bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the Nottingham Hip Fracture Score (NHFS) for the prediction of 30‐day mortality in a Swedish cohort of hip fractures
Authors: Olsen Fredrik , Lundborg Fredrika , Kristiansson Johan , Hård af Segerstad Mathias , Ricksten Sven‐Erik , Nellgård Bengt 
Published: August 2021

AbstractBackgroundHip fracture is a common osteoporotic fracture with great morbidity and mortality. The utility of ASA classification is limited, as most patients are ≥ASA 3. A reliable predictor of mortality risk could support decision‐making. We aimed to evaluate Nottingham hip fracture score (NHFS) for the prediction of 30‐day mortality and then to recalibrate the formula converting NHFS to risk of 30‐day mortality.MethodsAll patients >60 years with surgically treated hip fracture surgery during 2015–16 were assessed. Data was extracted manually from routinely collected clinical data in registry and medical records. Discriminative performance of NHFS and ASA was assessed with C‐statistics. The conversion formula from NHFS to risk of 30‐day mortality was recalibrated using logistic binominal regression. Observed vs expected ratios of 30‐day mortality were compared with the 2012 NHFS‐formula and recalibration was performed in a split dataset.Results1864 patients were included, with 213 deaths within 30 days. C‐statistic were 0.64 for NHFS and 0.62 for ASA. Comparing expected values from the 2012‐revision with our observed deaths gave a ratio of 1.37. Relating predicted levels of 30‐day mortality based on 70% of our cohort vs. 30% test portion of our Swedish dataset gave a ratio of 0.97.DiscussionNHFS underestimated mortality in our cohort and showed poor discrimination. Revision of the formula based on a split dataset improved calibration. We suggest NHFS to be routinely implemented to support clinical judgements, expand preoperative assessment and escalate intraoperative monitoring.
The antagonistic pleiotropy of insulin‐like growth factor 1
Authors: Zhang William B. , Ye Kenny , Barzilai Nir , Milman Sofiya 
Published: August 2021

AbstractWhile insulin‐like growth factor‐1 (IGF‐1) is a well‐established modulator of aging and longevity in model organisms, its role in humans has been controversial. In this study, we used the UK Biobank (n = 440,185) to resolve previous ambiguities in the relationship between serum IGF‐1 levels and clinical disease. We examined prospective associations of serum IGF‐1 with mortality, dementia, vascular disease, diabetes, osteoporosis, and cancer, finding two generalized patterns: First, IGF‐1 interacts with age to modify risk in a manner consistent with antagonistic pleiotropy; younger individuals with high IGF‐1 are protected from disease, while older individuals with high IGF‐1 are at increased risk for incident disease or death. Second, the association between IGF‐1 and risk is generally U‐shaped, indicating that both high and low levels of IGF‐1 may be detrimental. With the exception of a more uniformly positive relationship between IGF‐1 and cancer, these effects were remarkably consistent across a wide range of conditions, providing evidence for a unifying pathway that determines risk for most age‐associated diseases. These data suggest that IGF‐1 signaling could be harmful in older adults, who may actually benefit from the attenuation of biological growth pathways.
MeCP2 prevents age‐associated cognitive decline via restoring synaptic plasticity in a senescence‐accelerated mouse model
Authors: Huang Jin‐Lan , Zhang Fan , Su Min , Li Jiaxin , Yi Wen , Hou Li‐Xiang , Yang Si‐Man , Liu Jin‐Yuan , Zhang Hao‐An , Ma Tengfei , Wu Deng‐Pan 
Published: August 2021

