bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soil-borne and compost-borne Penicillium sp. and Gliocladium spp. as potential microbial biocontrol agents for the suppression of anthracnose-induced decay on tomato fruits
Authors: Hassine Marwa , Aydi-Ben-Abdallah Rania , Jabnoun-Khireddine Hayfa , Daami-Remadi Mejda 
Published: March 2022

Abstract
Background
Anthracnose is a soil-borne tomato (Solanum lycopersicum L.) disease caused by Colletotrichum coccodes and associated with early dying syndrome and postharvest fruits decays leading to significant yield losses. A biocontrol trial was conducted using Penicillium sp. and Gliocladium spp. isolates recovered from soil and compost for the evaluation of their antifungal potential against the target pathogen.

Results
Cell-free culture filtrates of the microbial agents tested at different concentrations displayed an important antifungal activity based on pathogen mycelial growth inhibition and spore germination suppression. The highest antifungal potential was induced by Penicillium sp. CH6, G. catenulatum Gc1 and G. virens Gv1 cell-free filtrates applied at 3 concentrations (10, 15 and 20% v/v). C. coccodes mycelial growth was significantly reduced by 16 to 84% with chloroform and ethyl acetate extracts of Penicillium sp. CH6 and G. catenulatum Gc1 isolates applied at the concentrations 1, 2.5 and 5% v/v. These treatments had induced an important morphological alteration to pathogen mycelium expressed mainly by a decrease in colony melanization. Testing on pathogen-inoculated fruits, treatment based on cell-free culture filtrates and organic extracts had significantly reduced anthracnose severity as compared to control. Rot lesion diameter was significantly decreased about 22% following treatments with Penicillium sp. CH6 and G. catenulatum Gc1 cell-free filtrates. All chloroform and ethyl acetate extracts of isolates tested had suppressed disease severity by 11 to 59% and 14 to 85%, respectively, as compared to the untreated control.

Conclusions
The results demonstrated the involvement of bioactive compounds in the cultural filtrates and organic extracts tested. These microbial agents may be explored as an alternative tool for the protection of tomato fruits from fungi-associated decays.
Utility of Modeling and Simulation Approach to Support the Clinical Relevance of Dissolution Specifications: a Case Study from Upadacitinib Development
Authors: Mohamed Mohamed-Eslam F. , Winzenborg Insa , Othman Ahmed A. , Marroum Patrick 
Published: March 2022

AbstractDissolution specifications are often essential in assuring the quality and consistency of therapeutic benefits of drug lots released to the market as in vitro dissolution is often considered to be a surrogate for bioavailability. Despite the importance of demonstrating the clinical relevance of the dissolution specifications, it is often challenging to achieve this goal. In this case study, a modeling and simulation approach was utilized to support the clinical relevance of the dissolution specifications for upadacitinib extended-release tablets. A level A in vitro in vivo correlation was developed and utilized in predicting upadacitinib plasma exposures for formulations which correspond to the upper and lower dissolution limits. Exposure-response models for upadacitinib efficacy and safety in patients with moderate to severe rheumatoid arthritis (RA) were utilized to conduct clinical trial simulations to evaluate the efficacy and safety of formulations at the upper and lower dissolution boundaries. Each simulated clinical trial consisted of three treatment arms: (1) upadacitinib 15 mg QD using the target formulation, (2) upadacitinib 15 mg QD using a formulation at the lower dissolution boundary, and (3) upadacitinib 15 mg QD using a formulation at the upper dissolution boundary. Each simulated trial included 300 patients per arm and simulations were replicated 200 times. Results demonstrated that formulations at the lower and upper dissolution boundaries are predicted to have noninferior efficacy and comparable safety to the target 15 mg extended-release formulation. This approach was successfully utilized in demonstrating the clinical relevance of upadacitinib extended-release tablet dissolution specifications.
A novel and efficient murine model of Bietti crystalline dystrophy
Authors: Wang Yafang , Liu Yang , Liu Shu , Li Xiaomeng , Liu Xinxin , Jiao Ming , Yang Yuqin , Luo Xueting , Wang Fenghua , Wan Xiaoling , Sun Xiaodong 
Published: March 2022

