKD, Non-AKI or AKD. We used restricted cubic spline and multivariate logistic regression models to adjust for confounding factors.

Results: AKI or AKD was significantly associated with each 10-minute epoch of central venous pressure (CVP) ≥10, 12, 16, 20 mmHg (all p < 0.001), with each 60-minute epoch of CVP ≥10, 12, 16, 20 mmHg area under the curve (AUC) (all p < 0.001). Regarding death, a 6% to 13% increase rate for each 10-minute epoch of CVP ≥10, 12, 16, 20 mmHg (all p ≤ 0.003), a 5% to 21% increase for each 60-minute epoch of CVP ≥10, 12, 16, 20 mmHg AUC (all p < 0.001). In terms of stroke risk, a 5% increase rate for every 10-minute increase in the CVP AUC above 16 mmHg, and an 11% increased risk for CVP AUC above 20 mmHg (p = 0.039 and p = 0.031, respectively).

Conclusion: Elevated CVP and lower MAP levels were linked to postoperative AKI and AKD risk. CVP showed stronger associations with mortality and stroke. Optimizing perioperative hemodynamic management may improve individualized interventions.

Introduction: Psoriasis (PsO) is a common chronic, inflammatory, immune-mediated disease. In 2023, a 4.4% prevalence of PsO was reported in Portugal. Currently, Tumor Necrosis Factor inhibitors (TNFi) are the recommended first-line (1 L) biologic agents in Portugal given their lower cost. However, TNFi may not be suitable for several patients. In these patients, interleukin inhibitors (ILi) should be considered as they provide more effective outcomes and a better safety profile.

Methods: Qualitative interviews with PsO experts were conducted to identify PsO biologic treatment needs, resulting in an online survey to explore clinical cases focused on subpopulations of PsO. A delphi study evaluated consensus on clinical criteria to initiate non-TNFi therapy in seven predefined subpopulations of patients.

Results: This study highlights the benefit of starting non-TNFi therapy in all PsO predefined subpopulations. Patients with infection risk, mild heart failure and associated comorbidities, autoimmune diseases and family history of demyelinating disease consensually benefit from starting non-TNFi therapy in 1 L. Several risks associated with latent tuberculosis, advanced age and oncological disease were also evaluated.

Conclusion: Given the existence of various risks associated with TNFi usage, this clinical perspective overview of Portuguese experts in PsO treatment emphasizes the need for a tailored therapeutic framework in the management of PsO.