Key Recommendations for Antimicrobial Resistance Surveillance: Takeaways From the CAPTURA Project.

Antimicrobial resistance (AMR) is a growing global public health challenge associated with 4.95 million deaths in 2019 and an estimated 10 million deaths per year by 2050 in the absence of coordinated action. A robust AMR surveillance system is therefore required to avert such a scenario. Based on an analysis of country-level AMR data in 8 Capturing Data on Antimicrobial Resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) countries, we present a list of key recommendations to strengthen AMR surveillance. We propose 10 primary considerations under 3 broad categories, including recommendations on (1) laboratory and testing practices, (2) data management and analysis, and (3) data use.

Methodological Approach to Identify and Expand the Volume of Antimicrobial Resistance (AMR) Data in the Human Health Sector in Low- and Middle-Income Countries in Asia: Implications for Local and Regional AMR Surveillance Systems Strengthening.

Antimicrobial resistance (AMR) is a multifaceted global health problem disproportionately affecting low- and middle-income countries (LMICs). The Capturing data on Antimicrobial resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) project was tasked to expand the volume of AMR and antimicrobial use data in Asia. The CAPTURA project used 2 data-collection streams: facility data and project metadata. Project metadata constituted information collected to map out data sources and assess data quality, while facility data referred to the retrospective data collected from healthcare facilities. A down-selection process, labelled "the funnel approach" by the project, was adopted to use the project metadata in prioritizing and selecting laboratories for retrospective AMR data collection. Moreover, the metadata served as a guide for understanding the AMR data once they were collected. The findings from CAPTURA's metadata add to the current discourse on the limitation of AMR data in LMICs. There is generally a low volume of AMR data generated as there is a lack of microbiology laboratories with sufficient antimicrobial susceptibility testing capacity. Many laboratories in Asia are still capturing data on paper, resulting in scattered or unused data not readily accessible or shareable for analyses. There is also a lack of clinical and epidemiological data captured, impeding interpretation and in-depth understanding of the AMR data. CAPTURA's experience in Asia suggests that there is a wide spectrum of capacity and capability of microbiology laboratories within a country and region. As local AMR surveillance is a crucial instrument to inform context-specific measures to combat AMR, it is important to understand and assess current capacity-building needs while implementing activities to enhance surveillance systems.

Interferon drives HCV scarring of the epigenome and creates targetable vulnerabilities following viral clearance.

BACKGROUND AND AIMS: Chronic HCV infection is a leading etiologic driver of cirrhosis and ultimately HCC. Of the approximately 71 million individuals chronically infected with HCV, 10%-20% are expected to develop severe liver complications in their lifetime. Epigenetic mechanisms including DNA methylation and histone modifications become profoundly disrupted in disease processes including liver disease. APPROACH AND RESULTS: To understand how HCV infection influences the epigenome and whether these events remain as "scars" following cure of chronic HCV infection, we mapped genome-wide DNA methylation, four key regulatory histone modifications (H3K4me3, H3K4me1, H3K27ac, and H3K27me3), and open chromatin in parental and HCV-infected immortalized hepatocytes and the Huh7.5 HCC cell line, along with DNA methylation and gene-expression analyses following elimination of HCV in these models through treatment with interferon-α (IFN-α) or a direct-acting antiviral (DAA). Our data demonstrate that HCV infection profoundly affects the epigenome (particularly enhancers); HCV shares epigenetic targets with interferon-α targets; and an overwhelming majority of epigenetic changes induced by HCV remain as "scars" on the epigenome following viral cure. Similar findings are observed in primary human patient samples cured of chronic HCV infection. Supplementation of IFN-α/DAA antiviral regimens with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine synergizes in reverting aberrant DNA methylation induced by HCV. Finally, both HCV-infected and cured cells displayed a blunted immune response, demonstrating a functional effect of epigenetic scarring. CONCLUSIONS: Integration of epigenetic and transcriptional data elucidate key gene deregulation events driven by HCV infection and how this may underpin the long-term elevated risk for HCC in patients cured of HCV due to epigenome scarring.

Electronic Cigarettes Induce Mitochondrial DNA Damage and Trigger TLR9 (Toll-Like Receptor 9)-Mediated Atherosclerosis.

