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Background: Epstein-Barr Virus (EBV) is associated with lung disease in immunocompromised patients, particularly transplant recipients. EBV DNA testing of lower respiratory tract specimens may have diagnostic utility., Methods: This was a retrospective, observational study of all patients with bronchoalveolar lavage (BAL) fluids submitted for EBV qPCR testing from February 2016 to June 2022 at the Stanford Clinical Virology Laboratory., Results: There were 140 patients that underwent 251 EBV qPCR BAL tests (median 1; range 1 - 10). These patients had a mean age of 15.9 years (standard deviation, 15.1 years) and 50 % were female. Transplant recipients accounted for 67.1 % (94/140) of patients, including 67.0 % (63/94) solid organ transplant (SOT) and 33.0 % (31/94) hematopoietic cell transplant. Diagnostic testing was performed more commonly than surveillance testing [57.0 % (143/251) v. 43.0 % (108/251)]; 96.2 % (104/108) of surveillance samples were from lung transplant recipients. Excluding internal control failures, 34.7 % (83/239) of BAL had detectable EBV DNA, encompassing a wide range of viral loads (median=3.03 log 10 IU/mL, range 1.44 to 6.06). Overall agreement of EBV DNA in BAL compared to plasma was 74.1 % [117/158; 95 % confidence interval (CI): 66.5 % to 80.7 %], with a kappa coefficient of 0.44 (95 % CI: 0.30 to 0.57). Only 20.1 % (48/239) of results were discussed in a subsequent clinical note, and one result (0.4 %; 1/239) changed clinical management., Conclusions: EBV qPCR testing on BAL offers limited clinical impact. Additional biomarkers are required to improve the diagnosis of EBV-associated lung diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

An increased risk for human infection with avian influenza A(H5N1) viruses is of concern. We developed an internally controlled, dual-target reverse transcription PCR for influenza A(H5) subtyping. This test could be used to detect influenza A(H5) in clinical samples.

Respiratory syncytial virus (RSV) causes a large burden of respiratory illness globally. It has two subtypes, RSV A and RSV B, but little is known regarding the predominance of these subtypes during different seasons and their impact on morbidity and mortality. Using molecular methods, we quantified RSV A and RSV B RNA in wastewater solids across multiple seasons and metropolitan areas to gain insight into the predominance of RSV subtypes. We determined the predominant subtype for each group using the proportion of RSV A to total RSV (RSV A + RSV B) in each wastewater sample ( P A,WW ) and conducted a comparative analysis temporally, spatially, and against clinical specimens. A median P A,WW of 0.00 in the first season and 0.58 in the second season indicated a temporal shift in the predominant subtype. Spatially, while we observed dominance of the same subtype, P A,WW was higher in some areas ( P A,WW = 0.58-0.88). The same subtype predominated in wastewater and clinical samples, but clinical samples showed higher levels of RSV A (RSV A positivity in clinical samples = 0.79, median P A,WW = 0.58). These results suggest that wastewater, alongside clinical data, holds promise for enhanced subtype surveillance.IMPORTANCERespiratory syncytial virus (RSV) causes a large burden of respiratory illness globally. It has two subtypes, RSV A and RSV B, but little is known regarding the predominance of these subtypes during different seasons and their impact on morbidity and mortality. The study illustrates that information on subtype predominance can be gleaned from wastewater. As a biological composite sample from the entire contributing population, wastewater monitoring of RSV A and B can complement clinical surveillance of RSV., Competing Interests: The authors declare no conflict of interest.

The present study aims to establish NaOCl as a potential oxidant in the COD removal of Acid Orange 8 using UVC light (λ = 254 nm) and Fe 2+ as catalysts. The different systems used in this study are NaOCl, Fe 2+ /NaOCl, UV/NaOCl, and Fe 2+ /NaOCl/UV. All these process were found to be operative in acidic, neutral and basic medium. The initial decolorisation and COD removal efficiency (COD eff ) for different systems follow the order: Fe 2+ /NaOCl/UV > UV/NaOCl > Fe 2+ /NaOCl > NaOCl. Nevertheless, NaOCl can alone be used in the treatment process considering its COD eff to the extent of 95% in 90 min. The change in pH of the solutions after treatment is an important observation - for non-UV systems it remained around 11.0 and 7.0 in other systems. Thus, UV systems are environmental benign. The effect of various anions on COD eff was tested in Fe 2+ systems. Presence of F - ions were found to accelerate COD eff in both the systems. However, the effect is more pronounced in Fe 2+ / NaOCl/UV, where complete COD eff was observed in the presence of 9.0 gl -1 of F - . The COD removal kinetics for all systems was studied using zero-order, first-order, second-order, and BMG kinetic models. BMG model was found to be more suitable among all and is in good agreement with COD eff of all systems. It is, therefore, established that NaOCl can serve as a powerful oxidant in the advanced oxidation process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A three-dimensional (3D) Ni-MOF of the formula [Ni(C 4 H 4 N 2 )(CHO 2 ) 2 ] n , has been reported, which shows a capacitance of 2150 F/g at a current density of 1A/g in a three-electrode setup (5.0 M KOH). Post-mortem analysis of the sample after three-electrode measurements revealed the bias-induced transformation of Ni-MOF to Ni(OH) 2 , which has organic constituents intercalated within the sample exhibiting better storage performance than bulk Ni(OH) 2 . Afterward, the synthesized MOF and reduced graphene (rGO) were used as the anode and cathode electrode material, respectively, and a two-electrode asymmetric supercapacitor device (ASC) setup was designed that exhibited a capacitance of 125 F/g (at 0.2 A/g) with a high energy density of 50.17 Wh/kg at a power density of 335.1 W/kg. The ASC further has a very high reversibility (97.9% Coulombic efficiency) and cyclic stability (94%) after 5000 constant charge-discharge cycles. Its applicability was also demonstrated by running a digital watch. Using sophisticated density functional theory simulations, the electronic properties, diffusion energy barrier for the electrolytic ions (K + ), and quantum capacitance for the Ni(OH) 2 electrode have been reported. The lower diffusion energy barrier (0.275 eV) and higher quantum capacitance (1150 μF/cm 2 ) are attributed to the higher charge storage performance of the Ni-MOF-transformed Ni(OH) 2 electrode as observed in the experiment.

