bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical validation of a commercially available deep learning software for synthetic CT generation for brain
Authors: Lerner Minna , Medin Joakim , Jamtheim Gustafsson Christian , Alkner Sara , Siversson Carl , Olsson Lars E.
Published: April 2021

Background

Most studies on synthetic computed tomography (sCT) generation for brain rely on in-house developed methods. They often focus on performance rather than clinical feasibility. Therefore, the aim of this work was to validate sCT images generated using a commercially available software, based on a convolutional neural network (CNN) algorithm, to enable MRI-only treatment planning for the brain in a clinical setting.

Methods

This prospective study included 20 patients with brain malignancies of which 14 had areas of resected skull bone due to surgery. A Dixon magnetic resonance (MR) acquisition sequence for sCT generation was added to the clinical brain MR-protocol. The corresponding sCT images were provided by the software MRI Planner (Spectronic Medical AB, Sweden). sCT images were rigidly registered and resampled to CT for each patient. Treatment plans were optimized on CT and recalculated on sCT images for evaluation of dosimetric and geometric endpoints. Further analysis was also performed for the post-surgical cases. Clinical robustness in patient setup verification was assessed by rigidly registering cone beam CT (CBCT) to sCT and CT images, respectively.

Results

All sCT images were successfully generated. Areas of bone resection due to surgery were accurately depicted. Mean absolute error of the sCT images within the body contour for all patients was 62.2 ± 4.1 HU. Average absorbed dose differences were below 0.2% for parameters evaluated for both targets and organs at risk. Mean pass rate of global gamma (1%/1 mm) for all patients was 100.0 ± 0.0% within PTV and 99.1 ± 0.6% for the full dose distribution. No clinically relevant deviations were found in the CBCT-sCT vs CBCT-CT image registrations. In addition, mean values of voxel-wise patient specific geometric distortion in the Dixon images for sCT generation were below 0.1 mm for soft tissue, and below 0.2 mm for air and bone.

Conclusions

This work successfully validated a commercially available CNN-based software for sCT generation. Results were comparable for sCT and CT images in both dosimetric and geometric evaluation, for both patients with and without anatomical anomalies. Thus, MRI Planner is feasible to use for radiotherapy treatment planning of brain tumours.
Pulmonary infection after cardiopulmonary bypass surgery in children: a risk estimation model in China
Authors: Ren Chunnian , Wu Chun , Pan Zhengxia , Wang Quan , Li Yonggang
Published: April 2021

Objectives

The occurrence of pulmonary infection after congenital heart disease (CHD) surgery can lead to significant increases in intensive care in cardiac intensive care unit (CICU) retention time, medical expenses, and risk of death risk. We hypothesized that patients with a high risk of pulmonary infection could be screened out as early after surgery. Hence, we developed and validated the first risk prediction model to verify our hypothesis.

Methods

Patients who underwent CHD surgery from October 2012 to December 2017 in the Children’s Hospital of Chongqing Medical University were included in the development group, while patients who underwent CHD surgery from December 2017 to October 2018 were included in the validation group. The independent risk factors associated with pulmonary infection following CHD surgery were screened using univariable and multivariable logistic regression analyses. The corresponding nomogram prediction model was constructed according to the regression coefficients. Model discrimination was evaluated by the area under the receiver operating characteristic curve (ROC) (AUC), and model calibration was conducted with the Hosmer-Lemeshow test.

Results

The univariate and multivariate logistic regression analyses identified the following six independent risk factors of pulmonary infection after cardiac surgery: age, weight, preoperative hospital stay, risk-adjusted classification for congenital heart surgery (RACHS)-1 score, cardiopulmonary bypass time and intraoperative blood transfusion. We established an individualized prediction model of pulmonary infection following cardiopulmonary bypass surgery for CHD in children. The model displayed accuracy and reliability and was evaluated by discrimination and calibration analyses. The AUCs for the development and validation groups were 0.900 and 0.908, respectively, and the P-values of the calibration tests were 0.999 and 0.452 respectively. Therefore, the predicted probability of the model was consistent with the actual probability.

