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Sedimentary basins provide a deep time archive of tectonic and Earth-surface processes that can be leveraged by detrital mineral U-Pb dating and geochemistry to track paleogeography, magmatism, and crustal evolution. Zircon preserves the long-term (billions of years) record of supercontinent cycles; however, it is biased toward preserving felsic crustal records. Detrital rutile complements the detrital zircon record by providing constraints on the time and temperature of rifting and mafic magmatism, metamorphism, exhumation of the middle and lower crust, subduction, and amagmatic orogenesis. We use detrital zircon U-Pb and detrital rutile U-Pb geochronology and trace element analysis of Permian to Eocene siliciclastic rocks in the southern Pyrenees to capture supercontinent cycles of ocean basins opening and closing. Detrital rutile age spectra show peaks at ca. 100 Ma associated with rifting and hyperextension in the Pyrenean realm, 200 Ma associated with the Central Atlantic Magmatic Province, and 330 Ma, 375 Ma, and 400 Ma associated with subduction and Rheic Ocean crust formation. Zr-in-rutile thermometry and rutile Cr-Nb systematics provide further insight into metamorphic facies (peak metamorphic temperatures) and source rock lithology (mafic versus felsic affinity). Detrital zircon age spectra have peaks at ca. 300 Ma, 450 Ma, and 600 Ma associated with major orogenic events and felsic magmatism, and Th/U ratios provide information on relative zircon formation temperatures. Comparison of these independent records shows that detrital rutile reflects rifting, magma-poor orogenesis, and oceanic lithospheric processes, while detrital zircon detects continental lithospheric processes. Integrated detrital zircon and rutile data sets archive past geological events across multiple Wilson cycles.

Despite widespread availability of human papillomavirus (HPV) vaccines and recommendations for routine use, awareness and uptake of HPV vaccination are not universal. We assessed self-reported history of HPV vaccination in a sample of low-income men and women recruited from the community using respondent-driven sampling as part of the National HIV Behavioral Surveillance (NHBS) survey in San Francisco. Of the 384 respondents, a minority (12.5%) reported they had received the HPV vaccine. In multivariate analysis, independent associations with HPV vaccination history were female sex (adjusted odds ratio [AOR] = 3.76, 95% confidence interval [CI] = [1.73, 8.17]), younger age (AOR = 0.89 per year, 95% CI = [0.86, 0.92]), and education above high school (AOR = 2.84, 95% CI = [1.37, 5.90]). Missed opportunities for HPV vaccination were evident in 84.4% of respondents having visited a health care provider in the last year, including 40.1% tested for a sexually transmitted infection, and entry into higher education programs (33.4%).

Abstract Transparency within biomedical research is essential for research integrity, credibility, and reproducibility. To increase adherence to optimal scientific practices and enhance transparency, we propose the creation of a journal transparency tool (JTT) that will allow users to obtain information about a given scholarly journal’s operations and transparency policies. This study is part of a program of research to obtain user preferences to inform the proposed JTT. Here, we report on our consultation with clinicians and researchers. This mixed-methods study was conducted in two parts. The first part involved a cross-sectional survey conducted on a random sample of authors from biomedical journals. The survey asked clinicians and researchers about the inclusion of a series of potential scholarly metrics and user features in the proposed JTT. Quantitative survey items were summarized with descriptive statistics. Thematic content analysis was employed to analyze text-based responses. Subsequent focus groups used survey responses to further explore the inclusion of items in the JTT. Items with less than 70% agreement were used to structure discussion points during these sessions. Participants voted on the use of user features and metrics to be considered within the journal tool after each discussion. Thematic content analysis was conducted on interview transcripts to identify the core themes discussed. A total of 632 participants (5.5% response rate) took part in the survey. A collective total of 74.7% of respondents found it either ‘occasionally, ‘often’, or ‘almost always’ difficult to determine if health information online is based on reliable research evidence. Twenty-two participants took part in the focus groups. Three user features and five journal tool metrics were major discussion points during these sessions. Thematic analysis of interview transcripts resulted in six themes. The use of registration was the only item to not meet the 70% threshold after both the survey and focus groups. Participants demonstrated low scholarly communication literacy when discussing tool metric suggestions. Our findings suggest that the JTT would be valuable for both researchers and clinicians. The outcomes of this research will contribute to developing and refining the tool in accordance with researchers and clinicians.

