bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of adverse events in patients with acute myeloid leukemia in remission receiving oral azacitidine: experience from the phase 3 randomized QUAZAR AML-001 trial
Authors: Ravandi Farhad , Roboz Gail J. , Wei Andrew H. , Döhner Hartmut , Pocock Christopher , Selleslag Dominik , Montesinos Pau , Sayar Hamid , Musso Maurizio , Figuera-Alvarez Angela , Safah Hana , Tse William , Sohn Sang Kyun , Hiwase Devendra , Chevassut Timothy , Pierdomenico Francesca , La Torre Ignazia , Skikne Barry , Bailey Rochelle , Zhong Jianhua , Beach C. L. , Dombret Herve 
Published: August 2021

AbstractBackgroundMost older patients with acute myeloid leukemia (AML) who attain morphologic remission with intensive chemotherapy (IC) will eventually relapse and post-relapse prognosis is dismal. In the pivotal QUAZAR AML-001 trial, oral azacitidine maintenance therapy significantly prolonged overall survival by 9.9 months (P < 0.001) and relapse-free survival by 5.3 months (P < 0.001) compared with placebo in patients with AML in first remission after IC who were not candidates for transplant. Currently, the QUAZAR AML-001 trial provides the most comprehensive safety information associated with oral azacitidine maintenance therapy. Reviewed here are common adverse events (AEs) during oral azacitidine treatment in QUAZAR AML-001, and practical recommendations for AE management based on guidance from international cancer consortiums, regulatory authorities, and the authors’ clinical experience treating patients in the trial.MethodsQUAZAR AML-001 is an international, placebo-controlled randomized phase 3 study. Patients aged ≥ 55 years with AML and intermediate- or poor-risk cytogenetics at diagnosis, who had attained first complete remission (CR) or CR with incomplete blood count recovery (CRi) within 4 months before study entry, were randomized 1:1 to receive oral azacitidine 300 mg or placebo once-daily for 14 days in repeated 28-day cycles. Safety was assessed in all patients who received ≥ 1 dose of study drug.ResultsA total of 469 patients received oral azacitidine (n = 236) or placebo (n = 233). Median age was 68 years. Patients received a median of 12 (range 1–80) oral azacitidine treatment cycles or 6 (1–73) placebo cycles. Gastrointestinal AEs were common and typically low-grade. The most frequent grade 3–4 AEs during oral azacitidine therapy were hematologic events. AEs infrequently required permanent discontinuation of oral azacitidine (13%), suggesting they were effectively managed with use of concomitant medications and oral azacitidine dosing modifications.ConclusionOral azacitidine maintenance had a generally favorable safety profile. Prophylaxis with antiemetic agents, and blood count monitoring every other week, are recommended for at least the first 2 oral azacitidine treatment cycles, and as needed thereafter. Awareness of the type, onset, and duration of common AEs, and implementation of effective AE management, may maximize treatment adherence and optimize the survival benefits of oral azacitidine AML remission maintenance therapy.Trial registrationThis trial is registered on clinicaltrials.gov: NCT01757535 as of December 2012.
Association between atypical endometriosis and ovarian malignancies in the real world
Authors: So Kyeong A , Hong Sung Ran , Kim Nae Ri , Yang Eun Jung , Shim Seung-Hyuk , Lee Sun Joo , Kim Tae Jin 
Published: August 2021

Abstract
Background
To evaluate the clinical outcome of atypical endometriosis and its association with ovarian malignancy.

Methods
This retrospective study included patients diagnosed with atypical endometriosis between January 2001 and December 2017. All patients had received surgical treatment for ovarian tumor. The clinical characteristics and histopathological results of all patients were reviewed.

