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Abstract Background Identifying individuals with mild cognitive impairment (MCI) who are likely to progress to Alzheimer’s disease and related dementia disorders (ADRD) would facilitate the development of individualized prevention plans. We investigated the association between MCI and comorbidities of ADRD. We examined the predictive potential of these comorbidities for MCI risk determination using a machine learning algorithm. Methods Using a retrospective matched case-control design, 5185 MCI and 15,555 non-MCI individuals aged ≥50 years were identified from MarketScan databases. Predictive models included ADRD comorbidities, age, and sex. Results Associations between 25 ADRD comorbidities and MCI were significant but weakened with increasing age groups. The odds ratios (MCI vs non-MCI) in 50–64, 65–79, and ≥ 80 years, respectively, for depression (4.4, 3.1, 2.9) and stroke/transient ischemic attack (6.4, 3.0, 2.1). The predictive potential decreased with older age groups, with ROC-AUCs 0.75, 0.70, and 0.66 respectively. Certain comorbidities were age-specific predictors. Conclusions The comorbidity burden of MCI relative to non-MCI is age-dependent. A model based on comorbidities alone predicted an MCI diagnosis with reasonable accuracy.

Abstract Introduction Alzheimer’s disease (AD) is a disease continuum from pathophysiologic, biomarker and clinical perspectives. With the advent of advanced technologies, diagnosing and managing patients is evolving. Methods A systematic literature review (SLR) of practice guidelines for mild cognitive impairment (MCI) and AD dementia was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). This systematic literature review (SLR) aimed to summarize current clinical practice guidelines for screening, testing, diagnosis, treatment and monitoring in the AD continuum. The results of this SLR were used to propose a way forward for practice guidelines given the possible introduction of biomarker-guided technology using blood- or plasma-based assays and disease-modifying treatments (DMTs) targeted for early disease. Results 53 clinical practice guidelines were identified, 15 of which were published since 2018. Screening for asymptomatic populations was not recommended. Biomarker testing was not included in routine diagnostic practice. There was no consensus on which neurocognitive tests to use to diagnose and monitor MCI or AD dementia. Pharmacologic therapies were not recommended for MCI, while cholinesterase inhibitors and memantine were recommended for AD treatment. Discussion The pre-2018 and post-2018 practice guidelines share similar recommendations for screening, diagnosis and treatment. However, once DMTs are approved, clinicians will require guidance on the appropriate use of DMTs in a clinical setting. This guidance should include strategies for identifying eligible patients and evaluating the DMT benefit-to-risk profile to facilitate shared decision-making among physicians, patients and care partners. Conclusion Regular evidence-based updates of existing guidelines for the AD continuum are required over the coming decades to integrate rapidly evolving technologic and medical scientific advances and bring emerging approaches for management of early disease into clinical practice. This will pave the way toward biomarker-guided identification and targeted treatment and the realization of precision medicine for AD.

Abstract Background Cadmium is a non-essential, third largest heavy metal contaminant with long retention time that poses environmental hazards. It emanating majorly from industrial processes and phosphate fertilizers. Cadmium is effortlessly assimilated by plants and leads to yield loss. Henceforth, identification of mechanisms to attenuate the heavy metal toxicity in crops is beneficial for enhanced yields. Results Beneficial soil bacteria have been known to combat both biotic and abiotic stress, thereby promoting plant growth. Amongst them, Pseudomonas fluorescens has been shown to enhance abiotic stress resistance in umpteen crops for instance maize and groundnut. Here, we investigated the role of P. fluorescens in conferring cadmium stress resistance in Arabidopsis thaliana. In silico analysis of PCR2 gene and promoter revealed the role, in cadmium stress resistance of A. thaliana. Real-time expression analysis employing qRT-PCR ratified the upregulation of AtPCR2 transcript under cadmium stress up to 6 folds. Total leaf (50%), biomass (23%), chlorophyll content (chlorophyll-a and b 40%, and 36 %) silique number (50%), and other growth parameters significantly improved on bacterial treatment of the 2mM Cd-stressed plants. Conclusion Moreover, generated 35s-promoter driven AtPCR2 over-expressing transgenic lines that exhibited resistance to cadmium and other heavy metal stress. Taken together, a crucial interplay of P. fluorscens mediated enhanced expression of AtPCR2 significantly induced cadmium stress resistance in Arabidopsis plants.

