Biomonitoring surveys from environmental DNA make use of metabarcoding tools to describe the community composition. These studies match their sequencing results against public genomic databases to identify the species. However, mitochondrial genomic reference data are yet incomplete, only a few genes may be available, or the suitability of existing sequence data is suboptimal for species level resolution. Here we present a dedicated and cost-effective workflow with no DNA amplification for generating complete fish mitogenomes for the purpose of strengthening fish mitochondrial databases. Two different long-fragment sequencing approaches using Oxford Nanopore sequencing coupled with mitochondrial DNA enrichment were used. One where the enrichment is achieved by preferential isolation of mitochondria followed by DNA extraction and nuclear DNA depletion (‘mitoenrichment’). A second enrichment approach takes advantage of the CRISPR-Cas9 targeted scission on previously dephosphorylated DNA (‘targeted mitosequencing’). The sequencing results varied between tissue, species, and integrity of the DNA. The mitoenrichment method yielded 0.17-12.33 % of sequences on target and a mean coverage ranging from 74.9-805-fold. The targeted mitosequencing experiment from native genomic DNA yielded 1.83-55 % of sequences on target and a 38-2123-fold mean coverage. This helped complete the mitogenome of species with homopolymeric regions, tandem repeats and gene rearrangements. We demonstrate that deep sequencing of long fragments of native fish DNA is possible, can be achieved with low computational resources in a cost-effective manner, exceeding the widespread genome skimming approach, and allowing the discovery of mitogenomes of non-model or understudied fish taxa to a broad range of laboratories worldwide.

Being able to link clinical outcomes to SARS-CoV-2 virus strains is a critical component of understanding COVID-19. Here we discuss how current processes hamper sustainable data collection to enable meaningful analysis and insights. Following ‘Fast Healthcare Interoperable Resource’ implementation guide, we introduce an ontology-based standard questionnaire to overcome these shortcomings and describe patient “journeys” in coordination with the World Health Organization. We identify steps in the clinical health data acquisition cycle and workflows that likely have the biggest impact in the data-driven understanding of this virus.

Background: Pain is the clinical hallmark of sickle cell disease (SCD) leading to hospitalization, psychological sequelae and a decreased health-related quality of life. The aim of this systematic literature review is to evaluate the efficacy of non-pharmacological interventions in reducing sickle cell-related pain in children with SCD. Methods: A comprehensive literature search up until October 2022 was performed to identify studies that investigated the efficacy of non-pharmacological interventions on (1) pain frequency and/or intensity, and (2) analgesic and health service use in children with SCD. Randomized controlled (RCTs) trials and quasi-experimental designed (QED) studies that investigated non-pharmacological interventions for pediatric patients with SCD until the age of 21 years were considered for inclusion. Results: Ten articles (5 RCTs and 5 QED studies) with 422 participants were included. They investigated cognitive behavioral therapy (CBT) (n =5), biofeedback (n=2), massage (n=1), virtual reality (n=1) and yoga (n=1). CBT, biofeedback, massage, virtual reality and yoga significantly reduced frequency and/or intensity of SCD-related pain. Biofeedback also significantly reduced analgesic use. Conclusion: Non-pharmacological interventions may be effective in reducing pain in pediatric SCD patients. However, due to the heterogeneity of the included studies a quantitative analysis could not be performed. Awaiting further supporting evidence, healthcare providers should consider implementing these interventions as valuable part of a comprehensive pain management strategy plan to improve the outcome of sickle cell-related pain.

We report mild COVID-19 manifestation in high-risk patient with sufficient plasma 25-OH-Vitamin D3 level. Given the global pandemic of vitamin D deficiency, as well as its likely beneficial effects during SARS-CoV-2 infection, report highlights importance of routine 25-OH-Vitamin D3 measurement, either for clinical course prediction or deciding on supplementation.