Abstract Alpha-synuclein (αSyn) forms pathologic aggregates in Parkinson’s disease (PD) and is implicated in mechanisms underlying neurodegeneration. While pathologic αSyn has been extensively studied, there is currently no method to evaluate αSyn within the brains of living patients. Patients with PD are often treated with deep brain stimulation (DBS) surgery in which surgical instruments are in direct contact with neuronal tissue; herein, we describe a method by which tissue is collected from DBS surgical instruments in PD and essential tremor (ET) patients and demonstrate that αSyn is detected. 24 patients undergoing DBS surgery for PD (17 patients) or ET (7 patients) were enrolled; from patient samples, 81.2 ± 44.8 µg of protein (n = 15), on average, was collected from surgical instruments. Light microscopy revealed axons, capillaries, and blood cells as the primary components of purified tissue (n = 3). ELISA assay further confirmed the presence of neuronal and glial tissue in DBS samples (n = 4). Further analysis was conducted using western blot, demonstrating that multiple αSyn antibodies are reactive in PD (n = 5) and ET (n = 3) samples; truncated αSyn (1–125 αSyn) was significantly increased in PD (n = 5) compared to ET (n = 3), in which αSyn misfolding is not expected (0.64 ± 0.25 vs. 0.25 ± 0.12, P = 0.046), thus showing that multiple forms of αSyn can be detected from living PD patients with this method.

Background: The Canadian fetal alcohol spectrum disorder (FASD) diagnostic guideline provides clinicians with the process and procedure to reach an accurate diagnosis. However, organisational structure, culture, and resource utilisation vary. The objectives of this study were to identify the key challenges and strengths of successful FASD diagnostic clinics. Method: Qualitative interviews were conducted with 12 key informants from 10 clinics representing different regions, populations served, and clinic structures. Data analysis was performed using iterative thematic inquiry. Results: Three themes related to challenges and four themes related to strengths were identified. Human resources were identified as both a challenge and strength. Additional challenges were diagnostic capacity and system level support. Additional strengths were clinic adaptability, relational connections, and culturally responsive approaches. Conclusions: FASD clinics are more alike than not in their approach to assessment and diagnosis. Some clinics are facing similar challenges that others have overcome, supporting the need for mentorship and consistent operating standards.

It is meaningful to create a comprehensive score to extract information from mass continuous data when they measure the same latent concept. Therefore, this study adopts the logic of psychometrics to conduct scales on continuous data under the Rasch models. This study also explores the effect of different data discretization methods on scale development by using financial profitability ratios as a demonstration. Results show that retaining more categories can benefit Rasch modeling because it can better inform the models. The dynamic clustering algorithm, k-median is a better method for extracting characteristic patterns of the continuous data and preparing the data for the Rasch model. This study illustrates that there is no one-way good discretization method for continuous data under the Rasch models. It is more reasonable to use the traditional algorithms if each continuous data variable has target benchmark(s), whereas the k-median clustering algorithm achieves good modeling results when benchmark information is lacking.

Introduction Infant immunization programs using pneumococcal conjugate vaccines (PCVs) have reduced the rates of pneumococcal disease through direct vaccine-induced protection in vaccinated children and through indirect protection in non-vaccinated children and adults.Areas covered This review summarizes current evidence on the indirect protection of adults conferred by pediatric pneumococcal vaccination, including the impact on invasive pneumococcal disease (IPD) incidence and mortality, pneumonia admissions, and nasopharyngeal carriage prevalence. Factors affecting indirect protection against IPD are also discussed.Expert opinion Pediatric immunization with PCVs has substantially decreased vaccine-serotype IPD and pneumonia through indirect protection in both older (≥65 years of age) and younger adults, including those with underlying medical conditions. However, serotype replacement by non-vaccine serotypes, the persistence of some vaccine serotypes, and divergence of serotypes between children and adults have limited the impact of pediatric PCV programs on adult populations. Designing complementary vaccines that leverage indirect protection from pediatric immunization and target the most prevalent adult serotypes may be a preferred strategy to maximize the public health impact of pneumococcal vaccination.

