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A large number of disease-modifying immunotherapies are available for the treatment of people with multiple sclerosis. Many disease-modifying immunotherapies show scarce or no safety data in pregnancy and breastfeeding and are labeled as being contraindicated during these periods in the Swiss summary of product characteristics. Some disease-modifying immunotherapies also have restrictions for male patients. Hence, family planning should always be considered in treatment decisions. If clinically necessary, the continuation of immunotherapy during pregnancy can be considered for some substances. In these situations, the “Good Off-Label Use Practice”, careful consideration of the benefit–risk profile, and interprofessional cooperation between the treating neurologist, obstetrician–gynecologist, and pharmacist/pharmacologist, ideally with the involvement of experienced centers, is necessary. Here, we present an update on disease-modifying immunotherapies in multiple sclerosis with a focus on family planning, pregnancy, and breastfeeding and provide consensus recommendations of the Medico-Scientific Advisory Board of the Swiss Multiple Sclerosis Society, the Swiss Neurological Society, and the Swiss Society for Gynecology and Obstetrics (represented by the Academy of Fetomaternal Medicine). These unified national recommendations are necessary, as guidelines from other countries differ and because of separate approval/reimbursement situations in Switzerland.

Implantable Cardiac Monitor (ICM) devices are demonstrating, as of today, the fastest-growing market for implantable cardiac devices. As such, they are becoming increasingly common in patients for measuring heart electrical activity. ICMs constantly monitor and record a patient’s heart rhythm, and when triggered, send it to a secure server where health care professionals (HCPs) can review it. These devices employ a relatively simplistic rule-based algorithm (due to energy consumption constraints) to make alerts for abnormal heart rhythms. This algorithm is usually parameterized to an over-sensitive mode in order to not miss a case (resulting in a relatively high false-positive rate), and this, combined with the device’s nature of constantly monitoring the heart rhythm and its growing popularity, results in HCPs having to analyze and diagnose an increasingly growing number of data. In order to reduce the load on the latter, automated methods for ECG analysis are nowadays becoming a great tool to assist HCPs in their analysis. While state-of-the-art algorithms are data-driven rather than rule-based, training data for ICMs often consist of specific characteristics that make their analysis unique and particularly challenging. This study presents the challenges and solutions in automatically analyzing ICM data and introduces a method for its classification that outperforms existing methods on such data. It carries this out by combining high-frequency noise detection (which often occurs in ICM data) with a semi-supervised learning pipeline that allows for the re-labeling of training episodes and by using segmentation and dimension-reduction techniques that are robust to morphology variations of the sECG signal (which are typical to ICM data). As a result, it performs better than state-of-the-art techniques on such data with, e.g., an F1 score of 0.51 vs. 0.38 of our baseline state-of-the-art technique in correctly calling atrial fibrillation in ICM data. As such, it could be used in numerous ways, such as aiding HCPs in the analysis of ECGs originating from ICMs by, e.g., suggesting a rhythm type.

This paper contributes to the understanding of the recent urban development of Ho Chi Minh City, Vietnam. Previous studies have aimed at quantifying the city’s spatial growth yet have disregarded its inherent morphological and socio-economic heterogeneity. To overcome this knowledge gap, we employ an urban structure type approach for the spatially explicit quantification of urbanisation patterns for the period 2010–⁠2020, categorising 77,000 blocks across the entire administrative area of 2095 km2. The approach allows us to understand the basic underlying processes of urbanisation, both quantitatively and qualitatively, and the main growth corridors along the rural–urban gradient. By contextualizing and combining our findings within current literature and official planning reports, we discern between traditional urban growth and the contemporary new town development patterns, highlighting their driving forces and policy implications. Incremental plot-by-plot development along the northwest development corridor is observed as the principal mode of urban development, whilst bypass urbanisation is seen along both the eastern and southern development corridors. Our block-based results highlight the city’s key growth challenges and provide insights on a scale that is meaningful for official spatial and infrastructure planning, and periodic analysis and monitoring. As far as the authors are aware, this is the first time that an urban structure type approach was applied to understand the rapid urban growth dynamics of an emerging megacity in Southeast Asia.

Objectives: This study aims to determine cirrhotic patients’ clinical and laboratory characteristics, thereby examining the correlation between lymphocyte-to-monocyte ratio and Child–Pugh and MELD/MELDNa scores. Methods: A cross-sectional study with an analysis of 153 patients admitted to the Department of Gastroenterology–Clinical Hematology at Can Tho Central General Hospital. Data were collected via patient interviews and medical records. Results: The included patients were more likely to be male (66.7%) and were ≥60 years old (51.6%). Excessive alcohol consumption and hepatitis B were the dominant causes of cirrhosis (35.3% and 34.0%). The clinical and laboratory characteristics were similar to previous studies in cirrhotic patients. The mean Child score was 9.3 ± 2.1, including 9.8% of patients with Child A, 44.4% for Child B, and 45.8% for Child C. The mean MELD and MELDNa scores were 16.9 ± 7.1 and 19.4 ± 8.1, respectively. The mean lymphocyte-to-monocyte ratio (LMR) is 2.0 ± 2.2 (from 0.09 to 25.3), being negatively correlated with the other scores (Pearson correlation coefficients were −0.238; −0.211 and −0.245, respectively, all p-values < 0.01). Patients with LMR below 3.31 were more likely to be classified as Child–Pugh B and C. Conclusion: The correlation between LMR with Child–Pugh, MELD, and MELDNa scores was weak and negative.

Background: Patient factors, such as sex and body mass index (BMI), are known to influence patient radiation exposure. Body surface area (BSA) and its association with patient radiation exposure has not been well studied. Methods and Results: We analysed height, weight, BMI and BSA in consecutive patients undergoing cardiac catheterisation and percutaneous coronary intervention (PCI) at a high-volume Australian centre between September 2016 and April 2020 to assess their association with dose–area product (DAP, Gycm2). The mean age of the cohort was 64.5 ± 12.3 years with males comprising 68.8% (n = 8100, 5124 diagnostic cardiac catheterisation cases and 2976 PCI cases). Median male BMI was 28.4 kg/m2 [IQR 25.2–32.1] versus 28.8 kg/m2 [24.7–33.7] for females, p = 0.01. Males had higher BSA (2.0 ± 0.2 m2) than females (1.78 ± 0.2 m2), p = 0.001. Each 0.4 m2 increase in BSA conferred a 1.32x fold change in DAP (95% CI 1.29–1.36, p ≤ 0.001). Each 5 kg/m2 increase in BMI was linked to a 1.13x DAP fold change (1.12–1.14, p ≤ 0.001). Male sex conferred a 1.23x DAP fold change (1.20–1.26, p ≤ 0.001). Multivariable modelling with BMI or BSA explained 14% of DAP variance (R2 0.67 vs. 0.53 for both, p ≤ 0.001). Conclusions: BSA is an important anthropometric measure between the sexes and a key predictor of radiation dose and radiation exposure beyond sex, BMI, and weight.

