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The synthesis and evaluation of silica sol-gels doped with cobalt hexacyanoferrate (CoHCF) for solid phase extraction of Cs+ from aqueous solution is described. The CoHCF is formed by first introducing K4Fe(CN)6 (HCF) into the sol-gel and subsequently contacting the porous solid to a solution containing Co2+. Generally, sols contain alcohol as a co-solvent, which limits the solubility of HCF. Inclusion of generation-4 polyamidoamine (G4-PAMAM) dendrimer in the sol-gel increases the level of HCF and, in turn, the CoHCF. The uptake capacity of this composite was 0.43±0.01 mmol Cs+ g-1. A second approach to increasing the level of HCF silica is to exclude alcohol from the sol and use ultrasound to obtain a homogeneous suspension; HCF concentrations up to 0.17 M in the sol were thereby achieved. After gelation and reaction with Co2+, the resulting composite had a capacity of 0.61±0.01 mmol Cs+ g-1. With 0.5 mM Cs+ as the sample, the presence of either 0.5–100 mM Na+ or 10 mM Ca2+ did not change that value at the 95% confidence level. [ABSTRACT FROM AUTHOR]

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In this work, a Dielectrically Modulated Junctionless Rectangular Gate All Around Field Effect Transistor (DM-JLRGAA-FET) is demonstrated and explored for label free detection of neutral biomolecules. In comparison to its conventional architectures, proposed biosensor exhibits a significantly improved sensing and conjugation performance due to its remarkable structure, which enhances its performance by providing substantial rejection to SCEs (short channel effects) and strengthened gate control over channel electrostatics. Drain current sensitivity, surface potential, transconductance and output conductance are employed to determine the sensing competence of the proposed biosensor. The proposed biosensor offers maximum drain current sensitivity of 8.09 for keratin biomolecule. The detection will become quite difficult during conjugation of two or more biomolecules. The conjugation analysis is also investigated by effective dielectric constant approach governed by Bruggeman's Model. The conjugations of Streptavidin-Keratin and Streptavidin-Zein is studied for various concentration in the cavity. Conjugations of Streptavidin and Keratin shows the highest sensitivity of 18.5%. The sensing performance of proposed biosensor is optimized for schottky source/drain contacts engineering and also for channel material engineering. [ABSTRACT FROM AUTHOR]

Objective: In this retrospective and cross-sectional study, it was aimed to evaluate the efficacy of tocilizumab (TCZ) treatment in critical COVID-19 patients who were hospitalized in the intensive care unit (ICU) and developed cytokine storm. Materials and Methods: The study included 219 critically ill COVID-19 patients followed in the ICU and treated with TCZ. All patients received 2 doses of 400 mg/day TCZ treatment during their stay in the ICU. Clinical conditions, laboratory data, inotrope requirement and chest radiographs before and after TCZ treatment were compared. Mortality rates at the 7th day, 28th day and total mortality rates of the patients were recorded. Results: It was observed that there was a significant decrease in CRP values over time after TCZ treatment. There was a significant increase in leukocyte, lymphocyte, lactate, urea, creatinine, AST, D-dimer, LDH and PCT values. The 7-day mortality of the patients was 21%, the 28-day mortality was 64.8%, and the total mortality rate was 65.3%. Conclusion: It was determined that after TCZ treatment, only CRP levels, which are among the inflammatory parameters, decreased significantly in patients, and the mortality rates were still high with the increase in the values of kidney and liver function tests of the patients. [ABSTRACT FROM AUTHOR]

We report a case of persistent disseminated mpox evolving over >6 months in an HIV/hepatitis B virus co-infected patient in France who had <200 CD4+ cells/mm3, pulmonary and hepatic necrotic lesions, persistent viremia, and nasopharyngeal excretion. Clinical outcome was favorable after 90 days of tecovirimat treatment and administration of human vaccinia immunoglobulins. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal infection (IFI) prophylaxis is recommended in patients with acute myeloid leukemia (AML) during induction chemotherapy. Posaconazole (POSA) is the recommended agent of choice; however, this medication can be associated with QTc prolongation, hepatotoxicity, and drug-drug interactions. Furthermore, there is conflicting evidence for the role of isavuconazole (ISAV) in this setting as an alternative to POSA. Objective: The primary objective of this study was to evaluate the use of ISAV prophylaxis for primary IFI prevention in patients with AML undergoing induction. Additionally, the study investigated the use of ISAV trough concentration monitoring and compared these results to the efficacy of POSA therapeutic drug monitoring (TDM). Other secondary objectives included assessing the rates of toxicities associated with either prophylactic agent. This study analyzed the impact these toxicities had on patient outcomes by examining the need to hold or discontinue therapy. The final endpoint considered the efficacy associated with multiple dosing strategies employed at the study institution. Specifically, this included the use of loading doses or foregoing these when initiating prophylaxis. Methods: This was a retrospective, single-center, cohort study. Patients included in this study were adults with AML admitted to Duke University Hospital between June 30, 2016 and June 30, 2021, who received induction chemotherapy and primary IFI prophylaxis for at least 7 days. Exclusion criteria included patients who received concomitant antifungal agents and patients who received antifungal agents as secondary prophylaxis. Results: 241 patients met inclusion criteria with 12 (4.98%) participants in the ISAV group and 229 (95.02%) participants in the POSA group. The IFI incidence in the POSA group was 14.5%, while the ISAV group did not have any occurrences of IFI. No significant difference was found in the rate of IFI occurrence between the two treatment groups (p = 0.3805). Furthermore, it was demonstrated that the use of a loading dose when initiating prophylaxis could impact rates of IFI for this patient population. Conclusion: Due to no difference in incidence, patient specific factors such as concomitant medications and baseline QTc should influence the choice between prophylactic agent. [ABSTRACT FROM AUTHOR]

