Changes in Prevalence of Idiopathic Intracranial Hypertension in the United States Between 2015 and 2022, Stratified by Sex, Race, and Ethnicity.

BACKGROUND AND OBJECTIVES: With the obesity epidemic within the United States, the prevalence of idiopathic intracranial hypertension (IIH) is predicted to rise. IIH prevalence and racial disparities have rarely been reported in the United States. The purpose of this study was to evaluate the prevalence of IIH in a large national database while stratifying by sex, age, race, and ethnicity. METHODS: This was a cross-sectional epidemiologic evaluation conducted in the TriNetX US Collaborative network using data from 2015 to 2022. Patients with an International Classification of Diseases code of IIH and papilledema or unspecified papilledema were included in the study. Any secondary cause of intracranial hypertension including cerebral neoplasms and hydrocephalus were excluded from the study. IIH trends were later compared with TriNetX cohort obesity trends. Prevalence and prevalence odds ratios (ORs) were calculated in Microsoft Excel and R Studio. RESULTS: Among 85 million patients in this database, a 1.35 times increase in the prevalence of IIH occurred between 2015 and 2022 from 7.3 (95% CI 6.9-7.7) individuals per 100,000 to 9.9 (95% CI 9.5-10.3) individuals per 100,000 in 2022. In 2022, Black female individuals had the highest prevalence of IIH with 22.7 individuals per 100,000 compared with the 13.7 White female individuals per 100,000. Patients aged 11-17 years showed the largest growth of IIH prevalence with female individuals increasing by 10 individuals per 100,000 by 2022. Overall, Black and Hispanic patients had the largest prevalence OR of IIH at 1.66 (95% CI 1.49-1.85) and 1.33 (95% CI 1.14-1.56), respectively, compared with White female patients. DISCUSSION: IIH is a rapidly increasing health care concern for the US population, particularly among adolescent patients. Black and Hispanic female individuals are most predominately affected by this incapacitating disorder.

Autologous Retinal Transplant Repeat Surgery after Initial Graft Failure: A Case Report.

Autologous retinal transplant (ART) has become an increasingly explored surgical option for managing large chronic holes refractory to standard surgical treatments. However, management strategies for patients who already failed a previous ART are less well-understood. Here, we report on a case of a successful repeat retinal transplant for a refractory macular hole after a previously dislocated ART graft. Subretinal injection of balanced salt solution was used to partially elevate the macular hole and secure the edge of the harvested retinal graft under the edge of the macular hole in the second operation. Postoperatively, the patient developed intraretinal fluid within the retinal graft with an appearance similar to cystoid macular edema, which was controlled with topical steroids. In addition, two separate choroidal neovascular membranes along the subretinal injection sites were seen and treated with vascular endothelial growth factor downregulation. This case illustrates successful repeat ART surgery, but further optimization of ART surgical techniques is necessary to minimize ART's complication rate.

Identification of Essential Genes in Caenorhabditis elegans with Lethal Mutations Maintained by Genetic Balancers.

Genetic balancer systems, which allow effective capture and maintenance of lethal mutations stably, play an important role in identifying essential genes. Whole-genome sequencing (WGS) followed by bioinformatics analysis, combined with genetic mapping data analysis, allows for an efficient and economical means of identifying genomic mutations in essential genes. Using this approach, we successfully identified 104 essential genes on ChrI, ChrIII, and ChrV in C. elegans. In this report, we described a protocol that sequences the genome of prebalanced Caenorhabditis elegans (C. elegans) strains to carry lethal mutations and identifies candidate causal mutations and candidate essential genes using a robust bioinformatics procedure.

Insights into the Ancient Adaptation to Intertidal Environments by Red Algae Based on a Genomic and Multiomics Investigation of Neoporphyra haitanensis.

