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Abstract In this community effort, we compare measurements between 34 laboratories from 19 countries, utilizing mixtures of labelled authentic synthetic standards, to quantify by mass spectrometry four clinically used ceramide species in the NIST (National Institute of Standards and Technology) human blood plasma Standard Reference Material (SRM) 1950, as well as a set of candidate plasma reference materials (RM 8231). Participants either utilized a provided validated method and/or their method of choice. Mean concentration values, and intra- and inter-laboratory coefficients of variation (CV) were calculated using single-point and multi-point calibrations, respectively. These results are the most precise (intra-laboratory CVs ≤ 4.2%) and concordant (inter-laboratory CVs < 14%) community-derived absolute concentration values reported to date for four clinically used ceramides in the commonly analyzed SRM 1950. We demonstrate that calibration using authentic labelled standards dramatically reduces data variability. Furthermore, we show how the use of shared RM can correct systematic quantitative biases and help in harmonizing lipidomics. Collectively, the results from the present study provide a significant knowledge base for translation of lipidomic technologies to future clinical applications that might require the determination of reference intervals (RIs) in various human populations or might need to estimate reference change values (RCV), when analytical variability is a key factor for recall during multiple testing of individuals.

Abstract Cluster analysis can also detect abnormalities besides building a basis for identifying elements into clusters. Detecting abnormalities is a highly developed feature in the field of unsupervised learning. However, existing studies have mainly focused on discrete data, not probability density functions. This paper enables a possibilistic approach to solving the clustering for probability density functions dealing with abnormal elements. First, the data are extracted using the density function. Then, they are passed through the proposed algorithm to produce a possibilistic partition. Finally, a decision rule is established to recognize which function is abnormal. We compare the proposed algorithm with baseline algorithms in clustering PDFs, such as k-means, FCF, and Self-Updated Clustering. The results of three numerical examples applied to the image are typical for this new method. Furthermore, The proposed algorithm reaches accuracy at 100% over simulated benchmark data and outperforms baseline methods. Additionally, two last examples apply to image data reaching G-mean up from 96 to 100% (Sensitivity: 92–100% and Specificity: 100%). The proposed method can be researched and used to understand the internal structures of big data in the digital age through the probability density functions.

Abstract Metal artifacts notoriously pose significant challenge in computed tomography (CT), leading to inaccuracies in image formation and interpretation. Artifact reduction tools have been designed to improve cone beam computed tomography (CBCT) image quality by reducing artifacts caused by certain high-density materials. Metal artifact reduction (MAR) tools are specific algorithms that are applied during image reconstruction to minimize or eliminate artifacts degrading CBCT images. The purpose of the study is to evaluate the effect of a MAR algorithm on image quality in CBCT performed for evaluating patients before transarterial radioembolization (TARE). We retrospectively included 40 consecutive patients (aged 65 ± 13 years; 23 males) who underwent 45 CBCT examinations (Allura FD 20, XperCT Roll protocol, Philips Healthcare, Best, The Netherlands) in the setting of evaluation for TARE between January 2017 and December 2018. Artifacts caused by coils, catheters, and surgical clips were scored subjectively by four readers on a 5-point scale (1 = artifacts affecting diagnostic information to 5 = no artifacts) using a side-by-side display of uncorrected and MAR-corrected images. In addition, readers scored tumor visibility and vessel discrimination. MAR-corrected images were assigned higher scores, indicating better image quality. The differences between the measurements with and without MAR were most impressive for coils with a mean improvement of 1.6 points (95%CI [1.5 1.8]) on the 5-point likert scale, followed by catheters 1.4 points (95%CI [1.3 1.5]) and clips 0.7 points (95%CI [0.3 1.1]). Improvements for other artifact sources were consistent but relatively small (below 0.25 points on average). Interrater agreement was good to perfect (Kendall’s W coefficient = 0.68–0.95) and was higher for MAR-corrected images, indicating that MAR improves diagnostic accuracy. A metal artifact reduction algorithm can improve diagnostic and interventional accuracy of cone beam CT in patients undergoing radioembolization by reducing artifacts caused by diagnostic catheters and coils, lowering interference of metal artifacts with adjacent major structures, and improving tumor visibility.

Abstract Protein turnover is critical for proteostasis, but turnover quantification is challenging, and even in well-studied E. coli, proteome-wide measurements remain scarce. Here, we quantify the turnover rates of ~3200 E. coli proteins under 13 conditions by combining heavy isotope labeling with complement reporter ion quantification and find that cytoplasmic proteins are recycled when nitrogen is limited. We use knockout experiments to assign substrates to the known cytoplasmic ATP-dependent proteases. Surprisingly, none of these proteases are responsible for the observed cytoplasmic protein degradation in nitrogen limitation, suggesting that a major proteolysis pathway in E. coli remains to be discovered. Lastly, we show that protein degradation rates are generally independent of cell division rates. Thus, we present broadly applicable technology for protein turnover measurements and provide a rich resource for protein half-lives and protease substrates in E. coli, complementary to genomics data, that will allow researchers to study the control of proteostasis.

Summary: Chimeric antigen receptor (CAR) T cell therapy often causes serious toxicities, such as cytokine release syndrome (CRS), mainly due to interleukin-6 (IL-6) secreted by monocyte lineage cells. Here, we describe a protocol to generate anti-CD19 CAR T cells and quantify human monocyte-derived IL-6 cocultured with CAR T cells and target tumor cells in vitro. We further describe a protocol to generate a humanized mouse model and evaluate CAR T cell-associated plasma IL-6 levels in vivo.For complete details on the use and execution of this protocol, please refer to Yoshikawa et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

BackgroundParagangliomas (PGL) are rare neuroendocrine tumors derived from the autonomic nervous system paraganglia. Urinary bladder paragangliomas (UBPGL) originate from the sympathetic neurons of the urinary bladder wall and represent 0.7% of all paragangliomas and A, p Q214Q), detected in the UBPGL, was proven to be somatic. Although this variant was seemingly synonymous, it was predicted to have a loss of function due to the splice site effect, which was further supported by the immunohistochemical loss of SDHB.ConclusionThis case highlights the challenges of diagnosing an extremely rare entity, bladder paraganglioma, with an emphasis on the multidisciplinary approach to navigate various clinical and imaging findings that may initially be misleading. In addition, a novel loss of function SDHB variant that could have been overlooked as a synonymous variant is herein reported, while also illustrating the importance of both germline and somatic mutation testing.

