bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Diversity and Thermal Performance in Invasive and Native Populations of African Fig Flies
Authors: Comeault Aaron A , Wang Jeremy , Tittes Silas , Isbell Kristin , Ingley Spencer , Hurlbert Allen H , Matute Daniel R 
Published: February 2020

AbstractDuring biological invasions, invasive populations can suffer losses of genetic diversity that are predicted to negatively impact their fitness/performance. Despite examples of invasive populations harboring lower diversity than conspecific populations in their native range, few studies have linked this lower diversity to a decrease in fitness. Using genome sequences, we show that invasive populations of the African fig fly, Zaprionus indianus, have less genetic diversity than conspecific populations in their native range and that diversity is proportionally lower in regions of the genome experiencing low recombination rates. This result suggests that selection may have played a role in lowering diversity in the invasive populations. We next use interspecific comparisons to show that genetic diversity remains relatively high in invasive populations of Z. indianus when compared with other closely related species. By comparing genetic diversity in orthologous gene regions, we also show that the genome-wide landscape of genetic diversity differs between invasive and native populations of Z. indianus indicating that invasion not only affects amounts of genetic diversity but also how that diversity is distributed across the genome. Finally, we use parameter estimates from thermal performance curves for 13 species of Zaprionus to show that Z. indianus has the broadest thermal niche of measured species, and that performance does not differ between invasive and native populations. These results illustrate how aspects of genetic diversity in invasive species can be decoupled from measures of fitness, and that a broad thermal niche may have helped facilitate Z. indianus’s range expansion.
Zinc exocytosis is sensitive to myosin light chain kinase inhibition in mouse and human eggs
Authors: Lee Hoi Chang , Edmonds Maxwell E , Duncan Francesca E , O’Halloran Thomas V , Woodruff Teresa K 
Published: February 2020

AbstractZinc dynamics are essential for oocyte meiotic maturation, egg activation, and preimplantation embryo development. During fertilisation and egg activation, the egg releases billions of zinc atoms (Zn2+) in an exocytotic event termed the ‘zinc spark’. We hypothesised that this zinc transport and exocytosis is dependent upon the intracellular trafficking of cortical granules (CG) which requires myosin-actin-dependent motors. Treatment of mature mouse and human eggs with ML-7, a myosin light chain kinase inhibitor (MLCK), resulted in an 80% reduction in zinc spark intensity compared to untreated controls when activated with ionomycin. Moreover, CG migration towards the plasma membrane was significantly decreased in ML-7-treated eggs compared with controls when activated parthenogenetically with ionomycin. In sperm-induced fertilisation via intracytoplasmic sperm injection (ICSI), ML-7-treated mouse eggs exhibited decreased labile zinc intensity and cortical CG staining. Collectively, these data demonstrate that ML-7 treatment impairs zinc release from both murine and human eggs after activation, demonstrating that zinc exocytosis requires myosin light chain kinase activity. Further, these results provide additional support that zinc is likely stored and released from CGs. These data underscore the importance of intracellular zinc trafficking as a crucial component of egg maturation necessary for egg activation and early embryo development.
The problem with transferrin saturation as an indicator of iron ‘sufficiency’ in chronic kidney disease
Authors: Besarab Anatole , Drueke Tilman B 
Published: February 2020

Abstract
After a brief review of physiological iron metabolism, we describe diagnostic tests for iron status and iron deficiency anemia in patients without chronic kidney disease (CKD) or inflammation. Thereafter we review the dysregulation of iron metabolism in CKD. Specific emphasis is placed on the role of the ‘inflammatory’ state that develops with the progression of CKD. It invokes changes in iron metabolism that are the exact opposite of those occurring during pure iron deficiency. As a result, transferrin saturation (TSAT) becomes a poorer index of iron availability to the bone marrow and serum ferritin no longer represents iron that can be used during erythropoiesis. We argue that serum iron may provide more information to guide iron therapy than TSAT. In other words, the emphasis on TSAT is misplaced. With the development of a number of hypoxia-inducible factor prolyl hydroxylase inhibitors, which restore iron metabolism toward the ‘physiologic state’, the iron indices indicating sufficient iron availability to avoid functional iron deficiency during therapy of CKD-associated anemia are likely to change. We summarize these changes in the section ‘A peek into things to come!’, citing the available data.
Genomic consequences of population decline in critically endangered pangolins and their demographic histories
Authors: Hu Jing-Yang , Hao Zi-Qian , Frantz Laurent , Wu Shi-Fang , Chen Wu , Jiang Yun-Fang , Wu Hong , Kuang Wei-Min , Li Haipeng , Zhang Ya-Ping , Yu Li 
Published: February 2020

AbstractPangolins are among the most critically endangered animals due to heavy poaching and worldwide trafficking. However, their demographic histories and the genomic consequences of their recent population declines remain unknown. We generated high-quality de novo reference genomes for critically endangered Malayan (Manis javanica, MJ) and Chinese (M. pentadactyla, MP) pangolins and re-sequencing population genomic data from 74 MJs and 23 MPs. We recovered the population identities of illegally traded pangolins and previously unrecognized genetic populations that should be protected as evolutionarily distinct conservation units. Demographic reconstruction suggested environmental changes have resulted in a population size fluctuation of pangolins. Additionally, recent population size declines due to human activities have resulted in an increase in inbreeding and genetic load. Deleterious mutations were enriched in genes related to cancer/diseases and cholesterol homeostasis, which may have increased their susceptibility to diseases and decreased their survival potential to adapt to environmental changes and high-cholesterol diets. This comprehensive study provides not only high-quality pangolin reference genomes, but also valuable information concerning the driving factors of long-term population size fluctuations and the genomic impact of recent population size declines due to human activities, which is essential for pangolin conservation management and global action planning.
Transforming personalized nutrition practice
Authors: Barrow Michelle , Bell Linda , Bell Celia 
Published: February 2020

Abstract
The strengths and limitations of current approaches to clinical nutrition practice and their underpinning research are explored in this article. It describes how a personalized nutrition practice approach supported by evidence-based pathophysiological reasoning could direct additional research, which could then transform practice and support food industry developments. Current use of the term “personalized nutrition” is reviewed and a definition is provided. Also explored are current approaches to personalized nutrition practice and evidence-based practice in clinical nutrition. Patient-centered practice, which involves individuals in their healthcare decisions, is currently being provided under the name “personalized.” An evidence-based personalized practice approach should include the use of robust, standardized, and validated tools that gather a patient’s signs and symptoms, health history, family history, genetics, environment, lifestyle, social life, diet, behavior and other factors that have an impact on physiological processes. It should also gather anthropometric measures as well as functional, diagnostic, and prognostic biomarkers for pathophysiological mechanisms. Such tools would pool n = 1 data into a case-by-case evidence base that uses computational network modelling to predict the efficacy of personalized nutrition interventions. Prediction of the efficacy of interventions should also be validated using, when possible, blinded, randomized, controlled, stratified intervention studies. This model would provide practitioners with data that support evidence-based pathophysiological reasoning. It would enable clinicians to prioritize interventions on the basis of the mechanisms of action of interventions and to ameliorate the mechanisms of pathophysiology, which are a priority for the individual. Interventions then may be applied using a patient-centered practice approach. This would transform evidence-based nutrition practice into a P4 medicine approach that is personalized, preventive, predictive, and participatory. Developing pathophysiological mechanistic understanding also provides new opportunities for stakeholders, including the food industry, researchers, healthcare practitioners, and consumers.
Evaluation of an Interdisciplinary Controlled Substance Review Committee on Opioid Prescribing in a Community Health Center
Authors: Bourgeois Holly C , Proteau Rachel C , Vielma Cassandra V , Hartung Daniel M , Irwin Adriane N 
Published: February 2020

AbstractObjectiveTo describe recommendations made by an interdisciplinary controlled substance committee and acceptance by primary care providers.DesignRetrospective cohort study.SettingMultisite federally qualified health center using an interdisciplinary committee to provide patient-specific recommendations to prescribers with patients using prescription opioids and other controlled substances.SubjectsPatients prescribed long-term opioids.MethodsWe identified and characterized committee recommendations to prescribers between January 1, 2013, and December 31, 2016. We manually reviewed electronic medical records to determine if recommendations were accepted at eight months. The primary outcome was the overall acceptance rate of recommendations. Secondary outcomes were the acceptance of recommendations to reduce opioid doses and change in opioid dose from baseline.ResultsThe committee made 337 recommendations for 94 patients. Of those, 169 recommendations (50.1%) were accepted within eight months. The most common recommendation was to change opioid prescribing (N = 53, 56.4%), but recommendations varied. For patients with a recommendation to change opioid prescribing, this was accepted in 31 of 53 patients (58.5%). Overall, opioid doses decreased from 60 morphine equivalents per day (interquartile range [IQR] = 27.5–135, range = 5–1,260) at baseline to 40 morphine equivalents per day (IQR = 15–105, range = 0–1,260) at eight months (P &lt; 0.001).ConclusionsAn interdisciplinary committee was well positioned to offer primary care providers with nonopioid options to manage chronic nonmalignant pain and provide support in reducing opioid doses. About half of recommendations were accepted by primary care providers. Future research should focus on strategies to improve the utility of this approach and its impact on clinical outcomes.
Advancement in Neuromodulation Technology with the Innovation of Design-Specific Peripheral Nerve Stimulators: Sural Nerve Stimulation for Radiculopathy
Authors: Langford Brendan , Mauck William D 
Published: February 2020

Abstract

Background
Peripheral nerve stimulation (PNS) is a form of neuromodulation that is used to treat chronic and refractory neuropathic pain. Peripheral nerve stimulation was first described in the early 1960s when Shelden implanted a PNS device for trigeminal neuralgia. Despite PNS being known since the 1960s, technology designed specifically for PNS was lacking. Within the past few years, design-specific PNS devices have become widely available, with favorable efficacy and safety profiles. Here we report a case of design-specific PNS that provided two years of pain relief in a patient with lower extremity neuropathic pain.

Case Presentation
A 53-year-old female with a history of congenital lumbar meningocele status post–L4-L5 laminectomy presented to the Mayo Clinic for treatment of foot pain that began three days after her laminectomy. She experienced a 6/10 burning, tingling sensation in the lateral dorsal portion of her right foot and posterolateral calf in addition to allodynia that prevented her from wearing shoes. She failed gabapentin, amitriptyline, cannabis, transforaminal epidural steroid injections, and two spinal cord stimulator trials. The patient ultimately underwent implantation of a right sural nerve stimulator, resulting in a 50% improvement in pain and functionality at two-year follow-up.

Conclusions
This report emphasizes the recent development of design-specific PNS devices and their successful use in this patient. Peripheral nerve stimulation technology and applications have diminished the role of spinal cord stimulation devices used for the periphery. Peripheral nerve stimulation should be considered for patients with isolated extremity pain, especially in those with spinal abnormalities (e.g., arachnoid cyst).
Commitment in Organizations and the Competition for Talent
Authors: Cooley Thomas , Marimon Ramon , Quadrini Vincenzo 
Published: February 2020

Abstract
We show that a change in organizational structure from partnerships to public companies—which weakens contractual commitment—can lead to higher investment in high return-and-risk activities, higher productivity (value added per employee) and greater income dispersion (inequality). These predictions are consistent with the observed evolution of the financial sector where the switch from partnerships to public companies has been especially important in the decades that preceded the 21st Century financial crisis.
Predicting response to topical non-steroidal anti-inflammatory drugs in osteoarthritis: an individual patient data meta-analysis of randomized controlled trials
Authors: Persson Monica S M , Stocks Joanne , Varadi Gyula , Hashempur Mohammad Hashem , van Middelkoop Marienke , Bierma-Zeinstra Sita , Walsh David A , Doherty Michael , Zhang Weiya 
Published: February 2020

AbstractObjectivesTo identify predictors of the specific (difference between treatment and placebo) and overall (change from baseline in treatment arm) treatment effects of topical NSAIDs in OA.MethodsRandomized controlled trials (RCTs) of topical NSAIDs in OA were identified through systematic literature searching and inquiry to pharmaceutical companies. The raw, de-identified data were analysed in one-stage individual patient data meta-analysis (IPD-MA). Negative values for treatment effects (0–100 scale) indicate pain reduction.ResultsOf 63 eligible RCTs, 15 provided IPD (n = 1951 on topical NSAID), including 11 placebo-controlled RCTs (n = 1587 on topical NSAIDs, 1553 on placebo). Seven potential predictors of response were examined. Topical NSAIDs were superior to placebo [−6 (95% CI −9, −4)], with a small, but statistically significant greater effect in women than men [difference −4 (95% CI −8, −1)]. The overall treatment effect was 4-fold larger than the specific effect [−25 (95% CI −31, −19)] and increased with greater baseline pain severity (P &lt; 0.001). No differences in efficacy were observed for age, BMI, features of inflammation, duration of complaints or radiographic OA severity.ConclusionTopical NSAIDs are effective for OA pain relief. Greater overall pain relief in individuals with more baseline pain might be due to contextual and non-specific effects, including regression to the mean. Additional factors that have been linked either mechanistically or through empirical evidence to outcomes should be selected for inclusion across future RCTs in order to facilitate the identification of response predictors through IPD-MA.
Obstetric antiphospholipid syndrome is not associated with an increased risk of subclinical atherosclerosis
Authors: Bettiol Alessandra , Emmi Giacomo , Finocchi Martina , Silvestri Elena , Urban Maria Letizia , Mattioli Irene , Scalera Antonella , Lupoli Roberta , Vannacci Alfredo , Di Minno Matteo Nicola Dario , Prisco Domenico 
Published: February 2020

AbstractObjectivesThe persistent positivity of aPLs, either isolated or associated with thrombotic and/or obstetric events (APS), has been associated with the increase of intima-media thickness (IMT) and carotid plaques. Despite the fact that aPLs can promote both thrombotic and obstetric complications, some pathogenic differences have been documented between the two entities. This study aimed to evaluate whether the atherosclerotic risk differs between subjects with obstetric and thrombotic APS.MethodsA total of 167 APS women (36 obstetric and 131 thrombotic) were compared with 250 aPLs negative controls. IMT of the common carotid artery (CCA) and of the bulb and the prevalence of carotid plaques were assessed.ResultsCCA- and bulb-IMT were significantly higher in women with thrombotic APS, while being similar between the obstetric APS and the controls [CCA-IMT: mean (s.d.) 0.97 (0.49), 0.78 (0.22) and 0.81 (0.12) mm for the thrombotic, obstetric and control groups, respectively, P &lt; 0.001 between thrombotic and controls, P = 0.002 between thrombotic and obstetric; bulb-IMT: mean (s.d.) 1.38 (0.79), 0.96 (0.27) and 0.96 (0.51) mm for the thrombotic, obstetric and control groups, P &lt; 0.001]. Women with thrombotic APS had significantly increased risk of presenting carotid plaques. This risk was significantly lower in obstetric APS.ConclusionUnlike thrombotic APS, obstetric APS is not associated with an increase of markers of subclinical atherosclerosis. If confirmed on wider populations, these results could suggest different pathogenetic role of aPLs in promoting atherosclerosis in vascular and obstetric APS, and raise questions on the risk–benefit profile of thromboprophylaxis in obstetric APS outside pregnancy periods.
Pulmonary adverse events of small molecule JAK inhibitors in autoimmune disease: systematic review and meta-analysis
Authors: Khoo Jun K , Barnes Hayley , Key Seraphina , Glaspole Ian N , Östör Andrew J 
Published: February 2020

Abstract

Objectives
Small molecule tyrosine kinase inhibitors [smTKI, comprising mostly of Janus kinase (JAK) and to a lesser extent, spleen tyrosine kinase (SyK) inhibitors] modulate the cytokine receptor-mediated intracellular signal cascade, and are an effective treatment for autoimmune diseases and malignancies. As smTKI are novel, long-term safety is uncertain. Due to increasing use, characterization of their true adverse event profile is critical.

Methods
We performed a systematic review and meta-analysis of all published trial data on the pulmonary and serious adverse effects of smTKIs in autoimmune disease. EMBASE, MEDLINE, CENTRAL and Pneumotox databases were searched up to April 2019 for randomized controlled trials, observational studies and post marketing surveillance, comparing any smTKI with placebo or another therapy, or as monotherapy at different doses. Primary outcomes comprised of any respiratory complications including upper and lower respiratory tract infections (URTI, LRTI), influenza, pneumonia, opportunistic respiratory infections, drug-induced interstitial lung disease, pulmonary embolism and lung neoplasm.

