bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Thousand-Pulsar-Array programme on MeerKAT – II. Observing strategy for pulsar monitoring with subarrays
Authors: Song X , Weltevrede P , Keith M J , Johnston S , Karastergiou A , Bailes M , Barr E D , Buchner S , Geyer M , Hugo B V , Jameson A , Parthasarathy A , Reardon D J , Serylak M , Shannon R M , Spiewak R , van Straten W , Venkatraman Krishnan V 
Published: December 2020

ABSTRACT
The Thousand-Pulsar-Array (TPA) programme currently monitors about 500 pulsars with the sensitive MeerKAT radio telescope by using subarrays to observe multiple sources simultaneously. Here we define the adopted observing strategy, which guarantees that each target is observed long enough to obtain a high-fidelity pulse profile, thereby reaching a sufficient precision of a simple pulse shape parameter. This precision is estimated from the contribution of the system noise of the telescope, and the pulse-to-pulse variability of each pulsar, which we quantify under some simplifying assumptions. We test the assumptions and choice of model parameters using data from the MeerKAT 64-dish array and the Lovell and Parkes telescopes. We demonstrate that the observing times derived from our method produce high-fidelity pulse profiles that meet the needs of the TPA in studying pulse shape variability and pulsar timing. Our method can also be used to compare strategies for observing large numbers of pulsars with telescopes capable of forming multiple subarray configurations. We find that using two 32-dish MeerKAT subarrays is the most efficient strategy for the TPA project. We also find that the ability to observe in different array configurations will become increasingly important for large observing programmes using the Square Kilometre Array telescope.
Model-independent discovery prospects for primordial black holes at LIGO
Authors: Lehmann Benjamin V , Profumo Stefano , Yant Jackson 
Published: December 2020

ABSTRACT
Primordial black holes may encode the conditions of the early Universe, and may even constitute a significant fraction of cosmological dark matter. Their existence has yet to be established. However, black holes with masses below ${\sim}{1}{\, \mathrm{M}_\odot }$ cannot form as an endpoint of stellar evolution, so the detection of even one such object would be a smoking gun for new physics, and would constitute evidence that at least a fraction of the dark matter consists of primordial black holes. Gravitational wave detectors are capable of making a definitive discovery of this kind by detecting mergers of light black holes. But since the merger rate depends strongly on the shape of the black hole mass function, it is difficult to determine the potential for discovery or constraint as a function of the overall abundance of black holes. Here, we directly maximize and minimize the merger rate to connect observational results to the actual abundance of observable objects. We show that LIGO can discover mergers of light primordial black holes within the next decade even if such black holes constitute only a very small fraction of dark matter. A single merger event involving such an object would (i) provide conclusive evidence of new physics, (ii) establish the nature of some fraction of dark matter, and (iii) probe cosmological history at scales far beyond those observable today.
MitImpact 3: modeling the residue interaction network of the Respiratory Chain subunits
Authors: Castellana Stefano , Biagini Tommaso , Petrizzelli Francesco , Parca Luca , Panzironi Noemi , Caputo Viviana , Vescovi Angelo Luigi , Carella Massimo , Mazza Tommaso 
Published: December 2020

Abstract
Numerous lines of evidence have shown that the interaction between the nuclear and mitochondrial genomes ensures the efficient functioning of the OXPHOS complexes, with substantial implications in bioenergetics, adaptation, and disease. Their interaction is a fascinating and complex trait of the eukaryotic cell that MitImpact explores with its third major release. MitImpact expands its collection of genomic, clinical, and functional annotations of all non-synonymous substitutions of the human mitochondrial genome with new information on putative Compensated Pathogenic Deviations and co-varying amino acid sites of the Respiratory Chain subunits. It further provides evidence of energetic and structural residue compensation by techniques of molecular dynamics simulation. MitImpact is freely accessible at http://mitimpact.css-mendel.it.
Precise and broad scope genome editing based on high-specificity Cas9 nickases
Authors: Wang Qian , Liu Jin , Janssen Josephine M , Le Bouteiller Marie , Frock Richard L , Gonçalves Manuel A F V 
Published: December 2020

