bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Combined Randomised and Observational Study of Surgery for Fractures In the distal Radius in the Elderly (CROSSFIRE): a statistical analysis plan
Authors: Lawson Andrew , Naylor Justine , Buchbinder Rachelle , Ivers Rebecca , Balogh Zsolt , Smith Paul , Mittal Rajat , Xuan Wei , Howard Kirsten , Vafa Arezoo , Yates Piers , Rieger Bertram , Smith Geoff , Elkinson Ilia , Kim Woosung , Sungaran Jai , Latendresse Kim , Wong James , Viswanathan Sameer , Landale Keith , Drobetz Herwig , Tran Phong , Page Richard , Hau Raphael , Mulford Jonathan , Incoll Ian , Kale Michael , Schick Bernard , Higgs Andrew , Oppy Andrew , Perriman Diana , Harris Ian 
Published: July 2020

Abstract
Background
We are performing a combined randomised and observational study comparing internal fixation to non-surgical management for common wrist fractures in older patients. This paper describes the statistical analysis plan.

Methods/design
A Combined Randomised and Observational Study of Surgery for Fractures In the distal Radius in the Elderly (CROSSFIRE) is a randomised controlled trial comparing two types of usual care for treating wrist fractures in older patients, surgical fixation using volar locking plates and non-surgical treatment using closed reduction and plaster immobilisation. The primary aim of this comparative-effectiveness study is to determine whether surgery is superior to non-surgical treatment with respect to patient-reported wrist function at 12 months post treatment. The secondary outcomes include radiographic outcomes, complication rates and patient-reported outcomes including quality of life, pain, treatment success and cosmesis. Primary analysis will use a two-sample t test and an intention-to-treat analysis using the randomised arm of the study. Statistical analyses will be two-tailed and significance will be determined by p < 0.05. Sensitivity analyses will be conducted to assess for differences in intention-to-treat, per-protocol and as-treated analyses. Sensitivity analyses will also be conducted to assess selection bias by evaluating differences in participants between the randomised and observational study arms, and for bias relating to any missing data. An economic analysis will be conducted separately if surgery is shown to provide superior outcomes to a level of clinical significance.

Discussion
This statistical analysis plan describes the analysis of the CROSSFIRE study which aims to provide evidence to aid clinical decision-making in the treatment of distal radius fractures in older patients.

Trial registration
CROSSFIRE was approved by The Hunter New England Human Research Ethics Committee (HNEHREC Reference No: 16/02/17/3.04). Registered on 22 July 2016 with The Australian and New Zealand Clinical Trials Registry (ANZCTR Number; ACTRN12616000969460).
This manuscript is based on v.11 of the statistical analysis plan. A copy of v.11, signed by the chief investigator and the senior statistician is kept at the administering institution.
Coexistence of mycobacterial infections – Mycobacterium tuberculosis and Mycobacterium leprae – in Sri Lanka: a case series
Authors: Keragala B. S. D. P. , Herath H. M. M. T. B. , Janapriya G. H. D. C. , Vanitha S. , Balendran Thanushah , Janani Thavarajah , Keragala T. S. , Gunasekera C. N. 
Published: July 2020

Abstract
Background
Leprosy is one of the oldest mycobacterial infections and tuberculosis is the most common mycobacterial infection with a higher degree of infectivity than leprosy. Although both diseases are prevalent in clusters in developing countries, simultaneous occurrence of them in an individual is a rare entity, even in an endemic setting.

Case presentation
We describe six cases of tuberculosis and leprosy coinfection: a 57-year-old Sinhalese woman, a 47-year-old Tamil woman, a 72-year-old Tamil man, a 59-year-old Sinhalese man, a 54-year-old Sinhalese man, and a 50-year-old Sinhalese man. In this case series, five patients had lepromatous leprosy and the majority of patients were men. Three patients were detected to have tuberculosis at the outset of treatment of leprosy, while two developed tuberculosis later and one had extrapulmonary tuberculosis 5 years before the diagnosis of leprosy. The latter developed pulmonary tuberculosis as a reactivation while on treatment for leprosy. A majority of our patients with pulmonary tuberculosis had positive Mantoux test, high erythrocyte sedimentation rate, radiological evidence, and acid-fast bacilli in sputum. Human immunodeficiency virus and diabetes were detected in one patient. One patient had rifampicin-resistant tuberculosis, while she was on monthly rifampicin therapy for leprosy.

