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This article presents current relevant data on the serogroups and antimicrobial susceptibility of Salmonella strains isolated in the southern provinces of the Socialist Republic of Vietnam. There were examined 189 Salmonella strains isolated from: human feces in acute diarrhea (86 strains); and pork samples (103 strains). Serological O-group identification was performed by slide agglutination with O- and H-antisera and multiplex PCR to detect H phase-1 and phase-2. Antimicrobial susceptibility testing was performed by using the disk-diffusion method according to the EUCAST (version 2019) recommendations. Strains isolated from humans predominantly belonged to O4 group (69.8%). The percentage of other serogroups varied from 1.2% (rare group O16) to 11.6% (O9). About a half of strains (44.7%) isolated from pork samples turned out to belong to the О3,10 serogroup (vs 7.0% of strains from humans). Serogroups О7, О4 and О8 were less frequent (22.3%, 14.6% and 13.6%, respectively). Single strains belonged to serogroups О9, О13, and О18. Regardless of the isolation source, about 80% of Salmonella strains were resistant to antibiotics from different antimicrobial groups (besides carbapenems): 67.0% were resistant to tetracycline; about half were resistant to pefloxacin, ampicillin and chloramphenicol (54.0%, 47.1%, 46.6%); and up to 40% were resistant to trimethoprim/sulfamethoxazole and nalidixic acid. The proportion of strains resistant to ceftriaxone and gentamycin was markedly higher in those of human vs pork origin: 12.8% vs 1.0% and 30.2 vs 1.9%, respectively. Moreover, 62.8% and 43.7% strains of human and pork origin, respectively, showed multidrug resistance (to 3 and more antimicrobial groups). In addition, simultaneous resistance to 6 antimicrobial groups was detected much more frequently in Salmonella strains isolated from humans vs pork samples (15.1% vs 1.0%, respectively). Multidrug resistance (MDR) was observed in strains of different serovars, predominantly S. Typhimurium (36.4%). The predominant MDR (30.3%) phenotype (AMP, TE, QN, C, SXT) was revealed in serovars of S. Typhimurium, S. Bredeney, S. Corvallis, S. Give, S. London, S. Rissen, and S. Meleagridis. Thus, Salmonella strains isolated in the southern Vietnamese provinces featured resistance to fluoroquinolones and cephalosporins. Taking into account simultaneous loss of susceptibility to old antimicrobials (ampicillin, chloramphenicol, trimethoprim/sulfamethoxazole), it crucially restricts the list of effective medicines to treat complicated salmonellosis cases.

IntroductionClinical tools are neither standardized nor ubiquitous to monitor volumetric or morphological changes in the periorbital region and ocular adnexa due to pathology such as oculofacial trauma, thyroid eye disease, and the natural aging process. We have developed a low-cost, three dimensionally printedPHotogrammetry forAutomatedCarE(PHACE) system to evaluate three-dimensional (3D) measurements of periocular and adnexal tissue.MethodsThe PHACE system uses two Google Pixel 3 smartphones attached to automatic rotating platforms to image a subject’s face through a cutout board patterned with registration marks. Photographs of faces were taken from many perspectives by the cameras placed on the rotating platform. Faces were imaged with and without 3D printed hemispheric phantom lesions (black domes) affixed on the forehead above the brow. Images were rendered into 3D models in Metashape (Agisoft, St. Petersburg, Russia) and then processed and analyzed in CloudCompare (CC) and Autodesk’s Meshmixer. The 3D printed hemispheres affixed to the face were then quantified within Meshmixer and compared to their known volumes. Finally, we compared digital exophthalmometry measurements with results from a standard Hertel exophthalmometer in a subject with and without an orbital prosthesis.ResultsQuantification of 3D printed phantom volumes using optimized stereophotogrammetry demonstrated a 2.5% error for a 244μL phantom, and 7.6% error for a 27.5μL phantom. Digital exophthalmometry measurements differed by 0.72mm from a standard exophthalmometer.ConclusionWe demonstrated an optimized workflow using our custom apparatus to analyze and quantify oculofacial volumetric and dimensions changes with a resolution of 244μL. This apparatus is a low-cost tool that can be used in clinical settings to objectively monitor volumetric and morphological changes in periorbital anatomy.

SARS-CoV-2 Omicron variants emerged in 2022 with >30 novel amino acid mutations in the spike protein alone. While most studies focus on the impact of receptor binding domain changes, mutations in the C-terminal of S1 (CTS1), adjacent to the furin cleavage site, have largely been ignored. In this study, we examined three Omicron mutations in CTS1: H655Y, N679K, and P681H. Generating a SARS-CoV-2 triple mutant (YKH), we found that the mutant increased spike processing, consistent with prior reports for H655Y and P681H individually. Next, we generated a single N679K mutant, finding reduced viral replicationin vitroand less diseasein vivo. Mechanistically, the N679K mutant had reduced spike protein in purified virions compared to wild-type; spike protein decreases were further exacerbated in infected cell lysates. Importantly, exogenous spike expression also revealed that N679K reduced overall spike protein yield independent of infection. Together, the data show that N679K is a loss-of-function mutation reducing overall spike levels during omicron infection, which may have important implications for disease severity, immunity, and vaccine efficacy.One Sentence SummarySpike substitution N679K attenuates SARS-CoV-2 Omicron variants by decreasing spike protein and has potential implications for immunity and vaccine efficacy.