ABSTRACT
Bietti crystalline dystrophy (BCD) is an autosomal recessive inherited retinal disease, resulting in blindness in most patients. The etiology and development mechanism of it remain unclear. Given the defects in previous mouse models of BCD, we generated a new Cyp4v3−/− mouse model, using CRISPR/Cas9 technology, for investigating the pathogenesis of BCD. We estimated the ocular phenotypes by fundus imaging, optical coherence tomography (OCT) and full-field scotopic electroretinography, and investigated the histological features by Hematoxylin and Eosin staining, Oil Red O staining and immunofluorescence. This model effectively exhibited age-related progression that mimicked the human ocular phenotypes. Moreover, gas chromatography-mass spectrometry and RNA-seq analysis indicated that the defect of Cyp4v3 led to the abnormal lipid metabolism, inflammation activation and oxidative stress of retina. Notably, inflammation activation and oxidative stress could also promote the progression of BCD in light-induced retinal degeneration. In conclusion, our data provided evidence that we established a novel and more effective Cyp4v3 knockout preclinical mouse model for BCD, which served as a useful tool for evaluating the effect of drugs and gene therapy in vivo.
Chemical Synthesis and Cell-Free Expression of Thiazoline Ring-Bridged Cyclic Peptides and Their Properties on Biomembrane Permeability
Authors: Tamura Takashi , Inoue Masaaki , Yoshimitsu Yuji , Hashimoto Ichihiko , Ohashi Noriyuki , Tsumura Kyosuke , Suzuki Koo , Watanabe Takayoshi , Hohsaka Takahiro 
Published: March 2022

Abstract
Cyclic peptides that exhibit biomembrane permeability provide a useful platform in the development of peptide drugs. Here, the reaction characteristics and versatility of a novel type of cyclic peptide having a thiazoline ring structure in the main chain were investigated. The thiazoline ring-bridged cyclic peptides were chemically synthesized by the intramolecular cyclization of linear peptides composed of N-terminal Cys and a non-natural amino acid having a cyano group on the side chain. The thiazoline ring-bridged cyclic peptides had higher model membrane permeability than amide- and thioether-bridged cyclic peptides with similar amino acid sequences. By comparing the solution structures, the factors that contribute to the higher membrane permeability were examined. In addition, the present peptide cyclization was applied to a cell-free translation system. The expression of peptides having the cyanated non-natural amino acids and subsequent spontaneous cyclization were successfully achieved.
An analysis of patient dose received during cone-beam computed tomography in relation to scan settings and imaging indications as seen in a dental institution in order to establish institutional diagnostic reference levels
Authors: Hung Kuo Feng , Hui Liuling , Yeung Andy Wai Kan , Jacobs Reinhilde , Leung Yiu Yan , Bornstein Michael M. 
Published: March 2022

Objectives: To investigate the dose-area product (DAP) of cone-beam computed tomography (CBCT) examinations for different scan settings and imaging indications, and to establish institutional diagnostic reference levels (DRLs) for dose optimisation. Methods: A retrospective analysis of the DAP values of 3568 CBCT examinations taken from two different devices at the Prince Philip Dental Hospital, Hong Kong between 2016 and 2021 was performed. Patient- (age, gender, and imaging indication) and imaging-related (CBCT device, field-of-view (FOV), and voxel size) were correlated with the DAPs. The indication-oriented third-quartile DAP values were compared with DRLs from the UK, Finland, and Switzerland. The obtained third-quartile DAPs lower than the national DRLs and those for which no national DRLs have been proposed were used to establish institutional DRLs. Results: In the investigated CBCTs, the DAP value for large FOV scans was significantly lower than medium/small FOVs. CBCTs with a small voxel size exhibited a significantly higher DAP than those with a medium/large voxel size. CBCTs for endodontic, periodontal, orthodontic, or orthognathic evaluation exhibited a significantly higher DAP than other indications. Twelve indication-oriented institutional DRLs were established and five of them were lower than the national DRLs: third molars (229 mGy×cm2), jaw cysts/tumours (410 mGy×cm2), maxillary sinus pathology (520 mGy×cm2), developing dentition (164 mGy×cm2), and periapical lesions (564 mGy×cm2). Conclusions: CBCT examinations for endodontic, periodontal, orthodontic, or orthognathic evaluation may deliver a higher radiation dose to the patient than other imaging tasks. A periodic review of the patient dose from CBCT imaging and establishment of institutional DRLs for specific clinical settings are needed for monitoring patient dose and to optimise indication-oriented scanning protocols.
Health care users’ acceptance of broad consent for storage of biological materials and associated data for research purposes in Uganda
Authors: Nansumba Hellen , Flaviano Mugalula , Patrick Semanda , Isaac Ssewanyana , Wassenaar Douglas 
Published: March 2022