Results
We identified 4667 citations for screening, and selected 319 studies for full text review. Seventy-nine studies were analysed, including 47 randomized controlled trials, 25 observational studies and seven post-marketing surveillance studies, comprising 159 652 participants. There were significantly increased risks of URTI [risk difference (RD) 0.03; 95% CI: 0.01, 0.05; P = 0.00; 36 studies, 14 724 participants], LRTI (RD 0.01; 95% CI: 0.00, 0.02; P = 0.02; 24 studies, 12 302 participants), influenza (RD 0.01; 95% CI: 0.00, 0.01; P = 0.04; 22 studies, 10 684 participants), and pneumonia (RD 0.00; 95% CI: 0.00, 0.01; P = 0.02; 33 studies, 15 511 participants). No increased risk was found for other respiratory complications, including pulmonary embolism.

Conclusion
SmTKI increases the risk of non-opportunistic respiratory infections compared with placebo. The risk of any serious pulmonary adverse events is low.
New variant in the IL1RN-gene (DIRA) associated with late-onset, CRMO-like presentation
Authors: Kuemmerle-Deschner Jasmin B , Welzel Tatjana , Hoertnagel Konstanze , Tsiflikas Ilias , Hospach Anton , Liu Xiao , Schlipf Susanne , Hansmann Sandra , Samba Samuel D , Griesinger Andreas , Benseler Susanne M , Weber Alexander N 
Published: February 2020

Abstract

Objective
To report a chronic recurrent multifocal osteomyelitis (CRMO)-like clinical phenotype with multisystem inflammation associated with a novel gene variant in the spectrum of IL-1-mediated diseases.

Methods
A 3-year-old boy presented with recurrent episodes of fever, serositis, pancreatitis and high inflammatory markers with onset at age 13 months. At age 3 years, he started limping. Imaging revealed multifocal pelvic bone inflammation suggestive of CRMO. Autoinflammation panel testing was non-contributory. Whole exome sequencing (WES) and advanced IL-1 pathway analysis was conducted.

Results
WES identified a novel homozygous interleukin receptor 1 (IL1RN) variant (c.62C&gt;G; p. Ser21*) (NM_173842.2). Functional analysis of IL1RN mRNA and IL-1 receptor antagonist (IL-1RA) protein confirmed the diagnosis of a deficiency of the IL-1 receptor antagonist (DIRA). Treatment with the nonselective IL-1 inhibitor anakinra resulting in rapid remission; switch to the selective IL-1β antagonist canakinumab led to a flare within 6 weeks. Re-start of anakinra recaptured remission, last documented at the recent 19-month follow-up.

Conclusion
This is the first report of a novel late-onset DIRA confirmed by advanced diagnostic testing. In patients with systemic inflammation and CRMO-like bone lesions, IL1RN testing should be considered; even in the absence of skin manifestations. Non-selective IL-1 inhibition is an effective therapy.
Frequencies and predictors of the Lupus Low Disease Activity State and remission in treatment-naïve patients with systemic lupus erythematosus
Authors: Gao Dai , Hao Yanjie , Mu Lin , Xie Wenhui , Fan Yong , Ji Lanlan , Zhang Zhuoli 
Published: February 2020

Abstract

Objectives
To evaluate the attainability of Lupus Low Disease Activity State (LLDAS) and definitions of remission in SLE (DORIS) in a treatment-naïve cohort of SLE.

Methods
LLDAS5 was defined as LLDAS with a prednisone dose ≤5 mg/day. There were four definitions in DORIS: clinical remission on treatment (RONT), complete RONT, clinical remission off treatment (ROFT) and complete ROFT. The treatment-naïve patients from Peking University First Hospital SLE cohort were enrolled. The time to each state and their annual cumulative probabilities were estimated. The frequencies of patients who achieved each component of LLDAS or DORIS during follow-up were determined. The predictors of time to each state were identified.

Results
A total of 218 patients were included, with a median follow-up of 4.48 years. Respectively, 190 (87.2%), 160 (73.4%), 148 (67.9%), 94 (43.1%), 23 (10.6%) and 18 (8.3%) patients achieved LLDAS, LLDAS5, clinical RONT, complete RONT, clinical ROFT and complete ROFT. The median time to LLDAS, LLDAS5, clinical RONT and complete RONT were 1.4, 2.3, 2.6 and 4.7 years, respectively. Positive anti-dsDNA, RP and anaemia were significantly associated with prolonged time to LLDAS, LLDAS5 or clinical RONT.

Conclusion
Our data confirmed that LLDAS is an attainable early treatment target for SLE. Though with more difficulty, RONT can be achieved in two-thirds of our patients. ROFT may not be an ideal treatment target at present as it is only attained in few patients.