PurposeTo compare a custom Photogrammetry for Anatomical CarE (PHACE) system with other cost-effective 3-dimensional (3D) facial scanning systems to objectively characterize morphology and volume of periorbital and adnexal anatomy.MethodsThe imaging systems evaluated include the low-cost custom PHACE system and commercial software product for the iPhone called Scandy Pro (iScandy) application (Scandy, USA), and the mid-priced Einscan Pro 2X (Shining3D Technologies, China) device and Array of Reconstructed Cameras 7 (ARC7) facial scanner (Bellus3D, USA). Imaging was performed on a manikin facemask and humans with various Fitzpatrick scores. Scanner attributes were assessed using mesh density, reproducibility, surface deviation, and emulation of 3D printed phantom lesions affixed above the superciliary arch (brow line).ResultsThe Einscan served as a reference for lower cost imaging systems because it qualitatively and quantitatively renders facial morphology with the highest mesh density, reproducibility (0.13 ± 0.10 mm), and volume recapitulation (approximately 2% of 33.5 μL). Compared to the Einscan, the PHACE system (0.35 ± 0.03 mm, 0.33 ± 0.16 mm) demonstrated non-inferior mean accuracy and reproducibility root mean square (RMS) compared to the iScandy (0.42 ± 0.13 mm, 0.58 ± 0.09 mm), and significantly more expensive ARC7 (0.42 ± 0.03 mm, 0.26 ± 0.09 mm). Similarly, the PHACE system showed non-inferior volumetric modeling when rendering a 124 μL phantom lesion compared to the iScandy and more costly ARC7 (mean percent difference from the Einscan: 4.68 ± 3.73%, 9.09 ± 0.94%, and 21.99 ± 17.91% respectively).ConclusionsThe affordable PHACE system accurately measures periorbital soft tissue as well as other established mid-cost facial scanning systems. Additionally, the portability, affordability, and adaptability of PHACE can facilitate widespread adoption of 3D facial anthropometric technology as an objective measurement tool in ophthalmology.PrecisWe demonstrate a custom system for facial photogrammetry (Photogrammetry for Anatomical CarE -PHACE) to produce 3D renderings of facial volume and morphology which compares with more expensive alternative 3D scanning technologies.

Background Small vessel childhood primary angiitis of the central nervous system (SV-cPACNS) is a rare disease characterized by inflammation within small vessels such as arterioles or capillaries. Case presentation We report a case of SV-cPACNS in an 8-year-old boy confirmed by brain biopsy. This patient was also incidentally found to have anti-glial fibrillary acidic protein (GFAP) antibodies in the cerebrospinal fluid (CSF) but had no evidence of antibody-mediated disease on brain biopsy. A literature review highlighted the rarity of SV-cPACNS and found no prior reports of CSF GFAP-associated SV-cPACNS in the pediatric age group. Conclusion We present the first case of biopsy proven SV-cPACNS vasculitis associated with an incidental finding of CSF GFAP antibodies. The GFAP antibodies are likely a clinically insignificant bystander in this case and possibly in other diseases with CNS inflammation. Further research is needed to determine the clinical significance of newer CSF autoantibodies such as anti-GFAP before they are used for medical decision-making in pediatrics.

Understanding the molecular basis of innate immune evasion by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important consideration for designing the next wave of therapeutics. Here, we investigate the role of the nonstructural protein 16 (NSP16) of SARS-CoV-2 in infection and pathogenesis. NSP16, a ribonucleoside 2’-O methyltransferase (MTase), catalyzes the transfer of a methyl group to mRNA as part of the capping process. Based on observations with other CoVs, we hypothesized that NSP16 2’-O MTase function protects SARS-CoV-2 from cap-sensing host restriction. Therefore, we engineered SARS-CoV-2 with a mutation that disrupts a conserved residue in the active site of NSP16. We subsequently show that this mutant is attenuated both in vitro and in vivo, using a hamster model of SARS-CoV-2 infection. Mechanistically, we confirm that the NSP16 mutant is more sensitive to type I interferon (IFN-I) in vitro. Furthermore, silencing IFIT1 or IFIT3, IFN-stimulated genes that sense a lack of 2’-O methylation, partially restores fitness to the NSP16 mutant. Finally, we demonstrate that sinefungin, a methyltransferase inhibitor that binds the catalytic site of NSP16, sensitizes wild-type SARS-CoV-2 to IFN-I treatment. Overall, our findings highlight the importance of SARS-CoV-2 NSP16 in evading host innate immunity and suggest a possible target for future antiviral therapies.ImportanceSimilar to other coronaviruses, disruption of SARS-CoV-2 NSP16 function attenuates viral replication in a type I interferon-dependent manner. In vivo, our results show reduced disease and viral replication at late times in the hamster lung, but an earlier titer deficit for the NSP16 mutant (dNSP16) in the upper airway. In addition, our results confirm a role for IFIT1, but also demonstrate the necessity of IFIT3 in mediating dNSP16 attenuation. Finally, we show that targeting NSP16 activity with a 2’-O methyltransferase inhibitor in combination with type I interferon offers a novel avenue for antiviral development.

The motion of domain walls is a crucial factor in piezoelectric properties and is usually related to the irreversible and hysteretic behaviors. Herein, we report on the investigation of inverse and transverse piezoelectric coefficients of capacitor-based and microcantilever-based Pb(Zr0.52Ti0.48)O3 films with a change in the DC bias and the AC applied voltage. A large inverse piezoelectric strain coefficient of about 350 p.m./V, and a low strain hysteresis of about 7.1%, are achieved in the film capacitors under a low applied voltage of 2 V (20 kV/cm) which can benefit the actuators for motion control in high-precision systems. The field-dependences of the transverse piezoelectric coefficients, obtained from four-point bending and microcantilever displacement, are in good agreement with each other. The results also reveal that the irreversible domain-wall motion is attributed to the nonlinearity in the field-dependent piezoelectric strain and cantilever displacement.