Objectives It is important to assess healthcare providers (HCPs) knowledge, attitudes, perceptions, and preferences towards new pneumococcal vaccines for adults.Methods HCPs who met eligibility criteria completed an online survey between March – May 2024 that included a discrete choice experiment (DCE) to elicit preferences.Results Among 340 participating HCPs, the average age was 44.9 years old, and the majority were male (55.6%), and White (85.3%). Most HCPs reported that they would support (90.3%) and implement (91.5%) a lower age-based recommendation for pneumococcal vaccines (from adults 65+ years to adults 50+ years). A majority of HCPs would offer a supplemental dose of a pneumococcal vaccine to high-risk adults 19–49 years, at-risk or high-risk adults 50–64 years, and adults 65+ years regardless of risk status to increase protection after completing the recommended series. DCE results showed that coverage of pneumococcal pneumonia and invasive pneumococcal disease (IPD) in adults 65+ years were the two most important attributes in evaluating pneumococcal vaccines.Conclusions HCPs preferred a pneumococcal vaccine with increased coverage against pneumococcal pneumonia and IPD, and they supported lowering the age recommendation for pneumococcal vaccination as well as a supplemental vaccine dose to provide additional coverage for adults.

Abstract Individuals with Down syndrome, the genetic condition caused by trisomy 21, exhibit strong inter-individual variability in terms of developmental phenotypes and diagnosis of co-occurring conditions. The mechanisms underlying this variable developmental and clinical presentation await elucidation. We report an investigation of human chromosome 21 gene overexpression in hundreds of research participants with Down syndrome, which led to the identification of two major subsets of co-expressed genes. Using clustering analyses, we identified three main molecular subtypes of trisomy 21, based on differential overexpression patterns of chromosome 21 genes. We subsequently performed multiomics comparative analyses among subtypes using whole blood transcriptomes, plasma proteomes and metabolomes, and immune cell profiles. These efforts revealed strong heterogeneity in dysregulation of key pathophysiological processes across the three subtypes, underscored by differential multiomics signatures related to inflammation, immunity, cell growth and proliferation, and metabolism. We also observed distinct patterns of immune cell changes across subtypes. These findings provide insights into the molecular heterogeneity of trisomy 21 and lay the foundation for the development of personalized medicine approaches for the clinical management of Down syndrome.

Background Preprints are scientific manuscripts that are made available on open-access servers but are not yet peer-reviewed. Although preprints are becoming more prevalent, uptake is not optimal. Understanding researchers’ opinions and attitudes toward preprints is valuable to optimize their use. Understanding knowledge gaps and researchers’ attitudes toward preprinting can assist stakeholders, such as journals, funding agencies, and universities, to use preprints more effectively. Here, we aimed to collect perceptions and behaviours regarding preprints across an international sample of biomedical researchers. Methods Corresponding authors of articles published in biomedical research journals were identified from a random sample of journals from the MEDLINE database. Their names and email addresses were extracted to invite them to our anonymous, cross-sectional survey, which asked participants questions about their knowledge, attitudes, and opinions regarding preprinting. Results The survey was completed by 730 respondents providing a response rate of 3.20% and demonstrated a wide range of attitudes and opinions about preprints with authors from various disciplines and career stages worldwide. Most respondents were familiar with the concept of preprints but most had not previously posted one. The lead author of the project and journal policy had the greatest impact on decisions to post a preprint, whereas employers/research institutes had the least impact. Supporting open science practices was the highest ranked incentive, while increasing authors’ visibility was the highest ranked motivation for publishing preprints. Conclusions Although many biomedical researchers recognize the benefits of preprints, there is still hesitation among others to engage in this practice. This may be due to the general lack of peer review of preprints and little enthusiasm from external organizations such as journals, funding agencies, and universities. Future work is needed to determine optimal ways to improve researchers’ attitudes through modifications to current preprint systems and policies.

