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As the 7th Earth Explorer Mission within the ESA Earth Observation Program, BIOMASS will be the first spaceborne P-band polarimetric interferometric SAR (PolInSAR) mission, dedicated to global forest remote sensing. Compared with airborne PolInSAR, BIOMASS PolInSAR faces several intrinsic limitations, including the reduced number of baselines, low bandwidth of 6 MHz, and the 3-day repeat-pass acquisition mode. In this study, the capabilities of three-baseline PolInSAR in BIOMASS configuration and the spaceborne system-induced impacts are systematically evaluated. First, the BIOMASS data were simulated using the airborne P-band SAR acquisitions collected over two different tropical forests in Paracou, French Guiana, and Mondah, Gabon. Second, the forest height was retrieved using a three-baseline algorithm based on polarimetric coherence optimization with multi-baseline joint diagonalization. Finally, the impacts of spaceborne PolInSAR were quantified and analyzed. The results show that the performance of PolInSAR inversion in the spaceborne configuration decreases compared to that of the original airborne data. However, the three-baseline method still yields acceptable results, with a root-mean-square error ranging from 4.92 to 6.07 m and a correlation coefficient (R2) from 0.32 to 0.85, within hectare-scale forest height statistics. This study demonstrates that the limited bandwidth of BIOMASS has a certain impact on refined forest structure parameter retrieval, while the three-baseline PolInSAR method remains effective for large-scale forest mapping, with accuracy meeting the design requirements of the BIOMASS mission.

Remote sensing satellites allow large-scale and fast detections of forest loss. Operational forest loss detection systems have been mainly developed over tropical forests; however, it is increasingly important to have access to accurate and up-to-date information on temperate forests. In this article, we adapted a Sentinel-1-based near real-time tropical forest loss detection method, based on the radar change ratio, to detect French temperate forests clear-cuts. Using ancillary data, annual and submonthly clear-cuts were assessed for broadleaf and conifer forests, for various tree species, over public and private forests. Using 967 validation plots, the maps exhibited recall and precision of 80.9% and 99.4%, respectively. The clear-cuts area shows remarkable stability over time from 2020. We found seven times more clear-cuts in private forests than in public forests, although the surface area of private forests is only three times that of public forests. It was also demonstrated that only 1.6% out of 4 530 dieback reference plots, and 6.2% of maps of forest bark beetle attacks, were confused with clear-cuts before clear-cuts actually occurred, which makes our maps complementary with forest dieback maps. Collectively, the findings of this study could have significant implications for the implementation of a radar-satellite-based system designed for the real-time detection of large-scale clear-cuts in European temperate forests.

Background: An unmet need exists when clinically assessing retinal and layer-based features of retinal diseases. Therefore, quantification of retinal-layer-thicknesses/fluid volumes using deep-learning-augmented platforms to reproduce human-obtained clinical measurements is needed. Methods: In this analysis, 210 spectral-domain optical coherence tomography (SD-OCT) scans (30 without pathology, 60 dry age-related macular degeneration [AMD], 60 wet AMD, and 60 diabetic macular edema [total 23,625 B-scans]) were included. A fully automated segmentation platform segmented four retinal layers for compartmental assessment (internal limiting membrane, ellipsoid zone [EZ], retinal pigment epithelium [RPE], and Bruch’s membrane). Two certified OCT readers independently completed manual segmentation and B-scan level validation of automated segmentation, with segmentation correction when needed (semi-automated). Certified reader metrics were compared to gold standard metrics using intraclass correlation coefficients (ICCs) to assess overall agreement. Across different diseases, several metrics generated from automated segmentations approached or matched human readers performance. Results: Absolute ICCs for retinal mean thickness measurements showed excellent agreement (range 0.980–0.999) across four cohorts. EZ-RPE thickness values and sub-RPE compartment ICCs demonstrated excellent agreement (ranges of 0.953–0.987 and 0.944–0.997, respectively) for full dataset, dry-AMD, and wet-AMD cohorts. Conclusions: Analyses demonstrated high reliability and consistency of segmentation of outer retinal compartmental features using a completely human/manual approach or a semi-automated approach to segmentation. These results support the critical role that measuring features, such as photoreceptor preservation through EZ integrity, in future clinical trials may optimize clinical care.

There is growing interest in using passive microwave observations and vegetation optical depth (VOD) to study the above-ground biomass (AGB) and carbon stocks evolution. L-band observations, in particular, have been shown to be very sensitive to AGB. Here, thanks to the multiangle capabilities of the soil moisture and ocean salinity mission, a new approach to estimate AGB directly from multiangular L-band brightness temperatures (TBs) is proposed, thus surpassing the use of intermediate variables such as VOD. The European Space Agency (ESA) Climate Change Initiative (CCI) Biomass maps for the years 2010, 2017, and 2018 are used as the AGB reference. AGB estimates from artificial neural networks (ANN) using a purely data-driven approach explained up to 88% of AGB variability globally; even so, a decrease in retrieval performance was observed when models are applied to data from years different than the year used for their training. A new training methodology based on multiyear training sets is presented, leading to results showing more stability for temporal analyses. The best set of predictors and an optimal learning dataset configuration are proposed based on an assessment of the accuracy of the estimates. The ANN methodology using TBs is a promising alternative with respect to the common method of using a parametric function to estimate AGB from VOD. ANNs AGB estimates showed a higher correlation with CCI AGB maps ($R$2 $\sim$0.87 instead of $\sim$0.84) and presented a stronger agreement with their spatial structure and less differences in residual maps.

Aspects extraction is the key task in the sentiment analysis problem, which includes extraction of both explicit and implicit aspects. Identifying implicit aspects is not a new task in sentiment analysis, but it still presents many challenges. Numerous studies have addressed the issue and offered different approaches, but there are still fundamental challenges as follows: solving the context word problem; the domain-specific problem; and the implicit aspects represented by sentiment words that do not appear explicitly in the text. This paper proposes a method for identifying implicit aspects of sentiment words. To address these above challenges, the system is built on the foundation of deep learning with context vectors, dependency grammar, anaphora coreference resolution, and sentiment ontology. The dependency parser and the entity coreference resolver are adopted to filter out the sentiment–aspect pairs data generated from embedding context words. Then, a fine-tuned technique is applied, and the classifier corresponding to each sentiment word is built to identify implicit aspects. This combination has produced positive results, reaching almost 90% accuracy.