Introduction: The first COVID-19 cases occurred in the US in January of 2020, leading to the implementation of shelter in place. This study seeks to define the impact of shelter in place on the epidemiology of pediatric trauma. Methods: We examined pediatric trauma admissions at 5 Level 1 and 1 Level 2 US pediatric trauma centers between January 1 and June 30, 2017–2020. Demographic and injury data were compared between pre– and post–shelter in place patient cohorts. Results: A total of 8772 pediatric trauma activations were reviewed. There was a 13% decrease in trauma volume in 2020, with a nadir at 16 days following implementation of shelter in place. Injury severity scores were higher in the post–shelter in place cohort. The incidence of nonmotorized vehicle accidents and gunshot wounds increased in the post–shelter in place cohort. Conclusion: We found an overall decrease in pediatric trauma volume following shelter in place. However, injuries tended to be more severe. Our findings help inform targeted injury prevention campaigns during future pandemics.

biocontrol agents (BCAs) are widely used to protect plants from diverse biotic and abiotic stresses in agricultural and ecological fields. Among the various microbes, many subspecies of the gram-positive genus, Bacillus, have been successfully industrialized as eco-friendly biological pesticides and fertilizers. In the current study, we demonstrated that Bacillus thuringiensis C25 exhibited antagonistic effects on the mycelial growth of Rosellinia necatrix, a fungal phytopathogen. Scanning electron microscopy analysis revealed that B. thuringiensis C25 degraded the cell wall structures of R. necatrix mycelia. In the functional genomic analysis of B. thuringiensis C25, we annotated 5,683 genes and selected the gene sets that potentially encoded fungal cell wall degrading enzymes (CWDEs). The growth inhibition effects on R. necatrix were highly correlated with the transcriptional activity of the mycelial cell wall degrading genes of B. thuringiensis C25. The transcript levels of CWDEs, including CshiA, B, and Glycos_transf_2 genes in B. thuringiensis C25, were enhanced following co-cultivation with R. necatrix. In conclusion, our study suggested that B. thuringiensis C25 could serve as a suitable candidate for controlling R. necatrix and could facilitate elucidating the mechanisms underlying the antifungal activities of BCAs against phytopathogens.

Abstract Previously termed “Green Crystals of Death,” bright blue‐green inclusion bodies within neutrophils are a rare clinical finding. They have been reported as a predictive sign of mortality in critically ill patients and often accompany acute liver failure, lactic acidosis with multisystem organ failure, or septic shock due to Escherichia coli.

Although dye removal from wastewater streams has been investigated via several approaches using adsorbents, resins, or membranes, it is still hard to avoid the fact that dyes are persistently left in the adsorption materials or washing solutions used to regenerate the used adsorbents. In particular, given that cleaning agents are composed of acid/base, organic solvents, or electrolytes, dye adsorption and adsorbent regeneration processes leave behind more hard-to-manage wastewater containing dyes. In this study, we demonstrated that cold plasma (CP) treatment, which is one of the advanced oxidation processes (AOPs), can be used for zero discharge of dyes and regeneration of a washing solution in a membrane-based dye removal process. Specifically, CP treatment was found to successfully remove dyes released from a washing process to regenerate a used membrane, thereby effectively recycling a cleaning solution. As a result, the regenerated washing solution was more favorable for the adsorbed dyes’ elution, leading to the successful regeneration of a used membrane without a significant loss of dye removal efficiency. This fact was evidenced by a comparative study on the effect of CP treatment on the reusability of membranes and washing solutions and the kinetic analysis of the AOP of the desorbed dyes. We hope that this study contributes to opening a new door for environmentally friendly and sustainable dye removal.