Abstract
RNA-guided nucleases (RGNs) based on CRISPR systems permit installing short and large edits within eukaryotic genomes. However, precise genome editing is often hindered due to nuclease off-target activities and the multiple-copy character of the vast majority of chromosomal sequences. Dual nicking RGNs and high-specificity RGNs both exhibit low off-target activities. Here, we report that high-specificity Cas9 nucleases are convertible into nicking Cas9D10A variants whose precision is superior to that of the commonly used Cas9D10A nickase. Dual nicking RGNs based on a selected group of these Cas9D10A variants can yield gene knockouts and gene knock-ins at frequencies similar to or higher than those achieved by their conventional counterparts. Moreover, high-specificity dual nicking RGNs are capable of distinguishing highly similar sequences by ‘tiptoeing’ over pre-existing single base-pair polymorphisms. Finally, high-specificity RNA-guided nicking complexes generally preserve genomic integrity, as demonstrated by unbiased genome-wide high-throughput sequencing assays. Thus, in addition to substantially enlarging the Cas9 nickase toolkit, we demonstrate the feasibility in expanding the range and precision of DNA knockout and knock-in procedures. The herein introduced tools and multi-tier high-specificity genome editing strategies might be particularly beneficial whenever predictability and/or safety of genetic manipulations are paramount.
‘Stat’ workflow modifications to expedite care after needlestick injuries
Authors: Smith J L , Banerjee R , Linkin D R , Schwab E P , Saberi P , Lanzi M 
Published: December 2020

Abstract

Background
Post-exposure prophylaxis (PEP) for human immunodeficiency virus (HIV) is recommended to start within hours of needlestick injuries (NSIs) among healthcare workers (HCWs). Delays associated with awaiting the results of testing from the source patient (whose blood was involved in the NSI) can lead to psychological consequences for the exposed HCW as well as symptomatic toxicities from empiric PEP.

Aims
After developing a ‘stat’ (immediate) workflow that prioritized phlebotomy and resulting of source patient bloodwork for immediate handling and processing, we retrospectively investigated whether our new workflow had (i) decreased HIV order-result interval times for source patient HIV bloodwork and (ii) decreased the frequency of HIV PEP prescriptions being dispensed to exposed HCWs.

Methods
We retrospectively analysed NSI records to identify source patient HIV order-result intervals and PEP dispensing frequencies across a 6-year period (encompassing a 54-month pre-intervention period and 16-month post-intervention period).

Results
We identified 251 NSIs, which occurred at similar frequencies before versus after our intervention (means 3.54 NSIs and 3.75 NSIs per month, respectively). Median HIV order-result intervals decreased significantly (P &lt; 0.05) from 195 to 156 min after our intervention, while the proportion of HCWs who received one or more doses of PEP decreased significantly (P &lt; 0.001) from 50% (96/191) to 23% (14/60).

Conclusion
Using a ‘stat’ workflow to prioritize source patient testing after NSIs, we achieved a modest decrease in order-result intervals and a dramatic decrease in HIV PEP dispensing rates. This simple intervention may improve HCWs’ physical and psychological health during a traumatic time.
Asleep Deep Brain Stimulator Placement in the Intraoperative Magnetic Resonance Imaging System Hybrid Operating Suite: 2-Dimensional Operative Video
Authors: Brock Andrea A , Kundu Bornali , Rolston John D 
Published: December 2020

