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Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma, is characterized by patches, plaques, and, in advanced stages, tumors and erythroderma. Early-stage MF may progress to advanced-stage disease in up to one-third of patients, conferring a worse prognosis and typically requiring systemic treatment for extracutaneous involvement. The most frequently reported signs and symptoms are pain, pruritus, scaling, and skin redness, with pruritus, the most bothersome symptom, exerting a profound impact on patients’ health-related quality of life (HRQoL). These dermatologic signs and symptoms can overlap with those of other benign inflammatory dermatoses, such as eczema and psoriasis, and therefore, diagnostic delay is common in patients with MF. Moreover, identifying patients with features adversely affecting prognosis (e.g. large-cell transformation or folliculotropic variant) is a significant challenge. We report the case of a 75-year-old female patient who was misdiagnosed with eczema and then pityriasis rubra pilaris and consequently did not receive treatment for MF for 4 years. The patient was eventually correctly diagnosed with MF [stage IIIB (T4 N1 M0 B1)] in September 2018. The patient received several systemic treatments; however, she did not respond to or tolerate the treatments. Due to lack of treatment response, in July 2021, she was initiated on mogamulizumab, an anti-CC chemokine receptor 4 antibody with demonstrated effectiveness and licensed approval for adults with MF/Sézary syndrome who have received one or more prior systemic therapies. Treatment rapidly led to a complete response in blood after 1 week and in skin after 4 months. Mogamulizumab was well tolerated by the patient, who also reported a significant improvement in her HRQoL. After 1 year in complete response, mogamulizumab was discontinued. This case highlights the need for accurate and early diagnosis of MF to initiate disease-specific treatment and the importance of considering patient HRQoL when treating this condition.

Abstract BackgroundThe Primary Trauma Care (PTC) course was originally developed to instruct health care workers in the management of patients with severe injuries in low- and middle-income countries (LMICs) with limited medical resources. PTC has now been taught for more than 25 years. Many studies have demonstrated that the 2-day PTC workshop is useful and informative to frontline health staff and has helped improve knowledge and confidence in trauma management; however, there is little evidence of the effect of the course on changes in clinical practice. The Kirkpatrick model (KM) and the knowledge, attitude, and practice (KAP) model are effective methods to evaluate this question. ObjectiveThe aim of this study was to investigate how the 2-day PTC course impacts the satisfaction, knowledge, and skills of health care workers in 2 Vietnamese hospitals using a conceptual framework incorporating the KAP model and the 4-level KM as evaluation tools. MethodsThe PTC course was delivered over 2 days in the emergency departments (EDs) of Thanh Hoa and Ninh Binh hospitals in February and March 2022, respectively. This study followed a prospective pre- and postintervention design. We used validated instruments to assess the participants’ satisfaction, knowledge, and skills before, immediately after, and 6 months after course delivery. The Fisher exact test and the Wilcoxon matched-pairs signed rank test were used to compare the percentages and mean scores at the pretest, posttest, and 6-month postcourse follow-up time points among course participants. ResultsA total of 80 health care staff members attended the 2-day PTC course and nearly 100% of the participants were satisfied with the course. At level 2 of the KM (knowledge), the scores on multiple-choice questions and the confidence matrix improved significantly from 60% to 77% and from 59% to 71%, respectively (PPP ConclusionsThe PTC course undertaken in 2 local hospitals in Vietnam was successful in demonstrating improvements at 3 levels of the KM for ED health care staff. The improvements in the confidence matrix and scenarios checklist were maintained for at least 6 months after the course. PTC courses should be effective in providing and sustaining improvement in knowledge and trauma care practice in other LMICs such as Vietnam.

