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The 9.4T scanner in Maastricht is a whole-body magnet with head gradients and parallel RF transmit capability. At the time of the design, it was conceptualized to be one of the best fMRI scanners in the world, but it has also been used for anatomical and diffusion imaging. 9.4T offers increases in sensitivity and contrast, but the technical ultra-high field (UHF) challenges, such as field inhomogeneities and constraints set by RF power deposition, are exacerbated compared to 7T. This article reviews some of the 9.4T work done in Maastricht. Functional imaging experiments included blood oxygenation level-dependent (BOLD) and blood-volume weighted (VASO) fMRI using different readouts. BOLD benefits from shorter T2* at 9.4T while VASO from longer T1. We show examples of both ex vivo and in vivo anatomical imaging. For many applications, pTx and optimized coils are essential to harness the full potential of 9.4T. Our experience shows that, while considerable effort was required compared to our 7T scanner, we could obtain high-quality anatomical and functional data, which illustrates the potential of MR acquisitions at even higher field strengths. The practical challenges of working with a relatively unique system are also discussed.

Background: Despite increased awareness for promoting diversity, orthopaedics remains one of the least diverse specialties. Studying health care providers in women’s professional sports provides a unique opportunity to analyze gender and racial diversity. Hypotheses: There would be low female and minority representation across the various women’s professional sports leagues. There would be an increased number of female head certified athletic trainers (ATCs) when compared with head team physicians (HTPs). Study Design: Cross-sectional study. Methods: We evaluated the perceived race and sex of designated HTPs and ATCs in the Women’s National Basketball Association, National Women’s Soccer League, and National Women’s Hockey League. Type of doctorate degree, specialty, and years in practice were also collected. Kappa (κ) coefficient measurements were used to determine interobserver agreement on race. Categorical and continuous variables were analyzed using chi-square and t tests, respectively. Results: There were significantly more female ATCs than female HTPs (74.1% vs 37.5%; P = .01). Minority representation between HTPs and ATCs was not significantly different (20.8% vs 40.7%; P = .13). Black HTPs (12.5%) and Black ATCs (22.2%) composed the largest proportion among the minority groups. There was high interobserver agreement of perceived race across HTPs (κ = 1.0) and ATCs (κ = 0.95). Conclusion: Although there were more female ATCs than HTPs in women’s professional sports leagues, both cohorts lack perceived racial diversity. These data suggest an opportunity for diversification in medical and training staff of women’s professional sports.

Background: breast cancer has a significant heritable basis, of which ∼60% remains unexplained. Testing for BRCA1/BRCA2 offers useful discrimination of breast cancer risk within families, and identification of additional breast cancer susceptibility genes could offer clinical utility. Patients and methods: we included 2135 invasive breast cancer cases recruited via the Breast and Ovarian Cancer Susceptibility study, a retrospective UK study of familial breast cancer. Eligibility criteria: female, BRCA-negative, white European ethnicity, and one of: (i) breast cancer family history, (ii) bilateral disease, (iii) young age of onset (Results: 159/2135 (7.4%) cases had a qualifying variant in an established breast cancer susceptibility gene, with minimal evidence of signal in other cancer susceptibility genes. Known breast cancer susceptibility genes PALB2, CHEK2, and ATM were the only genes to retain statistical significance after correcting for multiple testing. Due to the enrichment of hereditary cases in the series, we had good power (>80%) to detect a gene of BRCA1-like risk [odds ratio (OR) = 10.6] down to a population minor allele frequency of 4.6 × 10 −5 (1 in 10 799, less than one-tenth that of BRCA1)and of PALB2-like risk (OR = 5.0) down to a population minor allele frequency of 2.8 × 10 −4 (1 in 1779, less than half that of PALB2). Power was lower for identification of novel moderate penetrance genes (OR = 2-3) like CHEK2 and ATM. Conclusions: this is the largest case-control whole-exome analysis of enriched breast cancer published to date. Whilst additional breast cancer susceptibility genes likely exist, those of high penetrance are likely to be of very low mutational frequency. Contention exists regarding the clinical utility of such genes.

We conducted a preregistered multilaboratory project ( k = 36; N = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the paradigmatic replication approach. Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result ( d = 0.06). Confirmatory Bayesian meta-analyses using an informed-prior hypothesis (δ = 0.30, SD = 0.15) found that the data were 4 times more likely under the null than the alternative hypothesis. Hence, preregistered analyses did not find evidence for a depletion effect. Exploratory analyses on the full sample (i.e., ignoring exclusion criteria) found a statistically significant effect ( d = 0.08); Bayesian analyses showed that the data were about equally likely under the null and informed-prior hypotheses. Exploratory moderator tests suggested that the depletion effect was larger for participants who reported more fatigue but was not moderated by trait self-control, willpower beliefs, or action orientation.