Abstract
Asleep, image-guided deep brain stimulation (DBS) placement is rapidly gaining popularity because it offers greater patient comfort and comparable accuracy with frame-based methods using microelectrode recording.
1
In this video, we demonstrate our protocol to use the frameless, stereotactic ClearPoint system (MRI Interventions Inc, Irvine, California) to place DBS electrodes within an intraoperative magnetic resonance imaging hybrid operating suite (IMRIS; Deerfield Imaging Inc, Minnetonka, Minnesota).
1-4
This system uses a skull-mounted aiming device coupled with sequential, intraoperative magnetic resonance imaging guidance to direct DBS lead placement to subcortical targets.
2,5
Importantly, this method allows the patient to remain asleep during the operation and does not require medication holidays or additional microelectrode recording equipment. The literature indicates it has comparable accuracy
1,6
and outcomes
2
with the awake method. We demonstrate this technique with the case of a patient with Parkinson disease who required lead placement in the bilateral subthalamic nuclei.
7-9
The patient consented to the procedure and publication. Patient positioning, draping nuances, initial indirect targeting, and final direct targeting are demonstrated. Risks of the operation include a risk of hemorrhage, hardware failure, and infection.
10
DBS is currently an underutilized treatment option for patients with Parkinson disease.
11
Offering the asleep option may be more tolerable for many patients who are wary of awake surgery.
Innate immunology in COVID-19—a living review. Part II: dysregulated inflammation drives immunopathology
Authors: Rodrigues Patrícia R S , Alrubayyi Aljawharah , Pring Ellie , Bart Valentina M T , Jones Ruth , Coveney Clarissa , Lu Fangfang , Tellier Michael , Maleki-Toyserkani Shayda , Richter Felix C , Scourfield D Oliver , Gea-Mallorquí Ester , Davies Luke C 
Published: December 2020

Abstract
The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global health crisis and will likely continue to impact public health for years. As the effectiveness of the innate immune response is crucial to patient outcome, huge efforts have been made to understand how dysregulated immune responses may contribute to disease progression. Here we have reviewed current knowledge of cellular innate immune responses to SARS-CoV-2 infection, highlighting areas for further investigation and suggesting potential strategies for intervention. We conclude that in severe COVID-19 initial innate responses, primarily type I interferon, are suppressed or sabotaged which results in an early interleukin (IL)-6, IL-10 and IL-1β-enhanced hyperinflammation. This inflammatory environment is driven by aberrant function of innate immune cells: monocytes, macrophages and natural killer cells dispersing viral pathogen-associated molecular patterns and damage-associated molecular patterns into tissues. This results in primarily neutrophil-driven pathology including fibrosis that causes acute respiratory distress syndrome. Activated leukocytes and neutrophil extracellular traps also promote immunothrombotic clots that embed into the lungs and kidneys of severe COVID-19 patients, are worsened by immobility in the intensive care unit and are perhaps responsible for the high mortality. Therefore, treatments that target inflammation and coagulation are promising strategies for reducing mortality in COVID-19.
Obstetric Anesthetic Management for Parturients with Hereditary Angioedema: A Case Report and Suggested Protocol
Authors: Clark Kathryn J , Sviggum Hans P , Jacob Adam K , Arendt Katherine W , Volcheck Gerald W , Szymanski Linda M , Sharpe Emily E 
Published: December 2020

Abstract
Hereditary angioedema (HAE) is a disease manifested by repeated episodes of localized submucosal or subcutaneous edematous episodes, potentially triggered by emotional stress, mechanical trauma, or intake of estrogens. We present our experience managing two parturients with HAE. Multidisciplinary care is essential for planning and executing the specialized care of these patients, and management included extensive planning among obstetric, anesthesiology, and allergy and immunology teams. Pregnancy has been shown to have a variable effect on triggering HAE episodes. First-line treatment includes C1 esterase inhibitor concentrate, which can also be used for prophylaxis in high-risk patients. Neuraxial analgesia is recommended to avoid general anesthesia and was established early in both individuals. Vaginal delivery was well tolerated without need for emergent treatment for angioedema symptoms.
Comparative risks of cardiovascular disease events among SLE patients receiving immunosuppressive medications
Authors: Choi May Y , Li Daniel , Feldman Candace H , Yoshida Kazuki , Guan Hongshu , Kim Seoyoung C , Everett Brendan M , Costenbader Karen H 
Published: December 2020

Abstract

Objectives
SLE patients have elevated cardiovascular disease (CVD) risk, but it is unclear whether this risk is affected by choice of immunosuppressive drug. We compared CVD risks among SLE patients starting MMF, CYC or AZA.

