bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strategies to Move Entry-Level Nurse Practitioner Education to the Doctor of Nursing Practice Degree by 2025
Authors: Idzik Shannon , Buchholz Susan W. , Kelly-Weeder Susan , Finnegan Lorna , Bigley Mary Beth 
Published: October 2021

Background
The National Organization of Nurse Practitioner Faculties (NONPF) has made the commitment to move all entry-level nurse practitioner (NP) education to the Doctor of Nursing Practice (DNP) degree by 2025.

Problem
Although there are more than 250 DNP NP programs throughout the United States, many other NP programs have yet to transition to the doctoral level.

Approach
Leaders representing licensure, accreditation, certification, education, and practice organizations attended a NONPF 2017 Summit to discuss the DNP degree as entry into NP practice. Summit participants strategized on building collective strengths and addressed barriers to implementation. A solution-oriented discussion with action items has been operationalized for the last 4 years.

Outcomes
Four workgroups were created to address education, outcomes, capacity, and messaging related to moving all entry-level NP education to the DNP degree.

Conclusion
Ongoing collaborative efforts are critical to facilitate advancing all NP education programs to the DNP degree by 2025.
Incentive-Based Human Immunodeficiency Virus Screening in Low- and Middle-Income Countries: A Systematic Review
Authors: Finlay Jenise , Lambert Teresa , Krahn Jessica , Meyer Garret , Singh Ameeta E. , Caine Vera 
Published: October 2021

Background
The majority of new human immunodeficiency virus (HIV) infections that occur worldwide are in sub-Saharan Africa. While recent gains have been made in many low- and middle-income countries (LMICs), substantial disparities in sexually transmitted and blood-borne infections (STBBI) screening and treatment still exist between LMIC and high-income countries. In addition to increasing STBBI screening uptake, providing incentives for STBBI screening may decrease perceived stigma associated with STBBI screening.

Methods
Our review was conducted as part of a larger systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and guidance from the Cochrane Handbook for Systematic Reviews of Interventions. This review focuses on incentivized STBBI screening in LMIC; high-income countries were excluded. Articles were excluded if their primary focus was on children and youth (younger than 16 years), results retrieval, treatment, behavioral change only, behavior intention, treatment adherence, or provider incentive.

Results
The search yielded 6219 abstracts. The search and selection criteria included all STBBI; however, only articles examining incentivized HIV screening met our inclusion criteria. Five articles representing 4 distinct studies from South Africa, Uganda, and Zimbabwe were included, all of which focused on incentivized HIV screening. Populations screened included the following: men, first-time testers, population-based surveillance program families, and insurance health plan members. Incentive structures varied widely and incentives were mainly food vouchers, lottery prizes, or household items.

Conclusions
Our review was conducted to determine if patient incentives increase STBBI test uptake in LMIC. Overall, incentives were associated with an increase in HIV screening uptake. Most studies included focused solely on men. There is a significant void in understanding STBBI incentive-based screening outside of this context and in complex populations who should be targeted in incentivized HIV screening. Incentives appear most effective when developed specific to context and target population. Further research is needed to analyze incentivized screening across similar study designs, to evaluate long-term effectiveness, and to explore the ethical implications of incentivized care.
Examining the Relative Contributions of Methamphetamine Use, Depression, and Sexual Risk Behavior on Rectal Gonorrhea/Chlamydia Among a Cohort of Men Who Have Sex With Men in Los Angeles, California
Authors: Blair Cheríe S. , Needleman Jack , Javanbakht Marjan , Comulada W. Scott , Ragsdale Amy , Bolan Robert , Shoptaw Steven , Gorbach Pamina M. 
Published: October 2021

Background
Methamphetamine use, sexual risk behaviors, and depression contribute to ongoing human immunodeficiency virus (HIV) and sexually transmitted infection (STI) disparities among men who have sex with men (MSM). The relative contributions of these effects longitudinally are not well understood.

Methods
This analysis used visit-level data from a longitudinal cohort of MSM, half with HIV, in Los Angeles, CA. From August 2014 to March 2020, participants completed follow-up visits every 6 months and underwent testing for rectal gonorrhea/chlamydia (GC/CT) and completed questionnaires including depressive symptoms, number of receptive anal intercourse (RAI) partners, and methamphetamine use. Path analysis with structural equation modeling using concurrent and lagged covariates was used to identify relative contributions of methamphetamine use and depression on number of RAI partners and rectal GC/CT across time.