To delve into the intricacies of sustainable agricultural practices, our study investigates both the behavioral and non-behavioral factors influencing farmers' decision-making processes. Employing the New Ecological Model (NEP) to capture social factors, our research framework integrates insights from the sustainable livelihood framework, which delineates five crucial types of livelihood capital: (1) human capital, (2) natural capital, (3) financial capital, (4) physical capital, and (5) social capital. This comprehensive approach enables us to incorporate additional non-behavioral factors and their impacts on farmers' decisions. We underscore the pivotal role of farmers' decisions in fostering sustainable agriculture, aligning with seven of the Sustainable Development Goals (SDGs). Leveraging survey data collected from 303 Vietnamese farmers, we validate our research framework using two analytical models: Structural Equation Model (SEM) and binary logit analysis. Our findings underscore the significant influence of farmers' risk propensity and concerns regarding food safety and environmental conservation on the adoption of organic farming practices. Notably, farmers' level of knowledge emerges as a critical determinant shaping their inclination towards sustainable agriculture. The study underscores the importance of targeted educational initiatives and awareness campaigns, identifying key determinants such as proximity to green spaces and farm size in shaping farmers' choices towards sustainable practices.

Summary: Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%–68.2%), compared with 63.4% in the control group (95% CI 61.8%–65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%–20.7%), compared with 18.8% in the control group (95% CI 17.4%–20.2%) a difference of +0.6 percentage points (95% CI −1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.

Nowadays, video streaming has become a popular form of multimedia for communication and entertainment. The rapid traffic explosion spurred by the development of emerging video-centric services such as e-science, virtual reality, and video conference has caused network congestion and the degradation in quality of experience (QoE), especially in heterogeneous mobile networks. To cope with that, the development of QoE-efficient video streaming solutions, i.e., HTTP adaptive video streaming, is critical. In this work, we investigate HTTP adaptive video streaming solutions that are capable of improving QoE for heterogeneous mobile networks in which the network conditions including bandwidth are significantly varied. We propose an effective QoE-aware adaptive bitrate video streaming scheme that integrates a bandwidth prediction based on Gated Recurrent Unit (GRU) neural networks with an adaptive bitrate selection strategy to wisely determine the suitable quality level for each video chunk. Thanks to the accurate bandwidth estimation and the adaptation of each video chunk bitrate to the network conditions, QoE metrics have been enhanced. Numerical experiments have been deployed to verify the performance of our proposed solution in comparison with that of the notable conventional methods. The attained simulation results demonstrate that the developed solution is significantly more effective than the conventional methods. The proposed method obtains a performance increment, in terms of QoE, of up to 19.4% compared to the conventional ones.

Acute methanol intoxication is uncommon. Methanol is mildly toxic, but its metabolites are formic acid and formaldehyde, causing total metabolism, visual disturbances, and central nervous system disturbances, leading to coma and death. Magnetic resonance imaging (MRI) is very important for the diagnosis and prognosis of methanol intoxication. Putaminal necrosis with or without hemorrhage is the most frequently reported finding. Other affected areas that are reported in the literature are subcortical white matter, hippocampus, optic nerve, and cerebellum. We report 3 cases of methanol intoxication and discuss their brain lesions on MRI.

This study investigates the critical factors influencing shoot and root regeneration from Homalomena gigantea rhizome cuttings, providing valuable insights for rhizome cutting practices for this plant species. Three key experiments were conducted to assess the impact of plant growth regula- tor (PGR) concentrations, cutting length, and cutting section on regeneration. In the first experiment, different concentrations of α-NAA and BAP were examined, revealing that PGR selection and concentration play a pivotal role in shoot and root induction and plantlet development. The highest success rates were observed at 150 ppm α-NAA and 100 ppm BAP, although there was a trade-off between the quantity and quality of plantlets, emphasizing the need for a balanced plant regulator selection. The second experiment investigated the influence of rhizome cutting length. Longer cuttings, particularly at 5 and 7 cm, consistently led to better shoot and root development, highlighting the importance of selecting appropriate cutting lengths. In the third experiment, cutting sections (apical, middle, and distal) without PGR concentrations were assessed, with all sections showing high regeneration rates. However, the apical section produced the highest-quality plantlets with superior growth parameters, followed by the middle section, while the distal section exhibited lower effectiveness. In summary, these findings underscore the significance of PGR choice and concentration, cutting length, and cut- ting section for successful regeneration of H. gigantea from rhizome cuttings. These insights provide valuable guidance for enhancing rhizome cuttings methods for this plant species and promoting efficient propagation.

Summary: Background: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens. Methods: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array. Findings: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients. Interpretation: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study. Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children’s. BRACE trial funding is detailed in acknowledgements.

This study presents a streamlined fabrication process for lithium-ion battery (LIB) electrodes, involving the dispersion of carbon nanotubes (CNT), silicon (Si), and graphene oxide (GO) in an aqueous solution, followed by vacuum filtration to produce self-standing composite electrodes. Two reduction routes are employed to form reduced graphene oxide (rGO). The chemically reduced CNT/Si/rGO-5 %-Chem anode exhibits superior mechanical resilience compared to thermally reduced counterparts, which suffer from reduced strength and structural integrity. Chemical reduction also enhances electrochemical performance, increasing the initial capacity of the non-reduced CNT/Si/GO-5 % composite anode from 1,461 to 2,342 mAh g−1, with improved long-term cycling performance. Electrochemical impedance spectroscopy shows lower pre-cycle charge transfer resistance (148 Ω) and superior solid electrolyte interphase (SEI) resistance (43 Ω) for chemically reduced anodes compared to thermally reduced ones. After cycling, the chemically reduced composite anode exhibits reduced electrolyte resistance and charge transfer resistance, indicating stable electrochemical reactions. The composite structure undergoes adaptive rearrangements during cycling, optimizing active material utilization. In summary, CNTs accommodate silicon swelling, while chemically reduced rGO promotes stable SEI formation, highlighting the benefits of chemical reduction in enhancing mechanical durability and electrochemical performance, making the self-standing CNT/Si/rGO composite film a promising LIB anode.

