bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leader Change, Time in Office and the Determinants of Voter Perceptions
Authors: Bridgewater Jack 
Published: June 2021

Abstract
There is a significant literature on the role of both parties and leaders in electoral politics and a broad understanding of the strength of the relationship between the two in voters’ minds. However, less has been done to determine if there is systematic variation in whether voters see a party and its leader as one and the same. I address this question by using the Comparative Study of Electoral System to measure the impact of leader changes on voter perceptions. I find that new leaders are less likely to be evaluated according to the party they represent, with some evidence that maintaining the same leader over a long period of time increases the association between leader and party.
Fluorescent biosensors illuminating plant hormone research
Authors: Balcerowicz Martin , Shetty Kartika N. , Jones Alexander M. 
Published: June 2021

Abstract
Phytohormones act as key regulators of plant growth that coordinate developmental and physiological processes across cells, tissues and organs. As such, their levels and distribution are highly dynamic owing to changes in their biosynthesis, transport, modification and degradation that occur over space and time. Fluorescent biosensors represent ideal tools to track these dynamics with high spatiotemporal resolution in a minimally invasive manner. Substantial progress has been made in generating a diverse set of hormone sensors with recent FRET biosensors for visualising hormone concentrations complementing information provided by transcriptional, translational and degron-based reporters. In this review, we provide an update on fluorescent biosensor designs, examine the key properties that constitute an ideal hormone biosensor, discuss the use of these sensors in conjunction with in vivo hormone perturbations and highlight the latest discoveries made using these tools.
A facile, versatile hydrogel bioink for 3D bioprinting benefits long-term subaqueous fidelity, cell viability and proliferation
Authors: Chen Hongqing , Fei Fei , Li Xinda , Nie Zhenguo , Zhou Dezhi , Liu Libiao , Zhang Jing , Zhang Haitao , Fei Zhou , Xu Tao 
Published: June 2021

Abstract
Both of the long-term fidelity and cell viability of three-dimensional (3D)-bioprinted constructs are essential to precise soft tissue repair. However, the shrinking/swelling behavior of hydrogels brings about inadequate long-term fidelity of constructs, and bioinks containing excessive polymer are detrimental to cell viability. Here, we obtained a facile hydrogel by introducing 1% aldehyde hyaluronic acid (AHA) and 0.375% N-carboxymethyl chitosan (CMC), two polysaccharides with strong water absorption and water retention capacity, into classic gelatin (GEL, 5%)–alginate (ALG, 1%) ink. This GEL–ALG/CMC/AHA bioink possesses weak temperature dependence due to the Schiff base linkage of CMC/AHA and electrostatic interaction of CMC/ALG. We fabricated integrated constructs through traditional printing at room temperature and in vivo simulation printing at 37°C. The printed cell-laden constructs can maintain subaqueous fidelity for 30 days after being reinforced by 3% calcium chloride for only 20 s. Flow cytometry results showed that the cell viability was 91.38 ± 1.55% on day 29, and the cells in the proliferation plateau at this time still maintained their dynamic renewal with a DNA replication rate of 6.06 ± 1.24%. This work provides a convenient and practical bioink option for 3D bioprinting in precise soft tissue repair.
A Biobehavioral Pain Hygiene Model: Narrative Review and Conceptualization
Authors: Saravanan Anitha , Reagan Louise 
Published: June 2021

Objectives:
Chronic pain frequently coexists with other distressing symptoms (depressive mood, sleep disturbance, fatigue, and stress) and maladaptive beliefs (fear avoidance and pain catastrophizing) that together are linked with increased pain severity and interference, poor function, and quality of life. Although a tremendous amount of research has been conducted to identify risk factors and treatment targets for managing pain, too often the strategies are not combined in a way to make them useful for daily multimodal application. The purpose of this narrative review is to examine the existing literature on the co-occurring symptoms and maladaptive beliefs, lifestyle, and socioenvironmental factors associated with chronic pain and the current nonpharmacological treatment strategies designed to help patients manage chronic pain.

Methods:
Literature databases PubMed/Medline, CINAHL, and PsycINFO were searched to review the evidence on treatment strategies that have evidence of effectiveness in managing chronic pain and co-occurring symptoms. Conceptual models of chronic pain and nonpharmacological pain management strategies were reviewed.

