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Susan Kearney,1,* Leslie J Raffini,2 Tan P Pham,3 Xin Ying Lee,4 Sylvia von Mackensen,5,* Andrea Landorph,6 Hideyuki Takedani,7 Johannes Oldenburg8 1Center for Bleeding and Clotting Disorders, Children’s Hospital Minnesota, Minneapolis, MN, USA; 2Division of Hematology, The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; 3Mapi (an Icon plc company), Boston, MA, USA; 4Global Biopharm Patient Access, Biopharm Operations, Novo Nordisk A/S, Copenhagen, Denmark; 5Department of Medical Psychology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; 6Medical & Science, Biopharm Operations, Novo Nordisk A/S, Copenhagen, Denmark; 7Department of Joint Surgery, Research Hospital of the Institute of Medical Science, The University of Tokyo, Tokyo, Japan; 8Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany *These authors contributed equally to this work Background: Prophylactic treatment regimens lead to improvements in health-related quality-of-life (HRQoL) among individuals with hemophilia. Turoctocog alfa pegol (N8-GP) provides the benefit of extending the duration of protection from bleeding and reducing the number of injections, which is expected to impact HRQoL and treatment satisfaction (TS). Aim: To investigate the HRQoL and TS of patients with severe hemophilia A from two phase III trials evaluating the safety and efficacy of N8-GP. Methods: HRQoL was assessed using the Haemo-QoL (reported by children and their parents) and Haem-A-QoL (reported by adults). TS was assessed using Hemo-Sat. Domain and total scores for all questionnaires ranged from 0 to 100, with lower scores indicating a better HRQoL or TS. A negative change in score indicates an improvement in HRQoL/TS. Results: Mean changes in HRQoL scores were reported for 14 children aged 4–7 years, 21 children aged 8–11 years, 10 adolescents aged 13–16 years, and 163 adults (17 years and above). Mean changes in children/adolescents-reported Haemo-QoL total score were -14.0 for ages 4–7 years, -3.6 for ages 8–11 years, and -0.1 for ages 13–16 years. Mean changes in parent-reported Haemo-QoL total scores were -11.5 for 4–7 years, -8.6 for ages 8–11 years, and -4.0 for 13–16 years. Adults’ mean change in Haem-A-QoL total score was -3.1 for those receiving on-demand treatment and -2.3 for those receiving prophylaxis treatment. High levels of TS with N8-GP were reported by parents of children/adolescents and the adults at the end of the trial. Conclusion: While most patients reported a relatively good baseline HRQoL when entering the respective trials, the HRQoL of patients was either maintained or further improved when treated with N8-GP. Adults and parents of children and adolescents reported a high level of treatment satisfaction with N8-GP. Keywords: hemophilia A, turoctocog alfa pegol, health-related quality-of-life, children, adults, treatment satisfaction

The effective use of CRISPR technologies in emerging model organisms faces significant challenges in efficiently generating heritable mutations and in understanding the genomic consequences of induced DNA damages and the inheritance patterns of induced mutations. This study addresses these issues by 1) developing an efficient microinjection delivery method for gene editing in the microcrustacean Daphnia pulex; 2) assessing the editing dynamics of Cas9 and Cas12a nucleases in the scarlet knock-out mutants; and 3) investigating the transcriptomes of scarlet mutants to understand the pleiotropic effects of scarlet gene. Our reengineered microinjection method results in efficient biallelic editing with both nucleases. Our data suggest site-specific DNA cleavage mostly occurs in a stepwise fashion. Indels dominate the induced mutations. A few, unexpected on-site large deletions (>1 kb) are also observed. Notably, genome-wide analyses reveal no off-target mutations. Knock-in of a stop codon cassette to the scarlet locus was successful, despite complex induced mutations surrounding the target site. Moreover, extensive germline mosaicism exists in some mutants, which unexpectedly produce different phenotypes/genotypes in their asexual progeny. Lastly, our transcriptomic analyses unveil significant gene expression changes associated with scarlet knock-out and altered swimming behavior in mutants, including several genes involved in human neurodegenerative diseases., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to The Genetics Society.)

Aim: To determine the rate of prediabetes among and the pre-transplant plasma high-sensitivity C-reactive protein (hs-CRP) value predictive of prediabetes in patients during their first year post-living donor kidney transplant., Methods: A total of 538 patients underwent living donor kidney transplantation between January 2018 and December 2020, 413 of whom met the inclusion criteria for this study. All patients underwent oral glucose tolerance tests (OGTTs) with 75 g glucose/200 mL solution, starting 3 months post-transplant and repeating the test every 3 months for the first year. Clinical and paraclinical indicators and plasma hs-CRP concentrations were quantified the day prior to the transplant. Prediabetes was diagnosed according to the American Diabetes Association 2018 criteria as a 2-h OGTT result between 140 mg/dL (7.8 mmol/L) and 199 mg/dL (11.0 mmol/L)., Results: The rate of prediabetes among the study subjects was 38.3 % (158/413). Body mass index (BMI) and pre-transplant plasma triglycerides, high-density lipoprotein cholesterol (HDLC), and hs-CRP levels were related factors predictive of prediabetes in patients within the first year post-kidney transplant based on multivariate logistic regression and receiver operative characteristic curve models. Hs-CRP was the factor with the best predictive value (area under the curve = 0.89; p < 0.001)., Conclusions: Pre-transplant plasma hs-CRP levels were a good predictor of prediabetes in the first year post-living donor kidney transplant., Competing Interests: Declaration of competing interest The authors declare no conflict of interest, financial or otherwise., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To compare the frequency of clinically significant missed injuries in clinically stable trauma patients undergoing initial whole-body computed tomography (WBCT) versus selective imaging. Secondary objectives include comparisons of radiation exposure, incidental findings, ED length of stay (LOS), hospital LOS and mortality., Methods: We performed a retrospective cohort study of trauma activations at a tertiary trauma centre in patients with normal vital signs from 1st January 2022 to 31st December 2022. Data were collected from the trauma registry and chart review of medical records., Results: A total of 665 patients were included with 42% (n = 277) receiving a WBCT, compared to 58% (n = 388) undergoing selective imaging. Most patients (52%) did not have any traumatic axial injuries identified. Missed injuries were identified in 0.8% (n = 3/388) of patients in the selective imaging cohort, with no adverse patient outcomes or major alteration to inpatient management. No missed injuries were identified in the WBCT group. Mortality was rare (0.9%, n = 6/665), occurring exclusively in elderly patients and mostly attributed to non-traumatic pathologies. Patients undergoing WBCT had a significantly increased likelihood of incidental findings (75% vs 35%, P < 0.001), increased radiation exposure (mean 24.67 vs 8.19 millisieverts [mSv], P < 0.001), longer ED LOS (9.86 vs 8.43 h, P = 0.012) and a higher likelihood of admission (65.3% vs 55.7%, P = 0.012)., Conclusions: Missed injuries were rare and without major complications in this clinically stable cohort. The liberal use of WBCT, despite low rates of missed injuries, morbidity and mortality, suggests over-utilisation of WBCT for 'mechanism only' traumas., (© 2024 Australasian College for Emergency Medicine.)

