bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are individuals consistent? Endocrine reaction norms under different ecological challenges
Authors: Baldan Davide , Negash Mekail , Ouyang Jenny Q. 
Published: June 2021

ABSTRACT
Quantifying organismal capacity for compensatory mechanisms is essential to forecast responses to environmental change. Despite accumulating evidence for individual variation in physiological plasticity, the causes and consequences of this variation remain unclear. An outstanding question is whether individual reaction norms are consistent across different environmental challenges, i.e. whether an individual that is responsive to one environmental variable will be equally responsive to a different environmental variable. Additionally, are these reaction norms themselves consistent over time, i.e. repeatable? Here, we quantified individual baseline glucocorticoid responses in house sparrows, Passer domesticus, to sequential manipulations of temperature, wind speed and food unpredictability that were repeated in discrete blocks of sampling under both control and stressor-exposed conditions. Individuals significantly decreased their baseline corticosterone levels and increased their mass during treatment exposure. This response was consistent across environmental challenge types. There was high repeatability in the intercept and slope of the baseline corticosterone reaction norm between environmental challenges but broad credible intervals in the repeatability of the reaction norm slope, suggesting that although glucocorticoid levels during baseline conditions are repeatable, among-individual variation in the shape of the glucocorticoid response may be higher than within-individual variation. Within-subject variation in baseline corticosterone levels was mainly explained by within-individual variation in body mass during stressor exposure. Despite the high lability in physiological traits, endocrine plasticity is repeatable across environmental challenges and may be able to evolve as a result of genetic accommodation, in which selection acts on genetic variation of reaction norms.
Telomerase activity can mediate the effects of growth on telomeres during post-natal development in a wild bird
Authors: Noguera Jose C. , Velando Alberto 
Published: June 2021

ABSTRACT
In wild animals, telomere attrition during early development has been linked with several fitness disadvantages throughout life. Telomerase enzyme can elongate telomeres, but it is generally assumed that its activity is suppressed in most somatic tissues upon birth. However, recent evidence suggests that this may not be the case for long-lived bird species. We have therefore investigated whether telomerase activity is maintained during the postnatal growth period in a wild yellow-legged gull (Larus michahellis) population. Our results indicate that telomerase activity is not negligible in the blood cells, but activity levels sharply decline from hatching to fledging following a similar pattern to the reduction observed in telomere length. Our results further suggest that the observed variation in telomere length may be the result of a negative effect of fast growth on telomerase activity, thus providing a new mechanism through which growth rates may affect telomere dynamics and potentially life-history trajectories.
Οι γνώσεις των εκπαιδευτικών προσχολικής αγωγής ως προς τον αυτισμό και οι απόψεις τους απέναντι στη συμπερίληψη παιδιών με αυτισμό
Authors: Γρηγορόπουλος Ηρακλής Νικόλαος , Προβατά Αδαμαντίνη 
Published: June 2021

Σκοπός της παρούσας έρευνας ήταν να διερευνήσει τις γνώσεις εκπαιδευτικών προσχολικής αγωγής ως προς τον αυτισμό και τις απόψεις τους απέναντι στη συμπερίληψη παιδιών με αυτισμό στη γενική τάξη. Στην έρευνα συμμετείχαν 91 εκπαιδευτικοί προσχολικής αγωγής, από την ευρύτερη περιοχή της Δυτικής Μακεδονίας. Για τη διερεύνηση των παραπάνω ερωτημάτων χρησιμοποιήθηκε ένα ερωτηματολόγιο δημογραφικών στοιχείων και το ερωτηματολόγιο Autism Inclusion Questionnaire (AIQ) των Segall & Campbell (2007). Σύμφωνα με τα αποτελέσματα της συγκεκριμένης έρευνας, οι περισσότεροι από τους συμμετέχοντες εκπαιδευτικούς προσχολικής ηλικίας διέθεταν επαρκές επίπεδο γνώσεων, ωστόσο εμφανίζονταν ουδέτεροι απέναντι στη συμπερίληψη των παιδιών με αυτισμό στη γενική τάξη. Επιπλέον, η προηγούμενη εμπειρία τους με παιδιά στο φάσμα του αυτισμού και η επιπλέον επιμόρφωση τους στην ειδική αγωγή δε συσχετίστηκαν με θετικότερες απόψεις απέναντι στη συμπερίληψη των συγκεκριμένων παιδιών. Η διερεύνηση των απόψεων των εκπαιδευτικών μπορεί να συμβάλει ουσιαστικά στον καταλληλότερο σχεδιασμό πρακτικών συμπεριληπτικής εκπαίδευσης
Stage 2 Registered Report: Variation in neurodevelopmental outcomes in children with sex chromosome trisomies: testing the double hit hypothesis
Authors: Newbury Dianne F. , Simpson Nuala H. , Thompson Paul A. , Bishop Dorothy V. M. 
Published: June 2021