Group B enteroviruses, including coxsackievirus B3 (CVB3), can persistently infect cardiac tissue and cause dilated cardiomyopathy. Persistence is linked to 5’ terminal deletions of viral genomic RNAs that have been detected together with minor populations of full-length genomes in human infections. In this study, we explored the functions and interactions of the different viral RNA forms found in persistently-infected patients and their putative role(s) in pathogenesis. Since enterovirus cardiac pathogenesis is linked to the viral proteinase 2A, we investigated the effect of different terminal genomic RNA deletions on 2A activity. We discovered that 5’ terminal deletions in CVB3 genomic RNAs decreased the proteinase activity of 2A but could not abrogate it. Using newly-generated viral reporters encoding nano-luciferase, we found that 5’ terminal deletions resulted in decreased levels of viral protein and RNA synthesis in singly-transfected cardiomyocyte cultures. Unexpectedly, when full-length and terminally deleted forms were co-transfected into cardiomyocytes, a cooperative interaction was observed, leading to increased viral RNA and protein production. However, when viral infections were carried out in cells harboring 5’ terminally deleted CVB3 RNAs, a decrease in infectious particle production was observed. Our results provide a possible explanation for the necessity of full-length viral genomes during persistent infection, as they would stimulate efficient viral replication compared to that of the deleted genomes alone. To avoid high levels of viral particle production that would trigger cellular immune activation and host cell death, the terminally deleted RNA forms act to limit the production of viral particles, possibly as trans-dominant inhibitors.ImportanceEnteroviruses like coxsackievirus B3 are able to initiate acute infections of cardiac tissue and, in some cases, to establish a long-term persistent infection that can lead to serious disease sequelae, including dilated cardiomyopathy. Previous studies have demonstrated the presence of 5’ terminally-deleted forms of enterovirus RNAs in heart tissues derived from patients with dilated cardiomyopathy. These deleted RNAs are found in association with very low levels of full-length enterovirus genomic RNAs, an interaction that may facilitate continued persistence while limiting virus particle production. Even in the absence of detectable infectious virus particle production, these deleted viral RNA forms express viral proteinases at levels capable of causing viral pathology. Our studies provide mechanistic insights into how full length and deleted forms of enterovirus RNA cooperate to stimulate viral protein and RNA synthesis without stimulating infectious viral particle production. They also highlight the importance of targeting enteroviral proteinases to inhibit viral replication while at the same time limiting the long-term pathologies they trigger.

Background Penicillin allergy is the most commonly reported drug allergy in the pediatric population. However, most reports do not represent true IgE-mediated or late-onset severe hypersensitivity reactions. False allergy labels can lead to unnecessarily broad and/or non-first line antibiotic utilization, the development of antibiotic resistance, adverse drug side effects, and have implications for the use of antimicrobials in adulthood. In an effort to decrease inappropriate allergy labeling, we have implemented a multipronged approach for the evaluation of documented beta-lactam allergies in pediatric patients and potential “de-labeling” of inaccurate or outdated allergies. Methods We performed retrospective chart review of pediatric patients (0-18 years) with a documented beta-lactam allergy who were seen in clinic at a single tertiary medical center between 2014-2019. Prospective telephone screening then began to further characterize reaction symptoms and timing to determine patient candidacy for allergy testing (Fig. 1). Inpatient screening began in April 2022. If amenable to referral, eligible patients are then referred for outpatient Allergy and Immunology (A/I) assessment. Figure 1Process map for pediatric beta-lactam allergy risk-stratifying algorithm. Results A total of 1160 eligible pediatric patients were identified, and initial results are summarized (Fig. 2). Of those screened, 48 (57%) patients were referred. 5 (6%) patients were de-labeled via screening, of which 3 had received and tolerated repeat dosing. 11 (33%) patients have attended allergy appointments; 4 (36%) were tested and all were de-labeled (ages 6-11 years) from mostly non-IgE-mediated reactions. Additionally, 16 patients have upcoming appointments, and recruitment efforts are ongoing to include increased inpatient recruitment. Conclusion Use of an inpatient and outpatient algorithm can help identify pediatric patients less likely to have a true or persistent beta-lactam allergy (delayed-onset mild symptoms, or IgE-mediated reaction >5 years ago) and who could benefit from formal allergy testing to potentially remove their allergy label. In the future, algorithm implementation within the electronic medical record may assist clinicians in thorough documentation of beta-lactam allergies and expeditious referral for allergy testing when appropriate. Disclosures All Authors: No reported disclosures.

YggS is a pyridoxal 5'-phosphate (PLP)-binding protein of the conserved COG0325 family. Despite a connection with vitamin B6 homeostasis in many species, neither a precise biochemical activity nor the molecular mechanism of how YggS contributes to cellular function has been described. In a transposon mutagenesis screen, we found that insertions in aspC (encoding a PLP-dependent aspartate aminotransferase, EC 2.6.1.1) in a Salmonella enterica strain lacking yggS caused a synthetic growth defect, which could be rescued by the addition of exogenous aspartate. Characterization of spontaneous suppressors which improved the growth of the yggS aspC double mutant suggested that this synthetic aspartate limitation was dependent on TyrB, a PLP-dependent aromatic amino acid aminotransferase (EC 2.6.1.57). Genetic and biochemical data were consistent with the hypothesis that TyrB activity was inhibited by accumulated pyridoxine 5'-phosphate and α-keto acids caused by a yggS mutation. This study provides data consistent with a working model implicating YggS in modulating concentrations of B6 vitamers via transamination.