Conclusions

Identified the independent risk factors of pulmonary infection after cardiopulmonary bypass surgery. An individualized prediction model was developed to evaluate the pulmonary infection of patients after surgery. For high-risk patients, after surgery, targeted interventions can reduce the risk of pulmonary infection.
A framework for the evaluation of patients with congenital facial weakness
Authors: Webb Bryn D. , Manoli Irini , Engle Elizabeth C. , Jabs Ethylin W.
Published: April 2021

There is a broad differential for patients presenting with congenital facial weakness, and initial misdiagnosis unfortunately is common for this phenotypic presentation. Here we present a framework to guide evaluation of patients with congenital facial weakness disorders to enable accurate diagnosis. The core categories of causes of congenital facial weakness include: neurogenic, neuromuscular junction, myopathic, and other. This diagnostic algorithm is presented, and physical exam considerations, additional follow-up studies and/or consultations, and appropriate genetic testing are discussed in detail. This framework should enable clinical geneticists, neurologists, and other rare disease specialists to feel prepared when encountering this patient population and guide diagnosis, genetic counseling, and clinical care.
Economic burden in the management of transfusion-dependent thalassaemia patients in Malaysia from a societal perspective
Authors: Shafie Asrul Akmal , Wong Jacqueline Hui Yi , Ibrahim Hishamshah Mohd , Mohammed Noor Syahireen , Chhabra Irwinder Kaur
Published: April 2021

Background

Transfusion-dependent thalassaemia (TDT) is a hereditary blood disorder in which blood transfusion is the mainstay treatment to prolong survival and improve quality of life. Patients with this disease require blood transfusion at more than 100 ml/kg annually and iron-chelating therapy (ICT) to prevent iron overload (IOL) complications. There are substantial numbers of TDT patients in Malaysia, but limited data are available regarding the economic burden associated with this disease. The purpose of this study was to determine the lifetime cost of TDT from a societal perspective and identify potential factors increasing patient and family expenditures among thalassaemia populations.

Methods

The total lifetime cost per TDT patient (TC1) is the sum of lifetime healthcare cost (TC2) and lifetime patient and family healthcare expenditure (TC3). TC2 was simulated using the Markov model, taking into account all costs subsidized by the government, and TC3 was estimated through a cross-sectional health survey approach. A survey was performed using a two-stage sampling method in 13 thalassaemia centres covering all regions in Malaysia.

Results

A TDT patient is expected to incur TC2 of USD 561,208. ICT was the main driver of cost and accounted for 56.9% of the total cost followed by blood transfusion cost at 13.1%. TC3 was estimated to be USD 45,458. Therefore, the estimated TC1 of a TDT patient was USD 606,665. Sensitivity analyses showed that if all patients were prescribed oral ICT deferasirox for their lifetime, the total healthcare cost would increase by approximately 65%. Frequency of visits to health facilities for blood transfusion/routine monitoring and patients who were prescribed desferrioxamine were observed to be factors affecting patient and family monthly expenses.

Conclusion

The lifetime cost per TDT patient was USD 606,665, and this result may be useful for national health allocation planning. An estimation of the economic burden will provide additional information to decision makers on implementing prevention interventions to reduce the number of new births and medical service reimbursement.
Data silos are undermining drug development and failing rare disease patients
Authors: Denton Nathan , Molloy Monique , Charleston Samantha , Lipset Craig , Hirsch Jonathan , Mulberg Andrew E. , Howard Paul , Marsh Eric D.
Published: April 2021

