Beav: a bacterial genome and mobile element annotation pipeline.

Comprehensive and accurate genome annotation is crucial for inferring the predicted functions of an organism. Numerous tools exist to annotate genes, gene clusters, mobile genetic elements, and other diverse features. However, these tools and pipelines can be difficult to install and run, be specialized for a particular element or feature, or lack annotations for larger elements that provide important genomic context. Integrating results across analyses is also important for understanding gene function. To address these challenges, we present the Beav annotation pipeline. Beav is a command-line tool that automates the annotation of bacterial genome sequences, mobile genetic elements, molecular systems and gene clusters, key regulatory features, and other elements. Beav uses existing tools in addition to custom models, scripts, and databases to annotate diverse elements, systems, and sequence features. Custom databases for plant-associated microbes are incorporated to improve annotation of key virulence and symbiosis genes in agriculturally important pathogens and mutualists. Beav includes an optional Agrobacterium-specific pipeline that identifies and classifies oncogenic plasmids and annotates plasmid-specific features. Following the completion of all analyses, annotations are consolidated to produce a single comprehensive output. Finally, Beav generates publication-quality genome and plasmid maps. Beav is on Bioconda and is available for download at https://github.com/weisberglab/beav. IMPORTANCE: Annotation of genome features, such as the presence of genes and their predicted function, or larger loci encoding secretion systems or biosynthetic gene clusters, is necessary for understanding the functions encoded by an organism. Genomes can also host diverse mobile genetic elements, such as integrative and conjugative elements and/or phages, that are often not annotated by existing pipelines. These elements can horizontally mobilize genes encoding for virulence, antimicrobial resistance, or other adaptive functions and alter the phenotype of an organism. We developed a software pipeline, called Beav, that combines new and existing tools for the comprehensive annotation of these and other major features. Existing pipelines often misannotate loci important for virulence or mutualism in plant-associated bacteria. Beav includes custom databases and optional workflows for the improved annotation of plant-associated bacteria. Beav is designed to be easy to install and run, making comprehensive genome annotation broadly available to the research community.

An improved synthetic signal injection routine for the Haloscope At Yale Sensitive To Axion Cold dark matter (HAYSTAC).

Microwave cavity haloscopes are among the most sensitive direct detection experiments searching for dark matter axions via their coupling to photons. When the power of the expected microwave signal due to axion-photon conversion is on the order of 10-24 W, having the ability to validate the detector response and analysis procedure by injecting realistic synthetic axion signals becomes helpful. Here, we present a method based on frequency hopping spread spectrum for synthesizing axion signals in a microwave cavity haloscope experiment. It allows us to generate a narrow and asymmetric shape in frequency space that mimics an axion's spectral distribution, which is derived from a Maxwell-Boltzmann distribution. In addition, we show that the synthetic axion's power can be calibrated with reference to the system noise. Compared to the synthetic axion injection in the Haloscope At Yale Sensitive to Axion Cold dark matter (HAYSTAC) Phase I, we demonstrated synthetic signal injection with a more realistic line shape and calibrated power.

Characteristics, Treatment Patterns, and Clinical Outcomes After Heart Failure Hospitalizations During the COVID-19 Pandemic, March to October 2020.

