bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation and selection explain why many eukaryotic centromeric DNA sequences are often A + T rich
Authors: Barbosa Anne C , Xu Zhengyao , Karari Kazhal , Williams Wendi , Hauf Silke , Brown William R A 
Published: November 2021

AbstractWe have used chromosome engineering to replace native centromeric DNA with different test sequences at native centromeres in two different strains of the fission yeast Schizosaccharomyces pombe and have discovered that A + T rich DNA, whether synthetic or of bacterial origin, will function as a centromere in this species. Using genome size as a surrogate for the inverse of effective population size (Ne) we also show that the relative A + T content of centromeric DNA scales with Ne across 43 animal, fungal and yeast (Opisthokonta) species. This suggests that in most of these species the A + T content of the centromeric DNA is determined by a balance between selection and mutation. Combining the experimental results and the evolutionary analyses allows us to conclude that A + T rich DNA of almost any sequence will function as a centromere in most Opisthokonta species. The fact that many G/C to A/T substitutions are unlikely to be selected against may contribute to the rapid evolution of centromeric DNA. We also show that a neo-centromere sequence is not simply a weak version of native centromeric DNA and suggest that neo-centromeres require factors either for their propagation or establishment in addition to those required by native centromeres.
PAMP-INDUCED SECRETED PEPTIDE 3 modulates salt tolerance through RECEPTOR-LIKE KINASE 7 in plants
Authors: Zhou Huapeng , Xiao Fei , Zheng Yuan , Liu Guoyong , Zhuang Yufen , Wang Zhiyue , Zhang Yiyi , He Jiaxian , Fu Chunxiang , Lin Honghui 
Published: November 2021

Abstract
High soil salinity negatively affects plant growth and development, leading to a severe decrease in crop production worldwide. Here, we report that a secreted peptide, PAMP-INDUCED SECRETED PEPTIDE 3 (PIP3), plays an essential role in plant salt tolerance through RECEPTOR-LIKE KINASE 7 (RLK7) in Arabidopsis (Arabidopsis thaliana). The gene encoding the PIP3 precursor, prePIP3, was significantly induced by salt stress. Plants overexpressing prePIP3 exhibited enhanced salt tolerance, whereas a prePIP3 knockout mutant had a salt-sensitive phenotype. PIP3 physically interacted with RLK7, a leucine-rich repeat RLK, and salt stress enhanced PIP3–RLK7 complex formation. Functional analyses revealed that PIP3-mediated salt tolerance is dependent on RLK7. Exogenous application of synthetic PIP3 peptide activated RLK7, and salt treatment significantly induced RLK7 phosphorylation in a PIP3-dependent manner. Notably, MITOGEN-ACTIVATED PROTEIN KINASE3 (MPK3) and MPK6 were downstream of the PIP3–RLK7 module in salt response signaling. Activation of MPK3/6 was attenuated in pip3 or rlk7 mutants under saline conditions. Therefore, MPK3/6 might amplify salt stress response signaling in plants for salt tolerance. Collectively, our work characterized a novel ligand–receptor signaling cascade that modulates plant salt tolerance in Arabidopsis. This study contributes to our understanding of how plants respond to salt stress.
Risk of flare after tapering or withdrawal of biologic/targeted synthetic disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis or axial spondyloarthritis: a systematic review and meta-analysis
Authors: Uhrenholt Line , Christensen Robin , Dinesen Wilfred K H , Liboriussen Caroline H , Andersen Stine S , Dreyer Lene , Schlemmer Annette , Hauge Ellen-Margrethe , Skrubbeltrang Conni , Taylor Peter C , Kristensen Salome 
Published: November 2021

Abstract

Objective
To evaluate flare risk when tapering or withdrawing biologic or targeted synthetic DMARDs (bDMARDs or tsDMARDs) compared with continuation in patients with inflammatory arthritis in sustained remission or with low disease activity.

Methods
Articles were identified in the Cochrane Library, PubMed, Embase and Web of Science. Eligible trials were randomized controlled trials comparing tapering and/or withdrawal of bDMARDs and/or tsDMARDs with the standard dose in inflammatory arthritis. Random effects meta-analysis was performed with risk ratio (RR) or Peto’s odds ratio (POR) for sparse events and 95% CI.