This study develops a generalized H 2 observer to estimate the road profile in the semi-active automotive suspension system. The dynamics of the quarter-car model are represented in the descriptor nonlinear parameter-varying system framework, with the road profile as a system's state that is of arbitrary dynamics. Then, a road profile estimation method is designed by using a generalized H 2 observer, which utilizes the onboard accelerometers as the observer's input. The adverse impact of measurement noises on the accuracy of estimation results is alleviated via the generalized H 2 framework. The proposed observer is designed by solving an LMI-based constrained optimization problem. Frequency domain analysis and time domain simulations illustrate the efficiency of the proposed strategy., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Thanh-Phong Pham reports financial support was provided by The 10.13039/100016555University of Danang - University of Technology and Education. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background and Aims: Fish oil and krill oil are primary sources of Omega-3 polyunsaturated fatty acids (PUFAs), differing in their molecular forms and bioavailability. Understanding these differences can optimize their therapeutic use. This study aims to compare the bioavailability of Omega-3 PUFAs in fish oil and krill oil using a network meta-analysis approach. By evaluating various molecular forms and dosages, the study seeks to identify the most effective Omega-3 sources and dosing regimens to maximize health benefits. Methods: The study adhered to the explanation of the PRISMA network meta-analysis 2015 (registered PROSPERO ID: CRD42024532536). The risk of bias was evaluated using the PEDro scale. This network meta-analysis incorporated data from studies published between 2003 and 2023, sourced from five databases: ClinicalTrials.gov , PubMed, Cochrane CENTRAL, the International Clinical Trials Registry Platform-World Health Organization, and Embase. Statistical analysis was conducted using advanced models in R software to ensure a rigorous evaluation of bioavailability. Results: Out of 26 high-quality studies, findings reveal superior bioavailability of krill oil compared to fish oil. Specifically, fish oil above 3000 mg, in re-esterified triacylglycerol or ethyl ester formulations (100-2900 mg), and krill oil (100-1900 mg) significantly enhanced the Omega-3 index. At lower dosages (under 2000 mg), krill oil shows superior Omega-3 absorption compared to fish oil. Using fish oil ethyl ester at doses between 2000 and 2900 mg may be the most effective for reducing Tmax. However, this finding should be interpreted with caution due to high heterogeneity and limited statistical significance. The highest AUC values were observed in krill oil phospholipid/free fatty acid formulation. Emulsion forms of fish oil are more effective in increasing Cmax than other formulations. These results were supported by robust statistical evidence (Egger's test, p  > 0.05), highlighting the effectiveness of specific formulations and doses in optimizing Omega-3 absorption. Conclusion: The research highlights the importance of understanding the bioavailability of Omega-3 PUFAs from fish oil and krill oil. The findings suggest that low-dose krill oil and fish oil emulsions (under 2000 mg) are effective and potentially safer alternatives to high-dose fish oil, potentially minimizing the risk of adverse effects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Malaria remains a global health problem, and the standard membrane feeding assay (SMFA) is a key functional assay for development of new interventions to stop malaria transmission from human to mosquito. For SMFA, media with ~ 10% of human serum has been used for infectious gametocyte cultures, however, there are multiple challenges to obtain a suitable human serum. Here we show a human-serum-free culture medium (HSF), which was a mixture of two stem cell culture media and AlbuMAX, supported infectious gametocyte growth. Moreover, the HSF-induced gametocytes elicited significantly higher numbers of oocysts compared to gametocytes cultured with conventional human serum medium (Conv). While some caution is required when comparing percent transmission reducing activity data generated from HSF-SMFA and Conv-SMFA, the HSF method can facilitate the establishment of gametocyte cultures or SMFA by bypassing the need for human serum. Thus, this study will support future development of P. falciparum transmission-blocking interventions., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Pancreatic duct adenocarcinoma (PDAC) accounts for about 85-90% of all solid pancreatic tumors, which is well-known for poor prognosis and high morbidity. Despite the massive advent of chemotherapy and radiotherapy in recent years, surgical removal is still considered the cornerstone management option in this situation. Pancreaticoduodenectomy or Whipple procedure is generally contraindicated in metastasis or tumors that encase more than 50% of vessels. Vascular reconstruction is a state-of-the-art technique which requires the remarkable involvement of vascular experts in the setting of PDAC-invading vessels. In this article, we present an exceptional case of a 38-year-old male patient who underwent radical resection for advanced pancreatic cancer with superior mesenteric vein reconstruction by a great saphenous vein., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Competing Interests: The authors have no funding or conflicts of interest to disclose.

Introduction: Deucravacitinib, a novel, oral, selective allosteric tyrosine kinase 2 inhibitor, demonstrated superiority versus placebo and apremilast in the POETYK PSO-1 and PSO-2 studies. We describe patient-reported outcomes with deucravacitinib treatment versus placebo and apremilast in these studies., Methods: Two multicenter, global, double-blind, placebo- and active comparator-controlled studies randomized patients with moderate-to-severe plaque psoriasis 1:2:1 to placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. Score changes from baseline and meaningful within-patient change responses for Psoriasis Symptoms and Signs Diary (PSSD) and Dermatology Life Quality Index (DLQI) were assessed., Results: In POETYK PSO-1 (n = 666) and PSO-2 (n = 1020), respectively, improvement from baseline in PSSD total score was greater with deucravacitinib (- 27.8 and - 30.1) versus placebo (- 4.4 and - 5.9) and apremilast (- 18.9 and - 22.5) at Week 16 and versus apremilast at Week 24 (deucravacitinib: - 32.8 and - 30.7; apremilast: - 21.6 and - 22.8) (nominal p < 0.0001). Improvement from baseline in DLQI score was also greater with deucravacitinib (- 8.5 and - 7.6) versus placebo (- 3.3 and - 3.0) and apremilast (- 5.9 and - 5.8) at Week 16 and versus apremilast at Week 24 (deucravacitinib: - 8.6 and - 7.5; apremilast: - 5.6 and - 5.5) (nominal p < 0.0001). Achievement of meaningful within-patient change in PSSD total score and in DLQI score occurred more frequently with deucravacitinib than placebo and apremilast at Week 16 and versus apremilast at Week 24., Conclusions: Deucravacitinib demonstrated meaningful improvements in patient-reported outcomes in patients with moderate-to-severe plaque psoriasis compared with apremilast and placebo., Clinical Trial Registration: NCT03624127, NCT03611751., (© 2024. The Author(s).)

Cellulases are one of the most essential natural factors for cellulose degradation and, thus, have attracted significant interest for various applications. In this study, a cellulase from Paenibacillus elgii TKU051 was produced, purified, and characterized. The ideal fermentation conditions for cellulase productivity were 2% carboxymethyl cellulose (CMC) as the growth substrate, pH = 8, temperature of 31 °C, and 4 days of culturing. Accordingly, a 45 kDa cellulase (PeCel) was successfully purified in a single step using a High Q column with a recovery yield of 35% and purification of 42.2-fold. PeCel has an optimal activity at pH 6 and a temperature of 60 °C. The activity of cellulase was significantly inhibited by Cu 2+ and enhanced by Mn 2+ . The PeCel-catalyzed products of the CMC hydrolysis were analyzed by high-performance liquid chromatography, which revealed chitobiose and chitotriose as the major products. Finally, the clarity of apple juice was enhanced when treated with PeCel.

Organized chronic subdural hematoma is a rare form of chronic subdural hematoma. The optimal treatment method is still controversial. Preoperative middle meningeal artery embolization and craniotomy are effective methods for chronic subdural hematoma. However, there are not many reports investigating the effectiveness of these methods in treating organized chronic subdural hematoma. We report the case of a 61-year-old male patient who had a twist-drill craniostomy to treat a left hemisphere subdural hematoma. After surgery, there was a recurrence on the same side in the form of an organized subdural hematoma. The patient received preoperative left middle meningeal artery embolization. After 3 months of follow-up, a small portion of the hematoma remained, causing pressure and slightly shifting the midline to the right by 6.5 mm, and the patient no longer had clinical symptoms., (© 2024 The Authors.)