Conclusion
An immunocompromised status, such as human immunodeficiency virus infection, diabetes, and immunosuppressive drugs, are risk factors for tuberculosis infection. The use of steroids in the treatment of leprosy may increase the susceptibility to develop tuberculosis. Development of rifampicin resistance secondary to monthly rifampicin in leprosy is a major concern in treating patients coinfected with tuberculosis. Despite the paucity of reports of coinfection, it is advisable to screen for tuberculosis in patients with leprosy, especially if there are respiratory or constitutional symptoms, high erythrocyte sedimentation rate, and abnormal chest X-ray. The fact is that positive Mantoux and QuantiFERON Gold tests and presence of acid-fast bacilli in sputum are misleading, chest X-ray evidence of active tuberculosis and positive tuberculosis cultures are important diagnostic clues for active tuberculosis infection in a patient with leprosy. This is important to avoid monthly rifampicin in patients with suspected coinfections, which may lead to development of drug resistance to tuberculosis treatment. Whether prolonged steroid therapy in leprosy is a risk factor for development of tuberculosis is still controversial.
Postoperative visits by dedicated anesthesiologists in patients with elevated troponin: a retrospective cohort study evaluating postoperative care utility and early detection of complications
Authors: Akkermans Annemarie , Vernooij Lisette M. , van Klei Wilton A. , van Waes Judith A. 
Published: July 2020

Abstract
Background
An elevated cardiac troponin level after noncardiac surgery is associated with both morbidity and mortality. Guidelines suggest routine troponin monitoring in high-risk patients. We implemented a dedicated anesthesia team to conduct follow-up on patients with postoperative troponin elevation. We hypothesized that these visits would facilitate early detection of complications. Therefore, the aim of this study was to evaluate the effect of postoperative visits by dedicated anesthesiologists on early detection of complications and care utility.

Methods
This retrospective observational study included patients aged ≥ 60 years with an elevated troponin within the first 3 days after noncardiac surgery. Troponin elevation was detected by routine biomarker monitoring. The primary outcome was early detected myocardial infarctions by the dedicated anesthesiologist. Other outcomes were overall detected complications, additional diagnostic tests and treatment advised by the anesthesiologist, consultation of another medical specialist, and advised postoperative follow-up at the outpatient cardiac clinic within 1 week after surgery.

Results
Of the 811 patients, 509 (63%) received a postoperative consultation by the anesthesiologist. Anesthesiologists were involved in the early detection of 59% of all myocardial infarctions and in 12% of all complications. Besides cardiac ischemia, patients were also often diagnosed with noncardiac complications, including respiratory failure (8.9%), pneumonia (13.2%), and acute kidney injury (17.5%) within 1 week after surgery. In 75% of patients, anesthesiologists ordered additional diagnostics, most frequently existing of electrocardiograms and additional cardiac enzyme testing. Additionally, change in treatment was advised, most often a medication change, in 16% of patients.

Conclusions
Standard consultation of a dedicated anesthesiologist resulted in an early detection of 59% of all myocardial infarctions and involved a change in treatment in a considerable number of patients with postoperative troponin elevation. Whether this may improve patient outcomes remains to be elucidated.
Phytochemical screening, metabolite profiling and enhanced antimicrobial activities of microalgal crude extracts in co-application with silver nanoparticle
Authors: Hussein Hanaa Ali , Syamsumir Desy Fitrya , Radzi Siti Aisha Mohd , Siong Julius Yong Fu , Zin Nor Atikah Mohamed , Abdullah Mohd Azmuddin 
Published: July 2020