Objective To evaluate safety and mechanism of action of mezagitamab (TAK-079), an anti-CD38 monoclonal antibody, in patients with moderate to severe systemic lupus erythematosus (SLE).Methods A phase 1b double-blind, placebo-controlled, multicentre study was conducted in patients with SLE receiving standard background therapy. Eligible patients were adults who met the 2012 SLICC or ACR criteria for diagnosis, had a baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 and were positive for anti-double-stranded DNA antibodies and/or anti-extractable nuclear antigens antibodies. Patients received 45 mg, 90 mg or 135 mg of mezagitamab or placebo every 3 weeks over 12 weeks. Primary endpoints were safety and tolerability. Secondary endpoints included pharmacokinetics and pharmacodynamics. Exploratory assessments included disease activity scales, deep immune profiling and interferon pathway analysis.Results 22 patients received at least one dose of either mezagitamab or placebo. In patients exposed to mezagitamab (n=17), drug was well tolerated. Adverse event (AEs) were balanced across treatment groups, with no treatment emergent AEs exceeding grade 2. Responder analyses for Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and SLEDAI-2K did not reveal any observable differences across treatment groups. However, there was a trend for more profound skin responses among patients with higher CLASI scores (>10) at baseline. Pharmacodynamic analysis showed median CD38 receptor occupancy up to 88.4% on CD38+ natural killer cells with concurrent depletion of these cells up to 90% in the 135 mg group. Mean reductions in IgG and autoantibodies were less than 20% in all dose groups. Cytometry by time of flight and type 1 interferon gene analysis revealed unique fingerprints that are indicative of a broad immune landscape shift following CD38 targeting.Conclusions Mezagitamab had a favourable safety profile in patients with moderate to severe SLE and elicited a pharmacodynamic effect consistent with CD38+ cell depletion. These findings reveal novel insights into the drug’s mechanism of action and support the continued investigation of mezagitamab in autoimmune diseases.

Coconut (Cocos nucifera L.) is an important palm species that serves as the mainstay of several industries and contributes to the livelihoods of millions of smallholder farmers. International exchange of coconut germplasm has been undertaken for several decades to facilitate the conservation of selected varieties within global genebanks and for the distribution to farmers and scientists. In vitro systems are a convenient and an efficient method for the exchange of coconut germplasm. However, it is possible that these tissue culture systems can transfer lethal pathogens causing a threat to the importing countries. In this review, the following topics are discussed: the major disease-causing agents of concern, the various tissues that could be used for coconut germplasm exchange, and the techniques available for the detection and elimination of disease-causing agents from various transmission systems. Additionally, the lack of clear, science-backed guidelines to facilitate the exchange of in vitro coconut materials is raised, along with recommendations for future studies to ensure the safe movement of coconut germplasm without biosecurity risks.

This paper aims to investigate the fabrication of high strength low alloy (HSLA) steels by wire and arc-based directed energy deposition (WADED). Firstly, the relationship between the process variables (including the travel speed-V, the current-C, and the voltage-U) and the geometrical characteristics of weld beads (including the bead height (BH), bead width (BW), and melting pool length (MPL)) was investigated. Secondly, the optimal process variables were identified using the desirability approach. The results indicate that voltage-U has the highest impact on BW and MPL, meanwhile the travel speed-V is the most impacting factor on BH. The optimal variables for the WADED process of HSAL steels are V = 0.3 m/min, C = 160 A, and U = 19 V. The component fabricated with the optimal variables is fully dense without spatters and defects, confirming the efficiency of the WADED process for HSLA steels.