BACKGROUND AND PURPOSE: Dynamic contrast-enhanced MRI (DCE-MRI) can be employed to assess the blood-brain barrier (BBB) integrity. Detection of BBB leakage at lower field strengths (≤3T) is cumbersome as the signal is noisy, while leakage can be subtle. Utilizing the increased signal-to-noise ratio at higher field strengths, we explored the application of 7T DCE-MRI for assessing BBB leakage.METHODS: A dual-time resolution DCE-MRI method was implemented at 7T and a slow injection rate (0.3 ml/s) and low dose (3 mmol) served to obtain signal changes linearly related to the gadolinium concentration, that is, minimized for T2 * degradation effects. With the Patlak graphical approach, the leakage rate (Ki ) and blood plasma volume fraction (vp ) were calculated. The method was evaluated in 10 controls, an ischemic stroke patient, and a patient with a transient ischemic attack.RESULTS: Ki and vp were significantly higher in gray matter compared to white matter of all participants. These Ki values were higher in both patients compared to the control subjects. Finally, for the lesion identified in the ischemic stroke patient, higher leakage values were observed compared to normal-appearing tissue.CONCLUSION: We demonstrate how a dual-time resolution DCE-MRI protocol at 7T, with administration of half the clinically used contrast agent dose, can be used for assessing subtle BBB leakage. Although the feasibility of DCE-MRI for assessing the BBB integrity at 3T is well known, we showed that a continuous sampling DCE-MRI method tailored for 7T is also capable of assessing leakage with a high sensitivity over a range of Ki values.

Acinetobacter baumannii causes multi-system diseases in both nosocomial settings and a pre-disposed general population. The bacterium is not only desiccation-resistant but also notoriously resistant to multiple antibiotics and drugs of last resort including carbapenem, colistin, and sulbactam. The World Health Organization has categorized carbapenem-resistant A. baumannii at the top of its critical pathogen list in a bid to direct urgent countermeasure development. Several early-stage vaccines have shown a range of efficacies in healthy mice, but no vaccine candidates have advanced into clinical trials. Herein, we report our findings that both an ionizing γ-radiation-inactivated and a non-ionizing ultraviolet C-inactivated whole-cell vaccine candidate protects neutropenic mice from pulmonary challenge with virulent AB5075, a particularly pathogenic isolate. In addition, we demonstrate that a humoral response is sufficient for this protection via the passive immunization of neutropenic mice.

Medical device infections are costly, while preclinical assessment of antimicrobial properties for new materials is time intensive and imperfect at capturing the interrelated aspects of infection response and wound resolution. Herein, we developed an in vivo model for quantification of inflammatory and biocompatibility responses in the presence of a sustained implant-associated infection. The antimicrobial effectiveness of commercially available polymer materials was compared to that of thermoplastic polyurethane (TPU) materials modified with putative antimicrobial strategies as example test materials. Materials were incubated with bioluminescent Escherichia coli prior to implantation in a dorsal subcutaneous pocket in rats with an additional intraluminal bolus of bacteria. Infection kinetics were monitored with bioluminescence, and inflammatory infiltrate and fibrous capsule thickness were determined from stained histological sections. Our model resulted in a persistent infection, sensitive to antimicrobial effects, as the materials modified with a putative antimicrobial surface were able to significantly reduce the level of infection in animals at day 4 postimplantation with efficacy similar to that of commercially available antimicrobial drug-eluting polymers (positive controls). At day 30 postimplantation, the antimicrobial surface modified TPU tubing was found to promote complete elimination of intraluminal bacteria in the absence of antibiotics. Differences were also measurable in acute inflammation, as Wright-Giemsa staining demonstrated reduced inflammatory cell infiltration at day 4 postimplantation for antimicrobial TPU materials. Additionally, antimicrobial materials exhibited reduced fibrous capsule thickness coinciding with infection resolution, as compared to unmodified TPU controls. The developed model can be utilized for testing antimicrobial polymers in the context of a prolonged infection while also revealing concurrent differences in the infiltrating immune cell profiles and fibrous capsule thickness, thus improving the relevance of preclinical medical device material testing.