Data silos are proliferating while research and development activity explode following genetic and immunological advances for many clinically described disorders with previously unknown etiologies. The latter event has inspired optimism in the patient, clinical, and research communities that disease-specific treatments are on the way. However, we fear the tendency of various stakeholders to balkanize databases in proprietary formats, driven by current economic and academic incentives, will inevitably fragment the expanding knowledge base and undermine current and future research efforts to develop much-needed treatments. The proliferation of proprietary databases, compounded by a paucity of meaningful outcome measures and/or good natural history data, slows our ability to generate scalable solutions to benefit chronically underserved patient populations in ways that would translate to more common diseases. The current research and development landscape sets too many projects up for unnecessary failure, particularly in the rare disease sphere, and does a grave disservice to highly vulnerable patients. This system also encourages the collection of redundant data in uncoordinated parallel studies and registries to ultimately delay or deny potential treatments for ostensibly tractable diseases; it also promotes the waste of precious time, energy, and resources. Groups at the National Institutes of Health and Food and Drug Administration have started programs to address these issues. However, we and many others feel there should be significantly more discussion of how to coordinate and scale registry efforts. Such discourse aims to reduce needless complexity and duplication of efforts, as well as promote a pre-competitive knowledge ecosystem for rare disease drug development that cultivates and accelerates innovation.
Psychosocial burden and professional and social support in patients with hereditary transthyretin amyloidosis (ATTRv) and their relatives in Italy
Authors:   ATTRv Collaborators, Magliano Lorenza , Obici Laura , Sforzini Claudia , Mazzeo Anna , Russo Massimo , Cappelli Francesco , Fenu Silvia , Luigetti Marco , Tagliapietra Matteo , Gemelli Chiara , Leonardi Luca , Tozza Stefano , Pradotto Luca Guglielmo , Citarelli Giulia , Mauro Alessandro , Manganelli Fiore , Antonini Giovanni , Grandis Marina , Fabrizi Gian Maria , Sabatelli Mario , Pareyson Davide , Perfetto Federico , Merlini Giampaolo , Vita Giuseppe
Published: April 2021

Background

Hereditary transthyretin amyloidosis (hATTR), alias ATTR variant (ATTRv) is a severe and disabling disease causing sensory and motor neuropathy, autonomic dysfunction, and cardiomyopathy. The progressive decline of patient’s functional autonomy negatively affects the patient’s quality of life and requires increasing involvement of relatives in the patient’s daily life. Family caregiving may become particularly demanding when the patient is no longer able to move independently. This study is focused on the psychosocial aspects of ATTRv from the patient and relative perspectives. In particular, it explored: the practical and psychological burdens experienced by symptomatic patients with ATTRv and their key relatives and the professional and social network support they may rely on; whether burden varied in relation to patients’ and relatives’ socio-demographic variables, patients’ clinical variables, and perceived professional and social network support; and, any difference in burden and support between patients and their matched relatives.

Methods

The study was carried out on symptomatic patients included in the ATTRv Italian national registry and living with at least one adult relative not suffering from severe illness and being free from ATTRv symptoms. Patients and relatives’ assessments were performed using validated self-reported tools.

Results

Overall, 141 patients and 69 relatives were evaluated. Constraints of leisure activities, feelings of loss and worries for the future were the consequences of ATTRv most frequently reported by patients and relatives. Both in patients and their relatives, the burden increased with the duration of symptoms and the level of help in daily activities needed by the patient. In the 69 matched patient-relative pairs, the practical burden was significantly higher among the patients than among their relatives, while the psychological burden was similar in the two groups. Moreover, compared to their relatives, patients with ATTRv reported higher levels of professional and social network support.

Conclusions

These results show that ATTRv is a disease affecting quality of life of both patients and their families. Supporting interventions should be guaranteed to patients, to facilitate their adaptation to the disease, and to their families, to cope as best as possible with the difficulties that this pathology may involve.
Mapping geographical areas at risk for tick-borne encephalitis (TBE) by analysing bulk tank milk from Swedish dairy cattle herds for the presence of TBE virus–specific antibodies
Authors: Blomqvist Gunilla , Näslund Katarina , Svensson Linda , Beck Cécile , Valarcher Jean Francois
Published: April 2021