Rationale, aims and objectives In the US, the reluctance of the federal government to impose a national stay-at-home policy in wake of COVID19 pandemic has left the decision of how to achieve social distancing to individual state governors. We hypothesized that in the absence of formal guidelines, the decision to close a state reflects the classic Weber-Fechner law of psychophysics- the amount by which a stimulus (such as number of cases or deaths) must increase in order to be noticed as a fraction of the intensity of that stimulus. Methods On April 12, 2020 we downloaded data from the New York Times database from all 50 states and the District of Columbia; by that time all but 7 states had issued the stay-at-home orders. We fitted the Weber-Fechner logarithmic function by regressing the log2 of cases and deaths respectively against the daily counts. We also conducted Cox regression analysis to determine if the probability of issuing the stay-at-home order increases proportionally as the number of cases or deaths increases. Results We found that the decision to issue the state-at-home order reflects the Weber-Fechner law. Both the number of infections (p=<0.0001; R2=0.79) and deaths (p<0.0001; R2=0.63) were significantly associated with the decision to issue the stay-at-home orders. The results indicate that for each doubling of infections or deaths, an additional 4 to 6 states will issue stay-at-home orders. Cox regression showed that when the number of deaths reached 256 and the number of infected people were over 16,000 the probability of issuing “stay-at-home” order was close to 100%. We found no difference in decision-making according to the political affiliation; the results remain unchanged on July 16,2020. Conclusions when there are not clearly articulated rules to follow, decision-makers resort to simple heuristics, in this case one consistent with the Weber-Fechner law.

Aim A robust and user-friendly software tool was developed for the prediction of dopamine D2 receptor occupancy (RO) in patients with schizophrenia treated with either olanzapine or risperidone. This tool can facilitate clinician exploration of the impact of treatment strategies on RO using sparse plasma concentration measurements. Methods Previously developed population pharmacokinetic (PPK) models for olanzapine and risperidone were combined with a PD model for D2 receptor occupancy (RO) and implemented in the R programming language. MAP Bayesian estimation was used to provide predictions of plasma concentration and receptor occupancy and based on sparse PK measurements. Results The average (standard deviation) response times of the tools were 2.8 (3.1) and 5.3 (4.3) seconds for olanzapine and risperidone, respectively. The mean error (95% confidence interval) and root mean squared error (RMSE, 95% CI) of predicted versus observed concentrations were 3.73 ng/mL (-2.42 – 9.87) and 10.816 (6.71 – 14.93) for olanzapine, and 0.46 ng/mL (-4.56 – 5.47) and 6.68 (3.57 – 9.78) for risperidone and its active metabolite (9-OH risperidone). Mean error and RMSE of RO were -1.47% (-4.65 – 1.69) and 5.80 (3.89 – 7.72) for olanzapine and -0.91% (-7.68 – 5.85) and 8.87 (4.56 – 13.17) for risperidone. Conclusion Treatment of schizophrenia with antipsychotics offers unique challenges and requires careful monitoring to establish the optimal dosing regimen. Our monitoring software predicts RO in a reliable and accurate form.

Omicron BF.7 became the predominant SARS-CoV-2 variant in Beijing after the adjustment of COVID-19 response strategies in December 2022. The ability of antibodies elicited by BF.7 infection to cross-react with SARS-CoV-2-like viruses is unknown. This study aimed to investigate the cross-reactive neutralizing antibodies against SARS-CoV-2-related pangolin coronavirus GX_P2V in sera from vaccinated and/or SARS-CoV-2 infected individuals. All vaccinated individuals who recovered from Omicron BF.7 breakthrough infections exhibited substantially higher levels of neutralizing antibodies against GX_P2V among collected subject populations (geometric mean titer [GMT] = 362). Uninfected individuals who received four-mixed-dose vaccines also demonstrated higher levels of neutralizing antibodies (GMT = 44) against GX_P2V than those who received two- or three-dose vaccines and those who recovered from wild type SARS-CoV-2. This finding highlights the significance of prior and hybrid booster vaccinations with wild-type SARS-CoV-2 vaccines in generating potent cross-protective immunity against future spillovers of SARS-CoV-2-like viruses.

Biologic Pathways For Chronic Spontaneous Urticaria And Their Regulation By Benralizumab

Background and Purpose: Astrocytic nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a potential therapeutic target of ischemic preconditioning (IPC). Icariside Ⅱ (ICS Ⅱ) is a naturally occurring flavonoid derived from Herba Epimedii with Nrf2 induction potency. This study was designed to clarify whether ICS Ⅱ simulates IPC neuroprotection and to decipher if the astrocytic-Nrf2 is contributed to ICS Ⅱ preconditioning against ischemic stroke. Experimental Approach: Mice with transient middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia and oxygen-glucose deprivation (OGD)-injured primary astrocytes were used to explore the neuroprotective of ICS Ⅱ preconditioning. Additionally, Nrf2-deficient mice were pretreated with ICS Ⅱ to determine whether ICS Ⅱ exerts its neuroprotection by activating Nrf2. Key results: ICS Ⅱ pre-treatment dramatically mitigated the cerebral injury in ischemic stroke mice along with restoring long-term recovery. Furthermore, proteomics screening identified Nrf2 is a crucial gene evoked by ICS Ⅱ stimulation and is required for the anti-oxidative effect and anti-inflammatory effect of ICS Ⅱ. Most interestingly, ICS Ⅱ directly bound with Nrf2 and reinforced the transcriptional activity of Nrf2 after MCAO. Moreover, ICS Ⅱ pre-treatment exerted cytoprotective effect on astrocytes after lethal oxygen-glucose deprivation insult via promoting Nrf2 nuclear translocation and mediating OXPHOS/NF-κB/ferroptosis axis. While, abrogated neuroprotection in Nrf2-deficient mice and astrocyte potently supports Nrf2-dependent neuroprotection of ICS Ⅱ. Conclusions and implications: ICS Ⅱ preconditioning confers robust neuroprotection against ischemic stroke via astrocytic Nrf2-mediated OXPHOS/NF-κB/ferroptosis axis, it is concluded that ICS Ⅱ will be serve as a promising Nrf2 activator to rescue ischemic stroke.

Background: Mites represent the second largest group with diverse niches and feeding habits, except for insects. Scabies mites are the causative agents of highly contagious skin disease in humans and more than 100 mammals. Although several versions of Sarcoptes scabiei genome have been published, i.e. var. suis, var. canis and var. hominis, the chromosome-level genome and population divergence is still desired for the community. Besides, the molecular mechanisms that scabies mites adapt to a parasitic lifestyle remains unclear. The taxonomy and ancestral origin of the scabies mite is unknown. Results: Here, we reported the first chromosome-level reference genome of S. scabiei, which was isolated from rabbits. The genome has a contig N50 size of 5.92 Mb, a total assembled length of 57.30 Mb, and ~12.65% of repetitive sequences and 9,333 protein‑coding genes were predicted. Population genetics analysis supported that scabies mites isolated from different hosts can be subdivided by hosts, and humans are likely the primary hosts of scabies mites, followed by pigs, dogs, and rabbits. However, phylogeny results suggested that rabbit was infected with scabies long before they were domesticated by humans, contradicting previous hypothesis that humans transmitted scabies mites to animals through domestication. Comparative genomics between scabies mites and mites of other feeding habits provided clues concerning the mechanisms of adaptation to permanent parasitic life from morphology, detoxification, and metabolism. Conclusions: Together, the first chromosome-level S. scabiei genome and population genetics analysis indicated its genetic subdivisions and within-host species divergence, which also provide evidence for further control of this highly contagious skin disease.