Mean circulatory filling pressure, venous return curve, and Guyton's graphical analysis are basic concepts in cardiovascular physiology. However, some medical students may not know how to view and interpret or understand them adequately. To deepen students' understanding of the graphical analysis, in place of having to perform live animal experiments, we developed an interactive cardiovascular simulator, as a self-learning tool, as a web application. The minimum closed-loop model consisted of a ventricle, an artery, resistance, and a vein, excluding venous resistance. The simulator consists of three modules: setting (parameters and simulation modes), calculation, and presentation. In the setting module, the user can interactively customize model parameters, compliances, resistance, Emax of the ventricular contractility, total blood volume, and unstressed volume. The hemodynamics are calculated in three phases: filling (late diastole), ejection (systole), and flow (early diastole). In response to the user's settings, the simulator graphically presents the hemodynamics: the pressure–volume relations of the artery, vein, and ventricle, the venous return curves, and the stroke volume curves. The mean filling pressure is calculated at approximately 7 mmHg at the initial setting. The venous return curves, linear and concave, are dependent on the venous compliance. The hemodynamic equilibrium point is marked on the crossing point of venous return curve and the stroke volume curve. Users can interactively do discovery learning, and try and confirm their interests and get their questions answered about hemodynamic concepts by using the simulator. [ABSTRACT FROM AUTHOR]

Purpose of Review: The global outbreak of mpox has brought renewed attention to a previously neglected disease which is particularly severe in people with underlying untreated HIV co-infection. For this population, the disease is progressive, severe, and often lethal. In this review, we examine the pathogenesis of mpox disease and its collision with co-existent HIV infection and discuss key considerations for management as well as emerging clinical dilemmas and areas for future research. Recent Findings: Co-existent untreated HIV infection characterized by severe immunocompromise potentiates the nefarious effects of monkeypox virus infection leading to severe manifestations of mpox. Treating mpox in the context of HIV requires mpox-directed therapies, supportive care, and HIV-specific treatment to restore immune function. Preventative measures for PWH are like those in healthy individuals, but the effectiveness and durability of protection conferred by existing vaccines in PWH remain to be fully characterized. Summary: Mpox is an important opportunistic infection in PWH. Clinicians should be aware of the unique features of the disease in this population and approaches to care and management of mpox in PWH. [ABSTRACT FROM AUTHOR]

Background: Isavuconazole (ISA) is a newer antifungal used in patients with history of hematologic malignancies and hematopoietic transplant and cellular therapies (HM/TCT). Although it has a more favorable side‐effect profile, breakthrough invasive fungal infections (bIFIs) while on ISA have been reported. Methods: In this single‐center retrospective study evaluating HM/TCT patients who received prophylactic ISA for ≥7 days, we evaluated the incidence and potential risk factors for bIFIs. Results: We evaluated 106 patients who received prophylactic ISA. The patients were predominantly male (60.4%) with median age of 65 (range: 21–91) years. Acute myeloid leukemia (48/106, 45.3%) was the most common HM, with majority having relapsed and/or refractory disease (43/106, 40.6%) or receiving ongoing therapy (38/106, 35.8%). Nineteen patients (17.9%) developed bIFIs–nine proven [Fusarium (3), Candida (2), Mucorales plus Aspergillus (2), Mucorales (1), Colletotrichum (1)], four probable invasive pulmonary Aspergillus, and six possible infections. Twelve patients were neutropenic for a median of 28 (8–253) days prior to bIFI diagnosis. ISA levels checked within 7 days of bIFI diagnosis (median: 3.65 μg/mL) were comparable to industry‐sponsored clinical trials. All‐cause mortality among the bIFI cases was 47.4% (9/19).We also noted clinically significant cytomegalovirus co‐infection in 5.3% (1/19). On univariate analysis, there were no significant differences in baseline comorbidities and potential risk factors between the two groups. Conclusion: ISA prophylaxis was associated with a significant cumulative incidence of bIFIs. Despite the appealing side‐effect and drug‐interaction profile of ISA, clinicians must be vigilant about the potential risk for bIFIs. [ABSTRACT FROM AUTHOR]

Background We investigated the therapeutic response of tocilizumab (TCZ) therapy in patients with coronavirus disease 2019 (COVID-19) pneumonia. Methods This observational retrospective study included 205 patients with confirmed COVID-19 pneumonia with SpO2˂93% and a markedly increased level of at least two biomarkers of inflammation. The TCZ was given in combination with corticosteroids. Clinical and laboratory results were analyzed and compared before TCZ therapy and 7 d after. Results The mean value of C-reactive protein (CRP) was significantly lower (p=0.001) on the seventh day after administration of TCZ compared with before (10.7 and 173.6 mg/L, respectively). Only in 9/205 (4.3%) patients, the CRP level did not decrease during the week-long period, and this was related to disease progression. The mean level of interleukin-6 before TCZ administration was 88±113 pg/mL, while after it was 32.7±21.7 pg/mL (p=0.01). After 7 d of TCZ therapy, almost 50% of patients who needed high-flow oxygen or ventilation support started to receive low-flow oxygen, while 73/205 (35.6%) patients who received low-flow oxygen before TCZ administration did not receive further oxygen support anymore (p=0.001). Although they received TCZ treatment, 38/205 (18.5%) severely sick patients died. Conclusions Tocilizumab improves clinical outcomes in hospitalized COVID-19 patients. These advantages were evident independent of the patient's comorbidities and were in addition to the advantages of systemic corticosteroids. In COVID-19 patients at risk of cytokine storms, TCZ appears to be an effective therapy choice. [ABSTRACT FROM AUTHOR]