Results:
Evidence was found in support of cognitive-behavioral, lifestyle, and socioenvironmental factors and treatment strategies that are effective in managing chronic pain and co-occurring symptoms. The key factors identified and proposed include lifestyle factors (physical activity, diet, maintaining body weight, keeping a routine, and sleep habits), planned phases of activities (relaxing, pacing, and meditation at regular intervals), CBT strategies (stretching, breathing, meditation, and stress reduction), socioenvironmental factors (keeping a calm, peaceful, environment), and positive support system. On the basis of this evidence, a biobehavioral pain hygiene model is proposed that combines existing strategies in managing pain to make them useful for daily multimodal application and which may be used to integrate therapeutic interventions for chronic pain management.

Discussion:
Given the dearth of research on integrative multimodal pain management, this review and the biobehavioral pain hygiene model could drive future research in the management of chronic pain. Identification of the key strategies and combining them to be a useful multimodal application will be a first step toward identifying innovative methods that could help improve pain and function in patients with chronic pain.
Long-term Clinical Outcomes of Microendoscopic Laminotomy for Cervical Spondylotic Myelopathy
Authors: Minamide Akihito , Yoshida Munehito , Nakagawa Yukihiro , Okada Motohiro , Takami Masanari , Iwasaki Hiroshi , Tsutsui Shunji , Kozaki Takuhei , Murata Shizumasa , Taiji Ryo , Murakami Kimihide , Hashizume Hiroshi , Yukawa Yasutsugu , Taneichi Hiroshi , Yamada Hiroshi , Schoenfeld Andrew J. , Simpson Andrew K. 
Published: June 2021

Study Design:
This was a retrospective cohort study.

Objective:
The objective of this study was to characterize the long-term clinical and radiographic results of articular segmental decompression surgery using endoscopy [cervical microendoscopic laminotomy (CMEL)] for cervical spondylotic myelopathy (CSM) and to compare outcomes to conventional expansive laminoplasty (ELAP).

Summary of Background Data:
The spinal cord compression in CSM consists of a pincer mechanism due to bulging disk and a hypertrophied ligamentum flavum. The long-term clinical benefits of segmental decompression surgery, which removes the dorsal compressive elements of articular segment in CSM patients, have not yet been elucidated.

Materials and Methods:
Consecutive patients with CSM who required surgical treatment were enrolled. All enrolled patients (n=81) underwent CMEL or ELAP. All patients were followed postoperatively for >5 years. The preoperative and 5-year follow-up evaluation included neurological assessment [Japanese Orthopaedic Association (JOA) score], JOA recovery rates, axial neck pain (visual analog scale), and cervical sagittal alignment (C2–C7 subaxial cervical angle).

Results:
Sixty-four patients (CMEL group: 33, ELAP group: 31) were included for analysis. The preoperative JOA score was 10.1 points in the CMEL group and 11.1 points in the ELAP group (P=0.15). The JOA recovery rates were similar, 58.6% in the CMEL group and 55.2% in the ELAP group (P=0.55). The axial neck pain in the CMEL group was significantly lower than that in the ELAP group (P<0.01). At 5-year follow-up, cervical alignment was more favorable in the CMEL group, with an average 2.9 degrees gain in lordosis [vs. 2.3 degrees loss of lordosis in the ELAP group (P<0.05)] and lower incidence of postoperative kyphosis.

Conclusions:
CMEL is a novel, less invasive, technique that allows for multilevel posterior cervical decompression for treatment of CSM. Our 5-year follow-up data demonstrates that patients after CMEL have similar neurological outcomes to conventional laminoplasty, with significantly less postoperative axial pain and improved subaxial cervical lordosis when compared with their traditional laminoplasty counterparts.
Time to Lung Volume Stability After Pressure Change During High-Frequency Oscillatory Ventilation
Authors: Tingay David G. , Kiraly Nicholas , Mills John F. , Dargaville Peter A. 
Published: June 2021

OBJECTIVES:
Clinicians have little guidance on the time needed before assessing the effect of a mean airway pressure change during high-frequency oscillatory ventilation. We aimed to determine: 1) time to stable lung volume after a mean airway pressure change during high-frequency oscillatory ventilation and 2) the relationship between time to volume stability and the volume state of the lung.

DESIGN:
Prospective observational study.

SETTING:
Regional quaternary teaching hospital neonatal ICU.

PATIENTS:
Thirteen term or near-term infants receiving high-frequency oscillatory ventilation and muscle relaxants.