Abstract Leukemic cutaneous T‐cell lymphomas (L‐CTCL) are lymphoproliferative disorders of skin‐homing mature T‐cells causing severe symptoms and high mortality through chronic inflammation, tissue destruction, and serious infections. Despite numerous genomic sequencing efforts, recurrent driver mutations have not been identified, but chromosomal losses and gains are frequent and dominant. We integrated genomic landscape analyses with innovative pharmacologic interference studies to identify key vulnerable nodes in L‐CTCL. We detected copy number gains of loci containing the STAT3/5 oncogenes in 74% (n = 17/23) of L‐CTCL, which correlated with the increased clonal T‐cell count in the blood. Dual inhibition of STAT3/5 using small‐molecule degraders and multi‐kinase blockers abolished L‐CTCL cell growth in vitro and ex vivo, whereby PAK kinase inhibition was specifically selective for L‐CTCL patient cells carrying STAT3/5 gains. Importantly, the PAK inhibitor FRAx597 demonstrated encouraging anti‐leukemic activity in vivo by inhibiting tumor growth and disease dissemination in intradermally xenografted mice. We conclude that STAT3/5 and PAK kinase interaction represents a new therapeutic node to be further explored in L‐CTCL.

The intestinal microbiome is by now an undebatable key player in the clinical outcome of ICI therapies. However, no microbiome profiling method to aid therapy decision is yet validated. We conducted a multi-centric study in patients with stage III/IV melanoma, NSCLC, or RCC receiving ICI treatment. The stool microbiome profile of 63 patients was analyzed with BiomeOne®, a microbiome-based algorithm that anticipates whether a patient will achieve clinical benefit with ICIs prior to therapy initiation. Classification of patient samples as Rs and NRs was achieved with a sensitivity of 81% and a specificity of 50% in this validation cohort. An ICI-favorable response was characterized by an intestinal microbiome rich in bacteria such as Oscillospira sp., Clostridia UCG-014, Lachnospiraceae UCG-010 sp., Prevotella copri, and a decrease in Sutterella sp., Lactobacillales, and Streptococcus sp. Patients who developed immune-related adverse events (irAEs) had an overall increased microbial diversity and richness, and a stool microbiome depleted in Agathobacter. When compared with the programmed death-ligand 1 (PD-L1) expression test in the subcohort of NSCLC patients (n = 38), BiomeOne® exhibited a numerically higher sensitivity (78.6%) in identifying responders when compared with the PD-L1 test (67.9%). This study provides an evaluation of BiomeOne®, the first microbiome-based test for prediction of ICI response, to achieve market authorization. Validation with further indications and expansion to other microbiome-based interventions will be essential to bring microbiome-based diagnostics into standard clinical practice.

The problems of the foreign exchange market and the global financial crisis, the European public debt crisis in 2008-2011 made the economy of Vietnam facing many macroeconomic instabilities. The escalating inflation in 2008 and 2011 posed many challenges for macroeconomic management, especially controlling inflation in Vietnam. The realization of macroeconomic stability and inflation control at a reasonable level from 2012 in Vietnam was assessed to bring about remarkable results. In this article, the authors reviewed the studies of International and Vietnamese inflation, pointed out to the macroeconomic factors affecting inflation in Vietnam. At the same time, the authors used the VAR model to examine the impact of macroeconomic factors including money supply, credit, exchange rates, interest rates, real gross domestic product, international prices, inflation and give some discussions from the VAR model results.

The construction process generates a huge amount of waste. If not well managed, this amount of waste will cause unnecessary risks for the project construction process in particular and for the environment in general. Therefore, many studies on waste risk management from the construction industry have been carried out. In recent years, BIM technology has been developed and applied a lot in the field of project management. In this study, the authors give a new perspective on BIM application in the field of project management - BIM application in construction waste management in the construction stage. The first part of the paper will present the research method, the literature review of the research. The final result is the result after applying the proposed research process. The final part of the paper will present the results of the study.

In this article, the research team uses the VAR self-regression vector model to evaluate the impact of exchange rates on inflation and economic growth in Vietnam over the period 2005-2018. With six endogenous variables included in the VAR model: bilateral real exchange rate (Er), money supply (M2), exports (X), imports (IM), GDP at 2010 comparative prices (GDPR), the consumer price index (CPI) and the two exogenous variables, international price (Pw) and US Federal Reserve interest rate (Ifed), the research team examines the impact of exchange rates on endogenous variables in the model and considers the reaction of inflation and economic growth on various shocks. Based on the quantitative results, the research team will recommend some discus-sions to contribute for the improvement of Vietnam's macro environment, trade balance, inflation control, and economic growth support; implementing the goal of macroeconomic stability to suit the period of international economic integration and improving national competitiveness.

Background Checkpoint inhibitors revolutionized the treatment of metastatic melanoma patients. Although tumor burden and lactate dehydrogenase (LDH) are associated with overall survival (OS), the impact of tumor growth kinetics remains elusive and in part contradictory. The aims of this study were to develop a novel simple and rapid method that estimates pretreatment metastatic growth rate (MGR) and to investigate its prognostic impact in melanoma patients treated with antiprogrammed death receptor-1 (PD-1) antibodies.Methods MGR was assessed in three independent cohorts of a total of 337 unselected consecutive metastasized stage IIIB–IV melanoma patients (discovery cohort: n=53, confirmation cohort: n=126, independent multicenter validation cohort: n=158). MGR was computed during the pretreatment period before initiation of therapy with anti-PD-1 antibodies nivolumab or pembrolizumab by measuring the increase of the longest diameter of the largest target lesion. Tumor doubling time served as quality control. Kaplan-Meier analysis and univariable as well as multivariable Cox regression were used to examine the prognostic impact of MGR.Results Pretreatment MGR >3.9 mm/month was associated with impaired OS in the discovery cohort (HR 6.19, 95% CI 2.92 to 13.10, p

This study developed a simple two-step procedure to produce isomaltooligosaccharides (IMOs) from low-cost sweet potato starch (SPS). Effect of various reaction parameters on the steps of the synthesis process of IMOs was systematically investigated. The results show that Spezyme Xtra enzyme was the most suitable for the liquefaction step. The oligosaccharide components’ contents, including G1–G10 and G2–G6, reached 73.95 ± 0.02% and 49.24 ± 3.19%, respectively, after liquefaction. The simultaneous saccharification and transglycosylation (SST) reaction of SPS followed the liquefaction after the α-amylase activity was deactivated. This reaction was simultaneously treated by β-amylase, pullulanase, and α-transglucosidase. The effect of various reaction parameters, consisting of solution pH, reaction temperature, enzyme dosage, and reaction time, on the SST reaction to synthesize IMOs from SPS was fully studied. The results showed that the highest concentration of IMOs (IG234) reached 68.85 ± 1.82 g/L at the optimal condition. The purification of pristine IMO was performed by adding Saccharomyces cerevisiae var. diastaticus BE 134 yeast cells at the final step of the procedure. In particular, the SST reaction for the synthesis of IMOs from SPS shortened SST reaction time by three times compared with other three-step synthesis procedures of IMOs. These findings show that the SPS-derived IMOs can be applied as a novel and inexpensive prebiotic healthcare product for human gastrointestinal health, dieters, and diabetics.

ZnO/chitosan nanocomposite was successfully synthesized by in-situ precipitation method. The material was characterized by XRD, FESEM, TEM, FTIR, BET, and TGA. Results show that ZnO/chitosan nanocomposite has spherical shape with the average size of 20–25 nm. BET surface area and the average pore size of ZnO/chitosan nanocomposite are 2.2436 (m2/g) and 12.2 nm, respectively. The material was applied as an adsorbent for congo red removal from aqueous solutions. The congo red adsorption is better described by the Langmuir model (R2=0.996) than by the Freundlich model (R2=0.962). Therefore, it can be presumed that congo red was adsorbed in a single monolayer with the theoretical maximum adsorption capacity of 227.3 (mg/g). This is comparable to other available adsorbents. It can be suggested that ZnO/chitosan nanocomposite could serve as promising adsorbent for congo red in wastewater treatment technology.

The aim of this study was to assess the knowledge and influence of predatory journals in the field of dermatology in Austria. A total of 286 physicians (50.5% men) completed a questionnaire. The vast majority of subjects read scientific articles (n = 281, 98.3%) and took them into consideration in their clinical decision-making (n = 271, 98.5% of participants that regularly read scientific literature). Open access was known by 161 (56.3%), predatory journals by 84 (29.4%), and the Beall’s list by 19 physicians (6.7%). A total of 117 participants (40.9%) had been challenged by patients with results from the scientific literature, including 9 predatory papers. Participants who knew of predatory journals had a higher level of education as well as scientific experience, and were more familiar with the open-access system (p

Nivolumab belongs to the standard treatment options in metastatic renal cell carcinoma. Despite promising responses, a new spectrum of “immune-related” adverse effects has to be managed in daily clinical practice. A 74-year-old patient was treated with nivolumab in fourth-line. After 18 cycles, treatment was stopped due to severe adverse mucocutaneous reactions confirming a lichen ruber pemphigoides. CT scans during treatment discontinuation show stable disease since more than 14 months. Immunotherapy can cause mucocutaneous immune-mediated adverse reactions. The time of onset to cutaneous adverse effects is variable. Early recognition and treatment are essential in mitigating the severity of those adverse events. Keywords: Renal cell cancer, Nivolumab, Lichen ruber, Side effects, Cutaneous adverse event

The rapid developments of Science and Technology call for individuals to have strong academic knowledge and creativity. Research shows that students acquire creativity after either curricular or extracurricular activities in subject matters. However, there is not much research examining students' creativity through integrative learning activities, such as STEM activities. In this current study, we examine the potential of STEM clubs in terms of fostering students' creativity. We used the survey method to assess students' creativity in engineering design. We collected the data from 244 Vietnamese students, including members and non-members in STEM clubs. The quantitative analysis was performed to examine the differences between members' creativity and non-members' creativity. The results show that STEM club members have significantly more creativity than non-members. The results also show that STEM club members have significantly more creativity than non-members. Based on the results, STEM clubs demonstrate a significant impact on students' creativity. Consequently, STEM clubs should be implemented in high school to enhance students' creativity.

Alcohol-related myopathy (Alc-M) is highly prevalent among heavy drinkers, although its pathogenesis is not well understood. We hypothesize that Alc-M is mediated by combined effects of insulin/IGF resistance and oxidative stress, similar to the effects of ethanol on liver and brain. We tested this hypothesis using an established model in which adult rats were pair-fed for 8 weeks with isocaloric diets containing 0% (N = 8) or 35.5% (N = 13) ethanol by caloric content. Gastrocnemius muscles were examined by histology, morphometrics, qRT-PCR analysis, and ELISAs. Chronic ethanol feeding reduced myofiber size and mRNA expression of IGF-1 polypeptide, insulin, IGF-1, and IGF-2 receptors, IRS-1, and IRS-2. Multiplex ELISAs demonstrated ethanol-associated inhibition of insulin, IRS-1, Akt, and p70S6K signaling, and increased activation of GSK-3β. In addition, ethanol-exposed muscles had increased 4-hydroxy-2-nonenal immunoreactivity, reflecting lipid peroxidation, and reduced levels of mitochondrial Complex IV, Complex V, and acetylcholinesterase. These results demonstrate that experimental Alc-M is associated with inhibition of insulin/IGF/IRS and downstream signaling that mediates metabolism and cell survival, similar to findings in alcoholic liver and brain degeneration. Moreover, the increased oxidative stress, which could be mediated by mitochondrial dysfunction, may have led to inhibition of acetylcholinesterase, which itself is sufficient to cause myofiber atrophy and degeneration.

The mechanisms of alcohol-related peripheral neuropathy (ALPN) are poorly understood. We hypothesize that, like alcohol-related liver and brain degeneration, ALPN may be mediated by combined effects of insulin/IGF resistance and oxidative stress. Adult male Long Evans rats were chronically pair-fed with diets containing 0% or 37% ethanol (caloric), and subjected to nerve conduction studies. Chronic ethanol feeding slowed nerve conduction in the tibial (p = 0.0021) motor nerve, and not plantar sensory nerve, but it did not affect amplitude. Histological studies of the sciatic nerve revealed reduced nerve fiber diameters with increased regenerative sprouts, and denervation myopathy in ethanol-fed rats. qRT-PCR analysis demonstrated reduced mRNA levels of insulin, IGF-1, and IGF-2 polypeptides, IGF-1 receptor, and IRS2, and ELISAs revealed reduced immunoreactivity for insulin and IGF-1 receptors, IRS-1, IRS-4, myelin-associated glycoprotein, and tau in sciatic nerves of ethanol-fed rats (all p < 0.05 or better). The findings suggest that ALPN is characterized by (1) slowed conduction velocity with demyelination, and a small component of axonal degeneration; (2) impaired trophic factor signaling due to insulin and IGF resistance; and (3) degeneration of myelin and axonal cytoskeletal proteins. Therefore, ALPN is likely mediated by molecular and signal transduction abnormalities similar to those identified in alcoholic liver and brain degeneration.

Background: Trafficking is a crime of global proportions involving extreme forms of exploitation and abuse. Yet little research has been done of the health risks and morbidity patterns for men, women, and children trafficked for various forms of forced labour. Methods: We carried out face-to-face interviews with a consecutive sample of individuals entering 15 post-trafficking services in Cambodia, Thailand, and Vietnam. We asked participants about living and working conditions, experience of violence, and health outcomes. We measured symptoms of anxiety and depression with the Hopkins Symptoms Checklist and post-traumatic stress disorder with the Harvard Trauma Questionnaire, and used adjusted logistic regression models to estimate the effect of trafficking on these mental health outcomes, controlling for age, sector of exploitation, and time in trafficking. Findings: We interviewed 1102 people, of whom 1015 reached work destinations. Participants worked in various sectors including sex work (329 [32%]), fishing (275 [27%]), and factories (136 [13%]). 481 (48%) of 1015 experienced physical violence, sexual violence, or both, with 198 (35%) of 566 women and girls reporting sexual violence. 478 (47%) of 1015 participants were threatened and 198 (20%) were locked in a room. 685 (70%) of 985 who had data available worked 7 days per week and 296 (30%) of 989 worked at least 11 hours per day. 222 (22%) of 983 had a serious injury at work. 61·2% (95% CI 58·2–64·2) of participants reported symptom of depression, 42·8% (39·8–45·9) reported symptoms of anxiety, and 38·9% (36·0–42·0) reported symptoms of post-traumatic stress disorder. 5·2% (4·0–6·8) had attempted suicide in the past month. Participants who experienced extremely excessive overtime at work, restricted freedom, bad living conditions, threats, or severe violence were more likely to report symptoms of depression, anxiety, and post-traumatic stress disorder. Interpretation: This is the first health study of a large and diverse sample of men, women, and child survivors of trafficking for various forms of exploitation. Violence and unsafe working conditions were common and psychological morbidity was associated with severity of abuse. Survivors of trafficking need access to health care, especially mental health care. Funding: Anesvad Foundation and International Organization for Migration International Development Fund.

Global agricultural by‐products usually go to waste, especially in developing countries where agricultural products are usually exported as raw products. Such waste streams, once converted to "value‐added" products could be an additional source of revenue while simultaneously having positive impacts on the socio‐economic well‐being of local people. We highlight the utilization of thermochemical techniques to activate and convert agricultural waste streams such as rice and straw husk, coconut fiber, coffee wastes, and okara power wastes commonly found in the world into porous activated carbons and biofuels. Such activated carbons are suitable for various applications in environmental remediation, climate mitigation, energy storage, and conversions such as batteries and supercapacitors, in improving crop productivity and producing useful biofuels. [ABSTRACT FROM AUTHOR]