Methods
Using Medicaid Analytic eXtract (2000–2012), adult SLE patients starting MMF, CYC or AZA were identified and propensity scores (PS) were estimated for receipt of MMF vs CYC and MMF vs AZA. We examined rates of first CVD event (primary outcome), all-cause mortality, and a composite of first CVD event and all-cause mortality (secondary outcomes). After 1:1 PS-matching, Fine–Gray regression models estimated subdistribution hazard ratios (HRs.d.) for risk of CVD events. Cox regression models estimated HRs for all-cause mortality. The primary analysis was as-treated; 6- and 12-month intention-to-treat (ITT) analyses were secondary.

Results
We studied 680 PS-matched pairs of patients with SLE initiating MMF vs CYC and 1871 pairs initiating MMF vs AZA. Risk of first CVD event was non-significantly reduced for MMF vs CYC [HRs.d 0.72 (95% CI: 0.37, 1.39)] and for MMF vs AZA [HRs.d 0.88 (95% CI: 0.59, 1.32)] groups. In the 12-month ITT, first CVD event risk was lower among MMF than AZA new users [HRs.d 0.68 (95% CI: 0.47, 0.98)].

Conclusion
In this head-to-head PS-matched analysis, CVD event risks among SLE patients starting MMF vs CYC or AZA were not statistically reduced except in one 12-month ITT analysis of MMF vs AZA, suggesting longer-term use may convey benefit. Further studies of potential cardioprotective benefit of MMF are necessary.
Successes and challenges of implementing a lung cancer screening program in federally qualified health centers: a qualitative analysis using the Consolidated Framework for Implementation Research
Authors: Allen Caitlin G , Cotter Megan M , Smith Robert A , Watson Lesley 
Published: December 2020

Abstract
In recent years, studies have shown that low-dose computed tomography (LDCT) is a safe and effective way to screen high-risk adults for lung cancer. Despite this, uptake remains low, especially in limited-resource settings. The American Cancer Society (ACS) partnered with two federally qualified health centers and accredited screening facilities on a 2 year pilot project to implement an LDCT screening program. Both sites attempted to develop a referral program and care coordination practices to move patients through the screening continuum and identify critical facilitators and barriers to implementation. Evaluators conducted key informant interviews (N = 46) with clinical and administrative staff, as well as regional ACS staff during annual site visits. The Consolidated Framework for Implementation Research guided our analysis of factors associated with effective implementation and improved screening outcomes. One study site established a sustainable lung screening program, while the other struggled to overcome significant implementation barriers. Increased time spent with patients, disruption to normal workflows, and Medicaid reimbursement policies presented challenges at both sites. Supportive, engaged leaders and knowledgeable champions who provided clear implementation guidance improved staff engagement and were able to train, guide, and motivate staff throughout the intervention. A slow, stepwise implementation process allowed one site’s project champions to pilot test new processes and resolve issues before scaling up. This pilot study provides critical insights into the necessary resources and steps for successful lung cancer screening program implementation in underserved settings. Future efforts can build upon these findings and identify and address possible facilitators and barriers to screening program implementation.
A randomized controlled trial of online acceptance and commitment therapy to improve diet and physical activity among adults who are overweight/obese
Authors: Levin Michael E , Petersen Julie M , Durward Carrie , Bingeman Brittany , Davis Elizabeth , Nelson Cindy , Cromwell Shannon 
Published: December 2020

Abstract
Acceptance and commitment therapy (ACT) has shown benefit for improving diet, physical activity, and weight among adults who are overweight and obese. However, research to-date in this area has primarily evaluated ACT delivered through in-person interventions, which has more limited access relative to online formats. The present study evaluated an online guided self-help program that integrated ACT with nutrition education to improve healthy eating and physical activity. A sample of 79 adults who were overweight/obese was randomized to receive the 8-week ACT on Health program plus weekly phone coaching or to a waitlist. Participants completed 5.5 ACT sessions on average (out of 8) and reported moderately high program satisfaction. Participants in the ACT condition improved significantly more than the waitlist at posttreatment on the primary outcome of healthy eating index (HEI; based on 24-hr recall assessments) and almost all secondary outcomes assessing self-reported eating behaviors, weight, mental health, weight self-stigma, and psychological inflexibility. However, no intervention effects were found for self-reported physical activity. At 8-week follow-up, improvements were maintained for most outcomes in the ACT condition, but not for the HEI. Improvements in psychological inflexibility mediated treatment effects on some outcomes, but not HEI or weight. Overall, delivering ACT through online guided self-help combined with nutrition education appears promising for improving healthy eating, weight, and self-stigma, but results for physical activity and long-term behavior change are unclear, possibly due to limitations in the ACT on Health program.
Lumbar Perforator Flaps for Coverage of Extensive Defects With Osteomyelitis
Authors: Schaffer Clara , Guillier David , Raffoul Wassim , di Summa Pietro G. 
Published: December 2020

Introduction
Lumbar osteomyelitis is a rare, although serious condition if not appropriately treated, potentially leading to neurologic complications, such as radiculopathy. Traditionally, studies have suggested the preferred use of muscle or myocutaneous flaps to prevent recurrent infections. However, late evidence suggests that radical debridement and dead space obliteration are more important than the type of flap. The lumbar perforator flap is a reliable local option with low donor site morbidity. It is a powerful tool for local trunk reconstruction, but its use in case of osteomyelitis is scarcely described. We aimed to report long-term outcomes of lumbar perforator flaps to cover lumbar soft tissue defects with chronic osteomyelitis.

Material and Methods
This retrospective investigation was performed on a prospectively maintained database including 7 consecutive patients (10 flaps), all presenting extensive defects of the posterior midline at L2-S1 level (defect size 287 ± 136 cm2 [average ± SD]). Four patients presented defects after recurrent tumor resection, whereas in 2 patients, the defect was due to vascular jeopardy of internal iliac arteries with consequent necrosis. Last defect derived from debridement of a neglected wound in a paraplegic patient. All patients had concomitant bone infection. Infectious details and postoperative complications were recorded.

Results
Patients were in general poor medical condition (including peripheral arterial disease, hypertension, diabetes, or a combination of these). Eight flaps were raised as propeller perforator, whereas 2 as V-Y perforator. One propelled flap had venous congestion on postoperative day 1 and required a revision surgery to be converted to V-Y. Subsequent partial flap necrosis was treated conservatively. One patient presented a wound dehiscence that required surgical revision. All flaps were closed primarily except for 1 patient whose flap presented a mild intraoperative congestion, which was treated by delayed closure on postoperative day 6, with uneventful outcome. Time to complete healing was 29 ± 17 days (mean ± SD). No flap loss occurred, and all patients benefited from effective coverage at a mean follow-up of 20 months.

Conclusions
Lumbar perforator flap is a reliable option to cover large soft tissue defects in the lumbar area despite chronic osteomyelitis, with low morbidity and acceptable cosmetic outcome.
The Defensive Behavior of Indiana Mite-Biting Honey Bees AgainstVarroa destructorand the Structure of Bee Mandibles
Authors: Smith Jada , Cleare Xaryn L. , Given Krispn , Li-Byarlay Hongmei 
Published: December 2020

AbstractThe honey bee (Apis mellifera) is the most important managed pollinator to sustainable agriculture and our ecosystem. Yet managed honey bee colonies in the United States experience 30–40% losses annually. Among the many biotic stressors, the parasitic miteVarroa destructoris considered one of the main causes of colony losses. Bees’ mite-biting behavior has been selected as aVarroa-tolerant orVarroa-resistant trait in the state of Indiana for more than a decade. A survey of damaged mites from the bottom of a colony can be used as an extended phenotype to evaluate the mite-biting behavior of a colony. In this study, on average, 37% of mites sampled from the breeding stocks of 59 colonies of mite biters in Indiana were damaged or mutilated, which is significantly higher than the 19% of damaged mites found in commercial colonies in the southern United States. Indiana mite biter colonies had a higher proportion of damaged mites, although among the damaged mites, the number of missing legs was not significantly higher. In addition, the morphology of pollen-forager worker bee mandibles was compared by X-ray microcomputed tomography for six parameters in two populations, and a difference was detected in one parameter. Our results provide scientific evidence that potentially explains the defensive mechanism againstVarroamites: structural changes in the worker bee mandibles.