In this study, chemical components, α-glucosidase inhibitory activities, and molecular modelling studies of the essential oil extracted from the Cleistocalyx operculatus leaves were investigated. In total, thirty compounds were identified using GC/MS, representing 98.3% of the oil. Of these, the two most dominant constituents of the essential oil were determined as (Z)-β-ocimene (30.4%) and allo-ocimene (31.6%). The α-glucosidase inhibitory experiments indicated that the essential oil exhibited potent α-glucosidase inhibitory activities, with IC50 values of 61.82 ± 3.91 µg/mL. For further investigation into inhibitory mechanisms, molecular docking simulations were performed to investigate structural interactions between two dominant constituents and the α-glucosidase protein. The simulation revealed that allo-ocimene (31.6%) and (Z)-β-ocimene (30.4%) have protein binding affinities of −5.358 and −5.330 kcal/mol, respectively. Moreover, molecular dynamic simulation indicated that the complexes of two compounds and the target protein were stable over 100 ns. Overall, these findings suggest that the essential oil of C. operculatus leaves could be a natural source of potential α-glucosidase inhibitors.

Several previous studies in the field of assisted reproduction have focused on the use of blood gel derivatives, such as platelet-rich fibrin (PRF), as a treatment for endometrial rehabilitation. However, the ability to release growth factors and the gel form of this product led to the evolution of platelet lysates. In this study, blood gel derivatives, including PRF lysate, which was in liquid form, and PRF gel, were collected and evaluated for growth factors. It was shown to be effective in endometrial wound healing and regeneration in mouse injured uterine tissue models through structure and function (pinopode expression, embryo implantation) evaluation. The results demonstrated that the concentrations of growth factors, including PDGF-AB and VEGF-A, were higher in the PRF lysate compared to the PRF gel (p < 0.05). PRF lysate could release these growth factors for 8 days. Furthermore, both PRF gel and PRF lysate restored the morphology of injured endometrial tissues in terms of luminal and glandular epithelia, as well as uterine gland secretory activity. However, the presence of pinopodes and embryonic implantation were only observed in the PRF lysate group. It can be concluded that PRF lysate promotes wound healing in mouse injured tissue models in vitro, which can act as healing products in tissue repair.

In this study, various two-dimensional (2D) materials were used as supporting materials for the bimetallic Co and Mo sulfide/oxide (CMSO) heterostructure. The water electrolysis activity of CMSO supported on reduced graphene oxide (rGO), graphite carbon nitride (gC3N4), and siloxene (SiSh) was better than that of pristine CMSO. In particular, rGO-supported CMSO (CMSO@rGO) exhibited a large surface area and a low interface charge-transfer resistance, leading to a low overpotential and a Tafel slope of 259 mV (10 mA/cm2) and 85 mV/dec, respectively, with excellent long-term stability over 40 h of continuous operation in the oxygen evolution reaction.

Fucoxanthin extracted and purified from Vietnamese Sargassum oligocystum Montagne, 1845 exhibits various biological activities. In this study, the ability of fucoxanthin to inhibit acetylcholinesterase (AChE), the antioxidant activities, and the expression of antioxidant enzymes were investigated. Fucoxanthin isolated from Vietnamese S. oligocystum showed no cytotoxic effects; moreover, it exhibited AChE inhibitory activity (with an IC50 value of 130.12 ± 6.65 μg mL−1) and antioxidant activity (with an IC50 value of 3.42 ± 0.15 mg mL−1). At concentrations of 50 and 100 µg mL−1, fucoxanthin provided protection against amyloid β-protein fragment 25–35-induced neurotoxicity in a C6 neuronal cell line, and the survival of C6 cells was higher than 81.01% and 80.98%, respectively, compared to the control group (59%). Moreover, antioxidant enzyme activity and quantitative PCR analysis suggested that the neuroprotective effect of fucoxanthin resulted from regulation of the gene expression of antioxidant enzymes (CAT and GPx) and ER pathways (caspase-3 and Bax), as well as the promotion of expression of genes involved in PI3K/Akt signaling (GSK-3β), autophagy (p62 and ATG5), and the biosynthesis of ACh (VAChT and ChAT). Therefore, fucoxanthin extracted from the seaweed S. oligocystum in Vietnam is a potential feedstock source for the production of health foods that exert neuroprotective effects.

Astronauts are always faced with serious health problems during prolonged spaceflights. Previous studies have shown that weightlessness significantly affects the physiological function of female astronauts, including a change in reproductive hormones and ovarian cells, such as granulosa and theca cells. However, the effects of microgravity on these cells have not been well characterized, especially in granulosa cells. This study aimed to investigate the effects of simulated microgravity (SMG) on the proliferation and morphology of porcine granulosa cells (pGCs). pGC proliferation from the SMG group was inhibited, demonstrated by the reduced O.D. value and cell density in the WST-1 assay and cell number counting. SMG-induced pGCs exhibited an increased ratio of cells in the G0/G1 phase and a decreased ratio of cells in the S and G2/M phase. Western blot analysis indicated a down-regulation of cyclin D1, cyclin-dependent kinase 4 (cdk4), and cyclin-dependent kinase 6 (cdk6), leading to the prevention of the G1-S transition and inducing the arrest phase. pGCs under the SMG condition showed an increase in nuclear area. This caused a reduction in nuclear shape value in pGCs under the SMG condition. SMG-induced pGCs exhibited different morphologies, including fibroblast-like shape, rhomboid shape, and pebble-like shape. These results revealed that SMG inhibited proliferation and induced morphological changes in pGCs.