BackgroundCOVID-19 infections have been implicated in cerebral ischemia, but their relationship to cervical arterial dissections remains poorly characterized. Descriptions of cervical arterial dissections in patients with COVID-19 infections with details regarding their presenting symptomatology, imaging findings, and responses to treatment with antithrombotic therapy may be helpful to clinicians.Methods and observationsWe present six adult cases of cervical arterial dissections in the setting of recent COVID-19 infections from 2021 to 2022 at our institution. Four cases presented with dissections involving the internal carotid artery, while two cases had dissections of bilateral vertebral arteries. In one patient, we found imaging evidence for a possible inflammatory process. All patients were treated with either antiplatelet agents or direct oral anticoagulants.Conclusions and relevanceCOVID-19 infections may predispose patients to spontaneous cervical arterial dissections. Such patients can have variable neurologic presentations, though headaches and neck pain were common complaints. Most patients responded well to antithrombotic therapy, with improvement in symptoms and radiologic findings at follow-up. Clinicians should maintain a high degree of suspicion for cervical arterial dissections in patients who present acutely with severe headache/neck pain and/or new neurologic deficits in the setting of COVID-19 infections.

We conducted an international cross-sectional survey of biomedical researchers' perspectives on the reproducibility of research. This study builds on a widely cited 2016 survey on reproducibility and provides a biomedical-specific and contemporary perspective on reproducibility. To sample the community, we randomly selected 400 journals indexed in MEDLINE, from which we extracted the author names and emails from all articles published between October 1, 2020 and October 1, 2021. We invited participants to complete an anonymous online survey which collected basic demographic information, perceptions about a reproducibility crisis, perceived causes of irreproducibility of research results, experience conducting reproducibility studies, and knowledge of funding and training for research on reproducibility. A total of 1,924 participants accessed our survey, of which 1,630 provided useable responses (response rate 7% of 23,234). Key findings include that 72% of participants agreed there was a reproducibility crisis in biomedicine, with 27% of participants indicating the crisis was "significant." The leading perceived cause of irreproducibility was a "pressure to publish" with 62% of participants indicating it "always" or "very often" contributes. About half of the participants (54%) had run a replication of their own previously published study while slightly more (57%) had run a replication of another researcher's study. Just 16% of participants indicated their institution had established procedures to enhance the reproducibility of biomedical research and 67% felt their institution valued new research over replication studies. Participants also reported few opportunities to obtain funding to attempt to reproduce a study and 83% perceived it would be harder to do so than to get funding to do a novel study. Our results may be used to guide training and interventions to improve research reproducibility and to monitor rates of reproducibility over time. The findings are also relevant to policy makers and academic leadership looking to create incentives and research cultures that support reproducibility and value research quality.

Purpose of reviewCavernous malformations (CM) are vascular lesions in the brain and spinal cord, characterized by clusters of endothelial-lined caverns lacking proper tight junctions. These malformations may be discovered incidentally or present with symptoms such as headaches, focal neurologic deficits, or seizures, with or without hemorrhage. This review focuses on non-surgical management considerations important for women with CM, who face challenges related to pregnancy, exogenous hormone use, anticonvulsive therapy, bone health, and mental health.Recent findingsEmerging evidence suggests that both estrogen and progesterone may influence CM lesion behavior. Exogenous hormones, including those in oral contraceptives and oral hormone replacement therapy, indicate an elevated risk of symptomatic hemorrhage (SH) and may also influence seizure frequency and severity, particularly in women taking antiseizure medications (ASMs). Data suggest that the risk of CM hemorrhage during pregnancy is similar to the risk when not pregnant, although limitations to these studies will be reviewed.SummaryThis review synthesizes the current literature on the interplay between estrogen and progesterone and CM lesion behavior, highlighting the importance of gender- and sex-specific factors in clinical decision-making. Special attention is given to the implications of exogenous hormone use, seizure management, and the psychological well-being of women with CM, underscoring the need for a multidisciplinary approach tailored to the unique needs of this patient population.