Results
Atypical endometriosis was diagnosed in 101 patients. We analyzed 98 patients with a mean age of 34.8 years (range: 16–58 years). Ten patients (10.2%) had previously undergone endometriosis surgery more than once. In total, 12 (12.2%) patients had atypical endometriosis-associated ovarian malignancy—nine had carcinomas and three had borderline tumor. The tumors were pathologically classified as follows: five, clear cell carcinomas; two, endometrioid adenocarcinomas; one, mixed clear cell and endometrioid adenocarcinoma; one, seromucinous carcinoma; two, mucinous borderline tumors; and one, seromucinous borderline tumor.

Conclusion
Atypical endometriosis is most frequently associated with clear cell carcinoma and endometrioid adenocarcinoma. To identify the risk of ovarian malignancy and manage patients with endometriosis, diagnosing atypical endometriosis and recognizing its precancerous potential are important.
Clinical and healthcare improvement through My Health Record usage and education in general practice (CHIME-GP): a study protocol for a cluster-randomised controlled trial
Authors: Bonney Andrew , Metusela Christine , Mullan Judy , Barnett Stephen , Rhee Joel , Kobel Conrad , Batterham Marijka 
Published: August 2021

Abstract
Background
There is an international interest in whether improved primary care can lead to a more rational use of health resources. There is evidence that educational interventions can lead to improvements in the quality of rational prescribing and test ordering. A new national platform for shared medical records in Australia, My Health Record (MHR), poses new opportunities and challenges for system-wide implementation. This trial (CHIME-GP) will investigate whether components of a multifaceted education intervention in an Australian general practice setting on rational prescribing and investigation ordering leads to reductions in health-service utilisation and costs in the context of the use of a national digital health record system.

Methods
The trial will be undertaken in Australian general practices. The aim of the research is to evaluate the effectiveness of components of a web-based educational intervention for general practitioners, regarding rational use of medicines, pathology and imaging in the context of the use of the MHR system. Our target is to recruit 120 general practitioners from urban and regional regions across Australia. We will use a mixed methods approach incorporating a three-arm pragmatic cluster randomised parallel trial and a prospective qualitative inquiry. The effect of each education component in each arm will be assessed, using the other two arms as controls. The evaluation will synthesise the results embedding qualitative pre/post interviews in the quantitative results to investigate implementation of the intervention, clinical behaviour change and mechanisms such as attitudes, that may influence change. The primary outcome will be an economic analysis of the cost per 100 consultations of selected prescriptions, pathology and radiology test ordering in the 6 months following the intervention compared with 6 months prior to the intervention. Secondary outcome measures include the rates per 100 consultations of selected prescriptions, pathology and radiology test ordering 6 months pre- and post-intervention, and comparison of knowledge assessment tests pre- and post-intervention.

Discussion
The trial will produce robust health economic analyses on the evidence on educational intervention in reducing unnecessary prescribing, pathology and imaging ordering, in the context of MHR. In addition, the study will contribute to the evidence-base concerning the implementation of interventions to improve the quality of care in primary care practice.

Trial registration
ClinicalTrials.gov ACTRN12620000010998. Registered on 09 January 2020 with the Australian New Zealand Clinical Trials Registry
The impact of physical training on length of hospital stay and physical function in patients hospitalized with community-acquired pneumonia: protocol for a randomized controlled trial
Authors: Ryrsø Camilla Koch , Faurholt-Jepsen Daniel , Ritz Christian , Pedersen Bente Klarlund , Hegelund Maria Hein , Dungu Arnold Matovu , Sejdic Adin , Lindegaard Birgitte , Krogh-Madsen Rikke 
Published: August 2021

Abstract
Background
Community-acquired pneumonia (CAP) is a leading cause of hospitalization worldwide. Bed rest with low levels of physical activity is common during periods of hospitalization and leads to functional decline as well as increased risk of complications. The aim of this study is to assess the effect of supervised physical training during hospitalization with CAP compared with standard usual care for CAP on length of hospital stay, risk of readmission, mortality risk, physical capacity, muscle and fat mass, muscle strength, metabolic function, systemic inflammation, health-related quality of life, and physical activity level.