(1) Background: Exhaled nitric oxide (NO) has been considered as a biomarker of airway inflammation. The measurement of fractional exhaled NO (FENO) is a valuable test for assessing local inflammation in subjects with allergic rhinitis (AR). (2) Objective: To evaluate (a) the correlation between nasal FENO with anthropometric characteristics, symptoms of AR and nasal peak flows in children without and with AR; and (b) the cut-off of nasal FENO for diagnosis of AR in symptomatic children. (3) Methods: The study was a descriptive and cross-sectional study in subjects with and without AR < 18 years old. All clinical and functional characteristics of the study subjects were recorded for analysis. They were divided into healthy subjects for the control group and subjects with AR who met all inclusion criteria. (4) Results: 100 subjects (14 ± 3 years) were included, including 32 control subjects and 68 patients with AR. Nasal FENO in AR patients was significantly higher than in control subjects: 985 ± 232 ppb vs. 229 ± 65 ppb (p < 0.001). In control subjects, nasal FENO was not correlated with anthropometric characteristics and nasal inspiratory or expiratory peak flows (IPF or EPF) (p > 0.05). There was a correlation between nasal FENO and AR symptoms in AR patients and nasal IPF and EPF (p = 0.001 and 0.0001, respectively). The cut-off of nasal FENO for positive AR diagnosis with the highest specificity and sensitivity was ≥794 ppb (96.7% and 92.6%, respectively). (5) Conclusion: The use of nasal FENO as a biomarker of AR provides a useful tool and additional armamentarium in the management of allergic rhinitis.

Industrial wastewater often consists of toxic chemicals and pollutants, which are extremely harmful to the environment. Heavy metals are toxic chemicals and considered one of the major hazards to the aquatic ecosystem. Analytical techniques, such as potentiometric methods, are some of the methods to detect heavy metals in wastewaters. In this work, the quantitative structure–property relationship (QSPR) was applied using a range of machine learning techniques to predict the stability constant (logβML) and potentiometric sensitivity (PSML) of 200 ligands in complexes with the heavy metal ions Cu2+, Cd2+, and Pb2+. In result, the logβML models developed for four ions showed good performance with square correlation coefficients (R2) ranging from 0.80 to 1.00 for the training and 0.72 to 0.85 for the test sets. Likewise, the PSML displayed acceptable performance with an R2 of 0.87 to 1.00 for the training and 0.73 to 0.95 for the test sets. By screening a virtual database of coumarin-like structures, several new ligands bearing the coumarin moiety were identified. Three of them, namely NEW02, NEW03, and NEW07, showed very good sensitivity and stability in the metal complexes. Subsequent quantum-chemical calculations, as well as physicochemical/toxicological profiling were performed to investigate their metal-binding ability and developability of the designed sensors. Finally, synthesis schemes are proposed to obtain these three ligands with major efficiency from simple resources. The three coumarins designed clearly demonstrated capability to be suitable as good florescent chemosensors towards heavy metals. Overall, the computational methods applied in this study showed a very good performance as useful tools for designing novel fluorescent probes and assessing their sensing abilities.

Post-COVID-19 syndrome is an ongoing challenge for healthcare systems as well as for society. The clinical picture of post-COVID-19 syndrome is heterogeneous, including fatigue, sleep disturbances, pain, hair loss, and gastrointestinal symptoms such as chronic diarrhea. Neurological complaints such as fatigue, cognitive impairment, and sleep disturbances are common. Due to the short timeframe of experience and small amount of evidence in this field, the treatment of post-COVID-19 syndrome remains a challenge. Currently, therapeutic options for post-COVID-19 syndrome are limited to non-pharmaceutical interventions and the symptomatic therapy of respective symptoms. In this article, we summarize the current knowledge about therapeutic options for the treatment of neurological symptoms of post-COVID-19 syndrome.

Shortly after its emergence, Omicron and its sub-variants have quickly replaced the Delta variant during the current COVID-19 outbreaks in Vietnam and around the world. To enable the rapid and timely detection of existing and future variants for epidemiological surveillance and diagnostic applications, a robust, economical real-time PCR method that can specifically and sensitively detect and identify multiple different circulating variants is needed. The principle of target- failure (TF) real-time PCR is simple. If a target contains a deletion mutation, then there is a mismatch with the primer or probe, and the real-time PCR will fail to amplify the target. In this study, we designed and evaluated a novel multiplex RT real-time PCR (MPL RT-rPCR) based on the principle of target failure to detect and identify different variants of SARS-CoV-2 directly from the nasopharyngeal swabs collected from COVID-19 suspected cases. The primers and probes were designed based on the specific deletion mutations of current circulating variants. To evaluate the results from the MPL RT-rPCR, this study also designed nine pairs of primers for amplifying and sequencing of nine fragments from the S gene containing mutations of known variants. We demonstrated that (i) our MPL RT-rPCR was able to accurately detect multiple variants that existed in a single sample; (ii) the limit of detection of the MPL RT-rPCR in the detection of the variants ranged from 1 to 10 copies for Omicron BA.2 and BA.5, and from 10 to 100 copies for Delta, Omicron BA.1, recombination of BA.1 and BA.2, and BA.4; (iii) between January and September 2022, Omicron BA.1 emerged and co-existed with the Delta variant during the early period, both of which were rapidly replaced by Omicron BA.2, and this was followed by Omicron BA.5 as the dominant variant toward the later period. Our results showed that SARS-CoV-2 variants rapidly evolved within a short period of time, proving the importance of a robust, economical, and easy-to-access method not just for epidemiological surveillance but also for diagnoses around the world where SARS-CoV-2 variants remain the WHO’s highest health concern. Our highly sensitive and specific MPL RT-rPCR is considered suitable for further implementation in many laboratories, especially in developing countries.

Metagenomics revealed novel and routinely overlooked viruses, representing sources of unrecognized infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aim to describe DNA and RNA virus prevalence and kinetics in allo-HSCT recipients’ plasma for one year post HSCT. We included 109 adult patients with first allo-HSCT from 1 March 2017 to 31 January 2019 in this observational cohort study. Seventeen DNA and three RNA viral species were screened with qualitative and/or quantitative r(RT)-PCR assays using plasma samples collected at 0, 1, 3, 6, and 12 months post HSCT. TTV infected 97% of patients, followed by HPgV-1 (prevalence: 26–36%). TTV (median 3.29 × 105 copies/mL) and HPgV-1 (median 1.18 × 106 copies/mL) viral loads peaked at month 3. At least one Polyomaviridae virus (BKPyV, JCPyV, MCPyV, HPyV6/7) was detected in >10% of patients. HPyV6 and HPyV7 prevalence reached 27% and 12% at month 3; CMV prevalence reached 27%. HSV, VZV, EBV, HHV-7, HAdV and B19V prevalence remained