Background: Antioxidant therapy is gaining traction in managing sepsis and septic shock, owing to its perceived positive impact on patient outcomes. This study sought to compare the efficacy of five antioxidant therapies (melatonin, vitamin C, vitamin E, selenium, and N -acetylcysteine, both individually and in combination with other compounds such as vitamin B1, hydrocortisone, propolis, and glutamine) in treating sepsis or septic shock in the intensive care unit (ICU)., Methods: The study involved randomized and multi-arm trials with sepsis or septic shock patients using melatonin, vitamin C, vitamin E, selenium, or N -acetylcysteine. Studies were sourced from PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and WHO - Clinical Trials Registry Platform for the frequentist network meta-analysis on 28-day mortality and Sequential Organ Failure Assessment (SOFA) scores. The risk of bias was assessed using the Physiotherapy Evidence Database scale. Therapies were compared directly and indirectly using R software., Results: The study of 56 trials involving 9,366 patients was included. Bias assessment revealed that 89.3 % of trials achieved excellent or good quality. Based on treatment ranking and pairwise comparisons, melatonin with propolis (SUCRA = 93.29 %) is effective in improving SOFA scores, statistically significant, with no publication bias ( p= 0.73). High-dose vitamin C (SUCRA = 83.97 %), vitamin C with vitamin B1 (SUCRA = 78.72 %), and melatonin (SUCRA = 67.03 %) are potential therapies for organ dysfunction. Melatonin (SUCRA = 88.22 %) and high-dose vitamin C (SUCRA = 80.75 %) were the most effective in reducing 28-day mortality rates. However, analysis indicated that the results for 28-day mortality rates were not statistically significant. Also, these results contained publication bias ( p= 0.02)., Conclusion: The study offers fresh perspectives on antioxidant therapy treatments for sepsis or septic shock in ICU, emphasizing the combination of melatonin and propolis notably reduces SOFA scores for those patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Stochastic algorithms are well-known for their performance in the era of big data. In this article, we study nonsmooth stochastic Difference-of-Convex functions (DC) programs-the major class of nonconvex stochastic optimization, which have a variety of applications in divers domains, in particular, machine learning. We propose new online stochastic algorithms based on the state-of-the-art DC Algorithm (DCA)-a powerful approach in nonconvex programming framework, in the online context of streaming data continuously generated by some (unknown) source distribution. The new schemes use the stochastic approximations (SAs) principle: deterministic quantities of the standard DCA are replaced by their noisy estimators constructed using newly arriving samples. The convergence analysis of the proposed algorithms is studied intensively with the help of tools from modern convex analysis and martingale theory. Finally, we study several aspects of the proposed algorithms on an important problem in machine learning: the expected problem in principal component analysis (PCA).

Context: Artificial intelligence (AI) chatbot platforms are increasingly used by patients as sources of information. However, there is limited data on the performance of these platforms, especially regarding palliative care terms., Objectives: We evaluated the accuracy, comprehensiveness, reliability, and readability of three AI platforms in defining and differentiating "palliative care," "supportive care," and "hospice care.", Methods: We asked ChatGPT, Microsoft Bing Chat, Google Bard to define and differentiate "palliative care," "supportive care," and "hospice care" and provide three references. Outputs were randomized and assessed by six blinded palliative care physicians using 0-10 scales (10 = best) for accuracy, comprehensiveness, and reliability. Readability was assessed using Flesch Kincaid Grade Level and Flesch Reading Ease scores., Results: The mean (SD) accuracy scores for ChatGPT, Bard, and Bing Chat were 9.1 (1.3), 8.7 (1.5), and 8.2 (1.7), respectively; for comprehensiveness, the scores for the three platforms were 8.7 (1.5), 8.1 (1.9), and 5.6 (2.0), respectively; for reliability, the scores were 6.3 (2.5), 3.2 (3.1), and 7.1 (2.4), respectively. Despite generally high accuracy, we identified some major errors (e.g., Bard stated that supportive care had "the goal of prolonging life or even achieving a cure"). We found several major omissions, particularly with Bing Chat (e.g., no mention of interdisciplinary teams in palliative care or hospice care). References were often unreliable. Readability scores did not meet recommended levels for patient educational materials., Conclusion: We identified important concerns regarding the accuracy, comprehensiveness, reliability, and readability of outputs from AI platforms. Further research is needed to improve their performance., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

In today's fast paced, attention-demanding society, executive functions and attentional resources are often taxed. Individuals need ways to sustain and restore these resources. We first review the concepts of attention and restoration, as instantiated in Attention Restoration Theory (ART). ART emphasizes the role of nature in restoring attention. We then discuss the essentials of experiments on the causal influences of nature. Next, we expand the concept of ART to include modern, designed environments. We outline a wider perspective termed attentional ecology, in which attention behavior is viewed within a larger system involving the human and their interactions with environmental demands over time. When the ecology is optimal, mental functioning can be a positive "flow" that is productive, sustainable for the individual, and sometimes creative.

Competing Interests: The authors declare no conflict of interest.

Background: Avian influenza (AI) is a contagious disease that causes illness and death in poultry and humans. High pathogenicity AI (HPAI) H5N6 outbreaks commonly occur in Quang Ninh province bordering China. In June 2021, the first HPAI H5N8 outbreak occurred at a Quang Ninh chicken farm., Objectives: This study examined the risk factors associated with HPAI H5N6 and H5N8 outbreaks in Quang Ninh., Methods: A retrospective case-control study was conducted in Quang Ninh from Nov 2021 to Jan 2022. The cases were households with susceptible poultry with two or more clinical signs and tested positive by real-time reverse transcription polymerase chain reaction. The controls were households in the same village as the cases but did not show clinical symptoms of the disease. Logistic regression models were constructed to assess the risk factors associated with HPAI outbreaks at the household level., Results: There were 38 cases with H5N6 clade 2.3.4.4h viruses (n = 35) and H5N8 clade 2.3.4.4b viruses (n = 3). Compared to the 112 controls, raising poultry in uncovered or partially covered ponds (odds ratio [OR], 7.52; 95% confidence interval [CI], 1.44-39.27), poultry traders visiting the farm (OR, 8.66; 95% CI, 2.7-27.69), farms with 50-2,000 birds (OR, 3.00; 95% CI, 1.06-8-51), and farms with ≥ 2,000 birds (OR, 11.35; 95% CI, 3.07-41.94) were significantly associated with HPAI outbreaks., Conclusions: Combining biosecurity measures, such as restricting visitor entry and vaccination in farms with more than 50 birds, can enhance the control and prevention of HPAI in Quang Ninh and its spread across borders., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Korean Society of Veterinary Science.)