Results
Five hundred fifty-seven MSM with up to 6 visits (3 years) were included for a total of 2437 observations. Methamphetamine use and depressive symptoms were positively associated with number of RAI partners (β = 0.28, P < 0.001; β = 0.33, P = 0.018, respectively), which was positively associated with rectal GC/CT (β = 0.02, P < 0.001). When stratified by HIV status, depressive symptoms were positively associated with RAI partners for HIV-negative MSM (β = 0.50, P = 0.007) but were not associated for MSM living with HIV (β = 0.12, P = 0.57). Methamphetamine use was positively associated with RAI partners in both strata.

Conclusions
Factors and patterns, which contribute to risk behaviors associated with rectal GC/CT, may differ by HIV status. Our findings demonstrate the importance of combined treatment and prevention efforts that link screening and treatment of stimulant use and depression with STI prevention and treatment.
Blood product resuscitation mitigates the effects of aeromedical evacuation after polytrauma
Authors: Wallen Taylor E. , Singer Kathleen E. , Morris Mackenzie C. , Blakeman Thomas , Stevens-Topie Sabre M. , Strilka Richard , Pritts Timothy A. , Goodman Michael D. 
Published: October 2021

BACKGROUND
The combined injury of traumatic brain injury and hemorrhagic shock has been shown to worsen coagulopathy and systemic inflammation, thereby increasing posttraumatic morbidity and mortality. Aeromedical evacuation to definitive care may exacerbate postinjury morbidity because of the inherent hypobaric hypoxic environment. We hypothesized that blood product resuscitation may mitigate the adverse physiologic effects of postinjury flight.

METHODS
An established porcine model of controlled cortical injury was used to induce traumatic brain injury. Intracerebral monitors were placed to record intracranial pressure, brain tissue oxygenation, and cerebral perfusion. Each of the 42 pigs was hemorrhaged to a goal mean arterial pressure of 40 ± 5 mm Hg for 1 hour. Pigs were grouped according to resuscitation strategy used—Lactated Ringer's (LR) or shed whole blood (WB)—then placed in an altitude chamber for 2 hours at ground, 8,000 ft, or 22,000 ft, and then observed for 4 hours. Hourly blood samples were analyzed for proinflammatory cytokines and lactate. Internal jugular vein blood flow was monitored continuously for microbubble formation with altitude changes.

RESULTS
Cerebral perfusion, tissue oxygenation, and intracranial pressure were unchanged among the six study groups. Venous microbubbles were not observed even with differing altitude or resuscitation strategy. Serum lactate levels from hour 2 of flight to the end of observation were significantly elevated in 22,000 + LR compared with 8,000 + LR and 22,000 + WB. Serum IL-6 levels were significantly elevated in 22,000 + LR compared with 22,000 + WB, 8,000 + LR and ground+LR at hour 1 of observation. Serum tumor necrosis factor-α was significantly elevated at hour 2 of flight in 8,000 + LR versus ground+LR, and in 22,000 + LR vs. 22,000 + WB at hour 1 of observation. Serum IL-1β was significantly elevated hour 1 of flight between 8,000 + LR and ground+LR.

CONCLUSION
Crystalloid resuscitation during aeromedical transport may cause a prolonged lactic acidosis and proinflammatory response that can predispose multiple-injury patients to secondary cellular injury. This physiologic insult may be prevented by using blood product resuscitation strategies.
Impact of SARS-CoV-2 infection on vaccine-induced immune responses over time
Authors: Havervall Sebastian , Marking Ulrika , Greilert-Norin Nina , Gordon Max , Ng Henry , Christ Wanda , Phillipson Mia , Nilsson Peter , Hober Sophia , Blom Kim , Klingström Jonas , Mangsbo Sara , Åberg Mikael , Thålin Charlotte 
Published: October 2021

AbstractPeople with previous SARS-CoV-2 infection mount potent immune responses to COVID-19 vaccination, but long-term effects of prior infection on these immune responses are unknown. We investigated the long-term impact of prior SARS-CoV-2 infection on humoral and cellular immune responses in healthcare workers receiving the mRNA BNT162b2 or the adenovirus vectored ChAdOx1 nCoV-19 vaccine. Vaccination with both vaccine platforms resulted in substantially enhanced T cell immune responses, antibody responses to spike and neutralizing antibodies effective against ten SARS-CoV-2 variants following SARS-CoV-2 infection, compared to in naïve individuals. The enhanced immune responses sustained over seven months following vaccination. These findings imply that prior infection should be taken into consideration when planning booster doses and design of current and future COVID-19 vaccine programs.One-Sentence SummarySARS-CoV-2 infection prior to vaccination leads to substantial and durable increases in immune memory responses.
Long-term Complications of Unintentional Dural Puncture During Labor Epidural Analgesia: A Case-Control Study
Authors: Lacombe Alexandre , Downey Kristi , Ye Xiang Y. , Carvalho Jose C.A. 
Published: October 2021

