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Summary: Tick-borne diseases (TBD) remain prevalent worldwide, and risk assessment of tick habitat suitability is crucial to prevent or reduce their burden. This scoping review provides a comprehensive survey of models and data used to predict I. scapularis distribution and abundance in North America. We identified 4661 relevant primary research articles published in English between January 1st, 2012, and July 18th, 2022, and selected 41 articles following full-text review. Models used data-driven and mechanistic modelling frameworks informed by diverse tick, hydroclimatic, and ecological variables. Predictions captured tick abundance (n = 14, 34.1%), distribution (n = 22, 53.6%) and both (n = 5, 12.1%). All studies used tick data, and many incorporated both hydroclimatic and ecological variables. Minimal host- and human-specific data were utilized. Biases related to data collection, protocols, and tick data quality affect completeness and representativeness of prediction models. Further research and collaboration are needed to improve prediction accuracy and develop effective strategies to reduce TBD.

The current study investigates the underlying causes of the microstructural features, microhardness and high-temperature oxidation behaviour of the NiCrAlY powder cladded stainless steel (SS-304) substrate. The cladding was performed by utilizing an industrial multimode microwave apparatus, operating at 1.1 kW and 2.45 GHz with a 900 s processing time. The fabricated clad layer unveiled perfect metallurgical integration with the substrate and was noticed to be free from obvious flaws, including cracks or improper bonding at the clad-base material interface. The deposited clad layer revealed an equiaxed dendritic microstructure at the top while a typical columnar dendritic microstructure at the centre. The X-ray diffraction (XRD) examination of the clad sample revealed the existence of intermetallic compounds like γ′-Ni3Al, and Al5Y3O12 in addition to a solid solution of Iron (Fe) and Nickel (Ni) and chromium (Cr) enriched matrix. The microhardness of the clad layer was noticed to be higher than that of the uncladded SS-304 specimen. High-temperature oxidation investigation performed at 900 °C in air revealed weight gain by all the samples (bare and clad) in a parabolic fashion, initially for around 10 cycles of oxidation, beyond which the weight gain is noticed to saturate. The maximum oxidation resistance exhibited by the clad sample was credited with having intensified α-Al2O3 in the surface layer.

Summary: Traumatic brain injury (TBI) is a leading cause of chronic brain impairment and results in a robust, but poorly understood, neuroinflammatory response that contributes to the long-term pathology. We used single-nuclei RNA sequencing (snRNA-seq) to study transcriptomic changes in different cell populations in human brain tissue obtained acutely after severe, life-threatening TBI. This revealed a unique transcriptional response in oligodendrocyte precursors and mature oligodendrocytes, including the activation of a robust innate immune response, indicating an important role for oligodendroglia in the initiation of neuroinflammation. The activation of an innate immune response correlated with transcriptional upregulation of endogenous retroviruses in oligodendroglia. This observation was causally linked in vitro using human glial progenitors, implicating these ancient viral sequences in human neuroinflammation. In summary, this work provides insight into the initiating events of the neuroinflammatory response in TBI, which has therapeutic implications.

Recently, magnesium alloys have garnered a lot of interest as a potentially useful material for applications involving biodegradable implants. Cracking or fracture of metal-based implants under the combined action of corrosion and mechanical stresses, namely stress corrosion cracking (SCC) is an obviously critical criterion before any new material might be deployed as implants. Cracking or fracture of metal-based implants occurs under the simultaneous action of corrosion and mechanical stresses. This article gives a review of the existing literature on the SCC of magnesium alloys in corrosive environments, including simulated body fluid and the accompanying fracture process. It also indicates the knowledge gap that exists in this area of research. In addition, a high-level review of the preventative measures that may be taken to avoid potential corrosion fatigue failures in magnesium alloys is provided.