Since May 2022, there have been nearly 87,000 documented cases of mpox worldwide, with 119 deaths. Pharmacological interventions for mpox include the MVA-BN smallpox vaccine, tecovirimat, cidofovir, its pro-drug brincidofovir, and vaccinia immune globulin intravenous (VIGIV). The literature search and information gathering for this review included the PubMed database focusing on mpox and monkeypox, in combination with tecovirimat, brincidofovir, cidofovir, VIGIV, and smallpox vaccine. WHO.int, CDC.gov, FDA.gov, and ClinicalTrials.gov websites were accessed for the most recent information on the mpox outbreak. Mechanisms for deployment and access to treatment including expanded access, emergency use, and clinical trials will be discussed. Treatment outcomes with safety data will be presented. The vaccine as a preventive measure, along with numerous treatment options, largely controlled the outbreak, although deployment of each could be improved upon to hasten and broaden access. More widespread coverage by the vaccine is necessary to prevent future resurgence of mpox. Tecovirimat has emerged as a safe frontline treatment for mpox, while brincidofovir use has been limited by safety concerns. VIGIV and cidofovir should be reserved for the most severe cases in which other options are not fully effective. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal infections (IFIs) are a common infectious complication during the treatment of acute myeloid leukemia (AML), high‐risk myelodysplastic syndrome (MDS) or post hematopoietic cell transplantation (HCT). For these patients, the National Comprehensive Cancer Network recommends posaconazole or voriconazole for IFI prophylaxis. In clinical practice, however, there has been increased use of isavuconazole due to favorable pharmacokinetic and pharmacodynamic parameters despite limited data for this indication. The comparative prophylactic efficacy of antifungals in this patient population has not been reported, and an analysis is warranted. Methods: This retrospective, matched cohort, single‐center study, included AML, MDS, or HCT patients who began treatment or underwent transplant between January 1, 2015 and July 31, 2021. Isavuconazole patients were matched 1:2 with patients receiving posaconazole or voriconazole prophylaxis. Results: A total of 126 patients were included, 42 received isavuconazole, 81 received posaconazole, and three received voriconazole. The majority of patients were male receiving secondary IFI prophylaxis while receiving steroids for treatment of GVHD. The incidence of possible, probable or proven IFI was 16.7% in the isavuconazole group compared to 10.7% in the posaconazole and voriconazole group (OR 1.28, 95% CI −0.9–1.4; p =.67). Hepatotoxicity occurred in 16 total patients, 14 receiving posaconazole and two receiving isavuconazole. Conclusion: Patients who received isavuconazole prophylaxis during AML induction therapy or post‐HCT experienced a similar incidence of breakthrough fungal infections compared to those who received posaconazole or voriconazole. These results suggest no difference in antifungal prophylactic efficacy; however larger prospective comparative studies are needed. [ABSTRACT FROM AUTHOR]

If a noncommutative polynomial f is neither an identity nor a central polynomial of A = M n (ℂ) , then every trace zero matrix in A can be written as a sum of two matrices from f (A) − f (A) . Moreover, "two" cannot be replaced by "one". [ABSTRACT FROM AUTHOR]

Background and aims – Forests are among the most threatened ecosystems worldwide, and endemic plants are often a vulnerable component of the flora of a given territory. So far, however, understory forest endemics of southern Europe have received little attention and are poorly known for several aspects. Material and methods – We developed the first list of native vascular plants that are restricted to Italian forests. Available information on taxonomy, regional distribution, ecology, biology, functional traits, and conservation status was collected for each taxon, allowing to identify major knowledge gaps and calculate baseline statistics. Key results – The list includes 134 taxa, most of which are linked to closed-canopy forest habitats, while the others are also found in margins and gaps. The forest and non-forest Italian endemic flora differed in terms of taxonomic and life-form distribution. The rate and density of forest endemism increased with decreasing latitude and were highest in Sicily, Calabria, and Basilicata, where paleoendemic mono- or oligotypic genera also occur. Endemic phanerophytes were especially numerous on islands. Beech and deciduous oak forests were the most important habitats, but hygrophilous woodlands also host numerous endemics. Overall, the ecology, biology, and functional traits of the forest endemic taxa are still poorly known. The ratio diploids/polyploids was highest in the south and on the islands. Almost 24% of the taxa were assessed as “Critically Endangered”, “Endangered”, or “Vulnerable”, and 24% were categorized as “Data Deficient”, based on the IUCN system. Increasing frequency and intensity of fires was the most frequent threat. Conclusions – This work can contribute to implement the European forest plant species list and serve as a basis for further research on a unique biological heritage of the continent. However, more knowledge about these globally rare taxa is needed, to support their conservation in changing forest landscapes. [ABSTRACT FROM AUTHOR]

Vitrimer epoxy, capable of stress‐relaxation, has gathered attention for its ability to counter the brittleness and rigidity of thermosets. However, to date, only two strategies are proposed to address the high enthalpic barrier of a dynamic exchange reaction using high dosages of external catalysts or niche moieties as internal catalysts. Herein, solvate ionic liquids (SILs) are incorporated into commercial epoxy‐based vinylogous urethane (VU) vitrimers. During curing, the SILs facilitate epoxy ring‐opening and amine‐addition reactions, significantly reducing gel times. Furthermore, after network formation, the SILs accelerate transamination reaction within the VU networks at a dosage of only 0.5–2 mol%. This can be attributed to their high miscibilities and Lewis acidic characters, which significantly reduce the activation energy of transamination (24 kJ mol−1) in the SIL‐incorporated vitrimer. Thus, a high‐performing vitrimer epoxy is prepared, featuring a glassy modulus (>109 Pa) at room temperature and an extremely short stress‐relaxation time (≈19 s) at 160 °C. Moreover, a soft encapsulation approach is demonstrated using the vitrimer epoxy, proving the possibility of a simultaneous deformable (bent) encapsulation, reduced warpage of a flexible printed circuit board, and selective removal of encapsulants. [ABSTRACT FROM AUTHOR]

Patients with haematologic malignancies are at high risk of developing invasive fungal infections (IFIs). Current guidelines recommend the use of azoles for IFI prophylaxis; however, in many clinical situations, antifungal prophylaxis is used off-label. We conducted a systematic literature review to provide haematologists with the available evidence on the effectiveness and safety of isavuconazole in IFI prophylaxis in interventional and real-world, observational studies. Embase, MEDLINE and Cochrane Library databases, and relevant conference proceedings and clinical trial registries, were searched for studies on the effectiveness and safety of isavuconazole prophylaxis in adults at high risk of IFIs. Studies were assessed for inclusion and risk of bias. Nine studies were eligible for inclusion in the review, eight of which were in haematologic populations (patients undergoing haematopoietic stem cell transplantation or with acute myeloid leukaemia or myelodysplastic syndromes; n = 5) or included haematologic populations (n = 3). Evidence from these studies suggests isavuconazole is effective for IFI prophylaxis in the haematologic setting. However, the studies frequently lacked safety data, most were based on small patient populations from single centres and risk of bias could not be assessed for five studies. These findings provide evidence for isavuconazole as an alternative azole for prophylaxis in high-risk populations. Limitations include lack of applicability of risk of bias assessment tools, level of filtering applied in the search strategy and focus on English-language publications. Isavuconazole may be an effective azole for IFI prophylaxis in high-risk haematologic populations, although further studies are needed. [ABSTRACT FROM AUTHOR]

