bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of cilioretinal arteries in 11‐ to 12‐year‐old children and association with maternal smoking during pregnancy: the Copenhagen Child Cohort 2000 Eye Study
Authors: Jønsson Lise Halmø , Larsen Michael , Olsen Else Marie , Skovgaard Anne Mette , Munch Inger Christine 
Published: February 2021

AbstractPurposeTo estimate the incidence of cilioretinal arteries in a Danish child cohort and associations with birth parameters.MethodsThe population‐based Copenhagen Child Cohort 2000 Eye Study examined 1406 children aged 11–12 years. Colour fundus images of both eyes were graded for cilioretinal arteries in the three categories large temporal (defined as supplying the central macula), small temporal and nasal. Data on maternal smoking during pregnancy, gestational ageand birth weight were obtained from the Danish Medical Birth Registry.ResultsA total of 463/1338 (35%) children were found to have one or more cilioretinal arteries per child. Large temporal cilioretinal arteries were present in 280/1338 (21%) of children and were associated with tobacco smoking during pregnancy, being present in 70/246 (28%) of children with mothers who were smoking during pregnancy, but only in 191/990 (19%) of children whose mothers did not smoke during pregnancy (p = 0.0022). After adjustments for potential confounders, the odds ratio of having one or more large temporal cilioretinal arteries was 1.72 (CI95% 1.19–2.47; p = 0.0035) in the smoking versus none smoking category. No other associations with birth parameters were found.ConclusionCilioretinal arteries were present in more than one third of 11‐ to 12‐year‐old Danish children. Large temporal cilioretinal arteries were found in one fifth of children and were associated with maternal smoking during pregnancy. This finding suggests that the intrauterine environment may have an impact on the development of retinal vessels during foetal life.
A randomized single and multiple ascending dose study in healthy volunteers of LTI‐291, a centrally penetrant glucocerebrosidase activator
Authors: den Heijer Jonas M. , Kruithof Annelieke C. , van Amerongen Guido , de Kam Marieke L. , Thijssen Eva , Grievink Hendrika W. , Moerland Matthijs , Walker Mike , Been Kees , Skerlj Renato , Justman Craig , Dudgeon Lindsay , Lansbury Peter , Cullen Valerie C. , Hilt Dana C. , Groeneveld Geert Jan 
Published: February 2021

AimsA mutation in the GBA1 gene is the most common genetic risk factor for developing Parkinson's disease. GBA1 encodes the lysosomal enzyme glucosylceramidase beta (glucocerebrosidase, GCase) and mutations decrease enzyme activity. LTI‐291 is an allosteric modulator of GCase, enhancing its activity. These first‐in‐human studies evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of LTI‐291 in healthy volunteers.MethodsIn the single ascending dose (SAD) study, 40 healthy volunteers were randomly assigned to LTI‐291 (n = 8 per dose level) or placebo (n = 2 per dose level). Single doses of 3, 10, 30 and 90 mg LTI‐291 were investigated. In the multiple ascending dose (MAD) study, 40 healthy middle‐aged or elderly volunteers were randomly assigned to LTI‐291 (n = 8 per dose level) or placebo (n = 2 per dose level). Fourteen consecutive daily doses of 3, 10, 30 and 60 mg LTI‐291 or placebo were administered. In both the SAD and MAD studies, glycosphingolipid levels were measured and a test battery of neurocognitive tasks was performed.ResultsLTI‐291 was generally well tolerated and no deaths or treatment‐related SAEs occurred and no subject withdrew from a study due to AEs. Cmax, AUC0–24 and AUC0‐inf increased in a dose proportional manner. The median half‐life was 28.0 hours after multiple dosing. No dose‐dependent glycosphingolipid changes occurred. No neurocognitive adverse effects were detected.ConclusionsThese first‐in‐human studies demonstrated that LTI‐291 was well tolerated when given orally once daily for 14 consecutive days. This supports the continued clinical development and the exploration of LTI‐291 effects in a GBA1‐mutated Parkinson population.
Off‐label use of letrozole in Chinese short pubertal boys: Effectiveness, safety, and exposure–response analysis
Authors: Xu Yuan , Zhang Yan‐Hong , Zhang Qiu‐Ping , Zhao Qian‐Qian , Cao Xiao‐Fu , Zhang Mei , Li Xue , Liu Xi‐Ting , Sun Zhuo‐Xiang , Kan Min , Du Bin , Zhou Yue , Yang Fan , Ban Bo , Zhao Wei 
Published: February 2021