OBJECTIVE: Electronic cigarette (e-cig) use has recently been implicated in promoting atherosclerosis. In this study, we aimed to investigate the mechanism of e-cig exposure accelerated atherosclerotic lesion development. Approach and Results: Eight-week-old ApoE-/- mice fed normal laboratory diet were exposed to e-cig vapor (ECV) for 2 hours/day, 5 days/week for 16 weeks. We found that ECV exposure significantly induced atherosclerotic lesions as examined by Oil Red O staining and greatly upregulated TLR9 (toll-like receptor 9) expression in classical monocytes and in the atherosclerotic plaques, which the latter was corroborated by enhanced TLR9 expression in human femoral artery atherosclerotic plaques from e-cig smokers. Intriguingly, we found a significant increase of oxidative mitochondria DNA lesion in the plasma of ECV-exposed mice. Administration of TLR9 antagonist before ECV exposure not only alleviated atherosclerosis and the upregulation of TLR9 in plaques but also attenuated the increase of plasma levels of inflammatory cytokines, reduced the plaque accumulation of lipid and macrophages, and decreased the frequency of blood CCR2+ (C-C chemokine receptor type 2) classical monocytes. Surprisingly, we found that cytoplasmic mitochondrial DNA isolated from ECV extract-treated macrophages can enhance TLR9 activation in reporter cells and the induction of inflammatory cytokine could be suppressed by TLR9 inhibitor in macrophages. CONCLUSIONS: E-cig increases level of damaged mitochondrial DNA in circulating blood and induces the expression of TLR9, which elevate the expression of proinflammatory cytokines in monocyte/macrophage and consequently lead to atherosclerosis. Our results raise the possibility that intervention of TLR9 activation is a potential pharmacological target of ECV-related inflammation and cardiovascular diseases.

Potential role of IFN-α in COVID-19 patients and its underlying treatment options.

The coronavirus disease (COVID-19) caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide. Given that this contagious viral outbreak is still unfolding, it is urgent to understand the pathogenesis of SARS-CoV-2 infection and explore effective treatments to protect patients from developing a severe illness related to COVID-19. Recently, IFN-α has been considered a potential therapeutic strategy to treat COVID-19 disease, mainly because the innate immune system rapidly produces IFN-α as the first line of defense to combat viral infections. However, IFN-α can also play a role in immunoregulatory effects, causing pathogenic damage and uncontrolled inflammatory responses. There are 13 human IFN-α subtypes that bind to the same receptor and induce different interferon-stimulated gene (ISG) expression, regulating various antiviral and immunoregulatory effects. The varying degrees of inflammatory regulations may raise concerns about the possible side effects to enlarge the inflammatory responses, exacerbating the severity of infection. Thus, the analysis of various IFN-α subtype induction during SARS-CoV-2 infection is necessary in exploring the mechanism of COVID-19 pathogenesis. This review summarizes the current understanding of IFN-α in the pathogenesis of respiratory virus diseases and IFN-α based clinical intervention used in SARS-CoV-2 infection and other respiratory virus diseases. Besides, new ideas in selecting suitable IFN-α subtypes or combinations as drug candidates for viral infection treatment will also be discussed.Key Points• IFN-α plays an important role in anti-viral and immunoregulatory effects in COVID-19 patients caused by SARS-CoV-2.• The uncontrolled inflammation and disease severity correlated to the diversity of IFN-α subtype induction.• Selecting suitable IFN-α subtypes or combinations as drug candidates will be beneficial for the treatment of patients with COVID-19.

Identification of small molecules by screening a mixture-based scaffold compound library for treatment of alpha-1 antitrypsin deficiency.

This study aimed to identify small molecules that have the potential to treat alpha1-antitrypsin deficiency (AATD) by screening compounds available from a mixture-based scaffold library. 93 scaffold libraries (total diversity of >30 million compounds in mixture format) were screened using a cell model of AATD in order to identify samples that could either reduce intracellular aggregation of Z-form AAT protein, increase extracellular secretion of Z-AAT or both. Mixture libraries containing compounds with in vitro activity, for example library 1295, were screened further to identify individual active compounds. The mixture format of the scaffold library allowed for some preliminary structure-activity relationships to be developed and also enabled the rapid selection of a promising scaffold. Utilizing this scaffold, 1295, a collection of individual "control" compounds contained in the 1295 mixture sample were then screened. A sub-library of individual "control" compounds featuring structural diversity at position R1 (1295.R1), was screened and 7 compounds were found to reduce the intracellular accumulation of Z-AAT without affecting cell viability at a concentration of 25ug/ml (about 50 µM). Screening sub-libraries featuring structural diversity at R2 and R3 (1295.R2 and 1295.R3) identified an additional 15 active compounds. Titration experiments identified 3 compounds from the 1295.R2 library that retained activity at 5ug/ml (approx. 10uM). One compound (1295.263) from 1295.R2 decreased intracellular levels of Z-AAT without affecting cell viability and wild-type AAT levels at the concentration of 5ug/ml. Molecular docking of this compound to the Z-AAT crystal structure identified a potential binding site near the C-terminal domain, an identified polymerization site. Our results indicate that screening large mixture-based compound libraries can be used to identify small molecules that may have the potential to treat AATD and other disease.