Despite having high analytical sensitivities and specificities, qualitative SARS-CoV-2 nucleic acid amplification tests (NAATs) cannot distinguish infectious from non-infectious virus in clinical samples. In this study, we determined the highest cycle threshold (Ct) value of the SARS-CoV-2 targets in the Xpert Xpress SARS-CoV-2/Flu/RSV (Xpert 4plex) test that corresponded to the presence of detectable infectious SARS-CoV-2 in anterior nasal swab samples. A total of 111 individuals with nasopharyngeal swab specimens that were initially tested by the Xpert Xpress SARS-CoV-2 test were enrolled. A healthcare worker subsequently collected anterior nasal swabs from all SARS-CoV-2-positive individuals, and those specimens were tested by the Xpert 4plex test, viral culture, and laboratory-developed assays for SARS-CoV-2 replication intermediates. SARS-CoV-2 Ct values from the Xpert 4plex test were correlated with data from culture and replication intermediate testing to determine the Xpert 4plex assay Ct value that corresponded to the presence of infectious virus. Ninety-eight of the 111 (88.3%) individuals initially tested positive by the Xpert Xpress SARS-CoV-2 test. An anterior nasal swab specimen collected from positive individuals a median of 2 days later (range, 0-9 days) tested positive for SARS-CoV-2 by the Xpert 4plex test in 39.8% (39/98) of cases. Of these samples, 13 (33.3%) were considered to contain infectious virus based on the presence of cultivable virus and replication intermediates, and the highest Ct value observed for the Xpert 4plex test in these instances was 26.3. Specimens that yielded Ct values of ≤26.3 when tested by the Xpert 4plex test had a likelihood of containing infectious SARS-CoV-2; however, no infectious virus was detected in specimens with higher Ct values.IMPORTANCEUnderstanding the correlation between real-time PCR test results and the presence of infectious SARS-CoV-2 may be useful for informing patient management and workforce return-to-work or -duty. Further studies in different patient populations are needed to correlate Ct values or other biomarkers of viral replication along with the presence of infectious virus in clinical samples., Competing Interests: R.F.R. received research funding from Cepheid; K.V.B. works for Becton, Dickinson and Company; D.Y. works for DH Diagnostics LLC, a Danaher company; B.A.P. received research funding from Cepheid; M.J.L. works for Cepheid.

Aryl fluorosulfates have emerged as versatile SuFExable substrates, harnessing the reactivity of the S-F bond. In this study, we unveil their alternative synthetic utility in nickel-catalyzed borylation via C-O bond activation. This method highlights mild reaction conditions, a broad substrate scope, and moderate functional group tolerance, rendering it a practical and appealing approach for synthesizing a diverse array of aryl boronate esters. Furthermore, computational analysis sheds light on the reaction pathways, uncovering the participation of LNi(0) and LNi(II)ArX species. This insight is supported by the 31 P NMR reaction monitoring along with isolation and single-crystal X-ray structural elucidation of well-defined arylnickel(II) intermediates obtained from the oxidative addition of aryl fluorosulfates. A comprehensive investigation, merging experimental and computational approaches, deepens our understanding of the alternative reactivity of SuFExable substrates., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Suicide is defined as a fatal self-injurious act with some evidence of intent to die. Despite the evolution of sophisticated methods to commit suicide, hanging remains one of the commonest methods to commit suicide across the world. To evaluate the individuals using hanging as a method of suicide and identify the contributing factors for this behaviour., Material and Methods: The study was carried out in a tertiary care hospital, over a period of 1 year on the suicide attempters using the method of hanging. Semi-structured in-depth interviews were conducted with all the 46 attempters. The questions focused on the precipitating events present before the attempt. After the in interview the risk factors of the conversations were identified, tabulated and categorized using descriptive analysis., Results: Findings from descriptive analysis reveals that significant age group using this method was below 19 years followed by 20-29 age group, female attempters were more compared to male. Psychiatric diagnosis was present in 8 attempters and 4 attempters had alcohol/substance dependence. The most common personality component in attempters was impulsivity. The most common immediate stressor found were financial stress, conflict with family, spouse, humiliation, substance abuse, exam stress and domestic violence., Conclusion: This study demonstrates that the reasons for suicide attempt by hanging is multifactorial. which includes, psychiatric diagnosis, personality factors, immediate stressors, ease of use, and accessibility, Overall, our study adds to understanding the intricates of this method and will help in developing effective suicide prevention strategies., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Community Medicine.)

Harnessing the key intermediates in metal-catalyzed reactions is one of the most essential strategies in the development of selective organic transformations. The nitrogen group transfer reactivity of metal-nitrenoids to ubiquitous C-H bonds allows for diverse C-N bond formation to furnish synthetically valuable aminated products. In this study, we present an unprecedented reactivity of iridium and ruthenium nitrenoids to generate remote carbocation intermediates, which subsequently undergo nucleophile incorporation, thus developing a formal γ-C-H functionalization of carboxylic acids. Mechanistic investigations elucidated a unique singlet metal-nitrenoid reactivity to initiate an abstraction of γ-hydride to form the carbocation intermediate that eventually reacts with a broad range of carbon, nitrogen, and oxygen nucleophiles, as well as biorelevant molecules. Alternatively, the same intermediate can lead to deprotonation to afford β,γ-unsaturated amides in a less nucleophilic solvent.

Two-dimensional semiconductors such as monolayer MoS 2 have attracted considerable attention owing to their exceptional electronic and optical characteristics. However, their practical application has been hindered by the limited light absorption resulting from atomically thin thickness and low quantum yield. A highly effective approach to address these limitations is by integrating subwavelength plasmonic nanostructures with monolayer semiconductors. In this study, we employed electron beam lithography and nanoelectroplating techniques to develop a gold nanodisc (AuND) array plasmonic platform. Monolayer MoS 2 transferred on top of the AuND array yields up to 150-fold photoluminescence enhancement compared to a gold film without normalization with respect to plasmonic hot spots. In addition, the unique protocol of nanoelectroplating helps to get flat-top cylindrical discs which enable less tear during the delicate wet transfer of monolayer MoS 2 . We explain our experimental findings based on electromagnetic simulations.