The furin cleavage site (FCS), an unusual feature in the SARS-CoV-2 spike protein, has been spotlighted as a factor key to facilitating infection and pathogenesis by increasing spike processing. Similarly, the QTQTN motif directly upstream of the FCS is also an unusual feature for group 2B coronaviruses (CoVs). The QTQTN deletion has consistently been observed in in vitro cultured virus stocks and some clinical isolates. To determine whether the QTQTN motif is critical to SARS-CoV-2 replication and pathogenesis, we generated a mutant deleting the QTQTN motif (ΔQTQTN). Here, we report that the QTQTN deletion attenuates viral replication in respiratory cells in vitro and attenuates disease in vivo. The deletion results in a shortened, more rigid peptide loop that contains the FCS and is less accessible to host proteases, such as TMPRSS2. Thus, the deletion reduced the efficiency of spike processing and attenuates SARS-CoV-2 infection. Importantly, the QTQTN motif also contains residues that are glycosylated, and disruption of its glycosylation also attenuates virus replication in a TMPRSS2-dependent manner. Together, our results reveal that three aspects of the S1/S2 cleavage site—the FCS, loop length, and glycosylation—are required for efficient SARS-CoV-2 replication and pathogenesis.

The Lancet Countdown is an international collaboration, established to provide an independent, global monitoring system dedicated to tracking the emerging health profile of the changing climate. The 2020 report presents 43 indicators across five sections: climate change impacts, exposures, and vulnerability; adaptation, planning, and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. This report represents the findings and consensus of the 35 leading academic institutions and UN agencies that make up the Lancet Countdown, and draws on the expertise of climate scientists, geographers, and engineers; of energy, food, and transport experts; and of economists, social and political scientists, data scientists, public health professionals, and doctors.

Pyridoxal 5′-phosphate (PLP) is an essential cofactor for organisms in all three domains of life. Despite the central role of PLP, many aspects of vitamin B(6) metabolism, including its integration with other biological pathways, are not fully understood. In this study, we examined the metabolic perturbations caused by the vitamin B(6) antagonist 4-deoxypyridoxine (dPN) in a ptsJ mutant of Salmonella enterica serovar Typhimurium LT2. Our data suggest that PdxK (pyridoxal/pyridoxine/pyridoxamine kinase [EC 2.7.1.35]) phosphorylates dPN to 4-deoxypyridoxine 5′-phosphate (dPNP), which in turn can compromise the de novo biosynthesis of PLP. The data are consistent with the hypothesis that accumulated dPNP inhibits GlyA (serine hydroxymethyltransferase [EC 2.1.2.1]) and/or GcvP (glycine decarboxylase [EC 1.4.4.2]), two PLP-dependent enzymes involved in the generation of one-carbon units. Our data suggest that this inhibition leads to reduced flux to coenzyme A (CoA) precursors and subsequently decreased synthesis of CoA and thiamine. This study uncovers a link between vitamin B(6) metabolism and the biosynthesis of CoA and thiamine, highlighting the integration of biochemical pathways in microbes. IMPORTANCE PLP is a ubiquitous cofactor required by enzymes in diverse metabolic networks. The data presented here expand our understanding of the toxic effects of dPN, a vitamin B(6) antagonist that is often used to mimic vitamin B(6) deficiency and to study PLP-dependent enzyme kinetics. In addition to de novo PLP biosynthesis, we define a metabolic connection between vitamin B(6) metabolism and synthesis of thiamine and CoA. This work provides a foundation for the use of dPN to study vitamin B(6) metabolism in other organisms.

Graphical abstract, Highlights • LVD can rarely present in the subaortic position. • A muscular LVD has synchronous contraction; an aneurysm does not. • Subaortic LVD may be associated with aortic regurgitation, thrombus, and arrhythmia. • An isolated LVD may be followed conservatively with noninvasive imaging.

Lanthanide elements have been recently recognized as “new life metals” yet much remains unknown regarding lanthanide acquisition and homeostasis. In Methylorubrum extorquens AM1, the periplasmic lanthanide-dependent methanol dehydrogenase XoxF1 produces formaldehyde, which is lethal if allowed to accumulate. This property enabled a transposon mutagenesis study and growth studies to confirm novel gene products required for XoxF1 function. The identified genes encode an MxaD homolog, an ABC-type transporter, an aminopeptidase, a putative homospermidine synthase, and two genes of unknown function annotated as orf6 and orf7. Lanthanide transport and trafficking genes were also identified. Growth and lanthanide uptake were measured using strains lacking individual lanthanide transport cluster genes, and transmission electron microscopy was used to visualize lanthanide localization. We corroborated previous reports that a TonB-ABC transport system is required for lanthanide incorporation to the cytoplasm. However, cells were able to acclimate over time and bypass the requirement for the TonB outer membrane transporter to allow expression of xoxF1 and growth. Transcriptional reporter fusions show that excess lanthanides repress the gene encoding the TonB-receptor. Using growth studies along with energy dispersive X-ray spectroscopy and transmission electron microscopy, we demonstrate that lanthanides are stored as cytoplasmic inclusions that resemble polyphosphate granules.

Expanding traditional medicine (TM) coverage in health care is a priority in Vietnam. Continuous medical education (CME) plays an important role in ensuring the quality of TM. However, evidence about TM CME in TM practitioners in Vietnam is insufficient. This paper aimed to evaluate the awareness, practice, and demands on TM CME among TM providers in district hospitals of Vietnam. This cross-sectional descriptive study was performed at the district level at TM hospitals and TM departments of general hospitals in Thanh Hoa Province. Demographic characteristics, awareness, practice, and demand for TM CME were collected via face-to-face interviews. Descriptive statistics and multivariable logistic regression models were applied to examine the factors associated with awareness, practice, and demand for TM CME. The majority of the respondents had ever heard of TM CME (87.5%). Only 60% received TM training in the last five years. Most respondents had a demand for CME (86.8%). The non-Kinh ethnic group (OR = 0.2, 95% CI: 0.1–0.8) and people who had a temporary contract (OR = 0.2, 95% CI: 0.1–0.7) were less likely to be ever heard about TM CME. Higher levels of education (college, OR = 14.1, 95% CI = 1.0–195.9; undergraduate, OR = 9.1, 95% CI = 1.9–44.6) are more likely to be ever heard of TM CME than the vocational training group. Those who regularly update their knowledge are more likely to have heard about TM CME (OR = 7.7, 95% CI = 2.8–21.7) and are more likely to have demands on TM CME (OR = 3.7, 95% CI = 1.2–11.5). Those who had heard about TM CME were more likely to take these courses in the last five years (OR = 6.9, 95% CI = 2.5–18.8). However, this result was the opposite for people with more years of experience (OR = 0.9, 95% CI: 0.8–0.9). There were limited awareness and participation in TM CME but was a high need for CME among TM providers at district hospitals in Vietnam. Promoting lifelong learning and providing promptly supports would be potential to increase the TM CME demands and participation among TM providers.