AbstractIntroductionEpidural analgesia is the preferred method to manage pain during labor and delivery. The insertion of the epidural catheter can be complicated by unintentional dural puncture that may result in postdural puncture headache. There is limited evidence on the long term implications of this complication. We sought to investigate if women who sustained a dural puncture have a higher risk of developing chronic headache, low back pain and visual or auditory impairment.MethodsWe conducted a 1:1 case-control study with women who delivered at our institution from January 2015 to December 2019. Cases were women who received epidural analgesia and sustained an unintentional dural puncture and controls were women who received epidural analgesia but did not sustain such complication. We matched cases and controls for date of delivery, age, and BMI. All women completed an online survey with validated questionnaires for diagnosis of chronic headache and chronic back pain. We used dichotomic (yes/no) questions to look for the presence of chronic visual and auditory impairment.ResultsSixty-three case-control pairs were studied. Women who sustained a dural puncture during their epidural catheter insertion had a higher risk of developing chronic headache [14.3%, versus 4.8%, p=0.049, AOR: 3.36 (1.05, 12.82)] and chronic back pain [39.7% versus 19.1%, p=0.009, AOR: 2.67 (1.25, 5.72)] than women who did not sustain a dural puncture. The incidence of chronic auditory impairment was also higher in the dural puncture group [14.3% versus 1.6%, p=0.007, AOR: 9.98 (1.21, 82.62)].ConclusionsAn unintentional dural puncture during epidural catheter insertion in parturients is associated with increased risk of chronic headache, back pain and auditory impairment.
SSIM can robustly identify changes in 3D genome conformation maps
Authors: Ing-Simmons Elizabeth , Machnik Nick , Vaquerizas Juan M. 
Published: October 2021

AbstractWe previously presented Comparison of Hi-C Experiments using Structural Similarity (CHESS), an approach that applies the concept of the structural similarity index (SSIM) to Hi-C matrices1, and demonstrated that it could be used to identify both regions with similar 3D chromatin conformation across species, and regions with different chromatin conformation in different conditions. In contrast to the claim of Lee et al.2 that the SSIM output of CHESS is ‘independent’ of the input data, here we confirm that SSIM depends on both local and global properties of the input Hi-C matrices. We provide two approaches for using CHESS to highlight regions of differential genome organisation for further investigation, and expanded guidelines for choosing appropriate parameters and controls for these analyses.
Mass-selective and ice-free cryo-EM protein sample preparation via native electrospray ion-beam deposition
Authors: Esser Tim K. , Böhning Jan , Fremdling Paul , Agasid Mark T. , Costin Adam , Fort Kyle , Konijnenberg Albert , Bahm Alan , Makarov Alexander , Robinson Carol V. , Benesch Justin L. P. , Baker Lindsay , Bharat Tanmay A.M. , Gault Joseph , Rauschenbach Stephan 
Published: October 2021

AbstractElectron cryomicroscopy (cryo-EM) and single-particle analysis (SPA) have revolutionized structure determination of homogeneous proteins. However, obtaining high-resolution structures from heterogeneous samples remains a major challenge, as the various protein states embedded in thin films of vitreous ice may be classified incorrectly, resulting in detrimental averaging of features. Here we present native electrospray ion-beam deposition (native ES-IBD) for the preparation of extremely high-purity cryo-EM samples, based on mass selection in vacuum. Folded protein ions are generated by native electrospray ionization, mass-filtered, and gently deposited on cryo-EM grids, and subsequently frozen in liquid nitrogen. We demonstrate homogeneous coverage of ice-free cryo-EM grids with mass-selected proteins and protein assemblies. SPA reveals that they remain structurally intact, but variations in secondary and tertiary structure are currently limiting information in 2D classes and 3D EM density maps. Our results show the potential of native ES-IBD to increase the scope and throughput of cryo-EM structure determination.
Acute silencing uncovers multiple forms of activity-dependent neuronal survival in the mature entorhinal cortex
Authors: Zhao Rong , Grunke Stacy D. , Li Ming-Hua , Wood Caleb A. , Perez Gabriella A. , Comstock Melissa , Singh Anand K. , Park Kyung-Won , Jankowsky Joanna L. 
Published: October 2021