Severe dengue (SD) is a major cause of morbidity and mortality. To define dengue virus (DENV) target cells and immunological hallmarks of SD progression in children's blood, we integrated two single-cell approaches capturing cellular and viral elements: virus-inclusive single-cell RNA sequencing (viscRNA-Seq 2) and targeted proteomics with secretome analysis and functional assays. Beyond myeloid cells, in natural infection, B cells harbor replicating DENV capable of infecting permissive cells. Alterations in cell type abundance, gene and protein expression and secretion as well as cell-cell communications point towards increased immune cell migration and inflammation in SD progressors. Concurrently, antigen-presenting cells from SD progressors demonstrate intact uptake yet impaired interferon response and antigen processing and presentation signatures, which are partly modulated by DENV. Increased activation, regulation and exhaustion of effector responses and expansion of HLA-DR-expressing adaptive-like NK cells also characterize SD progressors. These findings reveal DENV target cells in human blood and provide insight into SD pathogenesis beyond antibody-mediated enhancement., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Cytomegalovirus (CMV) causes significant morbidity and mortality in immunocompromised patients, particularly transplant recipients. Quantitation of CMV DNA in peripheral blood is used to monitor prophylactic and pre-emptive approaches to prevent CMV disease, whereas CMV DNA testing of non-plasma specimens may aid in the diagnosis of end-organ disease., Methods: The analytical performance of the FDA-approved Aptima CMV Quant Assay was evaluated using reference CMV (SeraCare) diluted in defibrinated human plasma, as well as negative bronchoalveolar lavage fluid and tissue. Agreement was determined using 100 clinical acid-citrate-dextrose (ACD) plasma specimens, 77 bronchoalveolar lavage (BAL) fluids, and 101 tissues previously tested using artus CMV qPCR., Results: Aptima CMV lower limit of detection (LLOD) was 169 IU/mL for ACD plasma, 100 IU/mL for BAL, and 50 IU/mL for tissue. Positive percent agreement (PPA) was 100.0% (50/50; 95% CI: 92.9% - 100.0%) and negative percent agreement (NPA) was 94.0% (47/50; 95% CI: 83.5% - 98.8%) for ACD plasma. Bland-Altman analysis revealed a bias of 0.20 log 10 IU/mL (Aptima - artus) with 95% limits of agreement of -0.53 to 0.93. For BAL fluids, PPA was 70.0% (14/20; 95% CI: 45.7% - 88.1%) and NPA was 82.4% (43/51; 95% CI: 69.1% - 91.6%). For tissues, PPA was 90.0% (45/50; 95% CI: 78.2% - 96.7%) and NPA was 94.0% (47/50; 95% CI: 83.5% - 98.8%)., Conclusions: The Aptima CMV Quant Assay demonstrates high analytical sensitivity and good overall agreement using clinical plasma and tissue specimens., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Benjamin Pinsky reports research contracts from Hologic, Inc. and Altona Diagnostics, as well as travel support from Altona., (Copyright © 2023. Published by Elsevier B.V.)

Human immunodeficiency virus 1 (HIV-1) reverse transcriptase (RT) initiation depends on interaction between viral 5'-leader RNA, RT and host tRNA3 Lys . Therefore, we sought to identify co-evolutionary changes between the 5'-leader and RT in viruses developing RT-inhibitor resistance mutations. We sequenced 5'-leader positions 37-356 of paired plasma virus samples from 29 individuals developing the nucleoside RT inhibitor (NRTI)-resistance mutation M184V, 19 developing a non-nucleoside RT inhibitor (NNRTI)-resistance mutation and 32 untreated controls. 5'-Leader variants were defined as positions where ≥20 % of next-generation sequencing (NGS) reads differed from the HXB2 sequence. Emergent mutations were defined as nucleotides undergoing a ≥4-fold change in proportion between baseline and follow-up. Mixtures were defined as positions containing ≥2 nucleotides each present in ≥20 % of NGS reads. Among 80 baseline sequences, 87 positions (27.2 %) contained a variant; 52 contained a mixture. Position 201 was the only position more likely to develop a mutation in the M184V (9/29 vs 0/32; P =0.0006) or NNRTI-resistance (4/19 vs 0/32; P =0.02; Fisher's exact test) groups than the control group. Mixtures at positions 200 and 201 occurred in 45.0 and 28.8 %, respectively, of baseline samples. Because of the high proportion of mixtures at these positions, we analysed 5'-leader mixture frequencies in two additional datasets: five publications reporting 294 dideoxyterminator clonal GenBank sequences from 42 individuals and six National Center for Biotechnology Information (NCBI) BioProjects reporting NGS datasets from 295 individuals. These analyses demonstrated position 200 and 201 mixtures at proportions similar to those in our samples and at frequencies several times higher than at all other 5'-leader positions. Although we did not convincingly document co-evolutionary changes between RT and 5'-leader sequences, we identified a novel phenomenon, wherein positions 200 and 201 immediately downstream of the HIV-1 primer binding site exhibited an extraordinarily high likelihood of containing a nucleotide mixture. Possible explanations for the high mixture rates are that these positions are particularly error-prone or provide a viral fitness advantage.

The synergistically MXene (Ti 3 C 2 T x ) co-catalyst-decorated BiVO 4 -based heterostructured photocatalysts have been synthesized by a hydrothermal approach with varied loading concentrations of MXene (Ti 3 C 2 T x ) to drive the hexavalent chromium reduction efficiently. The formation of the heterostructured photocatalyst was confirmed by the appearance of X-ray diffraction (XRD) peaks corresponding to the monoclinic BiVO 4 phase and MXene (Ti 3 C 2 T x ) and also the antisymmetric (834 cm -1 ) and symmetric stretching (715 cm -1 ) of tetrahedral VO 4 and D (1330 cm -1 ) and G (1570 cm -1 ) bands corresponding to MXene (Ti 3 C 2 T x ) in the Raman spectrum. The worm-like structures of BiVO 4 nanocrystals grew onto the lamellar sheets of MXene (Ti 3 C 2 T x ) , as shown by field emission scanning electron microscopy (FESEM), and has an increased surface area of 15.62 m 2 g -1 in the case of BVO-20-TC . X-ray photoelectron spectroscopy (XPS) analysis confirms the presence of V 5+ and Ti 3+ states, and the uniform distribution of BiVO 4 nanocrystals over lamellar sheets of MXene (Ti 3 C 2 T x ) is evident from energy-dispersive X-ray (EDX) analysis. The ultraviolet-diffuse reflectance spectroscopy (UV-DRS) spectra suggest a decrease in the band gap energy of BVO-20-TC to 2.335 eV, promoting a higher degree of visible light harvesting. Upon optimization, by varying the pH, the amount of the photocatalyst, and the concentration of Cr(IV), BVO-20-TC exhibits the highest photocatalytic efficiency (96.39%) while using a Cr(VI) concentration of 10 ppm at pH 2 and 15 mg of the photocatalyst, and the photoreduction of Cr(VI) to Cr(III) follows the pseudo-first-order reaction. The decrease in the PL intensity in BVO-20-TC reveals a faster transfer of electrons from MXene (Ti 3 C 2 T x ) to BiVO 4 . Further, the higher degree of band bending at the BiVO 4 / MXene (Ti 3 C 2 T x ) heterojunction, revealed from the Mott-Schottky analysis, facilitates efficient charge transfer and eventually faster and efficient photoreduction of Cr(VI) to Cr(III). The reusability and stability test undertaken for BVO-20-TC reveals that even after five cycles, the Cr (VI) photoreduction efficacy is retained. This work provides insights into photoreduction of Cr (VI) by using such heterostructures.