Integrating the Epigenome to Identify Drivers of Hepatocellular Carcinoma.

Disruption of epigenetic mechanisms has been intimately linked to the etiology of human cancer. Understanding how these epigenetic mechanisms (including DNA methylation [5mC], hydroxymethylation [5hmC], and histone post-translational modifications) work in concert to drive cancer initiation and progression remains unknown. Hepatocellular carcinoma (HCC) is increasing in frequency in Western countries but lacks efficacious treatments. The epigenome of HCC remains understudied. To better understand the epigenetic underpinnings of HCC, we performed a genome-wide assessment of 5mC, 5hmC, four histone modifications linked to promoter/enhancer function (H3K4me1, H3K27ac, H3K4me3, and H3K27me3), and transcription across normal, cirrhotic, and HCC liver tissue. Implementation of bioinformatic strategies integrated these epigenetic marks with each other and with transcription to provide a comprehensive epigenetic profile of how and when the liver epigenome is perturbed during progression to HCC. Our data demonstrate significant deregulation of epigenetic regulators combined with disruptions in the epigenome hallmarked by profound loss of 5hmC, locus-specific gains in 5mC and 5hmC, and markedly altered histone modification profiles, particularly remodeling of enhancers. Data integration demonstrates that these marks collaborate to influence transcription (e.g., hyper-5hmC in HCC-gained active enhancers is linked to elevated expression) of genes regulating HCC proliferation. Two such putative epigenetic driver loci identified through our integrative approach, COMT and FMO3, increase apoptosis and decrease cell viability in liver-derived cancer cell lines when ectopically re-expressed. Conclusion: Altogether, integration of multiple epigenetic parameters is a powerful tool for identifying epigenetically regulated drivers of HCC and elucidating how epigenome deregulation contributes to liver disease and HCC.

A Novel Vaccine Targeting Glypican-3 as a Treatment for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) has a high morbidity and mortality rate worldwide, with limited treatment options. Glypican-3 (GPC3) is a glycosylphosphatidylinositol-anchored glycoprotein that is overexpressed in most HCC tissues but not in normal tissues. GPC3-targeting antibody therapy shows limited response in a clinical trial due to the lack of a tumor-specific cytotoxic T lymphocyte (CTL) response. Here, in C57/B6 mice, we demonstrated that intravenous infusion of GPC3-coupled lymphocytes (LC/GPC3+) elicited robust GPC3-specific antibody and CTL responses, which effectively restricted proliferation and lysed cultured-HCC cells. Treatment with LC/GPC3+ induced durable tumor regression in HCC-bearing C57/B6 mice. Administration of LC/GPC3+ induced elevated levels of the cytotoxic T cell bioactive factors tumor necrosis factor alpha (TNF-α), interferon-γ (IFN-γ), granzyme B, and perforin, and substantially increased the number of infiltrating CD8+ T cells in tumor tissues. Moreover, immune responses elicited by LC/GPC3+ selectively suppressed GPC3+ tumors, but didn't affect the GPC3- tumors in BALB/c mice. Our findings provide the first preclinical evidence that intravenous infusion of the LC/GPC3+ complex can induce a strong anti-HCC effect through regulating systemic and local immune responses. These results indicate that the LC/GPC3+ complex could be developed as precision therapeutics for HCC patients in the future.

Isolation of Pancreatic Cancer Cells from a Patient-Derived Xenograft Model Allows for Practical Expansion and Preserved Heterogeneity in Culture.

