bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum lithium test requesting across three UK regions: An evaluation of adherence to monitoring guidelines
Authors: Parfitt Ceri , Duff Christopher J , Scargill Jonathan , Green Lewis , Holland David , Heald Adrian H , Fryer Anthony A 
Published: January 2021

Abstract
Background: Bipolar disorder is the fourth most common mental health condition, affecting ~1% of UK adults. Lithium is an effective treatment for prevention of relapse and hospital admission, and is widely recommended as a first-line treatment. We previously showed in other areas that laboratory testing patterns are variable with sub-optimal conformity to guidance. We therefore examined lithium results and requesting patterns relative to monitoring recommendations.Methods: Data on serum lithium levels and intervals between requests were extracted from Clinical Biochemistry laboratory information systems at the University Hospitals of North Midlands, Salford Royal Foundation Trust and Pennine Acute Hospitals from 2012-2018 (46,555 requests; 3,371 individuals). Data were examined with respect to region/source of request, age and sex.Results: Across all sites, lithium levels on many requests were outside the recommended UK therapeutic range (0.4-0.99 mmol/L); 19.2% below the range and 6.1% above the range (median [Li]: 0.60 mmol/L). A small percentage were found at the extremes (3.2% at <0.1mmol/L, 1.0% at ≥1.4mmol/L). Most requests were from general practice (56.3%) or mental health units (34.4%), though those in the toxic range (≥1.4 mmol/L) were more likely to be from secondary care (63.9%). For requesting intervals, there was a distinct peak at 12 weeks, consistent with guidance for those stabilised on lithium therapy. There was no peak at 6 months, as recommended for those aged <65 years on unchanging therapy, though re-test intervals in this age group were more likely to be longer. There was a peak at 0-7 days, reflecting those requiring closer monitoring (e.g. treatment initiation, toxicity). However, for those with initial lithium concentrations within the BNF range (0.4-0.99 mmol/L), 69.4% of tests were requested outside expected testing frequencies.Conclusions: Our data showed: (a) lithium levels are often maintained at the lower end of the recommended therapeutic range, (b) patterns of lithium results and testing frequency were comparable across three UK sites with differing models of care and, (c) re-test intervals demonstrate a noticeable peak at the recommended 3-monthly, but not at 6-monthly intervals. Many tests were repeated outside expected frequencies, indicating the need for measures to minimise inappropriate testing.
School trajectory disruption among adolescents living with perinatal HIV receiving antiretroviral treatments: a case-control study in Thailand
Authors: Merville Ophélie , Puangmala Patcharee , Suksawas Pranee , Kliangpiboon Woranut , Keawvilai Waraporn , Tunkam Chorkanikar , Yama Suvimon , Sukhaphan Usa , Sathan Somporn , Marasri Siriporn , Rolland-guillard Louise , Sirirungsi Wasna , Coeur Sophie Le 
Published: January 2021