Methods
This study is a randomized controlled trial with three parallel experimental arms. Based on a sample size calculation, a total of 210 patients admitted with CAP at Nordsjællands Hospital, Hillerød, Denmark, will be recruited. Patients will be randomly allocated (1:1:1) to either (1) standard usual care, (2) standard usual care combined with in-bed cycling, or (3) standard usual care combined with exercises from a booklet. The primary outcome is differences in length of hospital stay between groups, with secondary outcomes being differences between groups in time to (1) 90-day readmission and (2) 180-day mortality. Further secondary outcomes are differences in changes from baseline between groups in (3) lean mass, (4) fat mass, (5) fat-free mass, (6) physical capacity, (7) health-related quality of life, (8) systemic inflammation, and (9) physical activity level after discharge. Data on length of hospital stay, readmission, and mortality will be collected from patient files, while total lean, fat, and fat-free mass will be quantitated by dual-energy x-ray absorptiometry and bioelectrical impedance analysis. Physical function will be assessed using grip strength, 30-s chair stand tests, and Barthel Index-100. Health-related quality of life will be assessed with the EQ-5D-5L questionnaire. Systemic inflammation will be assessed in blood samples, while accelerometers are used for measuring physical activity.

Discussion
If a simple physical training program appears to diminish the impact of critical illness and hospitalization on clinical outcome, mobility, and health-related quality of life, it may lead to novel therapeutic approaches in the treatment of patients hospitalized with CAP.

Trial registration
ClinicalTrials.gov NCT04094636. Registered on 1 April 2019
Reducing the burden of orthodontic care for children with clefts: evaluating the effectiveness of pre-alveolar bone graft orthodontics in unilateral non-syndromic cleft patients (PABO study)— A study protocol for a multicentric randomised controlled trial
Authors: Thiruvenkatachari Badri , Hussain Syed Altaf , Batra Puneet , Vijayakumar Charanya , Prathap. C Manoj 
Published: August 2021

Abstract
Background
An alveolar cleft commonly affects 75% of cleft lip and palate patients. While it is common practice to provide a course of orthodontic treatment before alveolar bone grafting, there are no previous high-quality studies reporting on the benefits of this type of treatment.

Aim
The aim of the study is to evaluate the effectiveness of pre-alveolar bone graft orthodontics for unilateral non-syndromic cleft palate patients.

Method
The PABO trial is a multicentric, parallel, two-arm, single-blinded randomised controlled trial. The inclusion criteria include unilateral cleft alveolus patients requiring bone graft and between the age group of 8 and 13 years with erupted upper central incisors. Participants will be recruited at three centres across India. Participants will be randomised to orthodontic treatment or no orthodontic treatment group. Both groups of participants will have alveolar bone graft surgery and will be followed up for 6 months after surgery. The primary outcome will be the success of the alveolar bone graft measured by anterior oblique radiograph and secondary outcomes include quality of life, cost analysis and quality of the dento-occlusal outcome. Data analysis will be carried out by an independent statistician at the end of the study.

Discussion
This study is the first to evaluate the effect of orthodontics on alveolar bone graft success. The increased burden of care for these patients with multiple treatments required from multiple specialists from birth to adult life highlights the need for reducing unnecessary treatment provision.

Trial Registration
Clinical Trials Registry – India, CTRI/2020/10/028756. Trial prospectively registered on 29 October 2020.
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Effectiveness of deep cervical fascial manipulation and yoga postures on pain, function, and oculomotor control in patients with mechanical neck pain: study protocol of a pragmatic, parallel-group, randomized, controlled trial
Authors: Raja G Prabu , Bhat N Shyamasunder , Fernández-de-las-Peñas César , Gangavelli Ranganath , Davis Fiddy , Shankar Ravi , Prabhu Anupama 
Published: August 2021

Abstract
Introduction
Mechanical neck pain (MNP) is a commonly occurring musculoskeletal condition that is usually managed using electrical modalities, joint mobilization techniques, and therapeutic exercises, but has limited evidence of their efficacy. Pathology (densification) of the deep cervical fascia that occurs due to the increased viscosity of hyaluronic acid (HA) may induce neck pain and associated painful symptoms of the upper quarter region. Fascial manipulation (FM) and yoga poses are considered to reduce the thixotropy of the ground substances of the deep fascia and improve muscle function. The purpose of this study is to investigate the effect of FM and sequential yoga poses (SYP) when compared to the usual care on pain, function, and oculomotor control in MNP.