AbstractBackgroundMicroalgae is one of the major sources of natural compounds with antimicrobial activity. The metabolite profiling of the extracts could identify the bioactive compounds based on methanol (MET), ethanol (ETH), chloroform (CHL), hexane (HEX) and water (W) solvent systems. The microalgal crude extracts in co-application with silver nanoparticles (AgNPs) had enhanced antimicrobial activity with potential to overcome the global problem of microbial antibiotic resistance.ResultsChlorellasp. exhibited the highest lipid,N. oculatathe highest total saturated fatty acids (TSFA), andT. suecicathe highest mono-unsaturated (MUFA) and poly-unsaturated fatty acids (PUFA). The highest carbohydrate, protein and total phenolics contents (TPCs) were attained byN. oculata. The highest total flavonoids contents (TFCs), and chlorophyllaandbwere inT. suecica, while comparable level of carotenoids were found in all species. For high-performance thin-layer chromatography (HPTLC) analyses, the eicosapentaenoic acid (EPA) with high peaks were detected inT. suecica-HEX andN. oculata-CHL; and β-carotene inChlorellasp.-ETH. The gas chromatography–mass spectrometry (GC–MS) analyses showed high 13-docosenamide (Z)- inT. suecica-HEX; phytol inN. oculata-HEX; and neophytadiene inChlorellasp.-ETH. The AgNPs–MCEs–MET and HEX at the 1.5:1 ratios exhibited strong activities againstBacillus subtilis,Streptococcus uberis, andSalmonellasp.; and the AgNPs–T. suecica-HEX and MET and AgNPs–Chlorellasp.-HEX at the 1.5:1 ratios exhibited activities againstKlebsiella pneumoniae.ConclusionDifferent bioactive components were detected in the MCEs based on the HPTLC and GC–MS analyses. Significant antimicrobial activities against the pathogenic microbes were demonstrated by the synergistic effects of the MCEs in co-application with the AgNPs. This could be beneficial in the fight against sensitive and multidrug-resistant bacteria.
Use of Aspergillus oryzae during sorghum malting to enhance yield and quality of gluten-free lager beers
Authors: Rubio-Flores Monica , García-Arellano Arnulfo Ricardo , Perez-Carrillo Esther , Serna-Saldivar Sergio O. 
Published: July 2020

AbstractSorghum has been used for brewing European beers but its malt generally lower beer yields and alcohol contents. The aim of this research was to produce lager beers using worts from sorghum malted with and without Aspergillus oryzae inoculation. Worts adjusted to 15° Plato from the sorghum malt inoculated with 1% A. oryzae yielded 21.5% and 5% more volume compared to sorghum malt and barley malt worts, respectively. The main fermentable carbohydrate in all worts was maltose. Glucose was present in higher amounts in both sorghum worts compared to barley malt worts. Sorghum–A. oryzae beer had similar specific gravity and alcohol compared to the barley malt beer. Sorghum–A. oryzae beer contained lower amounts of hydrogen sulfide, methanethiol, butanedione, and pentanedione compared to barley malt beer. Sorghum–A. oryzae lager beer had similar yield and alcohol content compared to the barley malt beer but differed in color, key volatiles and aromatic compounds.
Internet-based cognitive behavioural therapy programme as an intervention for people diagnosed with adult-onset, focal, isolated, idiopathic cervical dystonia: a feasibility study protocol
Authors: Wadon Megan E. , Winter Mia , Peall Kathryn J. 
Published: July 2020

Abstract
Background
Dystonia is one of the most common forms of movement disorder, caused by the co-contraction of antagonistic muscles, leading to abnormal postures and considerable disability. Non-motor symptoms, notably psychiatric disorders, are well recognised comorbid features of the disorder. However, there is no standardised model for the management of these symptoms in dystonia, with them frequently going undiagnosed and untreated. An internet-based cognitive behavioural therapy programme may provide a future model of care that also maximises available resources.

Methods
This study represents a two-armed randomised feasibility trail, aiming to recruit a total of 20 participants with a diagnosis of adult-onset primary focal cervical dystonia. Participants will be recruited from the Global Myoclonus Dystonia Registry and Dystonia Non-Motor Symptom Study (conducted at Cardiff University) based on presence of moderate symptoms of anxiety/depression as indicated by standardised questionnaires. All participants will undergo assessment at baseline, 3 and 6 months, with this including questionnaires for assessment of non-motor symptoms and clinical assessment of motor symptom severity. Participants will be randomised to either the control (n = 10) or treatment (n = 10) groups. The treatment group will be asked to complete one session of the online CBT program a week, for 8 weeks. The primary outcome measure will be the engagement of participants with the programme, with secondary outcomes of non-motor and motor symptom scores.