ObjectiveDespite advances in the treatment of psychiatric diseases, currently available therapies do not provide sufficient and durable relief for as many as 30-40% of patients. Neuromodulation, including deep brain stimulation (DBS), has emerged as a potential therapy for persistent disabling disease, however it has not yet gained widespread adoption. In 2016, the American Society for Stereotactic and Functional Neurosurgery (ASSFN) convened a meeting with leaders in the field to discuss a roadmap for the path forward. A follow-up meeting in 2022 aimed to review the current state of the field and to identify critical barriers and milestones for progress.DesignThe ASSFN convened a meeting on June 3, 2022 in Atlanta, Georgia and included leaders from the fields of neurology, neurosurgery, and psychiatry along with colleagues from industry, government, ethics, and law. The goal was to review the current state of the field, assess for advances or setbacks in the interim six years, and suggest a future path forward. The participants focused on five areas of interest: interdisciplinary engagement, regulatory pathways and trial design, disease biomarkers, ethics of psychiatric surgery, and resource allocation/prioritization. The proceedings are summarized here.ConclusionThe field of surgical psychiatry has made significant progress since our last expert meeting. Although weakness and threats to the development of novel surgical therapies exist, the identified strengths and opportunities promise to move the field through methodically rigorous and biologically-based approaches. The experts agree that ethics, law, patient engagement, and multidisciplinary teams will be critical to any potential growth in this area.

Abstract Introduction This study aimed to estimate and compare the lifetime clinical and economic burden of invasive pneumococcal diseases (IPD) attributable to the serotypes contained in a new 21-valent pneumococcal conjugate vaccine (V116) vs. the 20-valent pneumococcal conjugate vaccine (PCV20) among adults aged 18 years and above in the USA. Methods A state-transition Markov model was used to track IPD cases and deaths as well as the associated direct medical costs (in 2023 US dollars) from a US healthcare payer perspective at 3% annual discount rate. The results were summarized for V116, PCV20, and eight unique serotypes contained in V116. A sensitivity analysis was conducted to determine the most influential inputs on the overall total direct lifetime cost. Results For the total population of US adults aged 18 years and above in 2021 (approx. 258 million residents), the estimated lifetime numbers of cases of IPD, post-meningitis sequelae (PMS), and IPD-related deaths attributable to the serotypes contained in V116 were approximately 1.4 million, 17,608, and 186,200, respectively, with a total discounted lifetime direct cost of $32.6 billion. A substantial proportion (approx. 31%) of those were attributable to the unique eight serotypes. The corresponding estimates for PCV20 were approximately 35% lower—934,000, 11,500, and 120,000, respectively—with a total discounted direct lifetime cost of $21.9 billion. Conclusion These results show that V116 serotypes (compared to PCV20) are associated with substantially higher clinical and economic burden of IPD. The addition of V116 to vaccination recommendations can help to reduce the residual burden of IPD in US adults.

Abstract During a SARS-CoV-2 infection, macrophages recognize viral components resulting in cytokine production. While this response fuels virus elimination, overexpression of cytokines can lead to severe COVID-19. Previous studies suggest that the spike protein (S) of SARS-CoV-2 can elicit cytokine production via the transcription factor NF-κB and the toll-like receptors (TLRs). In this study, we found that: (i) S and the S2 subunit induce CXCL10, a chemokine implicated in severe COVID-19, gene expression by human macrophage cells (THP-1); (ii) a glycogen synthase kinase-3 inhibitor attenuates this induction; (iii) S and S2 do not activate NF-κB but do activate the transcription factor IRF; (iv) S and S2 do not require TLR2 to elicit CXCL10 production or activate IRF; and (v) S and S2 elicit CXCL10 production by peripheral blood mononuclear cells (PBMCs). We also discovered that the cellular response, or lack thereof, to S and S2 is a function of the recombinant S and S2 used. While such a finding raises the possibility of confounding LPS contamination, we offer evidence that potential contaminating LPS does not underly induced increases in CXCL10. Combined, these results provide insights into the complex immune response to SARS-CoV-2 and suggest possible therapeutic targets for severe COVID-19.

Abstract Obesity is a well-established risk factor for human cancer, yet the underlying mechanisms remain elusive. Immune dysfunction is commonly associated with obesity but whether compromised immune surveillance contributes to cancer susceptibility in individuals with obesity is unclear. Here we use a mouse model of diet-induced obesity to investigate tumor-infiltrating CD8 + T cell responses in lean, obese, and previously obese hosts that lost weight through either dietary restriction or treatment with semaglutide. While both strategies reduce body mass, only dietary intervention restores T cell function and improves responses to immunotherapy. In mice exposed to a chemical carcinogen, obesity-related immune dysfunction leads to higher incidence of sarcoma development. However, impaired immunoediting in the obese environment enhances tumor immunogenicity, making the malignancies highly sensitive to immunotherapy. These findings offer insight into the complex interplay between obesity, immunity and cancer, and provide explanation for the obesity paradox observed in clinical immunotherapy settings.