Commercially available, highly passaged pancreatic cancer (PC) cell lines are of limited translational value. Attempts to overcome this limitation have primarily consisted of cancer cell isolation and culture directly from human PC specimens. However, these techniques are associated with exceedingly low success rates. Here, we demonstrate a highly reproducible culture of primary PC cell lines (PPCLs) from patient-derived xenografts, which preserve, in part, the intratumoral heterogeneity known to exist in PC. PPCL expansion from patient-derived xenografts was successful in 100% of attempts (5 of 5). Phenotypic analysis was evaluated with flow cytometry, immunofluorescence microscopy, and short tandem repeat profiling. Importantly, tumorigenicity of PPCLs expanded from patient-derived xenografts was assessed by subcutaneous injection into nonobese diabeteic.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ mice. Morphologically, subcutaneous injection of all PPCLs into mice yielded tumors with similar characteristics to the parent xenograft. PPCLs uniformly expressed class I human leukocyte antigen, epithelial cell adhesion molecule, and cytokeratin-19. Heterogeneity within each PPCL persisted in culture for the frequency of cells expressing the cancer stem cell markers CD44, CD133, and c-Met and the immunologic markers human leukocyte antigen class II and programmed death ligand 1. This work therefore presents a reliable method for the rapid expansion of primary human PC cells and, thereby, provides a platform for translational investigation and, importantly, potential personalized therapeutic approaches.

Patient-derived xenograft models for pancreatic adenocarcinoma demonstrate retention of tumor morphology through incorporation of murine stromal elements.

Direct implantation of viable surgical specimens provides a representative preclinical platform in pancreatic adenocarcinoma. Patient-derived xenografts consistently demonstrate retained tumor morphology and genetic stability. However, the evolution of the tumor microenvironment over time remains poorly characterized in these models. This work specifically addresses the recruitment and incorporation of murine stromal elements into expanding patient-derived pancreatic adenocarcinoma xenografts, establishing the integration of murine cells into networks of invading cancer cells. In addition, we provide methods and observations in the establishment and maintenance of a patient-derived pancreatic adenocarcinoma xenograft model. A total of 25 histologically confirmed pancreatic adenocarcinoma specimens were implanted subcutaneously into nonobese diabetic severe combined immunodeficiency mice. Patient demographics, staging, pathological analysis, and outcomes were analyzed. After successful engraftment of tumors, histological and immunofluorescence analyses were performed on explanted tumors. Pancreatic adenocarcinoma specimens were successfully engrafted in 15 (60%) of 25 attempts. Successful engraftment does not appear to correlate with clinicopathologic factors or patient survival. Tumor morphology is conserved through multiple passages, and tumors retain metastatic potential. Interestingly, despite morphological similarity between passages, human stromal elements do not appear to expand with invading cancer cells. Rather, desmoplastic murine stroma dominates the xenograft microenvironment after the initial implantation. Recruitment of stromal elements in this manner to support and maintain tumor growth represents a novel avenue for investigation into tumor-stromal interactions.

Downstream mediators of the intratumoral interferon response suppress antitumor immunity, induce gemcitabine resistance and associate with poor survival in human pancreatic cancer.

The cancer microenvironment allows tumor cells to evade immune surveillance through a variety of mechanisms. While interferon-γ (IFNγ) is central to effective antitumor immunity, its effects on the microenvironment are not as clear and have in some cancers been shown to induce immune checkpoint ligands. The heterogeneity of these responses to IFNγ remains poorly characterized in desmoplastic malignancies with minimal inflammatory cell infiltration, such as pancreatic cancer (PC). Thus, the IFNγ response within and on key cells of the PC microenvironment was evaluated. IFNγ induced expression of human leukocyte antigen (HLA) class I and II on PC cell lines, primary pancreatic cancer epithelial cells (PPCE) and patient-derived tumor-associated stroma, concomitant with an upregulation of PDL1 in the absence of CD80 and CD86 expression. As expected, IFNγ also induced high levels of CXCL10 from all cell types. In addition, significantly higher levels of CXCL10 were observed in PC specimens compared to those from chronic pancreatitis, whereby intratumoral CXCL10 concentration was an independent predictor of poor survival. Immunohistochemical analysis revealed a subset of CXCR3-positive cancer cells in over 90 % of PC specimens, as well as on a subset of cultured PC cell lines and PPCE, whereby exposure to CXCL10 induced resistance to the chemotherapeutic gemcitabine. These findings suggest that IFNγ has multiple effects on many cell types within the PC microenvironment that may lead to immune evasion, chemoresistance and shortened survival.

Genome Sequence of a Recombinant SARS-CoV-2 Lineage XAM (BA.1.1/BA.2.9) Strain from a Clinical Sample in Santo Domingo, Dominican Republic.

Here, we report a recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage XAM (Omicron BA.1.1/BA.2.9) strain that was collected in Santo Domingo, Dominican Republic. This demonstrates how SARS-CoV-2 variants can vary greatly between regions and thus underlines the great importance of regional genomic surveillance efforts.

Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection.