The epidemic of infectious diseases caused by contagious pathogens is a life-threatening hazard to the entire human population worldwide. A timely and accurate diagnosis is the critical link in the fight against infectious diseases. Aptamer-based biosensors, the so-called aptasensors, employ nucleic acid aptamers as bio-receptors for the recognition of target pathogens of interest. This review focuses on the design strategies as well as state-of-the-art technologies of aptasensor-based diagnostics for infectious pathogens (mainly bacteria and viruses), covering the utilization of three major signal transducers, the employment of aptamers as recognition moieties, the construction of versatile biosensing platforms (mostly micro and nanomaterial-based), innovated reporting mechanisms, and signal enhancement approaches. Advanced point-of-care testing (POCT) for infectious disease diagnostics are also discussed highlighting some representative ready-to-use devices to address the urgent needs of currently prevalent coronavirus disease 2019 (COVID-19). Pressing issues in aptamer-based technology and some future perspectives of aptasensors are provided for the implementation of aptasensor-based diagnostics into practical application. [ABSTRACT FROM AUTHOR]

This paper presents a dual gate dielectric modulated FET (DGDMFET) biosensor with enhanced sensitivity for covid detection. In earlier literature, the biosensors are operated using the surface interaction with the virus biomolecules that are reflected through a channel or gate. The downside of these types of sensors has limited sensitivity. In this paper, we have considered that the change in the dielectric constant due to virus proteins results in a significant shift in the threshold voltage of FET. Enhancement of sensitivity is done by using the novel dual metal gate arrangement with different work functions (higher at the source end and lower at the drain end) and the chromic oxide (Cr2O3) layer, which is carved out vertically to form nanogap. At the same time, interface charge density is maintained nearly equal to 1.0 × 1011 cm−2 at the Si-SiO2 layer. To demonstrate the proposed biosensor, electrical parameters (electron concentration, surface potential, energy band distribution, and electric field) and the absolute percentage sensitivity of threshold voltage, subthreshold slope, ON current, and transconductance are evaluated and compared with related literature. The ATLAS device simulator is used for the simulation of the proposed device. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) infection is one of the leading causes of death in the world. According to WHO reports 2019, the average rate of decrease in global TB incidences was only 1.6% per year from 2000 to 2018, besides that the global decline in TB deaths was just 11%. Therefore, the dire need for early detection of the pathogen for the successful diagnosis of TB seems justified. Mycobacterium tuberculosis secretory proteins have gained more attention as TB biomarkers, for the early diagnosis and treatment of TB. Here in this review, we elaborate on the recent advancements made in the field of piezoelectric, magnetic, optical, and electrochemical biosensors, in addition to listing their merits and setbacks. Additionally, this review also discusses the construction of biosensors through modern integrated technologies, such as combinations of analytical chemistry, molecular biology, and nanotechnology. Integrated technologies enhance the detection for perceiving highly selective, specific, and sensitive signals to detect M. tuberculosis. Furthermore, this review highlights the recent challenges and scope of improvement in numerous biosensors developed for rapid, specific, selective, and sensitive detection of tuberculosis to reduce the TB burden and successful treatment. [ABSTRACT FROM AUTHOR]

Summary: Bolt connection is mostly used to transfer the load between the mechanical components and plays a significant role in fixing and connecting the parts, especially in complex engineering structures. About 20% of mechanical system failure cases are related to bolt looseness; hence, timely bolt condition detection and maintenance can extend the working life of the mechanical system. To this purpose, current research proposes an integrated approach that significantly simplifies the test system in the conventional method and facilitates the online monitoring of bolted state, especially for small size and compact measured components. Using the proposed integrated acoustic‐vibration frequency‐modulation (FM) method, the signal characteristics are analyzed in the frequency domain to find out the frequency components associated with bolt looseness. Further, the proposed method is also experimentally verified by applying it to examine the specimen containing fatigue cracks, and the damage characteristics are obtained without a reference signal. In this framework, the proposed method is found to be more convenient and flexible than the traditional FM technology in the application of contact nonlinear condition monitoring. [ABSTRACT FROM AUTHOR]

Erroneous immune responses in COVID-19 could have detrimental effects, which makes investigation of immune network underlying COVID-19 pathogenesis a requisite. This study aimed to investigate COVID-19 related alterations within the frame of innate and adaptive immunity. Thirty-four patients clinically diagnosed with mild, moderate and severe COVID-19 disease were enrolled in this study. Decreased ILC1 and increased ILC2 subsets were detected in mild and moderate patients compared to healthy controls. NK cell subsets and cytotoxic capacity of NK cells were decreased in severe patients. Moreover, CD3+ T cells were reduced in severe patients and a negative correlation was found between CD3+ T cells and D-dimer levels. Likewise, moderate and severe patients showed diminished CD3+CD8+ T cells. Unlike T and NK cells, plasmablast and plasma cells were elevated in patients and IgG and IgA levels were particularly increased in severe patients. Severe patients also showed elevated serum levels of pro-inflammatory cytokines such as TNF-a, IL-6 and IL-8, reduced intracellular IFN-g and increased intracellular IL-10 levels. Our findings emphasize that SARS-CoV-2 infection significantly alters immune responses and innate and acquired immunity are differentially modulated in line with the clinical severity of the disease. Elevation of IL-10 levels in NK cells and reduction of CD3+ and CD8+ T cells in severe patients might be considered as a protective response against the harmful effect of cytokine storm seen in COVID-19. [ABSTRACT FROM AUTHOR]