Understanding adaptive immunity against SARS-CoV-2 is a major requisite for the development of effective vaccines and treatments for COVID-19. CD4+ T cells play an integral role in this process primarily by generating antiviral cytokines and providing help to antibody-producing B cells. To empower detailed studies of SARS-CoV-2-specific CD4+ T cell responses in mouse models, we comprehensively mapped I-Ab-restricted epitopes for the spike and nucleocapsid proteins of the BA.1 variant of concern via IFNγ ELISpot assay. This was followed by the generation of corresponding peptide:MHCII tetramer reagents to directly stain epitope-specific T cells. Using this rigorous validation strategy, we identified 6 immunogenic epitopes in spike and 3 in nucleocapsid, all of which are conserved in the ancestral Wuhan strain. We also validated a previously identified epitope from Wuhan that is absent in BA.1. These epitopes and tetramers will be invaluable tools for SARS-CoV-2 antigen-specific CD4+ T cell studies in mice.

Objective Diet significantly contributes to dental decay (caries) yet monitoring and modifying patients’ diets is a challenge for many dental practitioners. While many oral health and diet-tracking mHealth apps are available, few focus on the dietary risk factors for caries. This study aims to present the development and key features of a dental-specific mobile app for diet monitoring and dietary behaviour change to prevent caries, and pilot data from initial user evaluation. Methods A mobile app incorporating a novel photo recognition algorithm and a localised database of 208,718 images for food item identification was developed. The design and development process were iterative and incorporated several behaviour change techniques commonly used in mHealth. Pilot evaluation of app quality was assessed using the end-user version of the Mobile Application Rating Scale (uMARS). Results User feedback from the beta-testing of the prototype app spurred the improvement of the photo recognition algorithm and addition of more user-centric features. Other key features of the final app include real-time prompts to drive actionable behaviour change, goal setting, comprehensive oral health education modules, and visual metrics for caries-related dietary factors (sugar intake, meal frequency, etc.). The final app scored an overall mean (standard deviation) of 3.6 (0.5) out of 5 on the uMARS scale. Conclusion We developed a novel diet-tracking mobile app tailored for oral health, addressing a gap in the mHealth landscape. Pilot user evaluations indicated good app quality, suggesting its potential as a useful clinical tool for dentists and empowering patients for self-monitoring and behavioural management.

ABSTRACT Phage therapy, an emerging strategy in the fight against recalcitrant bacterial infections, encounters a significant hurdle posed by the development of phage-resistant bacterial strains. To address this concern, we suggest a novel phage cocktail. By subjecting bacterial strains to a gradual selection process, we isolated and identified three novel phages augmenting one previously isolated phage. This diverse phage set formed the basis of a phage cocktail, displaying enhanced efficacy in curtailing the emergence of phage resistance, particularly evident in the notable stability achieved by three- and four-phage combinations. Our investigation further illuminated distinctive attributes exhibited by phage-resistant mutants: a concomitant reduction in growth rate and virulence offset by a noteworthy escalation in biofilm formation. The therapeutic modality underpinning our approach encompasses both the direct lethality of phages toward bacteria and the intricate landscape of bacterial genetic adaptations. Of intrigue was our observation that bacterial strains previously impervious to a given phage could regain susceptibility following resistance development against an unrelated phage. This phenomenon demonstrates the potential of phage cocktails as an efficacious countermeasure. Consequently, we suggest an innovative approach involving the design of phage cocktails that selectively encompass phages retaining susceptibility to bacteria that have developed resistance to other phages within the cocktail. Furthermore, we advocate for the comprehensive profiling of phage host ranges targeting both resistant strains and wild-type counterparts. The compilation of such intricate host-range data holds the promise of establishing a repository of diverse phages, meticulously tailored for refined and personalized phage therapy interventions. IMPORTANCE In this study, we aimed to design a novel and effective bacteriophage cocktail that can target both wild-type bacteria and phage-resistant mutants. To achieve this goal, we isolated four phages (U2874, phi_KPN_H2, phi_KPN_S3, and phi_KPN_HS3) that recognized different bacterial surface molecules using phage-resistant bacteria. We constructed three phage cocktails and tested their phage resistance-suppressing ability against multidrug-resistant Klebsiella pneumoniae. We argue that the phage cocktail that induces resensitization of phage susceptibility exhibited superior phage resistance-suppressing ability. Moreover, we observed trade-off effects that manifested progressively in phage-resistant bacteria. We hypothesize that such trade-off effects can augment therapeutic efficacy. We also recommend collating phage host range data against phage-resistant mutants in addition to wild-type bacteria when establishing phage banks to improve the efficiency of phage therapy. Our study underscores the importance of phage host range data in constructing effective phage cocktails for clinical use.

Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) present significant healthcare challenges due to limited treatment options. Bacteriophage (phage) therapy offers potential as an alternative treatment. However, the high host specificity of phages poses challenges for their therapeutic application. To broaden the phage spectrum, laboratory-based phage training using the Appelmans protocol was employed in this study. As a result, the protocol successfully expanded the host range of a phage cocktail targeting CRAB. Further analysis revealed that the expanded host range phages isolated from the output cocktail were identified as recombinant derivatives originating from prophages induced from encountered bacterial strains. These findings provide valuable genetic insights into the protocol's mechanism when applied to phages infecting A. baumannii strains that have never been investigated before. However, it is noteworthy that the expanded host range phages obtained from this protocol exhibited limited stability, raising concerns about their suitability for therapeutic purposes.

Background Understanding of the behavioural and social drivers (BeSD) of vaccination is key to addressing vaccine hesitancy and accessibility issues. Vietnam’s national COVID-19 vaccination programme resulted in high uptake of primary doses among adults, but lower booster doses for adults and primary doses for 5–11 years. This scoping review assessed BeSD influencing COVID-19 vaccine uptake in Vietnam to design interventions on reaching the national vaccination targets.Method We conducted a scoping review by searching PubMed, MedRxiv, LitCOVID, COVID-19 LOVE platform, WHO’s COVID-19 research database and seven dominant Vietnamese language medical journals published in English or Vietnamese between 28 December 2019 and 28 November 2022. Data were narratively synthesised and summarised according to the four components of the WHO BeSD framework. The drivers were then mapped along the timeline of COVID-19 vaccine deployment and the evolution of the pandemic in Vietnam.Results We identified 680 records, of which 39 met the inclusion criteria comprising 224 204 participants. Adults’ intention to receive COVID-19 vaccines for themselves (23 studies) ranged from 58.0% to 98.1%. Parental intention to vaccinate their under 11-year-old children (six studies) ranged from 32.8% to 79.6%. Key drivers of vaccination uptake were perceived susceptibility and severity of disease, perceived vaccine benefits and safety, healthcare worker recommendation, and positive societal perception. Commonly reported COVID-19 vaccines’ information sources (six studies) were social and mainstream media (82%–67%), television (72.7%–51.6%) and healthcare workers (47.5%–17.5%). Key drivers of COVID-19 uptake remained consistent for both adults and children despite changes in community transmission and vaccine deployment.Conclusion Key enablers of vaccine uptake for adults and children included perceived disease severity, perceived vaccine benefits and safety and healthcare worker recommendations. Future studies should assess vaccine communication targeted to these drivers, national policies and political determinants to optimise vaccine uptake.