OBJECTIVE: To compare clinical characteristics, treatment patterns, and 30-day all-cause readmission and mortality between patients hospitalized for heart failure (HF) before and during the coronavirus disease 2019 (COVID-19) pandemic. PATIENTS AND METHODS: The study was conducted at 16 hospitals across 3 geographically dispersed US states. The study included 6769 adults (mean age, 74 years; 56% [5033 of 8989] men) with cumulative 8989 HF hospitalizations: 2341 hospitalizations during the COVID-19 pandemic (March 1 through October 30, 2020) and 6648 in the pre-COVID-19 (October 1, 2018, through February 28, 2020) comparator group. We used Poisson regression, Kaplan-Meier estimates, multivariable logistic, and Cox regression analysis to determine whether prespecified study outcomes varied by time frames. RESULTS: The adjusted 30-day readmission rate decreased from 13.1% (872 of 6648) in the pre-COVID-19 period to 10.0% (234 of 2341) in the COVID-19 pandemic period (relative risk reduction, 23%; hazard ratio, 0.77; 95% CI, 0.66 to 0.89). Conversely, all-cause mortality increased from 9.7% (645 of 6648) in the pre-COVID-19 period to 11.3% (264 of 2341) in the COVID-19 pandemic period (relative risk increase, 16%; number of admissions needed for one additional death, 62.5; hazard ratio, 1.19; 95% CI, 1.02 to 1.39). Despite significant differences in rates of index hospitalization, readmission, and mortality across the study time frames, the disease severity, HF subtypes, and treatment patterns remained unchanged (P>0.05). CONCLUSION: The findings of this large tristate multicenter cohort study of HF hospitalizations suggest lower rates of index hospitalizations and 30-day readmissions but higher incidence of 30-day mortality with broadly similar use of HF medication, surgical interventions, and devices during the COVID-19 pandemic compared with the pre-COVID-19 time frame.

Relationships between type of hoof lesion and behavioral signs of lameness in Holstein cows housed in Canadian tiestall facilities.

Although foot pain can affect gait, the presence of a hoof lesion may or may not cause the cow to show visible changes in their gait. This can be dependent on the type and severity of the lesion; for example, the presence of a sole ulcer (SU) has been associated with increased gait scores, whereas digital dermatitis (DD) and sole hemorrhage (SH) have not. In tiestall facilities, gait scoring can be difficult to perform. An alternative method, known as stall lameness scoring (SLS), allows observers to assess cattle for lameness while they remain in their stall. Lameness is determined based on behavioral changes in weight bearing and foot positioning, which include: shifting weight, resting a foot, standing on the edge of the stall, and uneven weight bearing when stepping side to side. The aim of this study was to examine relationships between hoof lesions and these behavioral indicators. A total of 557 observations of SLS and corresponding hoof trimming records, collected during routine trimming events on 7 tiestall herds, were obtained. Trimming was performed by 2 trained hoof trimmers with good agreement on lesion identification, based on quizzes taken at the beginning and mid-way through the study. To ensure trimming had no effect on the behavioral indicators observed, SLS was always performed by a trained observer before trimming. Behavioral indicators focused on the hind limbs only; therefore, the analysis was confined to hind limb lesions using logistic regression to detect the presence of hoof lesion based on observations made during SLS. Seventy-five percent of observed cows had no SLS behavioral indicators, whereas, 11, 12, and 1% had 1, 2, and 3 behavioral indicators, respectively. At least one hind limb lesion was noted during trimming in 19% of cows, with the most common lesions being DD (7%), SU (6%), and SH (4%). A cow that was observed resting one foot and bearing weight unevenly when moving side to side had higher odds of having a hind limb hoof lesion than a cow not displaying these behaviors. When looking at specific hoof lesions, a cow observed resting one limb and bearing weight unevenly had higher odds of having a SU compared with those not displaying these behaviors. A cow observed shifting their weight from one foot to another had higher odds of having SH, and a cow observed bearing weight unevenly had higher odds of DD. Behavioral indicators in weight bearing and foot positioning can help identify cows in tiestalls with hind limb hoof lesions. Producers could routinely observe their cattle for these indicators to assist in the identification of cows that may require treatment. This could help reduce the duration of clinical lameness through earlier intervention.