This data article presents the experimental evidences of the effect of TiO2-fluorine doped tin oxide interface annealing and Ni(OH)2 cocatalysts on the photoelectrochemical, structural, morphological and optical properties of Ni(OH)2/CdS/ZnIn2S4/TiO2 heterojunction. The Raman spectroscopy exhibits the sharp features of the rutile phase of TiO2 and in agreement with the X-ray diffraction data. The band gap energy of the 500 °C sample was found to be 3.12 eV, further it was increased to 3.20, 3.22 eV for samples annealed at 600 and 700 °C respectively. The decrease in the band gap energy at 500 °C related to the oxygen vacancies and was analysed by photoluminescence spectroscopy analysis. The synthesis, characterization methods and other experimental details of TiO2 based heterostructure are also provided. The presence of CdS and ZnIn2S4 coating on surface of TiO2 electrodes providing a high surface area, extended visible absorption and helps to improve the change separation. This data article contains data related to the research article entitled “Highly efficient and stable 3D Ni(OH)2/CdS/ZnIn2S4/TiO2 heterojunction under solar light: Effect of an improved TiO2/FTO interface and cocatalyst” (Mahadik et al., 2017) [1]. Keywords: Annealed TiO2 nanorods, CdS/ZnIn2S4/TiO2 heterostructure, Ni(OH)2 cocatalyst, TiO2-FTO interface

A green, eco-friendly approach for the synthesis of silver and gold nanoparticles (AgNPs and AuNPs) using Erigeron annuus (L.) pers flower extract as both the reducing and capping agent is reported for the first time. Optimal nanoparticle production was achieved by adjusting various parameters including pH, extract concentration, metal ion concentration, and time. Initial verification of AgNP and AuNP production was done by visual observation and measuring surface plasmon spectra at 434 and 537 nm, respectively. The synthesized AgNPs and AuNPs were characterized by high resolution-transmission electron microscopy (HR-TEM), X-ray diffraction (XRD), energy dispersive spectrophotometry (EDS), Fourier transform infrared spectroscopy (FTIR) and zeta potential. The catalytic potential of E. annuus flower extract, silver ions, synthesized AgNPs, commercial grade AgNPs, and a mixture of flower extract and AgNPs immobilized on sodium alginate hydrogel beads (Na/Al HB) was analyzed. The ability of these immobilized materials to degrade methylene blue was investigated. Commercial grade AgNPs immobilized with Na/Al HB 1.5 g/20 mL were observed to have good catalytic activity followed by a mixture of synthesized AgNPs immobilized with Na/Al HB and E. annuus flower extract immobilized with Na/Al HB at 1.5 g/20 mL.

Adsorption using carbon-based materials has been established to be a feasible method for separating carbon dioxide and hydrogen to mitigate the emission of carbon dioxide into the atmosphere and for the collection of fuel for energy sources, simultaneously. We carried out density functional theory calculation with dispersion correction to investigate the physisorption characteristics of carbon allotropes such as graphene and graphyne for the competitive adsorption of CO2 and H2. It is worth noting that the graphyne represented preferable adsorption energies, short bond lengths and energy charges for both gases, compared with the characteristics observed with graphene. We found that in graphyne, both the affinitive adsorption of CO2, and the competitive adsorption of CO2 and H2, took place at the hollow site between acetylene links, which do not exist in graphene. We demonstrate that in the presence of H2, the CO2 adsorption selectivity of graphyne is higher than that of graphene, because of the improved electronic properties resulting from the acetylene links.

We calculated the band structures of a variety of N- and S-doped graphenes in order to understand the effects of the N and S dopants on the graphene electronic structure using density functional theory (DFT). Band-structure analysis revealed energy band upshifting above the Fermi level compared to pristine graphene following doping with three nitrogen atoms around a mono-vacancy defect, which corresponds to p-type nature. On the other hand, the energy bands were increasingly shifted downward below the Fermi level with increasing numbers of S atoms in N/S-co-doped graphene, which results in n-type behavior. Hence, modulating the structure of graphene through N- and S-doping schemes results in the switching of “p-type„ to “n-type„ behavior with increasing S concentration. Mulliken population analysis indicates that the N atom doped near a mono-vacancy is negatively charged due to its higher electronegativity compared to C, whereas the S atom doped near a mono-vacancy is positively charged due to its similar electronegativity to C and its additional valence electrons. As a result, doping with N and S significantly influences the unique electronic properties of graphene. Due to their tunable band-structure properties, the resulting N- and S-doped graphenes can be used in energy and electronic-device applications. In conclusion, we expect that doping with N and S will lead to new pathways for tailoring and enhancing the electronic properties of graphene at the atomic level.