Methods
This FaCe-Man trial will recruit 160 patients with subacute and chronic mechanical neck pain diagnosed using predefined criteria. Participants will be randomized to either the intervention group or the usual care group, using a random allocation ratio of 1:1. Patients in the intervention group will receive FM (4 sessions in 4 weeks) and SYP (12 weeks) whereas the standard care group will receive cervical mobilization/ thoracic manipulation (4 sessions in 4 weeks) and therapeutic exercises (12 weeks). The primary outcome is the change in the numeric pain rating scale (NPRS). The secondary outcomes include changes in the patient-specific functional scale and oculomotor control, myofascial stiffness, fear-avoidance behavior questionnaire, and elbow extension range of motion during neurodynamics test 1.

Discussion
If found effective, FM along with SYP investigated in this trial can be considered as a treatment strategy in the management of mechanical neck pain. Considering the magnitude of the problem, and the pragmatic and patient-centered approach to be followed, it is worth investigating this trial.

Trial registration
ClinicalTrials.gov CTRI/2020/01/022934. Registered on January 24, 2020 with ctri.nic.in. Clinical Trials Registry – India.
Randomized controlled trial of neurologic music therapy in Parkinson’s disease: research rehabilitation protocols for mechanistic and clinical investigations
Authors: Buard Isabelle , Lattanzio Lucas , Stewart Rebekah , Thompson Sarah , Sjoberg Kristin , Hookstadt Karen , Morrow Meghan , Holden Samantha K. , Sillau Stefan , Thaut Michael , Kluger Benzi 
Published: August 2021

Abstract
Background
Presently available medications and surgical treatments for Parkinson’s disease have limited effects on fine motor problems and often leave patients with significant fine motor disability. Standard of care occupational therapy (OT) yields low efficacy, potentially due to a lack of standard protocols. Neurologic music therapy (NMT) techniques, especially rhythmic auditory stimulation which relies on interaction between rhythm and movement, have shown to be effective in PD gait rehabilitation possibly through their reliance on neural pathways that are not affected by PD. Therapeutic instrumental music performance (TIMP) is one other NMT technique that holds promise but which mode of action and efficacy has not been investigated in PD yet.

Methods
One hundred PD participants will be randomly assigned to receive 15 sessions of either TIMP with rhythm or TIMP without rhythm, standard of care OT, or to be waitlisted (control) over 5 consecutive weeks. Brain oscillatory responses will be collected using magnetoencephalography during an auditory-motor task to understand the underlying mechanisms. The Grooved Pegboard, the UPDRS III finger tap, and the finger-thumb opposition will be assessed to investigate clinical changes related to fine motor function. This project will also serve to confirm or refute our pilot data findings suggesting NMT relies on compensatory brain networks utilized by the PD brain to bypass the dysfunctional basal ganglia.

Discussion
This study aims to use standardized TIMP and OT research protocols for investigating the neuronal pathways utilized by each intervention and possibly study their efficacy with respect to fine motor rehabilitation via a randomized control trial in the PD population.

