Bidirectional Multiphoton Communication between Remote Superconducting Nodes.

Quantum communication test beds provide a useful resource for experimentally investigating a variety of communication protocols. Here we demonstrate a superconducting circuit test bed with bidirectional multiphoton state transfer capability using time-domain shaped wave packets. The system we use to achieve this comprises two remote nodes, each including a tunable superconducting transmon qubit and a tunable microwave-frequency resonator, linked by a 2 m-long superconducting coplanar waveguide, which serves as a transmission line. We transfer both individual and superposition Fock states between the two remote nodes, and additionally show that this bidirectional state transfer can be done simultaneously, as well as being used to entangle elements in the two nodes.

Clarifying directional dependence among measures of early auditory processing and cognition in schizophrenia: leveraging Gaussian graphical models and Bayesian networks.

BACKGROUND: Research using latent variable models demonstrates that pre-attentive measures of early auditory processing (EAP) and cognition may initiate a cascading effect on daily functioning in schizophrenia. However, such models fail to account for relationships among individual measures of cognition and EAP, thereby limiting their utility. Hence, EAP and cognition may function as complementary and interacting measures of brain function rather than independent stages of information processing. Here, we apply a data-driven approach to identifying directional relationships among neurophysiologic and cognitive variables. METHODS: Using data from the Consortium on the Genetics of Schizophrenia 2, we estimated Gaussian Graphical Models and Bayesian networks to examine undirected and directed connections between measures of EAP, including mismatch negativity and P3a, and cognition in 663 outpatients with schizophrenia and 630 control participants. RESULTS: Chain structures emerged among EAP and attention/vigilance measures in schizophrenia and control groups. Concerning differences between the groups, object memory was an influential variable in schizophrenia upon which other cognitive domains depended, and working memory was an influential variable in controls. CONCLUSIONS: Measures of EAP and attention/vigilance are conditionally independent of other cognitive domains that were used in this study. Findings also revealed additional causal assumptions among measures of cognition that could help guide statistical control and ultimately help identify early-stage targets or surrogate endpoints in schizophrenia.

Early auditory processing abnormalities alter individual learning trajectories and sensitivity to computerized cognitive training in schizophrenia.

BACKGROUND: Auditory system plasticity is a promising target for neuromodulation, cognitive rehabilitation and therapeutic development in schizophrenia (SZ). Auditory-based targeted cognitive training (TCT) is a 'bottom up' intervention designed to enhance the speed and accuracy of auditory information processing, which has been shown to improve neurocognition in certain SZ patients. However, the dynamics of TCT learning as a function of training exercises and their impact on neurocognitive functioning and therapeutic outcomes are unknown. METHODS: Forty subjects (SZ, n = 21; healthy subjects (HS), n = 19) underwent comprehensive clinical, cognitive, and auditory assessments, including measurements of auditory processing speed (APS) at baseline and after 1-h of TCT. SZ patients additionally completed 30-hours of TCT and repeated assessments ~10-12 weeks later. RESULTS: SZ patients were deficient in APS at baseline (d = 0.96, p < 0.005) relative to HS. After 1-h of TCT, analyses revealed significant main effects of diagnosis (d = 1.75, p = 0.002) and time (d = 1.04, p < 0.001), and a diagnosis × time interaction (d = 0.85, p = 0.02) on APS. APS learning effects were robust after 1-h in SZ patients (d = 1.47, p < 0.001) and persisted throughout the 30-h of training. Baseline APS was associated with verbal learning gains after 30-h of TCT (r = 0.51, p = 0.02) in SZ. CONCLUSIONS: TCT learning metrics may have prognostic utility and aid in the prospective identification of individuals likely to benefit from TCT. Future experimental medicine studies may advance predictive algorithms that enhance TCT-related clinical, cognitive and functional outcomes.

Thermoresponsive Conductivity of Graphene-Based Fibers.