Numerous cross-sectional studies have examined physicians' health and coping during the COVID-19 pandemic, while longitudinal studies are lacking. This study explores the progression over one year of physicians' physical and mental health symptoms, their strategies used to cope and discusses coping strategies in relation to physical and mental health symptoms. Two surveys, one year apart, exploring physicians' physical, mental health symptoms and employed coping strategies were sent to all physicians practicing in the province of Saskatchewan, Canada. A total of 117 physicians participated in Round I (RI) (November 2020–January 2021) and 158 participated in Round II (RII) (October 2021–February 2022). Physicians' physical and mental health symptoms remained high, irrespective of their specialty or COVID-19 exposure. COVID-related Post-Traumatic Stress Disorder increased by five times at RII (p = 0.02). In RI anxiety was most prevalent in middle-aged females. In RII depression was most prevalent in physicians with no children. Most coping was adaptive (90%) and included Behavioural, Relational, Cognitive, Spiritual, and Interventional strategies. After one-year, Spiritual coping decreased, while Interventional coping increased by eight times (p = 0.01). Despite efforts to employ adaptive coping, physicians' rates of psychological and physical health difficulties remained high or worsened over one year, offering insight into the protracted health care crisis, and the need for solutions. Our observation of physicians’ needs for additional supports, camaraderie and appreciation as well as the shift in coping strategies as the pandemic progressed, offer targets for interventions meant to promote recovery.

Lung cancer is the leading cause of cancer-related deaths. Surgery remains the best option to treat lung cancer when feasible. However, many cases are diagnosed beyond the initial stages. There has been tremendous progress in the treatment of lung cancer over the last few years. Studies have shown that biomarker-driven targeted therapies lead to better outcomes. Due to the technical difficulties and significant procedural risk associated with repeated tissue biopsies, analysis of tumor constituents circulating in the blood, such as circulating tumor DNA (ctDNA) and various proteins, is becoming more widely recognized as an alternative method of tumor sampling, i.e., liquid biopsy. Liquid biopsy is superior to tissue biopsy, as it is minimally invasive and easily repeatable. Given the recent data on changes in mutations as the disease progresses or responds to treatment, liquid biopsies can help monitor the changes and guide us in giving targeted drugs. Here we present a case of advanced NSCLC who was initially started on Alectinib based on positivity for ALK gene rearrangement found in the FISH study. At the time of progression, molecular profiling liquid biopsy was obtained, which revealed KRAS-p.G12C mutation. Thus, the patient’s therapy was later on changed to sotorasib after the FDA approved a KRAS-p.G12C mutation inhibitor.

Little is known about how Talaromyces marneffei, a thermally dimorphic fungus that causes substantial morbidity and mortality in Southeast Asia, evades the human immune system. Polarization of macrophages into fungal-inhibiting M1-like and fungal-promoting M2-like types has been shown to play an important role in the innate immune response against fungal pathogens. This mechanism has not been defined for T. marneffei. Here, we demonstrated that T. marneffei promotes its survival in human macrophages by inducing them toward M2-like polarization. Our investigations of the mechanism revealed that T. marneffei infection led to SOCS3 protein degradation by inducing tyrosine phosphorylation, thereby relieving the inhibitory effect of SOCS3 on p-STAT6, a key factor for M2-like polarization. Our SOCS3-overexpression experiments showed that SOCS3 is a positive regulator of M1-like polarization and plays an important role in limiting M2-like polarization. Furthermore, we found that inhibition of the TLR9 pathway partially blocked T. marneffei-induced M2-like polarization and significantly enhanced the killing activity of macrophages against T. marneffei. Collectively, these results reveal a novel mechanism by which T. marneffei evades the immune response of human macrophages.

Fuel cells are a promising alternative to non-renewable energy production industries such as petroleum and natural gas. The cathodic oxygen reduction reaction (ORR), which makes fuel cell technology possible, is sluggish under normal conditions. Thus, catalysts must be used to allow fuel cells to operate efficiently. Traditionally, platinum (Pt) catalysts are often utilized as they exhibit a highly efficient ORR with low overpotential values. However, Pt is an expensive and precious metal, posing economic problems for commercialization. Herein, advances in carbon-based catalysts are reviewed for their application in ORRs due to their abundance and low-cost syntheses. Various synthetic methods from different renewable sources are presented, and their catalytic properties are compared. Likewise, the effects of heteroatom and non-precious metal doping, surface area, and porosity on their performance are investigated. Carbon-based support materials are discussed in relation to their physical properties and the subsequent effect on Pt ORR performance. Lastly, advances in fuel cell electrolytes for various fuel cell types are presented. This review aims to provide valuable insight into current challenges in fuel cell performance and how they can be overcome using carbon-based materials and next generation electrolytes.

Herein, an ionic material (IM) with Förster Resonance Energy Transfer (FRET) characteristics is reported for the first time. The IM is designed by pairing a Nile Blue A cation (NBA+) with an anionic near-infrared (NIR) dye, IR820−, using a facile ion exchange reaction. These two dyes absorb at different wavelength regions. In addition, NBA+ fluorescence emission spectrum overlaps with IR820− absorption spectrum, which is one requirement for the occurrence of the FRET phenomenon. Therefore, the photophysical properties of the IM were studied in detail to investigate the FRET mechanism in IM for potential dye sensitized solar cell (DSSCs) application. Detailed examination of photophysical properties of parent compounds, a mixture of the parent compounds, and the IM revealed that the IM exhibits FRET characteristics, but not the mixture of two dyes. The presence of spectator counterion in the mixture hindered the FRET mechanism while in the IM, both dyes are in close proximity as an ion pair, thus exhibiting FRET. All FRET parameters such as spectral overlap integral, Förster distance, and FRET energy confirm the FRET characteristics of the IM. This article presents a simple synthesis of a compound with FRET properties which can be further used for a variety of applications.