AimsRecently, letrozole has been used off‐label to treat short pubertal boys. The experience on letrozole effectiveness and safety has been obtained primarily from Caucasian children. A simple extrapolation of the data to Chinese paediatric populations is questionable because of the substantial ethnic differences between the two populations. Therefore, the present study aimed to determine the effectiveness and safety of letrozole use in Chinese short pubertal boys as well as to establish an exposure–response relationship.MethodsForty‐one Chinese boys were included in the study. Patients were given letrozole tablets (2.5 mg) once daily in combination with growth hormone, and follow‐up visits were made after 1, 3, 6 and 12 months of treatment. Plasma samples were taken from clinical examinations and analysed using high performance liquid chromatography with fluorescence detection.ResultsAfter 1 year of treatment, 35 (88%) boys showed increased predicted adult heights. However, possible adverse drug reactions were seen in nine boys (22%). Predicted adult heights increased significantly from 168.4 ± 3.7 to 173.0 ± 4.2 cm, while oestrogen levels dropped from 33.2 ± 7.4 to 21.6 ± 7.3 pg/mL. Increments in predicted adult height were significantly correlated with trough letrozole concentrations (r = 0.39, P = .01).ConclusionLetrozole treatment in Chinese pubertal populations should be further optimized, and more personalized therapies should be developed.
A cascade of interventions: A classification tree analysis of the determinants of primary cesareans in Australian public hospitals
Authors: Fox Haylee , Topp Stephanie M. , Lindsay Daniel , Callander Emily 
Published: February 2021

AbstractBackgroundBoth globally and in Australia, there has been a sharp rise in cesarean births (CB). Commonly, this rise has been attributed to the changing epidemiology of women giving birth. A significant body of knowledge exists on the risk factors associated with a greater need for cesarean. Yet, we have little information on the reasons recorded by clinicians as to why cesareans are provided. This study aimed to explore the drivers of primary cesareans in Australian public hospitals.MethodsUsing a linked administrative data set, the frequency and percent of mothers’ characteristics were compared between those who had a cesarean birth and those who had a vaginal birth (n = 98 967) with no history of previous cesareans in Queensland public hospitals between July 1, 2012, and June 30, 2015. The top 10 reasons recorded by clinicians for a primary cesarean were reported. Using a machine‐learning algorithm, two decision trees were built to determine factors driving primary cesarean birth.Results“Labour and delivery complicated by fetal heart rate anomaly” (23%) and “primary inadequate contractions” (22.8%) were the top two reasons for a primary cesarean birth. The most common characteristics among mothers who had fetal heart rate anomalies were as follows: artificial rupture of membranes (39%), oxytocin (32%), no obstruction of labor (42%), and epidural (52%). For women who had primary inadequate contractions, the most common characteristics were as follows: epidural (33%), oxytocin (49%), artificial rupture of membranes (45%), and fetal stress (56%).ConclusionsEfforts should be made by health practitioners during the antenatal period to maximize the use of preventative measures that minimize the need for medical interventions.
Society‐level social axiom moderates the association between growth mindset and achievement across cultures
Authors: Bernardo Allan B. I. , Cai Yuyang , King Ronnel B. 
Published: February 2021