Amine-templated 1D cobalt fluoro sulfate of the composition [(CH 3 ) 2 NH 2 ] 2 [Co 4 F 4 (SO 4 ) 3 (C 3 N 2 H 4 ) 4 ], consisting of Co 4 F 4 cubane-type secondary building unit, has been synthesized under solvothermal condition. The magnetic properties of the Co 4 F 4 cubane chain exhibited a low-temperature magnetic ordering below 17 K ( T c ) attributed to intra-cluster ferromagnetic coupling and did not show spin-glass freezing. The selenylation of the Co 4 F 4 cubane chain leads to the formation of sphere-like CoSe 2 in the hydrothermal route (CoSe 2 @HT). At the same time, nanorods of CoSe 2 encapsulated with carbon matrix were obtained in a sealed tube method (CoSe 2 @ST). Moreover, CoSe 2 @ST exhibited a higher hydrogen evolution reaction (HER) activity than CoSe 2 @HT in an acidic medium with 177 mV overpotential to achieve the benchmark current density of 10 mA cm -2 . The promising HER performance of derived CoSe 2 @ST could be attributed to an increase in the geometrical and specific activity due to the encapsulation of N-doped carbon matrix over the CoSe 2 nanorods that facilitate faster charge transfer at the electrode-electrolyte interface and higher electrochemical conductivity than the derived CoSe 2 @HT. This work demonstrates a low-temperature, solvent- and reducing agent-free new synthetic approach for synthesizing framework-derived materials.

Background: Quantitation of human herpesvirus-6 (HHV-6) DNA in clinical specimens is important for the diagnosis and management of HHV-6-associated infection and reactivation in immunocompromised patients, particularly transplant recipients., Methods: The analytical performance of the Altona RealStar ASR HHV-6 qPCR on the semi-automated AltoStar AM16 system was assessed using HHV-6 reference material in plasma and cerebral spinal fluid (CSF). Qualitative and quantitative agreement was determined using 123 clinical EDTA plasma specimens tested using a laboratory-developed HHV-6 qPCR., Results: The 95% Lower Limit of Detection was 20 IU/mL [95% confidence interval (CI): 10 to 29] in plasma and 78 IU/mL (95% CI: 55 to 146) in CSF. The assay was linear from 7.0 to 2.0 log 10 IU/mL in both matrices. Overall agreement of the RealStar ASR HHV-6 qPCR on the AltoStar AM16 with a laboratory-developed test was 95.9% (95% CI: 90.8 to 98.7). Passing-Bablok analysis of specimens quantifiable by both methods and at levels >1000 copies/mL revealed a regression line of Y = 1.00*X-0.20, with neither systematic (95% CI Y-intercept: -0.66 to 0.26) nor proportional (95% CI slope: 0.89 to 1.10) bias compared to the reference., Conclusions: The RealStar ASR HHV-6 qPCR on the AltoStar AM16 provides accurate quantitation for clinical monitoring of HHV-6 in immunocompromised hosts., Competing Interests: Benjamin A. Pinsky performed contracted research for Altona Diagnostics and Hologic, Inc. He also received travel support from Altona. The other authors report no declarations of interest., (© 2023 The Authors.)

Background and Objectives: Hepatitis E virus (HEV) is an underrecognized and emerging infectious disease that may threaten the safety of donor blood supply in many parts of the world. We sought to elucidate whether our local community blood supply is at increased susceptibility for transmission of transfusion-associated HEV infections., Materials and Methods: We screened 10,002 randomly selected donations over an 8-month period between 2017 and 2018 at the Stanford Blood Center for markers of HEV infection using commercial IgM/IgG serological tests and reverse transcriptase quantitative polymerase chain reaction assays (RT-qPCR). Donor demographic information, including gender, age, self-identified ethnicity, location of residence and recent travel, were obtained from the donor database and used to generate multivariate binary logistic regressions for risk factors of IgG seropositivity., Results: A total of 10,002 blood donations from 7507 unique donors were screened, and there was no detectable HEV RNA by RT-qPCR. The overall seropositivity rate was 12.1% for IgG and 0.56% for IgM. Multivariate analysis of unique donors revealed a significantly higher risk of IgG seropositivity with increasing age, White/Asian ethnicities and residence in certain local counties., Conclusion: Although HEV IgG seroprevalence in the San Francisco Bay Area is consistent with ongoing infection, the screening of a large donor population did not identify any viraemic blood donors. While HEV is an underrecognized and emerging infection in other regions, there is no evidence to support routine blood screening for HEV in our local blood supply currently; however, periodic monitoring may still be required to assess the ongoing risk., (© 2023 International Society of Blood Transfusion.)

Genetic analysis methods are foundational to advancing personalized medicine, accelerating disease diagnostics, and monitoring the health of organisms and ecosystems. Current nucleic acid technologies such as polymerase chain reaction (PCR) and next-generation sequencing (NGS) rely on sample amplification and can suffer from inhibition. Here, we introduce a label-free genetic screening platform based on high quality (high-Q) factor silicon nanoantennas functionalized with nucleic acid fragments. Each high-Q nanoantenna exhibits average resonant quality factors of 2,200 in physiological buffer. We quantitatively detect two gene fragments, SARS-CoV-2 envelope (E) and open reading frame 1b (ORF1b), with high-specificity via DNA hybridization. We also demonstrate femtomolar sensitivity in buffer and nanomolar sensitivity in spiked nasopharyngeal eluates within 5 minutes. Nanoantennas are patterned at densities of 160,000 devices per cm 2 , enabling future work on highly-multiplexed detection. Combined with advances in complex sample processing, our work provides a foundation for rapid, compact, and amplification-free molecular assays., (© 2023. The Author(s).)