Background: Childhood trauma (CT) has been linked to the development of various mental disorders. While traumatic history cannot be reversed, the shift in its perception can have significant implications. This study investigates how changes in the severity of attachment insecurity, depression and social anxiety influence CT trauma recollection one year later. Methods: Individuals with major depressive disorder with or without comorbid anxiety as well as controls were included (N = 76). Participants completed questionnaires on attachment, depression, social anxiety, and CT at baseline and one year later. Multivariable linear regressions were used to explore the associations. Results: Baseline scores of emotional abuse, physical neglect, and sexual abuse were significant predictors of their respective follow up scores (p

Herein, an inexpensive commercially available sensor is presented for the detection of 4-nitrophenol (4NP) pollutant. Sodium fluorescein (NaFl) is used as a sensor to detect trace amounts of 4NP in acetonitrile (MeCN). The photophysical properties of NaFl were studied in two different solvents, MeCN (aprotic) and water (protic), with varying concentrations of different nitroaromatics using UV-visible absorption and fluorescence spectrophotometry. In an aqueous medium, photophysical properties of NaFl did not change in the presence of nitroaromatics. However, examination of the photodynamics in MeCN demonstrated that NaFl is extremely sensitive to 4NP (limit of detection: 0.29 µg/mL). This extreme specificity of NaFl towards 4NP when dissolved in MeCN, as compared to other nitroaromatics, is attributed to hydrogen bonding of 4NP with NaFl in the absence of water, resulting in both static and dynamic quenching processes. Thus, NaFl is demonstrated as a simple, inexpensive, sensitive, and robust optical turn off sensor for 4NP.

Abstract Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) created an ABCD tool to assess staging and severity of COPD subgroups that respond to LAMA or LABA with improved quality of life and reduced exacerbations. Our study assesses perception of physicians at five community hospitals towards LAMA use for patients admitted with COPD exacerbations according to the GOLD guidelines and describes the experience at our hospital. Methods: Electronic survey forms regarding LAMA use and the GOLD criteria ABCD for COPD treating physicians were sent to five hospitals. A one-year chart review at our hospital determined prevalent use of a maintenance LAMA or LABA inhaler in patients admitted with acute COPD exacerbation. Currently, our EMR does not require a field for the GOLD ABCD categorization. Results: We obtained a 33% (45/136) response rate. Of these, 63% felt a LAMA to be essential on formulary; 60% were neutral or unlikely to initiate LAMA on admission; 47.7% likely or very likely to start a LAMA during hospitalization; 82% were neutral to very likely to discharge a patient on a LAMA if deemed necessary for maintenance. Of those admitted for acute COPD exacerbations to our hospital, over a third of COPD patients were not on a maintenance LAMA or LABA. Conclusions: Most physicians felt it important to prescribe a maintenance LAMA to COPD patients hospitalized for acute exacerbation. Our hospital’s use of LAMA or LABA demonstrates the need to incorporate strategies to encourage appropriate prescribing of these LA inhalers per GOLD guidelines.

Bruguiera parviflora (Rhizophoraceae) is one of the Bruguiera genus-based mangrove plants which has not been investigated for the chemical compositions as well as biological activities so far. The present study was aimed at investigating the phytochemicals as well as anti-inflammatory and α-glucosidase inhibitory activities of B. parviflora leaves. The results showed that the crude extract and its fractions significantly increased the percentage inhibitory activity against α-glucosidase and decreased NO production in LPS-stimulated RAW 264.7 cells in a dose-dependent manner. The most effective fraction BP5 was further chromatographed and purified. As a result, eight compounds were isolated and elucidated, including five flavonoids (1–5) and three triterpenoids (6–8). All isolated compounds were evaluated for the anti-inflammatory and α-glucosidase inhibitory effects. The results indicated that flavonoids namely taxifolin (1), quercetin (2), myricetin (3), rutin (4), and kaempferol (5) exhibited potent anti-inflammatory as well as α-glucosidase inhibitory activities. Among them, compound 2 showed the most potent inhibitory effect against an α-glucosidase activity with an IC50 value of 3.4±0.5 μg/mL and the LPS-induced NO production of 11.8 μM at the concentration of 100 μg/mL. These findings suggest that flavonoids (1–5) from B. parviflora leaves may be useful as the potential α-glucosidase inhibitor as well as anti-inflammatory agent.

In Vietnam, the aerial parts of Ruellia tuberosa L. are used to treat stress oxidation and inflammatory symptoms in diabetes mellitus. The present study was designed to determine the antioxidant and inflammatory inhibition activities of Ruellia tuberosa L. extract (RTE) and those of the isolated compounds by column chromatography. The crude ethanol extract and ethyl acetate fraction exhibited potent antioxidant activity in the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS) assays with an IC50 of 25.18 and 14.71 (DPPH test) and 18.22 and 15.27 µg/ml (ABTS test), respectively. The RTE contained high concentrations of polyphenols (308.21 mg GAE/g) and moderate concentrations of flavonoids (97.80 mg QE/g). In the anti-inflammatory screening assay, the crude ethanol extract, ethyl acetate, and methanol fractions suppressed the release of IL-6 and nitric oxide production, but the production of IL-10 was not enhanced in LPS-induced RAW 264.7 cells. Three potential anti-inflammatory compounds as hispidulin (6), physalin E (7), and physalin D (8) along with five other compounds named myricitrin (1), afzelin (2), apigenin (3), taraxerol (4), and lupeol (5) were isolated and identified from the ethyl acetate fraction. Physalin D (8) exhibited a strong, dose-dependent anti-inflammatory activity by inhibiting the production of IL-6 proinflammatory cytokines; however, the IL-10 expression was independent of its concentration in macrophages at noncytotoxic concentrations ranging from 5 to 40 μg/mL. Based on the data obtained, compounds 6–8 sourced from Ruellia tuberosa L are potentially bioactive compounds for the treatment of inflammation symptoms in type 2 diabetes mellitus.