Discussion
Promising results have been shown using face-to-face cognitive behavioural therapy to reduce levels of anxiety and depression in individuals with a diagnosis of dystonia. However, no studies to date have sought to determine the feasibility of an internet-delivered cognitive behavioural therapy programme. A number of effective internet-based programmes have been developed that combat anxiety and depression in the general population, suggesting the potential for its effectiveness in cervical dystonia patients. Success with this study would significantly impact the clinical care delivery for patients with cervical dystonia, as well as widening potential access to effective treatment.

Trial registration
This feasibility trial has been registered with Health and Care Research Wales Research Directory. Trial registration number 44245. Date of registration: 21 November 2019. https://www.healthandcareresearch.gov.wales/research-studies-in-wales/
Isolation and characterization of an acid and metal tolerant Enterobacter cloacae NZS strain from former mining lake in Selangor, Malaysia
Authors: Mazalan Nur Zurith Syafiqa , Oyeleye Ayokunmi , Rahman Raja Noor Zaliha Raja Abd. , Aris Ahmad Zaharin , Salleh Abu Bakar , Normi Yahaya M. 
Published: July 2020

Abstract
Background
Metal polluted environments have been found to harbor acid and metal tolerant bacterial communities. Metal oxidizing bacteria in particular are industrially important microorganisms that can be utilized for potential applications in biomining and bioremediation. However, some well-characterized strains are not readily culturable as they are obligate and fastidious chemolithotrophs requiring special techniques for their cultivation. Hence, this study was aimed at isolating, identifying, and characterizing indigenous metal tolerant heterotroph(s) from abandoned mines that can potentially be used for biomining or bioremediation processes in the future.

Results
Seventeen bacteria from former mining lakes were isolated and identified using 16S rRNA. Minimal inhibition concentration (MIC) and growth study of isolated bacteria carried out in Luria-Bertani media containing three different metals ions, zinc (II), copper (II), and iron (II), showed that a particular isolate termed Enterobacter cloacae NZS was found to exhibit better growth and tolerance for copper (up to 90 mM), zinc (up to 200 mM), and iron (up to 170 mM). Growth of the strain was notably well in the presence of iron (II). Compared to all the isolates, only E. cloacae NZS was able to be enumerated at pH lower than 5 while other strains were culturable only at pH 7. Its capability in iron (II) oxidation was preliminary assessed based on the pH, cell count, glucose consumption, and amount of iron oxidized throughout incubation in 9K media. E. cloacae NZS strain was found to be capable of oxidizing iron (II) supplied in 9K media to iron (III).

Conclusion
As preliminary investigation showed that E. cloacae NZS was able to oxidize iron (II) in 9K media at pH2, further optimization on the strain, medium, and culture conditions in future may be able to provide a better insight on this strain to be possibly used as an iron oxidizer for various applications.
A case report of rare isolated Ewing sarcoma of left maxillary sinus
Authors: Hamid Irfan Affandi , Md Arepen Siti Asmat , Hassan Nor Eyzawiah , Azman Mawaddah 
Published: July 2020

Abstract
Background
Ewing sarcoma is a malignant round cell neoplasm and categorized as part of Ewing family tumor (EFT). Only 1-4% of all Ewing sarcomas are primarily located in the head and neck region and the isolated primary sinonasal sarcoma represents a rare entity. This case was reported due to its rarity and dilemma in diagnosis of recurrent post-treatment.

Case presentation
We report a rare case of isolated left maxillary sinus Ewing sarcoma, presented with frequent unprovoked epistaxis, nasal blockage, and rhinorrhea from the left nostril for more than 2 years. Histopathological and immunohistochemical studies performed on the tissue taken from the left nasal mass confirmed Ewing sarcoma. He responded well to the 9 cycles of chemotherapy, evidenced by regression of mass from repeated CECT. However, the post-treatment scan showed multifocal nodular mucosal thickening involving the medial, anterior, and lateral walls of the maxillary sinus with corresponding bony resorption of the medial wall, raising a suspicion of residual disease. As such, he underwent endoscopic medial maxillectomy, which intraoperative findings revealed mild thickening of normal mucosa within the left maxillary sinus and histopathological examination showed no evidence of malignant cell. He showed no signs of recurrence during subsequent follow-up.