Measurement of the Spectral Shape of the ß-Decay of

We report on a comparison between the theoretically predicted and experimentally measured spectra of the first-forbidden nonunique ß-decay transition ^{137}Xe(7/2^{-})→^{137}Cs(7/2^{+}). The experimental data were acquired by the EXO-200 experiment during a deployment of an AmBe neutron source. The ultralow background environment of EXO-200, together with dedicated source deployment and analysis procedures, allowed for collection of a pure sample of the decays, with an estimated signal to background ratio of more than 99 to 1 in the energy range from 1075 to 4175 keV. In addition to providing a rare and accurate measurement of the first-forbidden nonunique ß-decay shape, this work constitutes a novel test of the calculated electron spectral shapes in the context of the reactor antineutrino anomaly and spectral bump.

Search for Neutrinoless Double-ß Decay with the Complete EXO-200 Dataset.

A search for neutrinoless double-ß decay (0νßß) in ^{136}Xe is performed with the full EXO-200 dataset using a deep neural network to discriminate between 0νßß and background events. Relative to previous analyses, the signal detection efficiency has been raised from 80.8% to 96.4±3.0%, and the energy resolution of the detector at the Q value of ^{136}Xe 0νßß has been improved from σ/E=1.23% to 1.15±0.02% with the upgraded detector. Accounting for the new data, the median 90% confidence level 0νßß half-life sensitivity for this analysis is 5.0×10^{25} yr with a total ^{136}Xe exposure of 234.1 kg yr. No statistically significant evidence for 0νßß is observed, leading to a lower limit on the 0νßß half-life of 3.5×10^{25} yr at the 90% confidence level.

Prevalence of lameness and associated risk factors on dairy farms in the Maritime Provinces of Canada.

Lameness in dairy cattle is a major issue for the industry due to the effects on the welfare of the animal, the economic impact, and consumer perception. The aim of this study was to determine the prevalence of lameness and explore potential risk factors in the Maritime Provinces of Canada. Cows were scored for lameness and potential risk factors and were assessed in 46 freestall herds and 33 tiestall herds in Nova Scotia, New Brunswick, and Prince Edward Island. In freestall herds, lameness was assessed using the most common method, locomotion scoring. A cow with a gait score of ≥3 out of 5 was considered to be lame. In tiestall herds, lameness was assessed using an alternative method known as stall lameness scoring. This assessment consisted of observation of the cow for 4 behavioral changes: standing on the edge of the stall, shifting weight, resting a limb, and uneven weight bearing when moved side to side. A cow displaying 2 or more of these behaviors was considered to be lame. At the time of the assessment, other animal-, environmental-, and management-based measurements were collected. These measurements were used in multivariable logistic regression analysis to determine risk factors that were associated with lameness for both freestalls and tiestalls independently. The prevalence of lameness was 21% for freestall-housed cattle and 15% for tiestall-housed cattle. Of the 1,488 tiestall-housed cows that were assessed, 68% showed no behavioral changes, whereas 15, 15, 2, and <1% showed 1, 2, 3, or 4 changes, respectively. In freestalls, higher odds of lameness were seen when cows spent ≥3 h/d in the holding area for milking compared with those that spent <3 h/d. In tiestall herds, higher odds of lameness were seen when bedding material was wet compared with when it was dry. For both lactating cow facility types, housing the dry cows and heifers on a deep bedded pack compared with tiestalls or freestalls was associated with a decreased odds of lameness. There were also many cow-level variables associated with lameness, including parity, daily milk production, stage of production, body condition, and width at the tuber coxae (hook bones). If producers become aware of the risk factors associated with lameness, they can make informed decisions on where to implement changes to help reduce the level of lameness in their herd.

Prevalence of hock, knee, and neck skin lesions and associated risk factors in dairy herds in the Maritime Provinces of Canada.