Systemic hyperinflammation is a hallmark of severe coronavirus disease-2019 (COVID-19). Tocilizumab (TCZ) (an interleukin-6 receptor blocker) therapy is currently used as an anti-inflammatory intervention alongside corticosteroids to modulate the hyperinflammatory response (cytokine storm) in hospitalized patients with severe COVID-19 to prevent mortality. There is, however, a wide uncertainty about its pros and cons in patients with COVID-19, particularly, its possible immunosuppressive effect is of serious concern for the clinicians. The present study aimed to report response of a cohort of severely-ill hospitalized COVID-19 pneumonia patients who were treated with tocilizumab after the initial corticosteroids therapy failed to improve the patients' clinical condition. This was a single-arm retrospective study of 100 severely-ill COVID-19 pneumonia patients who were admitted to the specialized COVID-19 units of Mayo Hospital, Lahore, Pakistan from March 12, 2020, to May 25, 2021. These COVID-19 patients had progressed to cytokine storm with persistent hypoxia, associated with pneumonia, and markedly elevated serum levels of inflammatory biomarkers including C-reactive protein (CRP), D-dimer, and ferritin. All the patients had received two separate doses of intravenous 400 mg (4 mg/kg) tocilizumab with an 8-hour interval alongside standard COVID-19 care which includes corticosteroid, antibiotics, and anticoagulants. Following tocilizumab intervention, 75 (75.0%) patients showed clinical improvement, continued to recover, and were safely discharged from the hospital, while in 25 (25.0%) patients, TCZ failed to prevent clinical deterioration, and patients eventually died in the hospital. Amongst the 25 (25.0%) deaths, 8 (32.0%) patients had a single comorbidity, while 9 (36.0%) had two or more comorbidities. The median IQR age for survivors was 57.0 (50.0, 60.0) years, and non-survivors was 60.0 (55.0, 70.0) years; and the period of hospitalization was 25 (20, 40) days and 20 (14, 34) days, respectively. Tocilizumab treatment improved serum inflammatory biomarker levels including CRP, D-dimer, and ferritin, by almost a similar magnitude in both survivors and non-survivors. Development of secondary infections were reported in 25 (25.0%) patients, including 21% patients with bacterial (Pseudomonas, Klebsiella, Acinetobacter) and 4% with fungal (Aspergillus) infection. The emergence of secondary infection was higher in patients who died (72.0%) as compared to those who survived (28.0%). In conclusion: in lowand middle-income countries in the presence of limited therapeutic options, a timely intervention of TCZ alongside corticosteroids may be a suitable anti-inflammatory therapy for severely-ill hospitalized COVID-19 pneumonia patients to prevent mortality. However, patients must be closely monitored for secondary bacterial/fungal infections. Early diagnosis and management of secondary infection can reduce morbidity and mortality. [ABSTRACT FROM AUTHOR]

The risks for invasive fungal infection (IFI) are enhanced by cytotoxic therapy-induced prolonged severe neutropenia, intestinal mucosal damage, and B- and T-cell immune suppression in patients receiving intensive therapy for acute myeloid leukemia (AML) or myelodysplasia (MDS) or hematopoietic stem cell transplantation (HSCT). Comparison of mold active triazoles as primary antifungal prophylaxis in patients with newly diagnosed acute myeloid leukemia in the era of molecularly targeted therapies. [Extracted from the article]

Exosomes are highly important in clinical diagnosis due to their high homology with their parental cells. However, conventional exosome detection methods still face the challenges of expensive equipment, low sensitivity, and complex procedures. Field effect transistors (FETs) are not only the most essential electronic component in the modern microelectronics industry but also show great potential for biomolecule detection owing to the advantages of rapid response, high sensitivity, and label-free detection. In this study, we proposed a Si nanowire field-effect transistor (Si-NW Bio-FET) device chemically modified with specific antibodies for the electrical and label-free detection of exosomes. The Si-NW FETs were fabricated by standard microelectronic processes with 45 nm width nanowires and packaged in a polydimethylsiloxane (PDMS) microfluidic channel. The nanowires were further modified with the specific CD63 antibody to form a Si-NW Bio-FET. The use of the developed Si-NW Bio-FET for the electrical and label-free detection of exosomes was successfully demonstrated with a limit of detection (LOD) of 2159 particles/mL. In contrast to other technologies, in this study, Si-NW Bio-FET provides a unique strategy for directly quantifying and real-time detecting exosomes without labeling, indicating its potential as a tool for the early diagnosis of cancer. [ABSTRACT FROM AUTHOR]

Background: There is currently much uncertainty regarding the most optimal treatment for COVID-19. This study analyze the change in the clinical condition of patients hospitalized for severe COVID-19 pneumonia and treated with remdesivir in a real-life setting, based on the WHO Ordinal Scale. Clinical complications, treatment safety, and impact of other associated drugs were also analyzed. Methods: We conducted an observational, retrospective study including patients treated with remdesivir. The need for admission to the ICU, the length of ICU and hospital stay, and the need for ventilatory support were analyzed. The laboratory parameters, drugs administered concomitantly, and difference in the length of hospital stay according to the concomitant treatment received were also evaluated. A univariate and multivariate Cox regression analysis was performed to analyze associated factors. Results: A total of 92 patients were included. The mean length of hospital stay was 15 days, and 90% of the patients had been discharged from the hospital 28 days after starting treatment with remdesivir. The likelihood of hospital discharge among patients not presenting with hypertension as a comorbidity was significantly higher than that of those with this condition (HR = 3.19, P = 0.008). Nineteen patients had to be admitted to the ICU (mean of 18 days). Approximately 11% required invasive mechanical ventilation (mean of 22 days). Almost 37% of the patients received high-flow oxygen therapy and 14% non-invasive mechanical ventilation. Four deaths were recorded within the first week. Main adverse events were increases in transaminase and creatinine levels. Nosocomial infections were more frequent when remdesivir was combined with immunosuppressive drugs. Conclusions: Patients with severe COVID-19 pneumonia and treated with remdesivir require relatively prolonged hospital stays, many with a need for ventilatory support and, in a considerable proportion of cases, admission to the ICU. However, the observed survival rate is high, and the drug is well tolerated. [ABSTRACT FROM AUTHOR]