Conclusion
As a conclusion, in a case of suspicious residual or recurrent disease detected post-chemotherapy, MRI is an option to differentiate between mucosal thickening and residual tumor. However, the role of surgical resection is equally important in assisting the tissue diagnosis and ensures a better local control, perhaps can increase the survival rate.
Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity
Authors: Jacobson Caron A. , Hunter Bradley D. , Redd Robert , Rodig Scott J. , Chen Pei-Hsuan , Wright Kyle , Lipschitz Mikel , Ritz Jerome , Kamihara Yusuke , Armand Philippe , Nikiforow Sarah , Rogalski Michael , Maakaron Joseph , Jaglowski Samantha , Maus Marcela V. , Chen Yi-Bin , Abramson Jeremy S. , Kline Justin , Budde Elizabeth , Herrera Alex , Mei Matthew , Cohen Jonathon B. , Smith Stephen D. , Maloney David G. , Gopal Ajay K. , Frigault Matthew J. , Acharya Utkarsh H. 
Published: July 2020

PURPOSE Axicabtagene ciloleucel (axi-cel) was approved by the Food and Drug Administration for relapsed aggressive B-cell non-Hodgkin lymphoma in part on the basis of durable remission rates of approximately 40% in a clinical trial population. Whether this efficacy, and the rates of toxicity, would be consistent in a postcommercial setting, with relaxed eligibility criteria and bridging therapy, is unknown. This study describes the efficacy and safety correlates and outcomes in this setting. PATIENTS AND METHODS One hundred twenty-two patients from 7 medical centers in the United States were treated with axi-cel and were included in a modified intent-to-treat (mITT) analysis. Seventy-six patients (62%) were ineligible for the ZUMA-1 trial. Response and toxicity rates, duration of response (DOR), survival, and covariates are described on the basis of the mITT population. Correlative studies on blood and tumor samples were performed to investigate potential biomarkers of response and resistance. RESULTS Median follow-up was 10.4 months. In the mITT population, the best overall and complete response (CR) rates were 70% and 50%, respectively. Median DOR and progression-free survival (PFS) were 11.0 and 4.5 months in all patients and were not reached (NR) in CR patients. Median overall survival (OS) was NR; 1-year OS was 67% (95% CI, 59% to 77%). Although response rates were similar in the ZUMA-1–eligible and ZUMA-1–ineligible groups (70% v 68%), there was a statistically significant improvement in CR rate (63% v 42%, P = .016), DOR (median, NR v 5.0 months; P = .014), PFS (median, NR v 3.3 months; P = .020), and OS (1-year OS, 89% v 54%; P < .001) in patients who were ZUMA-1 eligible. Rates of grade ≥ 3 cytokine release syndrome and neurotoxicty were 16% and 35%, respectively. CONCLUSION Axi-cel yields similar rates of overall response and toxicity in commercial and trial settings, although CR rates and DOR were more favorable in patients eligible for ZUMA-1.
Prediction of recombinant Mycobacterium tuberculosis α-crystallin oligomer chaperone activity using polynomial graphs
Authors: Krishnan Gautam , Roy Utpal 
Published: July 2020

Background: Mycobacterial α-crystallin (Acr) is a chaperone that prevents misfolding of proteins when Mycobacterium tuberculosis is found in a latent form in the host tissue. Methods: Using insulin as a model substrate and utilizing polynomial graphs, we attempted to predict molecular-level interactions that are a function of the oligomeric state of the recombinant protein. The chaperone activity of the recombinant oligomeric Acr was measured at 60°C with Acr samples obtained before gel filtration chromatography and compared with a gel-filtered sample. Results: The polynomial graphs constructed showed improved molecular coverage of the insulin B chain by the oligomer. The 2nd order coefficient is the one that changes with the oligomeric ratio of Acr and improves chaperone activity. Polynomial analysis suggested that it could be a useful parameter to predict chaperone activity for potential in vitro batches of M. tuberculosis Acr based on the dynamic nature of the association and disassociation of oligomers. Conclusions: The results showed that coverage of insulin B chain improved with higher ratio of 9-mer as compared to lower ratios. This was shown by both simulation plots and actual assay data. The polynomial graphs showed increase in the 2nd order coefficient, thus suggesting the important role of oligomerisation in improved molecular coverage of insulin B chain.