Background

The vector-borne human viral zoonosis tick-borne encephalitis (TBE) is of growing concern in Sweden. The area where TBE is considered endemic has expanded, with an increasing geographical distribution of Ixodes ricinus as the tick vector and a rising number of reported TBE cases in humans. Efforts to map TBE risk areas have been carried out by sentinel monitoring, mainly based on individual sampling and analysis of wild and domestic animals, as well as ticks, for tick-borne encephalitis virus (TBEV). However, the interpretation of the geographical distribution has been hampered by the patchy and focal nature of TBEV occurrence. This study presents TBEV surveillance data based on antibody analysis of bulk tank milk collected from dairy herds located throughout Sweden before (May) and after (November) the vector season. A commercial TBEV antibody ELISA was modified and evaluated for use in this study.

Results

The initial comparative TBEV antibody analysis revealed a good correlation between milk and serum antibody levels from individually sampled cows. Also, the TBEV-antibody levels for the mean-herd serum showed good comparability with TBEV antibody levels from bulk tank milk, thus indicating good predictability of seroprevalence when analysing bulk tank milk from a herd.

Analyses of bulk tank milk samples collected from 616 herds in May and 560 herds in November showed a geographical distribution of TBEV seropositive herds that was largely consistent with reported human TBE cases. A few TBEV-reactive herds were also found outside known locations of human TBE cases.

Conclusion

Serological examination of bulk tank milk from dairy cattle herds may be a useful sentinel surveillance method to identify geographical presence of TBEV. In contrast to individual sampling this method allows a large number of animals to be monitored. TBEV seropositive herds were mainly found in coastal areas of southern Sweden similar to human TBE cases. However, some antibody-reactive herds were found outside known TBE areas at the time of the study.
Working short and working long: can primary healthcare be protected as a public good in Lebanon today?
Authors: Hamadeh Randa Sami , Kdouh Ola , Hammoud Rawan , Leresche Enrica , Leaning Jennifer
Published: April 2021

In this commentary we propose four questions to be addressed while building a meaningful public primary healthcare response in Lebanon today. These questions emerge from two imperatives: the necessity to consider both short- and longer-term struggles in a context of protracted conflict and the need to protect public health as a public good whilst the public Primary Healthcare Network (PHCN) is facing the Covid19 pandemic. In order to identify how these questions are related to the need to be working short and long, we look at the imprints left by past and present shocks. Profound shocks of the past include the Lebanese civil war and the Syrian refugee crisis. We analyse how these shocks have resulted in the PHCN developing resilience mechanisms in order to ensure a space for healthcare provision that stands public in Lebanon today. Then, we consider how two present shocks -- the economic breakdown and the blast of ammonium nitrate in Beirut port -- are affecting and threatening the progress made by the PHCN to ensure that primary healthcare remains a public good, a fragile space acquired with difficulty in the past half century. We identify what questions emerge from the combined consequences of such traumas, when the immediate constraints of the present meet the impediments of the past. We consider what such questions mean more broadly, for the people living in Lebanon today, and for the PHCN ability to respond to the Covid 19 pandemic in a relevant way. Our hypothesis is that in a protracted conflict, such as the one defining the circumstances of Lebanon now, public access to primary healthcare might persist for the people as one safeguard, in which social and moral continuity can be anchored to protect a sense of public good.
Targeting neddylation E2s: a novel therapeutic strategy in cancer
Authors: Zheng Yi-Chao , Guo Yan-Jia , Wang Bo , Wang Chong , Mamun M. A. A. , Gao Ya , Liu Hong-Min
Published: April 2021