Background: The annual incidence and mortality rates of pancreatic cancer has been rising. We analyzed pancreatic cancer trends by demographics and geographic location. Methods: Data was obtained from the Surveillance, Epidemiology, and End Results (SEER) registry 17 were available to assess trends of pancreatic cancer incidence and mortality from 2000 to 2019. Results: The pancreatic cancer incidence and mortality rates consistently increased over time from 2000 to 2019. Incidence of pancreatic cancer was highest in males (14; 95% Cl, 13.9,14.1) and blacks (15.4 95% Cl,15.2, 15.6). The incidence was highest in Alaska (16.2; 95% Cl, 14.1, 18.5), and lowest in Utah (10.7; 95% Cl, 10.4, 11.0). Incidence increased at 0.85% per year (95% Cl, 0.76, 0.92; P < .001). Overall incidence increased significantly for all sex, race, stage sub-groups except for Blacks (APC of 0.04%; 95% Cl, -0.14, 0.22; P = 0.649), and American Indian/Alaska natives (APC of -0.22 %; 95% Cl, -1.33, 0.89; P= 0.679). There was an overall significant increase in incidence across all states except for Alaska. Incidence-based mortality of pancreatic cancer was highest in males (12.6; 95% Cl, 12.5,12.7) and blacks (14.1; 95% Cl, 13.9, 14.3). Mortality was highest in Alaska (15.1; 95% Cl, 13.1,17.3), and lowest in Utah (9.6; 95% Cl, 9.3,9.9). Mortality increased at 0.91% per year (95% Cl, 0.32, 1.50; P = .005). The overall incidence-based mortality increased significantly only in the males APC, 0.95% (95% Cl, 0.36, 1.54; P = 0.003), females APC 1.18 (95% Cl, 0.47, 1.89; P = 0.002) and whites APC 1.05% (95% Cl, 0.45, 1.66; P = 0.002). Furthermore, there was an overall significant increase in incidence-based mortality across all states except for Alaska, Hawaii and Washington. Conclusion: Pancreatic cancer incidence and mortality rates increased overall but differed by demographics and geographic location.

Aspergillus flavus and its mycotoxin aflatoxin (AF) are widely present in the environment and cause various acute and chronic diseases in humans and animals. UV irradiation has been a versatile method for disinfecting A. flavus and detoxifying AFs. Combined effects of UV and other agents were scarcely tested yet. Here, we investigated the combinatorial effects of UVC and peroxymonosulfate (PMS) on the disinfection of A. flavus and accumulation of AFB1 under aqueous conditions. UVC efficiently disinfected A. flavus in a dose-dependent manner. PMS (~4 mM) exhibited no disinfection but enhanced the inactivation activity of UVC. Notably, PMS or UVC (72 J/cm²) increased the accumulation of AFB1 in the mycelia. Higher (144 J/cm²) doses of UVC suppressed AFB1 accumulation. At the genetic level, PMS and UVC upregulated the expression of the AF biosynthetic genes aflS and aflR. In contrast, UVC degraded AFB1 in vitro, which was enhanced by PMS treatment. The in-vivo and in-vitro studies indicated that AFB1 accumulation may be compromised by the dual effects of UVC and PMS on the upregulation of AF biosynthesis and degradation activities. In conclusion, PMS and UVC are efficient disinfecting agents against A. flavus but also stimulate AF biosynthesis under moderate treatment conditions. [ABSTRACT FROM AUTHOR]