3D brain organoids have been used to investigate human brain development and pathology. Here the authors establish human ventral midbrain organoids coupled with single cell sequencing to study developing and mature dopamine neurons and use silk scaffolding to generate bioengineered brain organoids

Close-kin mark-recapture (CKMR) methods have recently been used to infer demographic parameters such as census population size and survival for fish of interest to fisheries and conservation. These methods have advantages over traditional mark-recapture methods as the mark is genetic, removing the need for physical marking and recapturing that may interfere with parameter estimation. For mosquitoes, the spatial distribution of close-kin pairs has been used to estimate mean dispersal distance, of relevance to vector-borne disease transmission and novel biocontrol strategies. Here, we extend CKMR methods to the life history of mosquitoes and comparable insects. We derive kinship probabilities for mother-offspring, father-offspring, full-sibling and half-sibling pairs, where an individual in each pair may be a larva, pupa or adult. A pseudo-likelihood approach is used to combine the marginal probabilities of all kinship pairs. To test the effectiveness of this approach at estimating mosquito demographic parameters, we develop an individual-based model of mosquito life history incorporating egg, larva, pupa and adult life stages. The simulation labels each individual with a unique identification number, enabling close-kin relationships to be inferred for sampled individuals. Using the dengue vector Aedes aegypti as a case study, we find the CKMR approach provides unbiased estimates of adult census population size, adult and larval mortality rates, and larval life stage duration for logistically feasible sampling schemes. Considering a simulated population of 3,000 adult mosquitoes, estimation of adult parameters is accurate when ca. 40 adult females are sampled biweekly over a three month period. Estimation of larval parameters is accurate when adult sampling is supplemented with ca. 120 larvae sampled biweekly over the same period. The methods are also effective at detecting intervention-induced increases in adult mortality and decreases in population size. As the cost of genome sequencing declines, CKMR holds great promise for characterizing the demography of mosquitoes and comparable insects of epidemiological and agricultural significance.

Cell migration is an essential process in health and in disease, including cancer metastasis. A comprehensive inventory of migration factors is nonetheless lacking—in part due to the difficulty in assessing migration using high‐throughput technologies. Hence, there are currently very few screens that systematically reveal factors controlling cell migration. Here, we introduce MigExpress as a platform for the ‘identification of Migration control genes by differential Expression’. MigExpress exploits the combination of in‐depth molecular profiling and the robust quantitative analysis of migration capacity in a broad panel of samples and identifies migration‐associated genes by their differential expression in slow‐ versus fast‐migrating cells. We applied MigExpress to investigate non‐small cell lung cancer (NSCLC), which is the most frequent cause of cancer mortality mainly due to metastasis. In 54 NSCLC cell lines, we comprehensively determined mRNA and protein expression. Correlating the transcriptome and proteome profiles with the quantified migration properties led to the discovery and validation of FLNC, DSE, CPA4, TUBB6, and BICC1 as migration control factors in NSCLC cells, which were also negatively correlated with patient survival. Notably, FLNC was the least expressed filamin in NSCLC, but the only one controlling cell migration and correlating with patient survival and metastatic disease stage. In our study, we present MigExpress as a new method for the systematic analysis of migration factors and provide a comprehensive resource of transcriptomic and proteomic data of NSCLC cell lines related to cell migration.

What happens to cells on engrafting into the brain in animal models to treat Parkinson’s disease is unclear. Here, the authors use scRNA-seq to examine ventral midbrain (VM)-patterned human embryonic stem cells after functional maturation in a pre-clinical rat model for Parkinson’s disease and identify perivascular-like cells.

Background: Disparities in healthcare access to internal migrants exist, and the gaps may widen further if appropriate steps are not taken. Innovative approaches are needed to better align the healthcare services with the migrants’ needs. Aim: The aim was to develop and test a supportive strategy of healthcare, which would achieve the desired level of access and delivery of maternal healthcare services to internal migrants living in nine Indian cities. Methods: This intervention with the quasi-experimental design was conducted with pre- vs post-intervention comparisons within the interventional groups and with the control group. The intervention was implemented with an inclusive partnership approach. Advocacy and community mobilization were the main intervention components. Findings: An increased proportion of women sought antenatal care during the intervention. More women initiated seeking antenatal care in the first trimester. Due to intervention, health workers’ prenatal (41.7% in the post- against 14.7% in the pre-interventional phase) and postnatal home visits increased (11.6% to 34.7%) considerably. Conclusions: Interventions with inclusive partnership would improve healthcare access to vulnerable communities such as migrants. Hence, efforts to strengthen the government healthcare system through novel strategies are crucial to provide better healthcare to migrants.

Synonymous mutations do not alter amino acid sequence but may exert oncogenic effects in other ways. Here, the authors present a catalogue of synonymous mutations in cancer and characterise their properties.