Abstract To report the results of ‘responsive’ deep brain stimulation (DBS) for Tourette syndrome (TS) in a National Institutes of Health funded experimental cohort. The use of ‘brain derived physiology’ as a method to trigger DBS devices to deliver trains of electrical stimulation is a proposed approach to address the paroxysmal motor and vocal tic symptoms which appear as part of TS. Ten subjects underwent bilateral staged DBS surgery and each was implanted with bilateral centromedian thalamic (CM) region DBS leads and bilateral M1 region cortical strips. A series of identical experiments and data collections were conducted on three groups of consecutively recruited subjects. Group 1 (n = 2) underwent acute responsive DBS using deep and superficial leads. Group 2 (n = 4) underwent chronic responsive DBS using deep and superficial leads. Group 3 (n = 4) underwent responsive DBS using only the deep leads. The primary outcome measure for each of the 8 subjects with chronic responsive DBS was calculated as the pre-operative baseline Yale Global Tic Severity Scale (YGTSS) motor subscore compared to the 6 month embedded responsive DBS setting. A responder for the study was defined as any subject manifesting a ≥ 30 points improvement on the YGTSS motor subscale. The videotaped Modified Rush Tic Rating Scale (MRVTRS) was a secondary outcome. Outcomes were collected at 6 months across three different device states: no stimulation, conventional open-loop stimulation, and embedded responsive stimulation. The experience programming each of the groups and the methods applied for programming were captured. There were 10 medication refractory TS subjects enrolled in the study (5 male and 5 female) and 4/8 (50%) in the chronic responsive eligible cohort met the primary outcome manifesting a reduction of the YGTSS motor scale of ≥ 30% when on responsive DBS settings. Proof of concept for the use of responsive stimulation was observed in all three groups (acute responsive, cortically triggered and deep DBS leads only). The responsive approach was safe and well tolerated. TS power spectral changes associated with tics occurred consistently in the low frequency 2–10 Hz delta-theta-low alpha oscillation range. The study highlighted the variety of programming strategies which were employed to achieve responsive DBS and those used to overcome stimulation induced artifacts. Proof of concept was also established for a single DBS lead triggering bi-hemispheric delivery of therapeutic stimulation. Responsive DBS was applied to treat TS related motor and vocal tics through the application of three different experimental paradigms. The approach was safe and effective in a subset of individuals. The use of different devices in this study was not aimed at making between device comparisons, but rather, the study was adapted to the current state of the art in technology. Overall, four of the chronic responsive eligible subjects met the primary outcome variable for clinical effectiveness. Cortical physiology was used to trigger responsive DBS when therapy was limited by stimulation induced artifacts.

Abstract Decades of research on multifunctional Green Infrastructure (GI) has yet to translate into holistic implementation in the built environment. This oversight stems from assumptions that many ecosystem services occur passively and thus potential synergies are overlooked during planning and design. This study offers specific guidance for coordinating GI planning, design, and construction by examining the current state of academic literature on these aspects. It identifies 15 GI elements (e.g., green roofs) and 15 objectives (e.g., biodiversity) to collectively consider before implementation. The literature tends to isolate discussions of “engineered” GI elements with water-related objectives, while more “natural” GI are linked to biodiversity and human well-being. Coordinating across GI objectives and elements remains imperative, but evaluating too many options risks a paradox of choice. This study recommends short-term adherence to principles of adaptive design and, in the long-term, reemphasizes multifunctionality assessments, inter and transdisciplinary collaboration, and political will.