AbstractNeurodegenerative diseases are characterized by selective vulnerability of distinct cell populations; however, the cause for this specificity remains elusive. Many circuits that degenerate in disease are shaped by neural activity during development, raising the possibility that mechanisms governing early cell loss may be misused when activity is compromised in the mature brain. Here we show that electrical activity and synaptic transmission are both required for neuronal survival in the adult entorhinal cortex, but these silencing methods trigger distinct means of degeneration in the same neuronal population. Competition between active and inactive cells drives axonal disintegration caused by synaptic inhibition, but not axon retraction due to electrical suppression. These findings suggest that activity-dependence may persist in some areas of the adult brain long after developmental critical periods have closed. We speculate that lifelong plasticity required to support memory may render entorhinal neurons vulnerable to prolonged activity changes in disease.
Senataxin and RNase H2 act redundantly to suppress genome instability during class switch recombination
Authors: Zhao Hongchang , Hartono Stella , De Vera Kirtney Mae , Yu Zheyuan , Satchi Krishni , Zhao Tracy , Sanz Lionel , Chedin Frederic , Barlow Jacqueline 
Published: October 2021

AbstractClass switch recombination generates antibody distinct isotypes critical to a robust adaptive immune system and defects are associated with auto-immune disorders and lymphomagenesis. Transcription is required during class switch to recruit the cytidine deaminase AID—an essential step for the formation of DNA double-strand breaks—and strongly induces the formation of R loops within the immunoglobulin heavy chain locus. However, the impact of R loops on double-strand break formation and repair during class switch recombination remains unclear. Here we report that cells lacking two enzymes involved in R loop removal— Senataxin and RNase H2—exhibit increased R loop formation and genome instability at the immunoglobulin heavy chain locus without impacting class switch recombination efficiency, transcriptional activity, or AID recruitment. Senataxin and RNase H2-deficient cells also exhibit increased insertion mutations at switch junctions, a hallmark of alternative end joining. Importantly, these phenotypes were not observed in cells lacking Senataxin or RNase H2B alone. We propose that Senataxin acts redundantly with RNase H2 to mediate timely R loop removal, promoting efficient repair while suppressing AID-dependent genome instability and insertional mutagenesis.
MIR822 modulates monosporic female gametogenesis through an ARGONAUTE9-dependent pathway in Arabidopsis thaliana
Authors: Tovar-Aguilar Andrea , Grimanelli Daniel , Acosta-García Gerardo , Vielle-Calzada Jean-Philippe , Badillo-Corona Jesús Agustín , Durán-Figueroa Noé 
Published: October 2021

ABSTRACTIn the ovule of flowering plants, the establishment of the haploid generation occurs when a somatic subepidermal cell specified as the gametophytic precursor differentiates into a Megaspore Mother Cell (MMC) and initiates meiosis. As most flowering plants, Arabidopsis thaliana (Arabidopsis) undergoes a monosporic type of gametogenesis as three meiotically derived cells degenerate without further division, and a single one – the functional megaspore (FM) - divides mitotically to form the female gametophyte. The genetic basis and molecular mechanisms that control monosporic gametogenesis remain largely unknown. In Arabidopsis, ARGONAUTE proteins are involved the control of megasporogenesis. In particular, mutations in ARGONAUTE9 (AGO9) lead to the ectopic differentiation of gametic precursors that can give rise to apomeiotically derived female gametophytes. Here, we show that Arabidopsis plants carrying loss-of-function mutations in the AGO9-interacting microRNA miR822a give rise to extranumerary surviving megaspores that acquire a FM identity and divide without giving rise to differentiated female gametophytes. The overexpression of three miR822a target genes encoding Cysteine/Histidine-Rich C1 domain proteins (At5g02350, At5g02330 and At2g13900) results in defects equivalent to those found in mir822 plants. All three miR822a targets are overexpressed in ago9 mutant ovules, confirming that miR822a acts through an AGO9-dependent pathway to negatively regulate Cysteine/Histidine-Rich C1 domain proteins and restricts the survival of meiotically derived cells to a single megaspore. Our results identify a microRNA-dependent mechanism that is involved in the control of megaspore degeneration and the most prevalent form of female gametogenesis in flowering plants.
Preclinical Efficacy of IMM-BCP-01, a Highly Active Patient-Derived Anti-SARS-CoV-2 Antibody Cocktail
Authors: Nikitin Pavel A. , DiMuzio Jillian M. , Dowling John P. , Patel Nirja B. , Bingaman-Steele Jamie L. , Heimbach Baron C. , Henriquez Noeleya , Nicolescu Chris , Polley Antonio , Sikorski Eden L. , Howanski Raymond J. , Nath Mitchell , Shukla Halley , Scheaffer Suzanne M. , Finn James P. , Liang Li-Fang , Smith Todd , Storm Nadia , McKay Lindsay G. A. , Johnson Rebecca I. , Malsick Lauren E. , Honko Anna N. , Griffiths Anthony , Diamond Michael S. , Sarma Purnanand , Geising Dennis H. , Morin Michael J. , Robinson Matthew K. 
Published: October 2021

