bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telehealth-enabled behavioral treatment for problem behaviors in boys with fragile X syndrome: a randomized controlled trial
Authors: Hall Scott S. , Monlux Katerina D. , Rodriguez Arlette Bujanda , Jo Booil , Pollard Joy S. 
Published: November 2020

Abstract
Background
Children with fragile X syndrome (FXS) are at increased risk for exhibiting problem behaviors such as aggression and self-injury. However, many children with FXS have limited access to behavioral treatments that have known efficacy due to the low availability of treatment providers and the wide geographical dispersion of families with FXS across the country. Telehealth may offer a cost-effective and practical solution to overcome these significant barriers. We examined the effect of administering an established behavior analytic intervention called functional communication training (FCT) via telehealth on levels of problem behaviors exhibited by boys with FXS. We also examined treatment acceptability, as well as the effect of the treatment on levels of parenting stress.

Methods
Boys with FXS, aged 3 to 10 years, who displayed problem behaviors daily, were randomized to receive FCT via telehealth (n = 30) or treatment as usual (n = 27) over 12 weeks. Outcome measures included in-session observations of problem behavior, the Aberrant Behavior Checklist—Community (ABC-C), the Treatment Acceptability Rating Form—Revised (TARF-R), and the Parenting Stress Index, 4th edition (PSI-4).

Results
Intention-to-treat analyses indicated that scores on the irritability subscale of the ABC-C, our primary outcome measure, decreased significantly for boys who received FCT via telehealth compared to boys who received treatment as usual (p < .001, Cohen’s d = 0.65). In-session observations conducted for those who received treatment showed that levels of problem behavior decreased by 91% from baseline. Levels of parenting stress related to child behavioral problems were also lower following FCT treatment, and caregivers reported that the intervention was acceptable.

Conclusions
These findings support telehealth-enabled FCT as a framework for expanding access to behavioral treatments for problem behaviors in children with FXS. Expanded delivery of behavior analytic treatment via telehealth also has the potential to lower healthcare costs, improve child and family quality of life, and lead to advances in the treatment of problem behavior in the broader population of individuals with neurodevelopmental disorders.

Trial registration
ClinicalTrials.gov, NCT03510156. Registered 27 April 2018
Identification of biomarkers for the accurate and sensitive diagnosis of three bacterial pneumonia pathogens using in silico approaches
Authors: Bakare Olalekan Olanrewaju , Keyster Marshall , Pretorius Ashley 
Published: November 2020

Abstract
Background
Pneumonia ranks as one of the main infectious sources of mortality among kids under 5 years of age, killing 2500 a day; late research has additionally demonstrated that mortality is higher in the elderly. A few biomarkers, which up to this point have been distinguished for its determination lack specificity, as these biomarkers fail to build up a differentiation between pneumonia and other related diseases, for example, pulmonary tuberculosis and Human Immunodeficiency Infection (HIV). There is an inclusive global consensus of an improved comprehension of the utilization of new biomarkers, which are delivered in light of pneumonia infection for precision identification to defeat these previously mentioned constraints. Antimicrobial peptides (AMPs) have been demonstrated to be promising remedial specialists against numerous illnesses. This research work sought to identify AMPs as biomarkers for three bacterial pneumonia pathogens such as Streptococcus pneumoniae, Klebsiella pneumoniae, Acinetobacter baumannii using in silico technology. Hidden Markov Models (HMMER) was used to identify putative anti-bacterial pneumonia AMPs against the identified receptor proteins of Streptococcus pneumoniae, Klebsiella pneumoniae, and Acinetobacter baumannii. The physicochemical parameters of these putative AMPs were computed and their 3-D structures were predicted using I-TASSER. These AMPs were subsequently subjected to docking interaction analysis against the identified bacterial pneumonia pathogen proteins using PATCHDOCK.

Results
The in silico results showed 18 antibacterial AMPs which were ranked based on their E values with significant physicochemical parameters in conformity with known experimentally validated AMPs. The AMPs also bound the pneumonia receptors of their respective pathogens sensitively at the extracellular regions.