Abstract
Background: Adolescents living with perinatal HIV often experience difficult living circumstances that can impact educational achievement and thus their transition to adult life. We explored their school trajectories and evaluated the contribution of perinatal HIV-infection, in Thailand, where education is free and compulsory until the age of 15.Methods: We used data from the Teens Living with Antiretrovirals (TEEWA) study, a cross-sectional case-control study conducted from 2011 to 2014 in Thailand. Participants were 707 adolescents living with perinatal HIV (ALPHIV, cases) aged 12–19 receiving antiretroviral therapy in 19 hospitals throughout Thailand and 689 HIV-uninfected adolescents (controls) living in the same institutions or, for those living in family settings, randomly selected from the general population and individually matched for sex, age, and place of residence. School trajectory disruption was defined as ≥ 1 year of academic delay or as early school dropout (before 15 years of age). Logistic regression models were used to assess factors independently associated with disrupted school trajectory and to estimate the proportion of school disruption attributable to HIV-infection. We used multivariate imputations by chained equations (MICE) to manage missing data and performed two sensitivity analyses to evaluate the main model’s reliability.Results: The study population’s median age was 14.5 years (58% female). School trajectory disruption was experienced by 37% of ALPHIV and 12% of the controls. After adjusting for sociodemographic factors, ALPHIV were 5 times more likely to experience disruption than controls ( =5.2 [3.7-7.2]). About 50% of school trajectory disruption was attributable to HIV-infection. Boys and adolescents living in institutions were more likely to experience school trajectory disruption ( =1.8 [1.3-2.4] and =11.0 [7.7-15.8], respectively). Among ALPHIV, neurocognitive difficulties and growth delay were significantly associated with disruption ( =3.3 [2.1-5.2] and =1.8 [1.3-2.6], respectively). For those living in families, disruption was also associated with having a caregiver who had less than a secondary-level education ( =2.1 [1.1-3.9]) or having experienced stigmatization ( =1.9 [1.2-3.1]). Conclusions: HIV and contextual factors combine to aggravate the educational disadvantage among ALPHIV. The impact of this disadvantage on their life prospects, especially regarding access to higher education and professional achievement, should be further explored.
Validation of multiplex PCR sequencing assay of SIV
Authors: Moriarty Ryan V , Fesser Nico , Sutton Matthew S , Venturi Vanessa , Davenport Miles P , Schlub Timothy , O'Connor Shelby L 
Published: January 2021

Abstract
Background: The generation of accurate and reproducible viral sequence data is necessary to understand the diversity present in populations of RNA viruses isolated from clinical samples. While various sequencing methods are available, they often require high quality templates and high viral titer to ensure reliable data.Methods: We modified a multiplex PCR and sequencing approach to characterize populations of simian immunodeficiency virus (SIV) isolated from nonhuman primates. We chose this approach with the aim of reducing the number of required input templates while maintaining fidelity and sensitivity. We conducted replicate sequencing experiments using different numbers of quantified viral RNA (vRNA) or viral cDNA as input material. We performed assays with clonal SIVmac239 to detect false positives, and we mixed SIVmac239 and a variant with 24 point mutations (SIVmac239-24X) to measure variant detection sensitivity.Results: We found that utilizing a starting material of quantified viral cDNA templates had a lower rate of false positives and increased reproducibility when compared to that of quantified vRNA templates. This study identifies the importance of rigorously validating deep sequencing methods and including replicate samples when using a new method to characterize low frequency variants in a population with a small number of templates.Conclusions: Because the need to generate reproducible and accurate sequencing data from diverse viruses from low titer samples, we modified a multiplex PCR and sequencing approach to characterize SIV from populations from non-human primates. We found that increasing starting template numbers increased the reproducibility and decreased the number of false positives identified, and this was further seen when cDNA was used as a starting material. Ultimately, we highlight the importance of vigorously validating methods to prevent overinterpretation of low frequency variants in a sample.
How joint line orientation affects the amount of bone resected in mechanically aligned TKA: a retrospective clinical-radiographic correlational study
Authors: Wang Zhiwei , Yu Yang , Wen Liang , Ma Desi , Qu Tiebing 
Published: January 2021