A 65-year-old man with diabetes, end-stage renal disease on hemodialysis, coronary artery disease, and a prosthetic aortic valve. He presented to the emergency department with hypothermia (96.6°F), several weeks of anorexia and chills, and bilateral lower extremity tissue necrosis with erythema and edema (Figure 1A). He had a peripherally inserted central catheter (PICC) line 8 weeks prior placed at another hospital for treatment of cellulitis. Laboratory results revealed anemia, azotemia, and leukocytosis (19,200 WBCs/mm

The extent to which physical therapy (PT) is used after meniscectomy is unknown. The objective of this study was to estimate the extent to which PT is implemented after meniscectomy and to identify factors associated with its utilization.The Mariner PearlDiver database was queried to identify patients who underwent uncomplicated meniscectomy. The number of PT visits for each patient was tabulated. Logistic regressions were used to compare demographic factors associated with no use of PT and use of nine or more PT visits.In total, 92,291 patients met inclusion criteria. Of these patients, 72.21% did not use PT and 27.8% used 1 or more PT visits. Of the patients who used PT, 19.76% had 1 to 8 PT visits and 8.03% had 9 or more PT visits. Older age and noncommercial insurance types were associated with no PT use. Male sex, Medicaid, and Medicare were associated with markedly lower odds of increased PT utilization.PT is used in the minority of the time after meniscectomy. Among patients who do use PT, however, notable variation exists in the amount of PT visits used. Patient age, sex, insurance status, and geographic variables were independently associated with PT utilization.

Antibody-secreting cells (ASC) or plasma cells secrete antibodies and form a cornerstone of humoral immunity. B cells that receive activation signals in the presence or absence of T cells initiate a differentiation program that requires epigenetic and transcriptional reprogramming in order to ultimately form ASC. Reprogramming is accomplished through the interplay of transcription factors that initiate gene expression programs and epigenetic mechanisms that maintain these programs and cell fates. An important consideration is that all of these factors are operating in the context of cell division. Recent technical advances now allow mechanistic studies to move beyond genetic studies to identify the promoters and enhancer repertoires that are regulated by epigenetic mechanisms and transcription factors in rare cell types and differentiation stages in vivo. This review will detail efforts to integrate transcriptional and epigenetic changes during B cell differentiation with cell division in vivo. What has emerged is a multi-phased differentiation model that requires distinct transcription factors and epigenetic programs at each step. The identification of markers that define each phase will help facilitate the manipulation of B cell differentiation for vaccine development or to treat diseases where antibodies are a component.

Additional co-authors: Ivan Ropovik, Balazs Aczel, Lena F. Aeschbach, Luca Andrighetto, Jack D. Arnal, Holly Arrow, Peter Babincak, Bence E. Bakos, Gabriel Banik, Ernest Baskin, Radomir Belopavlovic, Michael H. Bernstein, Michal Bialek, Nicholas G. Bloxsom, Bojana Bodroža, Diane B. V. Bonfiglio, Leanne Boucher, Florian Bruhlmann, Claudia C. Brumbaugh, Erica Casini, Yiling Chen, Carlo Chiorri, William J. Chopik, Oliver Christ, Antonia M. Ciunci, Heather M. Claypool, Sean Coary, Marija V. Cˇolic, W. Matthew Collins, Paul G. Curran, Chris R. Day, Anna Dreber, John E. Edlund, Filipe Falcao, Anna Fedor, Lily Feinberg, Ian R. Ferguson, Maire Ford, Michael C. Frank, Emily Fryberger, Alexander Garinther, Katarzyna Gawryluk, Kayla Ashbaugh, Mauro Giacomantonio, Steffen R. Giessner, Jon E. Grahe, Rosanna E. Guadagno, Ewa Halasa, Rias A. Hilliard, Joachim Huffmeier, Sean Hughes, Katarzyna Idzikowska, Michael Inzlicht, Alan Jern, William Jimenez-Leal, Magnus Johannesson, Jennifer A. Joy-Gaba, Mathias Kauff, Danielle J. Kellier, Grecia Kessinger, Mallory C. Kidwell, Amanda M. Kimbrough, Josiah P. J. King, Vanessa S. Kolb, Sabina Kolodziej, Marton Kovacs, Karolina Krasuska, Sue Kraus, Lacy E. Krueger, Katarzyna Kuchno, Caio Ambrosio Lage, Eleanor V. Langford, Carmel A. Levitan, Tiago Jesse Souza de Lima, Hause Lin, Samuel Lins, Jia E. Loy, Dylan Manfredi, Łukasz Markiewicz, Madhavi Menon, Brett Mercier, Mitchell Metzger, Venus Meyet, Jeremy K. Miller, Andres Montealegre, Don A. Moore, Rafal Muda, Gideon Nave, Austin Lee Nichols, Sarah A. Novak, Christian Nunnally, Ana Orlic, Anna Palinkas, Angelo Panno, Kimberly P. Parks, Ivana Pedovic, Emilian Pekala, Matthew R. Penner, Sebastiaan Pessers, Boban Petrovic, Thomas Pfeiffer, Damian Pienkosz, Emanuele Preti, Danka Puric, Tiago Ramos, Jonathan Ravid, Timothy S. Razza, Katrin Rentzsch, Juliette Richetin, Sean C. Rife, Anna Dalla Rosa, Kaylis Hase Rudy, Janos Salamon, Blair Saunders, Przemyslaw Sawicki, Kathleen Schmidt, Kurt Schuepfer, Thomas Schultze, Stefan Schulz-Hardt, Astrid Schutz, Ani N. Shabazian, Rachel L. Shubella, Adam Siegel, Ruben Silva, Barbara Sioma, Lauren Skorb, Luana Elayne Cunha de Souza, Sara Steegen, L. A. R. Stein, R. Weylin Sternglanz, Darko Stojilovic, Daniel Storage, Gavin Brent Sullivan, Barnabas Szaszi, Peter Szecsi, Orsolya Szoke, Attila Szuts, Manuela Thomae, Natasha D. Tidwell, Carly Tocco, Ann-Kathrin Torka, Francis Tuerlinckx, Wolf Vanpaemel, Leigh Ann Vaughn, Michelangelo Vianello, Domenico Viganola, Maria Vlachou, Ryan J. Walker, Sophia C. Weissgerber, Aaron L. Wichman, Bradford J. Wiggins, Daniel Wolf, Michael J. Wood, David Zealley, Iris Žeželj, Mark Zrubka, and Brian A. Nosek