Abstract Dengue and Zika viruses are mosquito-borne flaviviruses burdening millions every year with hemorrhagic fever and neurological symptoms. Baicalein was previously reported as a potential anti-flaviviral candidate and halogenation of flavones and flavanones potentiated their antiviral efficacies. Here, we reported that a chemically modified 8-bromobaicalein effectively inhibited all dengue serotypes and Zika viruses at 0.66–0.88 micromolar in cell-based system. The compound bound to dengue serotype 2 conserved pocket and inhibited the dengue RdRp activity with 6.93 fold more than the original baicalein. Moreover, the compound was mildly toxic against infant and adult C57BL/6 mice despite administering continuously for 7 days. Therefore, the 8-bromobaicalein should be investigated further in pharmacokinetics and efficacy in an animal model.

Abstract In a retrospective case series of 10 children with cryptogenic FIRES, we sought to describe the early clinical course and potential biomarkers following anakinra initiation. Six children achieved anesthetic withdrawal within 3 weeks of therapy and one in week four. Of the available cEEG (six children), CRP (10 children), and serum cytokine (six children) studies, there were temporal changes in highly epileptiform bursts (observed in three children), CRP, IL‐6, and IL‐10 levels that might parallel clinical progression. These observations may represent candidate biomarkers for monitoring clinical progression and therapeutic interventions including anakinra, which merits further investigation in future studies.

In this paper, we intend to examine the influence of national governance on the bank efficiency of joint venture and foreign commercial banks in Vietnam. Joint venture and foreign commercial banks have been instrumental in introducing new financial products to the Vietnamese market (e.g., mortgage services and medium-term certificates of deposit). At the same time, they have also penetrated the retail market through automobile and housing loans, and international credit card services. We use the DEA double bootstrap method to develop a bank network function to evaluate bank efficiency. The findings from our random-effects model demonstrate that world governance indicators as proposed by the World Bank independently determine the bank efficiency of the joint venture and foreign commercial banks in Vietnam. There are important implications to be highlighted for policymakers and stakeholders of joint venture and foreign commercial banks and other types of banks in the banking industry elsewhere around the world.

Summary: Background: Recurrences of herpes simplex virus (HSV) in the orofacial region (herpes labialis or cold sores) impact quality-of-life. We aimed to study whether the bacille Calmette-Guérin (BCG) vaccine can attenuate cold sore recurrences through off-target immunomodulatory effects. Methods: In this nested randomised controlled trial within the multicentre, phase 3 BRACE trial, 6828 healthcare workers were randomised in 36 sites in Australia, the Netherlands, Spain, the United Kingdom and Brazil, to receive BCG-Denmark or no BCG (1:1 ratio using a web-based procedure) and followed for 12 months with 3-monthly questionnaires. Exclusion criteria included contraindication to BCG vaccine or previous vaccination with BCG within the past year, any other live-attenuated vaccine within the last month, or any COVID-specific vaccine. The intervention group received one intradermal dose of 0.1 mL of BCG-Denmark corresponding to 2−8 x 105 colony forming units of Mycobacterium bovis, Danish strain 1331. The primary outcome was the difference in restricted mean survival time (i.e., time to first cold-sore recurrence), in participants with frequent recurrent herpes labialis (≥4 recurrences/year), analysed by intention-to-treat. Secondary outcomes addressed additional questions, including analyses in other sub-populations. Adverse events were monitored closely during the first 3 months and were reported in all participants who received one dose of study drug according to intervention received. The BRACE trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020 and February 18, 2021, 84 individuals with frequent recurrent cold sores were randomly assigned to BCG (n = 38) or control (n = 46). The average time to first cold-sore recurrence was 1.55 months longer in the BCG group (95% CI 0.27–2.82, p = 0.02) than the control group (hazard ratio 0.54, 95% CI 0.32–0.91; intention-to-treat). The beneficial effect of BCG was greater in the as-treated population (difference 1.91 months, 95% CI 0.69–3.12, p = 0.003; hazard ratio 0.45, 95% CI 0.26–0.76). In prespecified subgroup analyses, only sex modified the treatment effect (interaction p = 0.007), with benefit restricted to males. Over 12 months, a greater proportion of participants in the BCG group compared with the control group reported a decrease in duration (61% vs 21%), severity (74% vs 21%), frequency (55% vs 21%), and impact on quality of life (42% vs 15%) of cold sore recurrences. In participants who had ever had a cold sore, there was also a decrease in self-reported burden of recurrences in the BCG group. In participants who had never had a cold sore, there was an increased risk of a first episode in the BCG group (risk difference 1.4%; 95% CI 0.3–2.6%, p = 0.02). There were no safety concerns. Interpretation: BCG-Denmark vaccination had a beneficial effect on herpes labialis, particularly in males with frequent recurrences, but may increase the risk of a first cold sore. Funding: Bill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, and individual donors.

Abstract Background Mid-aortic syndrome (MAS) is characterized by the congenital coarctation of the abdominal aorta, abdominal and limb claudication, and hypertension. The etiology of this disorder is very diverse and often manifests in conjunction with Takayasu's arteritis, Williams-Beurens syndrome, and neurofibromatosis. The isolated mid-aortic syndrome is very rare with only a few cases reported in the literature. Case presentation A 45 years old man was admitted to the Emergency Department with sudden muscle weakness and facial paralysis on the left side. Imaging studies reveal right middle cerebral artery infarction at the M1 section. Incidental findings include multiple moderate to severe stenoses in the right internal carotid artery, and total abdominal aorta occlusion. A variant at the ELN gene (Elastin, OMIM*130,160): c.1768G > A/wt (p.Ala590Thr) was identified. Conclusion This is the first reported case of ELN related mid-aortic syndrome in Vietnam which was diagnosed through careful clinical and genetic workup. The finding of mid-aortic syndrome, in this case, was incidental and the decision to reverse the occlusion was postponed as there was no immediate risk of renal failure or reduced blood flow to the lower limb.