Abstract
Background: Discrepancies in bone resection between the medial and lateral compartments is very common in total knee replacement (TKA) when mechanical alignment (MA) is used. The purpose of this study was to explore whether and how joint line orientation affects the gross amount of bone resected in mechanically aligned TKA.Methods: A total of 112 patients (137 knees) diagnosed with osteoarthritis (OA) were included. Bone resection simulations were conducted in the coronal view using full-length weight-bearing radiographs per the technical parameters of MA, and the feasibility of simulated osteotomy was verified via intraoperative caliper measurement. Correlation and regression analyses were conducted comparing the amount of bone resected and various parameters, including hip-knee-ankle (HKA) angle, mechanical lateral distal femoral angle (mLDFA), joint line congruency angle (JLCA), and medial proximal tibial angle (MPTA). Moreover, any intraoperative bone resection adjustments that were made were retrospectively collected using a medical record query system.Results: All knees in the current case series could be artificially divided into 4 subgroups: 84 varus knees (61.3%) with valgus femurs in subgroup 1, 32 varus knees (23.4%) with varus femurs in subgroup 2, 14 valgus knees (10.2%) with varus tibias in subgroup 3, and 7 valgus knees (5.1%) with valgus tibias in subgroup 4. Simulated bone resection thickness was highly consistent with intraoperative measurements. MPTA and mLDFA were positively correlated with the amount of bone resected in subgroup 1. The regression equation was: Maximum resection thickness (mm) = 0.556*mLDFA (deg.) + 0.098*MPTA (deg.) -39.74; R2=0.808. Similarly, intraoperative bone resection adjustments also showed a correlation with mLDFA in subgroup 1.Conclusions: Deformities in knee OA can be divided into 4 subgroups based on the alignment of extremities and the joint line orientation. When TKA is performed in varus knees with valgus femurs using conventional instruments and mechanical alignment techniques, the amount of bone resected in the coronal plane demonstrates a linear relationship with the patient’s mLDFA.
DSSAM: Digitally Signed Secure Acknowledgement Method for Mobile Ad-hoc Network
Authors: Srivast Ashutosh , Gupta Sachin Kumar , Najim Mohd , Sahu Nitesh , Aggarwal Geetika , Mazumdar Bireshwar Dass 
Published: January 2021

Abstract
Mobile Ad-hoc Networks (MANETs) is an infrastructure-less, self-motivated, arbitrary, self-configuring, rapidly changing, multi-hop network that is self-possessing wireless bandwidth-conscious links without centrally managed router support. In such a network, wireless media is easy to snoop. It is firm to the surety to access any node, easier to insertion of bad elements or attackers for malicious activities in the network. Therefore, security issues become one of the significant considerations for such kind of networks. The deployment of an effective intrusion detection system is important in order to provide protection against various attacks. In this paper, a Digitally Signed Secure Acknowledgement Method (DSSAM) with the use of the RSA digital signature has been proposed and simulated. Three different parameters are considered viz. secure acknowledgment, node authentication and packet authentication for study. This article observes the DSSAM performance and compares it with two existing standard methods, namely, Watchdog and 2-ACK under standard Dynamic Source Routing (DSR) routing environment. In the end, it is noticed that the rate of detection of malicious behaviour is better in the case of the proposed method. However, associated overheads are high. A trade-off between performance and overhead has been considered.
Analysis of pain markers and epidural fibrosis caused by repeated spinal surgery in Sprague–Dawley rats
Authors: Quan Meiling , Kim Jae-Hoon , Hwang Won-Ha , KIM Young-Yul 
Published: January 2021

Abstract
Background: Epidural fibrosis is one of the aetiologies of pain following a spinal revision surgery. It is reported that the specific members of the mitogen – activated protein kinases (MAPK) family might mediate neuropathic pain. However, roles of epidural fibrosis caused by repeated spinal surgeries and pain-related proteins in causing the post spinal surgery syndrome remain unknown. Using a rat spinal surgery epidural fibrosis and adhesion model, in this study, we evaluated and investigated the relationship between pain markers and epidural fibrosis. Methods: Sprague–Dawley rats that underwent the spinal surgery were divided into three groups: group A (single laminectomy), group B (two repeated surgeries) and group C (three repeated surgeries). Dural thickness was measured in each experimental group, and immunohistochemical analysis and western blotting of mitogen-activated protein kinases were performed (ERK, p38 and JNK) using the spine cord. Results: Dural thickness was 6.363 ± 1.911 µm in group A, 13.238 ± 2.123 µm in group B and 19.4 ± 2.115 µm in group C, respectively. In the western blotting, phosphorylated ERK expression gradually increased with the number of repeated surgeries, and expression in groups B (1.77-fold) and C (2.42-fold) increased as compared to expression in group A. Phosphorylated p38 showed an increasing trend with the number of repeated surgeries, and groups B (1.17-fold) and C (1.33-fold) expression increased compared with group A. However, phosphorylated JNK expression did not gradually increase with the number of repeated surgeries, and groups B (1.62-fold) and C (1.43-fold) expression increased compared with group A. Excluding phosphorylated JNK, immunohistochemical analysis revealed that phosphorylated ERK and p38 expression gradually increased with the number of repeated surgeries in the spine dorsal horn, as evidenced by western blotting. Conclusions: Repeated spinal surgeries may increase dural thickness and expression of phosphorylated ERK and p38 in the spinal dorsal horn, and it suggests that the neuropathic pain is likely induced by epidural fibrosis and that the pain increases with the number of repeated surgeries.
Increased P450 aromatase levels in post-menopausal women after acute ischemic stroke
Authors: Manwani Bharti , Fall Pamela , Zhu Liang , O’Reilly Meaghan Roy , Conway Sarah , Staff Ilene , McCullough Louise D. 
Published: January 2021