Cellular deposition of protein aggregates, one of the hallmarks of neurodegeneration, disrupts cellular functions and leads to neuronal death. Mutations, posttranslational modifications, and truncations are common molecular underpinnings in the formation of aberrant protein conformations that seed aggregation. The major proteins involved in neurodegeneration include amyloid beta (Aβ) and tau in Alzheimer’s disease, α-synuclein in Parkinson’s disease, and TAR DNA-binding protein (TDP-43) in amyotrophic lateral sclerosis (ALS). These proteins are described as intrinsically disordered and possess enhanced ability to partition into biomolecular condensates. In this review, we discuss the role of protein misfolding and aggregation in neurodegenerative diseases, specifically highlighting implications of changes to the primary/secondary (mutations, posttranslational modifications, and truncations) and the quaternary/supramolecular (oligomerization and condensation) structural landscapes for the four aforementioned proteins. Understanding these aggregation mechanisms provides insights into neurodegenerative diseases and their common underlying molecular pathology.

The magnetic proximity effect (MPE) has recently been explored to manipulate interfacial properties of two-dimensional (2D) transition metal dichalcogenide (TMD)/ferromagnet heterostructures for use in spintronics and valleytronics. However, a full understanding of the MPE and its temperature and magnetic field evolution in these systems is lacking. In this study, the MPE has been probed in Pt/WS2/BPIO (biphase iron oxide, Fe3O4 and α-Fe2O3) heterostructures through a comprehensive investigation of their magnetic and transport properties using magnetometry, four-probe resistivity, and anomalous Hall effect (AHE) measurements. Density functional theory (DFT) calculations are performed to complement the experimental findings. We found that the presence of monolayer WS2 flakes reduces the magnetization of BPIO and hence the total magnetization of Pt/WS2/BPIO at T > ~120 K—the Verwey transition temperature of Fe3O4 (TV). However, an enhanced magnetization is achieved at T < TV. In the latter case, a comparative analysis of the transport properties of Pt/WS2/BPIO and Pt/BPIO from AHE measurements reveals ferromagnetic coupling at the WS2/BPIO interface. Our study forms the foundation for understanding MPE-mediated interfacial properties and paves a new pathway for designing 2D TMD/magnet heterostructures for applications in spintronics, opto-spincaloritronics, and valleytronics.

The synergistic effects of biological invasions have long been considered significant causes of biodiversity loss worldwide. Therefore, early detection monitoring is crucial in mitigating nonindigenous species (NIS) threats. In the marine environment, settlement plates were used as monitoring devices in ports, but this method was mainly applied to assess the sessile benthic community and is less efficient in collecting the mobile biota and accessing its diversity. Moreover, as the potential expansion of NIS to the surrounding coastal environment is still poorly understood, a pilot study was conducted focusing on two aspects: (i) improving the feasibility of the settling method under different environmental contexts and (ii) enhancing the capacity of the developed prototypes to collect more representative samples (i.e., sessile and mobile biota). Three different prototypes were designed: a box prototype consisting of PVC plates encapsulated by a plastic bottle, a CD prototype with CDs surrounded by a net, and a PVC prototype with uncovered PVC plates. The prototypes were deployed inside a marina and in an outside area on Madeira Island, Portugal. Results indicate that the PVC prototype was the most efficient regarding monitoring the sessile community, whereas the box prototype showed the highest abundance of the mobile fauna. The location influenced both the sessile community composition and the number of mobile taxa. Our findings suggest combining features from prototypes to encompass the whole benthic community better.

Probiotic feed additives can support the gut health of shrimp and thereby improve performance, production efficiency and disease resistance. Two experiments in white leg shrimp aimed to investigate the effects of a multi-species probiotic feed supplement (AquaStar®, 3 g/kg feed, Biomin GmbH, Getzersdorf, Austria) in feed formulations with different marine meal levels (32% and 15%) on growth performance and resistance against Vibrio parahaemolyticus. Juvenile shrimp were stocked in a recirculating aquaculture tank system at a density of 20 shrimp/46.8 L and were fed diets with and without the probiotic supplementation for 8 weeks. Afterwards, a bath immersion with V. parahaemolyticus was performed and mortality was observed over a period of 14 days. Independent of the diet formulation, probiotic supplementation significantly improved the survival rate of the shrimp and the specific growth rate while decreasing feed consumption and feed conversion ratio when compared to the control (p ≤ 0.042). After the Vibrio immersion challenge, mortality was significantly decreased by 13.33% with probiotic supplementation in the high marine meal diet experiment (p = 0.042) and numerically decreased by 11.67% in the low marine meal diet experiment (p = 0.133). Overall, the results suggest that the beneficial effects of the probiotic can occur independently of the diet formulation.

Storing potato tubers at cold temperatures, either for transport or continuity of supply, is associated with the conversion of sucrose to reducing sugars. When cold-stored cut tubers are processed at high temperatures, with endogenous asparagine, acrylamide is formed. Acrylamide is classified as a carcinogen. Potato processors prefer cultivars which accumulate fewer reducing sugars and thus less acrylamide on processing, and suitable processing cultivars may not be available. We used CRISPR-Cas9 to disrupt the genes encoding vacuolar invertase (VInv) and asparagine synthetase 1 (AS1) of cultivars Atlantic and Desiree to reduce the accumulation of reducing sugars and the production of asparagine after cold storage. Three of the four guide RNAs employed induced mutation frequencies of 17–98%, which resulted in deletions, insertions and substitutions at the targeted gene sites. Eight of ten edited events had mutations in at least one allele of both genes; for two, only the VInv was edited. No wild-type allele was detected in both genes of events DSpco7, DSpFN4 and DSpco12, suggesting full allelic mutations. Tubers of two Atlantic and two Desiree events had reduced fructose and glucose concentrations after cold storage. Crisps from these and four other Desiree events were lighter in colour and included those with 85% less acrylamide. These results demonstrate that multiplex CRISPR-Cas9 technology can generate improved potato cultivars for healthier processed potato products.

