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Summary Understanding the effects of genetic variants is crucial for accurately predicting traits and functional outcomes. Recent approaches have utilized artificial intelligence and protein language models to score all possible missense variant effects at the proteome level for a single genome, but a reliable tool is needed to explore these effects at the pan-genome level. To address this gap, we introduce a new tool called PanEffect. We implemented PanEffect at MaizeGDB to enable a comprehensive examination of the potential effects of coding variants across 50 maize genomes. The tool allows users to visualize over 550 million possible amino acid substitutions in the B73 maize reference genome and to observe the effects of the 2.3 million natural variations in the maize pan-genome. Each variant effect score, calculated from the Evolutionary Scale Modeling (ESM) protein language model, shows the log-likelihood ratio difference between B73 and all variants in the pan-genome. These scores are shown using heatmaps spanning benign outcomes to potential functional consequences. In addition, PanEffect displays secondary structures and functional domains along with the variant effects, offering additional functional and structural context. Using PanEffect, researchers now have a platform to explore protein variants and identify genetic targets for crop enhancement. Availability and implementation The PanEffect code is freely available on GitHub (https://github.com/Maize-Genetics-and-Genomics-Database/PanEffect). A maize implementation of PanEffect and underlying datasets are available at MaizeGDB (https://www.maizegdb.org/effect/maize/). [ABSTRACT FROM AUTHOR]

Two experiments were designed to evaluate later timepoints for fixed-time artificial insemination (FTAI) of beef heifers and cows, with the hypothesis that use of a later timepoint would allow a greater proportion of animals to express estrus prior to FTAI and result in greater conception rates among estrous females inseminated with sex-sorted semen. In Experiment 1, estrus was synchronized for 1640 heifers using the 14 d CIDR-PG protocol: insertion of an intravaginal progesterone-releasing insert (CIDR; 1.38 g progesterone) on Day −33 and removal on Day −19, and administration of prostaglandin F 2α (PG; 500 μg cloprostenol sodium) on Day −3. Heifers were inseminated at one of three FTAI timepoints: 66 h, 70 h, or 74 h after PG administration. In Experiment 2, estrus was synchronized for 414 beef cows using the 7 & 7 Synch protocol: administration of PG coincident with CIDR insertion on Day −17, gonadotropin-releasing hormone (GnRH; 100 μg gonadorelin) on Day −10, and PG coincident with CIDR removal on Day −3. Cows were inseminated at one of two FTAI timepoints: 66 h or 72 h after PG administration. In both experiments, only animals that expressed estrus prior to FTAI were inseminated with sex-sorted semen. In Experiment 1, the proportion of heifers that expressed estrus prior to FTAI (66 h: 62 %; 70 h: 67 %; 74 h: 71 %) was greater when FTAI was performed at 74 h versus 66 h (P = 0.0097); however, conception rate of heifers that expressed estrus and were serviced with sex-sorted semen did not differ among treatments (P = 0.67; 66 h: 56 %; 70 h: 53 %; 74 h: 53 %). In Experiment 2, the proportion of cows expressing estrus prior to FTAI did not differ between treatments (P = 0.30; 66 h: 71 %; 72 h: 76 %). Additionally, conception rate of estrous cows inseminated with sex-sorted semen did not differ between treatments (P = 0.24; 66 h: 45 %; 72 h: 40 %). These results indicate that performing FTAI later following the 14 d CIDR-PG protocol increases the proportion of heifers that express estrus and are serviced with sex-sorted semen but does not improve conception rates. Later timing of FTAI following the 7 & 7 Synch protocol was not observed to increase the proportion of cows expressing estrus prior to FTAI or improve conception rates among estrous cows inseminated with sex-sorted semen. Together, these results provide further insight into optimal timing of FTAI when using sex-sorted semen. • Delayed timing of FTAI when using sex-sorted semen was evaluated. • A greater proportion of heifers expressed estrus prior to FTAI at later timepoints. • Conception rates were not improved among animals inseminated at later timepoints. [ABSTRACT FROM AUTHOR]

Objectives Ageism is a prevalent, insidious social justice issue that has harmful effects on the health of older adults. Preliminary literature explores the intersectionality of ageism with sexism, ableism, and ageism experienced among LGBTQ+ older adults. Yet, the intersectionality of ageism with racism remains largely absent from the literature. Therefore, this study explores the lived experience of the intersectionality of ageism and racism among older adults. Methods This qualitative study applied a phenomenological approach. Twenty participants 60+ years of age (M = 69, standard deviation = 8.84) in the U.S. Mountain West identifying as Black, Latino(a), Asian–American/Pacific Islander, Indigenous, or White engaged in a 1-hr interview between February and July 2021. A 3-cycle coding process applied constant comparison methods. Five coders independently coded interviews, engaging in critical discussion to resolve disagreements. An audit trail, member checking, and peer debriefing enhanced credibility. Results This study focuses on individual-level experiences exemplified by 3 umbrella themes and 7 subthemes. The subthemes are (a) compounding oppression, (b) intersection of disparities, (c) White privilege, (d) racism and ageism: being tokenized or ignored, (e) ageism and racism: unspoken bias, (f) racism versus ageism: overt or covert? and (g) racism versus ageism: differentiated or ubiquitous? Discussion The findings indicate how ageism may be racialized through stereotypes related to mental (in)capability. Practitioners can apply the findings to enhance support for older adults by designing interventions aimed at reducing racialized ageist stereotypes and increasing collaboration through education across anti-ageism/anti-racism initiatives. Future research should focus on the impacts of the intersectionality of ageism and racism on specific health outcomes in addition to structural-level interventions. [ABSTRACT FROM AUTHOR]

Background: Asthma and COVID-19 have overlapping symptoms. During the 2019–2022 pandemic, pediatric asthma control appears to have improved, with some researchers theorizing that that is due to changes in asthma self-management. This study examined adolescents' views regarding how the pandemic impacted their asthma severity and self-management. Differences by urbanicity, sex, and race/ethnicity were explored. Methods: We utilized baseline data from adolescents with poorly controlled asthma (n = 183) who were participating in 1 of 2 school-based clinical trials—1 in rural schools and 1 in urban schools—testing the impact of interventions to improve asthma control. Adolescents reported if they believed their asthma severity remained the same, improved, or worsened during the pandemic, and if it changed, how it changed. They also reported if and how they modified their asthma management since the pandemic. We used multinomial logistic regression and binary logistic regression to assess the relationship between demographic factors and changes in asthma severity during the pandemic, and if adolescents altered their asthma management. Results: Adolescents' mean age was 15.9 years; most lived in rural communities (65.6%) and identified as female (66.7%). About half (56.2%) self-identified as black, 13.1% as Hispanic, and 10.4% as another race/ethnicity. Most (68.4%) reported that their asthma severity remained unchanged; 26.0% reported it worsened. Nearly 30% reported they altered how they managed their asthma, with most (80%) reporting additional efforts. Compared with asthma remaining the same, females had a higher relative risk than males of reporting that their asthma worsened [adjusted relative risk ratio = 3.65, 95% confidence interval (CI) = 1.34–9.90, P < 0.05]. Urban youth had greater odds (adjusted odds ratio = 5.4, 95% CI = 2.0–14.5, P < 0.001) of reporting they changed their asthma self-management compared with rural peers. Conclusion: This study demonstrates that during the 2019–2022 pandemic, adolescents generally believed their asthma severity stayed consistent and many took additional self-management efforts. [ABSTRACT FROM AUTHOR]

Background: With the advances in the high throughput next generation sequencing technologies, genome-wide association studies (GWAS) have identified a large set of variants associated with complex phenotypic traits at a very fine scale. Despite the progress in GWAS, identification of genotype-phenotype relationship remains challenging in maize due to its nature with dozens of variants controlling the same trait. As the causal variations results in the change in expression, gene expression analyses carry a pivotal role in unraveling the transcriptional regulatory mechanisms behind the phenotypes. Results: To address these challenges, we incorporated the gene expression and GWAS-driven traits to extend the knowledge of genotype-phenotype relationships and transcriptional regulatory mechanisms behind the phenotypes. We constructed a large collection of gene co-expression networks and identified more than 2 million co-expressing gene pairs in the GWAS-driven pan-network which contains all the gene-pairs in individual genomes of the nested association mapping (NAM) population. We defined four sub-categories for the pan-network: (1) core-network contains the highest represented ~ 1% of the gene-pairs, (2) near-core network contains the next highest represented 1–5% of the gene-pairs, (3) private-network contains ~ 50% of the gene pairs that are unique to individual genomes, and (4) the dispensable-network contains the remaining 50–95% of the gene-pairs in the maize pan-genome. Strikingly, the private-network contained almost all the genes in the pan-network but lacked half of the interactions. We performed gene ontology (GO) enrichment analysis for the pan-, core-, and private- networks and compared the contributions of variants overlapping with genes and promoters to the GWAS-driven pan-network. Conclusions: Gene co-expression networks revealed meaningful information about groups of co-regulated genes that play a central role in regulatory processes. Pan-network approach enabled us to visualize the global view of the gene regulatory network for the studied system that could not be well inferred by the core-network alone. [ABSTRACT FROM AUTHOR]

"Critical Gerontology for Social Workers" is a collection of scholarly writings, edited by Dr. Sandra Torres and Dr. Sarah Donnelly, that provides readers an overview of challenges faced by the growing older adult population using a critical gerontology lens. The book is divided into two sections that 1) provides readers with a contextual and theoretical foundation of gerontological social work and 2) applies these concepts to different practice settings to guide social workers in utilizing a critical gerontology lens in their work. Written by experts from different countries and backgrounds, this book teaches social workers how to employ a critical gerontology perspective to address issues faced by older adults, on both a macro and micro level, through research, policy, and practice. [ABSTRACT FROM AUTHOR]

Researchers have worked for many decades to master the rules of biomolecular design that would allow artificial biopolymer complexes to self-assemble and function similarly to the diverse biochemical constructs displayed in natural biological systems. The rules of nucleic acid assembly (dominated by Watson–Crick base-pairing) have been less difficult to understand and manipulate than the more complicated rules of protein folding. Therefore, nucleic acid nanotechnology has advanced more quickly than de novo protein design, and recent years have seen amazing progress in DNA and RNA design. By combining structural motifs with aptamers that act as affinity handles and add powerful molecular recognition capabilities, nucleic acid-based self-assemblies represent a diverse toolbox for use by bioengineers to create molecules with potentially revolutionary biological activities. In this review, we focus on the development of self-assembling nucleic acid nanostructures that are functionalized with nucleic acid aptamers and their great potential in wide ranging application areas. [ABSTRACT FROM AUTHOR]

Background Tuberculous meningitis (TBM) has a high fatality rate, with inadequate diagnostic tests being a major contributor. The rollout of Xpert MTB/Rif and Xpert MTB/RIF Ultra (Xpert Ultra) have improved time-to-diagnosis with sensitivities similar to culture, yet test availability and sensitivity are inadequate. The TB lipoarabinomannan lateral flow assay (AlereLAM) offers ease of use, but its low sensitivity in cerebrospinal fluid (CSF) limits clinical utility for TBM. The Fujifilm SILVAMP TB LAM (FujiLAM) assay has excellent sensitivity in urine, but performance on cerebrospinal fluid is uncertain. Methods We conducted a prospective cohort study at Kiruddu National Referral Hospital in Kampala, Uganda, enrolling patients suspected to have TBM. CSF was tested using AlereLAM, Xpert Ultra, culture, and FujiLAM. Results were compared with 2 reference standards: probable and definite TBM or definite TBM alone by the uniform TBM case definition. Results Of 101 patients enrolled (95/101 HIV-positive), 34 had definite TBM and 24 had probable TBM. FujiLAM sensitivity on CSF was 52% (30/58) for definite or probable TBM compared with 55% (32/58) for Xpert Ultra. AlereLAM had lower sensitivity than FujiLAM in the subgroup of patients tested with both assays (14% [4/28] vs 50% [14/28]; P <.01). FujiLAM specificity was 98% (42/43) for patients without probable or definite TBM. Conclusions FujiLAM showed higher sensitivity than AlereLAM, with sensitivity potentially approaching that of Xpert Ultra. FujiLAM could improve time-to-treatment-initiation, especially in settings where the more technical Xpert Ultra system might not be feasible. Large confirmatory studies are needed. [ABSTRACT FROM AUTHOR]

Highly differentiated and affiliative social relationships are observed in a variety of mammals, including primates, cetaceans, and social carnivores. Although there has been a transformation in our understanding of the form and function of social bonds in the past two decades, the role of early life social experiences in the development of bonds remains less clear. Few studies have examined whether social relationships during infancy and juvenility (aside from those between mothers and offspring) persist into adulthood. In this study, we used longitudinal data on wild chimpanzees (Pan troglodytes schweinfurthii) at Gombe National Park, Tanzania, to investigate the effects of party-level association during infancy and juvenility (hereafter immaturity) on affiliative relationships among adult males (the philopatric sex). In total, we examined behavioral data from focal follows between 1970 and 2015 (N = 23 adult males). We used maternal associations as proxies for the associations of immature males, and we measured adult male social relationships using party-level associations and grooming activity. We found that immature males that associated with individual adult males at higher rates had stronger relationships with those same adult males later in life. By contrast, rates of association between pairs of immature males did not predict the strength of their dyadic relationships as adults. Overall, these findings emphasize the importance of early socialization in male chimpanzee social development. These results also reinforce studies in mountain gorillas (Gorilla beringei) and bottlenose dolphins (Tursiops sp.), suggesting that the persistence of social relationships that do not involve the mother may be more likely to evolve in long-lived species where young adult males face challenges entering an adult hierarchy composed of stronger and/or more socially experienced competitors. [ABSTRACT FROM AUTHOR]

Background Among combat injured, invasive fungal infections (IFIs) result in significant morbidity. Cultures and histopathology are the primary diagnostic methods for IFIs, but they have limitations. We previously evaluated a panfungal polymerase chain reaction assay, which was 83% sensitive and 99% specific for angioinvasive IFIs. Here, we evaluated 3 less resource-intensive seminested assays targeting clinically relevant fungi in the order Mucorales and genera Aspergillus and Fusarium. Methods Formalin-fixed paraffin-embedded tissue specimens from a multicenter trauma IFI cohort (2009-2014) were used. Cases were US military personnel injured in Afghanistan with histopathologic IFI evidence. Controls were patients with similar injury patterns and no laboratory IFI evidence (negative culture and histopathology). Seminested assays specific to Mucorales (V4/V5 regions of 18S rDNA), Aspergillus (mitochondrial tRNA), and Fusarium (internal transcribed spacer [ITS]/28A regions of DNA) were compared with a panfungal assay amplifying the internal transcribed spacer 2 region of rDNA and to histopathology. Results Specimens from 92 injury sites (62 subjects) were compared with control specimens from 117 injuries (101 subjects). We observed substantial agreement between the seminested and panfungal assays overall, especially for the order Mucorales. Moderate agreement was observed at the genus level for Aspergillus and Fusarium. When compared with histopathology, sensitivity and specificity of seminested assays were 67.4% and 96.6%, respectively (sensitivity increased to 91.7% when restricted to sites with angioinvasion). Conclusions Prior studies of seminested molecular diagnostics have focused on culture-negative samples from immunocompromised patients. Our findings underscore the utility of the seminested approach in diagnosing soft-tissue IFIs using formalin-fixed paraffin-embedded tissue samples, especially with angioinvasion. [ABSTRACT FROM AUTHOR]

The recent assembly and annotation of the 26 maize nested association mapping population founder inbreds have enabled large-scale pan-genomic comparative studies. These studies have expanded our understanding of agronomically important traits by integrating pan-transcriptomic data with trait-specific gene candidates from previous association mapping results. In contrast to the availability of pan-transcriptomic data, obtaining reliable protein–protein interaction (PPI) data has remained a challenge due to its high cost and complexity. We generated predicted PPI networks for each of the 26 genomes using the established STRING database. The individual genome-interactomes were then integrated to generate core- and pan-interactomes. We deployed the PPI clustering algorithm ClusterONE to identify numerous PPI clusters that were functionally annotated using gene ontology (GO) functional enrichment, demonstrating a diverse range of enriched GO terms across different clusters. Additional cluster annotations were generated by integrating gene coexpression data and gene description annotations, providing additional useful information. We show that the functionally annotated PPI clusters establish a useful framework for protein function prediction and prioritization of candidate genes of interest. Our study not only provides a comprehensive resource of predicted PPI networks for 26 maize genomes but also offers annotated interactome clusters for predicting protein functions and prioritizing gene candidates. The source code for the Python implementation of the analysis workflow and a standalone web application for accessing the analysis results are available at https://github.com/eporetsky/PanPPI. [ABSTRACT FROM AUTHOR]

Visual signal transduction takes place within a stack of flattened membranous 'discs' enclosed within the light-sensitive photoreceptor outer segment. The highly curved rims of these discs, formed in the process of disc enclosure, are fortified by large hetero-oligomeric complexes of two homologous tetraspanin proteins, PRPH2 (a.k.a. peripherin-2 or rds) and ROM1. While mutations in PRPH2 affect the formation of disc rims, the role of ROM1 remains poorly understood. In this study, we found that the knockout of ROM1 causes a compensatory increase in the disc content of PRPH2. Despite this increase, discs of ROM1 knockout mice displayed a delay in disc enclosure associated with a large diameter and lack of incisures in mature discs. Strikingly, further increasing the level of PRPH2 rescued these morphological defects. We next showed that disc rims are still formed in a knockin mouse in which the tetraspanin body of PRPH2 was replaced with that of ROM1. Together, these results demonstrate that, despite its contribution to the formation of disc rims, ROM1 can be replaced by an excess of PRPH2 for timely enclosure of newly forming discs and establishing normal outer segment structure. [ABSTRACT FROM AUTHOR]

Introduction Battlefield-related wound infections are a significant source of morbidity among combat casualties. Seasonality of these infections was demonstrated in previous conflicts (e.g. Korea) but has not been described with trauma-related health care–associated infections from the war in Afghanistan. Methods The study population included military personnel wounded in Afghanistan (2009-2014) medevac'd to Landstuhl Regional Medical Center and transitioned to participating military hospitals in the United States with clinical suspicion of wound infections and wound cultures collected ≤7 days post-injury. Analysis was limited to the first wound culture from individuals. Infecting isolates were collected from skin and soft-tissue infections, osteomyelitis, and burn soft-tissue infections. Data were analyzed by season (winter [ December 1-February 28/29], spring [March 1-May 31], summer [June 1-August 31], and fall [September 1-November 30]). Results Among 316 patients, 297 (94.0%) sustained blast injuries with a median injury severity score and days from injury to initial culture of 33 and 3.5, respectively. Although all patients had a clinical suspicion of a wound infection, a diagnosis was confirmed in 198 (63%) patients. Gram-negative bacilli (59.5% of 316) were more commonly isolated from wound cultures in summer (68.1%) and fall (67.1%) versus winter (43.9%) and spring (45.1%; P  < .001). Multidrug-resistant (MDR) Gram-negative bacilli (21.8%) were more common in summer (21.8%) and fall (30.6%) versus winter (7.3%) and spring (19.7%; P  = .028). Findings were similar for infecting Gram-negative bacilli (72.7% of 198)—summer (79.5%) and fall (83.6%; P  = .001)—and infecting MDR Gram-negative bacilli (27.3% of 198)—summer (25.6%) and fall (41.8%; P  = .015). Infecting anaerobes were more common in winter (40%) compared to fall (11%; P  = .036). Gram-positive organisms were not significantly different by season. Conclusion Gram-negative bacilli, including infecting MDR Gram-negative bacilli, were more commonly recovered in summer/fall months from service members injured in Afghanistan. This may have implications for empiric antibiotic coverage during these months. [ABSTRACT FROM AUTHOR]

The first steps of vision take place within a stack of tightly packed disc-shaped membranes, or 'discs', located in the outer segment compartment of photoreceptor cells. In rod photoreceptors, discs are enclosed inside the outer segment and contain deep indentations in their rims called 'incisures'. The presence of incisures has been documented in a variety of species, yet their role remains elusive. In this study, we combined traditional electron microscopy with three-dimensional electron tomography to demonstrate that incisures are formed only after discs become completely enclosed. We also observed that, at the earliest stage of their formation, discs are not round as typically depicted but rather are highly irregular in shape and resemble expanding lamellipodia. Using genetically manipulated mice and frogs and measuring outer segment protein abundances by quantitative mass spectrometry, we further found that incisure size is determined by the molar ratio between peripherin-2, a disc rim protein critical for the process of disc enclosure, and rhodopsin, the major structural component of disc membranes. While a high perpherin-2 to rhodopsin ratio causes an increase in incisure size and structural complexity, a low ratio precludes incisure formation. Based on these data, we propose a model whereby normal rods express a modest excess of peripherin-2 over the amount required for complete disc enclosure in order to ensure that this important step of disc formation is accomplished. Once the disc is enclosed, the excess peripherin-2 incorporates into the rim to form an incisure. [ABSTRACT FROM AUTHOR]

This study examined the association between depressive symptoms and self-rated health (SRH) and whether and how such association varies by education among older adults with cancer. Data came from the 2019 National Health Interview Survey. A total of 2,470 participants aged 65 or older who had been diagnosed with cancer by a doctor or other health professional were included in this study. Ordinal logistic regression was used to examine the association between depressive symptoms and SRH and whether and how such association varies by education among older adults with cancer. More depressive symptoms were associated with worse SRH. Such association became stronger with higher education among older adults with cancer. Findings confirm the associations between depressive symptoms and SRH among older adults with cancer. The differential impact of education on SRH and on the association between depressive symptoms and SRH highlights the importance of considering patients' educational attainment in a more comprehensive way when working with older adults with cancer. When conducting distress screening among cancer survivors, oncology social workers should be aware of the complex relationship between education and depression in relation to cancer survivors' SRH. [ABSTRACT FROM AUTHOR]

Background: Environmental stress factors, such as biotic and abiotic stress, are becoming more common due to climate variability, significantly affecting global maize yield. Transcriptome profiling studies provide insights into the molecular mechanisms underlying stress response in maize, though the functions of many genes are still unknown. To enhance the functional annotation of maize-specific genes, MaizeGDB has outlined a data-driven approach with an emphasis on identifying genes and traits related to biotic and abiotic stress. Results: We mapped high-quality RNA-Seq expression reads from 24 different publicly available datasets (17 abiotic and seven biotic studies) generated from the B73 cultivar to the recent version of the reference genome B73 (B73v5) and deduced stress-related functional annotation of maize gene models. We conducted a robust meta-analysis of the transcriptome profiles from the datasets to identify maize loci responsive to stress, identifying 3,230 differentially expressed genes (DEGs): 2,555 DEGs regulated in response to abiotic stress, 408 DEGs regulated during biotic stress, and 267 common DEGs (co-DEGs) that overlap between abiotic and biotic stress. We discovered hub genes from network analyses, and among the hub genes of the co-DEGs we identified a putative NAC domain transcription factor superfamily protein (Zm00001eb369060) IDP275, which previously responded to herbivory and drought stress. IDP275 was up-regulated in our analysis in response to eight different abiotic and four different biotic stresses. A gene set enrichment and pathway analysis of hub genes of the co-DEGs revealed hormone-mediated signaling processes and phenylpropanoid biosynthesis pathways, respectively. Using phylostratigraphic analysis, we also demonstrated how abiotic and biotic stress genes differentially evolve to adapt to changing environments. Conclusions: These results will help facilitate the functional annotation of multiple stress response gene models and annotation in maize. Data can be accessed and downloaded at the Maize Genetics and Genomics Database (MaizeGDB). [ABSTRACT FROM AUTHOR]

Pan-genomes, encompassing the entirety of genetic sequences found in a collection of genomes within a clade, are more useful than single reference genomes for studying species diversity. This is especially true for a species like Zea mays , which has a particularly diverse and complex genome. Presenting pan-genome data, analyses, and visualization is challenging, especially for a diverse species, but more so when pan-genomic data is linked to extensive gene model and gene data, including classical gene information, markers, insertions, expression and proteomic data, and protein structures as is the case at MaizeGDB. Here, we describe MaizeGDB's expansion to include the genic subset of the Zea pan-genome in a pan-gene data center featuring the maize genomes hosted at MaizeGDB, and the outgroup teosinte Zea genomes from the Pan-Andropoganeae project. The new data center offers a variety of browsing and visualization tools, including sequence alignment visualization, gene trees and other tools, to explore pan-genes in Zea that were calculated by the pipeline Pandagma. Combined, these data will help maize researchers study the complexity and diversity of Zea , and to use the comparative functions to validate pan-gene relationships for a selected gene model. [ABSTRACT FROM AUTHOR]

Although rare among group-living primates, infanticide by females has been reported in several chimpanzee, Pan troglodytes , populations. We examined 13 infanticidal attacks over 47 years at Gombe National Park, Tanzania to evaluate three adaptive hypotheses. (1) Exploitation of the infant as a food resource – by eating a vulnerable neonate, attackers gain calories that may be important during periods of food scarcity or energetic stress. (2) Resource competition – Gombe females concentrate their foraging in overlapping core areas and dominance rank influences foraging success. By killing the infant of a female with high core area overlap, the perpetrator removes a current and future competitor, improving her access to food. (3) Low cost – female chimpanzees mature and reproduce slowly, and longevity increases reproductive success. Physical aggression causes risk of severe injury or death, so females will only mount attacks when risks to the perpetrator are low. In support of hypothesis 1, females usually consumed the carcass. However, attacks were not more likely in times of resource or energy scarcity. In support of hypothesis 2, females attacked others with whom they shared core areas, but attacks did not cause shifts in ranging patterns. In support of hypothesis 3, one or more attackers always outranked the victim, the attacks often involved coalitions and victims usually lacked kin support. Attacks were more likely to be successful when attackers were not hindered by clinging infants and victims could not retreat. Our results provide further evidence for female competition and the adaptive value of female-led infanticide in this species. • We documented 13 female-led infanticidal attacks in one chimpanzee community. • Infant victims were usually eaten, providing immediate nutrition to the attacker. • Attackers targeted likely competitors whose foraging areas overlapped their own. • Attackers usually targeted neonates of lower-ranking mothers who lacked kin support. [ABSTRACT FROM AUTHOR]

The aim of this qualitative, phenomenological study was to understand how older adults cope with experiences of ageism and racism through an intersectional lens. Twenty adults 60+ residing in the U.S. Mountain West who identified as Black, Hispanic/Latino(a), Asian-American/Pacific Islander, Indigenous, or White participated individually in a one-hour, semi-structured interview. A team of five coders engaged in an inductive coding process through independent coding followed by critical discussion. Peer debriefing enhanced credibility. Nine themes were organized by three umbrella categories: Coping with ageism: 1) distancing via self-determination/defying stereotypes, 2) distancing by helping others; Coping with racism: 3) resistance, 4) exhaustion; Coping with both ageism and racism: 5) increased awareness through aging, 6) healthy lifestyle, 7) education, 8) acceptance/ 'let it go', and 9) avoidance. Novel findings include how older adults may cope with ageism and racism via increased awareness through aging and with ageism specifically by helping peer older adults, although instances of internalized ageism were noted and discussed. The themes exemplify problem-focused (e.g., helping others) and emotion-focused (acceptance), as well as individual (e.g., self-determination) and collective (e.g., resistance) coping strategies. This study can serve as a resource for practitioners in applying a more nuanced understanding of the ways older adults cope with ageism and racism in later life. • This study applied an intersectional lens to describe how older adults cope with experiences of ageism and racism. • Increased awareness through aging is one way older adults may cope with both ageism and racism in later life. • Older adults appeared to cope with ageism by distancing themselves from negative age stereotypes and peer older adults. • Older adults responded to racism through protests, education, and resistance, which led to exhaustion. • Practitioners should tailor problem or emotion-focused coping strategies within the unique context of each client. [ABSTRACT FROM AUTHOR]

Protein structures play an important role in bioinformatics, such as in predicting gene function or validating gene model annotation. However, determining protein structure was, until now, costly and time-consuming, which resulted in a structural biology bottleneck. With the release of such programs AlphaFold and ESMFold, this bottleneck has been reduced by several orders of magnitude, permitting protein structural comparisons of entire genomes within reasonable timeframes. MaizeGDB has leveraged this technological breakthrough by offering several new tools to accelerate protein structural comparisons between maize and other plants as well as human and yeast outgroups. MaizeGDB also offers bulk downloads of these comparative protein structure data, along with predicted functional annotation information. In this way, MaizeGDB is poised to assist maize researchers in assessing functional homology, gene model annotation quality, and other information unavailable to maize scientists even a few years ago. [ABSTRACT FROM AUTHOR]

The aim of this study is to examine perceived quality of life in Chinese older adults living with cognitive impairment and explore its associations with caregivers' characteristics. Questionnaires were administered in person to 271 caregiver-care recipient dyads from urban communities in mainland China in 2019. We used the 40-item Alzheimer's Disease-related Quality of Life tool and asked caregiver respondents to indicate care recipients' life conditions. The questionnaire asked caregivers about their sociodemographic characteristics, levels of informal social support, caregiver burden, and depressive symptoms. Caregivers' higher levels of caregiver burden (β = > −0.19, p <.01) and depressive symptoms (β = > −0.19, p <.01) amongst caregivers were significantly associated with lower quality of life among care recipients. Informal support from relatives and friends to caregivers did not significantly affect quality of life of care recipients. The results suggested that reducing caregivers' burden and depressive symptoms are essential to promote quality of life of care recipients. Formal support from health professionals, service organizations, and communities are urgently called to promote the wellbeing of Chinese families affected by cognitive impairment. [ABSTRACT FROM AUTHOR]

Background Cryptococcal meningitis is a common cause of AIDS-related mortality. Although symptom recurrence after initial treatment is common, the etiology is often difficult to decipher. We sought to summarize characteristics, etiologies, and outcomes among persons with second-episode symptomatic recurrence. Methods We prospectively enrolled Ugandans with cryptococcal meningitis and obtained patient characteristics, antiretroviral therapy (ART) and cryptococcosis histories, clinical outcomes, and cerebrospinal fluid (CSF) analysis results. We independently adjudicated cases of second-episode meningitis to categorize patients as (1) microbiological relapse, (2) paradoxical immune reconstitution inflammatory syndrome (IRIS), (3) persistent elevated intracranial pressure (ICP) only, or (4) persistent symptoms only, along with controls of primary cryptococcal meningitis. We compared groups with chi-square or Kruskal-Wallis tests as appropriate. Results 724 participants were included (n = 607 primary episode, 81 relapse, 28 paradoxical IRIS, 2 persistently elevated ICP, 6 persistent symptoms). Participants with culture-positive relapse had lower CD4 (25 cells/μL; IQR: 9–76) and lower CSF white blood cell (WBC; 4 cells/μL; IQR: 4–85) counts than paradoxical IRIS (CD4: 78 cells/μL; IQR: 47–142; WBC: 45 cells/μL; IQR: 8–128). Among those with CSF WBC <5 cells/μL, 86% (43/50) had relapse. Among those with CD4 counts <50 cells/μL, 91% (39/43) had relapse. Eighteen-week mortality (from current symptom onset) was 47% among first episodes of cryptococcal meningitis, 31% in culture-positive relapses, and 14% in paradoxical IRIS. Conclusions Poor immune reconstitution was noted more often in relapse than IRIS as evidenced by lower CSF WBC and blood CD4 counts. These easily obtained laboratory values should prompt initiation of antifungal treatment while awaiting culture results. Clinical Trials Registration NCT01802385. [ABSTRACT FROM AUTHOR]

To provide a quantitative synthesis of studies on the relationship between vision impairment (VI) and cognitive outcomes in older adults. A systematic search was undertaken of relevant databases for original articles published before April 2020. Random effect models were used to obtain pooled estimates of the associations between VI and cognitive outcomes (cognitive impairment and dementia) with subgroup analyses of VI measures, cross-sectional associations of VI with cognitive impairment, and longitudinal associations of baseline VI with incident cognitive impairment and dementia. Potential sources of heterogeneity were explored by meta-regression. Publication bias was evaluated with Egger's test. Sixteen studies including 76,373 participants were included in this meta-analysis, with five cross-sectional studies and eleven longitudinal studies. There was a significantly increased risk of cognitive outcomes with VI identified by subjective measures (odds ratio (OR)=1.63; 95% confidence interval (CI): 1.26–1.99) and objective measures (OR = 1.59; 95% CI: 1.40–1.78). The odds of baseline cognitive impairment were 137% higher in older adults with VI compared with those without VI (OR = 2.37, 95% CI: 1.84–3.03) at baseline. Compared with older adults without VI at baseline, those with baseline VI had a higher relative risk (RR) of incident cognitive impairment (RR = 1.41; 95% CI: 1.31–1.51) and dementia (RR = 1.44, 95% CI: 1.19–1.75). VI was associated with increased risks of cognitive impairment and dementia across cross-sectional and longitudinal studies. Additional research and randomized clinical trials are warranted to examine the implications of treatment for VI, such as wearing glasses and cataract surgery, to avoid cognitive impairment and dementia. [ABSTRACT FROM AUTHOR]

Three experiments (EXP) were conducted to determine the effect of feed additives on performance, intestinal integrity, gastrointestinal volatile fatty acids (VFA), and energy and nutrient digestion in nonchallenged nursery pigs. In EXP 1, 480 pigs (6.36-kg body weight, BW) were placed into 96 pens with 5 pigs/pen, and allotted to 1 of 10 dietary treatments: 1) negative control containing no feed additive (NC), 2) NC + 44 mg chlortetracycline and 38.5 mg tiamulin/kg diet (CTsb), 3) NC + 5% resistant potato starch (RSpo), 4) NC + 5% soluble corn fiber (SCF), 5) NC + 5% sugar beet pulp (SBP), 6) NC + 0.30% fatty acid mix (FAM), 7) NC + 0.10% phytogenic blend of essential oils and flavoring compounds (PHY), 8) NC + 50 mg Cu and 1,600 mg zinc oxide/kg diet (CuZn), 9) NC + 5% resistant corn starch (RScn), and 10) NC + 0.05% β-glucan (BG) for 28 d. There was no impact of dietary treatment on BW gain or feed intake (P ≥ 0.22). Pigs fed diets containing SCF, CTsb, and RSpo resulted in microbial community differences compared to pigs fed the NC (P < 0.05). In EXP 2, 48 barrows (12.8 kg BW) were selected at the end of EXP 1 and fed the same dietary treatments they had previously received: 1) NC, 2) NC + 5% RScn, 3) NC + 5% SCF, and 4) NC + FAM for 8 d. There was no effect of feeding diets containing RScn, SCF, or FAM on in vivo intestinal permeability (P ≤ 0.21). Ileal or colon pH, concentrations of VFA did not differ due to dietary treatment (P ≥ 0.36), but pigs fed diets containing FAM resulted in a greater butyric acid concentration in the cecum compared to pigs fed the NC (P ≤ 0.05). In EXP 3, 156 pigs (6.11 kg BW) were placed into 52 pens with 3 pigs/pen and allotted to 1 of 4 dietary treatments arranged in a factorial manner: 1) NC, 2) NC + 5% RSpo, 3) NC + 0.30% FAM, and 4) NC + 5% RSpo + 0.30% FAM for 24 d. Feeding pigs diets containing RSpo did not affect BW gain (P = 0.91) while pigs fed diets containing FAM grew improved BW gain (P = 0.09). Colonic butyric acid concentrations were greater in pigs fed diets containing RSpo (P = 0.03), while pigs fed diets containing FAM exhibited reduced total VFA concentrations (P = 0.11). The results indicate that supplementing diets with digestively resistant but fermentable fibers, short- and medium-chain fatty acids, or antibiotics do not have a consistent effect, positive or negative, on markers of intestinal integrity or barrier function, intestinal VFA patterns, ATTD of energy and nutrients, or on pig performance. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic and associated restrictions pose a significant health threat to older adults. Fear of COVID-19 is associated with increased disease transmission and numerous psychosocial health challenges. While social support has been studied extensively in gerontological literature, there is a gap in understanding how social networks influence fear of COVID-19. This study drew from a convenience sample of 239 adults 60+ years of age in the United States who completed a 20-min survey. Regression results indicate that higher social network was significantly associated with decreased fear of COVID-19. Identifying as female and as an ethnic minority were associated with increased fear of COVID-19. These findings document the need for social workers to promote enhanced social networks in reducing fear of COVID-19 among older adults and attend to disparate levels of fear among older women and people of color. [ABSTRACT FROM AUTHOR]

An experiment was designed to evaluate later timepoints for fixed-time artificial insemination (FTAI) of beef heifers, with the hypothesis that use of a later timepoint would allow a greater proportion of heifers to express estrus prior to FTAI and result in greater conception rates among estrous heifers inseminated with sex-sorted semen. Estrus was synchronized using the 14-d CIDR®-PG protocol (1.38 g progesterone CIDR intravaginally inserted Day -33 and removed Day -19, PGF2a; 500 µg cloprostenol administered Day -3) for 1640 heifers in 7 locations. Heifers were blocked by reproductive tract score and body weight and randomly assigned to one of three FTAI timepoints: 66 ± 2 h, 70 ± 2 h, or 74 ± 2 h after PGF2a administration. Estrus detection aids (Estrotect) were applied at PGF2a administration, with activation recorded at FTAI. Heifers that expressed estrus prior to FTAI were serviced with sex-sorted semen (SexedULTRA 4M™). Heifers that failed to express estrus were serviced with conventional semen and administered gonadotropinreleasing hormone (GnRH; 100 µg gonadorelin). The proportion of heifers that expressed estrus by FTAI (66 h: 63%; 70 h: 68%; 74 h: 72%) was greater at 74 h versus 66 h (P < 0.01). Conception rates did not differ significantly between treatments among heifers that expressed estrus and were serviced with sex-sorted semen (66 h: 55%; 70 h: 53%; 74 h: 52%). Among heifers that failed to express estrus and were serviced with conventional semen, conception rates were greater (P = 0.02) when FTAI was performed at 66 h versus 70 h (66 h: 39%; 70 h: 26%; 74 h: 32%). Results indicate that performing FTAI later following the 14-d CIDR®-PG protocol increases the proportion of heifers that express estrus and are serviced with sex-sorted semen, but does not improve conception rates of estrous heifers inseminated at later timepoints. [ABSTRACT FROM AUTHOR]

Objectives: To examine the association between post-traumatic stress and depression and whether such an association differs by level of loneliness among older Puerto Ricans. Methods: Data were collected from 304 Puerto Ricans aged 60 and above living in the Greater Boston area who responded to questionnaires. We used ordinary least squares regression to examine the association between post-traumatic stress, loneliness, and depressive symptoms. Results: Post-traumatic stress was significantly associated with higher levels of depression. The association between post-traumatic stress and depression was stronger for those experiencing a higher degree of loneliness. Discussion: In working with older Puerto Ricans experiencing post-traumatic stress, it is important for mental health professionals to incorporate the assessment of loneliness and to prevent and reduce comorbid depression by addressing loneliness through improving social skills, enhancing social support, and reducing maladaptive social cognition. [ABSTRACT FROM AUTHOR]

The purpose of this study is to examine the reliability and validity of the ADRQL instrument among older adults with cognitive impairment in mainland China. Three hundred older adults with cognitive impairment and their primary family caregivers from Wuhan participated in structured interviews. Cronbach's α and Kuder–Richardson Formula 20 were used to examine internal consistency reliability. Confirmatory factor analysis, Heterotrait-Monotrait ratios, and ordinary least square regression were used to assess the factorial validity, discriminant validity, and criterion validity. The ADRQL had acceptable reliability and validity, which can be used to assess overall quality of life for this population. [ABSTRACT FROM AUTHOR]

A large body of literature demonstrates the adaptive benefits of social relationships between kin, including fitness and survival. Given that most social mammals are characterized by male-biased dispersal, the majority of research on kin selection and associated advantages focuses on social relationships between female kin. Meanwhile, research on social relationships between adult male and female kin has primarily focused on inbreeding avoidance or the benefit to adult sons, with less attention on potential advantages these social relationships may provide females. The general pattern of male dominance over females in most mammal species suggests that females may benefit from protective associations with adult male kin. Using 43 years of behavioural data on the wild chimpanzees, Pan troglodytes schweinfurthii , of Gombe National Park, Tanzania, we examined association patterns between females and their adult maternal male kin. We specifically focused on how these associations may represent a trade-off between inbreeding avoidance and protection for females, particularly against infanticide. In accordance with inbreeding avoidance, we predicted that females' association with adult kin would decrease when they were maximally tumescent, signalling sexual receptivity. To determine whether female–male kin associations provide protection to females, we examined female associations with adult male kin during their first year postpartum when infants are most vulnerable to infanticide. We predicted that during this first year postpartum, females would have a higher association with male kin than with unrelated males. We found that females associated more with adult sons and brothers than with unrelated males when they did not have a sexual swelling. Female association increased with all males across tumescence but females associated less with their brothers than they did with their sons and unrelated males when they were maximally tumescent, providing equivocal support for the inbreeding avoidance hypothesis. Furthermore, females associated more with both sons and brothers than with unrelated males in the first 6 months of the postpartum period. Higher association with brothers, relative to unrelated males, persisted throughout the first year postpartum. Together, these results speak to the cost–benefit trade-off in female and adult male kin associations, highlighting the potential protective advantage for females, especially during the postpartum period. • We examined association patterns between females and their adult maternal male kin. • Association with sons, brothers and unrelated males increased with swelling size. • Association with sons was higher than with other males during early postpartum. • Association with brothers was higher than with unrelated males 1 year postpartum. • Our results suggest a potential male kin protective advantage postpartum. [ABSTRACT FROM AUTHOR]

Maintaining water balance is essential for organismal health, and lactating females must balance individual needs with milk production and offspring hydration. Primate milk is dilute and presumed to be the primary source for infant hydration for a considerable time period. Few studies have investigated the hydration burden that lactation may place on female primates. In this study, we investigated sources of variation in female and offspring drinking frequency among wild chimpanzees (Pan troglodytes). We hypothesized females would experience seasonal and lactation hydration burdens and adjust their drinking behavior to accommodate these, but this hydration burden would vary between females of different dominance ranks. We also predicted that parity would relate to maternal drinking frequency since primiparous females are still investing in their own growth. Finally, we predicted that offspring would drink more in the dry season and as they aged and lost milk as a water source, but that offspring of high‐ranking females would be buffered from these effects. Using 41 years of long‐term data on the behavior of mothers and offspring of Gombe National Park, we found that mothers drank more in the dry season, but there was no significant difference between mothers of different ranks during this period. Low‐ranking females drank significantly more than mid‐ and high‐ranking females during late lactation. Offspring also drank more in the dry season and as they aged, but there was no evidence of buffering for those with high‐ranking mothers. While chimpanzees in our study population drank infrequently, they do demonstrate noticeable shifts in drinking behavior that suggests seasonal and reproductive hydration burdens. Highlights: Chimpanzee mothers and their offspring drank more water in the dry season, regardless of maternal dominance rank.Low‐ranking mothers drank significantly more than mid‐ and high‐ranking females during late lactation, when offspring are 3–4.5 years of age, but there was no evidence of this difference in offspring.The Gombe chimpanzees demonstrate noticeable shifts in drinking behavior that suggests seasonal and reproductive hydration burdens. [ABSTRACT FROM AUTHOR]

Introduction: During Operation Enduring Freedom in Afghanistan, an outbreak of combat-related invasive fungal wound infections (IFIs) emerged among casualties with dismounted blast trauma and became a priority issue for the Military Health System.Methods: In 2011, the Trauma Infectious Disease Outcomes Study (TIDOS) team led the Department of Defense IFI outbreak investigation to describe characteristics of IFIs among combat casualties and provide recommendations related to management of the disease. To support the outbreak investigation, existing IFI definitions and classifications utilized for immunocompromised patients were modified for use in epidemiologic research in a trauma population. Following the conclusion of the outbreak investigation, multiple retrospective analyses using a population of 77 IFI patients (injured during June 2009 to August 2011) were conducted to evaluate IFI epidemiology, wound microbiology, and diagnostics to support refinement of Joint Trauma System (JTS) clinical practice guidelines. Following cessation of combat operations in Afghanistan, the TIDOS database was comprehensively reviewed to identify patients with laboratory evidence of a fungal infection and refine the IFI classification scheme to incorporate timing of laboratory fungal evidence and include categories that denote a high or low level of suspicion for IFI. The refined IFI classification scheme was utilized in a large-scale epidemiologic assessment of casualties injured over a 5.5-year period.Results: Among 720 combat casualties admitted to participating hospitals (2009-2014) who had histopathology and/or wound cultures collected, 94 (13%) met criteria for an IFI and 61 (8%) were classified as high suspicion of IFI. Risk factors for development of combat-related IFIs include sustaining a dismounted blast injury, experiencing a traumatic transfemoral amputation, and requiring resuscitation with large-volume (>20 units) blood transfusions. Moreover, TIDOS analyses demonstrated the adverse impact of IFIs on wound healing, particularly with order Mucorales. A polymerase chain reaction (PCR)-based assay to identify filamentous fungi and support earlier IFI diagnosis was also assessed using archived formalin-fixed, paraffin-embedded tissue specimens. Although the PCR-based assay had high specificity (99%), there was low sensitivity (63%); however, sensitivity improved to 83% in tissues collected from sites with angioinvasion. Data obtained from the initial IFI outbreak investigation (37 IFI patients) and subsequent TIDOS analyses (77 IFI patients) supported development and refinement of a JTS clinical practice guideline for the management of IFIs in war wounds. Furthermore, a local clinical practice guideline to screen for early tissue-based evidence of IFIs among blast casualties at the Landstuhl Regional Medical Center was critically evaluated through a TIDOS investigation, providing additional clinical practice support. Through a collaboration with the Uniformed Services University Surgical Critical Care Initiative, findings from TIDOS analyses were used to support development of a clinical decision support tool to facilitate early risk stratification.Conclusions: Combat-related IFIs are a highly morbid complication following severe blast trauma and remain a threat for future modern warfare. Our findings have supported JTS clinical recommendations, refined IFI classification, and confirmed the utility of PCR-based assays as a complement to histopathology and/or culture to promote early diagnosis. Analyses underway or planned will add to the knowledge base of IFI epidemiology, diagnostics, prevention, and management. [ABSTRACT FROM AUTHOR]

Objectives: To examine (1) the association between perceived discrimination, including everyday perceived discrimination and major lifetime perceived discrimination, and cognitive function and (2) the mediating role of depression between discrimination and cognitive function among older Puerto Ricans. Methods: Data came from the Boston Puerto Rican Health Study, collected from 562 Puerto Ricans aged 60+. Structural Equation Modelling was used to examine the association between discrimination and cognitive function and the mediating effect of depression. Results: Everyday perceived discrimination was negatively associated with cognitive function, which was fully mediated by depression. Major Lifetime perceived discrimination was not associated with cognitive function. Conclusions: The findings contribute new information regarding the impact of perceived discrimination on cognitive function among older Puerto Ricans and underscore the importance of assessing experiences of discrimination to prevent depression and cognitive decline in this population. Key points: Everyday perceived discrimination was negatively associated with cognitive function, which was fully mediated by depressionMajor Lifetime perceived discrimination was not associated with cognitive function [ABSTRACT FROM AUTHOR]

Background: Intestinal anastomoses in military settings are performed in severely injured patients who often undergo damage control laparotomy in austere environments. We describe anastomotic outcomes of patients from recent wars.Methods: Military personnel with combat-related intra-abdominal injuries (June 2009-December 2014) requiring laparotomy with resection and anastomosis were analyzed. Patients were evacuated from Iraq or Afghanistan to Landstuhl Regional Medical Center (Germany) before being transferred to participating U.S. military hospitals.Results: Among 341 patients who underwent 1053 laparotomies, 87 (25.5%) required ≥1 anastomosis. Stapled anastomosis only was performed in 57.5% of patients, while hand-sewn only was performed in 14.9%, and 9.2% had both stapled and hand-sewn techniques (type unknown for 18.4%). Anastomotic failure occurred in 15% of patients. Those with anastomotic failure required more anastomoses (median 2 anastomoses, interquartile range [IQR] 1-3 vs. 1 anastomosis, IQR 1-2, P = .03) and more total laparotomies (median 5 laparotomies, IQR 3-12 vs. 3, IQR 2-4, P = .01). There were no leaks in patients that had only hand-sewn anastomoses, though a significant difference was not seen with those who had stapled anastomoses. While there was an increasing trend regarding surgical site infections (SSIs) with anastomotic failure after excluding superficial SSIs, it was not significant. There was no difference in mortality.Discussion: Military trauma patients have a similar anastomotic failure rate to civilian trauma patients. Patients with anastomotic failure were more likely to have had more anastomoses and more total laparotomies. No definitive conclusions can be drawn about anastomotic outcome differences between hand-sewn and stapled techniques. [ABSTRACT FROM AUTHOR]

Background: Cardiometabolic diseases (CMDs) are associated with depression. However, it is unclear whether coexisting CMDs may increase the risk of depression. We examined associations between cardiometabolic multimorbidity and depressive symptoms among middle-aged and older Chinese.Methods: Participants aged ≥45 years were enrolled from the China Health and Retirement Longitudinal Study 2011-2018 (N = 18,002). Cardiometabolic multimorbidity was defined as the coexistence of ≥2 CMDs, including stroke, heart disease, diabetes, hypertension, and dyslipidemia. Depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale. We used generalized estimating equation models to examine associations between cardiometabolic multimorbidity and depressive symptoms, including the dose effect of disease count and prevalent disease combinations, as well as individual and additive effects of specific CMDs.Results: The prevalence of cardiometabolic multimorbidity was 24.5%. A higher number of CMDs had an additive dose effect on depressive symptoms that persisted consistently in specific CMDs. Stroke only, heart disease only, and diabetes only were each associated with a higher risk of depressive symptoms compared with no CMDs. CMD combinations involving stroke, heart disease, or diabetes were each associated with an increased risk of depressive symptoms compared with the absence of stroke, heart disease, or diabetes.Limitation: Self-reported chronic conditions.Conclusion: Stroke, heart disease, and diabetes showed individual and additive effects on CMD combinations, whereas hypertension and dyslipidemia only showed associations with depressive symptoms in combinations with other CMDs. These results suggest person-centered healthcare of mental health prevention and treatment for middle-aged and older adults with individual or multiple CMDs. [ABSTRACT FROM AUTHOR]

Motivation Over the last decade, RNA-Seq whole-genome sequencing has become a widely used method for measuring and understanding transcriptome-level changes in gene expression. Since RNA-Seq is relatively inexpensive, it can be used on multiple genomes to evaluate gene expression across many different conditions, tissues and cell types. Although many tools exist to map and compare RNA-Seq at the genomics level, few web-based tools are dedicated to making data generated for individual genomic analysis accessible and reusable at a gene-level scale for comparative analysis between genes, across different genomes and meta-analyses. Results To address this challenge, we revamped the comparative gene expression tool qTeller to take advantage of the growing number of public RNA-Seq datasets. qTeller allows users to evaluate gene expression data in a defined genomic interval and also perform two-gene comparisons across multiple user-chosen tissues. Though previously unpublished, qTeller has been cited extensively in the scientific literature, demonstrating its importance to researchers. Our new version of qTeller now supports multiple genomes for intergenomic comparisons, and includes capabilities for both mRNA and protein abundance datasets. Other new features include support for additional data formats, modernized interface and back-end database and an optimized framework for adoption by other organisms' databases. Availability and implementation The source code for qTeller is open-source and available through GitHub (https://github.com/Maize-Genetics-and-Genomics-Database/qTeller). A maize instance of qTeller is available at the Maize Genetics and Genomics database (MaizeGDB) (https://qteller.maizegdb.org/), where we have mapped over 200 unique datasets from GenBank across 27 maize genomes. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Classical genetic studies have identified many cases of pleiotropy where mutations in individual genes alter many different phenotypes. Quantitative genetic studies of natural genetic variants frequently examine one or a few traits, limiting their potential to identify pleiotropic effects of natural genetic variants. Widely adopted community association panels have been employed by plant genetics communities to study the genetic basis of naturally occurring phenotypic variation in a wide range of traits. High-density genetic marker data—18M markers—from 2 partially overlapping maize association panels comprising 1,014 unique genotypes grown in field trials across at least 7 US states and scored for 162 distinct trait data sets enabled the identification of of 2,154 suggestive marker-trait associations and 697 confident associations in the maize genome using a resampling-based genome-wide association strategy. The precision of individual marker-trait associations was estimated to be 3 genes based on a reference set of genes with known phenotypes. Examples were observed of both genetic loci associated with variation in diverse traits (e.g. above-ground and below-ground traits), as well as individual loci associated with the same or similar traits across diverse environments. Many significant signals are located near genes whose functions were previously entirely unknown or estimated purely via functional data on homologs. This study demonstrates the potential of mining community association panel data using new higher-density genetic marker sets combined with resampling-based genome-wide association tests to develop testable hypotheses about gene functions, identify potential pleiotropic effects of natural genetic variants, and study genotype-by-environment interaction. [ABSTRACT FROM AUTHOR]

Objectives: Existing data on bonobo and chimpanzee dental eruption timing are derived predominantly from captive individuals or deceased wild individuals. However, recent advances in noninvasive photographic monitoring of living, wild apes have enabled researchers to characterize dental eruption in relatively healthy individuals under naturalistic conditions. At present, such data are available for only one population of wild chimpanzees. We report data for an additional population of wild chimpanzees and the first dental eruption data for wild bonobos. Materials and Methods: We collected photographs and video footage of teeth from the open mouths of wild bonobos and East African chimpanzees of known age from LuiKotale, Democratic Republic of the Congo, and Gombe National Park, Tanzania, respectively. We scored the presence and absence of deciduous teeth from photographs and video footage to characterize deciduous dental eruption timing in these two populations. Results: Deciduous dental eruption ages in our sample fall within the range of variation previously documented for captive chimpanzees, but eruption ages are later in wild than in captive contexts. We found substantial variation in deciduous canine eruption timing, particularly among bonobos. One bonobo had a deciduous canine present by 227 days old while another did not have a deciduous canine present at 477 days old. Discussion Our data indicate that deciduous teeth erupt later in wild individuals than in captive individuals. We also found that deciduous dental eruption timing varies considerably between individuals within our study populations, a pattern that is consistent with previous studies. Future studies should consider sources of variation in deciduous canine eruption timing and relationships with other aspects of life history as additional data become available. [ABSTRACT FROM AUTHOR]

Background High-dose rifampicin may improve outcomes of tuberculous meningitis (TBM). Little safety or pharmacokinetic (PK) data exist on high-dose rifampicin in human immunodeficiency virus (HIV) coinfection, and no cerebrospinal fluid (CSF) PK data exist from Africa. We hypothesized that high-dose rifampicin would increase serum and CSF concentrations without excess toxicity. Methods In this phase II open-label trial, Ugandan adults with suspected TBM were randomized to standard-of-care control (PO-10, rifampicin 10 mg/kg/day), intravenous rifampicin (IV-20, 20 mg/kg/day), or high-dose oral rifampicin (PO-35, 35 mg/kg/day). We performed PK sampling on days 2 and 14. The primary outcomes were total exposure (AUC0–24), maximum concentration (Cmax), CSF concentration, and grade 3–5 adverse events. Results We enrolled 61 adults, 92% were living with HIV, median CD4 count was 50 cells/µL (interquartile range [IQR] 46–56). On day 2, geometric mean plasma AUC0–24hr was 42.9·h mg/L with standard-of-care 10 mg/kg dosing, 249·h mg/L for IV-20 and 327·h mg/L for PO-35 (P  < .001). In CSF, standard of care achieved undetectable rifampicin concentration in 56% of participants and geometric mean AUC0–24hr 0.27 mg/L, compared with 1.74 mg/L (95% confidence interval [CI] 1.2–2.5) for IV-20 and 2.17 mg/L (1.6–2.9) for PO-35 regimens (P  < .001). Achieving CSF concentrations above rifampicin minimal inhibitory concentration (MIC) occurred in 11% (2/18) of standard-of-care, 93% (14/15) of IV-20, and 95% (18/19) of PO-35 participants. Higher serum and CSF levels were sustained at day 14. Adverse events did not differ by dose (P  = .34). Conclusions Current international guidelines result in sub-therapeutic CSF rifampicin concentration for 89% of Ugandan TBM patients. High-dose intravenous and oral rifampicin were safe and respectively resulted in exposures ~6- and ~8-fold higher than standard of care, and CSF levels above the MIC. [ABSTRACT FROM AUTHOR]

Many caregivers of patients with neurodegenerative disease experience physical and psychological strain, which is associated with negative health outcomes. Caregiver strain may be partly attributable to negative emotional responses (e.g.of resentment) to the behavioral, cognitive, and physical changes associated with patients' disease. The philosopher Peter Strawson observed that in dealing with people who have neurological impairments, we often choose to suspend such emotional responses, adopting what he labeled the "objective attitude," though this may come at the expense of our relationships with them. In this study, we assessed the mediating effect of caregivers' adoption of the objective attitude on caregiver strain and relationship closeness in the setting of disease progression. Caregivers of patients with neurodegenerative disorders (n = 215) completed the Clinical Dementia Rating, Relationship-Closeness scale, Caregiver Strain Index, and a novel questionnaire assessing the adoption of the objective attitude. A structural equation model assessing associations among these variables demonstrated good fit (χ2 (88)=164.621, p < 0.001; CFI = 0.929, RMSEA = 0.064.) and showed that adoption of the objective attitude mediated the association between disease progression and relationship closeness (total β= −0.233, 95% CI: −0.351, −0.113; indirect β= −0.483, 95% CI: −0.602, −0.364; direct β = 0.250, 95% CI: 0.117, 0.384), but did not mediate the association between disease progression and caregiver strain (total β = 0.323, 95% CI: 0.234, 0.412; indirect β = 0.089, 95% CI: −0.027, 0.206; direct β = 0.153, 95% CI: −0.043, 0.349). For future work, we propose longitudinal measurements of these constructs to test the directionality of associations and consideration of how models for caregiver support can draw upon interdisciplinary insights. [ABSTRACT FROM AUTHOR]

Research in the past decade has demonstrated that a single reference genome is not representative of a species' diversity. MaizeGDB introduces a pan-genomic approach to hosting genomic data, leveraging the large number of diverse maize genomes and their associated datasets to quickly and efficiently connect genomes, gene models, expression, epigenome, sequence variation, structural variation, transposable elements, and diversity data across genomes so that researchers can easily track the structural and functional differences of a locus and its orthologs across maize. We believe our framework is unique and provides a template for any genomic database poised to host large-scale pan-genomic data. [ABSTRACT FROM AUTHOR]

Recent reclassification of the Klebsiella genus to include Klebsiella variicola, and its association with bacteremia and mortality, has raised concerns. We examined Klebsiella spp. infections among battlefield trauma patients, including occurrence of invasive K. variicola disease. Klebsiella isolates collected from 51 wounded military personnel (2009–2014) through the Trauma Infectious Disease Outcomes Study were examined using polymerase chain reaction (PCR) and pulsed-field gel electrophoresis. K. variicola isolates were evaluated for hypermucoviscosity phenotype by the string test. Patients were severely injured, largely from blast injuries, and all received antibiotics prior to Klebsiella isolation. Multidrug-resistant Klebsiella isolates were identified in 23 (45%) patients; however, there were no significant differences when patients with and without multidrug-resistant Klebsiella were compared. A total of 237 isolates initially identified as K. pneumoniae were analyzed, with 141 clinical isolates associated with infections (remaining were colonizing isolates collected through surveillance groin swabs). Using PCR sequencing, 221 (93%) isolates were confirmed as K. pneumoniae, 10 (4%) were K. variicola, and 6 (3%) were K. quasipneumoniae. Five K. variicola isolates were associated with infections. Compared to K. pneumoniae, infecting K. variicola isolates were more likely to be from blood (4/5 versus 24/134, p = 0.04), and less likely to be multidrug-resistant (0/5 versus 99/134, p<0.01). No K. variicola isolates demonstrated the hypermucoviscosity phenotype. Although K. variicola isolates were frequently isolated from bloodstream infections, they were less likely to be multidrug-resistant. Further work is needed to facilitate diagnosis of K. variicola and clarify its clinical significance in larger prospective studies. [ABSTRACT FROM AUTHOR]