Background: Fully nutrition support for patients in developing countries like Vietnam is challenging. Aim: To estimate the prevalence of patients with nutritional risk at admission and describe feeding regimen of critically ill patients in a suburban hospital in Hanoi, Vietnam. Methods: An observational study was conducted among 154 patients at department of Intensive Care Unit (ICU). The Nutrition Risk Screening 2002 (NRS2002) and Modified Nutrition Risk in Critically Ill (mNUTRIC) were used for screening nutritional risk at admission. Body Mass Index (BMI), Mild-Upper Arm Circumference (MUAC), and personal information were recorded. The feeding regimen of patients was monitored from the first to seventh day. Results: the patients were aged 66.5 ± 15.4 years, with an APACHEII of 13.0 ± 5.5 and SOFA 3.1 ± 2.6: 47.4% were malnutrition by MUAC, 16.2% had a severely low BMI (<17.8), 20.8% had low BMI (17.8 to <20). According to NRS2002 and mNUTRIC, the prevalence of patients with high nutritional risk was 53.9% and 13%, respectively. The proportion of patients receiving less than 25 kcal/kg/day was 84%, 60%, and 47% on the first, the fifth, and the seventh day. Protein intake below 1.3 g/kg/day was 50% on the seventh day. Up to 27.4% of patients had no nutrition support on the first day. Conclusions: ICU patients had nutritional risk with high rate. The feeding regimen for patients achieved a progressive energy and protein intake over the first 7 days., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Change from baseline score on the validated Psoriasis Symptoms and Signs Diary (PSSD) is a widely used, patient-reported end point in clinical trials for psoriasis. Meaningful score change thresholds anchored to patient-reported assessments have not been established in a clinical trial setting., Objective: To evaluate meaningful within-patient score change thresholds for the PSSD using data from the phase 3 Program to Evaluate the Efficacy and Safety of Deucravacitinib, a Selective TYK2 Inhibitor (POETYK), PSO-1 clinical trial, which compared the efficacy and safety of deucravacitinib vs placebo and apremilast among adults with moderate to severe plaque psoriasis., Design, Setting, and Participants: In this predefined analysis using data from the POETYK PSO-1 multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, conducted from August 7, 2018, to September 2, 2020, 666 adults with moderate to severe plaque psoriasis completed the PSSD daily throughout the trial. Meaningful change thresholds were derived by anchoring mean PSSD score change from baseline to week 16 to category improvements on the Patient Global Impression of Change (PGI-C) and the Patient Global Impression of Severity (PGI-S)., Interventions: Deucravacitinib, 6 mg, once daily; placebo; or apremilast, 30 mg, twice daily., Main Outcome and Measures: The main outcome was score change from baseline to week 16 on the PSSD, anchored to the PGI-C and PGI-S., Results: The trial included 666 patients (mean [SD] age, 46.1 [13.4] years; 453 men [68.0%]). Three thresholds were identified using an analysis set of 609 patients. Score improvement of at least 15 points from baseline reflected meaningful within-patient change anchored to the PGI-C. Score improvements of 25 points were supported by both the PGI-C and the PGI-S, while a 30-point score change identified patients with greater improvements in their psoriasis symptoms and signs., Conclusions and Relevance: This analysis suggests that PSSD score improvements of 15, 25, or 30 points represent increasing improvements in disease burden that are meaningful to patients with psoriasis.

Despite the revolutionary impacts of CRISPR-Cas gene editing systems, the effective and widespread use of CRISPR technologies in emerging model organisms still faces significant challenges. These include the inefficiency in generating heritable mutations at the organismal level, limited knowledge about the genomic consequences of gene editing, and an inadequate understanding of the inheritance patterns of CRISPR-Cas-induced mutations. This study addresses these issues by 1) developing an efficient microinjection delivery method for CRISPR editing in the microcrustacean Daphnia pulex ; 2) assessing the editing efficiency of Cas9 and Cas12a nucleases, examining mutation inheritance patterns, and analyzing the local and global mutation spectrum in the scarlet mutants; and 3) investigating the transcriptomes of scarlet mutants to understand the pleiotropic effects of scarlet underlying their swimming behavior changes. Our reengineered CRISPR microinjection method results in efficient biallelic editing with both nucleases. While indels are dominant in Cas-induced mutations, a few on-site large deletions (>1kb) are observed, most likely caused by microhomology-mediated end joining repair. Knock-in of a stop codon cassette to the scarlet locus was successful, despite complex induced mutations surrounding the target site. Moreover, extensive germline mosaicism exists in some mutants, which unexpectedly produce different phenotypes/genotypes in their asexual progenies. Lastly, our transcriptomic analyses unveil significant gene expression changes associated with scarlet knock-out and altered swimming behavior in mutants, including several genes (e.g., NMDA1, ABAT, CNTNAP2) involved in human neurodegenerative diseases. This study expands our understanding of the dynamics of gene editing in the tractable model organism Daphnia and highlights its promising potential as a neurological disease model.

Purpose: The aim of this study was (a) to optimise the 99m Tc-SPECT reconstruction parameters for the pre-treatment dosimetry of 90 Y-selective internal radiation therapy (SIRT) and (b) to compare the accuracy of clinical dosimetry methods with full Monte-Carlo dosimetry (fMCD) performed with Gate., Methods: To optimise the reconstruction parameters, two hundred reconstructions with different parameters were performed on a NEMA phantom, varying the number of iterations, subsets, and post-filtering. The accuracy of the dosimetric methods was then investigated using an anthropomorphic phantom. Absorbed dose maps were generated using (1) the Partition Model (PM), (2) the Dose Voxel Kernel (DVK) convolution, and (3) the Local Deposition Method (LDM) with known activity restricted to the whole phantom (WP) or to the liver and lungs (LL). The dose to the lungs was calculated using the "multiple DVK" and "multiple LDM" methods., Results: Optimal OSEM reconstruction parameters were found to depend on object size and dosimetric criterion chosen (D mean or DVH-derived metric). The D mean of all three dosimetric methods was close (≤ 10%) to the D mean of fMCD simulations when considering large segmented volumes (whole liver, normal liver). In contrast, the D mean to the small volume (∅=31) was systemically underestimated (12%-25%). For lungs, the "multiple DVK" and "multiple LDM" methods yielded a D mean within 20% for the WP method and within 10% for the LL method., Conclusions: All three methods showed a substantial degradation of the dose-volume histograms (DVHs) compared to fMCD simulations. The DVK and LDM methods performed almost equally well, with the "multiple DVK" method being more accurate in the lungs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Introduction and Importance: Laparoscopic surgery is recommended to treat recurrent inguinal hernia (IH). Single-incision laparoscopic surgery transabdominal pre-peritoneal (SILS-TAPP) has been an option for IH repair but few studies on the application of this method for recurrent IH was conducted. We aimed to report our experience of SILS-TAPP for recurrent IH and the long-term outcomes of this technique., Case Presentation: Ten patients of recurrent IH, including three multiple recurrences, were successfully treated with SILS-TAPP. Previous surgeries were Bassini and Lichtenstein's procedures. No perioperative complications were observed; neither additional trocar nor conversion to open surgery was needed. Median operation time was 65 (range: 45-95) minutes. Post-operative pain lasted for two to three days. Neither long-term complications nor recurrence was seen until the median follow-up time of 37 (range: 16-53) months., Clinical Discussion: Although the surgical procedure of hernia repair of SILS-TAPP was the same as conventional TAPP, the manipulation of the instrument was technically challenging. This surgical method should be done by an SILS expert with application of several surgical tips to overcome difficulties adhering to single-port surgery. Also, meticulous and patient dissection of the inguinal site is suggested., Conclusion: SILS-TAPP is safe and feasible to repair recurrent inguinal hernia. However, it should be done by experienced surgeons., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The production of hydrogen and soluble metabolite products from water hyacinth via dark fermentation was modeled. The model was built on the assumption that the substrate exists in two forms (i.e., soluble and particulate) and undergoes two stages (i.e., hydrolysis and acidogenesis) in the dark fermentation process. The modified Michaelis-Menten and surface-limiting models were applied to describe the hydrolysis of soluble and particulate forms, respectively. Meanwhile, the acidogenesis stage was modeled based on the multi-substrate-single-biomass model. The effects of temperature, pH, and substrate concentration were integrated into the model to increase flexibility. As a result, the model prediction agreed with the experimental and literature data of water hyacinth-fed dark fermentation, with high coefficient of determination values of 0.92 - 0.97 for hydrogen and total soluble metabolite products. These results indicate that the proposed model could be further applied to dark fermentation's downstream and hybrid processes using water hyacinth and other substrates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The current limitation of ancient DNA data from Vietnam led to the controversy surrounding the prehistory of people in this region. The combination of high heat and humidity damaged ancient bones that challenged the study of human evolution, especially when using DNA as study materials. So far, only 4 k years of history have been recorded despite the 65 k years of history of anatomically modern human occupations in Vietnam. Here we report, to our knowledge, the oldest mitogenomes of two hunter-gatherers from Vietnam. We extracted DNA from the femurs of two individuals aged 6.2 k cal BP from the Con Co Ngua (CCN) site in Thanh Hoa, Vietnam. This archeological site is the largest cemetery of the hunter-gatherer population in Southeast Asia (SEA) that was discovered, but their genetics have not been explored until the present. We indicated that the CCN haplotype belongs to a rare haplogroup that was not detected in any present-day Vietnamese individuals. Further matrilineal analysis on CCN mitogenomes showed a close relationship with ancient farmers and present-day populations in SEA. The mitogenomes of hunter-gatherers from Vietnam debate the "two layers" model of peopling history in SEA and provide an alternative solution for studying challenging ancient human samples from Vietnam., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: Ravulizumab and eculizumab are complement C5 inhibitors approved for the treatment of atypical hemolytic uremic syndrome (aHUS). Ravulizumab requires less frequent infusions than eculizumab, which may reduce treatment burden. This study investigated patients' treatment preferences and the impact of both treatments on patient and caregiver quality of life. Materials & methods: Two surveys were conducted (one for adult patients with aHUS and one for caregivers of pediatric patients with aHUS) to quantitatively assess treatment preference and the patient- and caregiver-reported impact of ravulizumab and eculizumab on quality of life. Patients were required to have a diagnosis of aHUS, to be currently receiving treatment with ravulizumab and to have received prior treatment with eculizumab. Participants were recruited via various sources: the Alexion OneSource™ patient support program, the Rare Patient Voice recruitment agency, the aHUS Foundation and directly via a clinician involved in the study. Results: In total, 50 adult patients (mean age: 46.5 years) and 16 caregivers of pediatric patients (mean age: 10.1 years) completed the surveys. Most adult patients (94.0%) and all caregivers reported an overall preference for ravulizumab over eculizumab; infusion frequency was one of the main factors for patients when selecting their preferred treatment. Fewer patients reported disruption to daily life and the ability to go to work/school due to ravulizumab infusion frequency (4.0% and 5.7%, respectively) than eculizumab infusion frequency (72.0% and 60.0%), with similar results for caregivers. Conclusion: Adult patients and caregivers of pediatric patients indicated an overall preference for ravulizumab than eculizumab for the treatment of aHUS, driven primarily by infusion frequency. This study contributes to the emerging real-world evidence on the treatment impact and preference in patients with aHUS.