Background: Implementation of appropriate informed consent has become a cornerstone for the use of biological materials and data from clinical care to use in research. During 2017-2018, the Ugandan National Bio-repository has since sought prior informed consent for long-term storage and use of remnant clinical human biological materials, where a short informed consent statement (ICF) was incorporated on the laboratory investigation form. This project aimed at determining the acceptability rate of broad consent from health care users (HCUs) for storage of biological materials and data for research purposes in Uganda. Methods: A cross-sectional study was conducted at three Primary Health Care Facilities. 500 HCUs above 18 years of age seeking health care at outpatient departments between March to December 2020 were invited to enrol. A shortened experimental draft ICF for this study was developed and attached to the Laboratory investigation form. Results: Overall the acceptability of broad consent for storage of biological materials and data was 86.2% [95% CI: 82.9%-88.9%]. HCUs who did not understand the draft ICF were 90% less likely to accept broad consent compared to those who understood (OR=0.10, CI [0.03-0.32] while those who partly understood the ICF were 73% less likely to accept broad consent compared to those who understood (OR=0.27, CI [0.15-0.46]. 226 out of 431 respondents that accepted storage of biological materials and data, majority (61.7%) preferred to receive feedback on results of relevance to their health. Conclusion: Acceptance of broad consent for storage of biological materials and data for future research purposes was high among HCUs. A shortened and simplified ICF may trigger discussions between participants and health care workers hence increase research participant understanding of study related materials in biobanking. This in turn could enrich ethically collected biobank resources for future research of public health relevance.
The risk of all-cause mortality, heart outcomes, cancer, and neurodegenerative disorders with cobalt-chrome-containing total hip arthroplasty implants
Authors: Deere Kevin , Matharu Gulraj S. , Ben-Shlomo Yoav , Wilkinson J. Mark , Blom Ashley W. , Sayers Adrian , Whitehouse Michael R. 
Published: March 2022

Aims A recent report from France suggested an association between the use of cobalt-chrome (CoCr) femoral heads in total hip arthroplasties (THAs) and an increased risk of dilated cardiomyopathy and heart failure. CoCr is a commonly used material in orthopaedic implants. If the reported association is causal, the consequences would be significant given the millions of joint arthroplasties and other orthopaedic procedures in which CoCr is used annually. We examined whether CoCr-containing THAs were associated with an increased risk of all-cause mortality, heart outcomes, cancer, and neurodegenerative disorders in a large national database. Methods Data from the National Joint Registry was linked to NHS English hospital inpatient episodes for 374,359 primary THAs with up to 14.5 years' follow-up. We excluded any patients with bilateral THAs, knee arthroplasties, indications other than osteoarthritis, aged under 55 years, and diagnosis of one or more outcome of interest before THA. Implants were grouped as either containing CoCr or not containing CoCr. The association between implant construct and the risk of all-cause mortality and incident heart failure, cancer, and neurodegenerative disorders was examined. Results There were 158,677 individuals (42.4%) with an implant containing CoCr. There were 47,963 deaths, 27,332 heart outcomes, 35,720 cancers, and 22,025 neurodegenerative disorders. There was no evidence of an association between patients with CoCr implants and higher rates of any of the outcomes. Conclusion CoCr-containing THAs did not have an increased risk of all-cause mortality, or clinically meaningful heart outcomes, cancer, or neurodegenerative disorders into the second decade post-implantation. Our findings will help reassure clinicians and the increasing number of patients receiving primary THA worldwide that the use of CoCr-containing implants is not associated with significant adverse systemic effects. Cite this article: Bone Joint J 2022;104-B(3):359–367.
Complications and further surgery after reverse total shoulder arthroplasty
Authors: Kriechling Philipp , Zaleski Martin , Loucas Rafael , Loucas Marios , Fleischmann Marco , Wieser Karl 
Published: March 2022