AbstractAge‐related cognitive decline in neurodegenerative diseases, such as Alzheimer's disease (AD), is associated with the deficits of synaptic plasticity. Therefore, exploring promising targets to enhance synaptic plasticity in neurodegenerative disorders is crucial. It has been demonstrated that methyl‐CpG binding protein 2 (MeCP2) plays a vital role in neuronal development and MeCP2 malfunction causes various neurodevelopmental disorders. However, the role of MeCP2 in neurodegenerative diseases has been less reported. In the study, we found that MeCP2 expression in the hippocampus was reduced in the hippocampus of senescence‐accelerated mice P8 (SAMP8) mice. Overexpression of hippocampal MeCP2 could elevate synaptic plasticity and cognitive function in SAMP8 mice, while knockdown of MeCP2 impaired synaptic plasticity and cognitive function in senescence accelerated‐resistant 1 (SAMR1) mice. MeCP2‐mediated regulation of synaptic plasticity may be associated with CREB1 pathway. These results suggest that MeCP2 plays a vital role in age‐related cognitive decline by regulating synaptic plasticity and indicate that MeCP2 may be promising targets for the treatment of age‐related cognitive decline in neurodegenerative diseases.
Emergency medicine research: 2030 strategic goals
Authors: Neumar Robert W. , Blomkalns Andra L. , Cairns Charles B. , D’Onofrio Gail , Kuppermann Nathan , Lewis Roger J. , Newgard Craig D. , O’Neil Brian J. , Rathlev Niels K. , Rothman Richard E. , Wright David W. 
Published: August 2021

AbstractAll academic medical specialties have the obligation to continuously create new knowledge that will improve patient care and outcomes. Emergency medicine (EM) is no exception. Since its origins over 50 years ago, EM has struggled to fulfill its research mission. EM ranks last among clinical specialties in the percentage of medical school faculty who are National Institutes of Health (NIH)‐funded principal investigators (PIs; 1.7%) and the percentage of medical school departments with NIH‐funded PIs (33%). Although there has been a steady increase in the number of NIH‐funded projects and total NIH dollars, the slowing growth in the number of NIH‐funded PIs and lack of growth in the number of EM departments with NIH‐funded PIs is cause for concern. In response, the Association of Academic Chairs of Emergency Medicine (AACEM) Research Task Force proposes a set of 2030 strategic goals for the EM research enterprise that are based on sustaining historic growth rates in NIH funding. These goals have been endorsed by the AACEM Executive Committee and the boards of Society for Academic Emergency Medicine (SAEM), American College of Emergency Physicians (ACEP), and American Academy of Emergency Medicine (AAEM). The 2030 strategic goals include 200 NIH‐funded projects led by 150 EM PIs in at least 50 EM departments with over $100M in annual funding resulting in over 3% of EM faculty being NIH‐funded PIs. Achieving these goals will require a targeted series of focused strategies to increase the number of EM faculty who are competitive for NIH funding. This requires a coordinated, intentional effort with investments at the national, departmental, and individual levels. These efforts are ideally led by medical school department chairs, who can create the culture and provide the resources needed to be successful. The specialty of EM has the obligation to improve the health of the public and to fulfill its research mission.
Paternal alcohol exposure reduces acquisition of operant alcohol self‐administration and affects Bdnf DNA methylation in male and female offspring
Authors: Nieto Steven J. , Haile Colin N. , Quave Cana B. , Harding Mark J. , Nielsen David A. , Meisch Richard A. , Kosten Therese A. 
Published: August 2021

AbstractFamilial transmission of alcohol use disorder reflects genetic and environmental factors. Paternal alcohol exposure may affect rodent offspring via epigenetic modifications transmitted through the male germ line. While such exposure alters alcohol sensitivity in mouse offspring, no studies examined if it impacts the development of operant alcohol self‐administration in rats. We exposed male (sires) Wistar rats to chronic intermittent ethanol in vapour chambers (16 h/day; 5 days/week) or to air for 6 weeks. Eight weeks later, rats were mated with alcohol‐naive females. Adult alcohol‐ and control‐sired F1 offspring were assessed in acquisition of alcohol self‐administration in which increasing alcohol concentrations (2.5%, 5% and 10%, v/v) were delivered after one lever press (fixed ratio 1 or FR1). Prior to alcohol sessions, rats were trained to lever press for food delivery under an FR1 schedule of reinforcement. DNA methylation levels of the brain derived neurotrophic factor (Bdnf) gene were measured in sperm, nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) in sires and in offspring. Alcohol‐exposed sires had lower Bdnf DNA methylation levels in NAc and greater methylation levels in mPFC. Although this pattern was not recapitulated in offspring, alcohol‐sired offspring of both sexes did show aberrant Bdnf DNA methylation patterns compared to control‐sired offspring. Alcohol‐sired offspring self‐administered less alcohol (5% and 10%) with no group differences in food responding. Results indicate that paternal alcohol exposure prior to conception protects against alcohol's initial reinforcing effects but the pattern of dysregulated Bdnf methylation in reward‐related circuitry did not mimic changes seen in sires.
Transforming routinely collected residential aged care provider data into timely information: Current and future directions
Authors: Seaman Karla L. , Jorgensen Mikaela L. , Raban Magdalena Z. , Lind Kimberly E. , Bell J Simon , Westbrook Johanna I. 
Published: August 2021