Road traffic injuries (RTIs) are the sixth leading cause of deaths in India and about 400 deaths take place every day due to road traffic accidents. The present paper analyses the data of the India’s National Crime Record Bureau (NCRB) to assess the burden of RTI. In addition, it reports the health systems research initiated by the Indian Council of Medical Research (ICMR). As per NCRB data, in 2015, 6.3 million persons (50 persons per 10 million population) injured and out of them 1.4 million (11 persons per 10 million population) died in India. Except the NCRB data, there are no nation-wide data on RTI and the data remain poorly collected and sporadic in India. Hence, ICMR has initiated a multi-centric study to establish an electronic-based comprehensive and integrated RTI surveillance system. The second issue on which ICMR undertake research is timely and quality care of RTI patients as many deaths occur either at the scene or en route to the hospital. There is a clear survival and functional benefit for critically injured patients to receive appropriate care within the first 60 minutes of injury (‘golden hour’). Hence, this multi-centric study has been initiated to standardize structured evidence-based intervention for safety, efficacy and quality of post-crash pre-hospital and in-hospital trauma care services to improve the outcome in RTI victims. An android-based trauma registry is being built and will be used to assess the impact of interventions. These studies will provide first comprehensive estimates on various epidemiological issues related to RTI. Also, an evidence of improvement through quality post-crash prehospital and in-hospital trauma care services will emerge. These results will contribute to the setting of research and investment priorities and to formulate policies and guidelines.

Dopaminergic (DA) neurons derived from human pluripotent stem cells (hPSCs) represent a renewable and available source of cells useful for understanding development, developing disease models, and stem-cell therapies for Parkinson’s disease (PD). To assess the utility of stem cell cultures as an in vitro model system of human DA neurogenesis, we performed high-throughput transcriptional profiling of ~20,000 ventral midbrain (VM)-patterned stem cells at different stages of maturation using droplet-based single-cell RNA sequencing (scRNAseq). Using this dataset, we defined the cellular composition of human VM cultures at different timepoints and found high purity DA progenitor formation at an early stage of differentiation. DA neurons sharing similar molecular identities to those found in authentic DA neurons derived from human fetal VM were the major cell type after two months in culture. We also developed a bioinformatic pipeline that provided a comprehensive long noncoding RNA landscape based on temporal and cell-type specificity, which may contribute to unraveling the intricate regulatory network of coding and noncoding genes in DA neuron differentiation. Our findings serve as a valuable resource to elucidate the molecular steps of development, maturation, and function of human DA neurons, and to identify novel candidate coding and noncoding genes driving specification of progenitors into functionally mature DA neurons.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Transposable elements (TEs) are dynamically expressed at high levels in multiple human tissues, but the function of TE-derived transcripts remains largely unknown. In this study, we identify numerous TE-derived microRNAs (miRNAs) by conducting Argonaute2 RNA immunoprecipitation followed by small RNA sequencing (AGO2 RIP-seq) on human brain tissue. Many of these miRNAs originated from LINE-2 (L2) elements, which entered the human genome around 100-300 million years ago. L2-miRNAs derived from the 3' end of the L2 consensus sequence and thus shared very similar sequences, indicating that L2-miRNAs could target transcripts with L2s in their 3'UTR. In line with this, many protein-coding genes carried fragments of L2-derived sequences in their 3'UTR: these sequences served as target sites for L2-miRNAs. L2-miRNAs and their targets were generally ubiquitously expressed at low levels in multiple human tissues, suggesting a role for this network in buffering transcriptional levels of housekeeping genes. In addition, we also found evidence that this network is perturbed in glioblastoma. In summary, our findings uncover a TE-based post-transcriptional network that shapes transcriptional regulation in human cells.

Lung cancer continues to be the leading cause of cancer-related deaths worldwide, with little improvement in patient survival rates in the past decade. Long non-coding RNAs (lncRNAs) are gaining importance as possible biomarkers with prognostic potential. By large-scale data mining, we identified LINC00261 as a lncRNA which was significantly downregulated in lung cancer. Low expression of LINC00261 was associated with recurrence and poor patient survival in lung adenocarcinoma. Moreover, the gene pair of LINC00261 and its neighbor FOXA2 were significantly co-regulated. LINC00261 as well as FOXA2 negatively correlated with markers for epithelial-to-mesenchymal transition (EMT) and were suppressed by the EMT inducer TGFβ. Hierarchical clustering of gene expression data from lung cancer cell lines could further verify the association of high LINC00261/FOXA2 expression to an epithelial gene signature. Furthermore, higher expression of the LINC00261/FOXA2 locus was associated with lung cancer cell lines with lower migratory capacity. All these data establish LINC00261 and FOXA2 as an epithelial-specific marker pair, downregulated during EMT and lung cancer progression, and associated with lower cell migration potential in lung cancer cells.