Infant‐directed speech (IDS) is phonetically distinct from adult‐directed speech (ADS): It is typically considered to have special prosody—like higher pitch and slower speaking rates—as well as unique speech sound properties, for example, more breathy, hyperarticulated, and/or variable consonant and vowel articulation. These phonetic features are widely observed in the IDS of caregivers from urbanized contexts who speak a handful of very well‐researched languages. Yet studies with more diverse socio‐cultural and linguistic samples show that this "typical" IDS prosody is not consistently observed across cultures. We extended cross‐cultural work by examining IDS speech segment articulation, which—like prosody—is also thought to be a characteristic phonetic feature of IDS that might aid speech and language development. Here we asked whether IDS vowels have different articulatory features compared to ADS vowels in two distinct linguistic and socio‐cultural contexts: urban English‐speaking Canadian mothers, and rural Lenakel‐ and Southwest Tanna‐speaking ni‐Vanuatu mothers (n = 57, 20–46 years of age). Replicating prior work, Canadian mothers had more variable vowels in IDS compared to ADS, but also did not show clear register differences for breathiness or hyperarticulation. Vowels spoken by ni‐Vanuatu mothers showed very distinct articulatory tendencies, using less variable (and less breathy) IDS vowels. Along with other work showing diversity in IDS phonetics across populations, this paper suggests that any understanding of how IDS might aid speech and language development are best examined through a culturally‐ and linguistically‐specific lens. [ABSTRACT FROM AUTHOR]

Tocilizumab is one of few treatments that have been shown to improve mortality in patients with coronavirus disease 2019 (COVID-19), but increased demand has led to relative global shortages. Recently, it has been suggested that lower doses, or fixed doses, of tocilizumab could be a potential solution to conserve the limited global supply while conferring equivalent therapeutic benefit to the dosing regimens studied in major trials. The relationship between tocilizumab dose, exposure, and response in COVID-19 has not been adequately characterized. There are a number of pharmacokinetic (PK) parameters that likely differ between patients with severe COVID-19 and patients in whom tocilizumab was studied during the US FDA approval process. Likewise, it is unclear whether a threshold exposure is necessary for tocilizumab efficacy. The safety and efficacy of fixed versus weight-based dosing of tocilizumab has been evaluated outside of COVID-19, but it is uncertain if these observations are generalizable to severe or critical COVID-19. In the current review, we consider the potential advantages and limitations of alternative tocilizumab dosing strategies. Leveraging PK models and simulation analyses, we demonstrate that a fixed single dose of tocilizumab 400 mg is unlikely to produce PK exposures equivalent to those achieved in the REMAP-CAP trial, although weight-stratified dosing appears to produce more uniform exposure distribution. Data from current and future trials could provide PK/pharmacodynamic insight to better inform dosing strategies at the bedside. Ultimately, rational dosing strategies that balance available limited supply with patient needs are required. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (HSCT) and coronavirus disease 2019 (COVID-19) infection can both lead to severe cytokine release syndrome (sCRS) resulting in critical illness and death. In this single institution, preliminary comparative case-series study we compared clinical and laboratory co-variates as well as response to tocilizumab (TCZ)-based therapy of 15 allogeneic-HSCT- and 17 COVID-19-associated sCRS patients. Reaction to a TCZ plus posttransplant cyclophosphamide (PTCY) consolidation therapy in the allogeneic-HSCT-associated sCRS group yielded significantly inferior long-term outcome as compared to TCZ-based therapy in the COVID-19-associated group (P = 0.003). We report that a TCZ followed by consolidation therapy with a Janus kinase/signal transducer and activator of transcription (JAK/STAT) inhibitor given to 4 out of 8 critically ill COVID-19 patients resulted in their complete recovery. Non-selective JAK/STAT inhibitors influencing the action of several cytokines exhibit a broader effect than TCZ alone in calming down sCRS. Serum levels of cytokines and chemokines show similar changes in allogeneic-HSCT- and COVID-19-associated sCRS with marked elevation of interleukin-6 (IL-6), regulated upon activation normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 (MCP-1) and interferon γ -induced protein 10 kDa (IP-10) levels. In addition, levels of IL-5, IL-10, IL-15 were also elevated in allogeneic-HSCT-associated sCRS. Our multi-cytokine expression data indicate that the pathophysiology of allogeneic-HSCT and COVID-19-associated sCRS are similar therefore the same clinical grading system and TCZ-based treatment approaches can be applied. TCZ with JAK/STAT inhibitor consolidation therapy might be highly effective in COVID-19 sCRS patients. [ABSTRACT FROM AUTHOR]

Background: Tocilizumab is an IgG1 class recombinant humanized monoclonal antibody that directly inhibits the IL-6 receptor. Several randomized clinical trials have evaluated its safety and efficacy in patients with coronavirus disease 2019 (COVID-19), and these studies demonstrate conflicting results. Our study aimed to determine the association between tocilizumab treatment and microbial isolation and emergence of multidrug-resistant bacteria in critically ill patients with COVID-19.Methods: A multicenter retrospective cohort study was conducted at two tertiary government hospitals in Saudi Arabia. All critically ill patients admitted to intensive care units with a positive COVID-19 PCR test between March 1 and December 31, 2020, who met study criteria were included. Patients who received tocilizumab were compared to those who did not receive it.Results: A total of 738 patients who met our inclusion criteria were included in the analysis. Of these, 262 (35.5%) received tocilizumab, and 476 (64.5%) were included in the control group. Patients who received tocilizumab had higher odds for microbial isolation (OR 1.34; 95% CI 0.91-1.94, p = 0.13); however, the difference was not statistically significant. Development of resistant organisms (OR 1.00; 95% CI 0.51-1.98, p = 0.99) or detection of carbapenem-resistant Enterobacteriaceae (CRE) (OR 0.67; 95% CI 0.29-1.54, p = 0.34) was not statistically significant between the two groups.Conclusions: Tocilizumab use in critically ill patients with COVID-19 is not associated with higher microbial isolation, the emergence of resistant organisms, or the detection of CRE organisms. [ABSTRACT FROM AUTHOR]