Colonization of land from marine environments was a major transition for biological life on Earth, and intertidal adaptation was a key evolutionary event in the transition from marine- to land-based lifestyles. Multicellular intertidal red algae exhibit the earliest, systematic, and successful adaptation to intertidal environments, with Porphyra sensu lato (Bangiales, Rhodophyta) being a typical example. Here, a chromosome-level 49.67 Mb genome for Neoporphyra haitanensis comprising 9,496 gene loci is described based on metagenome-Hi-C-assisted whole-genome assembly, which allowed the isolation of epiphytic bacterial genome sequences from a seaweed genome for the first time. The compact, function-rich N. haitanensis genome revealed that ancestral lineages of red algae share common horizontal gene transfer events and close relationships with epiphytic bacterial populations. Specifically, the ancestor of N. haitanensis obtained unique lipoxygenase family genes from bacteria for complex chemical defense, carbonic anhydrases for survival in shell-borne conchocelis lifestyle stages, and numerous genes involved in stress tolerance. Combined proteomic, transcriptomic, and metabolomic analyses revealed complex regulation of rapid responses to intertidal dehydration/rehydration cycling within N. haitanensis. These adaptations include rapid regulation of its photosynthetic system, a readily available capacity to utilize ribosomal stores, increased methylation activity to rapidly synthesize proteins, and a strong anti-oxidation system to dissipate excess redox energy upon exposure to air. These novel insights into the unique adaptations of red algae to intertidal lifestyles inform our understanding of adaptations to intertidal ecosystems and the unique evolutionary steps required for intertidal colonization by biological life.

Eight soybean reference genome resources from varying latitudes and agronomic traits.

Comparative analysis of multiple reference genomes representing diverse genetic backgrounds is critical for understanding the role of key alleles important in domestication and genetic breeding of important crops such as soybean. To enrich the genetic resources for soybean, we describe the generation, technical assessment, and preliminary genomic variation analysis of eight de novo reference-grade soybean genome assemblies from wild and cultivated accessions. These resources represent soybeans cultured at different latitudes and exhibiting different agronomical traits. Of these eight soybeans, five are from new accessions that have not been sequenced before. We demonstrate the usage of these genomes to identify small and large genomic variations affecting known genes as well as screening for genic PAV regions for identifying candidates for further functional studies.

A statistical analysis of the novel coronavirus (COVID-19) in Italy and Spain.

The novel coronavirus (COVID-19) that was first reported at the end of 2019 has impacted almost every aspect of life as we know it. This paper focuses on the incidence of the disease in Italy and Spain-two of the first and most affected European countries. Using two simple mathematical epidemiological models-the Susceptible-Infectious-Recovered model and the log-linear regression model, we model the daily and cumulative incidence of COVID-19 in the two countries during the early stage of the outbreak, and compute estimates for basic measures of the infectiousness of the disease including the basic reproduction number, growth rate, and doubling time. Estimates of the basic reproduction number were found to be larger than 1 in both countries, with values being between 2 and 3 for Italy, and 2.5 and 4 for Spain. Estimates were also computed for the more dynamic effective reproduction number, which showed that since the first cases were confirmed in the respective countries the severity has generally been decreasing. The predictive ability of the log-linear regression model was found to give a better fit and simple estimates of the daily incidence for both countries were computed.

Count regression models for COVID-19.

At the end of 2019, the current novel coronavirus emerged as a severe acute respiratory disease that has now become a worldwide pandemic. Future generations will look back on this difficult period and see how our society as a whole united and rose to this challenge. Many reports have suggested that this new virus is becoming comparable to the Spanish flu pandemic of 1918. We provide a statistical study on the modelling and analysis of the daily incidence of COVID-19 in eighteen countries around the world. In particular, we investigate whether it is possible to fit count regression models to the number of daily new cases of COVID-19 in various countries and make short term predictions of these numbers. The results suggest that the biggest advantage of these methods is that they are simplistic and straightforward allowing us to obtain preliminary results and an overall picture of the trends in the daily confirmed cases of COVID-19 around the world. The best fitting count regression model for modelling the number of new daily COVID-19 cases of all countries analysed was shown to be a negative binomial distribution with log link function. Whilst the results cannot solely be used to determine and influence policy decisions, they provide an alternative to more specialised epidemiological models and can help to support or contradict results obtained from other analysis.

Genomic identification and functional analysis of essential genes in Caenorhabditis elegans.