Background: Tests that sensitively detect the presence of actively replicating SARS-CoV-2 may improve patient care by allowing the safe and timely discontinuation of isolation. Correlates of active replication include nucleocapsid antigen and virus minus-strand RNA., Methods: Qualitative agreement of the DiaSorin LIAISON SARS-CoV-2 nucleocapsid antigen chemiluminescent immunoassay (CLIA) with minus-strand RNA was determined using 402 upper respiratory specimens from 323 patients previously tested using a laboratory-developed SARS-CoV-2 strand-specific RT-qPCR. Nucleocapsid antigen levels, minus-strand and plus-strand cycle threshold values, as well as virus culture, were used to evaluate discordant specimens. Receiver operating characteristic curves were also used to identify virus RNA thresholds for active replication, including values harmonized to the World Health Organization International Standard., Results: Overall agreement was 92.0% [95% confidence interval (CI): 89.0 - 94.5], positive percent agreement was 90.6% (95% CI: 84.4 - 95.0), and negative percent agreement was 92.8% (95% CI: 89.0 - 95.6). The kappa coefficient was 0.83 (95% CI: 0.77 - 0.88). Discordant specimens contained low levels of nucleocapsid antigen and minus-strand RNA. 84.8% (28/33) were negative by culture. Sensitivity-optimized plus-strand RNA thresholds for active replication were 31.6 cycles or 3.64 log 10 IU/mL; resulting in 100.0% sensitivity (95% CI: 97.6 to 100.0) and 55.9 specificity (95% CI: 49.7 to 62.0)., Conclusions: Detection of nucleocapsid antigen by CLIA performs equivalently to minus-strand detection via strand-specific RT-qPCR, though these methods may overestimate replication-competent virus compared to culture. Careful implementation of biomarkers for actively replicating SARS-CoV-2 has the potential to inform infection control decision-making and patient management., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Plasma Epstein-Barr virus (EBV) DNA is an established biomarker for endemic nasopharyngeal carcinoma. However, existing real-time quantitative PCR (qPCR) assays are limited by poor interlaboratory reproducibility. This is a barrier to biomarker integration into staging systems and management. It was hypothesized that EBV digital PCR (dPCR) would have similar sensitivity but improved precision relative to qPCR. Using the World Health Organization EBV standard and patient specimens, the NRG-HN001 BamHI-W qPCR, two commercial EBNA-1 qPCR assays, and two laboratory-developed dPCR assays amplifying the BamHI-W, EBNA-1, and EBER targets were compared. Testing was conducted in the North American reference laboratory for the NRG-HN001 randomized trial. The EBV dPCR assays achieved similar performance compared with qPCR. Although dPCR does not require quantitation standards, different dPCR thresholding algorithms yielded significant qualitative and quantitative variation. This was most evident with low levels of EBV DNA. No-template control-informed thresholding (ddpcRquant) mitigated false-positive/false-negative findings. The NRG-HN001 BamHI-W qPCR and laboratory-developed BamHI-W droplet dPCR offered higher sensitivity, lower limit of blank, higher precision at low plasma EBV DNA levels (≤1500 IU/mL), and higher overall agreement with clinical specimens versus single-copy qPCR/dPCR targets (EBNA-1/EBER). These data confirm the rationale for using the BamHI-W target to define prognostic thresholds and indicate that both qPCR and dPCR methods harmonized to the World Health Organization standard can provide the necessary analytical performance., (Copyright © 2023 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Despite the sharp increase in mpox (formerly monkeypox) incidence and the wide geographic spread of mpox during the 2022 outbreak, the community prevalence of infection remains poorly characterized. This study is a retrospective epidemiologic survey to estimate mpox prevalence., Methods: Samples obtained for sexually transmitted infection (STI) testing from April to September 2022 in the public hospital and clinic system of San Mateo County, California were screened for mpox virus (MPXV) using polymerase chain reaction., Results: 16/1,848 samples from 11/1,645 individuals were positive for MPXV by qPCR. 4/11 individuals with positive MPXV testing were cisgender women, 2 of whom were pregnant at the time of sample collection. Both deliveries were complicated by chorioamnionitis. Anorectal and oropharyngeal samples were the most likely to be positive for MPXV (4/60 anorectal samples and 4/66 oropharyngeal samples compared with 5/1,264 urine samples and 3/445 vaginal samples)., Conclusions: Our study is one of the first epidemiologic surveys for MPXV infection outside of sexual health/STI clinic settings. Relatively high rates of MPXV from oropharyngeal and anorectal samples reinforces the importance of MPXV testing at various anatomic sites, particularly if patients are presenting with non-lesional symptoms (pharyngitis, proctitis). However, the United States Food and Drug Administration (FDA) has not yet authorized non-lesional MPXV testing. The identification of MPXV in women in our cohort suggests that the rates of mpox in women may have previously been underestimated and highlights the risk of pregnancy complications associated with mpox., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aripiprazole, a second-generation antipsychotic (SGA) medication, is an efficacious treatment for schizophrenia and bipolar disorder. However, its effects on pregnancy and lactation are not yet fully documented. Despite aripiprazole being available since 2002, there is only limited information on the risks and benefits of this treatment during pregnancy. Most of the information is limited to populationbased studies examining malformation risk or case studies or small case series. The knowledge in this topic is still insufficient and there is a need to expand the literature. In this report, we present 2 cases exposed to aripiprazole during pregnancy and lactational period. In both our cases of aripiprazole exposure, no teratogenic effects were reported, and it was reassuring that the mothers did not develop gestational diabetes. However, both patients reported lactation failure. Keyword: Mental illness, antipsychotics, aripiprazole, pregnancy.

The present study has been undertaken with an aim to design and develop safer and more efficient all solid-state electrolytes, so that the issues associated with the use of conventional room temperature ionic liquid-based electrolytes can be tackled. To fulfil this objective, a series of geminal di-cationic Organic Ionic Crystals (OICs), based on C 3 -, C 6 -, C 8 - and C 9 -alkylbridged bis-(methylpyrrolidinium)bromide are synthesized, and the structural features, thermal properties and phase behaviours of these as synthesized OICs have been investigated. Additionally, a number of electro-analytical techniques have been employed to assess their suitability as an efficient electrolyte composite (OIC:I 2 :TBAI) for all solid-state dye sensitised solar cells (DSSCs). The structural analysis has revealed that along with excellent thermal stability and well-defined surface morphology, all thsese OICs exhibit a well-ordered three-dimensional network of cations and anions that can serve as a conducting channel for the diffusion of iodide ions. Electrochemical investigations have shown that OICs with an intermediate length of alkyl bridge (C 6 - and C 8 -alkyl bridged) show better electrolytic performance than those that are based on OICs with a relatively shorter (C 3 -) or longer (C 9 -) alkyl-bridge chain. A careful analysis of the above data has essentially demonstrated that the length of the alkyl bridge chain plays a significant role in determining the structural organisation, morphology and eventually the ionic conductivity of OICs. Overall, the comprehensive knowledge on OICs that has been extracted from the current study is expected to be helpful to explore further new types of OIC-based all solid-state electrolytes with improved electrolytic performance for targeted applications.

Background: SARS-CoV-2 variant surveillance informs vaccine composition and decisions to de-authorize antibody therapies. Though detailed genetic characterization requires whole-genome sequencing, targeted mutation analysis may complement pandemic surveillance efforts., Methods: This study investigated the qualitative performance of a multiplex oligonucleotide ligation assay targeting 19 spike mutations using 192 whole genome sequenced upper respiratory samples representing SARS-CoV-2 variants of concern., Results: Initial valid results were obtained from 95.8% [95% confidence interval (CI): 92.0 - 98.2; 184/192] of samples. All eight invalid samples were valid on repeat testing. When comparing SARS-CoV-2 oligonucleotide ligase assay SARS-CoV-2 variant calls with whole genome sequencing, overall positive percent agreement was 100% (95% CI: 98.1 - 100.0; 192/192), as was the positive and negative percent agreement for each of the tested variants; Gamma, Delta, Omicron BA.1, BA.2, and BA.4/BA.5., Conclusions: This multiplexed oligonucleotide ligation assays demonstrated accurate SARS-CoV-2 variant typing compared to whole genome sequencing. Such an approach has the potential to provide improved turnaround compared to sequencing and more detailed mutation coverage than RT-qPCR., Competing Interests: Declaration of Competing Interest FK, TJB, SBH, JNW, and GBS are MSD employees. Testing was performed at Stanford using reagents and instruments provided by MSD to BAP., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

We retrospectively screened oropharyngeal and rectal swab samples originally collected in California, USA, for Chlamydia trachomatis and Neisseria gonorrhoeae testing for the presence of monkeypox virus DNA. Among 206 patients screened, 17 (8%) had samples with detectable viral DNA. Monkeypox virus testing from mucosal sites should be considered for at-risk patients.

Introduction: The routine clinical diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely restricted to real-time reverse transcription quantitative PCR (RT-qPCR), and tests that detect SARS-CoV-2 nucleocapsid antigen. Given the diagnostic delay and suboptimal sensitivity associated with these respective methods, alternative diagnostic strategies are needed for acute infection., Methods: We studied the use of a clinically validated liquid chromatography triple quadrupole method (LC/MS-MS) for detection of amino acids from plasma specimens. We applied machine learning models to distinguish between SARS-CoV-2-positive and negative samples and analyzed amino acid feature importance., Results: A total of 200 samples were tested, including 70 from individuals with COVID-19, and 130 from negative controls. The top performing model overall allowed discrimination between SARS-CoV-2-positive and negative control samples with an area under the receiver operating characteristic curve (AUC) of 0.96 (95%CI 0.91, 1.00), overall sensitivity of 0.99 (95%CI 0.92, 1.00), and specificity of 0.92 (95%CI 0.85, 0.95)., Discussion: This approach holds potential as an alternative to existing methods for the rapid and accurate diagnosis of acute SARS-CoV-2 infection., Competing Interests: A provisional patent covering the machine learning analysis for metabolomics diagnostics has been filed (CHo, PR, AL, TC, BP). The remianing authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Le, Wu, Khan, Phillips, Rajpurkar, Garland, Magid, Sibai, Huang, Sahoo, Mak, Bowen, Cowan, Pinsky and Hogan.)

Approximately 5 million dengue virus-infected patients progress to a potentially life-threatening severe dengue (SD) infection annually. To identify the immune features and temporal dynamics underlying SD progression, we performed deep immune profiling by mass cytometry of PBMCs collected longitudinally from SD progressors (SDp) and uncomplicated dengue (D) patients. While D is characterized by early activation of innate immune responses, in SDp there is rapid expansion and activation of IgG-secreting plasma cells and memory and regulatory T cells. Concurrently, SDp, particularly children, demonstrate increased proinflammatory NK cells, inadequate expansion of CD16 + monocytes, and high expression of the FcγR CD64 on myeloid cells, yet a signature of diminished antigen presentation. Syndrome-specific determinants include suppressed dendritic cell abundance in shock/hemorrhage versus enriched plasma cell expansion in organ impairment. This study reveals uncoordinated immune responses in SDp and provides insights into SD pathogenesis in humans with potential implications for prediction and treatment.

Human adenoviruses (HAdVs) cause severe disease in immunocompromised patients. Quantitation of HAdV DNA in peripheral blood is used to assess the risk of disseminated disease and to monitor response to therapy. The lower limit of detection, precision, and linearity of the semiautomated AltoStar adenovirus quantitative PCR (qPCR) was evaluated using reference HAdV-E4 in EDTA plasma and respiratory virus matrix. Qualitative and quantitative agreement was determined using 122 clinical EDTA plasma specimens previously tested using a laboratory-developed HAdV qPCR. The 95% lower limit of detection (LLOD) was 33 IU/mL (95% confidence interval [CI], 10 to 56) for EDTA plasma and 188 IU/mL (95% CI, 145 to 304) for respiratory swab matrix. In both matrices, the AltoStar HAdV qPCR was linear from 7.0 to 2.0 log 10 IU/mL. For the clinical specimens, overall agreement was 96.7% (95% CI, 91.8 to 99.1), positive percent agreement was 95.5% (95% CI, 87.6 to 98.5), and negative percent agreement was 98.2% (95% CI, 88.5 to 99.7). Passing-Bablok analysis of specimens quantifiable by both methods revealed a regression line of Y = 1.11 · X + 0.00; there was positive proportional bias (95% CI of the slope, 1.05 to 1.22) but no systematic bias (95% CI of the Y-intercept, -0.43 to 0.23) compared to the reference. The AltoStar platform provides accurate quantitation of HAdV DNA and provides a semiautomated option for the clinical monitoring of HAdV following transplantation. IMPORTANCE Accurate quantification of human adenovirus DNA in the peripheral blood plays a critical role in the management of adenovirus infections in transplant recipients. Many laboratories utilize in-house laboratory-based PCR assays for the quantification of human adenovirus, as there are few commercial options available. Here, we describe the analytical and clinical performance of the semiautomated AltoStar adenovirus quantitative PCR (Altona Diagnostics). This platform provides sensitive, precise, and accurate quantification of adenovirus DNA that is well suited for virological testing following transplantation. Prior to implementing a new quantitative test in the clinical laboratory, a rigorous evaluation is required to determine assay performance characteristics and to correlate results to current in-house methods of quantitation.

Sensing lower molecular weight in a diluted solution using a label-free biosensor is challenging and requires a miniaturized plasmonic structure, e.g. a vertical Au nanorod (AuNR) array-based metamaterials. The sensitivity of a sensor mainly depends on transducer properties and hence for instance, the AuNR array geometry requires optimization. Physical vapour deposition methods (e.g. sputtering and e-beam evaporation) require a vacuum environment to deposit Au, which is costly, time-consuming, and thickness-limited. On the other hand, chemical deposition, i.e. electroplating deposit higher thickness in less time and at lower cost, becomes an alternative method for Au deposition. In this work, we present a detailed optimization for the electroplating-based fabrication of these metamaterials. We find that slightly acidic (6.0 < pH < 7.0) gold sulfite solution supports immersion deposition, which should be minimized to avoid uncontrolled Au deposition. Immersion deposition leads to plate-like (for smaller radius AuNR) or capped-like, i.e. mushroom (for higher radius AuNR) structure formation. The electroplating time and DC supply are the tuning parameters that decide the geometry of the vertically aligned AuNR array in area-dependent electroplating deposition. This work will have implications for developing plasmonic metamaterial-based sensors., (© 2023 IOP Publishing Ltd.)

Introduction: School refusal is a broad term that encompasses a child-motivated refusal to attend or remain at school, or a clear and apparent difficulty in doing so. Different factors that may influence the development of school refusal include a genetic predisposition, the home and family environment, the school environment, and social pressures. the present study aimed at examining, the psychiatric diagnostic status of children and adolescents who presented with school refusal., Materials and Methods: 92 consecutive subjects who attended the Child guidance clinic at Tata Main Hospital Jamshedpur were taken up for this study. The Clinical Diagnosis was based on the classificatory system of the International classification of diseases-10(ICD-10) through interviews., Results: findings show that the mean age of the patient was 9.6 years. The prominent psychiatric co-morbidity present was Childhood emotional disorder unspecified, separation anxiety, conversion disorder, over-anxiety disorder, and somatoform disorder., Conclusion: Among children who refuse school, emotional reasons and anxiety disorders are most prevalent. This calls for early recognition and appropriate culturally relevant intervention to ensure early return to school., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Family Medicine and Primary Care.)

Introduction: Although most laboratories are capable of employing established protocols to perform full-genome SARS-CoV-2 sequencing, many are unable to assess sequence quality, select appropriate mutation-detection thresholds, or report on the potential clinical significance of mutations in the targets of antiviral therapy METHODS: We describe the technical aspects and benchmark the performance of Sierra SARS-CoV-2, a program designed to perform these functions on user-submitted FASTQ and FASTA sequence files and lists of Spike mutations. Sierra SARS-CoV-2 indicates which sequences contain an unexpectedly large number of unusual mutations and which mutations are associated with reduced susceptibility to clinical stage mAbs, the RdRP inhibitor remdesivir, or the Mpro inhibitor nirmatrelvir RESULTS: To assess the performance of Sierra SARS-CoV-2 on FASTQ files, we applied it to 600 representative FASTQ sequences and compared the results to the COVID-19 EDGE program. To assess its performance on FASTA files, we applied it to nearly one million representative FASTA sequences and compared the results to the GISAID mutation annotation. To assess its performance on mutations lists, we applied it to 13,578 distinct Spike RBD mutation patterns and showed that exactly or partially matching annotations were available for 88% of patterns CONCLUSION: Sierra SARS-CoV-2 leverages previously published data to improve the quality control of submitted viral genomic data and to provide functional annotation on the impact of mutations in the targets of antiviral SARS-CoV-2 therapy. The program can be found at https://covdb.stanford.edu/sierra/sars2/ and its source code at https://github.com/hivdb/sierra-sars2., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

The self-assembly of a carboxylate-based dinucleating ligand, N , N '-bis[2-carboxybenzomethyl]- N , N '-bis[2-pyridylmethyl]-1,3-diaminopropan-2-ol (H 3 cpdp), and copper(II) ions in the presence of various exogenous ancillary ligands results in the formation of the new dinuclear complex [Cu 2 (cpdp)(μ-Hisophth)] 4 ·2H 2 isophth·21H 2 O ( 1 ), trinuclear complex [Cu 3 (Hcpdp)(Cl) 4 ] ( 2 ), and tetranuclear complex [Cu 4 (cpdp)(μ-Hphth)(μ 4 -phth)(piconol)(Cl) 2 ]·3H 2 O ( 3 ) (H 2 phth = phthalic acid; H 2 isophth = isophthalic acid; piconol = 2-pyridinemethanol; Cl - = chloride). In methanol-water, the reaction of H 3 cpdp with CuCl 2 ·2H 2 O at room temperature leads to the formation of 2 . On the other hand, 1 and 3 have been obtained by carrying out the reaction of H 3 cpdp with CuCl 2 ·2H 2 O/ m -C 6 H 4 (CO 2 Na) 2 and CuCl 2 ·2H 2 O/ o -C 6 H 4 (CO 2 Na) 2 /piconol, respectively, in methanol-water in the presence of NaOH at ambient temperature. All three complexes have been characterized by elemental analysis, molar electrical conductivity and magnetic moment measurements, FTIR, UV-vis spectroscopy, and PXRD, including single-crystal X-ray structural analyses. The molecular structure of 1 is based on a μ-alkoxide and μ-isophthalate-bridged dimeric [Cu 2 ] core; the structure of 2 represents a trimeric [Cu 3 ] core in which a μ-alcohol-bridged dinuclear [Cu 2 ] unit is exclusively coupled with a [CuCl 2 ] species by two μ:η 1 :η 1 - syn-anti carboxylate groups forming a triangular motif; the structure of 3 embodies a tetrameric [Cu 4 ] core, with two copper(II) ions in a distorted-octahedral coordination environment, one copper(II) ion in a distorted-trigonal-bipyramidal coordination environment, and the other copper(II) ion in a square-planar coordination environment. In fact, 2 and 3 represent rare examples of copper(II)-based multinuclear complexes showing outstanding features of rich coordination chemistry: (i) using a symmetrical dinucleating ligand, trinuclear complex 2 is generated with four- and five-coordination environments around copper(II) ions; (ii) the unsymmetrical tetranuclear complex 3 is obtained by using the same ligand with four-, five- and six-coordination environments around copper(II) ions; (iii) tetracopper(II) complex 3 shows four different bridging modes of carboxylate groups simultaneously such as μ:η 2 , μ:η 1 :η 1 , μ 3 :η 2 :η 1 :η 1 , and μ 4 :η 1 :η 1 :η 1 :η 1 , the μ 4 :η 1 :η 1 :η 1 :η 1 mode of phthalate being unprecedented. The formation of these [Cu 2 ], [Cu 3 ], and [Cu 4 ] complexes can be controlled by changing the exogenous ancillary ligands and pH of the reaction solutions, thus allowing an effective tuning of the self-assembly. The magnetic susceptibility measurements suggest that the copper centers in all three complexes are antiferromagnetically coupled. The thermal properties of 1 - 3 have been investigated by thermogravimetric and differential thermal analytical (TGA and DTA) techniques, indicating that the decomposition of all three complexes proceeds via multistep processes., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: Cycle threshold (Ct) values from SARS-CoV-2 reverse transcription quantitative PCR (RT-qPCR) tests are used to measure viral burden. Calibration to the First WHO International Standard for SARS-CoV-2 RNA may improve quantitative inter-assay agreement., Methods: WHO standard was tested using four emergency use authorized RT-qPCRs to generate calibration curves and evaluate Ct value differences. Harmonization of two assays, Cepheid Xpert Xpress SARS-CoV-2 targeting E and nucleocapsid (N2) [Xpert (E) and Xpert (N2)] and a laboratory-developed test targeting E [LDT (E)], was assessed using 93 positive upper respiratory samples. Platform (target) pairs were compared via Bland-Altman analysis and Passing-Bablok regression., Results: Ct values with the WHO standard were comparable across platforms and targets, except Xpert (N2) for which the mean difference was a median of 3.68 cycles (Interquartile Range, IQR = 3.23 to 3.76 cycles) greater than other platform (target) pairs. Using clinical samples, the mean difference of Xpert (N2) to LDT (E) was 3.64 cycles (95% Confidence Interval, CI =1.51 to 5.76). After calibration, the mean difference of Xpert (N2) to LDT (E) was 0.08 log 10 IU/mL (95% CI = -0.56 to 0.71) and the regression was y = 1.00x * 0.08 (95% CI slope = 0.93 to 1.07, 95% CI intercept = 0.28 to 0.42)., Conclusions: Calibration to the WHO standard resulted in the harmonization of two RT-qPCR tests, whereas analysis by Ct value alone may have led to erroneous quantitation. Harmonization to the WHO standard has the potential to improve the generalizability of clinical associations with SARS-CoV-2 RNA levels., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Brains of 42 COVID-19 decedents and 107 non-COVID-19 controls were studied. RT-PCR screening of 16 regions from 20 COVID-19 autopsies found SARS-CoV-2 E gene viral sequences in 7 regions (2.5% of 320 samples), concentrated in 4/20 subjects (20%). Additional screening of olfactory bulb (OB), amygdala (AMY) and entorhinal area for E, N1, N2, RNA-dependent RNA polymerase, and S gene sequences detected one or more of these in OB in 8/21 subjects (38%). It is uncertain whether these RNA sequences represent viable virus. Significant histopathology was limited to 2/42 cases (4.8%), one with a large acute cerebral infarct and one with hemorrhagic encephalitis. Case-control RNAseq in OB and AMY found more than 5000 and 700 differentially expressed genes, respectively, unrelated to RT-PCR results; these involved immune response, neuronal constituents, and olfactory/taste receptor genes. Olfactory marker protein-1 reduction indicated COVID-19-related loss of OB olfactory mucosa afferents. Iba-1-immunoreactive microglia had reduced area fractions in cerebellar cortex and AMY, and cytokine arrays showed generalized downregulation in AMY and upregulation in blood serum in COVID-19 cases. Although OB is a major brain portal for SARS-CoV-2, COVID-19 brain changes are more likely due to blood-borne immune mediators and trans-synaptic gene expression changes arising from OB deafferentation., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Here, we use Raman spectroscopy to investigate temperature-dependent changes in the atomic-scale structure of the zeolitic imidazolate framework ZIF-7 in a CO 2 atmosphere and uncover the mechanism of maximal CO 2 adsorption at 206 K. At 301 K, the Raman spectra of ZIF-7 at various CO 2 gas pressures reveal a narrow-pore (np) to large-pore (lp) phase transition commencing at 0.1 bar as a result of adsorption of CO 2 , as evident in the appearance of Fermi resonance bands of CO 2 at 1272 and 1376 cm -1 . Moreover, the Raman inactive bending mode of CO 2 becomes active due to geometrical distortion of adsorbed CO 2 . It further splits into two peaks due to hydrogen bonding interactions between CO 2 and the benzene ring of the benzimidazole linker ZIF-7, as supported by our computational studies. In addition, the interaction between CO 2 molecules plays a key role. Upon reducing the temperature at 1 bar CO 2 gas pressure, ZIF-7 exhibits softening of the imidazole puckering mode and the Fermi resonance CO 2 band due to interactions between CO 2 and the framework through hydrogen bonding. At 206 K, substantial modification in the lattice mode and disappearance of the Raman inactive CO 2 bending mode confirm the changes in the size of the pore cavity through structural rearrangements of CO 2 .