Albarracín et al. (2008, Experiment 7) tested whether priming action or inaction goals (vs. no goal) and then satisfying those goals (vs. not satisfying them) would be associated with subsequent cognitive responding. They hypothesized and found that priming action or inaction goals that were not satisfied resulted in greater or lesser responding, respectively, compared with not priming goals ( N = 98). Sonnleitner and Voracek (2015) attempted to directly replicate Albarracín et al.’s (2008) study with German participants ( N = 105). They did not find evidence for the 3 × 2 interaction or the expected main effect of task type. The current study attempted to directly replicate Albarracín et al. (2008), Experiment 7, with a larger sample of participants ( N = 1,690) from seven colleges and universities in the United States. We also extended the study design by using a scrambled-sentence task to prime goals instead of the original task of completing word fragments, allowing us to test whether study protocol moderated any effects of interest. We did not detect moderation by protocol in the full 3 × 2 × 2 design (pseudo- r2 = 0.05%). Results for both protocols were largely consistent with Sonnleitner and Voracek’s findings (pseudo- r2s = 0.14% and 0.50%). We consider these results in light of recent findings concerning priming methods and discuss the robustness of action-/inaction-goal priming to the implementation of different protocols in this particular context.

Phaf suggests that, in order to address overpublication, academics should read more and publish less. Although many academics would like to take this advice, doing so is complicated by the audit culture that marketizes and metricizes everything they do. Working from the evolutionary metaphor introduced by Phaf, we argue that the evolution of science consists not simply in adapting theory to the demands of empirical investigation, but also in adapting scientific traditions and communities to the political and institutional forces that shape them. We point specifically to the generalized metrics (e.g., impact factors) that, in audit environments, arbitrate resources, in the process engineering professional precarity and overdetermining theory building. We argue that hyper-production can be understood as an adaptation to such an audit environment. We briefly discuss some suggestions for approaching the audit through relational accounting practices that disrupt and re-inscribe calculative audits, thus creating opportunities to read more and publish less.

Plant chromatin dynamics are generally recognized as playing a role in the genomic response to environmental stress. Although stress‐induced transcriptional activities of LTR‐retrotransposons have been reported, whether the stress response can be detected at the level of chromatin structure for LTR‐retrotransposons is largely unknown. Using differential nuclease sensitivity profiling, we identified that two out of 29 maize LTR‐retrotransposon families change their chromatin structure in response to drought stress in leaf tissue. The two LTR‐retrotransposon families, uloh and vegu, are classified as nonautonomous LTR‐retrotransposons. Differently from other families, the chromatin structure of these two families shifted from more open in normal conditions to more closed following drought stress. Although uloh and vegu lack sequence similarity, most of them shared an intriguing feature of having a new and uncharacterized insertion of a DNA sequence near one side of an LTR. In the uloh family, nine members with a strong drought response also exhibited a drought‐induced reduction of published H3K4me3 histone modification in the inserted DNA region, implicating this modification in the chromatin structural changes. Our results provide new insight into how LTR‐retrotransposons can alter their chromatin structure following stress response in plants.