BACKGROUND:Nuclear receptors are a large structural class of transcription factors that act with their co-regulators and repressors to maintain a variety of biological and physiological processes such as metabolism, development and reproduction. They are activated through the binding of small ligands, which can be replaced by drug molecules, making nuclear receptors promising drug targets. Transcriptional regulation of the genes that encode them is central to gaining a deeper understanding of the diversity of their biochemical and biophysical roles and their role in disease and therapy. Even though they share evolutionary history, nuclear receptor genes have fundamentally different expression patterns, ranging from ubiquitously expressed to tissue-specific and spatiotemporally complex. However, current understanding of regulation in nuclear receptor gene family is still nascent. METHODOLOGY/PRINCIPAL FINDINGS:In this study, we investigate the relationship between long-range regulation of nuclear receptor family and their known functionality. Towards this goal, we identify the nuclear receptor genes that are potential targets based on counts of highly conserved non-coding elements. We validate our results using publicly available expression (RNA-seq) and histone modification (ChIP-seq) data from the ENCODE project. We find that nuclear receptor genes involved in developmental roles show strong evidence of long-range mechanism of transcription regulation with distinct cis-regulatory content they feature clusters of highly conserved non-coding elements distributed in regions spanning several Megabases, long and multiple CpG islands, bivalent promoter marks and statistically significant higher enrichment of enhancer mark around their gene loci. On the other hand nuclear receptor genes that are involved in tissue-specific roles lack these features, having simple transcriptional controls and a greater variety of mechanisms for producing paralogs. We further examine the combinatorial patterns of histone maps associated with dynamic functional elements in order to explore the regulatory landscape of the gene family. The results show that our proposed classification capturing long-range regulation is strongly indicative of the functional roles of the nuclear receptors compared to existing classifications. CONCLUSIONS/SIGNIFICANCE:We present a new classification for nuclear receptor gene family capturing whether a nuclear receptor is a possible target of long-range regulation or not. We compare our classification to existing structural (mechanism of action) and homology-based classifications. Our results show that understanding long-range regulation of nuclear receptors can provide key insight into their functional roles as well as evolutionary history; and this strongly merits further study.

Perioperative medicine is an evolving area of medicine in which collaboration between internists, hospitalists, surgeons and anesthesiologists is the key to delivering high-quality care. Research in all areas of perioperative medicine, including perioperative anemia, is constantly evolving. Perioperative anemia is a major contributor to mortality and morbidity in the perioperative period. It is associated with an increased likelihood of postoperative wound complications, infections, delirium, increased length of stay and increased risk of readmissions. However, there is a lack of comprehensive guidelines for management of perioperative anemia. We performed an exhaustive review of contemporary literature on perioperative anemia and present evaluation and management recommendations that have the potential to impact clinical practice in the perioperative period. [ABSTRACT FROM AUTHOR]

Perioperative medicine continues to evolve as new literature emerges. This article provides an update on prevention of venous thromboembolism (VTE) in surgical patients. We reviewed articles on VTE prevention in surgical patients published in peer-reviewed journals since the publication of 2012 ACCP guidelines on VTE prevention in surgical patients. Methods of VTE prophylaxis include aggressive ambulation, mechanical prophylaxis, and pharmacological prophylaxis. In non-orthopedic surgery, the overall approach remains assessment of thrombosis risk with the recommendation to use a risk assessment tool such as the modified Caprini score. Low molecular weight heparin (LMWH) appears to be more effective than unfractionated heparin (UFH) for VTE prophylaxis in non-orthopedic surgery. For orthopedic surgery, recent studies now recognize aspirin as an option for VTE prophylaxis after total hip arthroplasty, total knee arthroplasty, and hip fracture surgery. Extended prophylaxis with LMWH reduces the risk of symptomatic VTE in high risk abdominal and pelvic cancer surgery without an appreciable increase in risk of bleeding and decreased symptomatic VTE in major orthopedic surgery but with more minor but not major bleeding. Prophylactic Inferior vena cava (IVC) filter placement or surveillance compression ultrasonography is not recommended in management or detection of VTE in surgical patients. This article aims to provide insight into data from last several years which has potential to change clinical practices in perioperative setting. [ABSTRACT FROM AUTHOR]