AbstractElectronic information systems are becoming increasingly common in residential aged care in Australia. These systems contain valuable data generated during day‐to‐day care delivery for older adults. These data (termed ‘routinely collected residential aged care provider data’) are currently underutilised, however have potential significant benefits for both care delivery and research purposes. Routinely collected residential aged care provider data are more readily accessible, contain up‐to‐date information and can be linked to existing national or state‐based administrative data sets, while providing more granular details about care delivered at the coalface. The aim of this paper is to provide clinicians, researchers, policymakers and providers with an understanding of the strengths of these types of data, as well as identifying areas that require future development to maximise their potential to drive improvements in resident care and outcomes. These considerations include data quality, data standardisation and models for data governance, consent and consumer involvement.
Maternal and fetal safety of intravenous immunoglobulin in women with reproductive failure
Authors: Han Aera , Lee Sung Ki , Park Joon Cheol , Park Chan Woo , Han Jae Won , Lee Ki Hwan 
Published: August 2021

AbstractProblemIntravenous immunoglobulin G (IVIG) is an emerging regimen for women with reproductive failures (RF) during‐ or pre‐pregnancy who have aberrant cellular immune reactions. Studies investigating teratogenicity of IVIG have been limited. Herein, we evaluated the fetal teratogenicity of IVIG and IVIG‐related obstetric complications.Method of studyWomen who used IVIG during pregnancy due to RF with cellular immune aberrances were enrolled from four medical centers in Korea. The pregnancy outcomes were collected.ResultsA total of 370 RF women who used IVIG during their pregnancy were enrolled. Most of the patients started the IVIG therapy before 12 weeks of gestation and 229 women continued IVIG treatment beyond 12 weeks of gestation. The mean age of the subjects was 34.8 years and the mean total dosage of IVIG was 125.3 g. A total of 307 women had livebirths and six of them were twins. Of 301 singleton livebirths, obstetric complications were developed as follows: preterm births (12.0%), gestational diabetes (7.0%), preeclampsia (4.0%), placental abruption (1.3%), placenta previa (4.3%), and placenta accrete (1.7%). Total six cases (1.99%) had major fetal anomalies in livebirths. The incidence of birth defects is similar to those of the general population in Korea and the previous report in infertile women. No IVIG ‐related viral contamination was noted.ConclusionIVIG use during pregnancy did not increase obstetric complications and fetal teratogenicity. This study can be an evidence of maternal and fetal safety of IVIG administration during pregnancy.
Vascular biomarkers from optical coherence tomography angiography and glaucoma: where do we stand in 2021?
Authors: Shin Joshua D. , Wolf Amber T. , Harris Alon , Verticchio Vercellin Alice , Siesky Brent , Rowe Lucas W. , Packles Michelle , Oddone Francesco 
Published: August 2021

AbstractBiomarkers of ocular blood flow originating from a wide variety of imaging modalities have been associated with glaucoma onset and progression for many decades. Advancements in imaging platforms including optical coherence tomography angiography (OCTA) have provided the ability to quantify vascular changes in glaucoma patients, alongside traditional measures such as retinal nerve fibre layer thickness and optic nerve head structure. Current literature on vascular biomarkers, as measured by OCTA, indicates significant relationships between glaucoma and blood flow and capillary density in the retina and ONH. The data currently available, however, are highly diverse and lack robust longitudinal data on OCTA vascular outcomes and glaucoma progression. Herein we discuss and summarize the relevant current literature on OCTA vascular biomarkers and glaucoma reviewed through March 1, 2021. Associations between OCTA vascular biomarkers and clinical structural and functional glaucoma outcomes as well as differences between glaucoma patients and healthy controls are reviewed and summarized. The available data identify significantly decreased flow density, flow index and vessel density in the ONH, peripapillary vascular layer and macula of glaucoma patients compared with controls. Whole image vessel density is also significantly decreased in glaucoma patients compared with controls, and this outcome has been found to correspond to severity of visual field loss. OCTA vascular biomarkers alongside clinical structural outcomes may aid in assessing overall risk for glaucoma in patients.
Familial confounding affected the associations between maternal smoking during pregnancy and offspring speech and language, scholastic and coordination disorders
Authors: Arrhenius Bianca , Sariaslan Amir , Suominen Auli , Sourander Andre , Gyllenberg David 
Published: August 2021