Smart materials are versatile material systems which exhibit a measurable response to external stimuli. Recently, smart material systems have been developed which incorporate graphene in order to share on its various advantageous properties, such as mechanical strength, electrical conductivity, and thermal conductivity as well as to achieve unique stimuli-dependent responses. Here, a graphene fiber-based smart material that exhibits reversible electrical conductivity switching at a relatively low temperature (60 °C), is reported. Using molecular dynamics (MD) simulation and density functional theory-based non-equilibrium Green's function (DFT-NEGF) approach, it is revealed that this thermo-response behavior is due to the change in configuration of amphiphilic triblock dispersant molecules occurring in the graphene fiber during heating or cooling. These conformational changes alter the total number of graphene-graphene contacts within the composite material system, and thus the electrical conductivity as well. Additionally, this graphene fiber fabrication approach uses a scalable, facile, water-based method, that makes it easy to modify material composition ratios. In all, this work represents an important step forward to enable complete functional tuning of graphene-based smart materials at the nanoscale while increasing commercialization viability.

Source decomposition of the frontocentral auditory steady-state gamma band response in schizophrenia patients and healthy subjects.

AIM: Gamma-band auditory steady-state response (ASSR) is a neurophysiologic index that is increasingly used as a translational biomarker in the development of treatments of neuropsychiatric disorders. While gamma-band ASSR is generated by distributed networks of highly interactive temporal and frontal cortical sources, the majority of human gamma-band ASSR studies using electroencephalography (EEG) highlight activity from only a single frontocentral scalp site, Fz, where responses tend to be largest and reductions in schizophrenia patients are most evident. However, no previous study has characterized the relative source contributions to Fz, which is a necessary step to improve the concordance of preclinical and clinical EEG studies. METHODS: A novel method to back-project the contributions of independent cortical source components was applied to assess the independent sources and their proportional contributions to Fz as well as source-resolved responses in 432 schizophrenia patients and 294 healthy subjects. RESULTS: Independent contributions of gamma-band ASSR to Fz were detected from orbitofrontal, bilateral superior/middle/inferior temporal, bilateral middle frontal, and posterior cingulate gyri in both groups. In contrast to expectations, the groups showed comparable source contribution weight to gamma-band ASSR at Fz. While gamma-band ASSR reductions at Fz were present in schizophrenia patients consistent with previous studies, no group differences in individual source-level responses to Fz were detected. CONCLUSION: Small differences in multiple independent sources summate to produce scalp-level differences at Fz. The identification of independent source contributions to a single scalp sensor represents a promising methodology for measuring dissociable and homologous biomarker targets in future translational studies.

Detection of coronaviruses in Pteropus & Rousettus species of bats from different States of India.

Background & objectives: Bats are considered to be the natural reservoir for many viruses, of which some are potential human pathogens. In India, an association of Pteropus medius bats with the Nipah virus was reported in the past. It is suspected that the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also has its association with bats. To assess the presence of CoVs in bats, we performed identification and characterization of bat CoV (BtCoV) in P. medius and Rousettus species from representative States in India, collected during 2018 and 2019. Methods: Representative rectal swab (RS) and throat swab specimens of Pteropus and Rousettus spp. bats were screened for CoVs using a pan-CoV reverse transcription-polymerase chain reaction (RT-PCR) targeting the RNA-dependent RNA polymerase (RdRp) gene. A single-step RT-PCR was performed on the RNA extracted from the bat specimens. Next-generation sequencing (NGS) was performed on a few representative bat specimens that were tested positive. Phylogenetic analysis was carried out on the partial sequences of RdRp gene sequences retrieved from both the bat species and complete viral genomes recovered from Rousettus spp. Results: Bat samples from the seven States were screened, and the RS specimens of eight Rousettus spp. and 21 Pteropus spp. were found positive for CoV RdRp gene. Among these, by Sanger sequencing, partial RdRp sequences could be retrieved from three Rousettus and eight Pteropus bat specimens. Phylogenetic analysis of the partial RdRp region demonstrated distinct subclustering of the BtCoV sequences retrieved from these Rousettus and Pteropus spp. bats. NGS led to the recovery of four sequences covering approximately 94.3 per cent of the whole genome of the BtCoVs from Rousettus bats. Three BtCoV sequences had 93.69 per cent identity to CoV BtRt-BetaCoV/GX2018. The fourth BtCoV sequence was 96.8 per cent identical to BtCoV HKU9-1. Interpretation & conclusions: This study was a step towards understanding the CoV circulation in Indian bats. Detection of potentially pathogenic CoVs in Indian bats stresses the need for enhanced screening for novel viruses in them. One Health approach with collaborative activities by the animal health and human health sectors in these surveillance activities shall be of use to public health. This would help in the development of diagnostic assays for novel viruses with outbreak potential and be useful in disease interventions. Proactive surveillance remains crucial for identifying the emerging novel viruses with epidemic potential and measures for risk mitigation.

Conceptualizations of Mental Disorder at a US Academic Medical Center.

How health care professionals conceptualize mental illness has received relatively little attention in existing literature. This survey explored how health care professionals, academic faculty, and trainees at a US academic medical center (departments of psychiatry, neurology, family medicine, and geriatric medicine, as well as medical students, nurses, and social workers) conceptualize the notion of mental disorder. Respondents (N = 209) were asked to rate their agreement or disagreement with a variety of conceptual statements. Overall, distress and impairment were seen as essential features of mental disorder, and the presence of a biological abnormality was not considered necessary. There was significant correlation between disease status and biological etiology attribution for all conditions except homosexuality. Psychology trainees and psychologists were significantly less likely to call a condition a disease compared with other groups. There was a general lack of consensus regarding conceptual issues fundamental to psychiatry. Conceptualizations of mental disorder held by respondents were complex and did not fit easily within the "biological psychiatry" paradigm.

Absence of ALOX5 gene prevents stress-induced memory deficits, synaptic dysfunction and tauopathy in a mouse model of Alzheimer's disease.

Although the initial events of Alzheimer's disease (AD) are still not known, it is clear that the disease in its sporadic form results from the combination of genetic and environmental risk factors. Among the latter, behavioral stress has been increasingly recognized as an important factor in the propagation of AD. However, the mechanisms underlying this modulation remain to be fully investigated. Since stress up-regulates the ALOX5 gene product, 5-lipoxygenase (5LO), herein we investigated its role in modulating stress-dependent development of the AD phenotype. To reach this goal, triple transgenic (3xTg) mice and 3xTg genetically deficient for 5LO were investigated after undergoing a restraint/isolation paradigm. In the present paper, we found that 28 days of restraint/isolation stress worsened tau phosphorylation and solubility, increased glycogen synthase kinase 3ß activity, compromised long-term potentiation and impaired fear-conditioned memory recall in 3xTg animals, but not in 3xTg animals lacking 5LO (3xTg/5LO-/-). These results highlight the novel functional role that the ALOX5 gene plays in the development of the biochemical, electrophysiological and behavioral sequelae of stress in the AD context. They provide critical support that this gene and its expressed protein are viable therapeutic targets to prevent the onset or delay the progression of AD in individuals exposed to this risk factor.

Effects of Memantine on the Auditory Steady-State and Harmonic Responses to 40 Hz Stimulation Across Species.

BACKGROUND: Click trains elicit an auditory steady-state response (ASSR) at the driving frequency (1F) and its integer multiple frequencies (2F, 3F, etc.) called harmonics; we call this harmonic response the steady-state harmonic response (SSHR). We describe the 40 Hz ASSR (1F) and 80 Hz SSHR (2F) in humans and rats and their sensitivity to the uncompetitive NMDA antagonist memantine. METHODS: In humans (healthy control participants, n = 25; patients with schizophrenia, n = 28), electroencephalography was recorded after placebo or 20 mg memantine in a within-participant crossover design. ASSR used 1 ms, 85-dB clicks presented in 250 40/s 500-ms trains. In freely moving rats (n = 9), electroencephalography was acquired after memantine (0, 0.3, 1, 3 mg/kg) in a within-participant crossover design; 65-dB click trains used 5-mV monophasic, 1-ms square waves (40/s). RESULTS: Across species, ASSR at 1F generated greater evoked power (EP) than the 2F SSHR. 1F > 2F intertrial coherence (ITC) was also detected in humans, but the opposite relationship (ITC: 2F > 1F) was seen in rats. EP and ITC at 1F were deficient in patients and were enhanced by memantine across species. EP and ITC at 2F were deficient in patients. Measures at 2F were generally insensitive to memantine across species, although in humans the ITC harmonic ratio (1F:2F) was modestly enhanced by memantine, and in rats, both the EP and ITC harmonic ratios were significantly enhanced by memantine. CONCLUSIONS: ASSR and SSHR are robust, nonredundant electroencephalography signals that are suitable for cross-species analyses that reveal potentially meaningful differences across species, diagnoses, and drugs.

Enteroviruses Associated with Hand Foot and Mouth Disease in Navi Mumbai, Maharashtra, India in 2022.

An outbreak of Hand Foot and Mouth Disease (HFMD) which occurred in August-September, 2022 in Navi Mumbai, India was prospectively investigated, to delineate the clinical manifestations and identify the etiological agent. Molecular characterization at ICMR-National Institute of Virology (NIV), Mumbai unit reported 69 (88.5%) cases out of 78 clinically diagnosed HFMD cases positive for enteroviruses. Thirty-nine (56.5%) children were positive for CVA6, 11 (15.9%) for CVA16, and one for CVA4 (1.4%). One case of co-infection (CVA16, CVA6) was reported. Fourteen (17.9%) cases had recurrent disease in the same season. CVA6 was associated with unusual extension of the rash beyond the conventional areas of hands, feet, and mouth, with involvement of body areas including face, axillae and trunk. Whole genome sequencing classified CVA6 as group D3 and CVA16 isolates as group B1c. Co-infection and recurrence of disease with atypical symptoms observed in this study highlight the need for continued vigilance of the evolutionary clinical characteristics of the enteroviruses causing HFMD.

Cholinergic Functioning, Cognition, and Anticholinergic Medication Burden in Schizophrenia.

Acetylcholine (ACh) signaling is critical for central nervous function and is known to be abnormal in schizophrenia (SZ), a chronic neuropsychiatric disorder in which cognitive deficits persist, despite treatment. This review provides a summary of the clinical evidence linking ACh abnormalities to SZ-associated cognitive deficits, an overview of ACh-based pro-cognitive strategies attempted in SZ, and a survey of recent studies that describe the impact of anticholinergic medication burden on cognitive outcomes in SZ. Methodological challenges that currently limit more substantial investigation of ACh in SZ patients and future directions are also discussed.

Post-COVID-19 Fungal Infection in the Aged Population.

Coronavirus disease 2019 (COVID-19) infection is currently a great cause of concern for the healthcare sector around the globe. SARS-CoV-2 is an RNA virus that causes a serious infection that is associated with numerous adverse effects and multiple complications associated with different organs and systems during its pathogenic cycle in humans. Individuals affected by COVID-19, especially elderly populations and immunocompromised people, are greatly vulnerable to opportunistic fungal pathogens. Aspergillosis, invasive candidiasis, and mucormycosis are widespread fungal coinfections in COVID-19 patients. Other fungal infections that are rare but are exhibiting increased incidence in the current scenario include infections caused by Pneumocystis jirovecii, Histoplasma sp., Cryptococcus sp., etc. By producing virulent spores, these pathogens increase the severity of the disease and increase the morbidity and fatality rates in COVID-19 patients globally. These infections generally occur in patients recovering from COVID-19 infection, resulting in rehospitalization. Older and immunocompromised individuals are at higher risk of developing opportunistic fungal infections. This review focuses on understanding the opportunistic fungal infections prevalent in COVID-19 patients, especially elderly people. We have also highlighted the important preventive methods, diagnostic approaches, and prophylactic measures for fungal infections.

Preliminary Evidence that Memantine Enhances Prepulse Effects on Startle Magnitude and Latency in Patients with Alzheimer's Disease.

BACKGROUND: The uncompetitive NMDA antagonist, memantine (MEM), enhances prepulse inhibition of startle (PPI) across species. MEM is used to treat Alzheimer's disease (AD); conceivably, its acute impact on PPI might be used to predict a patient's sensitivity to MEM's therapeutic effects. OBJECTIVE: To begin to test this possibility, we studied MEM effects on PPI and related measures in AD patients. METHODS: 18 carefully screened individuals with AD (mean age = 72.8 y; M:F=9 : 9) completed double-blind order-balanced testing with MEM (placebo versus 20 mg), assessing acoustic startle magnitude, habituation, PPI, and latency. RESULTS: Fifteen out of 18 participants exhibited reliable startle responses. MEM did not significantly impact startle magnitude or habituation. Compared to placebo responses, PPI was significantly increased after MEM (p < 0.04; d = 0.40); this comparison reached a large effect size for the 60 ms interval (d = 0.62), where maximal MEM effects on PPI were previously detected. Prepulses reduced peak startle latency ("latency facilitation") and this effect was amplified after MEM (p = 0.03; d = 0.41; for 60 ms intervals, d = 0.69). No effects of MEM were detected on cognition, nor were MEM effects on startle associated with cognitive or clinical measures. CONCLUSION: MEM enhances prepulse effects on startle magnitude and latency in AD; these changes in PPI and latency facilitation with MEM suggest that these measures can be used to detect an AD patient's neural sensitivity to acute MEM challenge. Studies in progress will determine whether such a "biomarker" measured at the outset on treatment can predict sensitivity to MEM's therapeutic effects.

Comparative pathogenicity of BA.2.12, BA.5.2 and XBB.1 with the Delta variant in Syrian hamsters.

Omicron variant is evolving into numerous sub variants with time and the information on the characteristics of these newly evolving variants are scant. Here we performed a pathogenicity evaluation of Omicron sub variants BA.2.12, BA.5.2 and XBB.1 against the Delta variant in 6-8-week-old Syrian hamster model. Body weight change, viral load in respiratory organs by real time RT-PCR/titration, cytokine mRNA quantification and histopathological evaluation of the lungs were performed. The intranasal infection of the BA.2.12, BA.5.2 and XBB.1 variants in hamster model resulted in body weight loss/reduced weight gain, inflammatory cytokine response and interstitial pneumonia with lesser severity compared to the Delta variant infection. Among the variants studied, BA.2.12 and XBB.1 showed lesser viral shedding through the upper respiratory tract, whereas the BA.5.2 showed comparable viral RNA shedding as that of the Delta variant. The study shows that the Omicron BA.2 sub variants may show difference in disease severity and transmissibility amongst each other whereas the overall disease severity of the Omicron sub variants studied were less compared to the Delta variant. The evolving Omicron sub variants and recombinants should be monitored for their properties.

Mismatch negativity predicts initial auditory-based targeted cognitive training performance in a heterogeneous population across psychiatric disorders.

Auditory-based targeted cognitive training (ATCT) programs are emerging pro-cognitive therapeutic interventions which aim to improve auditory processing to attenuate cognitive impairment in a "bottom up" manner. Biomarkers of early auditory information processing (EAIP) like mismatch negativity (MMN) and P3a have been used successfully to predict gains from a full 40 h course of ATCT in schizophrenia (SZ). Here we investigated the ability of EAIP biomarkers to predict ATCT performance in a group of subjects (n = 26) across SZ, MDD, PTSD and GAD diagnoses. Cognition was assessed via the MATRICS Consensus Cognitive Battery (MCCB) and MMN/P3a were collected prior to completing 1 h of "Sound Sweeps," a representative ATCT exercise. Baseline and final performance over the first two levels of cognitive training served as the primary dependent variables. Groups had similar MMN, but the SZ group had attenuated P3a. MMN and MCCB cognitive domain t-scores, but not P3a, were strongly correlated with most ATCT performance measures, and explained up to 61% of variance in ATCT performance. Diagnosis was not a significant predictor for ATCT performance. These data suggest that MMN can predict ATCT performance in heterogeneous neuropsychiatric populations and should be considered in ATCT studies across diagnostically diverse cohorts.

Reporting Rigor of Cancer Rehabilitation Interventions: Application of the CReDECI-2 Guidelines.

ABSTRACT: Clear reporting of cancer rehabilitation interventions is critical for interpreting and translating research into clinical practice. This study sought to examine the completeness of intervention reporting of cancer rehabilitation interventions addressing disability and to identify which elements are most frequently missing. This was a secondary analysis of randomized controlled trials included in two systematic reviews examining effectiveness of cancer rehabilitation interventions that address cancer-related disability, including functional outcomes. Eligible trials were reviewed for intervention reporting rigor using the Criteria for Reporting the Development and Evaluation of Complex Interventions in Healthcare 2 checklist. Intervention descriptions for cancer rehabilitation interventions were generally incomplete. Approximately 85% ( n = 157) of trials described ≤50% of Criteria for Reporting the Development and Evaluation of Complex Interventions in Healthcare 2 checklist items. Commonly underreported items included description of the intervention's underlying theoretical basis, fidelity, description of process evaluation or external conditions influencing intervention delivery, and costs or required resources for intervention delivery. The findings reveal that cancer rehabilitation intervention descriptions lacked necessary detail in this body of literature. Poor descriptions limit the translation of research to clinical practice. To ensure higher-quality study design and reporting, future intervention research should incorporate an intervention reporting checklist to ensure more complete descriptions for research and practice.

First detection of Varicella Zoster Virus clade 9 cases in India during mpox surveillance.

BACKGROUND: The multi-country mpox outbreak across the globe has led to the systematic surveillance of mpox cases in India. During the surveillance of mpox, we encountered cases of Varicella Zoster Virus (VZV) in suspected mpox cases amongst children & adults. This study focused on the genomic characterization of VZV in India. METHODS: A total of 331 mpox suspected cases were tested for VZV through real-time PCR, and the positive samples were subjected to next-generation sequencing to retrieve the whole genome of VZV using CLC genomics software. Phylogenetic analysis has been done in MEGA 11.0 software to identify circulating clades. RESULT: Of the 331 suspected cases, 28 cases with vesicular rashes were found to be positive for VZV. The maximum genome could be retrieved from the clinical specimens of 16 cases with coverage greater than 98% when mapped with reference strain Dumas (NC 001348). The phylogenetic analyses of these sequences determined the circulation of clades 1, 5, and 9 in India. Further, the sequence analysis demonstrated non-synonymous single nucleotide polymorphism (SNPs) among specific ORF of VZV including ORF 14, ORF 22, ORF 36, ORF 37 and ORF 51. Although clade 1 and 5 has been reported earlier, the circulation of clade 9 of VZV has been determined for the first time in India. CONCLUSION: Although the circulation of different clades of VZV was reported from India, the presence of clade 9 was detected for the first time during the mpox surveillance.

Genomic profile of SARS-CoV-2 Omicron variant and its correlation with disease severity in Rajasthan.

Background: Omicron, a new variant of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2), was first detected in November 2021. This was believed to be highly transmissible and was reported to evade immunity. As a result, an urgent need was felt to screen all positive samples so as to rapidly identify Omicron cases and isolate them to prevent the spread of infection. Genomic surveillance of SARS-CoV-2 was planned to correlate disease severity with the genomic profile. Methods: All the SARS-CoV-2 positive cases detected in the state of Rajasthan were sent to our Lab. Samples received from 24 November 2021 to 4 January 2022 were selected for Next-Generation Sequencing (NGS). Processing was done as per protocol on the Ion Torrent S5 System for 1,210 samples and bioinformatics analysis was done. Results: Among the 1,210 samples tested, 762 (62.9%) were Delta/Delta-like and other lineages, 291 (24%) were Omicron, and 157 (12.9%) were invalid or repeat samples. Within a month, the proportion of Delta and other variants was reversed, 6% Omicron became 81%, and Delta and other variants became 19%, initially all Omicron cases were seen in international travelers and their contacts but soon community transmission was seen. The majority of patients with Omicron were asymptomatic (56.7%) or had mild disease (33%), 9.2% had moderate symptoms, and two (0.7%) had severe disease requiring hospitalization, of which one (0.3%) died and the rest were (99.7%) recovered. History of vaccination was seen in 81.1%, of the previous infection in 43.2% of cases. Among the Omicron cases, BA.1 (62.8%) was the predominant lineage followed by BA.2 (23.7%) and B.1.529 (13.4%), rising trends were seen initially for BA.1 and later for BA.2 also. Although 8.9% of patients with Delta lineage during that period were hospitalized, 7.2% required oxygen, and 0.9% died. To conclude, the community spread of Omicron occurred in a short time and became the predominant circulating variant; BA.1 was the predominant lineage detected. Most of the cases with Omicron were asymptomatic or had mild disease, and the mortality rate was very low as compared to Delta and other lineages.