INTERVENTIONS:
One to two cm H2O mean airway pressure changes every 10 minutes as part of an open lung strategy based on oxygen response.

MEASUREMENTS AND MAIN RESULTS:
Continuous lung volume measurements (respiratory inductive plethysmography) were made during the mean airway pressure changes. Volume signals were analyzed with a biexponential model to calculate the time to stable lung volume if the model R
2 was greater than 0.6. If volume stability did not occur within 10 minutes, the model was extrapolated to maximum 3,600 s. One-hundred ninety-six mean airway pressure changes were made, with no volume change in 33 occurrences (17%). One-hundred twenty-five volume signals met modeling criteria for inclusion; median (interquartile range) R
2, 0.96 (0.91–0.98). The time to stable lung volume was 1,131 seconds (718–1,959 s) (mean airway pressure increases) and 647 seconds (439–1,309 s) (mean airway pressure decreases), with only 17 (14%) occurring within 10 minutes and time to stability being longer when the lung was atelectatic.

CONCLUSIONS:
During high-frequency oscillatory ventilation, the time to stable lung volume after a mean airway pressure change is variable, often requires more than 10 minutes, and is dependent on the preceding volume state.
CLASSIFYING ABCA4 MUTATION SEVERITY USING AGE-DEPENDENT ULTRA-WIDEFIELD FUNDUS AUTOFLUORESCENCE-DERIVED TOTAL LESION SIZE
Authors: Heath Jeffery Rachael C. , Thompson Jennifer A. , Lamey Tina M. , McLaren Terri L. , McAllister Ian L. , Constable Ian J. , Mackey David A. , De Roach John N. , Chen Fred K. 
Published: June 2021

Purpose:
To establish a mutation-specific age-dependent ultra-widefield fundus autofluorescence (UWF-FAF) trajectory in a large Stargardt disease (STGD1) cohort using total lesion size (TLS) and to develop a clinical method for variant classification.

Methods:
A retrospective study of patients with biallelic ABCA4 mutations that were evaluated with UWF-FAF. Boundaries of TLS, defined by stippled hyper/hypoautofluorescence, were outlined manually. Pathogenicity was assessed according to ACMG/AMP criteria, and mutation severities were classified based on the current literature. Age-dependent trajectories in TLS were examined in patients with nullizygous, mild, and intermediate mutations. Mutations of uncertain severities were classified using a clinical criterion based on age of symptom onset and TLS.

Results:
Eighty-one patients with STGD1 (mean age = 42 ± 20 years and mean visual acuity = 20/200) were recruited from 65 unrelated families. Patients with biallelic null/severe variants (n = 6) demonstrated an increase in TLS during their second decade reaching a mean ± SD of 796 ± 29 mm2 by age 40. Those harboring mild mutations c.5882G>A or c.5603A>T had lesions confined to the posterior pole with a mean ± SD TLS of 30 ± 39 mm2. Intermediate mutations c.6079C>T or c.[2588G>C;5603A>T] in trans with a null/severe mutation had a mean ± SD TLS of 397 ± 29 mm2. Thirty-two mutations were predicted to cause severe (n = 22), intermediate (n = 6), and mild (n = 5) impairment of ABCA4 function based on age of symptom onset and TLS.

Conclusion:
Age-dependent TLS showed unique ABCA4 mutation-specific trajectories. Our novel clinical criterion using age of symptom onset and TLS to segregate ABCA4 mutations into three severity groups requires further molecular studies to confirm its validity.
Craving Moderates the Effects of Intranasal Oxytocin on Anger in Response to Social Stress Among Veterans With Co-Occurring Posttraumatic Stress Disorder and Alcohol Use Disorder
Authors: Melkonian Alexander J. , Flanagan Julianne C. , Calhoun Casey D. , Hogan Jasara N. , Back Sudie E. 
Published: June 2021

Abstract

Purpose/Background
Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) commonly co-occur among US military veterans. Oxytocin may have therapeutic value in treating both conditions. The potential for oxytocin to augment affective features common to PTSD and AUD, such as anger, is relevant to inform emerging treatments.