Eisosomes are membrane furrows at the cell surface of yeast that have been shown to function in two seemingly distinct pathways, membrane stress response and regulation of nutrient transporters. We found that many stress conditions affect both of these pathways by changing plasma membrane tension and thus the morphology and composition of eisosomes. For example, alkaline stress causes swelling of the cell and an endocytic response, which together increase membrane tension, thereby flattening the eisosomes. The flattened eisosomes affect membrane stress pathways and release nutrient transporters, which aids in their down-regulation. In contrast, glucose starvation or hyperosmotic shock causes cell shrinking, which results in membrane slack and the deepening of eisosomes. Deepened eisosomes are able to trap nutrient transporters and protect them from rapid endocytosis. Therefore, eisosomes seem to coordinate the regulation of both membrane tension and nutrient transporter stability.

Purpose: To illustrate the regression of a metastatic lesion through ophthalmic imaging and correlating findings with standard chest imaging and treatment with osimertinib, an oral chemotherapy agent specific to Epidermal Growth Factor Receptor + Non-small Cell Lung Cancer (EGFR+ NSCLC). Case Report: A 63-year-old Asian male presented to ophthalmology with a complaint of left blurry vision. Initial ophthalmic exam revealed a choroidal lesion and imaging results highlighted a spiculated lung mass with brain and bony metastases. Osimertinib was chosen for its specificity and ability to cross the blood–brain barrier. Follow-up ophthalmic and radiographic imaging were repeated over the course of treatment. Conclusion: After the initiation of osimertinib, ophthalmic and computed tomography imaging highlighted the regression of the ocular metastatic disease and primary malignancy, respectively. Osimertinib is an effective first-line treatment of EGFR+ NSCLC and corresponding metastatic sites. Additionally, ophthalmic imaging can be used to monitor general response to chemotherapy agents when ocular metastasis is identified.

Although HIV prevalence among transgender women who have sex with men in Vietnam is high (16-18%), uptake of pre-exposure prophylaxis (PrEP) is low compared to other populations. When PrEP was initiated in 2017, gender-affirming healthcare was largely unavailable. Lack of access to competent, stigma-free healthcare is a well-documented barrier to transgender women's uptake of PrEP and primary healthcare (PHC). We aimed to demonstrate the utility of a PrEP quality improvement intervention in pinpointing and addressing barriers to PrEP use among transgender women in Vietnam.We applied a real-world participatory continuous quality improvement (CQI) and Plan-Do-Study-Act (PDSA) methodology to ascertain barriers to PrEP uptake among transgender women and determine priority actions for quality improvement. A CQI team representing transgender women leaders, key population (KP)-clinic staff, public-sector HIV managers and project staff applied PDSA to test solutions to identified barriers that addressed the primary quality improvement outcome of the monthly change in PrEP uptake among transgender women and secondary outcomes, including month-3 PrEP continuation, the impact of offering PHC on PrEP uptake and unmet PrEP need. We utilized routine programmatic data and a descriptive cross-sectional study enrolling 124 transgender women to measure these outcomes from October 2018 to September 2021.Five key barriers to PrEP uptake among transgender women were identified and corresponding solutions were put in place: (1) offering gender-affirming care training to KP-clinics and community-based organizations; (2) integrating gender-affirming services into 10 KP-clinics; (3) offering PHC through five one-stop shop (OSS) clinics; (4) implementing a campaign addressing concerns related to hormone use and PrEP interactions; and (5) developing national HIV and transgender healthcare guidelines. New PrEP enrolment and month-3 PrEP continuation increased significantly among transgender women. Of 235 transgender women who initially sought healthcare other than PrEP at OSS clinics, 26.4% subsequently enrolled in PrEP. About one-third of transgender women reported unmet PrEP need, while two-thirds indicated an interest in long-acting cabotegravir.Offering gender-competent, integrated PHC can increase PrEP enrolment and continuation, and can be an entry-point for PrEP among those seeking care within PHC clinics. More work is needed to expand access to transgender women-led and -competent healthcare in Vietnam.