Background: The first spatially resolved transcriptomics platforms, GeoMx (Nanostring) and Visium (10x Genomics) were launched in 2019 and were recognized as the method of the year by Nature Methods in 2020. The subsequent refinement and expansion of these and other technologies to increase -plex, work with formalin-fixed paraffin-embedded tissue, and analyze protein in addition to gene expression have only added to their significance and impact on the biomedical sciences. In this perspective, we focus on two platforms for spatial transcriptomics, GeoMx and Visium, and how these platforms have been used to provide novel insight into kidney disease. The choice of platform will depend largely on experimental questions and design. The application of these technologies to clinically sourced biopsies presents the opportunity to identify specific tissue biomarkers that help define disease etiology and more precisely target therapeutic interventions in the future. Summary: In this review, we provide a description of the existing and emerging technologies that can be used to capture spatially resolved gene and protein expression data from tissue. These technologies have provided new insight into the spatial heterogeneity of diseases, how reactions to disease are distributed within a tissue, which cells are affected, and molecular pathways that predict disease and response to therapy. Key Message: The upcoming years will see intense use of spatial transcriptomics technologies to better define the pathophysiology of kidney diseases and develop novel diagnostic tests to guide personalized treatments for patients.

Background We propose the creation of a journal transparency tool (JTT), which will allow users to obtain information about a given scholarly journal’s operations and policies. We are obtaining preferences from different stakeholders to inform the development of this tool. This study aimed to identify the publishing community’s preferences for the JTT. Methods We conducted a modified three-round Delphi survey. Representatives from publishing houses and journal publishers were recruited through purposeful and snowball sampling. The first two Delphi rounds involved an online survey with items about JTT metrics and user features. During the third round, participants discussed and voted on JTT metric items that did not reach consensus after round 2 within a virtual consensus meeting. We defined consensus as 80% agreement to include or exclude an item in the JTT. Results Eighty-six participants completed the round 1 survey, and 43 participants (50% of round 1) completed the round 2 survey. In both rounds, respondents voted on JTT user feature and JTT metric item preferences and answered open-ended survey questions regarding the JTT. In round 3, a total of 21 participants discussed and voted on JTT metric items that did not reach consensus after round 2 during an online consensus group meeting. Fifteen out of 30 JTT metric items and none of the four JTT user feature items reached the 80% consensus threshold after all rounds of voting. Analysis of the round 3 online consensus group transcript resulted in two themes: ‘factors impacting support for JTT metrics’ and ‘suggestions for user clarity.’ Conclusions Participants suggested that the publishing community’s primary concerns for a JTT are to ensure that the tool is relevant, user-friendly, accessible, and equitable. The outcomes of this research will contribute to developing and refining the tool in accordance with publishing preferences.

Summary: Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), is characterized by delayed neurodevelopment, accelerated aging, and increased risk of many co-occurring conditions. Hypoxemia and dysregulated hematopoiesis have been documented in DS, but the underlying mechanisms and clinical consequences remain ill defined. We report an integrative multi-omic analysis of ∼400 research participants showing that people with DS display transcriptomic signatures indicative of elevated heme metabolism and increased hypoxic signaling across the lifespan, along with chronic overproduction of erythropoietin, elevated biomarkers of tissue-specific hypoxia, and hallmarks of stress erythropoiesis. Elevated heme metabolism, transcriptional signatures of hypoxia, and stress erythropoiesis are conserved in a mouse model of DS and associated with overexpression of select triplicated genes. These alterations are independent of the hyperactive interferon signaling characteristic of DS. These results reveal lifelong dysregulation of key oxygen-related processes that could contribute to the developmental and clinical hallmarks of DS.

Antibrush border antibody (ABBA) disease is a rare cause of kidney disease characterized by progressive renal tubular injury associated with immune complex deposition along the basement membranes of the proximal tubule and circulating autoantibodies to brush border antigens. Several antigens have been identified as targets of autoantibodies in this disease, including low-density lipoprotein receptor related protein 2 (LRP2), cubilin, and amnionless proteins. We present 9 patients from 2 academic medical centers and describe the clinicopathologic characteristics and outcome data. All patients presented with acute kidney injury and proteinuria. Pathology confirmed immune complex deposition along proximal tubular basement membranes in all patients, but the majority (6/8) also showed segmental glomerular subepithelial immune complexes. Two of 3 patients treated with rituximab demonstrated stabilization of kidney function; 1 of these patients had mantle cell lymphoma. One patient with lung cancer showed stabilization of disease after treatment of the malignancy. The remaining patients progressed to end-stage kidney disease with either conservative therapy (3 patients) or immunosuppression with glucocorticoids (2 patients). This series highlights the poor prognosis of ABBA disease, but a potential benefit of anti-B cell therapy or treatment of an underlying malignancy in some cases.