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose serious threats to global health. We previously reported that AAK1, BIKE and GAK, members of the Numb-associated kinase family, control intracellular trafficking of multiple RNA viruses during viral entry and assembly/egress. Here, using both genetic and pharmacological approaches, we probe the functional relevance of NAKs for SARS-CoV-2 infection. siRNA-mediated depletion of AAK1, BIKE, GAK, and STK16, the fourth member of the NAK family, suppressed SARS-CoV-2 infection in human lung epithelial cells. Both known and novel small molecules with potent AAK1/BIKE, GAK or STK16 activity suppressed SARS-CoV-2 infection. Moreover, combination treatment with the approved anti-cancer drugs, sunitinib and erlotinib, with potent anti-AAK1/BIKE and GAK activity, respectively, demonstrated synergistic effect against SARS-CoV-2 infection in vitro. Time-of-addition experiments revealed that pharmacological inhibition of AAK1 and BIKE suppressed viral entry as well as late stages of the SARS-CoV-2 life cycle. Lastly, suppression of NAKs expression by siRNAs inhibited entry of both wild type and SARS-CoV-2 pseudovirus. These findings provide insight into the roles of NAKs in SARS-CoV-2 infection and establish a proof-of-principle that pharmacological inhibition of NAKs can be potentially used as a host-targeted approach to treat SARS-CoV-2 with potential implications to other coronaviruses., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Well-defined polyhedral ZIF-67 metal-organic frameworks (MOFs) are usually synthesized using methanol as solvent. In this work, methanol is replaced with deionized water as a solvent to synthesize ZIF-67 MOFs with unique nanoflake morphology. The ZIF-67 nanoflakes are synthesized directly by in situ method on reduced graphene oxide (rGO) to obtain ZIF-67/rGO- x precursors which are further transformed into NiCo-layered double hydroxide nanocomposites (NiCo-LDH/rGO- x , x  = 10, 30, 50 and 90 mg of rGO). The NiCo-LDH/rGO- x nanostructured composites are found to be excellent materials for battery type supercapacitor (supercapattery) applications. Among these samples, the NiCo-LDH/rGO-30 composite gives maximum specific capacity of 829 C g -1 (1658 F g -1 ) at a current density of 1 A g -1 and high rate capability. The as fabricated 2-electrode symmetric Swagelok deviceNiCo-LDH/rGO-30NiCo-LDH/rGO-30delivered a high energy density of 49.2 Wh kg -1 and a power density of 4511 W kg -1 , and enabled us to glow red, blue and white LED bulbs using three coin cells. The device can show good capacity retention even after 3000 continuous charge-discharge cycles. The NiCo-LDH/rGO-30 composite, in situ derived from ZIF-67 MOF in combination with optimal amount of rGO, is an excellent material to deliver both high energy density and high power density in supercapattery devices., (© 2022 IOP Publishing Ltd.)

Competing Interests: None

Since March 2020, SARS-CoV-2 has plagued the world with COVID-19 and individuals of all ages have experienced varying symptoms of disease. Older adults were experiencing more severe disease compared to children and were prioritized by vaccination efforts. While biologic therapies and vaccinations were implemented, there were changes in public health restrictions with subsequent surges resulting in more infected children. During these surges there was a rise of different SARS-CoV-2 variants with the dominant variant initially alpha (B.1.1.7 and other Pango lineages) and epsilon (B.1.427/B.1.429) in early 2021 and a dramatic shift to delta (B.1.617.2 and other Pango lineages) by mid-summer 2021. In this study we aimed to characterize the clinical severity and host factors associated with disease by SARS-CoV-2 variant and evaluate if there are differences in disease severity by circulating variant. We retrospectively included all individuals 0-25 years of age who presented to our center and had a positive SARS-CoV-2 RT-PCR, SARS-CoV-2 variant mutation testing, and documented clinical notes from 1 January 2021 through 31 December 2021. We identified 745 individuals who met inclusion criteria and found the delta variant was associated with severe/critical disease compared to the other variants studied. The results of the model showed that underlying respiratory disease and diabetes were risk factors for progression to severe disease. These insights are important when evaluating public health measures and treatment options for children as more variants arise., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Khan, Ichura, Wang, Rezende, Sahoo, Huang, Solis, Sibai, Yamamoto, Nyathi, Bayrau, Pinsky and LaBeaud.)