OBJECTIVE Pharmacy-driven antibiotic dosing services have been shown to improve clinical outcomes in adult patients. This study evaluated the effect of a pharmacist-driven antimicrobial dosing service on the percentage of therapeutic serum concentrations achieved following initial vancomycin or aminoglycoside dosing regimens. A secondary objective was to determine the effect of the dosing service on nephrotoxicity in pediatric patients. METHODS This single-center, retrospective study used data obtained from an electronic medical record to evaluate the utility of a pharmacist-driven vancomycin or aminoglycoside dosing protocol. Assessments of target, subtherapeutic, and supratherapeutic serum concentrations were evaluated. The occurrence of changes in serum creatinine and presentation of acute kidney injury (AKI) were also determined. RESULTS The incidence (n [%]) of a therapeutic initial serum concentration was not statistically significant between pre-protocol and post-protocol groups (21 [46.7%] vs 22 [48.9%], respectively; p = 0.834). The incidence of initial supratherapeutic concentrations (19 [42.2%] vs 7 [15.6%]; p = 0.005) and the average number of supratherapeutic concentrations per antibiotic course (0.76 vs 0.26; p = 0.01) were higher in the pre-protocol group compared with the post-protocol group. The incidence of AKI was significantly lower in the post-protocol group (2.2% vs 13.3%; p = 0.049). CONCLUSIONS Implementation of a pharmacist-driven dosing service did not affect the likelihood of achieving an initial therapeutic concentration. However, it did reduce the likelihood of both supratherapeutic concentrations and AKI. Additional studies in pediatric patients are needed to affirm the use of pharmacist dosing services.

First-principles computations are the driving force behind numerous discoveries of hydride-based superconductors, mostly at high pressures, during the last decade. Machine-learning (ML) approaches can further accelerate the future discoveries if their reliability can be improved. The main challenge of current ML approaches, typically aiming at predicting the critical temperature $T_{\rm c}$ of a solid from its chemical composition and target pressure, is that the correlations to be learned are deeply hidden, indirect, and uncertain. In this work, we showed that predicting superconductivity at any pressure from the atomic structure is sustainable and reliable. For a demonstration, we curated a diverse dataset of 584 atomic structures for which $\lambda$ and $\omega_{\log}$, two parameters of the electron-phonon interactions, were computed. We then trained some ML models to predict $\lambda$ and $\omega_{\log}$, from which $T_{\rm c}$ can be computed in a post-processing manner. The models were validated and used to identify two possible superconductors whose $T_{\rm c}\simeq 10-15$K at zero pressure. Interestingly, these materials have been synthesized and studied in some other contexts. In summary, the proposed ML approach enables a pathway to directly transfer what can be learned from the high-pressure atomic-level details that correlate with high-$T_{\rm c}$ superconductivity to zero pressure. Going forward, this strategy will be improved to better contribute to the discoveries of new superconductors.

Background In the past decades, climate change has been impacting human lives and health via extreme weather and climate events and alterations in labour capacity, food security, and the prevalence and geographical distribution of infectious diseases across the globe. Climate change and health indicators (CCHIs) are workable tools designed to capture the complex set of interdependent interactions through which climate change is affecting human health. Since 2015, a novel sub-set of CCHIs, focusing on climate change impacts, exposures, and vulnerability indicators (CCIEVIs) has been developed, refined, and integrated by Working Group 1 of the “Lancet Countdown: Tracking Progress on Health and Climate Change”, an international collaboration across disciplines that include climate, geography, epidemiology, occupation health, and economics. Discussion This research in practice article is a reflective narrative documenting how we have developed CCIEVIs as a discrete set of quantifiable indicators that are updated annually to provide the most recent picture of climate change’s impacts on human health. In our experience, the main challenge was to define globally relevant indicators that also have local relevance and as such can support decision making across multiple spatial scales. We found a hazard, exposure, and vulnerability framework to be effective in this regard. We here describe how we used such a framework to define CCIEVIs based on both data availability and the indicators’ relevance to climate change and human health. We also report on how CCIEVIs have been improved and added to, detailing the underlying data and methods, and in doing so provide the defining quality criteria for Lancet Countdown CCIEVIs. Conclusions Our experience shows that CCIEVIs can effectively contribute to a world-wide monitoring system that aims to track, communicate, and harness evidence on climate-induced health impacts towards effective intervention strategies. An ongoing challenge is how to improve CCIEVIs so that the description of the linkages between climate change and human health can become more and more comprehensive. This work is supported by an unrestricted grant from the Wellcome Trust (209734/Z/17/Z). Peer Reviewed "Article signat per 26 autors/es: Claudia Di Napoli, Alice McGushin, Marina Romanello, Sonja Ayeb-Karlsson, Wenjia Cai, Jonathan Chambers, Shouro Dasgupta, Luis E. Escobar, Ilan Kelman, Tord Kjellstrom, Dominic Kniveton, Yang Liu, Zhao Liu, Rachel Lowe, Jaime Martinez-Urtaza, Celia McMichael, Maziar Moradi-Lakeh, Kris A. Murray, Mahnaz Rabbaniha, Jan C. Semenza, Liuhua Shi, Meisam Tabatabaei, Joaquin A. Trinanes, Bryan N. Vu, Chloe Brimicombe & Elizabeth J. Robinson "

Introduction There have been no time-series studies of air pollution in Peru. Here we evaluate the effect of ambient PM2.5 on emergency room (ER) visits in Lima. Methods We estimated daily PM2.5 levels at a 1 km2 resolution during 2010-2016 using ground measurements, satellite data, and chemical transport model simulations. Population-weighted average daily PM2.5 levels were calculated for each district in Lima (n = 40), and assigned to patients based on residence. ER visits for respiratory and circulatory diseases were gathered from nine large public hospitals. Poisson regression was used to estimate the rate ratio for daily ER visits with change in daily PM2.5, controlling for meteorology, time trends, and district. Results For each interquartile range (IQR) increase in PM2.5, respiratory disease ER visits increased 4% (95% CI: 0-5%), stroke visits 10% (3-18%), and ischemic heart disease visits (adults, 18-64 years) 11% (-1, 24%). Districts with higher poverty showed significantly stronger associations of PM2.5 and respiratory disease ER visits than districts with lower poverty. Effects were diminished 24-42% using Lima-wide instead of district-specific PM2.5 levels. Conclusions Short-term exposure to ambient PM2.5 is associated with increases in ER visits in Lima for respiratory diseases and stroke, and among middle-aged adults, ischemic heart disease.