AbstractAimThis study examined the associations between prenatal smoking and speech and language, scholastic, coordination and mixed developmental disorders in offspring, using sibling and population controls.MethodsNational Finnish registers were used to identify all 690 654 singletons born between 1996 and 2007 and any cases diagnosed with speech and language, scholastic, coordination and mixed developmental disorders by the end of 2012. Cases were compared to population controls, biological full‐siblings and maternal half‐siblings born during the same period. Conditional logistic regression was used to assess any associations between smoking during pregnancy and the selected developmental disorders.ResultsPrenatal smoking was higher in the mothers of the 27 297 cases (21.7%) than the 99 876 population controls (14.5%). The adjusted odds ratio for smoking throughout pregnancy, and any diagnosis of speech and language, scholastic, coordination or mixed developmental disorders, was 1.29 (95% confidence interval 1.24–1.34). However, when we compared a subsample of 15 406 cases and their 20 657 siblings, the association was no longer statistically significant (odds ratio 1.09, 95% confidence interval 0.98–1.21).ConclusionThe sibling comparisons suggested that the associations between prenatal smoking and speech and language, scholastic, coordination and mixed developmental disorders were confounded by familial factors shared by differentially exposed siblings.
Towards a Solution to the Variety in Accounting Practices of Extractive Firms under IFRS
Authors: Nobes Christopher , Stadler Christian 
Published: August 2021

AbstractAccounting for exploration and evaluation (E&E) costs is one of the last major issues to remain largely unregulated by International Financial Reporting Standards (IFRS), even though extractive firms are an important part of several big stock markets. Under a temporary permissive standard (IFRS 6), which has been in place since 2004, firms use a wide range of accounting policies for E&E costs, thus undermining comparability. We review the IFRS annual reports of a large number of firms, looking for different policies. We identify many distinguishable methods of accounting. Along with this, we discover that disclosures are often confusing, partly because of the lack of definitions in IFRS 6. To aid insight into this complexity, we prepare a classification of these methods and give real examples of each. We then assess the methods in the context of IFRS 6 and other relevant parts of IFRS. We find that nearly all the methods comply with IFRS. This leads us to a proposal for narrowing the variety of practice by withdrawing IFRS 6, and putting E&E costs within the scope of IAS 38 Intangible Assets. As part of this, IAS 38 could be further revised to extend the scope of capitalisation of other development costs, thereby addressing one of the criticisms of current reporting practice and bringing IAS 38 more into line with the latest version of the Conceptual Framework.
Cultural competence and experiences of maternity health care providers on care for migrant women: A qualitative meta‐synthesis
Authors: Shorey Shefaly , Ng Esperanza Debby , Downe Soo 
Published: August 2021

AbstractBackgroundThe United Nations Sustainable Development Goals 2030 aim to reduce health care inequity and maternal and infant mortality rates amongst marginalized populations. To provide adequate and culturally relevant maternity care for minority ethnic groups, it is imperative to examine health care providers' views on care for migrant women. We reviewed published accounts of views and experiences of maternity health care providers providing maternity care for migrant women as a way of exploring their cultural competency.MethodA qualitative meta‐synthesis was conducted. Systematic searches were conducted in five electronic databases from inception dates through February 2021. Qualitative data were analyzed using a framework thematic analysis based on Campinha‐Bacote's five‐component cultural competency model.FindingsEleven studies were included. Findings were presented according to Campinha‐Bacote's model: cultural awareness, cultural knowledge (personal responsibility, familial role and cultural influence, the influence of social and system factors, conflicting maternity care expectations), cultural encounter (language and communication), and cultural desire (establishing trust and going the extra mile, resources to boost culturally competent care).DiscussionOur findings can inform the design of high‐quality behavioral change, health care management, sociological, and other relevant studies, along with reviews of what matters to service users about cultural responsiveness. Our data also suggest that health system constraints can exacerbate the lack of cultural competency. Improving the quality of care for migrant communities will necessitate a joint effort between health care organizations, health care providers, policymakers, and researchers in developing and implementing more culturally relevant maternity care policies and management interventions.
Involvement of P2Y12 receptors in a nitroglycerin‐induced model of migraine in male mice
Authors: Gölöncsér Flóra , Baranyi Mária , Iring András , Hricisák László , Otrokocsi Lilla , Benyó Zoltán , Sperlágh Beáta 
Published: August 2021

