bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dashboards as Mechanisms for Community Empowerment: Developing a Prototype for Child and Adolescent Well-being in California
Authors: Anderson Nathaniel W. , Russ Shirley A. , Eisenberg Daniel , Halfon Neal 
Published: May 2023

Context:
In recent years, stakeholders in public health have emphasized measuring young peoples' well-being as a more holistic and upstream approach to understanding their health and development. However, summarizing the available indicators of well-being in ways that strengthen ongoing policy and community efforts remains a challenge.

Program:
Our objective was to develop a measurement framework of young peoples' well-being that would be engaging and actionable to a broad and diverse set of stakeholders in California.

Implementation:
We began with a scan of the relevant literature documenting previous efforts to measure young peoples' well-being, both within the United States and internationally. Subsequently, we individually interviewed a set of key informants and then convened a multidisciplinary panel of experts to solicit feedback on our approach. Throughout this iterative and collaborative process, we developed and refined a measurement framework based on the information provided across these various sources.

Evaluation:
Findings suggest data dashboards are a promising approach for presenting a parsimonious yet holistic picture of young peoples' well-being. Dashboards can highlight well-being's multidimensionality by categorizing indicators over different domains. Our framework organizes indicators over 5 types: child-centric, subjective well-being, contextual determinants, developmental, and equity-focused. The design and flexibility of dashboards can also highlight important gaps in data collection that are of interest to end users such as indicators not yet collected among the broader population. Furthermore, dashboards can include interactive features, such as selecting key data elements, that can help communities articulate priority areas for policy action, thereby generating momentum and enthusiasm for future iterations and improvements.

Discussion:
Data dashboards are well suited for engaging a variety of stakeholders on complex multidimensional concepts such as young peoples' well-being. However, to fulfill their promise, they should be codesigned and codeveloped through an iterative process with the stakeholders and community members they intend to serve.
Understanding Over-immunization in North Dakota's Adult Population
Authors: Dykstra Allison , Woinarowicz Mary , Howell Molly 
Published: May 2023

Context:
Over-immunization, or administration of excess doses of vaccine, is an understudied topic in immunization. Adult over-immunization is particularly understudied, so building a basic understanding of the sources and scope of over-immunization is necessary to direct action.

Objective:
The aim of this evaluation was to quantify the extent of over-immunization in North Dakota's adult population from 2016 to 2021.

Design:
Records for all pneumococcal, zoster, and influenza vaccines administered to adults in North Dakota were extracted from the North Dakota Immunization Information System (NDIIS) from January 1, 2016, through December 31, 2021. The NDIIS is a state-wide immunization registry that captures all childhood and most adult immunizations.

Setting:
North Dakota.

Participants:
North Dakotan adults 19 years or older.

Main Outcome Measure:
The number and percentage of adults identified as over-immunized as well as the number and percentage of doses identified as an extra dose.

Results:
Frequency of over-immunization was less than 3% for all vaccines over the 6-year period assessed. Pharmacies and private practices were the most common sources of over-immunization of adults.

Conclusions:
These data show that over-immunization is still an issue in North Dakota, although the percentage of the adult population impacted is low. Reducing over-immunization is worth pursuing but should be balanced with the importance of improving low immunization coverage rates in the state. Improving utilization of the NDIIS by adult providers can help prevent over-immunization and under-immunization alike.
Impact of hepatitis C cure on risk of mortality and morbidity in people with HIV after antiretroviral therapy initiation
Authors: Chalouni Mathieu , Trickey Adam , Ingle Suzanne M. , Sepuvelda Maria Antonia , Gonzalez Juan , Rauch Andri , Crane Heidi M. , Gill M. John , Rebeiro Peter F. , Rockstroh Jürgen K. , Franco Ricardo A. , Touloumi Giota , Neau Didier , Laguno Montserrat , Rappold Michaela , Smit Colette , Sterne Jonathan A.C. , Wittkop Linda 
Published: May 2023