Results
The meta-analysis comprised 22 trials: 11 assessed tapering and 7 addressed withdrawal (4 assessed both). Only trials with an RA or axial SpA (axSpA) population were identified. An increased flare risk was demonstrated when b-/tsDMARD tapering was compared with continuation [RR 1.45 (95% CI 1.19, 1.77), I2 = 42.5%] and potentially increased for persistent flare [POR 1.56 (95% CI 0.97, 2.52), I2 = 0%]. Comparing TNF inhibitor (TNFi) withdrawal with continuation, a highly increased flare risk [RR 2.28 (95% CI 1.78, 2.93), I2 = 78%] and increased odds of persistent flare [POR 3.41 (95% CI 1.91, 6.09), I2 = 49%] were observed. No clear difference in flare risk between RA or axSpA was observed.

Conclusion
A high risk for flare and persistent flare was demonstrated for TNFi withdrawal, whereas an increased risk for flare but not for persistent flare was observed for b-/tsDMARD tapering. Thus tapering seems to be the more favourable approach.

Registration
PROSPERO (CRD42019136905).
Upadacitinib as monotherapy and in combination with non-biologic disease-modifying antirheumatic drugs for psoriatic arthritis
Authors: Nash Peter , Richette Pascal , Gossec Laure , Marchesoni Antonio , Ritchlin Christopher , Kato Koji , McDearmon-Blondell Erin L , Lesser Elizabeth , McCaskill Reva , Feng Dai , Anderson Jaclyn K , Ruderman Eric M 
Published: November 2021

Abstract

Objective
To assess the efficacy and safety of upadacitinib (UPA), an oral Janus kinase inhibitor, as monotherapy or in combination with non-biologic DMARDs (nbDMARDs) in patients with PsA.

Methods
Pooled data were analysed from patients with prior inadequate response or intolerance to one or more nbDMARD (SELECT-PsA 1) or one or more biologic DMARD (SELECT-PsA 2) who received placebo, UPA 15 mg once daily (QD) or UPA 30 mg QD as monotherapy or in combination with two or fewer nbDMARDs for 24 weeks. Efficacy outcomes included achievement of ACR responses, Psoriasis Area and Severity Index responses, minimal disease activity and change from baseline and clinically meaningful improvement in the HAQ Disability Index. Adverse events (AEs) were summarized.

Results
A total of 1916 patients were included; 574 (30%) received monotherapy and 1342 (70%) received combination therapy. Placebo-subtracted treatment effects for a 20% improvement in ACR criteria at week 12 were 33.7% (95% CI 24.4, 43.1) and 34.0% (95% CI 27.9, 40.1) for UPA 15 mg QD monotherapy and combination therapy, respectively, and 45.7% (95% CI 36.9, 54.5) and 39.6% (95% CI 33.7, 45.5) for UPA 30 mg QD monotherapy and combination therapy, respectively. Treatment effects for other outcomes were consistent between monotherapy and combination therapy. AE frequency was generally similar for UPA monotherapy and combination therapy, although hepatic disorders and creatine phosphokinase elevation were more common with combination therapy vs monotherapy.

Conclusion
The efficacy and safety of UPA were generally consistent when administered as monotherapy or in combination with nbDMARDs through 24 weeks, supporting the use of UPA with or without nbDMARDs in PsA.

Trial registration
ClinicalTrials.gov (https://clinicaltrials.gov): SELECT-PsA 1 (NCT03104400), SELECT-PsA 2 (NCT03104374)
Increased amygdala and decreased frontolimbic r
esting-
s
tate functional connectivity in children with aggressive behavior
Authors: Sukhodolsky Denis G , Ibrahim Karim , Kalvin Carla B , Jordan Rebecca P , Eilbott Jeffrey , Hampson Michelle 
Published: November 2021