Skin lesions are commonly seen in dairy herds and have been associated with animal-, environmental-, and management factors. These lesions are not only a welfare concern, but they also affect profitability. Three areas on the cattle were examined for skin lesions: the hock, knee, and neck. Previous Canadian studies estimating the prevalence of lesions and the risk factors associated with them have not included the Maritime Provinces. In this study, 73 herds in the Maritime Provinces were chosen voluntarily to participate, with both tiestalls (n = 33) and freestalls (n = 40) represented. Within each herd, 67 to 90% of the lactating cows were selected and assessed for potential animal-, environmental-, and management-based risk factors. If producers were aware of the potential risk factors, this could help them reduce the prevalence in their herd. Leg lesions were scored on a 4-point scale (0-3) based on hair loss, swelling, and scabs, with a lesion defined as a score of 2 or 3 on at least 1 hock or knee. Necks were scored on a 3-point scale (0-2), with a lesion defined as score 2. For freestalls, the prevalence (95% confidence interval) of hock lesions was 39% (29-49%), knee lesions was 14% (11-18%), and neck lesions was 1% (<1-2%). Similarly, for tiestalls the prevalence (95% confidence interval) of hock lesions was 39% (33-46%), knee lesions was 17% (13-22%), and neck lesions was 5% (3-8%). Due to differences in management and methods of assessment between facility types, tiestalls and freestalls were analyzed separately. Due to dichotomization of cows as having a skin lesion or not, random-effects multivariable logistic regression was used to determine the risk factors for each lesion and facility type. Several environmental-based measurements, such as the stall base, type and dryness of bedding, and type of milking parlor, were associated with leg lesions. An environmental-based measurement that was associated with neck lesions was the design of the feed rail barrier in freestalls and the dimensions of the tie rail in tiestalls. Animal-based risk factors, such as stage of lactation, parity, and body condition, were also associated with all 3 types of lesions. This study showed that lesions to the hock, knee, and neck were common in the Maritime Provinces of Canada. Although differences were seen between facility types, in general, the results suggest that improving stall design and management and feed bunk design would help producers reduce the number of skin lesions seen in dairy cattle.

Search for Neutrinoless Double-Beta Decay with the Upgraded EXO-200 Detector.

Results from a search for neutrinoless double-beta decay (0νßß) of ^{136}Xe are presented using the first year of data taken with the upgraded EXO-200 detector. Relative to previous searches by EXO-200, the energy resolution of the detector has been improved to σ/E=1.23%, the electric field in the drift region has been raised by 50%, and a system to suppress radon in the volume between the cryostat and lead shielding has been implemented. In addition, analysis techniques that improve topological discrimination between 0νßß and background events have been developed. Incorporating these hardware and analysis improvements, the median 90% confidence level 0νßß half-life sensitivity after combining with the full data set acquired before the upgrade has increased twofold to 3.7×10^{25} yr. No statistically significant evidence for 0νßß is observed, leading to a lower limit on the 0νßß half-life of 1.8×10^{25} yr at the 90% confidence level.

Caspase-2 promotes obesity, the metabolic syndrome and nonalcoholic fatty liver disease.

Obesity and its resulting metabolic disturbances are major health threats. In response to energy surplus, overtaxed adipocytes release fatty acids and pro-inflammatory factors into the circulation, promoting organ fat accumulation (including nonalcoholic fatty liver disease), insulin resistance and the metabolic syndrome. Recently, caspase-2 was linked to lipoapoptosis, so we hypothesized that caspase-2 might be a critical determinant of metabolic syndrome pathogenesis. Caspase-2-deficient and wild-type mice were fed a Western diet (high-fat diet, enriched with saturated fatty acids and 0.2% cholesterol, supplemented with fructose and glucose in the drinking water) for 16 weeks. Metabolic and hepatic outcomes were evaluated. In vitro studies assessed the role of caspase-2 in adipose tissue proliferative properties and susceptibility for lipoapoptosis. Caspase-2-deficient mice fed a Western diet were protected from abdominal fat deposition, diabetes mellitus, dyslipidemia and hepatic steatosis. Adipose tissue in caspase-2-deficient mice was more proliferative, upregulated mitochondrial uncoupling proteins consistent with browning, and was resistant to cell hypertrophy and cell death. The liver was protected from steatohepatitis through a decrease in circulating fatty acids and more efficient hepatic fat metabolism, and from fibrosis as a consequence of reduced fibrogenic stimuli from fewer lipotoxic hepatocytes. Caspase-2 deficiency protected mice from diet-induced obesity, metabolic syndrome and nonalcoholic fatty liver disease. Further studies are necessary to assess caspase-2 as a therapeutic target for those conditions.

Composite International Diagnostic Interview screening scales for DSM-IV anxiety and mood disorders.

BACKGROUND: Lack of coordination between screening studies for common mental disorders in primary care and community epidemiological samples impedes progress in clinical epidemiology. Short screening scales based on the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI), the diagnostic interview used in community epidemiological surveys throughout the world, were developed to address this problem. METHOD: Expert reviews and cognitive interviews generated CIDI screening scale (CIDI-SC) item pools for 30-day DSM-IV-TR major depressive episode (MDE), generalized anxiety disorder (GAD), panic disorder (PD) and bipolar disorder (BPD). These items were administered to 3058 unselected patients in 29 US primary care offices. Blinded SCID clinical reinterviews were administered to 206 of these patients, oversampling screened positives. RESULTS: Stepwise regression selected optimal screening items to predict clinical diagnoses. Excellent concordance [area under the receiver operating characteristic curve (AUC)] was found between continuous CIDI-SC and DSM-IV/SCID diagnoses of 30-day MDE (0.93), GAD (0.88), PD (0.90) and BPD (0.97), with only 9-38 questions needed to administer all scales. CIDI-SC versus SCID prevalence differences are insignificant at the optimal CIDI-SC diagnostic thresholds (χ2 1 = 0.0-2.9, p = 0.09-0.94). Individual-level diagnostic concordance at these thresholds is substantial (AUC 0.81-0.86, sensitivity 68.0-80.2%, specificity 90.1-98.8%). Likelihood ratio positive (LR+) exceeds 10 and LR- is 0.1 or less at informative thresholds for all diagnoses. CONCLUSIONS: CIDI-SC operating characteristics are equivalent (MDE, GAD) or superior (PD, BPD) to those of the best alternative screening scales. CIDI-SC results can be compared directly to general population CIDI survey results or used to target and streamline second-stage CIDIs.

Phylogenetic analysis reveals multiple introductions of Cynodon species in Australia.

The distinction between native and introduced flora within isolated land masses presents unique challenges. The geological and colonisation history of Australia, the world's largest island, makes it a valuable system for studying species endemism, introduction, and phylogeny. Using this strategy we investigated Australian cosmopolitan grasses belonging to the genus Cynodon. While it is believed that seven species of Cynodon are present in Australia, no genetic analyses have investigated the origin, diversity and phylogenetic history of Cynodon within Australia. To address this gap, 147 samples (92 from across Australia and 55 representing global distribution) were sequenced for a total of 3336bp of chloroplast DNA spanning six genes. Data showed the presence of at least six putatively introduced Cynodon species (C. transvaalensis, C. incompletus, C. hirsutus, C. radiatus, C. plectostachyus and C. dactylon) in Australia and suggested multiple recent introductions. C. plectostachyus, a species often confused with C. nlemfuensis, was not previously considered to be present in Australia. Most significantly, we identified two common haplotypes that formed a monophyletic clade diverging from previously identified Cynodon species. We hypothesise that these two haplotypes may represent a previously undescribed species of Cynodon. We provide further evidence that two Australian native species, Brachyachne tenella and B. convergens belong in the genus Cynodon and, therefore, argue for the taxonomic revision of the genus Cynodon.

Antioxidant micronutrient impact on hearing disorders: concept, rationale, and evidence.