BACKGROUND: Essential genes are required for an organism's viability and their functions can vary greatly, spreading across many pathways. Due to the importance of essential genes, large scale efforts have been undertaken to identify the complete set of essential genes and to understand their function. Studies of genome architecture and organization have found that genes are not randomly disturbed in the genome. RESULTS: Using combined genetic mapping, Illumina sequencing, and bioinformatics analyses, we successfully identified 44 essential genes with 130 lethal mutations in genomic regions of C. elegans of around 7.3 Mb from Chromosome I (left). Of the 44 essential genes, six of which were genes not characterized previously by mutant alleles, let-633/let-638 (B0261.1), let-128 (C53H9.2), let-511 (W09C3.4), let-162 (Y47G6A.18), let-510 (Y47G6A.19), and let-131 (Y71G12B.6). Examine essential genes with Hi-C data shows that essential genes tend to cluster within TAD units rather near TAD boundaries. We have also shown that essential genes in the left half of chromosome I in C. elegans function in enzyme and nucleic acid binding activities during fundamental processes, such as DNA replication, transcription, and translation. From protein-protein interaction networks, essential genes exhibit more protein connectivity than non-essential genes in the genome. Also, many of the essential genes show strong expression in embryos or early larvae stages, indicating that they are important to early development. CONCLUSIONS: Our results confirmed that this work provided a more comprehensive picture of the essential gene and their functional characterization. These genetic resources will offer important tools for further heath and disease research.

Estimated Brain Tissue Response Following Impacts Associated With and Without Diagnosed Concussion.

Kinematic measurements of head impacts are sensitive to sports concussion, but not highly specific. One potential reason is these measures reflect input conditions only and may have varying degrees of correlation to regional brain tissue deformation. In this study, previously reported head impact data recorded in the field from high school and collegiate football players were analyzed using two finite element head models (FEHM). Forty-five impacts associated with immediately diagnosed concussion were simulated along with 532 control impacts without identified concussion obtained from the same players. For each simulation, intracranial response measures (max principal strain, strain rate, von Mises stress, and pressure) were obtained for the whole brain and within four regions of interest (ROI; cerebrum, cerebellum, brain stem, corpus callosum). All response measures were sensitive to diagnosed concussion; however, large inter-athlete variability was observed and sensitivity strength depended on measure, ROI, and FEHM. Interestingly, peak linear acceleration was more sensitive to diagnosed concussion than all intracranial response measures except pressure. These findings suggest FEHM may provide unique and potentially important information on brain injury mechanisms, but estimations of concussion risk based on individual intracranial response measures evaluated in this study did not improve upon those derived from input kinematics alone.

Genomic Identification and Functional Characterization of Essential Genes in Caenorhabditis elegans.

Using combined genetic mapping, Illumina sequencing, bioinformatics analyses, and experimental validation, we identified 60 essential genes from 104 lethal mutations in two genomic regions of Caenorhabditis elegans totaling ∼14 Mb on chromosome III(mid) and chromosome V(left). Five of the 60 genes had not previously been shown to have lethal phenotypes by RNA interference depletion. By analyzing the regions around the lethal missense mutations, we identified four putative new protein functional domains. Furthermore, functional characterization of the identified essential genes shows that most are enzymes, including helicases, tRNA synthetases, and kinases in addition to ribosomal proteins. Gene Ontology analysis indicated that essential genes often encode for enzymes that conduct nucleic acid binding activities during fundamental processes, such as intracellular DNA replication, transcription, and translation. Analysis of essential gene shows that they have fewer paralogs, encode proteins that are in protein interaction hubs, and are highly expressed relative to nonessential genes. All these essential gene traits in C. elegans are consistent with those of human disease genes. Most human orthologs (90%) of the essential genes in this study are related to human diseases. Therefore, functional characterization of essential genes underlines their importance as proxies for understanding the biological functions of human disease genes.

Proline-Rich Chaperones Are Compared Computationally and Experimentally for Their Abilities to Facilitate Recombinant Butyrylcholinesterase Tetramerization in CHO Cells.