IntroductionAnthracyclines are effective in treating acute myeloid leukemia (AML) but limited by cardiotoxicity. CPX-351, a liposomal daunorubicin and cytarabine, may provide therapeutic benefit with less cardiotoxicity. Acute changes in left ventricular systolic function and cardiac biomarkers were evaluated after a cycle of CPX-351 in children with relapsed AML treated on the phase 1/2 Children's Oncology Group study, AAML1421.MethodsSubjects received 135 units/m2/dose of CPX-351 on days 1, 3, and 5 as cycle 1. Echocardiograms were performed and centrally quantitated at baseline and at the end of cycle 1 (day 29 +/− 1 week). High sensitivity troponin (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at baseline and serially through the end of cycle 1 (days 5, 8, 15, 22 and 29). Differences between baseline and post-CPX-351 echo/biomarker measures were analyzed using Wilcoxon signed rank tests. Linear regression was used to model post-CPX-351 left ventricular ejection fraction (LVEF) with cTnT/NT-proBNP at each time point, controlling for baseline LVEF. Cancer therapy related cardiac dysfunction (CTRCD) was defined as a decline in LVEF of ≥10%–

Trichoderma spp. represents a group of advantageous soil-borne microorganisms known for their capacity to enhance soil quality, facilitate plant growth, and serve as biocontrol agents against various plant diseases. Employing direct antagonism and competition, particularly within the rhizosphere, Trichoderma orchestrates microbial interactions, shaping the soil microbiome. This review comprehensively explores the potential applications and role of Trichoderma in soil for fostering sustainable agriculture. The initial focus is on how Trichoderma spp. contribute to plant growth and development, especially under biotic and abiotic stress conditions, and provide protection against plant pathogens. The article delves into diverse applications of Trichoderma species in agriculture, encompassing their use as biocontrol agents, biofertilizers, and seed treatments, collectively contributing to the sustainability of agricultural practices. A thorough examination of the advantages and challenges associated with Trichoderma utilization in agriculture is presented, including its impact on fungal and bacterial communities within the soil, crucial for safeguarding and preserving soil health. Notably, agricultural chemicals, including fungicides, pose a potential threat to Trichoderma species. Despite these challenges, the review highlights the numerous benefits of integrating Trichoderma spp. into agriculture, emphasizing its role in improving soil quality, enhancing agricultural productivity, and reducing reliance on chemical pesticides. The communication capabilities of Trichoderma with plants, whether through root colonization or acting as an endophyte, further solidify its potential as a biocontrol agent and plant growth promoter for diverse crop species. The safety, affordability, efficacy, and eco-friendly nature of Trichoderma spp. position them as a promising choice for sustainable agriculture expansion.

This candid perspective written by scholars from diverse disciplinary backgrounds is intended to advance conversations about the realities of peer review and its inherent limitations. Trust in a process or institution is built slowly and can be destroyed quickly. Trust in the peer review process for scholarly outputs (i.e., journal articles) is being eroded by high-profile scandals, exaggerated news stories, exposés, corrections, retractions, and anecdotes about poor practices. Diminished trust in the peer review process has real-world consequences and threatens the uptake of critical scientific advances. The literature on “crises of trust” tells us that rebuilding diminished trust takes time and requires frank admission and discussion of problems, creative thinking that addresses rather than dismisses criticisms, and planning and enacting short- and long-term reforms to address the root causes of problems. This article takes steps in this direction by presenting eight peer review reality checks and summarizing efforts to address their weaknesses using a harm reduction approach, though we recognize that reforms take time and some problems may never be fully rectified. While some forms of harm reduction will require structural and procedural changes, we emphasize the vital role that training editors, reviewers, and authors has in harm reduction. Additionally, consumers of science need training about how the peer review process works and how to critically evaluate research findings. No amount of self-policing, transparency, or reform to peer review will eliminate all bad actors, unscrupulous publishers, perverse incentives that reward cutting corners, intentional deception, or bias. However, the scientific community can act to minimize the harms from these activities, while simultaneously (re)building the peer review process. A peer review system is needed, even if it is imperfect.