Large randomized clinical trials in severe Coronavirus Disease 2019 (COVID-19) patients have proven efficacy of intravenous tocilizumab. Our aim was to describe the laboratory parameters predicting in-hospital mortality of patients with tocilizumab administration in COVID-19 associated cytokine release syndrome (CRS). We evaluated high-dose (8 mg/kg) intravenous tocilizumab administration in severe and critically ill COVID-19 adult patients fulfilling predefined strict CRS criteria. A single-centre, prospective, observational cohort study was carried out among consecutive adult (≥18 years of age) in-patients with COVID-19 between April 1 and December 31, 2020. The primary endpoint was 28-day all-cause mortality. The changes in laboratory parameters from baseline on day 7 and 14 after administration of tocilizumab were analysed. In total, 1801 patients were admitted to our centre during the study period. One hundred and six patients received tocilizumab, and among them 62 (58.5%) required intensive care unit admittance while 25 (23.6%) deceased. At day 7 after tocilizumab administration, inflammatory markers (CRP, IL-6, ferritin) and lactate dehydrogenase (LDH) values were significantly lower among survivors. Subsequently, at day 14, differences of IL-6 and LDH levels has become more pronounced between subgroups. Restoration of absolute lymphocyte count (ALC) by day 7 and 14 was insufficient among patients who died. In our cohort, administration of high-dose tocilizumab for COVID-19 patients with CRS demonstrated clinical and sustained biochemical parameter improvement in 76.4%. In this patient population high and increasing LDH, IL-6, and low ALC levels had a predictive role for mortality. [ABSTRACT FROM AUTHOR]

Patients with severe cases of COVID-19 infection can develop acute respiratory distress syndrome, septic shock, multiple system organ failure, bleeding, and coagulation dysfunction. Severe forms of COVID-19 are characterized by viral pneumonia patterns and are frequently associated with elevated serum levels of pro-inflammatory cytokines forming a "cytokine storm". Among the mediators of cytokines release syndrome, interleukin-6 is one of the key cytokines. Tocilizumab, a monoclonal antibody against interleukin-6 receptor, may provide clinical benefit for selected COVID-19 patients with high inflammatory biomarkers. In this prospective study, we aimed to correlate the blood levels of interleukin 6, C-reactive protein, procalcitonin and other biomarkers to the clinical course and outcome of COVID-19 patients in our study cohort. Our study shows that several biomarkers and in particular serum interleukin-6 levels differ according to disease severity in COVID-19 infection. Serum interleukin-6 levels were also significantly increased in non-survivors and could raise the potential benefit of tocilizumab for selected cases of COVID-19 infection. Data about the efficacy of tocilizumab are conflicting. However, our data about tocilizumab may suggest a potential benefit, and is in-line with previous data about the absence of significant risk of super-infection. The early short-term administration of methylprednisolone in a 250-500mg/daily dosage revealed good results with and without concurrent tocilizumab therapy. [ABSTRACT FROM AUTHOR]

Anosmia with or without dysgeusia is frequently associated with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) SARS-CoV-2 infection. SARS-CoV-2 virus affects the olfactory system and thus represents neurotropic and neuro-invasive nature of the virus. We found that tocilizumab's role in reducing mortality in severe covid-19 infection is still questionable and aim of our study was correlation of anosmia and severity of covid-19 infection and requirement of tocilizumab in anosmia patients. To establish relationship between anosmia and severity of COVID-19 infection along with requirement of tocilizumab. This was a retrospective cum prospective cross sectional study done on COVID-19 patients who were admitted in normal COVID-19 ward and intensive care unit of Employee's State Insurance Corporation Hospital, Udaipur and Maharaja Bhupal Hospital of Ravindra Nath Medical College between September 2020 and 15 January 2021 age group of 18 to 92 years, both sexes. We had asked about anosmia in all COVID-19 positive patients and followed all patients in perspective of severity of disease and tocilizumab. p value < 0.001 of prevalence of anosmia in COVID -19 patients who were isolated at home, admitted in ward and intensive care unit showed that anosmia is inversely related to severity of disease. Tocilizumab has no significant role in decreasing mortality in severe form of disease. Our study indicates that anosmia is related to the mildness of disease and there is no role of tocilizumab in decreasing the mortality in severe form of disease. [ABSTRACT FROM AUTHOR]

Due to their salient features, modular multilevel converters (MMCs) are particularly suitable for a high-voltage direct current (HVDC) transmission system. Nevertheless, for an HVDC system, each phase of the MMC terminal may consist of several hundreds of submodules. This imposes a particular challenge in terms of steady-state simulation and modeling. Steady-state modeling is usually needed for determining the operating point for the MMC controller design and for predicting harmonics propagation in a power network. In this article, an efficient and accurate steady-state model for an MMC system with high-voltage levels is proposed. The model is based on a model reduction technique, namely residual-time restarting Krylov subspace method. As will be shown in this article, the proposed method is able to model various MMC systems. The results obtained from the proposed model are highly agreeable with those from PSCAD/EMTDC. Moreover, it will also be shown that the proposed method can drastically reduce the computation time for obtaining steady-state solutions. [ABSTRACT FROM AUTHOR]