Ubiquitin-conjugating enzyme E2 M (UBE2M) and ubiquitin-conjugating enzyme E2 F (UBE2F) are the two NEDD8-conjugating enzymes of the neddylation pathway that take part in posttranslational modification and change the activity of target proteins. The activity of E2 enzymes requires both a 26-residue N-terminal docking peptide and a conserved E2 catalytic core domain, which is the basis for the transfer of neural precursor cell-expressed developmentally downregulated 8 (NEDD8). By recruiting E3 ligases and targeting cullin and non-cullin substrates, UBE2M and UBE2F play diverse biological roles. Currently, there are several inhibitors that target the UBE2M-defective in cullin neddylation protein 1 (DCN1) interaction to treat cancer. As described above, this review provides insights into the mechanism of UBE2M and UBE2F and emphasizes these two E2 enzymes as appealing therapeutic targets for the treatment of cancers.
Factors impacting the evidence‐based assessment, diagnosis and management of Acute Charcot Neuroarthropathy: a systematic review
Authors: Diacogiorgis D. , Perrin B. M. , Kingsley M. I. C.
Published: April 2021

Background

Acute Charcot Neuroarthropathy (CN) is a destructive condition that is characterised by acute fractures, dislocations and joint destruction in the weight‐bearing foot. The acute phase is often misdiagnosed and can rapidly lead to devastating health outcomes. Early diagnosis and management of CN is imperative to attenuate progression of this condition. Consequently, timely evidence‐based assessment, diagnosis and management of acute CN is imperative.

Objective

To identify the factors that impact the delivery of evidence‐based care in assessment, diagnosis and management of people with acute CN.

Method

Systematic searches were conducted in four databases to identify studies in English that included factors that impact the delivery of evidence‐based care in the assessment, diagnosis and management of people with acute CN. Articles and consensus/guideline documents were assessed for inclusion by the researchers and disagreements were resolved through consensus. Additionally backward citation searching was used to source other potentially relevant documents. Information relevant to the research question was extracted and thematic analyses were performed using qualitative synthesis.

Results

Thirty‐two articles and four additional consensus/guideline documents were included for data extraction and analyses. Information related to the research question was of expert opinion using the National Health and Medical Research Council (NHMRC) Levels of Evidence guidelines. Themes explaining practices that deviated from evidence‐based care in assessment, diagnosis and management of acute CN centred around patient, health professional and health organisation/environmental. Delay to diagnosis is particularly influenced by the patient's knowledge of when to seek help, practitioner knowledge in knowing how to recognise and refer for appropriate immediate care, confusion in imaging and offloading and geographical and local health service resources to appropriately manage the condition.

Conclusion

Individual and health professional awareness and geographical barriers are key challenges to the effective delivery of evidence‐based assessment, diagnosis and management of people with acute CN. Acute CN represents a medical emergency warranting the need for expedited assessment, diagnosis and management by appropriately trained health professionals in the appropriate.
Availability and service provision of multidisciplinary diabetes foot units in Australia: a cross‐sectional survey
Authors: Vo Uyen Giao , Gilfillan Molly , Hamilton Emma Jane , Manning Laurens , Munshi Bijit , Hiew Jonathan , Norman Paul Edward , Ritter Jens Carsten
Published: April 2021

Background

With growing global prevalence of diabetes mellitus, diabetes‐related foot disease (DFD) is contributing significantly to disease burden. As more healthcare resources are being dedicated to the management of DFD, service design and delivery is being scrutinised. Through a national survey, this study aimed to investigate the current characteristics of services which treat patients with DFD in Australia.

Methods

An online survey was distributed to all 195 Australian members of the Australian and New Zealand Society for Vascular Surgery investigating aspects of DFD management in each member's institution.

Results

From the survey, 52 responses were received (26.7%). A multidisciplinary diabetes foot unit (MDFU) was available in more than half of respondent's institutions, most of which were tertiary hospitals. The common components of MDFU were identified as podiatrists, endocrinologists, vascular surgeons and infectious disease physicians. Many respondents identified vascular surgery as being the primary admitting specialty for DFD patients that require hospitalisation (33/52, 63.5%). This finding was consistent even in centres with MDFU clinics. Less than one third of MDFUs had independent admission rights.