BackgroundMeta‐analytic studies show that the benefits of the growth mindset on academic achievement are heterogenous. Past studies have explored how individual characteristics and proximal environmental factors could explain these variations, but the role of the broader sociocultural environment has seldom been explored.AimsWe investigated society‐level social axioms to explain variations in growth mindset effects on achievement across cultures. We hypothesized that three society‐level social axioms (social complexity, fate control, and reward for application) imply social norms that would either support or obstruct the growth mindset effect.Sample and methodsWe conducted multilevel SEM with random slopes using data from 273,074 students nested within 39 countries/territories.ResultsWe found weaker growth mindset effects in societies with stronger social complexity beliefs; societies believing that there are multiple solutions to problems have social norms that obstruct the growth mindset effects on achievement. No moderating effects were found with other social axioms.ConclusionRelevant cultural‐level normative beliefs should be considered to better assess the relevance of the growth mindset construct.
Prognostic value of minimal residual disease measured by fusion‐gene transcript in infants with KMT2A‐rearranged acute lymphoblastic leukaemia treated according to the MLL‐Baby protocol
Authors: Tsaur Grigory , Popov Alexander , Riger Tatiana , Kustanovich Anatoly , Solodovnikov Alexander , Shorikov Egor , Demina Anna , Verzhbitskaya Tatiana , Streneva Olga , Makarova Olga , Lapotentova Elena , Aleinikova Olga , Miakova Natalia , Boichenko Elmira , Kondratchik Konstantin , Ponomareva Natalia , Karachunskiy Alexander , Roumiantsev Alexander , Fechina Larisa 
Published: February 2021

SummaryThe prognostic value of minimal residual disease (MRD) measured by fusion‐gene transcript (FGT) detection was investigated in 76 infants (aged ≤1 year) with acute lymphoblastic leukaemia (ALL) with lysine methyltransferase 2A (KMT2A) rearrangements. Either at the end of induction or at later time‐points, FGT‐MRD‐positivity was associated with poor outcome. FGT‐MRD‐positivity after first consolidation or first high‐risk block detected 46·5% of infants with extremely poor outcome [disease‐free survival (SE) 0·06 (0·06), cumulative incidence of relapse (SE) 0·91 (0·05)], which was also confirmed in multivariable analysis. Thus, FGT‐MRD measurement at a single time‐point clearly identifies infants with ALL who are curable with conventional chemotherapy and those who would benefit only from other treatment approaches.
Experiences and predictors of psychological distress in pregnant women living with HIV
Authors: Ogueji Ifeanyichukwu Anthony 
Published: February 2021

ObjectivesTo explore the experiences and predictors of psychological distress in pregnant women living with HIV.DesignA mixed‐methods research design.MethodsA representative randomly sampled 840 (age range 22–46 years) HIV‐positive pregnant women in Akwa Ibom, Benue, and Rivers States of Nigeria enrolled for the study. Data were collected using standardized questionnaires and in‐depth interviews for 4 months and 3 weeks in 6 HIV treatment centres. Collected data were analysed using IBM SPSS statistics (v. 22.0) and thematic analysis.ResultsThe mean score on psychological distress was 17.07 ± 5.86. Multiple regression analysis found a significant joint prediction of meaning in life, self‐compassion, and acceptance of illness on psychological distress, R = .64, R2 = .41; F (3,828) = 186.18; p = .000, with 41% variance explained. Further, there was a significant independent prediction of each predictor at meaning in life (β = −.19, t = −5.08; p = .000), self‐compassion (β = −.23, t = −5.59; p = .000), and acceptance of illness (β = −.30, t = −7.23; p = .000), with acceptance of illness exerting the greatest independent predictive impact. Socio‐demographic variables (age, length of living with HIV, high‐risk state, highest education attained, marital status, and religious affiliation) had no significant contribution to psychological distress. Qualitative analysis found ‘anxious concerns’, ‘depressive reports, loneliness, and regrets’, ‘self‐blame and guilt feelings’, as the experiences of psychological distress, and these experiences were determined by respondents’ socio‐cultural contexts.ConclusionThese findings emphasize the importance of psychosocial care for HIV‐positive pregnant women.
An alternative approach for detecting hearing loss in adults with learning disabilities
Authors: McShea Lynzee , Giles Karen , Murphy Ashley , Ling Jonathan 
Published: February 2021

Accessible Summary

Annual health checks for people with learning disabilities should include a check of hearing. However, this hearing check only involves asking questions about hearing and does not include an actual hearing test.

We tested the hearing of people with learning disabilities in the community.

We found that some people had hearing problems that had not been picked up at their annual health check.