Background Memorial University Medical Center conducts opt-out HIV screening in the Emergency Department (ED) for patients aged ≥ 13. After gaining consent, an electronic algorithm automatically orders an HIV test with the diagnostic evaluation for patients who meet CDC guidelines for HIV screening. Unfortunately, no pediatric patient aged 13–18 received HIV screening despite our out-opt testing protocol being in place since 2016. Approach Through a systematic analysis, implicit bias to gain consent was repeatedly identified as the most common barrier to HIV screening in this population. Pediatric leadership developed strategies to improve HIV screening, including education of parents and staff, on-site support for staff and parents/guardians, pediatric patient counseling, and adding HIV screening to syphilis tests. Despite these interventions, HIV screening in the pediatric population only improved about 37% from January 2017 through November 2020. As a final strategy HIV screening was added to the sexually transmitted infection (STI) order set for patients who met CDC guidelines for STI. Pediatric ED HIV education to clinical staff continued, specifically emphasizing the high prevalence of HIV in our community. Outcomes Persistence to drive change increased HIV screening by 61% from July 2020 to December 2020. Strategies producing the greatest impact were the inclusion of HIV testing in the standard STI panel and focused pediatric ED nurse education/support. As a result, current HIV screening in our pediatric patients aged 13–18 is now 88% of those who meet CDC guidelines to be screened. Significance Up to 20% of HIV diagnoses occur during adolescence making screening in this age group imperative. Removing implicit bias from HIV screening is difficult. However, continued persistence and automated testing protocols can lead to increases in pediatric ED HIV screening. Because of our high HIV screening rate, many pediatric patients will have early identification of HIV and linkage to care.

Psychology is in a replication crisis that has brought about a period of self-reflection and reform. Yet this reform appears in many ways to focus primarily on methodological and statistical practices, with little consideration for the foundational issues that concern many theoretical and philosophical psychologists and that may provide a richer account of the crisis. In this paper we offer an overview of the history of the replication crisis, the critiques and reforms at the heart of the crisis, and several points of intersection between the reform movement and broader theoretical and philosophical issues. We argue that the problems of the replication crisis and the concerns of the reform movement in fact provide various points of entry for theoretical and philosophical psychologists to collaborate with reformers in providing a more deeply philosophical critique and reform.

Sternal cleft (SC) is a rare congenital anomaly, occurring with associated developmental anomalies or in isolation. Surgery to reconstruct the sternum is indicated to protect the visceral organs from trauma, to ensure healthy cardiopulmonary function and growth, and to reconstruct the anterior chest wall. Although infection recognized as a postoperative complication following chest wall reconstruction, spontaneous mediastinal infection is rare. To the authors' knowledge, there is only 1 reported case of spontaneous mediastinal infection with concomitant SC in the literature. Here, the authors present a unique case of a medically complicated infant with a SC who presented with a spontaneous mediastinal abscess.

Multispectral imaging is increasingly used in specialty crops, but its benefits in assessment of disease severity and improvements in conventional scouting practice are unknown. Multispectral imaging was conducted using an unmanned aerial vehicle (UAV), and data were analyzed for five flights from Florida and Georgia commercial watermelon fields in 2017. The fields were rated for disease incidence and severity by extension agents and plant pathologists at randomized locations (i.e., conventional scouting) followed by ratings at locations that were identified by differences in normalized difference vegetation index (NDVI) and stress index (i.e., UAV-assisted scouting). Diseases identified by the scouts included gummy stem blight, anthracnose, Fusarium wilt, Phytophthora fruit rot, Alternaria leaf spot, and cucurbit leaf crumple disease. Disease incidence and severity ratings were significantly different between conventional and UAV-assisted scouting (P < 0.01, Bhapkar/exact test). Higher severity ratings of 4 and 5 on a scale of 1 to 5 from no disease to complete loss of the canopy were more consistent after the scouts used the multispectral images in determining sampling locations. The UAV-assisted scouting locations had significantly lower green, red, and red edge NDVI values and higher stress index values than the conventional scouting areas (P < 0.05, ANOVA/Tukey), and this corresponded to areas with higher disease severity. Conventional scouting involving human evaluation remains necessary for disease validation. Multispectral imagery improved watermelon field scouting owing to increased ability to identify disease foci and areas of concern more rapidly than conventional scouting practices with early detection of diseases 20% more often using UAV-assisted scouting.