Background: Half of diarrhea hospitalizations in children aged <5 years in Vietnam are due to rotavirus. Following introduction of a locally developed and licensed oral rotavirus vaccine, Rotavin-M1, into the routine immunization program in two Vietnamese provinces, Nam Dinh and TT Hue, we describe changes in rotavirus positivity among children hospitalized for diarrhea and calculate vaccine effectiveness against moderate-to-severe rotavirus hospitalizations., Methods: Active rotavirus surveillance among children <5 years began in December 2016 at sentinel hospitals in districts where rotavirus vaccine was introduced in December 2017. To estimate reductions in rotavirus detection, we calculated risk ratios comparing rotavirus positivity pre- and post-vaccine introduction. We used a test-negative case-control design to calculate vaccine effectiveness., Findings: From December 2016 to May 2021, 7228 children <5 years hospitalized for diarrhea were enrolled. Following introduction, Rotavin-M1 coverage was 77% (1066/1377) in Nam Dinh and 42% (203/489) in TT Hue. In Nam Dinh, rotavirus positivity among children <5 years significantly declined by 40.6% (95% CI: 34.8%-45.8%) during the three-year post-vaccine introduction period. In TT Hue, no change in rotavirus positivity was observed. Among children aged 6-23 months, a 2-dose series of Rotavin-M1 was 57% (95% CI: 39%-70%) effective against moderate-to-severe rotavirus hospitalizations., Interpretation: Higher vaccination coverage in Nam Dinh than TT Hue likely contributed to substantial declines in rotavirus positivity observed in Nam Dinh following rotavirus vaccine introduction. Robust vaccine effectiveness was observed through the second year of life. National rotavirus vaccine introduction with high coverage may have substantial impact on reducing rotavirus disease burden in Vietnam., Funding: Bill and Melinda Gates Foundation., Competing Interests: Huong Thuy Nguyen, Thao Phuong Thi Pham, Nguyen Dang Hien are the member of POLYVAC-Vietnam.

In the present study, it was aimed to investigate the optimized plan of radiotherapy with dose modulation in the pelvis to reduce the dose on the skin in patients having pelvic region radiotherapy. The series of images of 45 pelvic cancer patients were selected, intensity-modulated radiation therapy (IMRT) plan was made, the skin dose reduction was optimized, and evaluated verifying the plan verification. As a result, skin volume receiving dose ≥10, ≥20, ≥30, ≥40 and ≥50 Gy of the IMRT Skin plan were all less than those of the IMRT plan. Particularly, skin volumes receiving doses ≥20, ≥30, ≥40 and ≥50 Gy of the Skin IMRT plan were markedly lower than those of the IMRT plan, the reduction values were 8.76, 18.83, 46.84 and 100%, respectively. Furthermore, the Skin IMRT plan was no longer affected by the 50 Gy dose. In conclusion, the present study revealed that the skin's dose can be decreased with optimal plan processing; thus, this decrease of the skin's dose ensures the continuation of radiotherapy and improved life quality of the patient., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Vinh et al.)

Background: Outbreak of SARS-CoV-2 pandemic has caused millions of deaths and lifelong consequences since December 2019. We attempted to evaluate the incidence, distribution, and risk factors associated with death after applying the social distance strategy to the second wave of SARS-CoV-2 in the Danang outbreak in Vietnam., Methods: We retrospectively reviewed the online the Danang Hospital reports, gathering the epidemiological history of confirmed SARS-CoV-2 patients. We then conducted a descriptive analysis of Fisher's Phi Coefficient and Cramer's, along with multiple logistic regression models to test the effects of symptomatology and control measures performed by Vietnamese government. The last report we examined on August 29, 2020., Results: A total of 389 SARS-CoV-2 confirmed cases were related to the Danang outbreak are included in our analysis with a mean age of 47.1 (SD = 18.4), involving 154 men and 235 women, with 34 cases of death and 355 were alive. The study showed significant results related to age, quarantine measures, previous negative SARS-CoV-2 test, and a range of symptoms, including shortness of breath and myalgia (p-value <0.05). Our multiple-variable analysis suggested the significant risk of death was related to age, severe symptomology, undetected SARS-CoV-2 test results, and prior quarantined SARS-CoV-2 history., Conclusions: Vietnamese authorities had implemented successful quarantine practices to control the SARS-CoV-2 outbreaks. However, this virus has shown dynamic spread beyond the ability of the country to control its transmission. Adequate screening, social distancing, and adequate care of elderly and healthcare workers can lower the risk of future outbreaks., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Two strains, designated as Marseille-P2918 T and Marseille-P3646 T , were isolated from a 14-week-old Senegalese girl using culturomics: Urmitella timonensis strain Marseille-P2918 T (= CSUR P2918, = DSM 103634) and Marasmitruncus massiliensis strain Marseille-P3646 T (= CSUR P3646, = CCUG72353). Both strains were rod-shaped, anaerobic, spore forming motile bacteria. The 16S rRNA gene sequences of strains Marseille-P2918 T (LT598554) and Marseille-P3646 T (LT725660) shared 93.25% and 94.34% identity with Tissierella praeacuta ATCC 25539 T and Anaerotruncus colihominis CIP 107754 T , their respective phylogenetically closest species with standing in nomenclature. Therefore, strain Marseille-P2918 T is classified within the family Tissierellaceae and order Tissierellales whereas strain Marseille-P3646 T is classified within the family Oscillospiraceae and order Eubacteriales. The genome of strain Marseille-P2918 T had a size of 2.13 Mb with a GC content of 50.52% and includes six scaffolds and six contigs, and that of strain Marseille-P3646 T was 3.76 Mbp long consisting of five contigs with a 50.04% GC content. The genomes of both strains presented a high percentage of genes encoding enzymes involved in genetic information and processing, suggesting a high growth rate and adaptability. These new taxa are extensively described and characterised in this paper, using the concept of taxono-genomic description., (© 2022. The Author(s).)