Abstract
Childhood maladaptive aggression is associated with disrupted functional connectivity within amygdala-prefrontal circuitry. In this study, neural correlates of childhood aggression were probed using the intrinsic connectivity distribution, a voxel-wise metric of global resting-state brain connectivity. This sample included 38 children with aggressive behavior (26 boys, 12 girls) ages 8–16 years and 21 healthy controls (14 boys, 6 girls) matched for age and IQ. Functional MRI data were acquired during resting state, and differential patterns of intrinsic functional connectivity were tested in a priori regions of interest implicated in the pathophysiology of aggressive behavior. Next, correlational analyses tested for associations between functional connectivity and severity of aggression measured by the Reactive-Proactive Aggression Questionnaire in children with aggression. Children with aggressive behavior showed increased global connectivity in the bilateral amygdala relative to controls. Greater severity of aggressive behavior was associated with decreasing global connectivity in the dorsal anterior cingulate and ventromedial prefrontal cortex. Follow-up seed analysis revealed that aggression was also positively correlated with left amygdala connectivity with the dorsal anterior cingulate, ventromedial and dorsolateral prefrontal cortical regions. These results highlight the potential role of connectivity of the amygdala and medial prefrontal and anterior cingulate cortices in modulating the severity of aggressive behavior in treatment-seeking children.
Exposome mapping in chronic respiratory diseases: the added value of digital technology
Authors: Goossens Janne , Bullens Dominique M.A. , Dupont Lieven J. , Seys Sven F. 
Published: November 2021

Purpose of review
The development and progression of chronic respiratory diseases are impacted by a complex interplay between genetic, microbial, and environmental factors. Here we specifically summarize the effects of environmental exposure on asthma, allergic rhinitis, and chronic rhinosinusitis. We furthermore discuss how digital health technology may aid in the assessment of the environmental exposure of patients and how it may be of added value for them.

Recent findings
It is well established that one gets allergic symptoms if sensitized and exposed to the same allergen. Viruses, bacteria, pollutants, irritants, and lifestyle-related factors modify the risk of getting sensitized and develop symptoms or may induce symptoms themselves. Understanding these processes and how the various factors interact with each other and the human body require big data and advanced statistics. Mobile health technology enables integration of multiple sources of data of the patients’ exposome and link these to patient outcomes. Such technologies may contribute to the increased understanding of the development of chronic respiratory disease.

Summary
Implementation of digital technologies in clinical practice may in future guide the development of preventive strategies to tackle chronic respiratory diseases and eventually improve outcomes of the patient.
Mechanical circulatory support devices in geriatric patients: more than just age
Authors: Notarianni Andrew , Patel Bhoumesh 
Published: November 2021

Purpose of review
The use of mechanical circulatory support (MCS) devices, such as left ventricular assist device and extracorporeal membrane oxygenation in the elderly have been rapidly increasing in various clinical settings over the past two decades. This review briefly summarizes recent literature on the role and outcomes of such mechanical circulatory support devices use in the elderly.

Recent findings
Elderly patients are receiving increasing number of LVADs with improved survival and quality-of-life outcomes, despite multiple comorbidities. ECMO is a viable option in elderly patients but they have a higher risk of mortality after both VA ECMO and VV ECMO support. However, comorbidities, clinical presentation and timing of ECMO initiation seems to have a greater impact on prognosis than for younger patients.

Summary
MCS device use continue to rise in the elderly population. Meticulously selected elderly patients could be successfully supported with MCS devices with favorable outcomes and acceptable mortality and complication rate.
Outcome of Viral-associated Hemophagocytic Lymphohistiocytosis at a Tertiary Hospital
Authors: Nazir Hanan F. , Hassanein Nehad , Wali Yasser , Al Yazidi Laila S. 
Published: November 2021

Background:
Little is known about viral-associated hemophagocytic lymphohistiocytosis (HLH) in Oman. This study was done to assess the epidemiology, clinical features and outcome of viral-associated HLH in our setting.

Methods:
We retrospectively reviewed children (0–18 years) managed for viral-associated HLH at the Sultan Qaboos University Hospital, Oman, over a 15-year period (2006–2020). Patients’ medical records were used to describe their demographic, clinical and laboratory features, management and outcome.

Results:
Fifty-six children were managed for HLH at Sultan Qaboos University Hospital over the last 15 years (2006–2020) of whom a third (19; 34%) had a viral trigger. The median age at the time of diagnosis of viral-associated HLH was 83 (13–96) months. Fever, cytopenia, hyperferritinemia and evidence of hemophagocytosis in bone marrow were the most consistent findings. Most of these children had either genetic predisposition to HLH (8/19; 42%) or underlying immunodeficiency secondary to malignant conditions or chemotherapy/hematopoietic stem cell transplantation (6/19; 32%). Epstein-Barr virus (9; 47%) followed by cytomegalovirus (6; 31%) was the most common viral trigger in our setting. Treatment included antivirals (8; 42%), HLH 2004 protocol (4; 21%), rituximab (4; 21%) and hematopoietic stem cell transplantation (3; 16%). Fourteen children (74%) had full recovery.