Abstract
Background: Sex differences in stroke have been attributed to the neuroprotective effects of estrogen, yet most clinical trials of estrogen supplementation for stroke prevention have failed. The contribution of sex hormones to stroke outcome remains a subject of debate. Aromatization of testosterone to estradiol in neural tissue leads to sexual differentiation. Emerging data suggests aromatase activity increases in response to brain injury, and increased aromatase expression is seen in the ischemic penumbra in animal models. The objective of this study was to examine the levels of endogenous sex steroids after acute ischemic stroke and determine if levels of sex steroids were associated with acute stroke outcomes. Methods: Peripheral blood from ischemic stroke patients and controls was collected under an approved IRB within 24 hours of symptom onset. 17-β estradiol, testosterone and aromatase levels were measured in the serum of both men and women using ELISA. Hormone levels were compared in men vs. women in stroke and control groups and correlated with outcomes (NIHSS and change in the modified Rankin Scale (mRS), defined as difference of premorbid and discharge mRS) using multivariate regression. Results: We found no significant difference in estradiol levels 24 hours after stroke in men (p=0.86) or women (p=0.10). In men, testosterone significantly decreased after stroke as compared with controls (1.83±0.12 vs 2.86±0.65, p=0.01). Aromatase levels were significantly increased in women after stroke as compared with controls (2.27±0.22 vs 0.97±0.22, p=0.002), but not in men (p=0.84). Estradiol levels positively correlated with change in mRS in both women (r=0.38, p=0.02) and men (r=0.3, p=0.04).Conclusions: Estradiol levels correlated with functional outcomes (change in mRS) in both men and women, at least in the acute phase (24 hours) of stroke. However, no significant difference in estradiol levels is seen 24 hours post stroke in men or women. Testosterone levels decrease at 24 hours after stroke in men. As seen in animal models, aromatase levels increase after acute ischemic stroke, but this was only true for women. These indicate an active aromatization process in post-menopausal women after acute ischemic stroke.
Left hemispheric deficit in the sustained neuromagnetic response to periodic click trains in children with ASD.
Authors: Stroganova Tatiana A , Komarov Kirill S , Sysoeva Olga V , Goiaeva Dzerasa E , Obukhova Tatiana S , Ovsiannikova Tatiana M , Prokofiev Andrey O , Orekhova Elena V 
Published: January 2021