Human butyrylcholinesterase (BChE), predominantly tetramers with a residence time of days, offers the potential to scavenge organophosphorus pesticides and chemical warfare agents. Efficient assembly of human BChE into tetramers requires an association with proline-rich peptide chaperones. In this study, the incorporation of different proline-rich peptide chaperones into BChE is investigated computationally and experimentally. First, the authors applied molecular dynamic (MD) simulations to interpret the interactions between proline-rich chaperones with human BChE tetramer domains. The P24 chaperone which contains 24 prolines, promoted the association of BChE tetramer with a 74% simulated helicity of BChE subunits, whereas the control without chaperone and BChE with an 8-proline chaperone (P8) complex exhibited 55.8 and 60.6% predicted helicity, respectively. The interaction of proline-rich chaperones with BChE subunits (B-P) provides a conduit to facilitate the interactions between BChE subunits (B-B) of the complex, which is mainly attributed to hydrophobic interactions and hydrogen-bond binding. Experimental assessment of these two proline-rich chaperones plus a 14-proline chaperone (P14) was performed and confirmed that P24 has superior capability to facilitate recombinant BChE (rBChE) tetramerization with >60% rBChE tetramer in P24-transfected rBChE cells, whereas P14- and P8-transfected rBChE cells had 44 and 33% rBChE tetramer, respectively. The rBChE control had 14% tetramer. Finally, we developed a stable rBChE tetramer expression system in CHO cells by enriching P24 expression in rBChE expressing cells. Overall, our simulations provided a design concept for identifying proline-rich peptides that promote the rBChE tetramerization in CHO cells.

Genomics insights into different cellobiose hydrolysis activities in two Trichoderma hamatum strains.

BACKGROUND: Efficient biomass bioconversion is a promising solution to alternative energy resources and environmental issues associated with lignocellulosic wastes. The Trichoderma species of cellulolytic fungi have strong cellulose-degrading capability, and their cellulase systems have been extensively studied. Currently, a major limitation of Trichoderma strains is their low production of ß-glucosidases. RESULTS: We isolated two Trichoderma hamatum strains YYH13 and YYH16 with drastically different cellulose degrading efficiencies. YYH13 has higher cellobiose-hydrolyzing efficiency. To understand mechanisms underlying such differences, we sequenced the genomes of YYH13 and YYH16, which are essentially identical (38.93 and 38.92 Mb, respectively) and are similar to that of the T. hamatum strain GD12. Using GeneMark-ES, we annotated 11,316 and 11,755 protein-coding genes in YYH13 and YYH16, respectively. Comparative analysis identified 13 functionally important genes in YYH13 under positive selection. Through examining orthologous relationships, we identified 172,655, and 320 genome-specific genes in YYH13, YYH16, and GD12, respectively. We found 15 protease families that show differences between YYH13 and YYH16. Enzymatic tests showed that exoglucanase, endoglucanase, and ß-glucosidase activities were higher in YYH13 than YYH16. Additionally, YYH13 contains 10 families of carbohydrate-active enzymes, including GH1, GH3, GH18, GH35, and GH55 families of chitinases, glucosidases, galactosidases, and glucanases, which are subject to stronger positive selection pressure. Furthermore, we found that the ß-glucosidase gene (YYH1311079) and pGEX-KG/YYH1311079 bacterial expression vector may provide valuable insight for designing ß-glucosidase with higher cellobiose-hydrolyzing efficiencies. CONCLUSIONS: This study suggests that the YYH13 strain of T. hamatum has the potential to serve as a model organism for producing cellulase because of its strong ability to efficiently degrade cellulosic biomass. The genome sequences of YYH13 and YYH16 represents a valuable resource for studying efficient production of biofuels.

The impact of a preloaded intraocular lens delivery system on operating room efficiency in routine cataract surgery.