We think the annual health check should be changed to include a hearing test.

AbstractBackgroundAnnual health checks in primary care include hearing assessment, though current guidance recommends subjective assessment only. Previous studies suggest this is inadequate and recommend objective alternatives such as hearing screening. This study aimed to assess the feasibility of hearing screening and examine the last recorded annual health check outcome for hearing, for those diagnosed with hearing loss as a result of the screening process.MethodHearing screening took place in four locations and 75 people with learning disabilities participated. Contact was made with each individual's GP to share results and to request onward referral where indicated.FindingsWax occlusion prevented screening for 23%. Fifty‐seven people completed the screen, and 25 had suspected hearing loss. Of these, 22 people required referral to Audiology to verify their hearing thresholds. Only 13 were actually referred, and 11 individuals underwent assessment in Audiology, resulting in 10 being diagnosed with hearing loss. The most recent annual health check outcomes for hearing were examined for those diagnosed with hearing loss. Of the records we accessed, hearing loss had not been identified or actioned in every case.ConclusionsHearing screening is shown here to be a suitable method for detecting hearing loss. We recommend changing current annual health check practice to incorporate objective screening. Only 12% of those with suspected hearing loss were known to Audiology services, suggesting a substantial proportion of undetected hearing loss in the community. We found evidence of apparent reluctance around referral and hearing aid fitting and make suggestions for improvement.
Securitization of assets and risk transfer in a large emerging market: Evidence from Brazil
Authors: de Mendonça Helder Ferreira , Barcelos Vívian Íris 
Published: February 2021

AbstractThis study analyzes the impact of securitization on the soundness of financial institutions through the two main securitization products in Brazil: Credit Rights Investment Funds (FIDC) and Real Estate Receivables Certificates (CRI). On the basis of a panel data analysis regarding 92 financial institutions from 2003 to 2016, we performed several regressions for different samples and methods. The findings suggest that securitization may increase the insolvency risk. In particular, we observe that the effect on the insolvency risk caused by securitization from CRI operations is higher than from FIDC operations.
Reconstituting neurovascular unit with primary neural stem cells and brain microvascular endothelial cells in three‐dimensional matrix
Authors: Wang Hongjin , Yang Huan , Shi Yuhong , Xiao Yaping , Yin Yue , Jiang Baoxiang , Ren Huijing , Chen Weihai , Xue Qiang , Xu Xiaoyu 
Published: February 2021

AbstractNeurovascular dysfunction is a primary or secondary cause in the pathogenesis of several cerebrovascular and neurodegenerative disorders, including stroke. Therefore, the overall protection of the neurovascular unit (NVU) is a promising therapeutic strategy for various neurovascular diseases. However, the complexity of the NVU limits the study of the pathological mechanisms of neurovascular dysfunction. Reconstituting the in vitro NVU is important for the pathological study and drug screening of neurovascular diseases. In this study, we generated a spontaneously assembled three‐dimensional NVU (3D NVU) by employing the primary neural stem cells and brain microvascular endothelial cells in a Matrigel extracellular matrix platform. This novel model exhibits the fundamental structures and features of the NVU, including neurons, astrocytes, oligodendrocytes, vascular‐like structures, and blood–brain barrier‐like characteristics. Additionally, under oxygen‐glucose deprivation, the 3D NVU exhibits the neurovascular‐ or oxidative stress‐related pathological characteristics of cerebral ischemia and the injuries can be mitigated, respectively, by supplementing with the vascular endothelial growth factor or edaravone, which demonstrated that the availability of 3D NVU in ischemic stroke modeling. Finally, the 3D NVU promoted the angiogenesis and neurogenesis in the brain of cerebral ischemia rats. We expect that the proposed in vitro 3D NVU model will be widely used to investigate the relationships between angiogenesis and neurogenesis and to study the pathology and pharmacology of neurovascular diseases.
Health‐related quality of life in adults with osteogenesis imperfecta
Authors: Murali Chaya N. , Slater Brady , Musaad Salma , Cuthbertson David , Nguyen Dianne , Turner Alicia , Azamian Mahshid , Tosi Laura , Rauch Frank , Sutton V. Reid , Lee Brendan ,   Members of the BBD Consortium, Nagamani Sandesh C. S. 
Published: February 2021