This paper introduces a methodology for controlling parallel robots in case they are used as a kind of specialized fixture to expand the technological capabilities of machines. The parallel robot is mounted on the workbench to extend the number of degrees of freedom. However, there are always measurable kinematic errors of the workbench which will be eliminated by the robot’s motion. The actual working motion of the robot is then still performed by its active joints. Therefore, the displacement of each movable joint is now decided by two sources, one is due to the error compensation motion of the workbench, the other is the required work movement. According to the superposition principle, these two motions are combined into a single displacement characteristic curve to control the robot. The base exchange technique to determine the error compensation motion of the workbench, the technique of solving the inverse kinematics problem by the generalized reduced gradient (GRG) method, and the principle of joint motion combination are then introduced in detail in the paper. Finally, an example with the hexapod is presented. The obtained results, which use the robot itself to generate error-compensated movements of the workbench by means of the base exchange technique, will open up the possibility of intervening in hybrid machine systems to ensure the desired forming accuracy without no hardware intervention required.

Summary: Talaromycosis (penicilliosis) is an invasive mycosis that is endemic in tropical and subtropical Asia. Talaromycosis primarily affects individuals with advanced HIV disease and other immunosuppressive conditions, and the disease disproportionally affects people in low-income and middle-income countries, particularly agricultural workers in rural areas during their most economically productive years. Approximately 17 300 talaromycosis cases and 4900 associated deaths occur annually. Talaromycosis is highly associated with the tropical monsoon season, when flooding and cyclones can exacerbate the poverty-inducing potential of the disease. Talaromycosis can present as localised or disseminated disease, the latter causing cutaneous lesions that are disfiguring and stigmatising. Despite up to a third of diagnosed cases resulting in death, talaromycosis has received little attention and investment from regional and global funders, policy makers, researchers, and industry. Diagnostic and treatment modalities remain extremely insufficient, however control of talaromycosis is feasible with known public health strategies. This Viewpoint is a global call for talaromycosis to be recognised as a neglected tropical disease to alleviate its impact on susceptible populations.

The aim of this study was to develop a robust methodology for evaluating the spatiotemporal dynamics of the inundation status in tropical wetlands with the currently available Global Navigation Satellite System-Reflectometry (GNSS-R) data by proposing a new quality control technique called the “precision index”. The methodology was applied over the Mekong Delta, one of the most important rice-production systems comprising aquaculture areas and natural wetlands (e.g., mangrove forests, peatlands). Cyclone Global Navigation Satellite System (CyGNSS) constellation data (August 2018–December 2021) were used to evaluate the spatiotemporal dynamics of the reflectivity Γ over the delta. First, the reflectivity Γ, shape and size of each specular footprint and the precision index were calibrated at each specular point and reprojected to a 0.0045° resolution (approximately equivalent to 500 m) grid at a daily temporal resolution (Lv. 2 product); then, the results were obtained considering bias-causing factors (e.g., the velocity/effective scattering area/incidence angle). The Lv. 2 product was temporally integrated every 15 days with a Kalman smoother (+/− 14 days temporal localization with Gaussian kernel: 1σ = 5 days). By applying the smoother, the regional-annual dynamics over the delta could be clearly visualized. The behaviors of the GNSS-R reflectivity and the Advanced Land Observing Satellite-2 Phased-Array type L-band Synthetic Aperture Radar-2 quadruple polarimetric scatter signals were compared and found to be nonlinearly correlated due to the influence of the incidence angle and the effective scattering area.

ABSTRACT: The effect of methods to remove protein content on the properties of glucosamine hydrochloride from the shells of white leg shrimp (Litopenaeus vannamei) and black tiger shrimp (Penaeus monodon) was investigated. Chitin from shrimp shells was obtained by demineralization in 6% HCl for 12h, deproteinization by two different methods (first group soaked in 8% NaOH for 36h and second group treated in Alcalase enzyme at the concentration of 0.2% for 36h). Two group samples were converted to glucosamine hydrochloride by soaking in 36.76% HCl solution for 5h at 85 °C. The results of fourier transform infrared spectroscopy (FTIR), solubility and recovery yield analysis showed that deproteinization methods did not significantly affect the properties of glucosamine hydrochloride. However, glucosamine hydrochloride from white leg shrimp shells contained higher recovery yield and solubility than black tiger shrimp shells.

The paper examined the impact of microeconomic factors on the abnormal return of listed stocks on the Vietnam stock market. The research team performed regression analysis based on the data collected from 149 companies listed on Ho Chi Minh City Stock Exchange between 2012 and 2017. The research results show that the variables of profitability, capital structure and the growth rate all had positive impacts on the abnormal return of listed companies. Meanwhile, the size of enterprises was proven to have the reverse impact on the abnormal return.

In the present study, the anthelmintic activity of a human tyrosine kinase inhibitor, AG-1295, and 14 related tetrahydroquinoxaline analogues against Haemonchus contortus was explored. These compounds were screened against parasitic larvae - exsheathed third-stage (xL3) and fourth-stage (L4) - using a whole-organism screening assay. All compounds were shown to have inhibitory effects on larval motility, development and growth, and induced evisceration through the excretory pore in xL3s. The estimated IC50 values ranged from 3.5 to 52.0 μM for inhibition of larval motility or development. Cytotoxicity IC50 against human MCF10A cells was generally higher than 50 μM. Microscopic studies revealed that this eviscerated (Evi) phenotype occurs rapidly (

ABSTRACTThe dimorphic fungus Talaromyces marneffei (TM) is a common cause of HIV-associated opportunistic infections in Southeast Asia. Cotrimoxazole (CTX) inhibits folic acid synthesis which is important for the survival of many bacteria, protozoa, and fungi and has been used to prevent several opportunistic infections among HIV/AIDS patients. We question whether CTX is effective in preventing TM infection. To investigate this question, we conducted an 11-year (2005–2016) retrospective observational cohort study of all patients on the Chinese national antiretroviral therapy (ART) programme in Guangxi, a province with high HIV and TM burden in China. Survival analysis was conducted to investigate TM cumulative incidence, and Cox regression and propensity score matching (PSM) were used to evaluate the effect of CTX on TM incidence. Of the 3359 eligible individuals contributing 10,504.66 person-years of follow-up, 81.81% received CTX within 6 months after ART initiation, and 4.73% developed TM infection, contributing 15.14/1,000 person-year TM incidence rate. CTX patients had a significantly lower incidence of TM infection than non-CTX patients (4.11% vs. 7.53%; adjusted hazard ratio (aHR) = 0.50, 95% CI 0.35–0.73). CTX reduced TM incidence in all CD4+ cell subgroups (

The penetration capability of P-band radar waves through dense vegetation, along with the ability of tomography to separate the contributions of different layers in a vertical reflectivity profile, make P-band radar tomography a promising tool for digital terrain modeling in forested areas, specifically in dense tropical forests under which terrain topography remains poorly known. This paper aims to assess the overall quality of a digital terrain model (DTM) produced using tomographic processing of airborne P-band SAR imagery acquired during the TropiSAR campaign in French Guiana. Many quality descriptors are used to evaluate the quality of this DTM. Position and slope accuracies are computed based on a lidar DTM considered as the reference, and the impact of several parameters on these accuracies is studied, namely, slope, slope orientation, off-nadir angle and local incidence angle. The realism of the landforms is also studied according to geomorphological criteria. The results of this multicriteria accuracy assessment show the high potential of P-band SAR tomography in depicting the topography under forests, despite the intrinsic limitations related to the slant range geometry: the absolute elevation error is around 2 m; the slope is overestimated with an error of about 16°, mainly due to a processing artifact for which easy and direct solutions exist. Indeed, this error is equal to about 3° in flat artifact-free areas. These errors vary depending on the acquisition parameters and the local topography. The shapes are globally well preserved. These results are also discussed in the frame of the upcoming BIOMASS mission developed by the European Space Agency (ESA) and expected to be launched in 2024.

Clinical research in hematologic malignancies is continually advancing with emerging concepts in therapy and evolving results from clinical protocols. Targeting of the PI3K pathway remains a valuable treatment across both hematologic and solid malignancies. There are currently four United States Food and Drug Administration (FDA)-approved PI3K inhibitors, with several others in development. Copanlisib is a pan-PI3K inhibitor currently FDA-approved for the treatment of relapsed/refractory follicular lymphoma (FL) following two lines of therapy. Since FDA approval, there have been further investigations into the long-term safety profile of copanlisib, as well as treatment of FL and other lymphoma subtypes, both indolent and aggressive. Here, we review the most recent available data from clinical trials, describe the management of the most common side effects, and explore future concepts. The use of copanlisib as part of a combination therapy for various hematologic malignancies will also be discussed. Copanlisib is a unique drug compared with other PI3K inhibitors, with remarkable potential to improve our armamentarium in cancer treatment.

Background: Long-term neurocognitive outcomes following first-line suppressive anti-retroviral therapy (ART) remain uncertain for individuals with HIV and hepatitis C (HCV) co-infection. The study examined neurocognitive performance before and after 72 weeks of ART using repeated multivariate analyses and latent trajectory models.Methods: One hundred and sixty adults with chronic, untreated HIV infection (n = 80 with HCV co-infection and n = 80 HIV mono-infected) and 80 demographically similar healthy controls were recruited from the Hospital for Tropical Diseases in Ho Chi Minh City and the surrounding community, respectively. Neurocognitive measures (adapted for use in Vietnam) and liver enzyme tests were compared across groups at baseline. Repeated multivariate and group-based trajectory analyses (GBTA) examined neurocognitive subgroup profiles of the co-infected individuals after 72 weeks of de novo efavirenz- (n = 41) or raltegravir-based (n = 39) ART.Results: Baseline analyses revealed worse motor function in HIV-HCV co-infected individuals compared to both comparison groups. Longitudinal analyses revealed improved neurocognitive performance by week 48 for most participants regardless of treatment arm. GBTA identified a subgroup (35% of HIV-HCV sample) with persistent motor impairment despite otherwise successful ART. Higher HIV viral load and lower CD4+ T cell count at baseline predicted persistent motor dysfunction. Liver indices and ART regimen did not predict neurocognitive outcomes in HIV-HCV co-infected individuals.Conclusions: Most HIV-HCV co-infected individuals achieve normative neurocognitive performance after 48 weeks of de novo suppressive ART. However, individuals with more severe HIV disease prior to ART exhibited motor impairment at baseline and 72 weeks after otherwise successful treatment. Interventions aimed at improving motor symptoms at the time of HIV treatment onset may improve long-term clinical outcomes in HIV-HCV co-infected adults.

Polycyclic aromatic hydrocarbons (PAHs), the family of organic contaminations, have been shown to have negative effects on human health. However, until now, the comprehension on occurrence, distribution, and risk assessment of human exposure to PAHs has been limited in Vietnam. In this work, a capillary gas chromatography coupled with electron impact ionization tandem mass spectrometry (GC-EI-MS/MS) has been introduced for analysis of 16 PAHs in some particulate matter samples. PAHs have been separated on the TG 5 ms capillary gas chromatographic column and detected by tandem mass spectrometry in multiple reaction monitoring mode. The PAHs in the particulate matter (PM 2.5 and PM 10) samples were extracted by ultrasonic-assisted liquid extraction and cleaned up by an acidic silica gel solid phase extraction. The linearity range of all analyzed PAHs was from 5 to 2000 ng mL−1 with R2 ≥0.9990. Limit of detection (LOD) of PAHs in particulate matter sample was from 0.001 ng m−3 (Br-Naph) to 0.276 ng m−3 (Fln). The recovery of PAHs was investigated by international proficiency testing samples. The recoveries of PAHs in proficiency testing sample ranged from 79.3% (Chr) to 109.8% (IcdP). The in-house validated GC-EI-MS/MS method was then applied to analysis of some particulate matter samples that were collected in the Hanoi areas. The total concentrations of PAHs in several brands of samples collected from Hanoi were found in the range of 226.3 ng m−3–706.43 ng m−3. Among the studied compounds, naphthalene was found at high frequency and ranged from 106.5 ng m−3 to 631.1 ng m−3. The main distribution of the PAHs in particulate matter samples was two-ring and three-ring compounds.