PURPOSE: The aim of this study was to evaluate the operational impact of using preloaded intraocular lens (IOL) delivery systems compared with manually loaded IOL delivery processes during routine cataract surgeries. METHODS: Time and motion data, staff and surgery schedules, and cost accounting reports were collected across three sites located in the US, France, and Canada. Time and motion data were collected for manually loaded IOL processes and preloaded IOL delivery systems over four surgery days. Staff and surgery schedules and cost accounting reports were collected during the 2 months prior and after introduction of the preloaded IOL delivery system. RESULTS: The study included a total of 154 routine cataract surgeries across all three sites. Of these, 77 surgeries were performed using a preloaded IOL delivery system, and the remaining 77 surgeries were performed using a manual IOL delivery process. Across all three sites, use of the preloaded IOL delivery system significantly decreased mean total case time by 6.2%-12.0% (P<0.001 for data from Canada and the US and P<0.05 for data from France). Use of the preloaded delivery system also decreased surgeon lens time, surgeon delays, and eliminated lens touches during IOL preparation. CONCLUSION: Compared to a manual IOL delivery process, use of a preloaded IOL delivery system for cataract surgery reduced total case time, total surgeon lens time, surgeon delays, and eliminated IOL touches. The time savings provided by the preloaded IOL delivery system provide an opportunity for sites to improve routine cataract surgery throughput without impacting surgeon or staff capacity.

Single-molecule real-time transcript sequencing facilitates common wheat genome annotation and grain transcriptome research.

BACKGROUND: The large and complex hexaploid genome has greatly hindered genomics studies of common wheat (Triticum aestivum, AABBDD). Here, we investigated transcripts in common wheat developing caryopses using the emerging single-molecule real-time (SMRT) sequencing technology PacBio RSII, and assessed the resultant data for improving common wheat genome annotation and grain transcriptome research. RESULTS: We obtained 197,709 full-length non-chimeric (FLNC) reads, 74.6 % of which were estimated to carry complete open reading frame. A total of 91,881 high-quality FLNC reads were identified and mapped to 16,188 chromosomal loci, corresponding to 13,162 known genes and 3026 new genes not annotated previously. Although some FLNC reads could not be unambiguously mapped to the current draft genome sequence, many of them are likely useful for studying highly similar homoeologous or paralogous loci or for improving chromosomal contig assembly in further research. The 91,881 high-quality FLNC reads represented 22,768 unique transcripts, 9591 of which were newly discovered. We found 180 transcripts each spanning two or three previously annotated adjacent loci, suggesting that they should be merged to form correct gene models. Finally, our data facilitated the identification of 6030 genes differentially regulated during caryopsis development, and full-length transcripts for 72 transcribed gluten gene members that are important for the end-use quality control of common wheat. CONCLUSIONS: Our work demonstrated the value of PacBio transcript sequencing for improving common wheat genome annotation through uncovering the loci and full-length transcripts not discovered previously. The resource obtained may aid further structural genomics and grain transcriptome studies of common wheat.

Genome-Wide Mutational Signature of the Chemotherapeutic Agent Mitomycin C in Caenorhabditis elegans.

Cancer therapy largely depends on chemotherapeutic agents that generate DNA lesions. However, our understanding of the nature of the resulting lesions as well as the mutational profiles of these chemotherapeutic agents is limited. Among these lesions, DNA interstrand crosslinks are among the more toxic types of DNA damage. Here, we have characterized the mutational spectrum of the commonly used DNA interstrand crosslinking agent mitomycin C (MMC). Using a combination of genetic mapping, whole genome sequencing, and genomic analysis, we have identified and confirmed several genomic lesions linked to MMC-induced DNA damage in Caenorhabditis elegans. Our data indicate that MMC predominantly causes deletions, with a 5'-CpG-3' sequence context prevalent in the deleted regions of DNA. Furthermore, we identified microhomology flanking the deletion junctions, indicative of DNA repair via nonhomologous end joining. Based on these results, we propose a general repair mechanism that is likely to be involved in the biological response to this highly toxic agent. In conclusion, the systematic study we have described provides insight into potential sequence specificity of MMC with DNA.

Statistical Analysis of the Exchange Rate of Bitcoin.

Bitcoin, the first electronic payment system, is becoming a popular currency. We provide a statistical analysis of the log-returns of the exchange rate of Bitcoin versus the United States Dollar. Fifteen of the most popular parametric distributions in finance are fitted to the log-returns. The generalized hyperbolic distribution is shown to give the best fit. Predictions are given for future values of the exchange rate.

Assessment of the coordinated role of ST3GAL3, ST3GAL4 and ST3GAL6 on the α2,3 sialylation linkage of mammalian glycoproteins.