The objective of this work was to analyze the content and the chemical diversity of the essential oils from the aerial parts of eight species belonging to Zingiberaceae family collected in Binh Chau-Phuoc Buu Nature Reserve, Vietnam. The essential oils were isolated by hydrodistillation and their constituents were investigated by gas chromatography-mass spectrometry. The essential oils from the aerial parts of eight studied species, including Zingiber zerumbet, Zingiber pellitum, Curcuma pierreana, Globba macrocarpa, Globba globulifera, Alpinia conchigera, Stahlianthus campanulatus and Amomum sp. were obtained in a yield of 0.01%, 0.008%, 0.01%, 0.012%, 0.012%, 0.02%, 0.015 and 0.3%, respectively. There were a total of 75 compounds identified from the essential oils obtained from eight studied species. Four main clusters and three subclusters were formed by the cluster analysis. Cluster I consisted of A. conchigera with the presence of β-elemene (51.76%) and caryophyllene (28.1%). Cluster II contained five species, including Z. zerumbet, Z. pellitum, C. pierreana, G. globulifera and S. campanulatus with high concentration of β-pinene (11.81%, 5.32%, 4.43%, 25.42% and 1.57%), caryophyllene (13.61%, 23.45%, 19.78%, 34.26% and 18.72%), caryophyllene oxide (4.66%, 4.00%, 13.65%, 8.15% and 24.69%). Cluster III consisted of G. macrocarpa, and presented 4-isobutylquinoline (24.43%), β-copaene (21.69%), α-farnesene (20.73%), 2-tert-butylquinoline (6.05%), 3-Dihydroxydiphenylamine (5.47%), β-panasinsene (5.13%) as major compounds. Cluster IV contained Amomum sp. and had eucalyptol (25.22%), camphor (24.51%), camphene (14.57%), β-pinene (13.45%), Isoborneol (9.17%), α-Selinene (6.21%) as main constituents. The present study identified a total of 75 compounds of the essential oils from the aerial parts of eight species of the Zingiberaceae family collected in Binh-Chau_Phuoc-Buu Nature Reserve, Southern Vietnam. Four main clusters and three subclusters were formed by the cluster analysis. Cluster I consisted of A. conchigera with the presence of β-elemene (51.76%) and caryophyllene (28.1%). Cluster II contained five species, including Z. zerumbet, Z. pellitum, C. pierreana, G. globulifera and S. campanulatus with high concentration of β-pinene (11.81%, 5.32%, 4.43%, 25.42% and 1.57%), caryophyllene (13.61%, 23.45%, 19.78%, 34.26% and 18.72%), caryophyllene oxide (4.66%, 4.00%, 13.65%, 8.15% and 24.69%). Cluster III consisted of G. macrocarpa, and presented 4-isobutylquinoline (24.43%), β-copaene (21.69%), α-farnesene (20.73%), 2-tert-butylquinoline (6.05%), 3-dihydroxydiphenylamine (5.47%), β-Panasinsene (5.13%) as major compounds. Cluster IV contained Amomum sp. and had eucalyptol (25.22%), camphor (24.51%), camphene (14.57%), β-pinene (13.45%), isoborneol (9.17%), α-selinene (6.21%) as main constituents.

Here the authors address how embryos control the timing of specific gene activation in early frog development. They find transcription factors for early gene activation are maternally loaded and remain at constant levels, and rather that order of activation is based on their sequential entry into the nucleus based largely on their respective affinity to importins.

Abstract Several mutations that cause Parkinson’s disease (PD) have been identified over the past decade. These account for 15–25% of PD cases; the rest of the cases are considered sporadic. Currently, it is accepted that PD is not a single monolithic disease but rather a constellation of diseases with some common phenotypes. While rodent models exist for some of the PD-causing mutations, research on the sporadic forms of PD is lagging due to a lack of cellular models. In our study, we differentiated PD patient-derived dopaminergic (DA) neurons from the induced pluripotent stem cells (iPSCs) of several PD-causing mutations as well as from sporadic PD patients. Strikingly, we observed a common neurophysiological phenotype: neurons derived from PD patients had a severe reduction in the rate of synaptic currents compared to those derived from healthy controls. While the relationship between mutations in genes such as the SNCA and LRRK2 and a reduction in synaptic transmission has been investigated before, here we show evidence that the pathogenesis of the synapses in neurons is a general phenotype in PD. Analysis of RNA sequencing results displayed changes in gene expression in different synaptic mechanisms as well as other affected pathways such as extracellular matrix-related pathways. Some of these dysregulated pathways are common to all PD patients (monogenic or idiopathic). Our data, therefore, show changes that are central and convergent to PD and suggest a strong involvement of the tetra-partite synapse in PD pathophysiology.

Abstract Background Laccase-based biosensors are efficient for detecting phenolic compounds. However, the instability and high cost of laccases have hindered their practical utilization. Results In this study, we developed hierarchical manganese dioxide–copper phosphate hybrid nanoflowers (H–Mn–Cu NFs) as excellent laccase-mimicking nanozymes. To synthesize the H–Mn–Cu NFs, manganese dioxide nanoflowers (MnO2 NFs) were first synthesized by rapidly reducing potassium permanganate using citric acid. The MnO2 NFs were then functionalized with amine groups, followed by incubation with copper sulfate for three days at room temperature to drive the coordination interaction between the amine moieties and copper ions and to induce anisotropic growth of the petals composed of copper phosphate crystals, consequently yielding H–Mn–Cu NFs. Compared with those of free laccase, at the same mass concentration, H–Mn–Cu NFs exhibited lower K m (~ 85%) and considerably higher V max (~ 400%), as well as significantly enhanced stability in the ranges of pH, temperature, ionic strength, and incubation periods evaluated. H–Mn–Cu NFs also catalyzed the decolorization of diverse dyes considerably faster than the free laccase. Based on these advantageous features, a paper microfluidic device incorporating H–Mn–Cu NFs was constructed for the convenient visual detection of phenolic neurotransmitters, including dopamine and epinephrine. The device enabled rapid and sensitive quantification of target neurotransmitters using an image acquired using a smartphone. Conclusions These results clearly show that H–Mn–Cu NFs could be potential candidates to replace natural laccases for a wide range of applications in biosensing, environmental protection, and biotechnology. Graphical Abstract

Vietnam is known as an agricultural country with a variety of agricultural crops. In addition to agricultural by-products, bio-waste is the by-product from livestock waste, forestry, industry, and daily life. They affect the soil, water, and air environment by self-degradation processes in the environment. Therefore, researchers have come up with ideas for the usage of the by-products to decrease the amount of waste and minimize the environmental effects. In Vietnam, the by-products were used by researchers to produce bio-ethanol, fertilizers, composites, and activated carbon (AC). AC is one of the materials used to rapidly reduce the number of agricultural by-products by researchers. The synthesis process is optimized for the highest yield, while the physicochemical properties are also clearly analyzed through the X-ray diffraction, Fourier transform infrared, and Bacterial endotoxin testing assays. The average recorded specific surface area was about 300 m2 g−1. The functional groups and surface structure showed that the material has an amorphous structure with –OH, –CH, –CC, –C═C, –C═O groups. The AC from agricultural waste had been studied and applied to treat pollutants present in water.