Background: The presence of an extra sex chromosome is associated with an increased rate of neurodevelopmental difficulties involving language. The 'double hit' hypothesis proposes that the adverse impact of the extra sex chromosome is amplified when genes that are expressed from the sex chromosomes interact with autosomal variants that usually have only mild effects. We predicted that the impact of an additional sex chromosome on neurodevelopment would depend on common autosomal variants involved in synaptic functions. Methods: We analysed data from 130 children with sex chromosome trisomies (SCTs: 42 girls with trisomy X, 43 boys with Klinefelter syndrome, and 45 boys with XYY). Two comparison groups were formed from 370 children from a twin study. Three indicators of phenotype were: (i) Standard score on a test of nonword repetition; (ii). A language factor score derived from a test battery; (iii) A general scale of neurodevelopmental challenges based on all available information. Preselected regions of two genes, CNTNAP2 and NRXN1, were tested for association with neurodevelopmental outcomes using Generalised Structural Component Analysis. Results: There was wide phenotypic variation in the SCT group, as well as overall impairment on all three phenotypic measures. There was no association of phenotype with CNTNAP2 or NRXN1 variants in either the SCT group or the comparison groups. Supplementary analyses found no indication of any impact of trisomy type on the results, and exploratory analyses of individual SNPs confirmed the lack of association. Conclusions: We cannot rule out that a double hit may be implicated in the phenotypic variability in children with SCTs, but our analysis does not find any support for the idea that common variants in CNTNAP2 or NRXN1 are associated with the severity of language and neurodevelopmental impairments that often accompany an extra X or Y chromosome. Stage 1 report: http://dx.doi.org/10.12688/wellcomeopenres.13828.2
Study protocol for a phase 2A trial of the safety and tolerability of increased dose rifampicin and adjunctive linezolid, with or without aspirin, for HIV-associated tuberculous meningitis [LASER-TBM]
Authors: Davis Angharad G. , Wasserman Sean , Maxebengula Mpumi , Stek Cari , Bremer Marise , Daroowala Remy , Aziz Saalikha , Goliath Rene , Stegmann Stephani , Koekemoer Sonya , Jackson Amanda , Lai Sai Louise , Kadernani Yakub , Sihoyiya Thandi , Liang C.Jason , Dodd Lori , Denti Paolo , Crede Thomas , Naude Jonathan , Szymanski Patryk , Vallie Yakoob , Banderker Ismail , Moosa Shiraz , Raubenheimer Peter , Lai Rachel P.J. , Joska John , Nightingale Sam , Dreyer Anna , Wahl Gerda , Offiah Curtis , Vorster Isak , Candy Sally , Robertson Frances , Meintjes Ernesta , Maartens Gary , Black John , Meintjes Graeme , Wilkinson Robert J. 
Published: June 2021

Background: Tuberculous meningitis (TBM) is the most lethal form of tuberculosis with a mortality of ~50% in those co-infected with HIV-1. Current antibiotic regimens are based on those known to be effective in pulmonary TB and do not account for the differing ability of the drugs to penetrate the central nervous system (CNS). The host immune response drives pathology in TBM, yet effective host-directed therapies are scarce. There is sufficient data to suggest that higher doses of rifampicin (RIF), additional linezolid (LZD) and adjunctive aspirin (ASA) will be beneficial in TBM yet rigorous investigation of the safety of these interventions in the context of HIV associated TBM is required. We hypothesise that increased dose RIF, LZD and ASA used in combination and in addition to standard of care for the first 56 days of treatment with be safe and tolerated in HIV-1 infected people with TBM. Methods: In an open-label randomised parallel study, up to 100 participants will receive either; i) standard of care (n=40, control arm), ii) standard of care plus increased dose RIF (35mg/kg) and LZD (1200mg OD for 28 days, 600mg OD for 28 days) (n=30, experimental arm 1), or iii) as per experimental arm 1 plus additional ASA 1000mg OD (n=30, experimental arm 2). After 56 days participants will continue standard treatment as per national guidelines. The primary endpoint is death and the occurrence of solicited treatment-related adverse events at 56 days. In a planned pharmacokinetic (PK) sub-study we aim to assess PK/pharmacodynamic (PD) of oral vs IV rifampicin, describe LZD and RIF PK and cerebrospinal fluid concentrations, explore PK/PD relationships, and investigate drug-drug interactions between LZD and RIF. Safety and pharmacokinetic data from this study will inform a planned phase III study of intensified therapy in TBM. Clinicaltrials.gov registration: NCT03927313 (25/04/2019)
Robotic arm-assisted versus conventional medial unicompartmental knee arthroplasty: five-year clinical outcomes of a randomized controlled trial
Authors: Banger Matthew , Doonan James , Rowe Philip , Jones Bryn , MacLean Angus , Blyth Mark J. B. 
Published: June 2021

Aims Unicompartmental knee arthroplasty (UKA) is a bone-preserving treatment option for osteoarthritis localized to a single compartment in the knee. The success of the procedure is sensitive to patient selection and alignment errors. Robotic arm-assisted UKA provides technological assistance to intraoperative bony resection accuracy, which is thought to improve ligament balancing. This paper presents the five-year outcomes of a comparison between manual and robotically assisted UKAs. Methods The trial design was a prospective, randomized, parallel, single-centre study comparing surgical alignment in patients undergoing UKA for the treatment of medial compartment osteoarthritis (ISRCTN77119437). Participants underwent surgery using either robotic arm-assisted surgery or conventional manual instrumentation. The primary outcome measure (surgical accuracy) has previously been reported, and, along with secondary outcomes, were collected at one-, two-, and five-year timepoints. Analysis of five-year results and longitudinal analysis for all timepoints was performed to compare the two groups. Results Overall, 104 (80%) patients of the original 130 who received surgery were available at five years (55 robotic, 49 manual). Both procedures reported successful results over all outcomes. At five years, there were no statistical differences between the groups in any of the patient reported or clinical outcomes. There was a lower reintervention rate in the robotic arm-assisted group with 0% requiring further surgery compared with six (9%) of the manual group requiring additional surgical intervention (p < 0.001). Conclusion This study has shown excellent clinical outcomes in both groups with no statistical or clinical differences in the patient-reported outcome measures. The notable difference was the lower reintervention rate at five years for roboticarm-assisted UKA when compared with a manual approach. Cite this article: Bone Joint J 2021;103-B(6):1088–1095.
Ten-year follow-up of stemmed hemiarthroplasty for acute proximal humeral fractures
Authors: Amundsen Alexander , Brorson Stig , Olsen Bo S. , Rasmussen Jeppe V. 
Published: June 2021

Aims There is no consensus on the treatment of proximal humeral fractures. Hemiarthroplasty has been widely used in patients when non-surgical treatment is not possible. There is, despite extensive use, limited information about the long-term outcome. Our primary aim was to report ten-year patient-reported outcome after hemiarthroplasty for acute proximal humeral fractures. The secondary aims were to report the cumulative revision rate and risk factors for an inferior patient-reported outcome. Methods We obtained data on 1,371 hemiarthroplasties for acute proximal humeral fractures from the Danish Shoulder Arthroplasty Registry between 2006 and 2010. Of these, 549 patients (40%) were alive and available for follow-up. The Western Ontario Osteoarthritis of the Shoulder (WOOS) questionnaire was sent to all patients at nine to 14 years after primary surgery. Revision rates were calculated using the Kaplan-Meier method. Risk factors for an inferior WOOS score were analyzed using the linear regression model. Results Mean age at surgery was 67 years (24 to 90) and 445 (81%) patients were female. A complete questionnaire was returned by 364 (66%) patients at a mean follow-up of 10.6 years (8.8 to 13.8). Mean WOOS score was 64 (4.3 to 100.0). There was no correlation between WOOS scores and age, sex, arthroplasty brand, or year of surgery. The 14-year cumulative revision rate was 5.7% (confidence interval 4.1 to 7.2). Patients aged younger than 55 years and patients aged between 55 to 74 years had 5.6-times (2.0 to 9.3) and 4.3-times (1.9 to 16.7) higher risk of revision than patients aged older than 75 years, respectively. Conclusion This is the largest long-term follow-up study of acute proximal humeral fractures treated with hemiarthroplasty. We found a low revision rate and an acceptable ten-year patient-reported outcome. The patient-reported outcome should be interpreted with caution as we have no information about the patients who died or did not return a complete WOOS score. The long-term outcome and revision rate suggest that hemiarthroplasty offers a valid alternative when non-surgical treatment is not possible. Cite this article: Bone Joint J 2021;103-B(6):1063–1069.
Is 2 mm a wide margin in high-grade conventional chondrosarcomas of the pelvis?
Authors: Kurisunkal Vineet , Laitinen Minna K. , Kaneuchi Yoichi , Kapanci Bilal , Stevenson Jonathan , Parry Michael C. , Reito Aleksi , Fujiwara Tomohiro , Jeys Lee M. 
Published: June 2021

Aims Controversy exists as to what should be considered a safe resection margin to minimize local recurrence in high-grade pelvic chondrosarcomas (CS). The aim of this study is to quantify what is a safe margin of resection for high-grade CS of the pelvis. Methods We retrospectively identified 105 non-metastatic patients with high-grade pelvic CS of bone who underwent surgery (limb salvage/amputations) between 2000 and 2018. There were 82 (78%) male and 23 (22%) female patients with a mean age of 55 years (26 to 84). The majority of the patients underwent limb salvage surgery (n = 82; 78%) compared to 23 (22%) who had amputation. In total, 66 (64%) patients were grade 2 CS compared to 38 (36%) grade 3 CS. All patients were assessed for stage, pelvic anatomical classification, type of resection and reconstruction, margin status, local recurrence, distant recurrence, and overall survival. Surgical margins were stratified into millimetres: < 1 mm; > 1 mm but < 2 mm; and > 2 mm. Results The disease-­specific survival (DSS) at five years was 69% (95% confidence interval (CI) 56% to 81%) and 51% (95% CI 31% to 70%) for grade 2 and 3 CS, respectively (p = 0.092). The local recurrence-free survival (LRFS) at five years was 59% (95% CI 45% to 72%) for grade 2 CS and 42% (95% CI 21% to 63%) for grade 3 CS (p = 0.318). A margin of more than 2 mm was a significant predictor of increased LRFS (p = 0.001). There was a tendency, but without statistical significance, for a > 2 mm margin to be a predictor of improved DSS. Local recurrence (LR) was a highly significant predictor of DSS, analyzed in a competing risk model (p = 0.001). Conclusion Obtaining wide margins in the pelvis remains challenging for high-grade pelvic CS. On the basis of our study, we conclude that it is necessary to achieve at least a 2 mm margin for optimal oncological outcomes in patients with high-grade CS of the pelvis. Cite this article: Bone Joint J 2021;103-B(6):1150–1154.
Early functional rehabilitation compared with traditional immobilization for acute Achilles tendon ruptures
Authors: Liu Xuan , Dai Tian-Jiao , Li Bao-Lin , Li Chen , Zheng Zhou-Yuan , Liu Ye 
Published: June 2021

Aims The aim of this meta-analysis was to assess the prognosis after early functional rehabilitation or traditional immobilization in patients who underwent operative or nonoperative treatment for rupture of the Achilles tendon. Methods PubMed, Embase, Web of Science, and Cochrane Library were searched for randomized controlled trials (RCTs) from their inception to 3 June 2020, using keywords related to rupture of the Achilles tendon and rehabilitation. Data extraction was undertaken by independent reviewers and subgroup analyses were performed based on the form of treatment. Risk ratios (RRs) and weighted mean differences (WMDs) (with 95% confidence intervals (CIs)) were used as summary association measures. Results We included 19 trials with a total of 1,758 patients. There was no difference between the re-rupture rate (RR 0.84 (95% CI 0.56 to 1.28); p = 0.423), time to return to work (WMD -1.29 (95% CI -2.63 to 0.05); p = 0.060), and sporting activity (WMD -1.50 (95% CI -4.36 to 1.37); p = 0.306) between the early functional rehabilitation and the traditional immobilization treatment strategies. Early rehabilitation up to 12 weeks yielded significantly better Achilles tendon Total Rupture Scores ((ATRS) WMD 5.11 (95% CI 2.10 to 8.12); p < 0.001). Patients who underwent functional rehabilitation had significantly lower limb symmetry index of heel-rise work ((HRW) WMD -4.19 (95% CI -8.20 to 0.17); p = 0.041) at one year. Conclusion Early functional rehabilitation is safe and provides better early function and the same functional outcome in the longer term. Cite this article: Bone Joint J 2021;103-B(6):1021–1030.
Patients with an increased time to treatment initiation have a poorer overall survival after definitive surgery for localized high-grade soft-tissue sarcoma in the extremity or trunk
Authors: Ogura Koichi , Fujiwara Tomohiro , Healey John H. 
Published: June 2021

Aims Time to treatment initiation (TTI) is generally defined as the time from the histological diagnosis of malignancy to the initiation of first definitive treatment. There is no consensus on the impact of TTI on the overall survival in patients with a soft-tissue sarcoma. The purpose of this study was to determine if an increased TTI is associated with overall survival in patients with a soft-tissue sarcoma, and to identify the factors associated with a prolonged TTI. Methods We identified 23,786 patients from the National Cancer Database who had undergone definitive surgery between 2004 and 2015 for a localized high-grade soft-tissue sarcoma of the limbs or trunk. A Cox proportional hazards model was used to examine the relationship between a number of factors and overall survival. We calculated the incidence rate ratio (IRR) using negative binomial regression models to identify the factors that affected TTI. Results Patients in whom the time to treatment initiation was prolonged had poorer overall survival than those with a TTI of 0 to 30 days. These were: 31 to 60 days (hazard ratio (HR) 1.08, p = 0.011); 61 to 90 days (HR 1.11, p = 0.044); and 91 days (HR 1.22; p = 0.003). The restricted cubic spline showed that the hazard ratio increased substantially with a TTI longer than 50 days. Non-academic centres (vs academic centres; IRR ranging from 0.64 to 0.86; p < 0.001) had a shorter TTI. Those insured by Medicaid (vs private insurance; IRR 1.34), were uninsured (vs private insurance; IRR 1.17), or underwent a transition in care (IRR 1.62) had a longer TTI. Conclusion A time to treatment initiation of more than 30 days after diagnosis was independently associated with poorer survival. The hazard ratio showed linear increase, especially if the TTI was more than 50 days. We recommend starting treatment within 30 days of diagnosis to achieve the highest likelihood of cure for localized high-grade soft-tissue sarcomas in the limbs and trunk, even when a patient needs to be referred to a specialist centre. Cite this article: Bone Joint J 2021;103-B(6):1142–1149.
The effect of time to irrigation and debridement on the rate of reoperation in open fractures
Authors: Johal Herman , Axelrod Daniel , Sprague Sheila , Petrisor Brad , Jeray Kyle J. , Heels-Ansdell Diane , Bzovsky Sofia , Bhandari Mohit 
Published: June 2021

AimsDespite long-standing dogma, a clear relationship between the timing of surgical irrigation and debridement (I&D) and the development of subsequent deep infection has not been established in the literature. Traditionally, I&D of an open fracture has been recommended within six hours of injury based on animal studies from the 1970s, however the clinical basis for this remains unclear. Using data from a multicentre randomized controlled trial of 2,447 open fracture patients, the primary objective of this secondary analysis is to determine if a relationship exists between timing of wound I&D (within six hours of injury vs beyond six hours) and subsequent reoperation rate for infection or healing complications within one year for patients with open limb fractures requiring surgical treatment.MethodsTo adjust for the influence of patient and injury characteristics on the timing of I&D, a propensity score was developed from the dataset. Propensity-adjusted regression allowed for a matched cohort analysis within the study population to determine if early irrigation put patients independently at risk for reoperation, while controlling for confounding factors. Results were reported as odds ratios (ORs), 95% confidence intervals (CIs), and p-values. All analyses were conducted using STATA 14.ResultsIn total, 2,286 of 2,447 patients randomized to the trial from 41 orthopaedic trauma centres across five countries had complete data regarding time to I&D. Prior to matching, the patients managed with early I&D had a higher proportion requiring reoperation for infection or healing complications (17% vs 13%; p = 0.019), however this does not account for selection bias of more severe injuries preferentially being treated earlier. When accounting for propensity matching, early irrigation was not associated with reoperation (OR 0.71 (95% CI 0.47 to 1.07); p = 0.73).ConclusionWhen accounting for other variables, late irrigation does not independently increase risk of reoperation. Cite this article: Bone Joint J 2021;103-B(6):1055–1062.