Trial registration
ClinicalTrials.gov NCT03049033. Registered on September 29, 2020
Conversion of organosolv pretreated hardwood biomass into 5-hydroxymethylfurfural (HMF) by combining enzymatic hydrolysis and isomerization with homogeneous catalysis
Authors: Dedes Grigorios , Karnaouri Anthi , Marianou Asimina A. , Kalogiannis Konstantinos G. , Michailof Chrysoula M. , Lappas Angelos A. , Topakas Evangelos 
Published: August 2021

Abstract
Background
Over the last few years, valorization of lignocellulosic biomass has been expanded beyond the production of second-generation biofuels to the synthesis of numerous platform chemicals to be used instead of their fossil-based counterparts. One such well-researched example is 5-hydroxymethylfurfural (HMF), which is preferably produced by the dehydration of fructose. Fructose is obtained by the isomerization of glucose, which in turn is derived by the hydrolysis of cellulose. However, to avoid harsh reaction conditions with high environmental impact, an isomerization step towards fructose is necessary, as fructose can be directly dehydrated to HMF under mild conditions. This work presents an optimized process to produce fructose from beechwood biomass hydrolysate and subsequently convert it to HMF by employing homogeneous catalysis.

Results
The optimal saccharification conditions were identified at 10% wt. solids loading and 15 mg enzyme/gsolids, as determined from preliminary trials on pure cellulose (Avicel® PH-101). Furthermore, since high rate glucose isomerization to fructose requires the addition of sodium tetraborate, the optimum borate to glucose molar ratio was determined to 0.28 and was used in all experiments. Among 20 beechwood solid pulps obtained from different organosolv pretreatment conditions tested, the highest fructose production was obtained with acetone (160 °C, 120 min), reaching 56.8 g/100 g pretreated biomass. A scale-up hydrolysis in high solids (25% wt.) was then conducted. The hydrolysate was subjected to isomerization eventually leading to a high-fructose solution (104.5 g/L). Dehydration of fructose to HMF was tested with 5 different catalysts (HCl, H3PO4, formic acid, maleic acid and H-mordenite). Formic acid was found to be the best one displaying 79.9% sugars conversion with an HMF yield and selectivity of 44.6% and 55.8%, respectively.

Conclusions
Overall, this work shows the feasibility of coupling bio- and chemo-catalytic processes to produce HMF from lignocellulose in an environmentally friendly manner. Further work for the deployment of biocatalysts for the oxidation of HMF to its derivatives could pave the way for the emergence of an integrated process to effectively produce biobased monomers from lignocellulose.
Isolation of Tibet Orbivirus from Culicoides jacobsoni (Diptera, Ceratopogonidae) in China
Authors: Duan Ying Liang , Yang Zhen Xing , Bellis Glenn , Li Le 
Published: August 2021

Abstract
Background
Tibet Orbivirus (TIBOV) is a recently discovered Orbivirus known to infect cattle, Asian buffalo and goats in south-western China. It was first isolated from mosquitoes and subsequently from biting midges (Culicoides spp.) in Yunnan, China, indicating that it is an arbovirus. Little is known of its potential to cause disease, but the economic importance of related viruses promoted an investigation of potential Culicoides spp. vectors of TIBOV.

Methods
Biting midges were collected approximately once per week between May and December 2020, at a cattle farm in Wulong village, Shizong County, Yunnan Province, China. Approximately 3000 specimens of nine species were subsequently used in attempts to isolate virus, and a further 2000 specimens of six species were tested for the presence of bluetongue virus (BTV) and TIBOV using a RT-qPCR test.

Results
Virus isolation attempts resulted in the isolation of three viruses. One isolate from a pool of Culicoidesjacobsoni was identified as TIBOV, while the other two viruses from C.orientalis and C.tainanus remain unidentified but are not BTV or TIBOV. RT-qPCR analysis did not detect BTV in any specimens, but a single pool containing five specimens of C. jacobsoni and another containing five specimens of C. tainanus produced PCR quantification cycle (Cq) values of around 28 that may indicate infection with TIBOV.

Conclusions
The isolation of TIBOV from C. jacobsoni satisfies one criterion required to prove its status as a vector of this virus. This isolation is supported by a low Cq value produced from a different pool of this species in the RT-qPCR test. The low Cq value obtained from a pool of C. tainanus suggests that this species may also be able to satisfy this criterion. Both of these species are widespread throughout Asia, with C. jacobsoni extending into the Pacific region, which raises the possibility that TIBOV may be more widespread than is currently known.

Graphical abstract