Neonatal screening for congenital adrenal hyperplasia (CAH) faces many specific challenges. It must be done using a performant analytical approach that combines sensitivity and specificity to capture the potential causes of mortality during the first week of life, such as salt wasting and glucocorticoid deficiency. Here, we confirm that maternal inhaled corticosteroid intake during pregnancy is a possible cause of missed CAH diagnosis. Thanks to liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis, we were able to quantify endogenous steroid metabolites and also detect the presence of exogenous steroids in the dried blood spot of a newborn. Adding LC-MS/MS analysis as second-tier test, especially one that includes both 17-hydroxyprogesterone and 21-deoxycortisol measurements, would probably improve CAH diagnosis. In familial neonatal screening one could also look for maternal corticosteroid therapies that are hidden to prevent false-negative tests.

The objective of the study is to evaluate the effect of renewable energy and factors such as financial development, foreign direct investment, population size and urbanization rate on CO2 emissions in six typical Southeast Asian country between 2000 and 2020. Using quantitative analysis, the study results confirm that the use of renewable energy has the potential to improve environmental quality due to its ability to reduce energy CO2 emissions. However, increasing urbanization rate has a negative impact on environmental quality because urbanization is associated with labor mobility and increased CO2 emissions. There is no evidence of between population size, financial development, foreign direct investment and CO2 emissions.

As an alternate non-destructive analytical modality for monitoring from pre-harvest to post-storage, optical imaging with near-infrared wavelength is used to forecast the quality of numerous fruits. In the near-infrared spectrum, bio-chemicals are identified and measured with light by penetrating deeply into food components. In addition, apples and other fruits with a high water content benefit from water absorption capabilities. The optical approaches are efficient, inexpensive, and environmentally beneficial. This study is performed to examine the setup of reflection imaging to pick the near-infrared wavelength and optimize the distance between the detector and the light source. Molecular Optical Simulation Environment (MOSE) and Monte Carlo multi-layered programs (MCML) were used to simulate the light propagation in a model of apple tissue to select the appropriate wavelength for evaluating food quality in experiments and optimize the position of the reflected signal receiver. As a consequence, the 700–900 nm wavelength has great promise for use in assessing food quality, particularly apple quality. One centimeter is the optimal distance between the detector and the light source. The data may be used to organize an experiment and create an evaluation tool for determining the quality of fruits using optical methods, particularly apples.

Abstract Objectives To assay salivary anti-nuclear antibody (ANA) and its isotypes in patients with systemic lupus erythematosus (SLE) and to investigate relevant clinical associations. Methods Saliva samples were collected from SLE patients and assayed for salivary ANA using immunofluorescence (IF). Isotypes of salivary ANA, including IgG-ANA, IgA-ANA, and IgM-ANA, were quantified using enzyme-linked immunosorbent assay. The correlations between clinical parameters and levels of salivary ANA and isotypes were evaluated. Results Salivary ANA IF intensities were significantly higher in SLE patients than in healthy controls, irrespective of SLE patient disease activity, and strongly correlated with serum ANA titers. Salivary ANA was detected in 67.14% of SLE patients and 10.00% of healthy controls (p

Caenorhabditis elegans, often referred to as the ‘roundworm’, provides a powerful model for studying cell autonomous and cell–cell interactions through the direct observation of embryonic development in vivo. By leveraging the precisely mapped cell lineage at single cell resolution, we are able to study at a systems level how early embryonic cells communicate across morphogenetic domains for the coordinated processes of gene expressions and collective cellular behaviors that regulate tissue morphogenesis. In this study, we developed a computational framework for the exploration of the morphogenetic domain cell signaling networks that may regulate C. elegans gastrulation and embryonic organogenesis. We demonstrated its utility by producing the following results, i) established a virtual reference model of developing C. elegans embryos through the spatiotemporal alignment of individual embryo cell nuclear imaging samples; ii) integrated the single cell spatiotemporal gene expression profile with the established virtual embryo model by data pooling; iii) trained a Machine Learning model (Random Forest Regression), which predicts accurately the spatial positions of the cells given their gene expression profiles for a given developmental time (e.g. total cell number of the embryo); iv) enabled virtual 4-dimensional tomographic graphical modeling of single cell data; v) inferred the biology signaling pathways that act in each of morphogenetic domains by meta-data analysis. It is intriguing that the morphogenetic domain cell signaling network seems to involve some crosstalk of multiple biology signaling pathways during the formation of tissue boundary pattern. Lastly, we developed the Software tool ‘Embryo aligner version 1.0’ and provided it as an Open Source program to the research community for virtual embryo modeling, and phenotype perturbation analyses (https://github.com/csniuben/embryo_aligner/wiki and https://bioinfo89.github.io/C.elegansEmbryonicOrganogenesisweb/).

Abstract Conventional vapor–liquid–solid mechanism of nanowire growth opens up new opportunities of fabricating nanowires with controllable morphologies and aspect ratios. However, gaseous precursors have disadvantages of high material and processing cost, high toxicity, and limited scalability. By contrast, synthesizing nanowires via solid–liquid–solid mechanism could be a facile alternative since the low cost and nontoxic solid precursor is adopted in the process. In this study, the cooling control is found to be very critical for the solid–liquid–solid nanowire growth. Without a sufficient negative vertical temperature gradient, the nucleation and continuous growth of silicon nanowires could not occur. High volume gas flow cooling, fluctuating the heating temperature, decreasing the cooling rate, and applying a heat sink are all efficacious to promote silicon nanowire formation. In addition to the nanowires formed under high gas flow cooling on the silicon wafer sputtered with a nickel thin film, the solid–liquid–solid mechanism‐derived silicon nanowire growth can also be economically achieved by adopting a solution‐based coating of a nickel precursor onto the silicon substrate paired with a programmed slow cooling condition without using any gas, which could be transferred to other eutectic systems for cost‐effective nanomaterial fabrication.

Abstract Background A high proportion of patients with Cystic Fibrosis (CF) also present the rare skin disease aquagenic palmoplantar keratoderma. A possible link between this condition and absence of a functional CF Transmembrane conductance Regulator protein in the sweat acinus and collecting duct remains unknown. Methods In‐depth characterization of sweat proteome profiles was performed in 25 CF patients compared to 12 healthy controls. A 20 μL sweat sample was collected after pilocarpine iontophoresis and liquid chromatography tandem mass spectrometry (LC‐MS/MS) proteomic analysis was performed. Results Sweat proteome profile of CF patients was significantly different from that of healthy subjects with 57 differentially expressed proteins. Cystic Fibrosis sweat proteome was characterized by an increase in 25 proteins including proteases (Kallikrein 7 and 13, Phospholipase B domain containing 1, Cathepsin A L2 and B, Lysosomal Pro‐X carboxypeptidase); proinflammatory proteins (Annexin A2, Chitinase‐3‐like protein 1); cytochrome c and transglutaminases. Thirty‐two proteins were downregulated in CF sweat including proteases (Elastase 2), antioxidative protein FAM129 B; membrane‐bound transporter SLC6A14 and regulator protein Sodium‐hydrogen antiporter 3 regulator 1. Conclusion This study is the first to report in‐depth characterization of endogenous peptides in CF sweat and could help understand the complex physiology of the sweat gland. The proteome profile highlights the unbalanced proteolytic and proinflammatory activity of sweat in CF. These results also suggest a defect in pathways involved in skin barrier integrity in CF patients. Sweat proteome profile could prove to be a useful tool in the context of personalized medicine in CF.

The COVID-19 pandemic severely affected the lives of families and the well-being of both parents and their children. Various factors, including prenatal stress, dysregulated stress response systems, and genetics may have influenced how the stress caused by the pandemic impacted the well-being of different family members. The present work investigated if emotional well-being during the COVID-19 pandemic could be predicted by developmental stress-related and genetic factors. Emotional well-being of 7–10 year-old children (n = 263) and mothers (n = 241) (participants in a longitudinal German birth cohort (POSEIDON)) was assessed during the COVID-19 pandemic using the CRISIS questionnaire at two time periods (July 2020–October 2020; November 2020–February 2021). Associations of the children’s and mothers’ well-being with maternal perceived stress, of the children’s well-being with their salivary and morning urine cortisol at 45 months, and polygenic risk scores (PRSs) for depression, schizophrenia, loneliness were investigated. Lower emotional well-being was observed in both children and mothers during compared to before the pandemic, with the children’s but not the mothers’ emotional well-being improving over the course of the pandemic. A positive association between the child and maternal emotional well-being was found. Prenatally assessed maternal perceived stress was associated with a lower well-being in children, but not in mothers. Cortisol measures and PRSs were not significantly associated with the children’s emotional well-being. The present study confirms that emotional well-being of children and mothers are linked, and were negatively affected by the COVID-19 pandemic, with differences in development over time.

Neonatal hepatic abscess (NHA) is a fatal condition in neonates. NHA can be caused by many organisms including bacteria, parasites, and fungi. Fungal NHA is a rare but troublesome cause in terms of diagnosis and treatment. We present three cases of fungal NHA caused by Candida. In these three cases, different underlying problems associated with NHA had been found.

Due to the significant resemblance in visual appearance, pill misuse is prevalent and has become a critical issue, responsible for one-third of all deaths worldwide. Pill identification, thus, is a crucial concern that needs to be investigated thoroughly. Recently, several attempts have been made to exploit deep learning to tackle the pill identification problem. However, most published works consider only single-pill identification and fail to distinguish hard samples with identical appearances. Also, most existing pill image datasets only feature single pill images captured in carefully controlled environments under ideal lighting conditions and clean backgrounds. In this work, we are the first to tackle the multi-pill detection problem in real-world settings, aiming at localizing and identifying pills captured by users during pill intake. Moreover, we also introduce a multi-pill image dataset taken in unconstrained conditions. To handle hard samples, we propose a novel method for constructing heterogeneous a priori graphs incorporating three forms of inter-pill relationships, including co-occurrence likelihood, relative size, and visual semantic correlation. We then offer a framework for integrating a priori with pills' visual features to enhance detection accuracy. Our experimental results have proved the robustness, reliability, and explainability of the proposed framework. Experimentally, it outperforms all detection benchmarks in terms of all evaluation metrics. Specifically, our proposed framework improves COCO mAP metrics by 9.4% over Faster R-CNN and 12.0% compared to vanilla YOLOv5. Our study opens up new opportunities for protecting patients from medication errors using an AI-based pill identification solution.

Attention to technology integration in teaching and learning has created a big change in the education landscape. There is no limit to the application of information technology in education in general and in mathematics education in particular. Although there have been many studies on the opportunities and applications of ICT in Mathematics education in the world, many aspects remain unexplored. In this study, the authors apply bibliometric analysis for the purpose of evaluating the scientific results of publications involving in the use of ICT in Mathematics education, which were indexed in the Scopus database. 205 publications were cited to analyze growth trends, contributions of authors, research institutions, co-authors in the research field and the development of research direction. The analysis results show that publications that mainly appear in recent years are published on sources with low citation index; Indonesia, Malaysia and Australia are the most influential countries in studies on this topic; Research cooperation in this field is not strong; The main research topics and trends are online teaching, realistic mathematics education, and computer-aided teaching. From the research results obtained, the authors also furnish some recommendations in the article for future research in this field.