Methods/Procedures
We examined the influence of intranasally administered oxytocin on connections between alcohol craving and stress-induced anger in a sample of 73 veterans (91.3% men) with co-occurring PTSD and AUD. Participants self-administered oxytocin (40 IU) or placebo (saline) 45 minutes before completing the Trier Social Stress Task (TSST). Self-reports of alcohol craving and anger were assessed pre- and post-TSST using a modified visual analog scale. Multiple regression analysis, including main effects for group, baseline craving, and their interaction, was used to predict post-TSST anger.

Findings/Results
A marginally significant interaction was observed, suggesting a positive association between baseline craving and anger for those in the oxytocin group (B = 0.65, P = 0.01). Among those reporting low craving, participants in the oxytocin group reported significantly lower post-TSST anger than those in the placebo group.

Implications/Conclusions
The current study is among the first to examine relevant psychosocial moderators that may influence the effects of oxytocin among veterans with comorbid PTSD and AUD. Although oxytocin attenuated ratings of anger after a stress task among those with low baseline craving, findings suggest that oxytocin may not be as effective at reducing anger, a highly salient factor in PTSD, for individuals experiencing high levels of craving. Findings are consistent with the social salience hypothesis and suggest that individual differences in alcohol craving should be considered when evaluating oxytocin as a potential treatment for individuals with comorbid PTSD and AUD.
Waldenstrom's macroglobulinemia with peripheral neuropathy and favorable long-term treatment responses
Authors: Cabacang Mary Lou Anne Y. , Rosales Raymond L. 
Published: June 2021

Abstract

Rationale:
Waldenstrom's Macroglobulinemia (WM), is a rare hematological disorder with an indolent course that affects about 1 in 1,000,000 people over the age of 50. The two cases presented here highlight the favorable responses to targeted therapies and that such responses may show a longer progression-free survival than the standard regimens for WM (Dexamethasone + Rituximab + Cyclophosphamide and Bendamustine + Rituximab).

Patient concerns:
We report 2 Filipino patients with WM presenting with symptoms of peripheral nerve involvement characterized by numbness, dysesthesia and weakness.

Diagnosis:
Serum immunoelectrophoresis showed distinct bands in IgM and Kappa light chain channels, indicative of IgM kappa monoclonal gammopathy. Bone marrow aspirate flow cytometry showed a B-lymphoid population, bright expression of Kappa light chain surface immunoglobulin, all consistent with a B-cell neoplasm.

Interventions:
The first case received Dexamethasone + Rituximab + Cyclophosphamide. The second case was successfully treated with Rituximab + Bendamustine.

Outcomes:
The first case achieved complete remission for 9 years. However, in the 10th year of follow-up, there was recurrence of peripheral nerve symptomatology, which prompted a repeat course Rituximab monotherapy, with favorable response. The second case was successfully treated with Rituximab + Bendamustine over a 3-year course.

Lessons:
To the best of our knowledge, WM presenting with peripheral neuropathy with a long progression-free survival as described in these patients have not been reported before. The two cases highlight the potentially favorable responses to targeted therapies. Though the possibility of developing recurrence cannot be discounted, favorable outcomes with the use of the standard chemotherapies could still be expected.
OFF-periods reduce the complexity of neocortical activity during sleep
Authors: González Joaquín , Cavelli Matias , Tort Adriano BL , Torterolo Pablo , Rubido Nicolás 
Published: June 2021

AbstractComplexity of electroencephalographic signals decreases during slow-wave sleep (SWS), however, the neural mechanism for this decrease remains elusive. Here, we show that this complexity reduction is caused by synchronous neuronal OFF-periods. We analyse in-vivo recordings from neocortical neuronal populations, finding that OFF-periods in SWS trap cortical dynamics, making the population activity more recurrent, deterministic, and less chaotic than during REM sleep or Wakefulness. Importantly, when we exclude OFF-periods, SWS becomes indistinguishable from Wakefulness or REM sleep. In fact, we show that spiking activity for all states has a universal scaling compatible with critical phenomena. We complement these results by a critical branching model that replicates our experimental findings, where we show that forcing OFF-periods to a percentage of neurons suffices to generate a decrease in complexity that replicates SWS.
A TPR scaffold couples signal detection to OdhI phosphorylation in metabolic control by the protein kinase PknG
Authors: Lisa María-Natalia , Sogues Adrià , Barilone Nathalie , Baumgart Meike , Gil Magdalena , Graña Martín , Durán Rosario , Biondi Ricardo M. , Bellinzoni Marco , Bott Michael , Alzari Pedro M. 
Published: June 2021