Background: Smile aesthetics has a vital role to play in an individual’s life and one of the factors affecting the beauty of the smile is gingival color. A gingival color change or gingival hyperpigmentation causes an unesthetic smile line, especially in patients with a gummy smile, which is also known as a black gummy smile. Numerous gingival depigmentation methods have been performed successfully for ablating gingival melanin pigmented epithelium. Thus, the aim of this study is to evaluate the treatment efficacy of gingival hyperpigmentation by using a carbon dioxide (CO2) laser. Methods: A cross-sectional descriptive study was carried out with 38 patients at a hospital in Vietnam. Ponnaiyan classification and the Hedin melanin index were used to assess the distribution and extent of gingival pigmentation in the study. Pain assessment was performed using the Visual Analog Scale (VAS) to evaluate the intensity of pain during the laser treatment. In addition, clinical evaluation (i.e., wound healing) of each treatment procedure was conducted using the three level Dummett–Gupta Oral Pigmentation Index (DOPI) assessment. Results: This study showed that less pain was experienced by patients treated by CO2 laser; the rates of no pain, mild pain and moderate pain after treatment were, respectively, 21%, 76% and 2.6%; there was 100% complete epithelization after 1 week. The DOPI rates for turning from a DOPI score of 1, 2 or 3 to a DOPI score of 0 after a 12-week treatment were 87.5%, 76.9% and 24%, respectively. Conclusions: Using a CO2 laser for gingival melanin pigmentation treatment is a safe and effective procedure.

Aurantiochytrium is a heterotrophic marine microalga that has potential industrial applications. The main objectives of this study were to isolate an Aurantiochytrium strain from Sand Cay (Son Ca) Island, Vietnam, optimize its culture conditions, determine its nutritional composition, extract polyunsaturated fatty acids (PUFAs) in the free (FFA) and the alkyl ester (FAAE) forms, and evaluate the antioxidation and neuroprotection properties of the PUFAs. Aurantiochytrium sp. SC145 can be grown stably under laboratory conditions. Its culture conditions were optimized for a dry cell weight (DCW) of 31.18 g/L, with total lipids comprising 25.29%, proteins 7.93%, carbohydrates 15.21%, and carotenoid at 143.67 µg/L of DCW. The FAAEs and FFAs extracted from Aurantiochytrium sp. SC145 were rich in omega 3–6–9 fatty acids (40.73% and 44.00% of total fatty acids, respectively). No acute or subchronic oral toxicity was determined in mice fed with the PUFAs in FFA or FAAE forms at different doses over 90 days. Furthermore, the PUFAs in the FFA or FAAE forms and their main constituents of EPA, DHA, and ALA showed antioxidant and AChE inhibitory properties and neuroprotective activities against damage caused by H2O2- and amyloid-ß protein fragment 25–35 (Aβ25-35)-induced C6 cells. These data suggest that PUFAs extracted from Aurantiochytrium sp. SC145 may be a potential therapeutic target for the treatment of neurodegenerative disorders.

Many factors may influence the risk of being infected by SARS-CoV-2, the coronavirus responsible for coronavirus disease 2019 (COVID-19). Exposure to the virus cannot explain the variety of an individual’s responses to the virus and the high differences of effect that the virus may cause to some. While a person’s preexisting condition and their immune defenses have been confirmed to play a major role in the disease progression, there is still much to learn about hosts’ genetic makeup towards COVID-19 susceptibility and risk. The host genetic makeup may have direct influence on the grade of predisposition and outcomes of COVID-19. In this study, we aimed to investigate the presence of relevant genetic single nucleotide polymorphisms (SNPs), the peripheral blood level of IL6, vitamin D and arterial blood gas (ABG) markers (pH, oxygen-SpO2 and carbon dioxide-SpCO2) on two groups, COVID-19 (n = 41, study), and the healthy (n = 43, control). We analyzed cytokine and interleukin genes in charge of both pro-inflammatory and immune-modulating responses and those genes that are considered involved in the COVID-19 progression and complications. Thus, we selected major genes, such as IL1β, IL1RN (IL-1 β and α receptor) IL6, IL6R (IL-6 receptor), IL10, IFNγ (interferon gamma), TNFα (tumor necrosis factor alpha), ACE2 (angiotensin converting enzyme), SERPINA3 (Alpha-1-Antiproteinase, Antitrypsin member of Serpin 3 family), VDR (vitamin D receptor Tak1, Bsm1 and Fok1), and CRP (c-reactive protein). Though more research is needed, these findings may give a better representation of virus pleiotropic activity and its relation to the immune system.

Background: Dystrophic Epidermolysis bullosa (DEB) is a rare inherited mechanobullous disease characterised by the hyperfragility of the skin and mucous membranes. It is (typically) caused by (loss-of-function) mutations in the COL7A1 gene that impair the formation of collagen type VII, which represents the major constituent of anchoring fibrils within the basement membrane zone of epithelialised tissues. In a 4-year-old patient diagnosed with the clinical features of recessive DEB, genotyping via Next-Generation EB Panel Sequencing initially revealed the homozygosity of the maternal c.425A>G mutation, while the paternal heterozygosity in exon 3 was lacking. This genetic profile suggested incongruent gene transmission due to uniparental isodisomy (UPD) or the occurrence of a hemizygous deletion of unknown size. Methods: Thus, the EB panel sequencing of genomic DNA, followed by a paternity test and analysis of microsatellite markers, as well as multiplex ligation-dependent probe amplification (MLPA) copy number analysis using patient and parental DNA, were performed. Results: This approach revealed a paternally derived hemizygous deletion spanning from exon 3 to exon 118. Linear amplification-mediated PCR (LAM-PCR) determined the breaking points within intron 2 of the COL7A1 gene, comprising a 40kb segment within intron 1 of the adjacent PFKFB4 gene. Conclusion: This report highlights the relevance of advanced molecular profiling to determine new/exceptional/unusual genotypes and the accurate mode of genetic transmission in DEB.

Background: Titanium (Ti) is one of the most popular implant materials, and its surface titanium dioxide (TiO2) provides good biocompatibility. The coagulation of blood on Ti implants plays a key role in wound healing and cell growth at the implant site; however, researchers have yet to fully elucidate the mechanism underlying this process on TiO2. Methods: This study examined the means by which blood coagulation was affected by the crystal structure of TiO2 thin films (thickness < 50 nm), including anatase, rutile, and mixed anatase/rutile. The films were characterized in terms of roughness using an atomic force microscope, thickness using an X-ray photoelectron spectrometer, and crystal structure using transmission electron microscopy. The surface energy and dielectric constant of the surface films were measured using a contact angle goniometer and the parallel plate method, respectively. Blood coagulation properties (including clotting time, factor XII contact activation, fibrinogen adsorption, fibrin attachment, and platelet adhesion) were then assessed on the various test specimens. Results: All of the TiO2 films were similar in terms of surface roughness, thickness, and surface energy (hydrophilicity); however, the presence of rutile structures was associated with a higher dielectric constant, which induced the activation of factor XII, the formation of fibrin network, and platelet adhesion. Conclusions: This study provides detailed information related to the effects of TiO2 crystal structures on blood coagulation properties on Ti implant surfaces.