Disseminated neoplasia (DN) is one of the most challenging and unrecognised diseases occurring in aquatic fauna. It has been diagnosed in four bivalve species from the Gulf of Gdańsk (Southern Baltic Sea) with the highest frequency in Limecola balthica (formerly Macoma balthica), reaching up to 94% in some populations. The aetiology of DN in the Baltic Sea has not yet been identified, with earlier studies trying to link its occurrence with environmental pollution. Taking into account recent research providing evidence that DN is horizontally transmitted as clonal cells between individuals in some bivalve species, we aimed to test whether DN is a transmissible cancer in the population of L. balthica from the Gulf of Gdańsk highly affected with cancer. We examined mitochondrial cytochrome c oxidase I (mtCOI) and elongation factor 1α (EF1α) sequences of genomes obtained from haemolymph and tissues of neoplastic and healthy individuals. Sequence analysis resulted in detection of an independent transmissible cancer lineage occurring in 4 neoplastic clams that is not present in healthy animals. This paper describes the first case of transmissible DN in the clam L. balthica providing further insights for studies on this disease.

Background. We sought to evaluate the impact of changes in estimates of COVID-19 vaccine effectiveness on the incidence of laboratory-confirmed infection among frontline workers at high risk for SARS-CoV-2. Methods. We analyzed data from a prospective frontline worker cohort to estimate the incidence of COVID-19 by month as well as the association of COVID-19 vaccination, occupation, demographics, physical distancing and mask use with infection risk. Participants completed baseline and quarterly surveys, and each week self-collected mid-turbinate nasal swabs and reported symptoms. Results. Among 1,018 unvaccinated and 3,531 fully vaccinated workers, the monthly incidence of laboratory-confirmed SARS-CoV-2 infection in January 2021 was 13.9 (95% confidence interval [CI]: 10.4-17.4), declining to 0.5 (95% CI -0.4-1.4) per 1000 person-weeks in June. By September 2021, when the Delta variant predominated, incidence had once again risen to 13.6 (95% CI 7.8-19.4) per 1000 person-weeks. In contrast, there was no reportable incidence among fully vaccinated participants at the end of January 2021, and incidence remained low until September 2021 when it rose modestly to 4.1 (95% CI 1.9-3.8) per 1000. Below average facemask use was associated with a higher risk of infection for unvaccinated participants during exposure to persons who may have COVID-19, and vaccinated participants during hours in the community. Conclusions. COVID-19 vaccination was significantly associated with a lower risk of SARS-CoV-2 infection despite Delta variant predominance. Our data demonstrate the added protective benefit of facemask use among both unvaccinated and vaccinated frontline workers.

Artiodactyl prey species of Chile, especially guanacos (Lama guanicoe) are reported to be very susceptible to predation by pack hunting feral dogs. It has been previously suggested that guanacos and endemic South American deer may have evolved in the absence of pack-hunting cursorial predators. However, the paleoecology of canid presence in southern South America and Chile is unclear. Here, we review the literature on South American and Chilean canids, their distributions, ecologies and hunting behaviour. We consider both wild and domestic canids, including Canis familiaris breeds. We establish two known antipredator defense behaviours of guanacos: predator inspection of ambush predators, e.g. Puma concolor, and rushing at and kicking smaller cursorial predators, e.g. Lycalopex culpaeus. We propose that since the late Pleistocene extinction of hypercarnivorous group-hunting canids east of the Andes, there were no native species creating group-hunting predation pressures on guanacos. Endemic deer of Chile may have never experienced group hunting selection pressure from native predators. Even hunting dogs (or other canids) used by indigenous groups in the far north and extreme south of Chile (and presumably the center as well) appear to have been used primarily within ambush hunting strategies. This may account for the susceptibility of guanacos and other prey species to feral dog attacks. We detail seven separate hypotheses that require further investigation in order to assess how best to respond to the threat posed by feral dogs to the conservation of native deer and camelids in Chile and other parts of South America.