ABSTRACTSignal transduction is essential for bacteria to adapt to changing environmental conditions. Among many forms of post-translational modifications, reversible protein phosphorylation has evolved as a ubiquitous molecular mechanism of protein regulation in response to specific stimuli. The Ser/Thr protein kinase PknG modulates the fate of intracellular glutamate by controlling the phosphorylation status of the 2-oxoglutarate dehydrogenase regulator OdhI, a function that is conserved among diverse actinobacteria. PknG has a modular organization characterized by the presence of regulatory domains surrounding the catalytic domain. Here we present an investigation through in vivo experiments as well as biochemical and structural methods of the molecular bases of the regulation of PknG from C. glutamicum (CgPknG), in the light of previous knowledge available for the kinase from M. tuberculosis (MtbPknG). We found that OdhI phosphorylation by CgPknG is regulated by a conserved mechanism that depends on a C-terminal domain composed of tetratricopeptide repeats (TPR) essential for metabolic homeostasis. Furthermore, we identified a conserved structural motif that physically connects the TPR domain and a flexible N-terminal extension of the kinase that is involved in docking interactions with OdhI. Based on our results and previous reports, we propose a model in which the TPR domain of PknG couples signal detection to the specific phosphorylation of OdhI. Overall, the available data indicate that conserved PknG domains in distant actinobacteria retain their roles in kinase regulation in response to nutrient availability.IMPORTANCEBacteria control the metabolic processes by which they obtain nutrients and energy in order to adapt to the environment. In this way, the metabolic characteristics of a microorganism determine its ecological role and its usefulness in industrial processes. Here, we use genetic, biochemical, and structural approaches to study a key component in a system that regulates glutamate production in C. glutamicum, a species that is used for the industrial production of amino acids. We elucidated molecular mechanisms involved in metabolic control in C. glutamicum, which are conserved in related pathogenic bacteria. The findings have broader significance for diverse actinobacteria, including microorganisms that cause disease as well as environmental species used to produce billions of dollars of amino acids and antibiotics every year.
Evolution of the open-access CIViC knowledgebase is driven by the needs of the cancer variant interpretation community
Authors: Krysiak Kilannin , Danos Arpad M , Kiwala Susanna , McMichael Joshua F , Coffman Adam C , Barnell Erica K , Sheta Lana , Saliba Jason , Grisdale Cameron J , Kujan Lynzey , Pema Shahil , Lever Jake , Spies Nicholas C , Chiorean Andreea , Rieke Damian T , Clark Kaitlin A , Jani Payal , Takahashi Hideaki , Horak Peter , Ritter Deborah I , Zhou Xin , Ainscough Benjamin J , Delong Sean , Lamping Mario , Marr Alex R , Li Brian V , Lin Wan-Hsin , Terraf Panieh , Salama Yasser , Campbell Katie , Farncombe Kirsten M , Ji Jianling , Zhao Xiaonan , Xu Xinjie , Kanagal-Shamanna Rashmi , Cotto Kelsy C , Skidmore Zachary L , Walker Jason R , Zhang Jinghui , Milosavljevic Aleksandar , Patel Ronak Y , Giles Rachel H , Kim Raymond H , Schriml Lynn M , Mardis Elaine R , Jones Steven JM , Raca Gordana , Rao Shruti , Madhavan Subha , Wagner Alex H , Griffith Obi L , Griffith Malachi 
Published: June 2021

AbstractCIViC (Clinical Interpretation of Variants in Cancer;civicdb.org) is a crowd-sourced, public domain knowledgebase composed of literature-derived evidence characterizing the clinical utility of cancer variants. As clinical sequencing becomes more prevalent in cancer management, the need for cancer variant interpretation has grown beyond the capability of any single institution. With nearly 300 contributors, CIViC contains peer-reviewed, published literature curated and expert-moderated into structured data units (Evidence Items) that can be accessed globally and in real time, reducing barriers to clinical variant knowledge sharing. We have extended CIViC’s functionality to support emergent variant interpretation guidelines, increase interoperability with other variant resources, and promote widespread dissemination of structured curated data. To support the full breadth of variant interpretation from basic to translational, including integration of somatic and germline variant knowledge and inference of drug response, we have enabled curation of three new evidence types (predisposing, oncogenic and functional). The growing CIViC knowledgebase distributes clinically-relevant cancer variant data currently representing >2500 variants in >400 genes from >2800 publications.