Conclusions
The propensity of these AMPs to bind pneumonia pathogens proteins justifies that they would be potential applicant biomarkers for the recognizable detection of these bacterial pathogens in a point-of-care POC pneumonia diagnostics. The high sensitivity, accuracy, and specificity of the AMPs likewise justify the utilization of HMMER in the design and discovery of AMPs for disease diagnostics and therapeutics.
Transoral intraarticular cage distraction and C-JAWS fixation for revision of basilar invagination with irreducible atlantoaxial dislocation
Authors: Zou Xiaobao , Wang Binbin , Yang Haozhi , Ge Su , Ouyang Bieping , Chen Yuyue , Ni Ling , Zhang Shuang , Xia Hong , Ma Xiangyang 
Published: November 2020

Abstract
Background
The revision surgery of basilar invagination (BI) with irreducible atlantoaxial dislocation (IAAD) after a previous occipitocervical fusion (OCF) is challenging. Transoral revision surgery has more advantages than a combined anterior and posterior approach in addressing this pathology. The C-JAWS is a cervical compressive staple that has been used in the lower cervical spine with many advantages. Up to now, there is no report on the application of C-JAWS in the atlantoaxial joint. We therefore present this report to investigate the clinical outcomes of transoral intraarticular cage distraction and C-JAWS fixation for revision of BI with IAAD.

Methods
From June 2011 to June 2015, 9 patients with BI and IAAD were revised by this technique after previous posterior OCF in our department. Plain cervical radiographs, computed tomographic scans and magnetic resonance imaging were obtained pre- and postoperatively to assess the degree of atlantoaxial dislocation and compression of the cervical cord. The Japanese Orthopedic Association (JOA) score was used to evaluate the neurological function.

Results
The revision surgeries were successfully performed in all patients. The average follow-up duration was 18.9 ± 7.3 months (range 9–30 months). The postoperative atlas-dens interval (ADI), cervicomedullary angle (CMA), distance between the top of the odontoid process and the Chamberlain line (CL) and JOA score were significantly improved in all patients (P < 0.05). Bony fusion was achieved after 3–9 months in all cases. No patients developed recurrent atlantoaxial instability.

Conclusions
Transoral revision surgery by intraarticular cage distraction and C-JAWS fixation could provide a satisfactory outcome for BI with IAAD after a previous unsuccessful posterior operation.
STAT4 targets KISS1 to promote the apoptosis of ovarian granulosa cells
Authors: Jiang Yao , Xin Xiaoping , Pan Xiangchun , Zhang Ailing , Zhang Zhe , Li Jiaqi , Yuan Xiaolong 
Published: November 2020

Abstract
Background
In mammals, it is known that the estradiol-17β (E2) is mainly synthetized in ovarian granulosa cells (GCs), and the excessive apoptosis of GCs induces the follicular atresia. Many studies have implicated the essential role of KISS1, with the pro-synthetic effect of E2 and the anti-apoptotic effect on GCs, in the mammalian folliculogenesis, and several STAT4 potential binding sites were previously predicted on the promoter of KISS1 in pigs. However, the biological effects of STAT4 on GCs and the molecular regulation between STAT4 and KISS1 remained largely unknown.

Methods
Using the porcine GCs as the cellular model, the overexpression plasmid, small interfering RNA, 5′-deletion and luciferase assay were applied to investigate the molecular mechanisms for STAT4 regulating the expression of KISS1.

Results
In this study, the STAT4 negatively regulated the mRNA and protein levels of KISS1 in porcine GCs, and the mRNA level of STAT4 was observed to significantly decrease from immature to mature follicles, which was inversed with that of KISS1. The relative luciferase activity of KISS1 promoter was significantly increased with deletion of the fourth potential binding site (− 305/− 295), and ChIP further confirmed that the STAT4 bound at − 305/− 295 region of KISS1. Besides, the STAT4 significantly regulated the mRNA levels of PDK1, FOXO3 and TSC2 of PI3K signaling pathway to promote the cell apoptosis and the percentage of cells at G0/G1 phase of cell cycle in GCs. Alternatively, the STAT4 significantly decreased the mRNA levels of CYP17, 3B-HSD, 17B-33 HSD, ESR1, and ESR2, as well as the concentration of E2 in GCs. Furthermore, interfering with the expression of STAT4 was observed to significantly stimulate the pro-synthetic effect of E2 and anti-apoptotic effect of KISS1 in GCs.

Conclusions
Collectively, the STAT4 might directly target at − 305/− 295 region of KISS1 to negatively regulate the transcription of KISS1, promote the cell apoptosis via PI3K signaling pathway, suppress the synthesis of E2 through the estrogen signaling pathway in porcine GCs. These proposed works could provide useful insight in further investigations on the molecular functionalities of STAT4 and KISS1 in the folliculogenesis of mammals.
Transparency, trust, and community welfare: towards a precision public health ethics framework for the genomics era
Authors: Juengst Eric T. , Van Rie Annelies 
Published: November 2020

AbstractInfectious disease control is experiencing a paradigm shift, as pathogen sequencing technologies and digital applications are increasingly implemented for control of diseases such as tuberculosis, Ebola, and COVID-19. A new ethical framework should be a critical part of this emerging paradigm to ensure that the benefit of precision public health interventions based on advances in genomics research is not outweighed by the risks they pose to individuals, families, and vulnerable segments of the population. We suggest that the ethical framework guiding practice in this domain combines standard precepts from public health ethics with emerging ethics principles from precision medicine.
Cabozantinib as the causative agent of high-grade fever in a patient with a background of metastatic clear cell renal cell carcinoma: a case report
Authors: Chen H. M. N. , Morris M. , Manders P. M. 
Published: November 2020

Abstract
Background
Fever, as an adverse event, is well documented in a wide array of drugs including multiple tyrosine kinase inhibitors however, it is not a previously well described consequence of the novel multi-targeted tyrosine kinase inhibitor, cabozantinib.

Case presentation
In this paper we document the first detailed review of high-grade fevers in a 54 year old male (Caucasian) with a background of metastatic clear cell renal cell carcinoma recently commenced on cabozantinib. After detailed investigation, we exclude infection and other common causes of fever as the causative agent and further, definitively resolve the recurrent fever by ceasing cabozantinib and starting a short course of oral corticosteroids.

Conclusions
We have demonstrated that cabozantinib should always be considered in the aetiology of high-grade fever in relevant patients. Further, we demonstrate that temporary cessation of cabozantinib and a course of short-term steroids can induce resolution of fever and allow for recommencement of cabozantinib safely thereafter.
Bisphenol A disrupts inflammatory responses via Nod-like receptor protein 3 pathway in macrophages
Authors: Lee Hee-Weon , Ha Sang Keun , Kim Yoonsook 
Published: November 2020

AbstractBisphenol A (BPA) is a harmful endocrine disruptor that is found in polycarbonate plastics such as plastic food containers and in epoxy resins such as dental resins. In the current study, we investigated the effect of BPA on function of inflammatory responses involving activation of Nod-like receptor protein 3 (NLRP3) inflammasome. Treatment with BPA decreased nitric oxide (NO) production and expression levels of inducible NO synthase (iNOS), prostaglandin E2(PGE2), and cyclooxygenase (Cox)-2 in RAW 264.7 macrophages. BPA also suppressed activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B activity (NF-κB). BPA significantly down-regulated the secretion of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-18. The decreased production of IL-1β and IL-18 induced by BPA was associated with inactivation of the activity of the NLRP3 inflammasome. Collectively, these data suggested that BPA could act as a disruptor of the inflammation activity by regulating the NF-κB/MAPK pathways and NLRP3 inflammasome activation.
Misperception of sleep in bipolar disorder: an exploratory study using questionnaire versus actigraphy
Authors: Ihler Henrik Myhre , Meyrel Manon , Hennion Vincent , Maruani Julia , Gross Gregory , Geoffroy Pierre A. , Lagerberg Trine Vik , Melle Ingrid , Bellivier Frank , Scott Jan , Etain Bruno 
Published: November 2020

Abstract
Background
The concept of misperception of sleep refers to the estimated discrepancy between subjective and objective measures of sleep. This has been assessed only in a few prior studies in individuals with Bipolar Disorder (BD) as compared to Healthy Controls (HC) and with mixed results.

Methods
We assessed a sample of 133 euthymic individuals with BD and 63 HC for retrospective subjective (Pittsburgh Sleep Quality Index) and objective (21 days of actigraphy recording) measures of total sleep time, sleep latency and sleep efficiency. We first investigated the correlations between these subjective and objective measures in the two groups. We then compared individuals with BD and HC for the absolute values of the differences between subjective and objective sleep parameters, used as a proxy of the magnitude of misperception of sleep. Finally, we undertook regression analyses to assess associations between clinical groups, core demographics, clinical factors and misperception of sleep.

Results
The correlation coefficients between subjective and objective measures of sleep did not differ between groups (total sleep time: rho = .539 in BD and rho = .584 in HC; sleep latency: rho = .190 in BD and rho = .125 in HC; sleep efficiency: rho = .166 in BD and rho = .222 in HC). Individuals with BD did not differ from HC in the magnitude of misperception of total sleep time, sleep latency nor sleep efficiency. Individuals with BD type 1 misperceived their sleep efficiency significantly more than individuals with BD type 2, with no further difference between BD type 1 and BD type 2 regarding sleep latency and sleep duration misperceptions. Three factors (age, symptoms of obstructive sleep apnea, and mild depressive symptoms), were the main contributors to the magnitude of misperception of sleep.

Conclusions
Misperception of sleep was not associated with a diagnosis of BD. In this sample, mild depressive symptoms, older age, or symptoms of obstructive sleep apnea may be related to greater sleep misperception. In that case, the reliability of subjective measures may decrease as the misperception of sleep increases. This study may help guide clinicians in selecting the best approach for assessing sleep (objective versus subjective measures) in individuals with BD.
Defining phenotypes of long-term lithium and valproate response, including combination therapy: a modified application of the Alda scale in patients with bipolar disorders
Authors: Lee Jinyoung , Baek Ji Hyun , Lee Dongbin , Ahn Sung Woo , Yang So-Yung , Choi Yujin , Bahk Yong Chun , Hong Kyung Sue 
Published: November 2020

Abstract
Background
When evaluating the long-term treatment response to mood stabilizers using the Alda scale, mood stabilizer combination therapy is typically considered a confounding factor, and patients receiving combination therapy are excluded from the analysis. However, this may result in bias if those under combination therapy are worse treatment responders. This study aims to explore whether the Alda scale is applicable to patients taking lithium and valproate combination therapy. We compared long-term treatment response in patients receiving monotherapy and combination therapy of the two drugs, and investigated clinical correlates of the responses to each drug.

Methods
The study subjects consisted of 102 patients with bipolar I (BD-I) or bipolar II (BD-II) disorder who had been undergoing maintenance treatment with lithium and/or valproate for more than 2 years at a single specialized bipolar disorder clinic. Long-term treatment response was measured using the Alda scale and compared among the lithium monotherapy group, the valproate monotherapy group, and the mood stabilizer combination group. Clinical correlates of long-term treatment response were evaluated in lithium users and valproate users separately.

Results
There were no significant differences in terms of baseline illness characteristics among groups. The combination group showed the worst treatment response for all the response measurements applied. This group also had the higher rate of ‘poor responder’ with a statistically significant difference compared to valproate group. Older age at onset and (hypo)manic episode at onset showed significant positive associations with total Alda score in lithium users, while comorbid anxiety disorders, obsessive–compulsive disorder and mixed episode showed significant negative associations in valproate users.

Conclusions
The combination group had poorer long-term treatment response but did not show distinct clinical characteristics compared to the monotherapy groups. When exploring the long-term effects of mood stabilizers, excluding patients undergoing combination treatment could result in bias because they may represent a poor response group. The long-term treatment responses of lithium and valproate had different clinical correlates.
A portrait of Italian ‘Family houses’: diversified heritage in a redefined territorial and demographic context
Authors: Zanfi Federico , Merlini Chiara , Giavarini Viviana , Manfredini Fabio 
Published: November 2020

AbstractThe ‘family house’ has played a major role within the urbanisation processes that have been transforming the Italian landscape since the 1960s. It is a common feature of the widespread settlements that are part of what has been labelled the ‘diffuse city’ and was the subject of numerous studies during the 1990s. More than 20 years later, this paper returns to the topic of the Italian family house using a renewed methodological approach to describe relevant changes. The hypothesis here is that in order to grasp the tensions affecting ‘family houses’ in today’s context of demographic transition and increased imbalances between dynamic and declining areas, and to contemplate their future, the qualitative gaze adopted by scholars in the 1990s must be integrated with other investigative tools, focusing on demographic change, uses, and the property values of buildings. Using this perspective, the paper provides a series of ‘portraits’ rooted in four meaningful territorial contexts, portraits which may help scholars to redefine their imagery associated with family house and be useful for dedicated building policies.
Safety and efficacy of intravenous thrombolysis in stroke patients on prior antiplatelet therapy in the WAKE-UP trial
Authors:   on behalf of the WAKE-UP investigators, Frey Benedikt M. , Boutitie Florent , Cheng Bastian , Cho Tae-Hee , Ebinger Martin , Endres Matthias , Fiebach Jochen B. , Fiehler Jens , Ford Ian , Galinovic Ivana , Königsberg Alina , Puig Josep , Roy Pascal , Wouters Anke , Magnus Tim , Thijs Vincent , Lemmens Robin , Muir Keith W. , Nighoghossian Norbert , Pedraza Salvador , Simonsen Claus Z. , Gerloff Christian , Thomalla Götz 
Published: November 2020

Abstract
Background
One quarter to one third of patients eligible for systemic thrombolysis are on antiplatelet therapy at presentation. In this study, we aimed to assess the safety and efficacy of intravenous thrombolysis in stroke patients on prescribed antiplatelet therapy in the WAKE-UP trial.

Methods
WAKE-UP was a multicenter, randomized, double-blind, placebo-controlled clinical trial to study the efficacy and safety of MRI-guided intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time. The medication history of all patients randomized in the WAKE-UP trial was documented. The primary safety outcome was any sign of hemorrhagic transformation on follow-up MRI. The primary efficacy outcome was favorable functional outcome defined by a score of 0–1 on the modified Rankin scale at 90 days after stroke, adjusted for age and baseline stroke severity. Logistic regression models were fitted to study the association of prior antiplatelet treatment with outcome and treatment effect of intravenous alteplase.

Results
Of 503 randomized patients, 164 (32.6%) were on antiplatelet treatment. Patients on antiplatelet treatment were older (70.3 vs. 62.8 years, p <  0.001), and more frequently had a history of hypertension, atrial fibrillation, diabetes, hypercholesterolemia, and previous stroke or transient ischaemic attack. Rates of symptomatic intracranial hemorrhage and hemorrhagic transformation on follow-up imaging did not differ between patients with and without antiplatelet treatment. Patients on prior antiplatelet treatment were less likely to achieve a favorable outcome (37.3% vs. 52.6%, p = 0.014), but there was no interaction of prior antiplatelet treatment with intravenous alteplase concerning favorable outcome (p = 0.355). Intravenous alteplase was associated with higher rates of favorable outcome in patients on prior antiplatelet treatment with an adjusted odds ratio of 2.106 (95% CI 1.047–4.236).

Conclusions
Treatment benefit of intravenous alteplase and rates of post-treatment hemorrhagic transformation were not modified by prior antiplatelet intake among MRI-selected patients with unknown onset stroke. Worse functional outcome in patients on antiplatelets may result from a higher load of cardiovascular co-morbidities in these patients.