Aims The aim of this study was to report the incidence of implant-related complications, further operations, and their influence on the outcome in a series of patients who underwent primary reverse total shoulder arthroplasty (RTSA). Methods The prospectively collected clinical and radiological data of 797 patients who underwent 854 primary RTSAs between January 2005 and August 2018 were analyzed. The hypothesis was that the presence of complications would adversely affect the outcome. Further procedures were defined as all necessary operations, including reoperations without change of components, and partial or total revisions. The clinical outcome was evaluated using the absolute and relative Constant Scores (aCS, rCS), the Subjective Shoulder Value (SSV) scores, range of motion, and pain. Results The overall surgical site complication rate was 22% (188 complications) in 152 patients (156 RTSAs; 18%) at a mean follow-up of 46 months (0 to 169). The most common complications were acromial fracture (in 44 patients, 45 RTSAs; 5.3%), glenoid loosening (in 37 patients, 37 RTSAs; 4.3%), instability (in 23 patients, 23 RTSAs; 2.7%), humeral fracture or loosening of the humeral component (in 21 patients, 21 RTSAs; 2.5%), and periprosthetic infection (in 14 patients, 14 RTSAs; 1.6%). Further surgery was undertaken in 79 patients (82 RTSAs) requiring a total of 135 procedures (41% revision rate). The most common indications for further surgery were glenoid-related complications (in 23 patients, 23 RTSAs; 2.7%), instability (in 15 patients, 15 RTSAs; 1.8%), acromial fractures (in 11 patients, 11 RTSAs; 1.3%), pain and severe scarring (in 13 patients, 13 RTSAs; 1.5%), and infection (in 8 patients, 8 RTSAs; 0.9%). Patients who had a complication had significantly worse mean rCS scores (57% (SD 24%) vs 81% (SD 16%)) and SSV scores (53% (SD 27%) vs 80% (SD 20%)) compared with those without a complication. If revision surgery was necessary, the outcome was even further compromised (mean rCS score: 51% (SD 23%) vs 63% (SD 23%); SSV score: 4% (SD 25%) vs 61% (SD 27%). Conclusion Although the indications for, and use of, a RTSA are increasing, it remains a demanding surgical procedure. We found that about one in five patients had a complication and one in ten required further surgery. Both adversely affected the outcome. Cite this article: Bone Joint J 2022;104-B(3):401–407.
Synovial fluid calprotectin performs better than synovial fluid polymerase chain reaction and interleukin-6 in the diagnosis of periprosthetic joint infection
Authors: Cheok Tim , Smith Thomas , Siddiquee Shihab , Jennings Matthew P. , Jayasekera Narlaka , Jaarsma Ruurd L. 
Published: March 2022

AimsThe preoperative diagnosis of periprosthetic joint infection (PJI) remains a challenge due to a lack of biomarkers that are both sensitive and specific. We investigated the performance characteristics of polymerase chain reaction (PCR), interleukin-6 (IL6), and calprotectin of synovial fluid in the diagnosis of PJI.MethodsWe performed systematic search of PubMed, Embase, The Cochrane Library, Web of Science, and Science Direct from the date of inception of each database through to 31 May 2021. Studies which described the diagnostic accuracy of synovial fluid PCR, IL6, and calprotectin using the Musculoskeletal Infection Society criteria as the reference standard were identified.ResultsOverall, 31 studies were identified: 20 described PCR, six described IL6, and five calprotectin. The sensitivity and specificity were 0.78 (95% confidence interval (CI) 0.67 to 0.86) and 0.97 (95% CI 0.94 to 0.99), respectively, for synovial PCR;, 0.86 (95% CI 0.74 to 0.92), and 0.94 (95% CI 0.90 to 0.96), respectively, for synovial IL6; and 0.94 (95% CI 0.82 to 0.98) and 0.93 (95% CI 0.85 to 0.97), respectively, for synovial calprotectin. Likelihood ratio scattergram analyses recommended clinical utility of synovial fluid PCR and IL6 as a confirmatory test only. Synovial calprotectin had utility in the exclusion and confirmation of PJI.ConclusionSynovial fluid PCR and IL6 had low sensitivity and high specificity in the diagnosis of PJI, and is recommended to be used as confirmatory test. In contrast, synovial fluid calprotectin had both high sensitivity and specificity with utility in both the exclusion and confirmation of PJI. We recommend use of synovial fluid calprotectin studies in the preoperative workup of PJI. Cite this article: Bone Joint J 2022;104-B(3):311–320.
Animal experimental investigation on the efficacy of antibiotic therapy with linezolid, vancomycin, cotrimoxazole, and rifampin in treatment of periprosthetic knee joint infections by MRSA
Authors: Goetz Julia , Keyssner Verena , Hanses Frank , Greimel Felix , Leiß Franziska , Schwarz Timo , Springorum Hans-Robert , Grifka Joachim , Schaumburger Jens 
Published: March 2022