Conclusions:
In our small cohort, viral-associated HLH was more frequently encountered in children with genetic predisposition to HLH or children with underlying immunodeficiency. In addition, we found that the outcome is overall good for children who have no genetic predisposition to HLH and children with genetic predisposition who underwent hematopoietic stem cell transplantation.
Patient with dissociation of corneal topography and epithelial mapping
Authors: Santhiago Marcony R. 
Published: November 2021

A 21-year-old man was referred for refractive surgery evaluation. Spectacle dependence and poor visual quality in his left eye is his chief complaint. He cannot tolerate contact lenses (CLs). The corrected distance visual acuity (CDVA) was 20/20 in the right eye (−1.50 −2.00 × 180) and 20/30 in the left eye (−1.25 −1.50 × 170). The patient denied any history of ocular trauma, systemic disease, or medications.
Corneal topography with different technologies revealed an inferior steepening in the left eye (Figure 1), whereas keratoconus indices from different strategies are within normal limits in both eyes (Supplemental Figures 1–4, http://links.lww.com/JRS/A496). Pachymetry maps from different devices present absolute values of thinnest point within normal ranges. Epithelial mapping revealed a localized thickening in the left eye (Supplemental Figures 5 and 6, http://links.lww.com/JRS/A496).
Slitlamp showed a total clear cornea with no signs of abnormality. The patient presents no signs of blepharitis or dry-eye syndrome either. Intraocular pressure is 14 mm Hg in both eyes. The retina was normal, bilaterally.
Considering the findings, what would be your main diagnostic hypothesis and, if any, which refractive surgery option would you consider for this patient?
Why Not Home?
Authors: Chovanec Kelli A. , Arsene Camelia , Beck Amanda , Liedel Bethany 
Published: November 2021

Purpose of Study:
Accountable Care Organizations (ACOs) aiming to reduce healthcare expenditure adopt strategies targeting costly postacute service utilization, asking “why not home?” as a part of the hospital discharge planning paradigm. This study examined the impact of an interventional approach to implement evidence-based interventions to improve transitions of care to the least restrictive next site of care on the rate of skilled nursing facility (SNF) admissions per 1,000, SNF length of stay (LOS), and total SNF cost.

Primary Practice Setting:
The impact of the interventional approach for an ACO-attributed Medicare population, analyzing Medicare Shared Savings Plan Part A and Part B beneficiary claims data, was examined.

Methodology and Sample:
A pre-/postintervention analysis was conducted, for dates of service 12 months pre- and postintervention for patients admitted to any hospital within the integrated health care system. The outcome variables were defined as SNF admission rate, SNF LOS, cost of care (total SNF cost, SNF cost per admission), and hospital LOS prior to SNF discharge.

Results:
There was early evidence of the effectiveness of the multifaceted interventions that involved the delivery of interprofessional team member education focused on the tenets of value-based care and discharging patients to the least restrictive setting, as appropriate. In the normalized data review, it was noted that the rate of SNF discharges per 1,000 patients changed from 73 per 1,000 patients in the preintervention period to 70 per 1,000 patients in the postintervention period. The total SNF cost in the postintervention period only increased by 3%, with a difference of $616,014, despite the 10% increase in the total ACO-attributed patient population during the same period.

Implications for Case Management Practice:
The results of this study imply that a multifaceted intervention with aims to shift the transitional care planning paradigm toward discharging to the least restrictive next site of care is an effective strategy for ACOs with aspirations to improve the utilization and expenditure in the postacute setting. The analyses suggest that providing education to interprofessional team members that reinforces the tenets of value-based care and the importance of asking, “why not home?” for every hospitalized patient, and leveraging technology-based insights positively impact discharge rates to SNF and other ACO outcomes.
Best Solutions for Perineal and Pressure Sore Reconstruction
Authors: Bialowas Christie , Nguyen Brittany , Patel Ashit 
Published: November 2021

Learning Objectives:
After studying this article, the participant should be able to: 1. Understand variations of the myocutaneous rectus abdominis muscle flap as it is used for perineal reconstruction and discuss common and alternative options for perineal defect reconstruction. 2. Review primary options and alternatives to pressure sore reconstruction if the primary option is not available and recognize when pressure sore reconstruction is not feasible. 3. Highlight pertinent anatomy and techniques for the flaps described.