Background and purpose: In neuro-oncology, high spatial accuracy is needed for clinically acceptable high-precision radiation treatment planning (RTP). In this study, the clinical applicability of anatomically optimised 7-Tesla (7T) MR images for reliable RTP is assessed with respect to standard clinical imaging modalities. Materials and methods: System- and phantom-related geometrical distortion (GD) were quantified on clinically-relevant MR sequences at 7T and 3T, and on CT images using a dedicated anthropomorphic head phantom incorporating a 3D grid-structure, creating 436 points-of-interest. Global GD was assessed by mean absolute deviation (MADGlobal). Local GD relative to the magnetic isocentre was assessed by MADLocal. Using 3D displacement vectors of individual points-of-interest, GD maps were created. For clinically acceptable radiotherapy, 7T images need to meet the criteria for accurate dose delivery (GD

Background: Discrepancies in race, ethnicity, and sex among health care providers and their patients have been shown to affect the patient-provider relationship as well as the quality of care. Currently, minority and female representation among orthopaedic surgeons remains low. Given the large proportion of minority athletes and their degree of public visibility, professional sports serves as an important arena within which to analyze the diversity of health care providers. Purpose: To describe and evaluate the current level of diversity of head team physicians (HTPs) and head athletic trainers (ATCs), primarily in terms of race and sex, within men’s professional sports leagues in the United States. Study Design: Cross-sectional study. Methods: Five major US professional sports leagues were evaluated: National Basketball Association, National Football League, National Hockey League, Major League Soccer, and Major League Baseball. Publicly available data were collected to identify the HTPs and head ATCs for each team within these leagues. Two independent observers analyzed photographs and names of these individuals to determine his or her perceived race and sex, with disagreements being resolved by a third independent observer. Other physician data collected included graduate degree(s), specialty, and number of years in practice. Kappa coefficients (κ) were employed to evaluate interobserver reliability. Chi-square, Fisher exact, and t tests were used for statistical comparisons across leagues. Results: The κ values for perceived race were 0.85 for HTPs and 0.89 for head ATCs, representing near-perfect interobserver agreement. Minorities comprised 15.5% of HTPs and 20.7% of ATCs ( P = .24). Women comprised 3.9% of HTPs and 1.3% of head ATCs ( P = .017). The majority of HTPs were orthopaedic surgeons with medical doctorates. Female HTPs had significantly fewer years in practice compared with male HTPs (15.0 ± 4.9 vs 23.1 ± 9.6; P = .04). Conclusion: The lead physicians and athletic training providers for men’s professional sports teams demonstrated low rates of minority and female representation, denoting a highly visible area for discussing the role of increased diversity in health care.

Background In the past decade, the zebrafish community has widely embraced targeted mutagenesis technologies, resulting in an abundance of mutant lines. While many lines have proven to be useful for investigating gene function, many have also shown no apparent phenotype, or phenotypes not of interest to the originating lab. In order for labs to document and share information about these lines, we have created ZebraShare as a new resource offered within ZFIN. Methods ZebraShare involves a form-based submission process generated by ZFIN. The ZebraShare interface (https://zfin.org/action/zebrashare) can be accessed on ZFIN under “Submit Data”. Users download the Submission Workbook and complete the required fields, then submit the completed workbook with associated images and captions, generating a new ZFIN publication record. ZFIN curators add the submitted phenotype and mutant information to the ZFIN database, provide mapping information about mutations, and cross reference this information across the appropriate ZFIN databases. We present here examples of ZebraShare submissions, including phf21aa, kdm1a, ctnnd1, snu13a, and snu13b mutant lines. Results Users can find ZebraShare submissions by searching ZFIN for specific alleles or line designations, just as for alleles submitted through the normal process. We present several potential examples of submission types to ZebraShare including a phenotypic mutants, mildly phenotypic, and early lethal mutants. Mutants for kdm1a show no apparent skeletal phenotype, and phf21aa mutants show only a mild skeletal phenotype, yet these genes have specific human disease relevance and therefore may be useful for further studies. The p120-catenin encoding gene, ctnnd1, was knocked out to investigate a potential role in brain development or function. The homozygous ctnnd1 mutant disintegrates during early somitogenesis and the heterozygote has localized defects, revealing vital roles in early development. Two snu13 genes were knocked out to investigate a role in muscle formation. The snu13a;snu13b double mutant has an early embryonic lethal phenotype, potentially related to a proposed role in the core splicing complex. In each example, the mutants submitted to ZebraShare display phenotypes that are not ideally suited to their originating lab’s project directions but may be of great relevance to other researchers. Conclusion ZebraShare provides an opportunity for researchers to directly share information about mutant lines within ZFIN, which is widely used by the community as a central database of information about zebrafish lines. Submissions of alleles with a phenotypic or unexpected phenotypes is encouraged to promote collaborations, disseminate lines, reduce redundancy of effort and to promote efficient use of time and resources. We anticipate that as submissions to ZebraShare increase, they will help build an ultimately more complete picture of zebrafish genetics and development.