Abstract
Background: Deficits in perception and production of vocal pitch are often observed in people with autism spectrum disorder (ASD), but the neural basis of these deficits is unknown. In magnetoencephalogram (MEG), spectrally complex periodic sounds trigger two continuous neural responses – the auditory steady state response (ASSR) and the sustained field (SF). It has been shown that the SF in neurotypical individuals is associated with low-level analysis of pitch in the ‘pitch processing center’ of the Heschl’s gyrus. Therefore, alternations in this auditory response may reflect atypical processing of vocal pitch. The SF, however, has never been studied in people with ASD. Methods: We used MEG and individual brain models to investigate the ASSR and SF evoked by monaural 40 Hz click trains in boys with ASD (N=35) and neurotypical (NT) boys (N=35) aged 7-12-years.Results: In agreement with the previous research in adults, the cortical sources of the SF in children were located in the left and right Heschl’s gyri, anterolateral to those of the ASSR. In both groups, the SF and ASSR dominated in the right hemisphere and were higher in the hemisphere contralateral to the stimulated ear. The ASSR increased with age in both NT and ASD children and did not differ between the groups. The SF amplitude did not significantly change between the ages of 7 and 12 years. It was moderately attenuated in both hemispheres and was markedly delayed and displaced in the left hemisphere in boys with ASD. The SF delay in participants with ASD was present irrespective of their intelligence level and severity of autism symptoms. Limitations: We did not test the language abilities of our participants. Therefore, the link between SF and processing of vocal pitch in children with ASD remains speculative. Conclusion: Children with ASD demonstrate atypical processing of spectrally complex periodic sound at the level of the core auditory cortex of the left-hemisphere. The observed neural deficit may contribute to speech perception difficulties experienced by children with ASD, including their poor perception and production of linguistic prosody.
Generation and Selection of Driver-Behavior-Based Transferable Motion Primitives
Authors: Guan Haijie , Wang Boyang , Wei Jiaming , Lu Yaomin , Chen Huiyan , Gong Jianwei 
Published: January 2021

Abstract
In order to achieve the integration of driver experience and heterogeneous vehicle platform characteristics in the motion planning algorithm, based on the driver-behavior-based transferable motion primitives, a general motion planning framework for offline generation and online selection of motion primitives (MPs) is proposed. The optimal control theory is applied to solve the boundary value problems in the process of generating MPs, where the driver behaviors and the vehicle motion characteristics are integrated into the optimization in the form of constraints. Moreover, this paper proposes a layered, unequal-weighted MPs selection framework and utilizes the combination of environmental constraints, nonholonomic vehicle constraints, trajectory smoothness, and collision risk as the single-step extension evaluation index. The library of MPs generated offline demonstrates that the proposed generation method realizes the effective expansion of the MP types and achieves the diverse generation of MPs with various velocity attributes and platform types. We also present how the MP selection algorithm utilizes the unique MP library to achieve the online extension of MP sequences. The results show that the proposed motion planning framework can not only improve the efficiency and rationality of the algorithm based on driving experience but also can transfer between heterogeneous vehicle platforms and highlight the unique motion characteristics of the platform.
Parent-perceived barriers to accessing services for their child’s mental health problems.
Authors: Hansen Anna Sofie , Telléus Gry Kjaersdam , Mohr-Jensen Christina , Lauritsen Marlene Briciet 
Published: January 2021

Abstract
Background Many children and adolescents with impairing mental health disorders are not in contact with specialized child and adolescent mental health services (CAMHS). In order to close the service gap, it is important to increase our knowledge of barriers to access. The aim of this study was to investigate parent perceived barriers to accessing services for their child’s mental health problems to identify potential areas for improvement of access to CAMHS. Method In this cross-sectional observational study 244 parents of children and adolescents referred to outpatient psychiatric assessment were interviewed using the Children’s services interview regarding barriers to accessing child mental health services across healthcare, educational services and social services. Parent reported barriers were analyzed in relation to the child’s age, referral reason, symptom duration and impairment of the child. Results The most commonly reported barriers were lack of information about were to seek help (60.3%), the perception that professionals did not listen (59.8%) and professionals refusing to initiate interventions or provide referral to services (53.7%). Lack of knowledge, stigmatization and unavailability of services were common themes across barriers to help-seeking. Long symptom duration and parent rated impairment was associated with increased risk of reporting several barriers to help-seeking.Conclusion Parents seeking help for their child’s mental health encounter numerous barriers that could explain part of the treatment gap and long duration of mental health problems in children prior to referral to CAMHS.