Summary:
Perineal reconstruction following tumor resection is often complicated by irradiated tissue and multiple comorbidities, making reconstruction challenging. Management of these conditions can have complication rates as high as 66 percent, which further compounds the costs and implications of managing these wounds. These complication rates can be significantly decreased using flap closure rather than primary closure. Pressure ulcers also occur in patients with poor overall health, multiple comorbidities, and often numerous prior failed reconstruction attempts. Comprehensive management of pressure sores is a significant burden to the health care system, at a cost of $9.1 to $11.6 billion per year. There exists an extensive body of literature describing the pathophysiology and management strategies for these problems. The focus of this article is to discuss best solutions for perineal and pressure ulcer reconstruction, and to explore alternative options for reconstruction.
Fractional Carbon Dioxide Laser or Erbium:Yttrium-Aluminum-Garnet Laser Assisted by Topical Application/Intradermal Injection of Platelet-Rich Plasma for Postacne Scars
Authors: Chen Jianguo , Wan Yingying , Lin Yan , Jiang Haiyue 
Published: November 2021

Background:Fractional carbon dioxide or erbium:yttrium-aluminum-garnet (YAG) laser combined with platelet-rich plasma has been used for postacne scars. Nevertheless, there is limited evidence on its use because of the small size of relevant studies. This study aims to evaluate the efficacy of platelet-rich plasma–assisted laser for postacne scars.Methods:Randomized controlled trials comparing carbon dioxide or erbium:YAG laser combined with platelet-rich plasma to laser alone were searched for using the PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar databases.Results:In total, 13 studies involving 672 cases were included. The overall degree of clinical improvement favored platelet-rich plasma combined with carbon dioxide laser (mean difference, 0.55; 95 percent CI, 0.40 to 0.70) or erbium:YAG laser (mean difference, 0.63; 95 percent CI, 0.31 to 0.96). Notably, the use of carbon dioxide laser combined with platelet-rich plasma was more effective in both greater than 50 percent improvement of acne scars (OR, 1.63; 95 percent CI, 1.10 to 2.42) and greater than 75 percent improvement of acne scars (OR, 2.78; 95 percent CI, 1.75 to 4.42), compared with laser alone. Erbium:YAG laser combined with platelet-rich plasma was more effective in greater than 75 percent improvement of acne scars compared with laser alone (OR, 3.45; 95 percent CI, 1.31 to 9.05). Moreover, patient satisfaction was significantly higher with platelet-rich plasma combined with carbon dioxide laser (OR, 2.98; 95 percent CI, 1.72 to 5.16) or erbium:YAG laser (OR, 2.88; 95 percent CI, 1.33 to 6.21) compared to laser alone.Conclusion:This meta-analysis provides reliable evidence that fractional carbon dioxide or erbium:YAG laser combined with platelet-rich plasma is an effective and safe combination therapy for postacne scars.CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, II.
Plastic Surgeon Financial Compensation–Incentivization Models in Surgical Care Delivery: The Past, Present, and Future
Authors: Lopez Joseph , Offodile Anaeze C. , Shenaq Deana , Schechter Loren , Chavis Larry , Hultman Charles S. , Dorafshar Amir H. 
Published: November 2021

Background:
Surgeons are critical for the success of any health care enterprise. However, few studies have examined the potential impact of value-based care on surgeon compensation.

Methods:
This review presents value-based financial incentive models that will shape the future of surgeon compensation. The following incentivization models will be discussed: pay-for-reporting, pay-for-performance, pay-for-patient-safety, bundled payments, and pay-for-academic-productivity. Moreover, the authors suggest the application of the congruence model—a model developed to help business leaders understand the interplay of forces that shape the performance of their organizations—to determine surgeon compensation methods applicable in value-based care-centric environments.

Results:
The application of research in organizational behavior can assist health care leaders in developing surgeon compensation models optimized for value-based care. Health care leaders can utilize the congruence model to determine total surgeon compensation, proportion of compensation that is short term versus long term, proportion of compensation that is fixed versus variable, and proportion of compensation based on seniority versus performance.

Conclusion:
This review provides a framework extensively studied by researchers in organizational behavior that can be utilized when designing surgeon financial compensation plans for any health care entity shifting toward value-based care.