AbstractPatient‐reported outcome measures (PROMs) are increasingly utilized as endpoints in clinical trials. The Short Form Health Survey‐12 (SF‐12v2) is a generic PROM for adults. We sought to evaluate the validity of SF‐12v2 in adults with osteogenesis imperfecta (OI). Physical and mental health‐related quality of life (HRQoL) were assessed in a large cohort of adults in a multicenter, observational, natural history study. Physical HRQoL scores were correlated with the Gillette Functional Assessment Questionnaire (GFAQ). We calculated sample sizes required in clinical trials with crossover and parallel‐group designs to detect clinically meaningful changes in physical HRQoL. Three hundred and two adults with OI types I, III, and IV were enrolled. Physical HRQoL scores in the study population were lower than population norms. Physical HRQoL scores moderately correlated with GFAQ for OI types I and IV. We found no correlations between mental and physical HRQoL. From a clinical trial readiness perspective, we show that SF‐12v2 reliably measures physical function in adults with OI and can be utilized in crossover trials to detect meaningful physical HRQoL changes with small sample sizes. This study shows that SF‐12v2 can be used to measure changes in physical HRQoL in response to interventions in OI.
Novel pathogenic variants in NLRP7, NLRP5, and PADI6 in patients with recurrent hydatidiform moles and reproductive failure
Authors: Rezaei Maryam , Suresh Beena , Bereke Eric , Hadipour Zahra , Aguinaga Monica , Qian Jianhua , Bagga Rashmi , Fardaei Majid , Hemida Reda , Jagadeesh Sujatha , Majewski Jacek , Slim Rima 
Published: February 2021

AbstractRecurrent hydatidiform moles (RHMs) are human pregnancies with abnormal embryonic development and hyperproliferating trophoblast. Biallelic mutations in NLRP7 and KHDC3L, members of the subcortical maternal complex (SCMC), explain the etiology of RHMs in only 60% of patients. Here we report the identification of seven functional variants in a recessive state in three SCMC members, five in NLRP7, one in NLRP5, and one in PADI6. In NLRP5, we report the first patient with RHMs and biallelic mutations. In PADI6, the patient had four molar pregnancies, two of which had fetuses with various abnormalities including placental mesenchymal dysplasia and intra‐uterine growth restriction, which are features of Beckwith‐Wiedemann syndrome and Silver Russell syndrome, respectively. Our findings corroborate recent studies and highlight the common oocyte origin of all these conditions and the continuous spectrum of abnormalities associated with deficiencies in the SCMC genes.
Instructed Hand Movements Affect Students’ Learning of an Abstract Concept From Video
Authors: Zhang Icy (Yunyi) , Givvin Karen B. , Sipple Jeffrey M. , Son Ji Y. , Stigler James W. 
Published: February 2021

AbstractProducing content‐related gestures has been found to impact students’ learning, whether such gestures are spontaneously generated by the learner in the course of problem‐solving, or participants are instructed to pose based on experimenter instructions during problem‐solving and word learning. Few studies, however, have investigated the effect of (a) performing instructed gestures while learning concepts or (b) producing gestures without there being an implied connection between the gestures and the concepts being learned. The two studies reported here investigate the impact of instructed hand movements on students’ subsequent understanding of a concept. Students were asked to watch an instructional video—focused on the concept of statistical model—three times. Two experimental groups were given a secondary task to perform while watching the video, which involved moving their hands to mimic the placement and orientation of red rectangular bars overlaid on the video. Students were told that the focus of the study was multitasking, and that the instructed hand movements were unrelated to the material being learned. In the content‐match group the placement of the hands reinforced the concept being explained, and in the content‐mismatch group it did not. A control group was not asked to perform a secondary task. In both studies, findings indicate that students in the content‐match group performed better on the posttest, and showed less variation in performance, than did students in the content‐mismatch group, with control students falling in between. Instructed hand movement—even when presented as an unrelated, secondary task—can affect students’ learning of a complex concept.