Many flatfish species utilize coastal areas during at least one of their life-history stages. Estuaries on the eastern US Atlantic coast provide important settlement and nursery habitat for flatfishes. Small tidal creeks serve as transition zones between upland and estuarine environments and are a consistent settlement and nursery habitat for flatfish. Flatfish habitat use in Wylly Creek, a southeastern US tidal creek, was examined to determine whether assemblage composition has changed over a decadal time period (2004–2007 vs. 2016–2019). In addition, the potential effect of cold winters on juvenile flatfish recruitment and subsequent spring flatfish assemblage composition were examined. Flatfish assemblages have undergone subtle shifts in composition between initial and recent time periods, with decreases (5–16-fold) in abundance occurring for ocellated flounder Ancylopsetta quadrocellata, summer flounder Paralichthys dentatus, and southern flounder Paralichthys lethostigma, while abundances of more common species, bay whiff Citharichthys spilopterus and blackcheek tonguefish Symphurus plagiusa, remained relatively consistent. Bay whiff recruitment into the creek occurred in early spring, but was delayed in most years with colder winters. Minimum residency for bay whiff within an approximately 350 m stretch of creek was estimated to be approximately 5–10 days. Flatfish habitat use in this small tidal creek adjacent to a relatively undeveloped coastal area may reflect a shifting baseline against which potential assemblage shifts in developed areas can be assessed.

Development of novel anti-tuberculosis combination regimens that increase efficacy and reduce treatment timelines will improve patient compliance, limit side-effects, reduce costs, and enhance cure rates. Such advancements would significantly improve the global TB burden and reduce drug resistance acquisition. Bioenergetics has received considerable attention in recent years as a fertile area for anti-tuberculosis drug discovery. Targeting the electron transport chain (ETC) and oxidative phosphorylation machinery promises not only to kill growing cells but also metabolically dormant bacilli that are inherently more drug tolerant. Over the last two decades, a broad array of drugs targeting various ETC components have been developed. Here, we provide a focused review of the current state of art of bioenergetic inhibitors of Mtb with an in-depth analysis of the metabolic and bioenergetic disruptions caused by specific target inhibition as well as their synergistic and antagonistic interactions with other drugs. This foundation is then used to explore the reigning theories on the mechanisms of antibiotic-induced cell death and we discuss how bioenergetic inhibitors in particular fail to be adequately described by these models. These discussions lead us to develop a clear roadmap for new lines of investigation to better understand the mechanisms of action of these drugs with complex mechanisms as well as how to leverage that knowledge for the development of novel, rationally-designed combination therapies to cure TB.

The development of vaccinations changed the face of medicine starting in the late 1700s with the introduction of the vaccine that led to the eradication of smallpox, by providing active and passive immunity against infectious diseases that had plagued many generations. The result by the beginning of the twenty-first century was the near eradication of these morbid illnesses in the western world, including measles, rubella, and varicella-zoster viruses. Recent developments in the anti-vaccination movement have led to widespread refusal of vaccinations, subsequently resurrecting many viruses that have not been battled for centuries. Outbreaks, seen throughout the world, have seen high mortality rates in immunocompetent and immunocompromised individuals, alike. Those who have survived the illnesses have suffered severe complications, especially since treatment for these viruses is limited. In this chapter, we review reemerging viral infections with primary and secondary cutaneous manifestations. We also discuss the factors spurring the anti-vaccination movement and the obstacles healthcare faces in abating its consequences.