Objective: Anti-CD20-treated patients are at risk of a reduced humoral immune response during the SARS-CoV-2 pandemic. Our aim was to compare the antibody response after two vaccinations with the mRNA vaccines BNT162b2 or mRNA-1273 in patients with multiple sclerosis. Methods: Data from the University Hospital of Bern and Cantonal Hospital of Lucerne were retrospectively collected from medical records and then analyzed. Anti-spike IgG serum titers were collected from both centers and were considered to be protective from a value of ≥100 AU/mL. Continuous variables were given as the mean and 95% confidence interval (95% CI); categorical variables were given as frequencies. A Mann–Whitney test and Fisher’s exact test as well as a multivariable linear regression analysis with anti-spike IgG (AU/mL) as the dependent variable were run using SPSS Statistic 25 (IBM Corp., Amonk, NY, USA). Results: A total of 74 patients were included; 41/74 (63.51%) were female patients and the mean age was 46.6 years (95% CI 43.4–49.9). Of these patients, 36/74 were vaccinated with BNT162b2 and 38/74 with mRNA-1273, following the national vaccination recommendation. In both vaccine groups, protective anti-spike IgG titers (≥100 AU/mL) were infrequently achieved (5/74: mRNA-1273 3/38; BNT162b2 2/36). Conclusions: In addition to a low rate of protective anti-spike IgG titers in both vaccine groups, we identified a drop in anti-spike IgG serum titers over time. This observation bears therapeutic consequences, as initial positive titers should be checked in case of an infection with the SARS-CoV-2 virus to identify patients who would benefit from an intravenous anti-spike IgG treatment against acute COVID-19.

For effective management of water quantity and quality, it is absolutely essential to estimate the pollution level of the existing surface water. This case study aims to evaluate the performance of twelve machine learning (ML) models, including five boosting-based algorithms (adaptive boosting, gradient boosting, histogram-based gradient boosting, light gradient boosting, and extreme gradient boosting), three decision tree-based algorithms (decision tree, extra trees, and random forest), and four ANN-based algorithms (multilayer perceptron, radial basis function, deep feed-forward neural network, and convolutional neural network), in estimating the surface water quality of the La Buong River in Vietnam. Water quality data at four monitoring stations alongside the La Buong River for the period 2010–2017 were utilized to calculate the water quality index (WQI). Prediction performance of the ML models was evaluated by using two efficiency statistics (i.e., R2 and RMSE). The results indicated that all twelve ML models have good performance in predicting the WQI but that extreme gradient boosting (XGBoost) has the best performance with the highest accuracy (R2 = 0.989 and RMSE = 0.107). The findings strengthen the argument that ML models, especially XGBoost, may be employed for WQI prediction with a high level of accuracy, which will further improve water quality management.

Giao co lam (Gynostemma pentaphyllum (Thunb.) Makino) is used in Northeast and Southeast Asia countries for the treatment of various diseases, including hepatitis, diabetes, and cardiovascular disease. G. pentaphyllum saponins (gypenosides) are the major components responsible for the pharmacological activities. In this study, different concentrations of abiotic (25–200 μM methyl jasmonate-MeJA and salicylic acid-SA) or biotic elicitors (1–5 g/L yeast extract-YE and Fusarium biomass) were used as plant elicitors, in order to investigate their influences on cell growth and gypenosides accumulation in G. pentaphyllum suspension cells. Suspension cells were grown on a MS medium containing 2.0 mg/L KIN and 0.5 mg/L IBA, with initial inoculum sizes of 3 g and shaking speeds of 120 rpm for 18 days. Gypenoside and Rb1 contents were measured by colorimetric and HPLC methods. Among three elicitors, SA was suitable for gypenosides accumulation in individual treatment. The cell biomass had the same values in elicitated and control suspension cells. Gypenosides content in cells treated with 100 μM salicylic acid after 6 days of culture reached a maximum value of 79.721 mg gypenoside/g dry biomass (including 0.093 mg ginsenoside Rb1/mg dry weight), which was 2.18-folds higher than that of the natural product. The elicitation promises an efficiency strategy for the production gypenosides in Gynostemma pentaphyllum suspension cells.

Vascular smooth muscle cell (VSMC) proliferation and migration play key roles in the progression of atherosclerosis and restenosis. A variety of ginsenosides exert various cardiovascular benefits. However, whether and how ginsenoside Rh1 (Rh1) inhibits VSMC dysfunction remain unclear. Here, we investigated the inhibitory effects of Rh1 on rat aortic smooth muscle cell (RASMC) migration and proliferation induced by angiotensin II (Ang II) and the underlying mechanisms. Cell proliferation and migration were evaluated using sulforhodamine B and wound-healing assay. The molecular mechanisms were investigated using Western blotting, quantitative reverse-transcription polymerase chain reaction analysis, immunofluorescence staining, and luciferase assay. Reactive oxygen species (ROS) production was measured using dihydroethidium and MitoSOX staining. We found that Rh1 dose-dependently suppressed Ang II-induced cell proliferation and migration. Concomitantly, Ang II increased protein levels of osteopontin, vimentin, MMP2, MMP9, PCNA, and cyclin D1, while these were reduced by Rh1 pretreatment. Notably, Ang II enhanced both the protein expression and promoter activity of KLF4, a key regulator of phenotypic switching, whereas pretreatment with Rh1 reversed these effects. Mechanistically, the effects of Rh1 on VSMC proliferation and migration were found to be associated with inhibition of ERK1/2/p90RSK signaling. Furthermore, the inhibitory effects of Rh1 were accompanied by inhibition of ROS production. In conclusion, Rh1 inhibited the Ang II-induced migration and proliferation of RASMCs by suppressing the ROS-mediated ERK1/2/p90RSK signaling pathway.

Work motivation plays a vital role in the development of organizations, as it increases employee productivity and effectiveness. To expand insights into individuals’ work motivation, the authors investigated the influence of individuals’ competence, autonomy, and social relatedness on their work motivation. Additionally, the country-level moderating factors of those individual-level associations were examined. Hierarchical linear modeling (HLM) was used to analyze data from 32,614 individuals from 25 countries, obtained from the World Values Survey (WVS). Findings showed that autonomy and social relatedness positively impacted work motivation, while competence negatively influenced work motivation. Moreover, the individual-level associations were moderated by the country-level religious affiliation, political participation, humane orientation, and in-group collectivism. Contributions, practical implications, and directions for further research were then discussed.

The growing concern for food safety and quality motivates governments and private sectors to improve consumers’ confidence in food systems, such as through adopting certifications and traceability systems. The recent emergence of diverse food labelling schemes and the turbulence in food systems in emerging countries have sparked questions about consumers’ valuation of such labels. Nonetheless, little is known on how the familiarity with, trust in and knowledge of these food labelling schemes affect consumers’ willingness to pay for labelling schemes in emerging market contexts. This study aims to address these literature gaps by investigating consumers’ valuation of existing certifications, branding and traceability labelling schemes in Vietnam. A face-to-face survey was conducted, including a discrete choice experiment on water spinach in Ho Chi Minh City, Vietnam. The findings indicated that Vietnamese consumers are generally willing to pay price premia for food labelling schemes, such as VietGAP certification, EU and USDA organic certifications, private branding and traceable Quick Response (QR) coding. While familiarity and understanding had no significant impact on Vietnamese consumers’ valuation, trust was found to be a critical factor shaping willingness to pay for products bearing VietGAP label. Policy implications and marketing strategies for organic certifications and traceability schemes in Vietnam are discussed.

Respiratory viral infections (RVIs) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients can be of concern due to the patients’ depressed immune status, but few data are available about the significance of a pre-transplant positive testing. In this retrospective observational study, we analyzed a cohort of patients that were transplanted between 1 January 2010 and 31 October 2019 in the Geneva University Hospitals with at least one RVI before or after transplantation. At least one RVI was detected in 319/533 (63.5%) transplanted patients. Rhinoviruses were most frequently identified (37%), followed by human coronaviruses (17.1%), parainfluenza viruses (13.9%), and influenza viruses (9.9%). First infection in the post-transplant period occurred at a mean time of 334 days (SD 338). Specific analysis of a subgroup of 65 patients with pre-transplant RVIs was performed. Among them, 39 (59%) patients had symptoms and 14 (21.2%) had a lower respiratory tract infection. Four patients (6.1%) (three rhinovirus and one influenza) needed an intensive care unit admission, of which, three (4.5%) (two rhinovirus and one influenza) were intubated. The patient with influenza infection diagnosed the day of the transplantation died within the first 30 days of the infection. Two patients with rhinovirus infection died within 3 months of unrelated causes. Our data show that rhinovirus infections are predominant in allo-HSCT patients, including among pre-transplant infections; however, mortality due to pre-transplant RVI is low and was only clearly identified in one patient with influenza infection. RVI within the month preceding allo-HSCT is not associated with direct morbidity or mortality in this cohort.

The requesting of detailed information on new drugs including drug-drug interactions or targets is often unavailable and resource-intensive in assessing adverse drug events. To shorten the common evaluation process of drug-drug interactions, we present a machine learning framework-HAINI to predict DDI types for histamine antagonist drugs using simplified molecular-input line-entry systems (SMILES) combined with interaction features based on CYP450 group as inputs. The data used in our research consisted of approved drugs of histamine antagonists that are connected to 26,344 DDI pairs from the DrugBank database. Various classification algorithms such as Naive Bayes, Decision Tree, Random Forest, Logistic Regression, and XGBoost were used with 5-fold cross-validation to approach a large-scale DDIs prediction among histamine antagonist drugs. The prediction performance shows that our model outperformed previously published works on DDI prediction with the best precision of 0.788, a recall of 0.921, and an F1-score of 0.838 among 19 given DDIs types. An important finding of the study is that our prediction is based solely on the SMILES and CYP450 and thus can be applied at the early stage of drug development.

Background: Oncological patients have a higher risk of prolonged SARS-CoV-2 shedding, which, in turn, can lead to evolutionary mutations and emergence of novel viral variants. The aim of this study was to analyze biological samples of a cohort of oncological patients by deep sequencing to detect any significant viral mutations. Methods: High-throughput sequencing was performed on selected samples from a SARS-CoV-2-positive oncological patient cohort. Analysis of variants and minority variants was performed using a validated bioinformatics pipeline. Results: Among 54 oncological patients, we analyzed 12 samples of 6 patients, either serial nasopharyngeal swab samples or samples from the upper and lower respiratory tracts, by high-throughput sequencing. We identified amino acid changes D614G and P4715L as well as mutations at nucleotide positions 241 and 3037 in all samples. There were no other significant mutations, but we observed intra-host evolution in some minority variants, mainly in the ORF1ab gene. There was no significant mutation identified in the spike region and no minority variants common to several hosts. Conclusions: There was no major and rapid evolution of viral strains in this oncological patient cohort, but there was minority variant evolution, reflecting a dynamic pattern of quasi-species replication.

Background: Based on recent findings, we speculated the existence of the lung, heart, and kidney axis as the main pathway for the COVID-19 disease progression. Methods: This paper reports on an observational study conducted by a team of researchers and doctors of the 118-Pre-Hospital and Emergency Department of SG Moscati of Taranto City in Italy. The study was conducted on a totality of 185 participants that were divided into three groups. The study group included COVID-19 affected patients (PP n = 80), the first control group included patients with different pathologies (non-COVID-19 NNp n = 62) of the SG Moscati Hospital, and the second control group included healthy individuals (NNh n = 43). The core of the current trial was focused on assessing the level of the vitamin D (serum 25(OH) D concentration), IL-6, and the renal glomerular filtrate (eGFR) in COVID-19 disease and non-COVID-19 patients in both groups. Results: It was observed that the majority of COVID-19-infected patients showed a progressive multi-organ involvement, especially in regard to the lung, kidney, and heart. The majority of the COVID-19 patients exhibited preexisting comorbidities which include cardiovascular, respiratory, and renal disorders accompanied by a severely low level of vitamin D, extremely high level of IL-6, and low glomerular filtration rate (eGFR). The significant overall damages exerted by the immune-mediated responses under the hyper-expression of proinflammatory cytokines and interleukins, such as IL-6, may be facilitated by either a decreased level of vitamin D or the ageing process. The reduced presence of vitamin D was often found together with a reduced functionality of renal activity, as revealed by the low eGFR, and both were seen to be concomitant with an increased mortality risk in patients with lung disorders and heart failure (HF), whether it is showed at baseline or it develops during manifestation of COVID-19. Therefore, the documentation of the modifiable risk factors related to SARS-CoV-2 and lung impairment in older patients with kidney and heart disease may help the clinician to better manage the situation. Conclusions: This paper addresses how a low level of vitamin D and older age may be indicative of systemic worsening in patients with COVID-19, with a goal of providing a broader context in which to view a better therapeutic approach.