Aims Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA. Methods For this purpose, sterilized steel implants were implanted into the femur of 77 rats. The metal devices were inoculated with suspensions of two different MRSA strains. The animals were divided into groups and treated with vancomycin, linezolid, cotrimoxazole, or rifampin as monotherapy, or with combination of antibiotics over a period of 14 days. After a two-day antibiotic-free interval, the implant was explanted, and bone, muscle, and periarticular tissue were microbiologically analyzed. Results Vancomycin and linezolid were able to significantly (p < 0.05) reduce the MRSA bacterial count at implants. No significant effect was found at the bone. Rifampin was the only monotherapy that significantly reduced the bacterial count on implant and bone. The combination with vancomycin or linezolid showed significant efficacy. Treatment with cotrimoxazole alone did not achieve a significant bacterial count reduction. The combination of linezolid plus rifampin was significantly more effective on implant and bone than the control group in both trials. Conclusion Although rifampicin is effective as a monotherapy, it should not be used because of the high rate of resistance development. Our animal experiments showed the great importance of combination antibiotic therapies. In the future, investigations with higher case numbers, varied bacterial concentrations, and changes in individual drug dosages will be necessary to be able to draw an exact comparison, possibly within a clinical trial. Cite this article: Bone Joint Res 2022;11(3):143–151.
Prioritising elective arthroplasty: a further challenge of COVID-19 Can a prioritisation scoring tool help with reducing waiting lists?
Authors: Hainsworth L , Smith LK , Price M , Odutola A 
Published: March 2022

INTRODUCTIONThe COVID-19 pandemic has had a significant impact on the delivery of elective orthopaedic care in the UK, leading to a hugely increased number of patients on waiting lists. The focus has therefore now turned to reducing the backlog. We sought to develop a clear, objective and reproducible system for prioritising elective hip arthroplasty.METHODSThe prioritisation scoring system was constructed using the Federation of Surgical Specialty Associations (FSSA) guidelines as a framework. This included current Oxford hip scores, review of imaging, waiting list duration and previous cancellations. The inter-rater and intra-rater reliability for the final prioritisation scores was tested using the Kappa statistic by two blinded surgeons independently reviewing a selection of patients on two separate occasions.RESULTSA random sample of 20 scores from 125 of the 136 patients on the waiting list were included in the study. The level of prioritisation was assessed by two consultant surgeons. No statistically significant intra-rater or inter-rater reliability was demonstrated.CONCLUSIONSDeveloping an equitable hip arthroplasty prioritisation system is an essential but challenging task. This scoring system was designed as an objective means of determining prioritisation for the elective arthroplasty waiting list within the FSSA categories of priority 3 and 4. Further refinement in light of the evolving guidelines will allow improved reliability.
March 2022 Pulmonary Case of the Month: A Sore Back Leading to Sore Lungs
Authors:   Mayo Clinic Arizona, Scottsdale, AZ USA, Wesselius Lewis , Larsen Brandon 
Published: March 2022

No abstract available. Article truncated after 150 words. History of Present Illness An 82-year-old woman from Colorado was referred because of progressive shortness of breath over the past year. Her primary care physician had prescribed Trelegy® which did not improve her dyspnea. An outside pulmonologist noted abnormal findings on her thoracic CT scan and a bronchoscopy with bronchoalveolar lavage (BAL) was preformed which was positive for Mycobacterium Avium Complex (MAC). She was treated with a 3-drug regimen (azithromycin, rifampin, ethambutol) for 6 months with mild improvement. After the treatment was stopped, she noted more dyspnea and required supplemental oxygen. She underwent a fundoplication and initially improved but a month later her shortness of breath seemed to worsen. She was started on prednisone which was tapered to 10 mg/day. She was referred to the Mayo Clinic for possible VATS lung biopsy. Past Medical History (PMH), Social History (SH), Family History (FH) PMH •	Hiatal Hernia/GERD •	Ulcerative Colitis •	Hypertension •	Chronic back …