Acinetobacter baumannii is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved. Herein, we rapidly produced protective whole-cell immunogens from planktonic and biofilm-like cultures of A. baumannii, strain AB5075 grown using a variety of methods. After selecting a panel of five cultures based on distinct protein profiles, replicative activity was extinguished by exposure to 10 kGy gamma radiation in the presence of a Deinococcus antioxidant complex composed of manganous (Mn2+) ions, a decapeptide, and orthophosphate. Mn2+ antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic A. baumannii vaccine candidates. Mice were immunized and boosted twice with 1.0 × 107 irradiated bacterial cells and then challenged intranasally with AB5075 using two mouse models. Planktonic cultures grown for 16 h in rich media and biofilm cultures grown in static cultures underneath minimal (M9) media stimulated immunity that led to 80–100% protection.

Background Epithelioid hemangioma is a rare, benign vascular lesion classically presenting with painless nodules in the head and neck region. Hemangioma lesions are typically small, located within the dermis and subcutaneous tissue, and rarely exceed 10 cm in size. Complete surgical excision, with negative margins, is the recommended treatment as local recurrence is common. We describe an unusual presentation of epithelioid hemangioma that, to our knowledge, has not been previously described in the literature, epithelioid. Case presentation We report an atypical case of a large epithelioid hemangioma lesion with deep intramuscular involvement in a 16-year-old male. Ultrasound and MRI showed a hypervascular mass on the patient’s left upper back, and biopsy confirmed the diagnosis. Treatment consisted of preoperative embolization followed by excision and local tissue rearrangement. Conclusions Epithelioid hemangiomas are considered uncommon in the pediatric population. Moreover, it is challenging to diagnose these lesions due to their similarities to other vascular anomalies. We aim to increase awareness of this condition and obtain more precision in diagnosis, thus standardizing the approach for those treating individuals with vascular anomalies.

Memory B cells (MBC) are a heterogenous population that consist of immunoglobin class switched and non-class switched MBC, and these populations can arise via germinal center dependent or independent mechanisms. The timing of MBC development influences the fate outcome of MBC populations. These different populations of MBC are regulated by cell signaling, but it is not clearly defined what epigenetic factors influence MBC differentiation. EZH2 is an important histone methyltransferase that catalyzes H3K27me3 resulting in gene repression. EZH2 has been shown to regulate B cell differentiation into germinal centers and plasma cells; however, it is unknown if EZH2 regulates MBC development. To address this, a knockout model has been established where EZH2 is conditionally deleted using the CD19 and AICDA driven CRE expression. Here we used the influenza PR8 model to ascertain the kinetics of MBC differentiation and formation in the spleen, dLN, and lungs following a live infection in wild-type and EZH2-KO cohorts. Using B cell tetramers, antigen-specific MBC will be analyzed to define the kinetics of MBC development and determine the similarities and differences between the different populations of MBC. Overall, these data define the early kinetics of MBC establishment and the developmental timing that EZH2-dependent H3K27me3 remodeling is required for MBC formation. Supported by NIH/NIAID to CDS (R01 AI148471)

About 70% of the world's main crops depend on insect pollination. Climate change is already affecting the abundance and distribution of insects, which could cause geographical mismatches between crops and their pollinators. Crops that rely primarily on wild pollinators (e.g., crops that cannot be effectively pollinated by commercial colonies of honey bees) could be particularly in jeopardy. However, limited information on plant-pollinator associations and pollinator distributions complicate the assessment of climate change impacts on specific crops. To study the potential impacts of climate change on pollination of a specific crop in North America, we use the case of open-field tomato crops, which rely on buzz pollinators (species that use vibration to release pollen, such as bumble bees) to increase their production. We aimed to (1) assess potential changes in buzz pollinator distribution and richness, and (2) evaluate the overlap between areas with high densities of tomato crops and high potential decrease in richness. We used baseline (1961-1990) climate and future (2050s and 2080s) climatic projections in ecological niche models fitted with occurrences of wild bees, documented in the literature as pollinators of tomatoes, to estimate the baseline and future potential distribution of suitable climatic conditions of targeted species and to create maps of richness change across North America. We obtained reliable models for 15 species and found important potential decreases in the distribution of some pollinators (e.g., Lasioglossum pectorale and Augochlorella aurata). We observed geographical discrepancies in the projected change in species richness across North America, detecting important declines in the eastern United States (up to 11 species decrease for 2050s). After overlapping the maps of species richness change with a tomato crop map for the United States, we found spatial correspondence between richness declines and areas with high concentration of tomato crops. Disparities in the effects of climate change on the potential future distribution of different wild pollinators and geographical variation in richness highlight the importance of crop-specific studies. Our study also emphasizes the challenges of compiling and modeling crop-specific pollinator data and the need to improve our understanding of current distribution of pollinators and their community dynamics under climate change.