PURPOSE: Although auditory disorders are complex conditions, device-related modalities dominate current treatment. However, dysfunction from the central cortex to the inner ear apparatus is increasingly thought to be related to biochemical pathway abnormalities and to free radical-induced oxidative damage and chronic inflammation. Therefore, considering appropriate biologic therapy as an adjunct to standard care against these damaging factors may provide rational expansion of treatment options for otolaryngologists and audiologists. METHODS: This review outlines the biologic concepts related to some auditory and vestibular conditions and details the current rationale for utilizing antioxidants for a spectrum of hearing disorders. The strategy is based on the authors' collective experience in antioxidant science and supported with published research, pilot animal data and preliminary clinical observations. RESULTS: A comprehensive micronutrient approach was developed to exploit these pathways, and demonstrated safety and efficacy against oxidative damage and inflammation and clinically relevant neuroprotection. Cooperative research with Department of Defense institutions used prospective, randomized designs to show (1) reduction in oxidative damage measured in plasma and urine over six months, (2) protection against oxidative damage during 12 weeks of intense military training, (3) protection against inflammation after total body blast exposure (rodents), (4) strong neuroprotection against chemically-induced Parkinson's disease (rodents), (5) nerve VIII function improvement after concussive head injury in military personnel, and (6) tinnitus improvement in majority of patients after 90-day evaluation. CONCLUSION: This systematic review of biologic strategies against hearing disorders combined with new animal and human observations may provide a rational basis for expanding current practice paradigms.

Effect of vitamin D analog (1alpha hydroxy D5) immunoconjugated to Her-2 antibody on breast cancer.

We previously showed that a new vitamin D analog, 1alpha(OH)D5 (D5), induced differentiation and inhibited the growth of breast cancer cells. In this report, we examined whether D5 specifically delivered to breast cancer cells could have any therapeutic effect. D5 was linked to Her-2 antibody using sulfosuccinimidyl 6-4 azido nitrophenylamido hexanode (SANPAH) as a linker. The Her-2 antibody selected in our study had no significant effect on the in vitro or in vivo growth of breast cancer cells; however, it had cell-differentiating action. In vitro, D5-Her-2 antibody conjugate (IMC) showed the ability to specifically bind to Her-2-expressing cells, to compete with Her-2 antibody for surface receptor and to cause internalization. IMC (equivalent to 5 microg Her-2 antibody given intraperitoneally once weekly for 6 weeks) significantly inhibited the growth of BT-474 cells transplanted into athymic mice. The in vivo growth-inhibitory effect of IMC treatment was similar to that observed in animals receiving D5 continuously as a dietary supplement. These results show that the targeted delivery of D5 by immunoconjugation to cell surface receptor antibodies may be of potential therapeutic value for the treatment of Her-2 positive breast cancer.

Strongyloidiasis in a Cope's grey tree frog (Hyla chrysoscelis).

A male Cope's grey tree frog (Hyla chrysoscelis) died spontaneously with ventral subcutaneous edema and was necropsied. Thickening of the intestinal mucosa was observed histopathologically, with villous atrophy and intraepithelial nematodes present. Adult female Strongyloides sp. nematodes were isolated from the fixed intestinal tract, the first time this nematode genus has been recovered from this frog genus. Intestinal strongyloidiasis should be considered as a cause for protein-losing enteropathy and death in frogs.

Prevention of deep vein thrombosis in aesthetic surgery patients.

Like other surgical patients, those undergoing elective aesthetic surgery are at risk for deep vein thrombosis. The author discusses ways to reduce this risk, such as limiting the number of procedures performed in the same operative session, using mechanical devices and pharmacologic agents, and doing careful postoperative assessment.

Atypical presentation of risperidone toxicity.

A new class of antipsychotic medication, the "atypical antipsychotics" are gaining popularity. We report 2 cases of toxicity associated with 1 of these new antipsychotics, risperidone. Both patients presented with fatigue, orthostasis, dry mucous membranes, and the unusual finding of miosis. The pathophysiology and clinical presentation of overdose with this agent are discussed.