Forests are one of the key elements in ecological transition policies in Europe. Sustainable forest management is needed in order to optimise wood harvesting, while preserving carbon storage, biodiversity and other ecological functions. Forest managers and public bodies need improved and cost-effective forest monitoring tools. Research studies have been carried out to assess the use of optical and radar images for producing forest height or biomass maps. The main limitations are the quantity, quality and representativeness of the reference data for model training. The Global Ecosystem Dynamics Investigation (GEDI) mission (full waveform LiDAR on board the International Space Station) has provided an unprecedented number of forest canopy height samples from 2019. These samples could be used to improve reference datasets. This paper aims to present and validate a method for estimating forest dominant height from open access optical and radar satellite images (Sentinel-1, Sentinel-2 and ALOS-2 PALSAR-2), and then to assess the use of GEDI samples to replace field height measurements in model calibration. Our approach combines satellite image features and dominant height measurements, or GEDI metrics, in a Support Vector Machine regression algorithm, with a feature selection process. The method is tested on mixed uneven-aged broadleaved and coniferous forests in France. Using dominant height measurements for model training, the cross-validation shows 7.3 to 11.6% relative Root Mean Square Error (RMSE) depending on the forest class. When using GEDI height metrics instead of field measurements for model training, errors increase to 12.8–16.7% relative RMSE. This level of error remains satisfactory; the use of GEDI could allow the production of dominant height maps on large areas with better sample representativeness. Future work will focus on confirming these results on new study sites, improving the filtering and processing of GEDI data, and producing height maps at regional or national scale. The resulting maps will help forest managers and public bodies to optimise forest resource inventories, as well as allow scientists to integrate these cartographic data into climate models.

Abstract Introduction Low‐ and middle‐income countries have rapidly increasing numbers of people with dementia, yet little evidence on family caregiving interventions. We tested the preliminary efficacy and feasibility of a family caregiving intervention in northern Vietnam. Methods Nine clusters comprising 60 family caregivers were randomized to a culturally adapted version of a four‐ to six‐session, multicomponent intervention delivered in‐home over 2 to 3 months, or enhanced control. Eligible caregivers were ≥18 years of age and scored ≥6 on the Zarit Burden Inventory (ZBI). Results Fifty‐one caregivers (85%) completed the study. Using analysis of covariance with 3‐month assessment as the outcome and baseline assessment as a covariate, intervention group caregivers had an average ZBI (primary outcome) score 1.2 standard deviation (SD) lower (P = .02) and Patient Health Questionnaire‐4 (psychological distress) score 0.7 SD lower (P = .03) than controls. Discussion In the first study of its kind in Vietnam, a culturally adapted, manualized, family caregiver intervention was both efficacious and feasible.

Lakes play a key role in the global water cycle, providing essential water resources and ecosystem services for humans and wildlife. Quantifying long-term changes in lake volume at a global scale is therefore important to the sustainability of humanity and natural ecosystems. Yet, such an estimate is still unavailable because, unlike lake area, lake volume is three-dimensional, challenging to be estimated consistently across space and time. Here, taking advantage of recent advances in remote sensing technology, especially NASA’s ICESat-2 satellite laser altimeter launched in 2018, we generated monthly volume series from 2003 to 2020 for 9065 lakes worldwide with an area ≥ 10 km2. We found that the total volume of the 9065 lakes increased by 597 km3 (90% confidence interval 239–2618 km3). Validation against in situ measurements showed a correlation coefficient of 0.98, an RMSE (i.e., root mean square error) of 0.57 km3 and a normalized RMSE of 2.6%. In addition, 6753 (74.5%) of the lakes showed an increasing trend in lake volume and were spatially clustered into nine hot spots, most of which are located in sparsely populated high latitudes and the Tibetan Plateau; 2323 (25.5%) of the lakes showed a decreasing trend in lake volume and were clustered into six hot spots—most located in the world’s arid/semi-arid regions where lakes are scarce, but population density is high. Our results uncovered, from a three-dimensional volumetric perspective, spatially uneven lake changes that aggravate the conflict between human demands and lake resources. The situation is likely to intensify given projected higher temperatures in glacier-covered regions and drier climates in arid/semi-arid areas. The 15 hot spots could serve as a blueprint for prioritizing future lake research and conservation efforts.

We report human pegivirus 2 (HPgV-2) infection in Vietnam. We detected HPgV-2 in some patients with hepatitis C virus/HIV co-infection but not in patients with HIV or hepatitis A, B, or C virus infection, nor in healthy controls. HPgV-2 strains in Vietnam are phylogenetically related to global strains.

Talaromyces marneffei infection is a major cause of death in HIV-infected individuals in South and Southeast Asia. Talaromycosis immune reconstitution inflammatory syndrome has not been well described. Here we report the clinical features, management, and outcomes of three HIV-infected patients with talaromycosis-associated paradoxical immune reconstitution inflammatory syndrome in Ho Chi Minh City, Vietnam.

In this study, we demonstrate the ability of a new operational system to detect forest loss at a large scale accurately and in a timely manner. We produced forest loss maps every week over Vietnam, Cambodia, and Laos (>750,000 km2 in total) using Sentinel-1 data. To do so, we used the forest loss detection method based on shadow detection. The main advantage of this method is the ability to avoid false alarms, which is relevant in Southeast Asia where the areas of forest disturbance may be very small and scattered and detection is used for alert purposes. The estimated user accuracy of the forest loss map was 0.95 for forest disturbances and 0.99 for intact forest, and the estimated producer’s accuracy was 0.90 for forest disturbances and 0.99 for intact forest, with a minimum mapping unit of 0.1 ha. This represents an important step forward compared to the values achieved by previous studies. We also found that approximately half of forest disturbances in Cambodia from 2018 to 2020 occurred in protected areas, which emphasizes the lack of efficiency in the protection and conservation of natural resources in protected areas. On an annual basis, the forest loss areas detected using our method are found to be similar to the estimations from Global Forest Watch. These results highlight the fact that this method provides not only quick alerts but also reliable detections that can be used to calculate weekly, monthly, or annual forest loss statistics at a national scale.