The furin cleavage site (FCS), an unusual feature in the SARS-CoV-2 spike protein, has been spotlighted as a factor key to facilitating infection and pathogenesis by increasing spike processing 1,2. Similarly, the QTQTN motif directly upstream of the FCS is also an unusual feature for group 2B coronaviruses (CoVs). The QTQTN deletion has consistently been observed in in vitro cultured virus stocks and some clinical isolates 3. To determine whether the QTQTN motif is critical to SARS-CoV-2 replication and pathogenesis, we generated a mutant deleting the QTQTN motif (ΔQTQTN). Here we report that the QTQTN deletion attenuates viral replication in respiratory cells in vitro and attenuates disease in vivo. The deletion results in a shortened, more rigid peptide loop that contains the FCS, and is less accessible to host proteases, such as TMPRSS2. Thus, the deletion reduced the efficiency of spike processing and attenuates SARS-CoV-2 infection. Importantly, the QTQTN motif also contains residues that are glycosylated4, and disruption its glycosylation also attenuates virus replication in a TMPRSS2-dependent manner. Together, our results reveal that three aspects of the S1/S2 cleavage site – the FCS, loop length, and glycosylation – are required for efficient SARS-CoV-2 replication and pathogenesis.

COVID-19 has become a major cause of global mortality and driven massive health and economic disruptions. Mass global vaccination offers the most efficient pathway towards ending the pandemic. The development and deployment of first-generation COVID-19 vaccines, encompassing mRNA or viral vectors, has proceeded at a phenomenal pace. Going forward, nanoparticle-based vaccines which deliver SARS-CoV-2 antigens will play an increasing role in extending or improving vaccination outcomes against COVID-19. At present, over 26 nanoparticle vaccine candidates have advanced into clinical testing, with ∼60 more in pre-clinical development. Here, we discuss the emerging promise of nanotechnology in vaccine design and manufacturing to combat SARS-CoV-2, and highlight opportunities and challenges presented by these novel vaccine platforms.

Unc18 and SNARE proteins form the core of the membrane fusion complex at synapses. To understand the functional interactions within the core machinery, we adopted an "interspecies complementation" approach in

This study describes the net ecosystem exchange of CO2 in a rice summer-autumn growth season in the lower Mekong Delta, Vietnam. Eddy Covariance and bio-meteorological systems were used to continually record the net CO2 exchange between the paddy field and the atmosphere, together with environmental variables affecting the exchange rate. Rice plant growth (height, above-, and belowground biomass) was measured every 15 days during the entire crop. Our study paddy field emitted CO2 at the mean rate of 5.06 ± 2.49 µmol m-2 s-1, while the rate of CO2 capturing was 18.65 ± 11.76 µmol m-2 s-1 throughout the entire crop. The paddy field acted as a CO2 sink almost during the crop. The quick increase of leaf area from the 15th to the 60th day led to the rise in CO2 influx. The decrease in influx rate after the 60th day resulted from the senescence and death of the aboveground biomass. The drainage in the last ten days of the crop probably contributed to the increase in CO2 effluxes and hence, turned the paddy field into a CO2 source. Ambient temperature was an important factor affecting the rate of CO2 exchange affects the photosynthesis, plant respiration, photorespiration, and organic matter decomposition.

The dielectric properties, tunability and figure-of-merit (FOM) of relaxor Pb0.9La0.1(Zr0.52Ti0.48)O3 (PLZT) films have been investigated. Dielectric measurements indicated that the dielectric constant (at zero-bias field), tunability and FOM are enhanced as the film thickness increases, which are mainly attributed to the presence of an interfacial layer near the film-electrode interface. Experimental results illustrated that a slight reduction is observed in both dielectric constant and tunability (−2%) in a wide-frequency range (10 kHz–1 MHz), meanwhile, the FOM value decreases significantly (−17%) with increasing frequency, arising from the higher dielectric loss value. The 1000-nm PLZT film shows the largest tunability of 94.6% at a maximum electric-field of 1450 kV/cm, while the highest FOM factor is 37.6 at 1000 kV/cm, due to the combination of medium tunability (88.7%) and low dielectric loss (0.0236). All these excellent results indicated that the relaxor PLZT films are promising candidates for specific applications in microwave devices.

While SARS-CoV-2 continues to adapt for human infection and transmission, genetic variation outside of the spike gene remains largely unexplored. This study investigates a highly variable region at residues 203–205 in SARS-CoV-2 nucleocapsid protein. Recreating the alpha variant mutation in an early pandemic (WA-1) background, we found that the R203K/G204R mutation is sufficient to enhance replication, fitness, and pathogenesis of SARS-CoV-2. Importantly, the R203K/G204R mutation increases nucleocapsid phosphorylation, providing a molecular basis for these phenotypes. Notably, an analogous alanine substitution mutant also increases SARS-CoV-2 fitness and phosphorylation, suggesting that infection is enhanced through ablation of the ancestral ‘RG’ motif. Overall, these results demonstrate that variant mutations outside spike are also key components in SARS-CoV-2’s continued adaptation to human infection., One-Sentence Summary: A mutation in the nucleocapsid gene of the SARS-CoV-2 alpha variant is found to enhance replication, fitness, and pathogenesis.

Over the past 20 years, Nipah virus (NiV) has emerged as a significant, highly pathogenic bat-borne paramyxovirus causing severe respiratory disease and encephalitis in humans, and human-to-human transmission has been demonstrated in multiple outbreaks. In addition to causing serious illness in humans, NiV is a zoonotic pathogen capable of infecting a wide range of other mammalian species, including pigs and horses. While NiV has caused less than 700 human cases since its discovery in 1998/1999, the involvement of intermediate agricultural hosts can result in significant economic consequences. Owing to the severity of disease, capacity for human-to-human transmission, zoonotic potential, and lack of available approved therapeutic treatment options, NiV has been listed by the World Health Organization in their Blueprint list of priority pathogens as one of the eight most dangerous pathogens to monitor and prepare countermeasures to prevent a pandemic. Here, we discuss progress towards the development of therapeutic measures for the treatment of NiV infection and disease.