Breast cancer (BC) a very common cancer in women worldwide. Triple negative breast cancer (TNBC) has been shown to have a poor prognosis with a high level of tumor metastatic spread. Here, the inhibitory effects of ginsenoside-Rh1 (Rh1) on BC metastasis, and its underlying signaling pathway in TNBC were investigated. Rh1-treated MDA-MB-231 cells were analyzed for metastasis using a wound healing assay, transwell migration and invasion assay, western blotting, and qRT-PCR. Rh1 treatment significantly inhibited BC metastasis by inhibiting the both protein and mRNA levels of MMP2, MMP9, and VEGF-A. Further, Rh1-mediated inhibitory effect on BC migration was associated with mitochondrial ROS generation. Rh1 treatment significantly eliminated STAT3 phosphorylation and NF-κB transactivation to downregulate metastatic factors, such as MMP2, MMP9, and VEGF-A. In addition, Mito-TEMPO treatment reversed Rh1 effects on the activation of STAT3, NF-κB, and their transcriptional targets. Rh1 further enhanced the inhibitory effects of STAT3 or NF-κB specific inhibitor, stattic or BAY 11-7082 on MMP2, MMP9, and VEGF-A expression, respectively. In summary, our results revealed the potent anticancer effect of Rh1 on TNBC migration and invasion through mtROS-mediated inhibition of STAT3 and NF-κB signaling.

Background: A novel coronavirus (SARS-CoV-2)-induced pneumonia (COVID-19) emerged in December 2019 in China, spreading worldwide. The aim of the present investigation was to evaluate the immunological response and the clinical subset of peripheral lymphocyte subset alteration in COVID-19 infection. Methods: the study was conducted on four different clinical groups (n = 4; total n = 138). Each individual was assigned to different groups based on specific criteria evaluated at the admission such as fever, dyspnea, arterial blood gas analysis (ABG), oral-nasopharyngeal swab/RT-PCR, and thoracic CT-scan. Treatment was performed only after blood samples were collected from each patient (PP and PP) at day 1. The blood samples were analyzed and tested the same day (CBC and Flowcytometry). The positive–positive group (PP n = 45; F = 18/ M = 27; median age = 62.33), comprised individuals affected by COVID-19 who showed fever, dyspnea (ABG = pO2 < 60), confirmed positive by oral-nasopharyngeal swab/RT-PCR and with CT-scan showing ground-glass opacities. The negative–positive (NP; n = 37; F = 11/M = 26; median age = 75.94) or “COVID-like” group comprised individuals with fever and dyspnea (ABG = pO2 < 60), who tested negative to nasopharyngeal swab/RT-PCR, with CT-scans showing ground-glass opacities in the lungs. The negative–affected group (NA; n = 40; F = 14/M = 26; median age = 58.5) included individuals negative to COVID-19 (RT-PCR) but affected by different chronic respiratory diseases (the CT-scans didn’t show ground-glass opacities). Finally, the negative–negative group (NN; n = 16; F = 14/M = 2) included healthy patients (NN; n = 16; median age = 42.62). Data and findings were collected and compared. Results: Lymphocytes (%) cells showed a decline in COVID-19 patients. The subsets showed a significant association with the inflammatory status in COVID-19, especially with regard to increased neutrophils, T-killer, T-active, T-suppressor, and T-CD8+CD38+ in individuals belong to the either COVID-19 and Covid-like NP group. Conclusions: Peripheral lymphocyte subset alteration was associated with the clinical characteristics and progression of COVID-19. The level of sub-set cells T-lymphocytes (either high or low) and B-lymphocytes could be used as an independent predictor for COVID-19 severity and treatment efficacy.

Our objective in this study was to promote the growth of bone cells on biomedical titanium (Ti) implant surfaces via surface modification involving sandblasting, alkaline etching, and type I collagen immobilization using the natural cross-linker genipin. The resulting surface was characterized in terms topography, roughness, wettability, and functional groups, respectively using field emission scanning electron microscopy, 3D profilometry, and attenuated total reflection-Fourier transform infrared spectroscopy. We then evaluated the adhesion, proliferation, initial differentiation, and mineralization of human bone marrow mesenchymal stem cells (hMSCs). Results show that sandblasting treatment greatly enhanced surface roughness to promote cell adhesion and proliferation and that the immobilization of type I collagen using genipin enhanced initial cell differentiation as well as mineralization in the extracellular matrix of hMSCs. Interestingly, the nano/submicro-scale pore network and/or hydrophilic features on sandblasted rough Ti surfaces were insufficient to promote cell growth. However, the combination of all proposed surface treatments produced ideal surface characteristics suited to Ti implant applications.

To date, several cases of thrombosis have been confirmed to be related to Sars-CoV-2 infection. Multiple attempts detected the prolonged occurrence of Sars-CoV-2 viral RNA (long COVID) in whole blood suggesting that virus byproducts may remain within cells and tissues well over the disease has finished. Patients may develop severe thrombocytopenia, acute anemia of inflammation and, systemic thrombosis with the fatal course of disease, which is suggestive of further interferences of Sars-CoV-2 on hematopoietic stem cells (HSCs) within the differentiation process towards erythroid and megakaryocytic cells. Therefore, we speculated whether Sars-CoV-2 propagates in or compartmentalizes with hematopoietic progenitor, erythroid, and megakaryocytic cells as the main cause of thrombotic events in either COVID-19 patients or vaccinated individuals. Results: The Sars-CoV-2 RNA replication, protein translation and infectious particle formation as the spike proteins in hematopoietic cell lines take place via the angiotensin-converting enzyme 2 (ACE2) entry pathway within primary CD34+ HSCs inducing, ex vivo, the formation of defected erythroid and megakaryocytic cells that eventually become targets of humoral and adaptive immune cells. Conclusions: Viral particles from affected CD34+ HSCs or the cellular component of RBC units and eventually platelets, present the greatest risk for sever thrombosis-transmitted Sars-CoV-2 infections.