BackgroundDengue is the most prevalent arboviral disease of humans. Virus neutralizing antibodies are likely to be critical for clinical immunity after vaccination or natural infection. A number of human monoclonal antibodies (mAbs) have previously been characterized as able to neutralize the infectivity of dengue virus (DENV) for mammalian cells in cell-culture systems.Methodology/principle findingsWe tested the capacity of 12 human mAbs, each of which had previously been shown to neutralize DENV in cell-culture systems, to abrogate the infectiousness of dengue patient viremic blood for mosquitoes. Seven of the twelve mAbs (1F4, 14c10, 2D22, 1L12, 5J7, 747(4)B7, 753(3)C10), almost all of which target quaternary epitopes, inhibited DENV infection of Ae. aegypti. The mAbs 14c10, 747(4)B7 and 753(3)C10 could all inhibit transmission of DENV in low microgram per mL concentrations. An Fc-disabled variant of 14c10 was as potent as its parent mAb.Conclusions/significanceThe results demonstrate that mAbs can neutralize infectious DENV derived from infected human cells, in the matrix of human blood. Coupled with previous evidence of their ability to prevent DENV infection of mammalian cells, such mAbs could be considered attractive antibody classes to elicit with dengue vaccines, or alternatively, for consideration as therapeutic candidates.

An ultrahigh-performance liquid chromatography in combination with high-resolution mass spectrometry Thermo Q-Extractive Focus Orbitrap MS has been introduced for analysis of multiclass pesticides in vegetable samples collected in Hanoi, Vietnam. Multiclass pesticides were separated on the Thermo Hypersil Gold PFP column utilizing a gradient of the mobile phase consisting of 5 mM ammonium formate, 0.1% formic acid in deionized water, and methanol. The target analytes were detected in the full-scan mode on Thermo Scientific Q-Exactive Focus Orbitrap MS for quantitation at the optimum operating conditions. These conditions included, but not limit to, the resolution of 70000 at the full width at half maximum in both positive and negative mode, mass range from 80 to 1000 m/z, and optimized parameters for the heated electrospray ionization source. The identification of the analytes in real samples was based on retention times, mass to charge ratios, mass accuracies, and MS/MS spectra at the confirmation mode with the inclusion list of target analytes. The mass accuracies of target analytes were from −4.14 ppm (dinotefuran) to 1.42 ppm (cinosulfuron) in the neat solvent and from −3.91 ppm (spinosad D) to 1.29 ppm (cinosulfuron) in the matrix-matched solution. Target analytes in the vegetable-based matrix were extracted by the QuEChERS method. Some critical parameters of the analytical method such as linearity, repeatability, limit of detection, and limit of quantitation have been evaluated and implemented. Excellent LOD and LOQ of the developed method were achieved at the range of 0.04–0.85 and 0.13–2.9 μg·kg−1, respectively. Intraday and interday repeatability of the analytical signal (peak area, n=6) of the developed method were below 3% and 10%, correspondingly. The matrix effect, extraction recovery, and overall recovery were fully investigated by spiking experiments. Experimental results demonstrated that the ionization suppression or enhancement was the main contribution on the overall recoveries of target analytes. Finally, the in-house validated method was applied to pesticides screening in vegetables samples in local villages in Hanoi, Vietnam. The concentrations of all target analytes were below limit of quantitation and lower than US-FDA or EU maximum residue levels.

BackgroundThe highest burden of disease from hepatitis C virus (HCV) is found in Southeast Asia, but our understanding of the epidemiology of infection in many heavily burdened countries is still limited. In particular, there is relatively little data on acute HCV infection, the outcome of which can be influenced by both viral and host genetics which differ within the region. We studied HCV genotype and IL28B gene polymorphism in a cohort of acute HCV-infected patients in Southern Vietnam alongside two other cohorts of chronic HCV-infected patients to better understand the epidemiology of HCV infection locally and inform the development of programs for therapy with the increasing availability of directly acting antiviral therapy (DAAs).MethodsWe analysed plasma samples from patients with acute and chronic HCV infection, including chronic HCV mono-infection and chronic Human Immunodeficiency Virus (HIV)-HCV coinfection, who enrolled in four epidemiological or clinical research studies. HCV infection was confirmed with RNA testing. The 5' UTR, core and NSB5 regions of HCV RNA positive samples were sequenced, and the genotype and subtype of the viral strains were determined. Host DNA from all HCV positive patients and age- and sex-matched non-HCV-infected control individuals were analysed for IL28B single nucleotide polymorphism (SNP) (rs12979860 and rs8099917). Geolocation of the patients were mapped using QGIS.Results355 HCV antibody positive patients were analysed; 54.6% (194/355) and 46.4% (161/355) were acute and chronic infections, respectively. 50.4% (81/161) and 49.6.4% (80/161) of chronic infections had HCV mono-infection and HIV-HCV coinfection, respectively. 88.7% (315/355) and 10.1% (36/355) of the patients were from southern and central regions of Vietnam, respectively. 92.4% (328/355) of patients were HCV RNA positive, including 86.1% (167/194) acute and 100% (161/161) chronic infections. Genotype could be determined in 98.4% (322/328) patients. Genotypes 1 (56.5%; 182/322) and 6 (33.9%; 109/322) predominated. Genotype 1 including genotype 1a was significantly higher in HIV-HCV coinfected patients compared to acute HCV patients [43.8% (35/80) versus 20.5% (33/167)], (p = ConclusionHCV genotype 6 is highly prevalent in Vietnam and the high prevalence in treatment naïve chronic HCV patients may results from poor spontaneous clearance of acute HCV infection with genotype 6.

Carbon and iron co-doped titanium dioxide catalyst coated on activated carbon (Fe-C-TiO2/AC) was successfully synthesized using the sol-gel method, followed by hydrothermal treatment. Commercial activated carbon was treated by HNO3 prior to being coated by the as-synthesized catalyst. The composite was characterized by XPS, XRD, UV-Vis spectrophotometry, IR, TEM, HR-TEM, and BET. The performance of the supported catalysts was evaluated in the degradation of rhodamine B (RhB) in the solution under visible-light irradiation. The results showed that, with the appropriate amount of activated carbon, prepared Fe-C-TiO2/AC catalysts exhibited higher catalytic activities and Fe-C-TiO2/AC system showed the best performance. The photocatalytic degradation efficiency of Fe-C-TiO2/AC was enhanced due to the synergistic effect between AC (adsorption effect) and Fe-C-TiO2 (photocatalysis effect). This facilitated the photocatalytic degradation of RhB by Fe-C-TiO2.