Recently, nanosized metal oxides play an essential role in the photocatalytic system due to their ability to create charge carriers during the light irradiation. Metal oxide nanoparticles display excellent light absorption properties, outstanding charge transport characteristics, which are suitable in the photocatalytic system for the treatment of wastewater. Most of the photocatalysts found in the literature are in the form of powders. Only a few supported photocatalytic systems have been reported. The advantages of supported photocatalysts, such as that they produce a small pressure drop, have good mechanical stability and are easily separated from the reaction medium, make them superior to conventional powder photocatalysts. In this chapter, the definition of supported-metal oxide nanoparticles as the photocatalyst and their synthesis methodology are detailed discussed.

Humans perceive light in the visible spectrum (400-700 nm). Some night vision systems use infrared light that is not perceptible to humans and the images rendered are transposed to a digital display presenting a monochromatic image in the visible spectrum. We sought to develop an imaging algorithm powered by optimized deep learning architectures whereby infrared spectral illumination of a scene could be used to predict a visible spectrum rendering of the scene as if it were perceived by a human with visible spectrum light. This would make it possible to digitally render a visible spectrum scene to humans when they are otherwise in complete “darkness” and only illuminated with infrared light. To achieve this goal, we used a monochromatic camera sensitive to visible and near infrared light to acquire an image dataset of printed images of faces under multispectral illumination spanning standard visible red (604 nm), green (529 nm) and blue (447 nm) as well as infrared wavelengths (718, 777, and 807 nm). We then optimized a convolutional neural network with a U-Net-like architecture to predict visible spectrum images from only near-infrared images. This study serves as a first step towards predicting human visible spectrum scenes from imperceptible near-infrared illumination. Further work can profoundly contribute to a variety of applications including night vision and studies of biological samples sensitive to visible light.

Background: Comorbidity is common and causes poor stroke outcomes. We aimed to examine the modifying impacts of physical activity (PA) and diet quality on the association between comorbidity and disability in stroke patients. Methods: A cross-sectional study was conducted on 951 stable stroke patients in Vietnam from December 2019 to December 2020. The survey questionnaires were administered to assess patients’ characteristics, clinical parameters (e.g., Charlson Comorbidity Index items), health-related behaviors (e.g., PA using the International Physical Activity Questionnaire- short version), health literacy, diet quality (using the Dietary Approaches to Stop Hypertension Quality (DASH-Q) questionnaire), and disability (using the World Health Organization Disability Assessment Schedule II (WHODAS II)). Linear regression models were used to analyze the associations and interactions. Results: The proportion of comorbidity was 49.9% (475/951). The scores of DASH-Q and WHODAS II were 29.2 ± 11.8, 32.3 ± 13.5, respectively. Patients with comorbidity had a higher score of disability (regression coefficient, B, 8.24, 95% confidence interval, 95%CI, 6.66, 9.83, p &lt, 0.001) as compared with those without comorbidity. Patients with comorbidity and higher tertiles of PA (B, −4.65 to −5.48, 0.05), and a higher DASH-Q score (B, −0.32, 0.001) had a lower disability score, as compared with those without comorbidity and the lowest tertile of PA, and the lowest score of DASH-Q, respectively. Conclusions: Physical activity and diet quality significantly modified the negative impact of comorbidity on disability in stroke patients. Strategic approaches are required to promote physical activity and healthy diet which further improve stroke rehabilitation outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing Abs target the receptor binding domain of the spike (S) protein, a focus of successful vaccine efforts. Concerns have arisen that S-specific vaccine immunity may fail to neutralize emerging variants. We show that vaccination with a human adenovirus type 5 vector expressing the SARS-CoV-2 nucleocapsid (N) protein can establish protective immunity, defined by reduced weight loss and viral load, in both Syrian hamsters and K18-hACE2 mice. Challenge of vaccinated mice was associated with rapid N-specific T cell recall responses in the respiratory mucosa. This study supports the rationale for including additional viral Ags in SARS-CoV-2 vaccines, even if they are not a target of neutralizing Abs, to broaden epitope coverage and immune effector mechanisms.

The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a pandemic causing significant damage to public health and the economy. Efforts to understand the mechanisms of Coronavirus Disease 2019 (COVID-19) have been hampered by the lack of robust mouse models. To overcome this barrier, we used a reverse genetic system to generate a mouse-adapted strain of SARS-CoV-2. Incorporating key mutations found in SARS-CoV-2 variants, this model recapitulates critical elements of human infection including viral replication in the lung, immune cell infiltration, and significant in vivo disease. Importantly, mouse adaptation of SARS-CoV-2 does not impair replication in human airway cells and maintains antigenicity similar to human SARS-CoV-2 strains. Coupled with the incorporation of mutations found in variants of concern, CMA3p20 offers several advantages over other mouse-adapted SARS-CoV-2 strains. Using this model, we demonstrate that SARS-CoV-2–infected mice are protected from lethal challenge with the original Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), suggesting immunity from heterologous Coronavirus (CoV) strains. Together, the results highlight the use of this mouse model for further study of SARS-CoV-2 infection and disease., Studying cross-protection from different coronaviruses is important to inform the research for a universal vaccine. This study uses a mouse-adapted SARS-CoV-2 strain to show that it confers protection from SARS-CoV challenge, suggesting possible immunity from heterologous challenge following natural infection.