The modular multilevel matrix converter (M3C) is introduced and applied to a single-stage ac/dc solid-state transformer (SST), which uses only one concentrated medium-frequency transformer (MFT) for isolation. As a result, the transformer insulation design is simplified significantly and higher power density could be achieved. Meanwhile, a novel decoupling transformation based on two internal three-phase circulating systems is proposed to improve the previous method. Through this transformation, the unbalanced capacitor voltage components can be divided into four independent dimensions, which correspond to four kinds of capacitor voltage ripple frequency. And a dc-side vector model is then established to calculate the required circulating current reference for capacitor balancing. Besides, under the application of SST, the capacitor voltage ripple suppression strategy via injection of extra circulating current is proposed. The amplitude and frequency index is optimized to obtain the best effect. Therefore, the submodule capacitor volume can be reduced to achieve higher power density. Simulation and experimental results are also provided to verify the theoretical analysis. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection is necessary but insufficient for progression of epithelial cells from dysplasia to carcinoma- in situ (CIS) to invasive cancer. The combination of mutant cellular and viral oncogenes that regulate progression of cervical cancer (CC) remains unclear. Using combinations of HPV16 E6/E7 (E+), mutant Kras (m Kras) (K+) and/or loss of Pten (P−/−), we generated autochthonous models of CC without exogenous estrogen, carcinogen or promoters. Furthermore, intravaginal instillation of adenoCre virus enabled focal activation of the oncogenes/inactivation of the tumor suppressor gene. In P+/+ mice, E6/E7 alone (P+/+E+K−) failed to cause premalignant changes, while m Kras alone (P+/+E−K+) caused persistent mucosal abnormalities in about one-third of mice, but no cancers. To develop cancer, P+/+ mice needed both E6/E7 and m Kras expression. Longitudinal endoscopies of P+/+E+K+ mice predicted carcinoma development by detection of mucosal lesions, found on an average of 23 weeks prior to death, unlike longitudinal quantitative PCRs of vaginal lavage samples from the same mice. Endoscopy revealed that individual mice differed widely in the time required for mucosal lesions to appear after adenoCre and in the time required for these lesions to progress to cancer. These cancers developed in the transition zone that extends, unlike in women, from the murine cervix to the distal vagina. The P−/−E+K+ genotype led to precipitous cancer development within a few weeks and E6/E7 -independent cancer development occurred in the P−/−E−K+ genotype. In the P−/−E+K− genotype, mice only developed CIS. Thus, distinct combinations of viral and cellular oncogenes are involved in distinct steps in cervical carcinogenesis. [ABSTRACT FROM AUTHOR]

Rapid and frequent screening of cytokines as immunomodulation agents is necessary for precise interventions in severe pathophysiological conditions. In addition to high-sensitivity detection of such analytes in complex biological fluids such as blood, saliva, and cell culture medium samples, it is also crucial to work out miniaturized bioanalytical platforms with potential for high-density integration enabling screening of multiple analytes. In this work, we show a compact, point-of-care-ready bioanalytical platform for screening of cytokines such as interleukin-4 (IL-4) and interleukin-2 (IL-2) based on one-dimensional ion-sensitive field-effect transistors arrays (nanoISFETs) of silicon fabricated at wafer-scale via nanoimprint lithography. The nanoISFETs biofunctionalized with receptor proteins alpha IL-4 and alpha IL-2 were deployed for screening cytokine secretion in mouse T helper cell differentiation culture media, respectively. Our nanoISFETs showed robust sensor signals for specific molecular binding and can be readily deployed for real-time screening of cytokines. Quantitative analyses of the nanoISFET-based bioanalytical platform was carried out for IL-4 concentrations ranging from 25 fg/mL (1.92 fM) to 2.5 μg/mL (192 nM), showing a limit of detection down to 3–5 fM, which was found to be in agreement with ELISA results in determining IL-4 concentrations directly in complex cell culture media. [ABSTRACT FROM AUTHOR]

Copyright of Asian Journals of Ecotoxicology is the property of Gai Kan Bian Wei Hui and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Theories indicate that price and peer influence are important factors that impact purchase decisions. Brand trust is another key factor for consideration when looking at why individuals purchase certain products. This empirical study tested nine hypotheses focusing on how brand trust, brand loyalty, peer influence and price sensitivity affected computer brand choice among university students. The purpose of this empirical research was to investigate the association between price sensitivity, brand trust, brand loyalty and peer influence on a purchase decision. Companies have to stay competitive by maintaining relationships with customers. Research reveals that it costs more to acquire new customers rather than to maintain existing ones. Therefore, it is crucial for companies to build brand relationships by developing trust with their customers. In addition, social groups may influence individual purchase decisions. The results revealed that students' choice of a higher-end and more expensive computer brand were influenced by the computer brands used by their peers as well as brand trust and brand loyalty. Price sensitivity was negatively influenced by peer influence and brand trust. These results revealed that it is essential to build brand trust to ensure brand loyalty and that brand loyalty is an important factor in student choice of more expensive computer brands. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPVs) of genus betapapillomavirus (betaHPV) are implicated in skin carcinogenesis, but their exact role in keratinocyte transformation is poorly understood. We show an interaction of HPV5 and HPV8 oncoproteins E6 and E7 with the nuclear mitotic apparatus protein 1 (NuMA). Binding of E6 or E7 to NuMA induces little aneuploidy, cell cycle alterations, or aberrant centrosomes. Intracellular localization of NuMA is not altered by E6 and E7 expression in 2D cultures. However, the localization profile is predominantly cytoplasmic in 3D organotypic skin models. Both viral proteins colocalize with NuMA in interphase cells, while only E7 colocalizes with NuMA in mitotic cells. Intriguingly, a small subset of cells shows E7 at only one spindle pole, whereas NuMA is present at both poles. This dissimilar distribution of E7 at the spindle poles may alter cell differentiation, which may in turn be relevant for betaHPV-induced skin carcinogenesis. [ABSTRACT FROM AUTHOR]

When PP is the fractional Laplacian (−Δ)a, 0 < a < 1, or a pseudodifferential generalization thereof, the Dirichlet problem for the associated heat equation over a smooth set Ω ⊂ Rn: r + Pu(x,t) + ∂tu(x,t) = f(x,t) on Ω × ]0,T, u(x,t) = 0 for x ∉ Ω, u(x,0) = 0, is known to be solvable in relatively low-order Sobolev or Hölder spaces. We now show that in contrast with differential operator cases, the regularity of u in x at ∂Ω when f is very smooth cannot in general be improved beyond a certain estimate. An improvement requires the vanishing of a Neumann boundary value. --- There is a similar result for the Schrödinger Dirichlet problem r+ Pv(x) + Vv(x) = g(x) on Ω, supp v ⊂ Ω, with V(x) ∈ C∞. The proofs involve a precise description, of interest in itself, of the Dirichlet domains in terms of regular functions and functions with a dist(x,∂Ω)a singularity. [ABSTRACT FROM AUTHOR]

Focuses on instantaneous normal mode (INM) analysis undertaken for several ionic melts. Sodium chloride at six distinct thermodynamic states; Ratio between the diffusion constants for cations and anions; Prediction from the average frequency of the real and imaginary frequency modes of the projection of the total density of states on cations and anions.