Objective:Hepatitis C virus (HCV) co-infection is associated with increased morbidity and mortality in people with HIV (PWH). Sustained virological response (SVR) decreases the risk of HCV-associated morbidity. We compared mortality, risk of AIDS-defining events, and non-AIDS nonliver (NANL) cancers between HCV-co-infected PWH who reached SVR and mono-infected PWH.Design:Adult PWH from 21 cohorts in Europe and North America that collected HCV treatment data were eligible if they were HCV-free at the time of ART initiation.Methods:Up to 10 mono-infected PWH were matched (on age, sex, date of ART start, HIV acquisition route, and being followed at the time of SVR) to each HCV-co-infected PWH who reached SVR. Cox models were used to estimate relative hazards (hazard ratio) of all-cause mortality, AIDS-defining events, and NANL cancers after adjustment.Results:Among 62 495 PWH, 2756 acquired HCV, of whom 649 reached SVR. For 582 of these, at least one mono-infected PWH could be matched, producing a total of 5062 mono-infected PWH. The estimated hazard ratios comparing HCV-co-infected PWH who reached SVR with mono-infected PWH were 0.29 [95% confidence interval (CI) 0.12–0.73] for mortality, 0.85 [0.42–1.74] for AIDS-defining events, and 1.21 [0.86–1.72] for NANL cancer.Conclusion:PWH who reached SVR a short time after HCV acquisition were not at higher risk of overall mortality compared with mono-infected PWH. However, the apparent higher risk of NANL cancers in HCV-co-infected PWH who reached SVR after a DAA-based treatment compared with mono-infected PWH, though compatible with a null association, suggests a need for monitoring of those events following SVR.
Tryptophan metabolism, gut microbiota, and carotid artery plaque in women with and without HIV infection
Authors: Luo Kai , Wang Zheng , Peters Brandilyn A. , Hanna David B. , Wang Tao , Sollecito Christopher C. , Grassi Evan , Wiek Fanua , Peter Lauren St , Usyk Mykhaylo , Post Wendy S. , Landay Alan L. , Hodis Howard N. , Weber Kathleen M. , French Audrey , Golub Elizabeth T. , Lazar Jason , Gustafson Deborah , Sharma Anjali , Anastos Kathryn , Clish Clary B. , Knight Rob , Kaplan Robert C. , Burk Robert D. , Qi Qibin 
Published: May 2023

Objective:
The perturbation of tryptophan (TRP) metabolism has been linked with HIV infection and cardiovascular disease (CVD), but the interrelationship among TRP metabolites, gut microbiota, and atherosclerosis remain unclear in the context of HIV infection.

Methods:
We included 361 women (241 HIV+, 120 HIV-) with carotid artery plaque assessments from the Women's Interagency HIV Study, measured ten plasma TRP metabolites and profiled fecal gut microbiome. TRP metabolites-related gut bacteria were selected through the Analysis of Compositions of Microbiomes with Bias Correction method. Associations of TRP metabolites and related microbial features with plaque were examined using multivariable logistic regression.

Results:
While plasma kynurenic acid (KYNA) (odds ratio [OR] = 1.93, 95% confidence interval [CI]:1.12, 3.32 per one SD increase; P = 0.02) and KYNA/TRP (OR = 1.83 [95%CI:1.08, 3.09], P = 0.02) were positively associated with plaque, indole-3-propionate (IPA) (OR = 0.62 [95%CI:0.40, 0.98], P = 0.03) and IPA/KYNA (OR = 0.51[95%CI:0.33, 0.80], P < 0.01) were inversely associated with plaque. Five gut bacterial genera and many affiliated species were positively associated with IPA (FDR-q < 0.25), including Roseburia sp., Eubacterium sp., Lachnospira sp., and Coprobacter sp.; but no bacterial genera were found to be associated with KYNA. Furthermore, an IPA-associated-bacteria score was inversely associated with plaque (OR = 0.47[95%CI:0.28, 0.79], P < 0.01). But no significant effect modification by HIV serostatus was observed in these associations.

Conclusions:
In a cohort of women living with and without HIV infection, plasma IPA levels and related gut bacteria were inversely associated with carotid artery plaque, suggesting a potential beneficial role of IPA and its gut bacterial producers in atherosclerosis and CVD.
Lincoln Sign in a Case of Primary Hyperparathyroidism on 18F-Fluorocholine PET/CT
Authors: Prakash Sneha , Damle Nishikant Avinash , Kumar Praveen , Dharmashaktu Yamini , Bal C.S. 
Published: May 2023

Abstract
Lincoln sign or black beard sign is one of the signs that have been classically described on bone scintigraphy in monostotic Paget disease, when mandible is involved. Extensive involvement of the mandible causes increased radiotracer uptake from one mandibular condyle to the other, resembling a black beard. We present the case of a 14-year-old girl with primary hyperparathyroidism who underwent an 18F-fluorocholine PE/CT to locate the parathyroid adenoma. MIP image of the PET/CT incidentally showed black beard sign due to increased radiotracer uptake in the mandible.
Amyloid-β exposed astrocytes induce iron transport from endothelial cells at the blood-brain barrier by altering the ratio of apo- and holo-transferrin
Authors: Baringer Stephanie L. , Lukacher Avraham S. , Palsa Kondaiah , Kim Hyosung , Lippmann Ethan S. , Spiegelman Vladimir S. , Simpson Ian A. , Connor James R. 
Published: May 2023

AbstractExcessive brain iron accumulation is observed in early in the onset of Alzheimer’s disease, notably prior to widespread proteinopathy. These findings suggest that increases in brain iron levels are due to a dysregulation of the iron transport mechanism at the blood-brain barrier. Astrocytes release signals (apo- and holo-transferrin) that communicate brain iron needs to endothelial cells in order to modulate iron transport. Here we use iPSC-derived astrocytes and endothelial cells to investigate how early-disease levels of amyloid-β disrupt iron transport signals secreted by astrocytes to stimulate iron transport from endothelial cells. We demonstrate that conditioned media from astrocytes treated with amyloid-β stimulates iron transport from endothelial cells and induces changes in iron transport pathway protein levels. The mechanism underlying this response begins with increased iron uptake and mitochondrial activity by the astrocytes which in turn increases levels of apo-transferrin in the amyloid-β conditioned astrocyte media leading to increased iron transport from endothelial cells. These novel findings offer a potential explanation for the initiation of excessive iron accumulation in early stages of Alzheimer’s disease. What’s more, these data provide the first example of how the mechanism of iron transport regulation by apo- and holo-transferrin becomes misappropriated in disease to detrimental ends. The clinical benefit from understanding early dysregulation in brain iron transport in AD cannot be understated. If therapeutics can target this early process, they could possibly prevent the detrimental cascade that occurs with excessive iron accumulation.Significance StatementExcessive brain iron accumulation is hallmark pathology of Alzheimer’s disease that occurs early in the disease staging and before widespread proteinopathy deposition. This overabundance of brain iron has been implicated to contribute to disease progression, thus understandingthe mechanism of early iron accumulation has significant therapeutic potential to slow to halt disease progression. Here, we show that in response to low levels of amyloid-β exposure, astrocytes increase their mitochondrial activity and iron uptake, resulting in iron deficient conditions. Elevated levels of apo (iron free)-transferrin stimulate iron release from endothelial cells. These data are the first to propose a mechanism for the initiation of iron accumulation and the misappropriation of iron transport signaling leading to dysfunctional brain iron homeostasis and resultant disease pathology.
A retinotopic code structures the interaction between perception and memory systems
Authors: Steel Adam , Silson Edward H. , Garcia Brenda D. , Robertson Caroline E. 
Published: May 2023

AbstractConventional views of brain organization suggest that the cortical apex processes internally-oriented information using an abstract, amodal neural code. Yet, recent reports have described the presence of retinotopic coding at the cortical apex, including the default mode network. What is the functional role of retinotopic coding atop the cortical hierarchy? Here, we report that retinotopic coding structures interactions between internally-oriented (mnemonic) and externally-oriented (perceptual) brain areas. Using fMRI, we observed robust, inverted (negative) retinotopic coding in category-selective memory areas at the cortical apex, which is functionally linked to the classic (positive) retinotopic coding in category-selective perceptual areas in high-level visual cortex. Specifically, these functionally-linked retinotopic populations in mnemonic and perceptual areas exhibit spatially-specific opponent responses during both bottom-up perception and top-down recall, suggesting that these areas are interlocked in a mutually-inhibitory dynamic. Together, these results show that retinotopic coding structures interactions between perceptual and mnemonic neural systems, thereby scaffolding their dynamic interaction.
New permanent stem cell niche for development and regeneration in a chordate
Authors: Vanni Virginia , Caicci Federico , Peronato Anna , Martello Graziano , Asnicar Davide , Gasparini Fabio , Ballarin Loriano , Manni Lucia 
Published: May 2023

AbstractStem cell niches are defined as the microenvironments where stem cells home, receiving stimuli defining their fate. In vertebrates, stem cell niches are stable and physically confined compartments.Botryllus schlosseriis an invertebrate colonial chordate where temporary stem cell niches have been identified in adult individuals that are cyclically resorbed and replaced by a new generation of clonal zooids.B. schlosserialso displays remarkable regenerative abilities, being capable of whole-body regeneration, but the cellular source of these processes is still unknown. Here we identified by means of a high-resolution morphological characterization a new putative stem cell niche in the ampullae of the circulatory system acting as a stem cell source during asexual reproduction. Stem cells of the ampullae travel via the circulatory system and contribute to the development of several organs and could explain where stem cells contributing to whole-body regeneration are stored. The ampullae niches are stable during the life cycle and regeneration ofB. schlosseri, while additional niches of the zooid are dynamically established and colonised by circulating stem cells. Our results reveal an unprecedented dynamicity of stem cell niches in highly regenerative invertebrates.
Tumor Cytokine-Induced Hepatic Gluconeogenesis Contributes to Cancer Cachexia: Insights from Full Body Single Nuclei Sequencing
Authors: Liu Ying , Dantas Ezequiel , Ferrer Miriam , Liu Yifang , Comjean Aram , Davidson Emma E. , Hu Yanhui , Goncalves Marcus D. , Janowitz Tobias , Perrimon Norbert 
Published: May 2023

SummaryA primary cause of death in cancer patients is cachexia, a wasting syndrome attributed to tumor-induced metabolic dysregulation. Despite the major impact of cachexia on the treatment, quality of life, and survival of cancer patients, relatively little is known about the underlying pathogenic mechanisms. Hyperglycemia detected in glucose tolerance test is one of the earliest metabolic abnormalities observed in cancer patients; however, the pathogenesis by which tumors influence blood sugar levels remains poorly understood. Here, utilizing aDrosophilamodel, we demonstrate that the tumor secreted interleukin-like cytokine Upd3 induces fat body expression ofPepck1andPdk, two key regulatory enzymes of gluconeogenesis, contributing to hyperglycemia. Our data further indicate a conserved regulation of these genes by IL-6/JAK STAT signaling in mouse models. Importantly, in both fly and mouse cancer cachexia models, elevated gluconeogenesis gene levels are associated with poor prognosis. Altogether, our study uncovers a conserved role of Upd3/IL-6/JAK-STAT signaling in inducing tumor-associated hyperglycemia, which provides insights into the pathogenesis of IL-6 signaling in cancer cachexia.Graphical Abstract
Resistance to anti-orthopoxviral drug tecovirimat (TPOXX®) during the 2022 mpox outbreak in the US
Authors: Smith Todd G. , Gigante Crystal M. , Wynn Nhien T. , Matheny Audrey , Davidson Whitni , Yang Yong , Condori Rene Edgar , O’Connell Kyle , Kovar Lynsey , Williams Tracie L. , Yu Yon C. , Petersen Brett W. , Baird Nicolle , Lowe David , Li Yu , Satheshkumar Panayampalli S. , Hutson Christina L. 
Published: May 2023

AbstractBackgroundDuring the 2022 multinational outbreak of monkeypox virus (MPXV) clade IIb, the antiviral drug tecovirimat (TPOXX®) was deployed in the US on a large scale for the first time ever. The MPXV F13L gene homolog encodes the target of tecovirimat, and single amino acid changes in the F13 protein are known to cause resistance to tecovirimat in orthopoxviruses (OPXV).MethodsWhole genome metagenomic sequencing and amplicon-based sequencing targeting the F13L gene was used to identify nine mutations previously reported to cause resistance in other OPXV along with ten novel mutations that have been identified from the 2022 mpox outbreak. A cytopathic effect assay, previously established at CDC as part of WHO smallpox research, was adapted to MPXV for tecovirimat phenotype testing of virus isolated from mpox patients.ResultsAs of March 2023, in total, 70 isolates from 40 patients were tested, and 50 of these isolates from 26 patients were found to have a resistant phenotype. Most resistant isolates were associated with severely immunocompromised mpox patients on multiple courses of TPOXX treatment; while isolates with F13 mutations identified by routine surveillance of patients not treated with TPOXX have remained sensitive.ConclusionsThese data indicate that tecovirimat resistance is developing in immunocompromised patients treated with TPOXX and that for isolates that we have analyzed, the frequency of resistant viruses remain relatively low (< 1%) compared to the total number of patients treated with TPOXX. These findings inform our understanding of when tecovirimat resistance is likely to occur and highlight the need for additional OPXV therapeutics.
A C/ebpα isoform-specific differentiation program in primary myelocytes
Authors: Garcia-Cuellar Maria-Paz , Akan Selin , Slany Robert K. 
Published: May 2023