Abstract The mechanisms underlying the development of glomerular lesions during aging are largely unknown. It has been suggested that senescence might play a role, but the pathophysiological link between senescence and lesion development remains unexplained. Here, we uncovered an unexpected role for glomerular endothelial cells during aging. In fact, we discovered a detrimental cross‐talk between senescent endothelial cells and podocytes, through PAI‐1. In vivo, selective inactivation of PAI‐1 in endothelial cells protected glomeruli from lesion development and podocyte loss in aged mice. In vitro, blocking PAI‐1 in supernatants from senescent endothelial cells prevented podocyte apoptosis. Consistently, depletion of senescent cells prevented podocyte loss in old p16 INK‐ATTAC transgenic mice. Importantly, these experimental findings are relevant to humans. We showed that glomerular PAI‐1 expression was predictive of poor outcomes in transplanted kidneys from elderly donors. In addition, we observed that in elderly patients, urinary PAI‐1 was associated with age‐related chronic kidney disease. Altogether, these results uncover a novel mechanism of kidney disease and identify PAI‐1 as a promising biomarker of kidney dysfunction in allografts from elderly donors.

We report a case of a 40-year-old female patient admitted to the hospital due to lumbar pain that spread to both legs and was associated with weakness of the lower extremities. Magnetic resonance imaging revealed an intradural - extramedullary tumor at the level of the T12 - L2 vertebra. The lesion was over 7 cm in greatest diameter and compressed the conus medullaris. The patient underwent surgery to remove the entire tumor. Postoperative pathology confirmed the diagnosis of schwannoma. The symptoms resolved almost completely without significant complications.

We report three cases with Herlyn-Werner-Wunderlich syndrome in adolescents and young female. The objective of this report was to describe the clinical presentation, ultrasound (US) and magnetic resonance imaging (MRI) findings of Herlyn-Werner-Wunderlich syndrome. The three patients were 12, 13 and 34 years old, respectively. The reason for admission and clinical symptoms varied between the 3 patients, including menstrual cramps, vaginal bleeding, and dull pain in the hypogastric region. Nevertheless, the sonographic and MRI findings of all three cases were typical for HWWS, including didelphys uterus, obstructed hemivagina, and ipsilateral renal agenesis.

Abstract Background Alternative polyadenylation (APA) is emerging as an important mechanism in the post-transcriptional regulation of gene expression across eukaryotic species. Recent studies have shown that APA plays key roles in biological processes, such as cell proliferation and differentiation. Single-cell RNA-seq technologies are widely used in gene expression heterogeneity studies; however, systematic studies of APA at the single-cell level are still lacking. Results Here, we described a novel computational framework, SAPAS, that utilizes 3′-tag-based scRNA-seq data to identify novel poly(A) sites and quantify APA at the single-cell level. Applying SAPAS to the scRNA-seq data of phenotype characterized GABAergic interneurons, we identified cell type-specific APA events for different GABAergic neuron types. Genes with cell type-specific APA events are enriched for synaptic architecture and communications. In further, we observed a strong enrichment of heritability for several psychiatric disorders and brain traits in altered 3′ UTRs and coding sequences of cell type-specific APA events. Finally, by exploring the modalities of APA, we discovered that the bimodal APA pattern of Pak3 could classify chandelier cells into different subpopulations that are from different laminar positions. Conclusions We established a method to characterize APA at the single-cell level. When applied to a scRNA-seq dataset of GABAergic interneurons, the single-cell APA analysis not only identified cell type-specific APA events but also revealed that the modality of APA could classify cell subpopulations. Thus, SAPAS will expand our understanding of cellular heterogeneity.

Abstract Background A complex cascade of genes, enzymes, and transcription factors regulates AmpC β-lactamase overexpression. We investigated the network of AmpC β-lactamase overexpression in Klebsiella aerogenes and identified the role of AmpG in resistance to β-lactam agents, including cephalosporins and carbapenems. Methods A transposon mutant library was created for carbapenem-resistant K. aerogenes YMC2008-M09-943034 (KE-Y1) to screen for candidates with increased susceptibility to carbapenems, which identified the susceptible mutant derivatives KE-Y3 and KE-Y6. All the strains were subjected to highly contiguous de novo assemblies using PacBio sequencing to investigate the loss of resistance due to transposon insertion. Complementation and knock-out experiments using lambda Red-mediated homologous recombinase and CRISPR–Cas9 were performed to confirm the role of gene of interest. Results In-depth analysis of KE-Y3 and KE-Y6 revealed the insertion of a transposon at six positions in each strain, at which truncation of the AmpG permease gene was common in both. The disruption of the AmpG permease leads to carbapenem susceptibility, which was further confirmed by complementation. We generated an AmpG permease gene knockout using lambda Red-mediated recombineering in K. aerogenes KE-Y1 and a CRISPR–Cas9-mediated gene knockout in multidrug-resistant Klebsiella pneumoniae-YMC/2013/D to confer carbapenem susceptibility. Conclusions These findings suggest that inhibition of the AmpG is a potential strategy to increase the efficacy of β-lactam agents against Klebsiella aerogenes.

Osteochondroma is the most common bone tumor representing 20%–50% of all benign bone tumors and 10%–15% of all bone tumors. Osteochondroma has similar radiological appearance in both solitary and multiple forms; the latter is an autosomal dominant disorder termed hereditary multiple exostoses. Associated complications of osteochondroma include deformity, fracture, neurovascular compromise, bursa formation, and malignant transformation. Measurement of the cartilage cap thickness is an important index suggesting secondary malignancy of osteochondroma. The upper limit of cap thickness after skeletal maturation is 1.5 cm which can be reliably measured on ultrasound or magnetic resonance imaging. Hereditary multiple exostoses are linked to the mutations of different exostoses genes located on chromosome 8, 11, and 19. We reported cases of two siblings presented with multiple osteochondromas managed by surgical excision. We evaluated their clinical and radiological presentation, genetic correlations and compared with the literature.

Abstract Following their inoculation by the bite of an infected Anopheles mosquito, the malaria parasite sporozoite forms travel from the bite site in the skin into the bloodstream, which transports them to the liver. The thrombospondin-related anonymous protein (TRAP) is a type 1 transmembrane protein that is released from secretory organelles and relocalized on the sporozoite plasma membrane. TRAP is required for sporozoite motility and host infection, and its extracellular portion contains adhesive domains that are predicted to engage host receptors. Here, we identified the human platelet-derived growth factor receptor β (hPDGFRβ) as one such protein receptor. Deletion constructs showed that the von Willebrand factor type A and thrombospondin repeat domains of TRAP are both required for optimal binding to hPDGFRβ-expressing cells. We also demonstrate that this interaction is conserved in the human-infective parasite Plasmodium vivax, but not the rodent-infective parasite Plasmodium yoelii. We observed expression of hPDGFRβ mainly in cells associated with the vasculature suggesting that TRAP:hPDGFRβ interaction may play a role in the recognition of blood vessels by invading sporozoites.