This paper considers minimizers of the following inhomogeneous $L^2$-subcritical energy functional \[E(u):=\int_{\R^N}|\nabla u|^{2}dx-\frac{2}{p+1}\int_{\R^N}m(x)|u|^{p+1}dx,%\ u\in H^{1}(\R^N), \] under the mass constraint $\|u\|^{2}_{2}=M$. Here $N\geq1$, $p\in(1,1+\frac{4}{N})$, $M>0$ and the inhomogeneous term $m(x)$ satisfies $0

Calcium (Ca 2+) is an important second messenger in plants. The activation of Ca 2+ signaling cascades is critical in the activation of adaptive processes in response to perceived environmental stimuli, including biotic stresses. The colonization of roots by the plant growth promoting endophyte Serendipita indica involves the increase of cytosolic Ca 2+ levels in Arabidopsis thaliana. In this study, we investigated transcriptional changes in Arabidopsis roots during symbiosis with S. indica. RNA-seq profiling disclosed the significant induction of CALCINEURIN B-LIKE 7 ( CBL7) during early- and later phases of the interaction. Consistent with the transcriptomics analysis, reverse genetic evidence and yeast two-hybrid studies highlighted the functional relevance of CBL7 and tested the involvement of a CBL7-CBL-INTERACTING PROTEIN KINASE 13 (CIPK13) signaling pathway in the establishment of the mutualistic relationship that promotes plant growth. The loss-of-function of CBL7 abolished the growth promoting effect of S. indica and affected the colonization of the root by the fungus. The subsequent transcriptomics analysis of cbl7 revealed the involvement of this Ca 2+ sensor in activating plant defense responses. Furthermore, we report on the contribution of CBL7 to potassium transport in Arabidopsis. Triggered by the differential expression of a small number of K + channels/transporter genes, we analyzed K + contents in wild-type and cbl7 plants and observed a significant accumulation of K + in root of cbl7 plants, while shoot tissues demonstrated K + depletion. Taken together, our work associates CBL7 with an important role in the mutual interaction between Arabidopsis and S. indica and links the CBL7 Ca 2+ receptor protein to K + transport.

Bangladesh recently faced large outbreaks of both COVID-19 and Dengue fever. A 28-year-old woman suffered from symptoms including hemoptysis as first presentation followed by high-grade fever, sore throat, and fatigue. SARS-CoV-2 was confirmed by RT-PCR and also diagnosed dengue later on.COVID-19 and dengue fever could be a harmful combination.

As sessile organisms, plants are constantly challenged by a dynamic growing environment. This includes fluctuations in temperature, water availability, light levels, and atmospheric conditions. In concert with changes in abiotic conditions, plants experience changes in biotic stress pressures, including plant pathogens, viruses, and herbivores. Human-induced increases in atmospheric carbon dioxide (CO 2) levels have led to alterations in plant growth environments that challenge their productivity and nutritional quality. Additionally, it is predicted that climate change will alter the prevalence and virulence of plant pathogens, further challenging plant productivity. A knowledge gap exists in the complex interplay between plant responses to biotic and abiotic stress conditions. Closing this gap is crucial for developing climate resilient crops in the future. Here, we review the physiological responses of plants to elevated CO 2, temperature, tropospheric ozone (O 3), and drought conditions, as well as the interaction of these abiotic stress factors with plant pathogen pressure. Additionally, we describe the crosstalk and trade-offs involved in plant responses to both abiotic and biotic stress, and outline targets for future work to develop a more sustainable future food supply in light of future climate change.

Level and duration of protective immunity against SARS-CoV-2 after primary infection is of crucial importance for preventive approaches. In order to provide evidence for the longevity of specific antibodies, we investigated the generation and maintenance of neutralizing antibodies of convalescent SARS-CoV-2-afflicted patients over a five month period post primary infection using an immunofluorescence assay, a commercial chemiluminescent immunoassay and an in-house enzyme-linked plaque-reduction neutralization assay. We present the successful application of an improved version of the plaque-reduction neutralization assay, which can be analyzed optometrically, significantly simplifying the interpretation of the results. Based on the results of the plaque-reduction neutralization assay, neutralizing antibodies were maintained in 85.3% of convalescent individuals without significant decay over five months. Furthermore, a positive correlation between severity of infection and neutralizing titer was shown. In conclusion, SARS-CoV-2-afflicted individuals have been proven to be able to establish and maintain neutralizing antibodies over a five months’ period after primary infection which allows to hope for long-lasting presumably protective humoral immunity after wild-type infection or even after vaccination.