Background and PurposeP2Y12 receptors regulate different forms of pain and inflammation. In this study, we investigated the participation of P2Y12 receptors in an animal model of migraine.Experimental ApproachWe tested the effect of the centrally administered selective P2Y12 antagonist PSB‐0739 and P2Y12 receptor gene (P2ry12‐/‐) deficiency in acute nitroglycerin‐treated mice. Additionally, platelet depletion was used to investigate the role of platelet P2Y12 receptors during migraine‐like pain.Key ResultsNitroglycerin induced sensory hypersensitivity of C57BL/6 wild‐type (P2ry12+/+) mice accompanied by an increase in c‐fos and CGRP expression in the upper cervical spinal cord (C1–C2) and trigeminal nucleus caudalis. Similar changes were also observed in P2Y12 gene‐deficient (P2ry12−/−) mice. Prophylactic intrathecal application of PSB‐0739 reversed thermal hyperalgesia and head grooming time in wild‐type mice but had no effect in P2ry12−/− mice. Furthermore, PSB‐0739 was also effective when applied as a post‐treatment. PSB‐0739 administration suppressed the expression of c‐fos in C1–C2 and trigeminal nucleus caudalis, and decreased the levels of dopamine and 5‐hydroxytryptamine in C1‐C2 in wild‐type mice. Nitroglycerin treatment itself did not change adenosine diphosphate (ADP)‐induced platelet activation measured by CD62P up‐regulation in wild‐type mice. Platelet depletion by anti‐mouse CD41 antibody and clopidogrel attenuated nitroglycerin‐induced thermal hypersensitivity and head grooming time in mice.Conclusion and ImplicationsOur findings show that acute inhibition of P2Y12 receptors alleviates migraine‐like pain in mice by modulating the expression of c‐fos and that platelet P2Y12 receptors might contribute to this effect. Thus the blockade of P2Y12 receptors may have therapeutic potential against migraine.
Remote local photoactivation of morphine produces analgesia without opioid‐related adverse effects
Authors: López‐Cano Marc , Font Joan , Aso Ester , Sahlholm Kristoffer , Cabré Gisela , Giraldo Jesús , De Koninck Yves , Hernando Jordi , Llebaria Amadeu , Fernández‐Dueñas Víctor , Ciruela Francisco 
Published: August 2021

Background and PurposeOpioid‐based drugs are the gold standard medicines for pain relief. However, tolerance and several side effects (i.e. constipation and dependence) may occur upon chronic opioid administration. Photopharmacology is a promising approach to improve the benefit/risk profiles of these drugs. Thus, opioids can be locally activated with high spatiotemporal resolution, potentially minimizing systemic‐mediated adverse effects. Here, we aimed at developing a morphine photo‐derivative (photocaged morphine), which can be activated upon light irradiation both in vitro and in vivo.Experimental ApproachLight‐dependent activity of pc‐morphine was assessed in cell‐based assays (intracellular calcium accumulation and electrophysiology) and in mice (formalin animal model of pain). In addition, tolerance, constipation and dependence were investigated in vivo using experimental paradigms.Key resultsIn mice, pc‐morphine was able to elicit antinociceptive effects, both using external light‐irradiation (hind paw) and spinal cord implanted fibre‐optics. In addition, remote morphine photoactivation was devoid of common systemic opioid‐related undesired effects, namely, constipation, tolerance to the analgesic effects, rewarding effects and naloxone‐induced withdrawal.Conclusion and ImplicationsLight‐dependent opioid‐based drugs may allow effective analgesia without the occurrence of tolerance or the associated and severe opioid‐related undesired effects.LINKED ARTICLESThis article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc