bluuebunny/crossref_metadata_2025_split huggingface dataset:
Axitinib in combination with radiotherapy for advanced hepatocellular carcinoma: a phase I clinical trial
Authors: Yang Kai-Lin , Chi Mau-Shin , Ko Hui-Ling , Huang Yi-Ying , Huang Su-Chen , Lin Yu-Min , Chi Kwan-Hwa 
Published: January 2021

AbstractBackgroundTo investigate maximum tolerated dose (MTD) of axitinib, a selective vascular endothelial growth factor receptor 1–3 inhibitor, in combination with radiotherapy (RT) for advanced hepatocellular carcinoma (HCC).MethodsThis phase I study followed the rule of traditional 3 + 3 design. Major eligibility included: (1) patients with advanced HCC unsuitable for surgery, radiofrequency ablation or transarterial chemoembolization, or who failed after prior local–regional treatment; (2) failure on sorafenib or no grant for sorafenib from health insurance system. Eligible patients with advanced HCC received axitinib for total 8 weeks during and after RT. Three cohorts with axitinib dose escalation were planned: 1 mg twice daily (level I), 2 mg twice daily (level II) and 3 mg twice daily (level III). The prescribed doses of RT ranged from 37.5 to 67.5 Gy in 15 fractions to liver tumor(s) and were determined based on an upper limit of mean liver dose of 18 Gy (intended isotoxic RT for normal liver). The primary endpoint was MTD of axitinib in combination with RT. The secondary endpoints included overall response rate (ORR), RT in-field response rate, acute and late toxicities, overall survival (OS) and progression free survival (PFS).ResultsTotal nine eligible patients received axitinib dose levels of 1 mg twice daily (n = 3), 2 mg twice daily (n = 3) and 3 mg twice daily (n = 3). Dose-limiting toxicity (DLT) did not occur in the 3 cohorts; the MTD was defined as 3 mg twice daily in this study. ORR was 66.7%, including 3 complete responses and 3 partial responses, at 3 months after treatment initiation. With a median follow-up of 16.6 months, median OS was not reached, 1-year OS was 66.7%, and median PFS was 7.4 months.ConclusionsAxitinib in combination with RT for advanced HCC was well tolerated with an axitinib MTD of 3 mg twice daily in this study. The outcome analysis should be interpreted with caution due to the small total cohort.Trial registrationClinicalTrials.gov (Identifier: NCT02814461), Registered June 27, 2016—Retrospectively registered,https://clinicaltrials.gov/ct2/show/NCT02814461
miRNA-128 modulates bone neoplasms cells proliferation and migration through the WNT/β-catenin and EMT signal pathways
Authors: Li Yang , Long Xiaotao , Wang Ji , Peng Jing , Shen Kai 
Published: January 2021

Abstract
Background
Bone neoplasms present poor prognosis due to recurrence and metastasis. Although the role microRNAs (miRNAs) in inhibiting growth and metastasis of bone neoplasms has been investigated, the underlying potential molecular mechanisms mediated by miRNA-128 (miR-218) for the invasiveness of bone neoplasms cells are still not completely understood. The purpose of this study was to identify the regulatory mechanisms of miR-218 in bone neoplasms cells.

Methods
Western blotting, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Counting Kit-8 assay, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, luciferase activity assay immunofluorescence, and immunohistochemistry were used to analyze the regulatory effects of miR-218 on bone neoplasms cells.

Results
Here, the results showed that transfection of miR-128 suppressed bone neoplasms cells proliferation, migration, and invasion. Genetic knockdown of miR-128 in bone neoplasms cells suppressed the activation of the Wnt/β-catenin and epithelial-mesenchymal transition (EMT) signaling pathways. Activation of Wnt or EMT blocked miR-128-inhibited cells proliferation and migration in bone neoplasms cells. Exogenously introduced miR-128 markedly inhibited tumor regeneration in bone neoplasms xenograft models.

Conclusions
These results define a tumor-regulated function for miR-128 in bone neoplasms by down-regulation of the Wnt/β-catenin and EMT signal pathways, which provided a potential target for bone neoplasms gene therapy.
Treatment preference among patients with spinal muscular atrophy (SMA): a discrete choice experiment
Authors: Monnette Alisha , Chen Er , Hong Dongzhe , Bazzano Alessandra , Dixon Stacy , Arnold W. David , Shi Lizheng 
Published: January 2021

AbstractObjectiveTo examine patient/caregiver preference for key attributes of treatments for spinal muscular atrophy (SMA).BackgroundIn the rapidly evolving SMA treatment landscape, it is critically important to understand how attributes of potential treatments may impact patient/caregiver choices.Design/methodsA discrete choice experiment survey was developed based on qualitative interviews. Patients with SMA (≥ 18 years) and caregivers of patients were recruited through a U.S. patient organization. Respondents made choices in each of 12 sets of hypothetical treatments. The relative importance of five treatment characteristics was compared (measured by regression coefficients [RC] of conditional logit models): (1) improvement or stabilization of motor function, (2) improvement or stabilization of breathing function, (3) indication for all ages or pediatric patients only, (4) route of administration [repeated intrathecal (IT) injections, one-time intravenous (IV) infusion, daily oral delivery] and (5) potential harm (mild, moderate, serious/life threatening).ResultsPatient ages ranged from less than 1 to 67 years (n = 101, 65 self-reported and 36 caregiver-reported) and 64 were female. Total SMA subtypes included: type 1 (n = 21), type 2 (n = 48), type 3 (n = 29), other (n = 3). Prior spinal surgery was reported in 47 patients. Nusinersen and onasemnogene abeparvovec-xioi use were reported in 59 and 10 patients, respectively. Improvement in motor and breathing function was highly valued [RC: 0.65, 95% confidence interval (CI): 0.47–0.83 and RC: 0.79, 95% CI: 0.60–0.98, respectively]. Oral medication and one-time infusion were strongly preferred over repeated IT injections (RC: 0.80, 95% CI: 0.60–0.98 and RC: 0.51, 95% CI: 0.30–0.73, respectively). Patients least preferred an age-restricted label/approved use (≤ 2 years of age) (RC: − 1.28, 95% CI: − 1.47 to − 1.09). Cross-attributes trade-off decision suggested a lower willingness for a high-risk therapy despite additional efficacy gain. For some patients, there may be willingness to trade off additional gains in efficacy for a change in route of administration from repeated intrathecal administration to oral medication.ConclusionsImprovements in motor/breathing function, broad indication, oral or one-time infusion, and minimal risk were preferred treatment attributes. Treatment decisions should be made in clinical context and be tailored to patient needs.
Qualitative research of informal caregivers’ personal experiences caring for older adults with dementia in Lithuania
Authors: Kontrimiene Ausrine , Sauseriene Jolanta , Blazeviciene Aurelija , Raila Gediminas , Jaruseviciene Lina 
Published: January 2021

Abstract
Background
In many communities around the world, informal caregivers of older adults with dementia represent an essential, yet often underappreciated, source of long-term care. The present study aimed to determine the personal experiences of such caregivers, which could be instrumental for developing means of improving the quality of care for both care receivers and their informal caregivers.

Methods
Five semi-structured focus-group discussions were held. The participants (n = 31) were all informal caregivers of older adults with dementia. The focus-group discussions were audio-recorded and transcribed verbatim. An inductive approach was used, and thematic data analysis was applied.

Results
Four thematic categories were identified: learning caregiving through personal experience; implications of caregiving on social wellbeing; caregivers’ contradictory emotions regarding care delivery; and addressing challenges regarding care provision.

Conclusions
This study revealed, among the informal caregivers, a variety of experiences, contradicting feelings, and problem-solving strategies relating to the care of older adults with mental disorders. Becoming an effective caregiver involves professional and psychological development. Developing caregiving skills, supportive environment and positive attitude can help facilitate providing care. Caregiving largely impacts the emotional, physical, and social wellbeing of the person; thus, comprehensive approaches are needed to prevent burnout and associated social disadvantages.
Serum neurofilament measurement improves clinical risk scores for outcome prediction after cardiac arrest: results of a prospective study
Authors: Hunziker Sabina , Quinto Adrian , Ramin-Wright Maja , Becker Christoph , Beck Katharina , Vincent Alessia , Tisljar Kai , Disanto Giulio , Benkert Pascal , Leppert David , Pargger Hans , Marsch Stephan , Raoul Sutter  , Peters Nils , Kuhle Jens 
Published: January 2021

Abstract
Background
A recent study found serum neurofilament light chain (NfL) levels to be strongly associated with poor neurological outcome in patients after cardiac arrest. Our aim was to confirm these findings in an independent validation study and to investigate whether NfL improves the prognostic value of two cardiac arrest-specific risk scores.

Methods
This prospective, single-center study included 164 consecutive adult after out-of-hospital cardiac arrest (OHCA) patients upon intensive care unit admission. We calculated two clinical risk scores (OHCA, CAHP) and measured NfL on admission within the first 24 h using the single molecule array NF-light® assay. The primary endpoint was neurological outcome at hospital discharge assessed with the cerebral performance category (CPC) score.

Results
Poor neurological outcome (CPC > 3) was found in 60% (98/164) of patients, with 55% (91/164) dying within 30 days of hospitalization. Compared to patients with favorable outcome, NfL was 14-times higher in patients with poor neurological outcome (685 ± 1787 vs. 49 ± 111 pg/mL), with an adjusted odds ratio of 3.4 (95% CI 2.1 to 5.6, p < 0.001) and an area under the curve (AUC) of 0.82. Adding NfL to the clinical risk scores significantly improved discrimination of both the OHCA score (from AUC 0.82 to 0.89, p < 0.001) and CAHP score (from AUC 0.89 to 0.92, p < 0.05). Adding NfL to both scores also resulted in significant improvement in reclassification statistics with a Net Reclassification Index (NRI) of 0.58 (p < 0.001) for OHCA and 0.83 (p < 0.001) for CAHP.

Conclusions
Admission NfL was a strong outcome predictor and significantly improved two clinical risk scores regarding prognostication of neurological outcome in patients after cardiac arrest. When confirmed in future outcome studies, admission NfL should be considered as a standard laboratory measures in the evaluation of OHCA patients.
Evaluation of the efficacy and safety of icatibant and C1 esterase/kallikrein inhibitor in severe COVID-19: study protocol for a three-armed randomized controlled trial
Authors: Mansour Eli , Bueno Flávia F. , de Lima-Júnior José C. , Palma Andre , Monfort-Pires Milena , Bombassaro Bruna , Araujo Eliana P. , Bernardes Ana Flavia , Ulaf Raisa G. , Nunes Thyago A. , Ribeiro Luciana C. , Falcão Antônio Luís E. , Santos Thiago Martins , Trabasso Plinio , Dertkigil Rachel P. , Dertkigil Sergio S. , Maia Rafael P. , Benaglia Tatiana , Moretti Maria Luiza , Velloso Licio A. 
Published: January 2021

Abstract
Background
SARS-CoV-2, the virus that causes COVID-19, enters the cells through a mechanism dependent on its binding to angiotensin-converting enzyme 2 (ACE2), a protein highly expressed in the lungs. The putative viral-induced inhibition of ACE2 could result in the defective degradation of bradykinin, a potent inflammatory substance. We hypothesize that increased bradykinin in the lungs is an important mechanism driving the development of pneumonia and respiratory failure in COVID-19.

Methods
This is a phase II, single-center, three-armed parallel-group, open-label, active control superiority randomized clinical trial. One hundred eighty eligible patients will be randomly assigned in a 1:1:1 ratio to receive either the inhibitor of C1e/kallikrein 20 U/kg intravenously on day 1 and day 4 plus standard care; or icatibant 30 mg subcutaneously, three doses/day for 4 days plus standard care; or standard care alone, as recommended in the clinical trials published to date, which includes supplemental oxygen, non-invasive and invasive ventilation, antibiotic agents, anti-inflammatory agents, prophylactic antithrombotic therapy, vasopressor support, and renal replacement therapy.

Discussion
Accumulation of bradykinin in the lungs is a common side effect of ACE inhibitors leading to cough. In animal models, the inactivation of ACE2 leads to severe acute pneumonitis in response to lipopolysaccharide (LPS), and the inhibition of bradykinin almost completely restores the lung structure. We believe that inhibition of bradykinin in severe COVID-19 patients could reduce the lung inflammatory response, impacting positively on the severity of disease and mortality rates.

Trial registration
Brazilian Clinical Trials Registry Universal Trial Number (UTN) U1111-1250-1843. Registered on May/5/2020.
Socio-demographic influences on the prevalence of intestinal parasitic infections among workers in Qatar
Authors: Younes Nadin , Behnke Jerzy M. , Ismail Ahmed , Abu-Madi Marawan A. 
Published: January 2021

Abstract
Background
The rapid growth of Qatar in the last two decades has been associated with an enormous expansion of building programs in its cities and in the provision of new service industries. This in turn has attracted a large influx of immigrant workers seeking employment in jobs associated with food handling, domestic service, and the building industry. Many of these immigrants come from countries in the tropics and subtropics where intestinal parasitic infections are common. In this study, we explored the environmental and socio-demographic characteristics of immigrant workers in Doha Qatar, which might explain the persistence of the parasites that they harbor.

Methodology
This cross-sectional survey was conducted among 2486 newly arrived immigrant workers and those who visited Qatar previously during the period 2012–2014. Through questionnaires and census data, we characterized the socio-demographic conditions at an individual, family, and neighborhood levels.

Results
Overall, the prevalence of combined protozoan infection was 11.7% and that of helminth was 7.0%. Combined protozoan infections were significantly associated with immigrant workers arriving in Doha for the first time. In univariate log-linear statistical models fitted in phase 1 of the analysis, significant associations were observed between the prevalence of combined protozoan infections and personal and familial factors that included religion, the level of education of subjects, both parents’ educational levels and their jobs, and the number of siblings. Furthermore, environmental effects on the prevalence of protozoan infections including the country of origin, the floor of the house, toilet type, household content index, provision of household water, farming background showed strong associations with protozoan infections. However, in phase 2, multifactorial binary logistic generalized linear models focusing only on the significant effects identified in phase 1, showed that only five factors retained significance (age class, floor of the house, household contents index, father’s education, and the number of siblings). The only factors that had a significant effect on the prevalence of helminth infections were the subjects’ age class and the mother’s educational level.

Conclusions
The prevalence of intestinal protozoan parasites among immigrant workers in Qatar is clearly multifactorial in origin determined by key familial relationships of subjects and also the environment, in which the subjects lived prior to their arrival in Qatar. Moreover, our results suggest that screening protocols for applicants for visas/work permits need to be revised giving more careful attention to the intestinal protozoan infections that potential immigrant workers may harbor.

Graphical Abstract
Predicting the impact of outdoor vector control interventions on malaria transmission intensity from semi-field studies
Authors: Denz Adrian , Njoroge Margaret M. , Tambwe Mgeni M. , Champagne Clara , Okumu Fredros , van Loon Joop J. A. , Hiscox Alexandra , Saddler Adam , Fillinger Ulrike , Moore Sarah J. , Chitnis Nakul 
Published: January 2021

Abstract
Background
Semi-field experiments with human landing catch (HLC) measure as the outcome are an important step in the development of novel vector control interventions against outdoor transmission of malaria since they provide good estimates of personal protection. However, it is often infeasible to determine whether the reduction in HLC counts is due to mosquito mortality or repellency, especially considering that spatial repellents based on volatile pyrethroids might induce both. Due to the vastly different impact of repellency and mortality on transmission, the community-level impact of spatial repellents can not be estimated from such semi-field experiments.

Methods
We present a new stochastic model that is able to estimate for any product inhibiting outdoor biting, its repelling effect versus its killing and disarming (preventing host-seeking until the next night) effects, based only on time-stratified HLC data from controlled semi-field experiments. For parameter inference, a Bayesian hierarchical model is used to account for nightly variation of semi-field experimental conditions. We estimate the impact of the products on the vectorial capacity of the given Anopheles species using an existing mathematical model. With this methodology, we analysed data from recent semi-field studies in Kenya and Tanzania on the impact of transfluthrin-treated eave ribbons, the odour-baited Suna trap and their combination (push–pull system) on HLC of Anopheles arabiensis in the peridomestic area.

Results
Complementing previous analyses of personal protection, we found that the transfluthrin-treated eave ribbons act mainly by killing or disarming mosquitoes. Depending on the actual ratio of disarming versus killing, the vectorial capacity of An. arabiensis is reduced by 41 to 96% at 70% coverage with the transfluthrin-treated eave ribbons and by 38 to 82% at the same coverage with the push–pull system, under the assumption of a similar impact on biting indoors compared to outdoors.

Conclusions
The results of this analysis of semi-field data suggest that transfluthrin-treated eave ribbons are a promising tool against malaria transmission by An. arabiensis in the peridomestic area, since they provide both personal and community protection. Our modelling framework can estimate the community-level impact of any tool intervening during the mosquito host-seeking state using data from only semi-field experiments with time-stratified HLC.

Graphical Abstract
Intra-operative scleral rupture during 23 gauge pars plana vitrectomy: a case report
Authors: Agarwal Lalit , Agrawal Nisha , Aditya Kshitij 
Published: January 2021

AbstractBackgroundUse of perfluorocarbon liquid (PFCL) has been increasingly growing as an adjuvant in vitreo-retina surgeries. Some commonly encountered complications with its use include subretinal migration, formation of sticky silicone oil or retained PFCL in vitreous cavity and anterior chamber. Scleral rupture during PFCL injection has a rare occurrence. We report an unexpected event of scleral rupture during PFCL injection and discuss the management challenges faced by the surgeon.Case presentationA 66 year indo-aryan male was undergoing pars-plana vitrectomy (PPV) with diagnosis of subtotal rhegmatogenous retinal detachment (RD) with Proliferative Vitreo-retonipathy (PVR)-B. After near total vitrectomy PFCL was being injected and then there was sudden poor visualization of fundus with development of bullous RD and globe hypotony. The surgeon was not able to figure out the cause of hypotony and air was switched on in the infusion cannula. This further complicated the situation resulting in migration of air in the anterior chamber, posterior dislocation of intraocular lens complex, 180° inferior retinal dialysis and ballooning of the conjunctiva which gave a clue of probable scleral rupture. Conjunctival peritomy was performed superiorly and scleral defect was noted. Intraocular tissue incarceration and air leak was visible from the wound. This confirmed scleral rupture during PFCL injection. Repositioning of incarcerated retina was not possible and retinectomy was performed followed by repair of scleral rupture with lots of difficulty in a vitrectomised eye.ConclusionPFCL injection, a crucial step of vitreoretina surgery, should be performed slowly with extreme caution maintaining an optimal intraocular pressure to prevent devastating complications like scleral rupture.
Non-primary progressive language impairment in neurodegenerative conditions: protocol for a scoping review
Authors: Savage Sharon A. , Suárez-González Aida , Cassani Alice , Gopalan Ragaviveka , Stott Joshua 
Published: January 2021

Abstract
Background
Progressive language difficulties arise in many neurodegenerative conditions, causing significant impact upon patients and families. This occurs most obviously in primary progressive aphasia (PPA) but can also occur within other forms of progressive disease. In these cases, language decline may be significant, but as they are not the presenting or dominant symptom, may be overlooked in favour of more prominent cognitive, behaviour or motor deficits. To date, there has been no systematic investigation into non-primary progressive aphasia. This scoping review aims to describe the currently reported language impairments found in non-language-led dementias and identify their clinical relevance, defined as the impact on everyday living. It also seeks to identify the reported interventions for language impairment in this patient group to-date.

Method
We will conduct a scoping review of published studies that have assessed and/or treated aphasia in people diagnosed with a neurodegenerative condition other than primary progressive aphasia. The systematic search will include the electronic databases PubMed, MEDLINE, OVID-EMBASE, PsycINFO, and speechBITE, using search terms for specific non-language-led dementia subtypes. Findings will be mapped and described according to the type of language difficulties identified and rehabilitation approaches employed. Intervention studies will be evaluated for their methodological rigour using validated scales.

Discussion
This scoping review will provide an overview of the types of aphasia found in neurodegenerative conditions where language dysfunction is not the primary focus. Current treatment approaches (and gaps in the provision of treatment) will be identified.