Autosomal recessive osteopetrosis (ARO) is a group of disease characterized by osteoclast dysfunction inhibiting bone resorption and bone turnover, with TCIRG1-associated ARO being more common leading to autosomal recessive infantile malignant osteopetrosis (OPTB1, MIM entry number # 259700). While most patients with TCIRG1-associated osteopetrosis present a malignant clinical course and shortened lifespan, a few cases of non-malignant TCIRG1-associated osteopetrosis have been reported. 24-year-old female patient came to us with limp gait, hip pain in both sides, and severe stiffness. She had suffered many fractures, bilateral hip osteoarthritis, right leg was 2 cm shorter compared with left leg. Whole Exome Sequencing was conducted, the result and subsequent Sanger's sequencing shown the patient had a compound heterozygous genotype at TCIRG1 (c.1194dup, p.Gly399ArgTer and c.334G>A, p.Gly112Arg), these two variants found were not previously reported. Sanger's sequencing revealed two other siblings whom suffer the same disorder had similar genotype to the proband; the parents were found to be heterozygous. This is the first case of TCIRG1-associated osteopetrosis reported in Vietnam and one of the few cases of nonmalignant TCIRG1-associated osteopetrosis, in which detailed clinical and genetic work-up were performed., (© 2022 Wiley Periodicals LLC.)

During development of a subunit vaccine, monitoring integrity of the recombinant protein for process development and quality control is critical. Pfs230 is a leading malaria transmission blocking vaccine candidate and the first to reach a Phase 2 clinical trial. The Pfs230 protein is expressed on the surface of gametes, and plays an important role in male fertility. While the potency of Pfs230 protein can be determined by a standard membrane-feeding assay (SMFA) using antibodies from immunized subjects, the precision of a general in vivo potency study is known to be poor and is also time-consuming. Therefore, using a well-characterized Pfs230 recombinant protein and two human anti-Pfs230 monoclonal antibodies (mAbs), which have functional activity judged by SMFA, a sandwich ELISA-based in vitro potency assay, called the Antigen Integrity Assay (AIA), was developed. Multiple validation parameters of AIA were evaluated to qualify the assay following International Conference on Harmonization (ICH) Q2(R1) guidelines. The AIA is a high throughput assay and demonstrated excellent precision (3.2 and 5.4% coefficients of variance for intra- and inter-assay variability, respectively) and high sensitivity (>12% impurity in a sample can be detected). General methodologies and the approach to assay validation described herein are amenable to any subunit vaccine as long as more than two functional, non-competing mAbs are available. Thus, this study supports future subunit vaccine development.

Malaria transmission-blocking vaccines (TBVs) aim to elicit human antibodies that inhibit sporogonic development of Plasmodium falciparum in mosquitoes, thereby preventing onward transmission. Pfs48/45 is a leading clinical TBV candidate antigen and is recognized by the most potent transmission-blocking monoclonal antibody (mAb) yet described; still, clinical development of Pfs48/45 antigens has been hindered, largely by its poor biochemical characteristics. Here, we used structure-based computational approaches to design Pfs48/45 antigens stabilized in the conformation recognized by the most potently inhibitory mAb, achieving >25°C higher thermostability compared with the wild-type protein. Antibodies elicited in mice immunized with these engineered antigens displayed on liposome-based or protein nanoparticle-based vaccine platforms exhibited 1-2 orders of magnitude superior transmission-reducing activity, compared with immunogens bearing the wild-type antigen, driven by improved antibody quality. Our data provide the founding principles for using molecular stabilization solely from antibody structure-function information to drive improved immune responses against a parasitic vaccine target., Competing Interests: Declaration of interests The authors declare no competing interests. A patent application has been filed that relates to this work., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Context: The COVID-19 pandemic caused unprecedented global disruption and continues to wreak havoc. Dire predictions were made about the risks to smallholder farmers in lower- and middle- income, but hard data have been lacking. We present the results from 9201 interviews with smallholder farmers from seven countries., Objective: The objectives are to describe: i) how farmers perceive the key effects of the COVID-19 pandemic and containment measures on livelihoods and food security; ii) the effects on agricultural activities; iii) the coping strategies households deployed., Methods: Household surveys were conducted as part of ongoing monitoring programs during the latter half of 2020. Sites in seven countries were covered: Burundi; Kenya; Rwanda; Tanzania; Uganda; Zambia; and Vietnam. Findings are representative of smallholder farmers across multiple districts per country., Results and Conclusions: The effects of the COVID-19 containment measures were widespread and often perceived to be severe. Food purchase, off-farm income, sale of farm produce, and access to crop inputs were all affected. In locations under more stringent restrictions during the time of the survey, up to 80% of households had to reduce food consumption and/or variety. Almost all households with off-farm incomes reported reductions, by half on average. A half to three-quarters of households (depending on the location) with income from farm sales reported losses compared to the pre-pandemic situation. In locations with more relaxed containment measures in place during the time of the survey, less frequent and less severe economic and food security outcomes were perceived by the respondent, with around 20% of households reporting negative outcomes. Mobility restrictions, reduced market access, crashes in sale price for agricultural goods, and soaring prices for food purchase were key factors. Sale prices generally dropped for all agricultural products in any given location, and affected not only high-value perishable products, but also staple crops such as maize and cassava. Depending on the location, between 30% and 90% of the households applied coping strategies in response to the pandemic during 2020. There was an almost complete absence of official aid amongst households interviewed., Significance: Our results raise the thorny issue of how best to balance containment of disease against the wellbeing of the vulnerable rural population in lower- and middle-income countries. There is a risk that the buffering capacity of rural people will become exhausted. Possible policy measures to limit negative outcomes include i) tiered mobility restrictions with travel allowed for economic reasons; ii) short-term price guarantee schemes to stabilise the food system; iii) direct aid; iv) the timely re-installation of distribution channels for agricultural inputs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Two bacterial strains were isolated and identified using microbial culturomics and characterised according to the taxono-genomics strategy. The strictly anaerobic strain, Marseille-P3773 T , forms smooth and translucent colonies consisting of Gram-stain negative, non-motile and non-spore-forming rod-shaped cells. Strain Marseille-P3787 T consists of Gram-stain positive, motile and spore-forming cells resulting in grey and translucent colonies. The phylogenetic analysis of the 16S rRNA gene of strains Marseille-P3773 T and Marseille-P3787 T revealed a 96.9% similarity level with Lachnotalea glycerini strain DLD10 and 97% identity with Paenibacillus uliginis strain N3/975, respectively. The genome of strain Marseille-P3773 is 4,260,534 bp long with a 40.3 mol% G + C content and includes 3879 predicted genes of which 3769 are protein-coding genes, 76 RNAs and 34 are pseudo-genes. Strain Marseille-P3787 had a genome size of 4,833,032 bp with a 47.9 mol% G + C and has 4481 predicted genes of which 4265 are protein-coding genes, 101 RNAs and 115 are pseudo-genes. According to the data collected on these strains and, more specifically to the genomic comparison, we suggest the creation of a new genus and species, Konateibacter massiliensis gen. nov., sp. nov. with strain Marseille-P3773 T (=CSURP3773 and CCUG71331) as its type strain within the Lachnospiraceae family, as well as a new species, Paenibacillus faecalis sp. nov. with strain Marseille-P3787 T (=CSURP3787 and CCUG71650) as its type strain within the Paenibacillus genus., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pfs230 is a leading malaria transmission blocking vaccine (TBV) candidate. Comprising 3135 amino acids (aa), the large size of Pfs230 necessitates the use of sub-fragments as vaccine immunogens. Therefore, determination of which regions induce functional antibody responses is essential. We previously reported that of 27 sub-fragments spanning the entire molecule, only five induced functional antibodies. A "functional" antibody is defined herein as one that inhibits Plasmodium falciparum parasite development in mosquitoes in a standard membrane-feeding assay (SMFA). These five sub-fragments were found within the aa 443-1274 range, and all contained aa 543-730. Here, we further pinpoint the location of epitopes within Pfs230 that are recognized by functional antibodies using antibody depletion and enrichment techniques. Functional epitopes were not found within the aa 918-1274 region. Within aa 443-917, further analysis showed the existence of functional epitopes not only within the aa 543-730 region but also outside of it. Affinity-purified antibodies using a synthetic peptide matching aa 543-588 showed activity in the SMFA. Immunization with a synthetic peptide comprising this segment, formulated either as a carrier-protein conjugate vaccine or with a liposomal vaccine adjuvant system, induced antibodies in mice that were functional in the SMFA. These findings provide key insights for Pfs230-based vaccine design and establish the feasibility for the use of synthetic peptide antigens for a malaria TBV., (© 2022. The Author(s).)

To clarify the influence of dioxin exposure on brain morphometry, the present study investigated associations between dioxin exposure at high levels and brain structural irregularities in 32 Vietnamese men. Two exposure markers were used: blood dioxin levels, as a marker of exposure in adulthood, and perinatal dioxin exposure, estimated by maternal residency in a dioxin-contaminated area during pregnancy. All subjects underwent brain magnetic resonance imaging (MRI) scans. We analyzed correlations between regional gray matter volumes and blood dioxin levels, and compared regional volumes between men with and without perinatal dioxin exposure using the voxel-based morphometry (VBM) tool from Statistical Parametric Mapping 12 (SPM12). Blood 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was associated with low volume of the medial temporal pole and fusiform gyrus. Toxic equivalency (TEQ)-PCDDs were correlated with low medial temporal pole volume. However, 1,2,3,4,7,8-HxCDD was associated with high middle frontal gyrus and cerebellum volume. In men with perinatal dioxin exposure, the left inferior frontal gyrus pars orbitalis volume was significantly lower than in those without perinatal exposure. These results suggest that dioxin exposure during the perinatal period and in adulthood may alter regional brain volume, which might lead to cognitive deficits and unusual social emotional behavior in Vietnamese men living in dioxin-contaminated areas.

We investigate the impact of financing and legal obstacles on firm growth across different firm sizes before and after the global financial crisis (GFC). Using two enterprise surveys in Vietnam, we find firms facing higher financing obstacles have lower sales and employment growth. The smallest firms are the most adversely affected by financing obstacles. The legal obstacles impede the employment growth of SMEs more than large enterprises, which is attributable to the tendency of firms to avoid tall poppy syndrome and the scrutiny of tax officials. Furthermore, we find that the negative effects of financing obstacles on small firms' sales and employment growth reduce in the post-GFC period. We attribute it to a higher proportion of small firms being able to borrow from commercial banks after the financial crisis, partly due to the introduction of new policies supporting SMEs from the Vietnamese Government. Overall, our findings recommend to policymakers that improvement in access to finance is imperative for productivity increases and job creation for small and medium firms., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Published by Elsevier Ltd.)

Nutrient acquisition systems are often crucial for pathogen growth and survival during infection, and represent attractive therapeutic targets. Here, we study the protein machinery required for heme uptake in the opportunistic pathogen Acinetobacter baumannii. We show that the hemO locus, which includes a gene encoding the heme-degrading enzyme, is required for high-affinity heme acquisition from hemoglobin and serum albumin. The hemO locus includes a gene coding for a heme scavenger (HphA), which is secreted by a Slam protein. Furthermore, heme uptake is dependent on a TonB-dependent receptor (HphR), which is important for survival and/or dissemination into the vasculature in a mouse model of pulmonary infection. Our results indicate that A. baumannii uses a two-component receptor system for the acquisition of heme from host heme reservoirs., (© 2021. The Author(s).)

Plasmodium falciparum transmission-blocking vaccines (TBVs) targeting the Pfs25 antigen have shown promise in mice but the same efficacy has never been achieved in humans. We have previously published pre-clinical data related to a TBV candidate Pfs25-IMX313 encoded in viral vectors which was very promising and hence progressed to human clinical trials. The results from the clinical trial of this vaccine were very modest. Here we unravel why, contrary to mice, this vaccine has failed to induce robust antibody (Ab) titres in humans to elicit transmission-blocking activity. We examined Pfs25-specific B cell and T follicular helper (Tfh) cell responses in mice and humans after vaccination with Pfs25-IMX313 encoded by replication-deficient chimpanzee adenovirus serotype 63 (ChAd63) and the attenuated orthopoxvirus modified vaccinia virus Ankara (MVA) delivered in the heterologous prime-boost regimen via intramuscular route. We found that after vaccination, the Pfs25-IMX313 was immunologically suboptimal in humans compared to mice in terms of serum Ab production and antigen-specific B, CD4 + and Tfh cell responses. We identified that the key determinant for the poor anti-Pfs25 Ab formation in humans was the lack of CD4 + T cell recognition of Pfs25-IMX313 derived peptide epitopes. This is supported by correlations established between the ratio of proliferated antigen-specific CD4 + /Tfh-like T cells, CXCL13 sera levels, and the corresponding numbers of circulating Pfs25-specific memory B cells, that consequently reflected on antigen-specific IgG sera levels. These correlations can inform the design of next-generation Pfs25-based vaccines for robust and durable blocking of malaria transmission., Competing Interests: AH is named inventor on patent applications covering malaria vaccines and immunization regimens. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zaric, Marini, Nielsen, Gupta, Mekhaiel, Pham, Elias, Taylor, de Graaf, Payne, Li, Silk, Williams, Hill, Long, Miura and Biswas.)

Objective: This study aims to describe the angiographic imaging characteristics of superficial venous malformations and evaluate the treatment effectiveness of digital subtraction angiography (DSA)-guided foam sclerotherapy with polidocanol. Materials and Methods : This prospective study was conducted in 18 patients with venous malformation treated by DSA-guided sclerotherapy. Treatment outcomes were evaluated based on pain improvement and reduction in lesion size on magnetic resonance imaging (MRI) 6-months posttreatment. Results: A total 21 lesions and 46 sclerotherapy sessions were analyzed. MRI findings presented 8/21 lesions (38.1%) with excellent response, 9/21 (42.9%) with good response, and 3/21 (14.3%) with average response, while one patient (4.8%) showed no response. All patients experienced pain. A significant reduction (p<0.01) was observed in the pre- to posttreatment pain score (5.45 and 0.64, respectively). Over a follow-up period of 1-4 years, three out of four patients (75%) in the retrospective cohort experienced recurrence; one patient had an increased lesion size and pain score, while the other two patients only showed an increased lesion size. No severe complications were seen. Conclusion: DSA-guided sclerotherapy with polidocanol is a safe and effective procedure for reducing lesion size and pain in symptomatic patients with superficial venous malformations., Competing Interests: Disclosure StatementThe authors declare no conflict of interest., (© 2021 The Editorial Committee of Annals of Vascular Diseases.)

Endothelial cells can acquire a mesenchymal phenotype through a process called Endothelial-to-Mesenchymal transition (EndMT). This event is found in embryonic development, but also in pathological conditions. Blood vessels lose their ability to maintain vascular homeostasis and ultimately develop atherosclerosis, pulmonary hypertension, or fibrosis. An increase in inflammatory signals causes an upregulation of EndMT transcription factors, mesenchymal markers, and a decrease in endothelial markers. In our study, we show that the induction of EndMT results in an increase in long non-coding RNA AERRIE expression. JMJD2B, a known EndMT regulator, induces AERRIE and subsequently SULF1 . Silencing of AERRIE shows a partial regulation of SULF1 but showed no effect on the endothelial and mesenchymal markers. Additionally, the overexpression of AERRIE results in no significant changes in EndMT markers, suggesting that AERRIE is marginally regulating mesenchymal markers and transcription factors. This study identifies AERRIE as a novel factor in EndMT, but its mechanism of action still needs to be elucidated.

Background: In efforts to reduce misuse of opioids, new abuse deterrent formulations of medications have been developed. Insurers increasingly give abuse-deterrent opioid formulations preferred formulary status, which can result in required formulation rotation for patients. Xtampza® (oxycodone myristate extended-release) is an abuse-deterrent opioid formulation that maintains its extended-release properties with any physical manipulation. Blood levels of oxycodone myristate extended-release (OxyM-ER) may vary with dietary caloric and fat intake., Case Description: A woman with metastatic breast carcinoma had severe myalgias and arthralgias well-managed with oxycodone hydrochloride extended-release (OxyHCl-ER) and hydrocodone/acetaminophen. A switch from OxyHCl-ER to OxyM-ER resulted in worsened pain management, decreased functional status, and a referral to palliative care (PC). Recognizing calorie-depending pharmacokinetic variability with OxyM-ER, the interdisciplinary PC team obtained a detailed dietary history from the patient, which revealed a low-fat, low-calorie healthy diet with inconsistent meals. After repeated education, the patient changed her diet and had improved pain and functional status without increasing her total daily opioid dose., Conclusion: The efficacy of OxyM-ER may be compromised in patients with cancer experiencing anorexia, decreased or inconsistent food intake, or low-fat/low-calorie diets. An interdisciplinary team approach can improve pain control in the setting of "forced" formulary switches to OxyM-ER.

Glomerular filtration rate (GFR) is an important indicator of renal function. Many methods have been developed to determine GFR in clinical examinations. This study aims to correlate between radionuclide plasma sampling methods (single and double blood samples, in vitro methods) and in vivo Gate's method using 99m Tc-diethylene triamine penta-acetic acid ( 99m Tc-DTPA) renography., Materials and Methods: 43 patients underwent this study, including 31 renal donors (Group 1) and 12 patients with obstructive uropathy (Group 2). All patients were administered with a range of 5-7 mCi of 99m Tc-DTPA. Then, renography performed simultaneously after injection and GFR calculation followed by Gate's method. Blood samples were collected at 60- and 120-min postinjection, samples were counted by a thyroid uptake system, and GFR was calculated using a single plasma sample method (SPSM) and a double plasma sample method (DPSM)., Results: The mean GFRs calculated by Gate's method in Groups 1 and 2 were 85.8 ± 18.2 ml/min and 118.4 ± 13.9 ml/min, respectively. Meanwhile, using the in vitro blood sampling methods (DPSM and SPSM), the mean GFRs in Group 1 were 73.8 ± 15.4 ml/min and 56.4 ± 20.9 ml/min, respectively, and in Group 2 were 116.8 ± 12.9 ml/min and 106.3 ± 18.5 ml/min, respectively. There is a high correlation between Gate's method and DPSM in two groups ( r = 0.86 and 0.72, respectively), and a moderate correlation was found between Gate's method and SPSM in both groups ( r = 0.49 and r = 0.37, respectively). The two in vitro methods (DPSM and SPSM) revealed that moderate correlation in both groups ( r = 0.74 and r = 0.67, respectively) was observed., Conclusion: Renography is a simple method but considered inaccurate for GFR determination. However, in vitro plasma sampling is rarely used in Vietnam. In this study, Gate's method correlated well with DPSM and tended to overestimate GFR. Further, the in vitro methods can be applied to correct the in vivo method as a confirmatory test in some cases., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Nuclear Medicine.)

Negative interaction between alleles that arise independently in diverging populations (i.e., Dobzhansky-Muller incompatibilities) can cause reduction of fitness in their hybrids. However, heterosis in hybrids can emerge if hybridization breaks down detrimental epistatic interaction within parental lineages. In this study, we examined the life-history fitness of the inter-specific F 1 s of two recently diverged microcrustacean species Daphnia pulex and D. pulicaria as well as intra-specific crosses of D. pulex . We identified heterosis in two out of five life-history traits in the inter-specific F 1 s. According to theories that heterosis can transiently emerge in early speciation, the observation of heterosis in these life-history traits suggests that there are no major genetic incompatibilities between these two species affecting these traits and that D. pulex and D. pulicaria are at an early stage of speciation.

This study examined how different types of social interaction and competitive information in exergaming affect older adults' motivation and attitude toward playing exergames. A 2 (time: pre- vs. posttest) × 3 (social interaction: play alone vs. play with peer vs. play with youth) × 2 (competition: competition informed vs. noncompetition informed) mixed experiment was conducted with 319 Singaporean older adults over 6 weeks through a three-way analysis of variance. Social interaction was found to significantly affect the changes of extrinsic motivation over time, while competitive information affected intrinsic motivation significantly. The results showed significant three-way interaction effects between time, social interaction, and competitive information on older adults' extrinsic and intrinsic motivations. The changes of attitude over time were not affected by either social interaction or competitive information. The findings contribute to aging research and advance the knowledge of potential factors that promote the effective implementation of exergames for community older adults.

Background: Scrolling is a perceived barrier in the use of bring your own device (BYOD) to capture electronic patient reported outcomes (ePROs). This study explored the impact of scrolling on the measurement equivalence of electronic patient-reported outcome measures (ePROMs) in the presence and absence of scrolling., Methods: Adult participants with a chronic condition involving daily pain completed ePROMs on four devices with different scrolling properties: a large provisioned device not requiring scrolling; two provisioned devices requiring scrolling - one with a "smart-scrolling" feature that disabled the "next" button until all information was viewed, and a second without this feature; and BYOD with smart-scrolling. The ePROMs included were the SF-12, EQ-5D-5L, and three pain measures: a visual analogue scale, a numeric response scale and a Likert scale. Participants completed English or Spanish versions according to their first language. Associations between ePROM scores were assessed using intraclass correlation coefficients (ICCs), with lower bound of 95% confidence interval (CI) > 0.7 indicating comparability., Results: One hundred fifteen English- or Spanish-speaking participants (21-75y) completed all four administrations. High associations between scrolling and non-scrolling were observed (ICCs: 0.71-0.96). The equivalence threshold was met for all but one SF-12 domain score (bodily pain; lower 95% CI: 0.65) and two EQ-5D-5L item scores (pain/discomfort, usual activities; lower 95% CI: 0.64/0.67). Age, language, and device size produced insignificant differences in scores., Conclusions: The measurement properties of PROMs are preserved even in the presence of scrolling on a handheld device. Further studies that assess scrolling impact over long-term, repeated use are recommended.