The chronic infection hypothesis for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant emergence is increasingly gaining credence following the appearance of Omicron. Here, we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral genome copies. During the infection, we find an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately 2-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution results in the emergence and persistence of at least three genetically distinct genotypes, suggesting the establishment of spatially structured viral populations continually reseeding different genotypes into the nasopharynx. Finally, we track the temporal dynamics of genetic diversity to identify advantageous mutations and highlight hallmark changes for chronic infection. Our findings demonstrate that untreated chronic infections accelerate SARS-CoV-2 evolution, providing an opportunity for the emergence of genetically divergent variants.

One-stage Reconstruction with the Composite Anterolateral Thigh Flap for Skin and Extensor Tendon Defects of the Thumb by Snakebite.

Venomous snakebites can cause severe injury. The loss of tendon and skin of the hand is incredibly challenging for the surgeon. A single-staged reconstruction with the free composite anterolateral thigh flap is an acceptable option for a complex thumb injury. In this case, reconstruction for a 23-year-old patient with a complex cobra-induced thumb injury had failed to cover the defect with a skin graft. There was a limitation in choice, and the patient was treated with the free composite anterolateral thigh (ALT) flap and fascia lata flap in one stage to reconstruct both the extensor tendon and the soft tissue coverage. The flap was well-vascularized, and no complications were reported. A single-stage reconstruction with a composite ALT flap with vascularized fascia was chosen as a suitable alternative. The result is satisfying both aesthetically and functionally. This technique can help shorten treatment time and restore function quickly, allowing patients to return to work in less time. The disadvantages of this technique are flap thickness, which can affect finger movement and aesthetics. The composite ALT flap with vascularized fascia lata shows that it is a reliable procedure for single-staged reconstruction, especially combined with the tendon preparation in the hand.

Evaluation of polyhydroxyalkanoate (PHA) synthesis by Pichia sp. TSLS24 yeast isolated in Vietnam.

Following the rising concern on environmental issues caused by conventional fossil-based plastics and depleting crude oil resources, polyhydroxyalkanoates (PHAs) are of great interest by scientists and biodegradable polymer market due to their outstanding properties which include high biodegradability in various conditions and processing flexibility. Many polyhydroxyalkanoate-synthesizing microorganisms, including normal and halophilic bacteria, as well as algae, have been investigated for their performance in polyhydroxyalkanoate production. However, to the best of our knowledge, there is still limited studies on PHAs-producing marine yeast. In the present study, a halophilic yeast strain isolated from Spratly Island in Vietnam were investigated for its potential in polyhydroxyalkanoate biosynthesis by growing the yeast in Zobell marine agar medium (ZMA) containing Nile red dye. The strain was identified by 26S rDNA analysis as Pichia kudriavzevii TSLS24 and registered at Genbank database under code OL757724. The amount of polyhydroxyalkanoates synthesized was quantified by measuring the intracellular materials (predicted as poly(3-hydroxybutyrate) -PHB) by gravimetric method and subsequently confirmed by Fourier transform infrared (FTIR) spectroscopic and nuclear magnetic resonance (NMR) spectroscopic analyses. Under optimal growth conditions of 35 °C and pH 7 with supplementation of glucose and yeast extract at 20 and 10 gL-1, the isolated strain achieved poly(3-hydroxybutyrate) content and concentration of 43.4% and 1.8 gL-1 after 7 days of cultivation. The poly(3-hydroxybutyrate) produced demonstrated excellent biodegradability with degradation rate of 28% after 28 days of incubation in sea water.

Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose.

The emergence of the SARS-CoV-2 Omicron sublineages resulted in increased transmission rates and reduced protection from vaccines. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their efficiency in improving protective immunity remain sparse, especially among vulnerable populations, including older adults. The inactivated CoronaVac vaccine was among the most widely distributed vaccine worldwide and was essential in the early control of SARS-CoV-2-related hospitalizations and deaths. However, it is not well understood whether homologous versus heterologous booster doses in those fully vaccinated with CoronaVac induce distinct humoral responses or whether these responses vary across age groups. We analyzed plasma antibody responses from CoronaVac-vaccinated younger or older individuals who received a homologous CoronaVac or heterologous BNT162b2 or ChAdOx1 booster vaccine. All three evaluated boosters resulted in increased virus-specific IgG titers 28 days after the booster dose. However, we found that both IgG titers against SARS-CoV-2 Spike or RBD and neutralization titers against Omicron sublineages were substantially reduced in participants who received homologous CoronaVac compared with the heterologous BNT162b2 or ChAdOx1 booster. This effect was specifically prominent in recipients >50 years of age. In this group, the CoronaVac booster induced low virus-specific IgG titers and failed to elevate neutralization titers against any Omicron sublineage. Our results point to the notable inefficiency of CoronaVac immunization and boosting in mounting protective antiviral humoral immunity, particularly among older adults, during the Omicron wave. These observations also point to benefits of heterologous regimens in high-risk populations fully vaccinated with CoronaVac.