AbstractThe transcription factor CCAAT-enhancer binding factor alpha (C/ebpα) is a master controller of myeloid differentiation that is expressed as long (p42) and short (p30) isoform. Mutations within theCEBPAgene selectively deleting p42 are frequent in human acute myeloid leukemia. Here we investigated the individual genomics and transcriptomics of p42 and p30. Both proteins bound to identical sites across the genome. For most targets, they induced a highly similar transcriptional response with the exception of a few isoform-specific genes. Amongst those we identified early growth response 1 (Egr1) and tribbles 1 (Trib1) as key targets selectively induced by p42 that are also underrepresented inCEBPA-mutated AML. Egr1 executed a program of myeloid differentiation and growth arrest. Oppositely, Trib1 established a negative feedback loop through activation of Erk1/2 kinase thus placing differentiation under control of signaling. Unexpectedly, differentiation elicited either by removal of an oncogenic input or by G-CSF did not peruse C/ebpα as mediator but rather directly affected the cell cycle core by upregulation of p21/p27 inhibitors. This points to functions downstream of C/ebpα as intersection point where transforming and differentiation stimuli converge and this finding offers a new perspective for therapeutic intervention.
A gene silencing pipeline to interrogate human cDC1 and pDC development and functions
Authors: Luo Xinlong , Lahaye Xavier , Jaeger Alix , Michea-Veloso Paula , Manel Nicolas , Dalod Marc 
Published: May 2023

AbstractType 1 conventional dendritic cells (cDC1s) and plasmacytoid dendritic cells (pDCs) are thought to be critical for anti-tumor or antiviral immunity. In vitro differentiation systems have unlocked the ability to produce large numbers of these cells. However, a method is lacking to systematically identify the cell-intrinsic factors controlling their differentiation and functions that remain therefore poorly understood, in contrast to the situation in mice. Here, we developed a workflow for efficient gene silencing and its tracing in human cDC1s/pDCs generated in vitro. As proof of concept, we confirmed the key role of IRF8 in their development, and of IRF7/MyD88 in human pDC production of interferons-α/λ. We found that SAMHD1 and RAB7B promote human cDC1 differentiation, while SEPT3 promotes human pDC differentiation. We also found that PPT1 and RAB5 are required for optimal differentiation of pDCs and cDC1s. Finally, we identified BCL11A, PPT1 and RAB7 as novel HIV-1 restriction factors in cDC1s/pDCs. This approach will enable broader genetic screens to advance our understanding of human cDC1s/pDCs and harness them against viral infections or cancer.
The contribution of an X chromosome QTL to non-Mendelian inheritance and unequal chromosomal segregation inA. freiburgense
Authors: Al-Yazeedi Talal , Adams Sally , Tandonnet Sophie , Turner Anisa , Kim Jun , Lee Junho , Pires-daSilva Andre 
Published: May 2023

AbstractAuanema freiburgenseis a trioecious nematode with co-existing males, females, and selfing hermaphrodites. Crosses of XO males with XX females result in a low percentage of XO sons due to the elimination of the nullo-X spermatids by the fathers. This process yields most viable sperm containing an X chromosome, leading to a higher transmission probability of the X chromosome compared to expected transmission via random segregation. The mechanism underlying this process involves the asymmetric distribution of essential cellular organelles during sperm formation, which likely depends on the X chromosome. Specifically, sperm components segregate with the X chromosome daughter cell, while other components are discarded in the nullo-X daughter cell. Here we found that intercrossing two strains ofA. freiburgenseresults in lines in which males produce viable nullo-X sperm. Thus, crosses of those hybrid males with females result in a high percentage of sons. To uncover the genetic basis of nullo-spermatid elimination and X-chromosome drive, we generated a genome assembly forA. freiburgenseand genotyped the intercrossed lines. We identified a QTL encompassing several genes on the X chromosome that are associated with its non-Mendelian inheritance observed inA. freiburgense. This finding provides valuable clues to the underlying factors involved in asymmetric organelle partitioning during male meiotic division and thus non-Mendelian transmission of the X chromosome and sex ratios.