Objectives: The study of autonomic responses to cardiac arrest (CA) resuscitation deserves attention due to the impact of autonomic function on survival and arousal. Orexins are known to modulate autonomic function, but the role of endogenous orexin in hyperacute recovery of autonomic function postresuscitation is not well understood. We hypothesized that endogenous orexin facilitates hyperacute cardiovascular sympathetic activity post-resuscitation, and this response could be attenuated by suvorexant, a dual orexin receptor antagonist. Methods: A well-established 7-min asphyxial CA rat model was studied. Heart rate (HR) and blood pressure were monitored from baseline to 90-min postresuscitation. Autonomic function was evaluated by spectral analysis of HR variability, whereby the ratio of low- and high-frequency components (LF/HF ratio) represents the balance between sympathetic/parasympathetic activities. Plasma orexin-A levels and orexin receptors immunoreactivity in the rostral ventrolateral medulla (RVLM), the key central region for regulating sympathetic output, were measured post-resuscitation. Neurological outcome was assessed via neurologic-deficit score at 4-h post-resuscitation. Key results: A significant increase in HR was found over 25-40 min postresuscitation (p < 0.01 vs. baseline), which was attenuated by suvorexant significantly (p < 0.05). Increased HR (from 15-to 25-min post-resuscitation) was correlated with better neurological outcomes (rs = 0.827, p = 0.005). There was no evident increase in mean arterial pressure over 25-40 min post-resuscitation, while systolic pressure was reduced greatly by suvorexant (p < 0.05). The LF/HF ratio was higher in animals with favorable outcomes than in animals injected with suvorexant over 30-40 min post-resuscitation (p < 0.05). Plasma orexin-A levels elevated at 15-min and peaked at 30-min post-resuscitation (p < 0.01 vs. baseline). Activated orexin receptors-immunoreactive neurons were found co-stained with tyrosine hydroxylase-immunopositive cells in the RVLM at 2-h post-resuscitation. Conclusion: Together, increased HR and elevated LF/HF ratio indicative of sympathetic arousal during a critical window (25-40 min) post-resuscitation are observed in animals with favorable outcomes. The orexin system appears to facilitate this hyperacute autonomic response post-CA. [ABSTRACT FROM AUTHOR]

Background: Dipeptidyl peptidase-4 (DPP4) inhibitors are frequently prescribed for patients with type 2 diabetes; however, their cost can pose a significant barrier for those with impaired kidney function. This study aimed to estimate the economic benefits of substituting non-renal dose-adjusted (NRDA) DPP4 inhibitors with renal dose-adjusted (RDA) DPP4 inhibitors in patients with both impaired kidney function and type 2 diabetes. Methods: This retrospective cohort study was conducted from January 1, 2012 to December 31, 2018, using data obtained from common data models of five medical centers in Korea. Model 1 applied the prescription pattern of participants with preserved kidney function to those with impaired kidney function. In contrast, model 2 replaced all NRDA DPP4 inhibitors with RDA DPP4 inhibitors, adjusting the doses of RDA DPP4 inhibitors based on individual kidney function. The primary outcome was the cost difference between the two models. Results: In total, 67,964,996 prescription records were analyzed. NRDA DPP4 inhibitors were more frequently prescribed to patients with impaired kidney function than in those with preserved kidney function (25.7%, 51.3%, 64.3%, and 71.6% in patients with estimated glomerular filtration rates [eGFRs] of =60, <60, <45, and <30 mL/min/1.73 m2, respectively). When model 1 was applied, the cost savings per year were 7.6% for eGFR <60 mL/min/1.73 m2 and 30.4% for eGFR <30 mL/min/1.73 m2. According to model 2, 15.4% to 51.2% per year could be saved depending on kidney impairment severity. Conclusion: Adjusting the doses of RDA DPP4 inhibitors based on individual kidney function could alleviate the economic burden associated with medical expenses. [ABSTRACT FROM AUTHOR]

We investigated the potential association between ketonuria during treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors and its renoprotective effect in patients with type 2 diabetes. We included 192 patients who had received SGLT2 inhibitors for more than 6 months. After propensity score matching, 52 patients each were allocated into groups with or without ketonuria, respectively. The estimated glomerular filtration rate exhibited a significant improvement only in subjects with ketonuria (without ketonuria: mean difference, -0.02 mL/min/1.73 m2 [95% confidence interval (CI), -3.87 to 3.83 mL/min/1.73 m2] vs. with ketonuria: mean difference, 6.81 mL/min/1.73 m2 [95% CI, 3.16 to 10.46 mL/min/1.73 m2]; P<0.001). Improvement in estimated glomerular filtration rate at 6 months was associated with female sex and lower baseline body weight, blood pressure, and triglyceride levels in patients with ketonuria. In conclusion, the presence of ketonuria was associated with the renoprotective effect of SGLT2 inhibitors, and female sex and the absence of metabolic syndrome components may serve as additional indicators of these medications' substantial renoprotective effects in individuals with ketonuria. [ABSTRACT FROM AUTHOR]