The impact of globalization and modernization of laws and theories on the modernization of philosophy in Vietnam: mediating role of modern societies.

Globalization of the world needs the modernization of laws, theory, and philosophy, especially since World War II. This could increase researchers' attention towards the modernization of philosophy. The goals also include examining the mediating impact of modern societies among the links of globalization, modernization of laws and theories, and modernization of philosophy in Vietnam. This study has taken the quantitative method and received the data from researchers in philosophy, politics and sociology (university lecturers, researchers and activists in the field of philosophy, politics and sociology) of Vietnam using questionnaires. The smart-PLS was executed to test the relationships between the understudy constructs. The results indicated that globalization, modernization of laws, and theories positively and significantly associated with the modernization of philosophy in Vietnam. The outcomes also revealed that modern societies significantly mediate the links among globalization, modernization of laws and theories, and modernization of philosophy in Vietnam. These results motivate the regulators to focus on the modernization of philosophies in terms of globalization and modernization of laws, theories, and societies.

Starch and sugars as determinants of postharvest shelf life and quality: some new and surprising roles.

Starch and sugars account for most of the dry weight of horticultural crops and in many species, are known determinants of quality. However, we posit that these carbohydrates often have less-obvious roles in plant tissues with direct implications for the postharvest quality and produce shelf life. The latter has not been given as much attention, but with the recent interest in reducing the scale of postharvest waste and loss, we highlight how dynamic changes in the spatial-temporal accumulation of carbohydrates, can influence myriads of biological processes affecting postharvest attributes. Versatile roles, some surprising, that carbohydrates play in determining produce of high value to consumers, are highlighted, and gene targets for biotechnological improvement are specified.

Emerging Trends in the Pathological Research of Human Papillomavirus-positive Oropharyngeal Squamous Cell Carcinoma.

Oropharyngeal squamous cell carcinomas (OPSCCs) have shown an alarming rate of increase in incidence over the past several decades, markedly in men. In the United States, transcriptionally-active human papillomavirus (HPV), particularly HPV 16, has become the highest contributive agent of OPSCCs, affecting approximately 16,000 people a year. Compared to patients with HPV-negative OPSCCs, patients with HPV-positive OPSCCs exhibit better health responses to chemoradiotherapy and an overall increase in long-term survival. Despite promising treatment options, many OPSCCs are discovered at an advanced stage, and ~20% of cases will recur after definitive treatment. Therefore, extensive research is ongoing to identify new targets for precision treatment and to stratify tumor prognosis. The aim of this review is to capture the most updated research on HPV-positive OPSCCs, emphasizing their relevance as potential new targets for precision medicine and survival prognosis.

SaliVISION: a rapid saliva-based COVID-19 screening and diagnostic test with high sensitivity and specificity.

The Coronavirus disease 2019 (COVID-19) pandemic-caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)- has posed a global threat and presented with it a multitude of economic and public-health challenges. Establishing a reliable means of readily available, rapid diagnostic testing is of paramount importance in halting the spread of COVID-19, as governments continue to ease lockdown restrictions. The current standard for laboratory testing utilizes reverse transcription quantitative polymerase chain reaction (RT-qPCR); however, this method presents clear limitations in requiring a longer run-time as well as reduced on-site testing capability. Therefore, we investigated the feasibility of a reverse transcription looped-mediated isothermal amplification (RT-LAMP)-based model of rapid COVID-19 diagnostic testing which allows for less invasive sample collection, named SaliVISION. This novel, two-step, RT-LAMP assay utilizes a customized multiplex primer set specifically targeting SARS-CoV-2 and a visual report system that is ready to interpret within 40 min from the start of sample processing and does not require a BSL-2 level testing environment or special laboratory equipment. When compared to the SalivaDirect and Thermo Fisher Scientific TaqPath RT-qPCR testing platforms, the respective sensitivities of the SaliVISION assay are 94.29% and 98.28% while assay specificity was 100% when compared to either testing platform. Our data illustrate a robust, rapid diagnostic assay in our novel RT-LAMP test design, with potential for greater testing throughput than is currently available through laboratory testing and increased on-site testing capability.