AbstractUsing an unbiased interrogation of the memory B cell repertoire of convalescent COVID-19 patients, we identified human antibodies that demonstrated robust antiviral activity in vitro and efficacy in vivo against all tested SARS-CoV-2 variants. Here, we describe the pre-clinical characterization of an antibody cocktail, IMM-BCP-01, that consists of three unique, patient-derived recombinant neutralizing antibodies directed at non-overlapping surfaces on the SARS-CoV-2 spike protein. Two antibodies, IMM20184 and IMM20190 directly block spike binding to the ACE2 receptor. Binding of the third antibody, IMM20253, to its unique epitope on the outer surface of RBD, alters the conformation of the spike trimer, promoting release of spike monomers. These antibodies decreased SARS-CoV-2 infection in the lungs of Syrian golden hamsters, and efficacy in vivo efficacy was associated with broad antiviral neutralizing activity against multiple SARS-CoV-2 variants and robust antiviral effector function response, including phagocytosis, ADCC, and complement pathway activation. Our pre-clinical data demonstrate that the three antibody cocktail IMM-BCP-01 shows promising potential for preventing or treating SARS-CoV-2 infection in susceptible individuals.One sentence summaryIMM-BCP-01 cocktail triggers Spike Trimer dissociation, neutralizes all tested variants in vitro, activates a robust effector response and dose-dependently inhibits virus in vivo.
The landscape of extrachromosomal circular DNA in medulloblastoma
Authors: Chapman Owen S , Luebeck Jens , Wani Sameena , Tiwari Ashutosh , Pagadala Meghana , Wang Shanqing , Larson Jon D , Lange Joshua T , Wong Ivy Tsz-Lo , Dehkordi Siavash R , Chandran Sahaana , Adam Miriam , Lin Yingxi , Juarez Edwin , Robinson James T , Sridhar Sunita , Malicki Denise M , Coufal Nicole , Levy Michael , Crawford John R , Pomeroy Scott L , Rich Jeremy , Scheuermann Richard H , Carter Hannah , Dixon Jesse , Mischel Paul S , Fraenkel Ernest , Wechsler-Reya Robert J , Bafna Vineet , Mesirov Jill P , Chavez Lukas 
Published: October 2021

SUMMARYExtrachromosomal circular DNA (ecDNA) is an important driver of aggressive tumor growth, promoting high oncogene copy number, intratumoral heterogeneity, accelerated evolution of drug resistance, enhancer rewiring, and poor outcome. ecDNA has been reported in medulloblastoma (MB), the most common malignant pediatric brain tumor, but the ecDNA landscape and its association with specific MB subgroups, its impact on enhancer rewiring, and its potential clinical implications, are not known. We assembled a retrospective cohort of 468 MB patient samples with available whole genome sequencing (WGS) data covering the four major MB subgroups WNT, SHH, Group 3 and Group 4. Using computational methods for the detection and reconstruction of ecDNA1, we find ecDNA in 82 patients (18%) and observe that ecDNA+ MB patients are more than twice as likely to relapse and three times as likely to die of disease. In addition, we find that individual medulloblastoma tumors often harbor multiple ecDNAs, each containing different amplified oncogenes along with co-amplified non-coding regulatory enhancers. ecDNA was substantially more prevalent among 31 analyzed patient-derived xenograft (PDX) models and cell lines than in our patient cohort. By mapping the accessible chromatin and 3D conformation landscapes of MB tumors that harbor ecDNA, we observe frequent candidate “enhancer rewiring” events that spatially link oncogenes with co-amplified enhancers. Our study reveals the frequency and diversity of ecDNA in a subset of highly aggressive tumors and suggests enhancer rewiring as a frequent oncogenic mechanism of ecDNAs in MB. Further, these results demonstrate that ecDNA is a frequent and potent driver of poor outcome in MB patients.