Rice is the primary staple food of more than half of the world’s population and plays an especially important role in global economy, food security, water use, and climate change. The usefulness of Synthetic Aperture Radars (SAR) for rice mapping and monitoring has been demonstrated locally in many studies, in particular in the last five years with the availability of an unprecedented amount of free Sentinel-1 data within the Copernicus program. However, although earlier studies from the 1990s have laid the foundations of the physical understanding of the SAR response of rice fields, the more recent studies tend to overlook this aspect and to favor instead approaches driven by supervised learning which provide accurate results locally but cannot necessarily be extended to wide areas. The objective of this study is to analyze in detail the backscatter temporal variation of rice fields, using Sentinel-1 from 2015 to 2020 and in-situ data for the 5 rice seasons over 2 years 2017–2018, in order to derive robust SAR-based indicators useful for rice monitoring applications, which are essential for planning, monitoring and food security applications. The test region is the An Giang province, in the Mekong River Delta, Vietnam, one of the world’s major rice regions which presents a diversity in rice cultivation practices, in cropping density, and in crop calendar. The SAR data have been analyzed as a function of rice parameters, and the temporal and polarization behaviors of the radar backscatter of different rice varieties have been interpreted physically. New backscatter indicators for the detection of rice paddy area, the estimation of the sowing date, phenological stage and the mapping of the short cycle and long cycle rice varieties have been developed and discussed regarding the generality of the methods with respect to the rice cultural practices and the SAR data characteristics.

BIOMASS is ESA’s seventh Earth Explorer mission, scheduled for launch in 2022. The satellite will be the first P-band SAR sensor in space and will be operated in fully polarimetric interferometric and tomographic modes. The mission aim is to map forest above-ground biomass (AGB), forest height (FH) and severe forest disturbance (FD) globally with a particular focus on tropical forests. This paper presents the algorithms developed to estimate these biophysical parameters from the BIOMASS level 1 SAR measurements and their implementation in the BIOMASS level 2 prototype processor with a focus on the AGB product. The AGB product retrieval uses a physically-based inversion model, using ground-canceled level 1 data as input. The FH product retrieval applies a classical PolInSAR inversion, based on the Random Volume over Ground Model (RVOG). The FD product will provide an indication of where significant changes occurred within the forest, based on the statistical properties of SAR data. We test the AGB retrieval using modified airborne P-Band data from the AfriSAR and TropiSAR campaigns together with reference data from LiDAR-based AGB maps and plot-based ground measurements. For AGB estimation based on data from a single heading, comparison with reference data yields relative Root Mean Square Difference (RMSD) values mostly between 20% and 30%. Combining different headings in the estimation process significantly improves the AGB retrieval to slightly less than 20%. The experimental results indicate that the implemented retrieval scheme provides robust results that are within mission requirements.

The rapidly developing urbanization since the last decade of the 20th century has led to extensive groundwater extraction, resulting in subsidence in Ho Chi Minh City, Vietnam. Recent advances in multi-temporal spaceborne SAR interferometry, especially with a persistent scatters interferometry (PSI) approach, has made this a robust remote sensing technique for measuring large-scale ground subsidence with millimetric accuracy. This work has presented an advanced PSI analysis, to provide an unprecedented spatial extent and continuous temporal coverage of the subsidence in Ho Chi Minh City from 2006 to 2010. The study shows that subsidence is most severe in the Holocene silt loam areas along the Sai Gon River and in the southwest of the city. The groundwater extraction resulting from urbanization and urban growth is mainly responsible for the subsidence. Subsidence in turn leads to more flooding and water nuisance. The correlation between the reference leveling velocity and the estimated PSI result is R2 = 0.88, and the root mean square error is 4.3 (mm/year), confirming their good agreement. From 2006 to 2010, the estimation of the average subsidence rate is -8.0 mm/year, with the maximum value up to -70 mm/year. After four years, in regions along Sai Gon River and in the southwest of the city, the land has sunk up to -12 cm. If not addressed, subsidence leads to the increase of inundation, both in frequency and spatial extent. Finally, regarding climate change, the effects of subsidence should be considered as appreciably greater than those resulting from rising sea level. It is essential to consider these two factors, because the city is inhabited by more than 7.5 million people, where subsidence directly impacts urban structures and infrastructure.

BACKGROUND:Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) coinfection is a major global health problem especially among people who inject drugs (PWID), with significant clinical implications. Mathematical models have been used to great effect to shape HIV care, but few have been proposed for HIV/HCV. METHODS:We constructed a deterministic compartmental ODE model that incorporated layers for HIV disease progression, HCV disease progression and PWID demography. Antiretroviral therapy (ART) and Methadone Maintenance Therapy (MMT) scale-ups were modeled as from 2016 and projected forward 10 years. HCV treatment roll-out was modeled beginning in 2026, after a variety of MMT scale-up scenarios, and projected forward 10 years. RESULTS:Our results indicate that scale-up of ART has a major impact on HIV though not on HCV burden. MMT scale-up has an impact on incidence of both infections. HCV treatment roll-out has a measurable impact on reductions of deaths, increasing multifold the mortality reductions afforded by just ART/MMT scale-ups. CONCLUSION:HCV treatment roll-out can have major and long-lasting effects on averting PWID deaths on top of those averted by ART/MMT scale-up. Efficient intervention scale-up of HCV alongside HIV interventions is critical in Vietnam.

Cell banking, disease modeling, and cell therapy applications have placed increasing demands on hiPSC technology. Specifically, the high-throughput derivation of footprint-free hiPSCs and their expansion in systems that allow scaled production remains technically challenging. Here, we describe a platform for the rapid, parallel generation, selection, and expansion of hiPSCs using small molecule pathway inhibitors in stage-specific media compositions. The platform supported efficient and expedited episomal reprogramming using just OCT4/SOX2/SV40LT combination (0.5%–4.0%, between days 12 and 16) in a completely feeder-free environment. The resulting hiPSCs are transgene-free, readily cultured, and expanded as single cells while maintaining a homogeneous and genomically stable pluripotent population. hiPSCs generated or maintained in the media compositions described exhibit properties associated with the ground state of pluripotency. The simplicity and robustness of the system allow for the high-throughput generation and rapid expansion of a uniform hiPSC product that is applicable to industrial and clinical-grade use.