In this research, we examined which genes are involved in N-linked sialylation in Chinese Hamster Ovary (CHO) cells using siRNA knockdown approaches. Three genes from the sialyltransferase family (ST3GAL3, ST3GAL4 and ST3GAL6) were chosen as knockdown targets with siRNA applied to reduce their expression. Single, double and triple gene knockdowns were investigated, and the reduction levels of sialylation on the total cell lysate were monitored by enzyme-linked lectin absorption assays (ELLA) and sialic acid quantification with high performance liquid chromatography (HPLC). All transfection groups showed effective reduction in 2,3-linked sialylation whereas the trend of reduction levels of triple siRNA transfection outweighed both the dual siRNA groups and single siRNA transfection groups. Next, this transfection approach was applied to CHO cells producing erythropoietin (EPO). Quantification of EPO sialylation showed similar result to total cell lysate except that the ST3GAL4 siRNA transfection exhibited the largest reduction according to the HPLC analysis as compared with other single siRNA transfections. Finally, the N-glycan released from the EPO transfected with ST3GAL4 siRNA showed a prominent reduction in sialyation level among the single siRNA transfections. From these experiments, we concluded that each of these three genes were involved in N-linked sialylation and ST3GAL4 may play the critical role in glycoprotein sialylation of recombinant proteins such as EPO.

Fresh frozen plasma and spray-dried plasma mitigate pulmonary vascular permeability and inflammation in hemorrhagic shock.

BACKGROUND: In retrospective and prospective observational studies, fresh frozen plasma (FFP) has been associated with a survival benefit in massively transfused trauma patients. A dry plasma product, such as spray-dried plasma (SDP), offers logistical advantages over FFP. Recent studies on FFP have demonstrated that FFP modulates systemic vascular stability and inflammation. The effect of SDP on these measures has not been previously examined. This study compares SDP with FFP using in vitro assays of endothelial function and in vivo assays of lung injury using a mouse model of hemorrhagic shock (HS) and trauma. METHODS: FFP, SDP, and lactated Ringer's (LR) solution were compared in vitro using assays of endothelial cell (EC) permeability, cytokine production and content, gene expression, as well as tight and adherens junction stability. All resuscitation products were also compared in a murine model of HS. Mean arterial pressures and physiologic measures were assessed. Pulmonary vascular permeability was measured using tagged dextran. Lung tissues were stained for CD68, VE-cadherin, and occludin. RESULTS: Treatment of ECs with FFP and SDP, but not LR, preserved the integrity of EC monolayers in vitro and resulted in similar EC gene expression patterns and cytokine/growth factor production. FFP and SDP also reduced HS-induced pulmonary vascular permeability in vivo to the same extent. In mice with HS, mean arterial pressures and base excess were corrected by both FFP and SDP to levels observed in sham-treated mice. Treatment after HS with FFP and SDP but not LR solution reduce alveolar wall thickening, leukocyte infiltration, and the breakdown of EC junctions, as measured by staining for VE-cadherin, and occludin. CONCLUSION: Both FFP and SDP similarly modulate pulmonary vascular integrity, permeability, and inflammation in vitro and in vivo in a murine model of HS and trauma.

Biomechanics of head impacts associated with diagnosed concussion in female collegiate ice hockey players.

Epidemiological evidence suggests that female athletes may be at a greater risk of concussion than their male counterparts. The purpose of this study was to examine the biomechanics of head impacts associated with diagnosed concussions in a cohort of female collegiate ice hockey players. Instrumented helmets were worn by 58 female ice hockey players from 2 NCAA programs over a three year period. Kinematic measures of single impacts associated with diagnosed concussion and head impact exposure on days with and without diagnosed concussion were evaluated. Nine concussions were diagnosed. Head impact exposure was greater in frequency and magnitude on days of diagnosed concussions than on days without diagnosed concussion for individual athletes. Peak linear accelerations of head impacts associated with diagnosed concussion in this study are substantially lower than those previously reported in male athletes, while peak rotational accelerations are comparable. Further research is warranted to determine the extent to which female athletes' biomechanical tolerance to concussion injuries differs from males.