Conclusions

The present study suggests that many tertiary centres in Australia provide their diabetic foot service in a multidisciplinary environment however their composition and function remain heterogeneous. These findings provide an opportunity to evaluate current practice and, to initiate strategies aimed to improve outcomes of patients with DFD.
A 5G-powered robot-assisted teleultrasound diagnostic system in an intensive care unit
Authors: Duan Shaobo , Liu Luwen , Chen Yongqing , Yang Long , Zhang Ye , Wang Shuaiyang , Hao Liuwei , Zhang Lianzhong
Published: April 2021

Background

Teleultrasound provides an effective solution to problems that arise from limited medical resources, a lack of local expertise, and scenarios where the risk of infection is high. This study aims to explore the feasibility of the application of a 5G-powered robot-assisted teleultrasound diagnostic system in an intensive care unit.

Methods

In this study, the robot-assisted teleultrasound diagnostic system MGIUS-R3 was used. Using 5G network technology, the doctor manipulates the robotic arm to perform teleultrasound examination. The doctor can adjust parameters via the teleultrasound control panel, and real-time transmission of audio, video and ultrasound images can facilitate simultaneous communication between both parties. All patients underwent robot-assisted teleultrasound examination and bedside ultrasound examination of the liver, gallbladder, pancreas, spleen, kidney, as well as assessment for pleural effusion and abdominal effusion. We evaluated the feasibility of the application of the robot-assisted teleultrasound diagnosis system in the intensive care unit in terms of consultation duration, image quality, and safety. We also compared diagnostic consistency and differences.

Results

Apart from one patient who was excluded due to severe intestinal gas interference and poor image quality, a total of 32 patients were included in this study. Every patient completed all relevant examinations. Among them, 20 patients were male; 12 were female. The average age of the patients was 61 ± 20 years. The average duration of teleultrasound diagnosis was 17 ± 7 min. Of the 32 patients, 26 had positive results, 6 had negative results, and 5 had inconsistent diagnoses. The overall diagnostic results were basically the same, and there were no differences in diagnostic levels between the two. The overall average image quality score was 4.73 points, which represented a high-quality image. After robot-assisted teleultrasound examination, no significant changes were observed in the vital signs of patients as compared to before examination, and no examination-related complications were found.

Conclusion

The 5G-powered robot-assisted teleultrasound diagnostic system was associated with the benefits of clear images, simple operation, relatively high levels of consistency in terms of diagnostic results, higher levels of safety, and has considerable application value in the intensive care unit.
Effect of a prebiotic supplement on knee joint function, gut microbiota, and inflammation in adults with co-morbid obesity and knee osteoarthritis: study protocol for a randomized controlled trial
Authors: Fortuna Rafael , Hart David A. , Sharkey Keith A. , Schachar Rachel A. , Johnston Kelly , Reimer Raylene A.
Published: April 2021

Background

Osteoarthritis (OA) is a chronic and painful condition where the articular cartilage surfaces progressively degenerate, resulting in loss of function and progressive disability. Obesity is a primary risk factor for the development and progression of knee OA, defined as the “metabolic OA” phenotype. Metabolic OA is associated with increased fat deposits that release inflammatory cytokines/adipokines, thereby resulting in systemic inflammation which can contribute to cartilage degeneration. There is currently no cure for OA. Prebiotics are a type of dietary fiber that can positively influence gut microbiota thereby reducing systemic inflammation and offering protection of joint integrity in rodents. However, no human clinical trials have tested the effects of prebiotics in adults with obesity suffering from knee OA. Therefore, the purpose of this double-blind, placebo-controlled, randomized trial is to determine if prebiotic supplementation can, through positive changes in the gut microbiota, improve knee function and physical performance in adults with obesity and knee OA.

Methods

Adults (n = 60) with co-morbid obesity (BMI > 30 kg/m2) and knee OA (Kellgren-Lawrence grade II–III) will be recruited from the Alberta Hip and Knee Clinic and the Rocky Mountain Health Clinic and surrounding community of Calgary, Canada, and randomized (stratified by sex, BMI, and age) to prebiotic (oligofructose-enriched inulin; 16 g/day) or a calorie-matched placebo (maltodextrin) for 6 months. Anthropometrics, performance-based tests, knee pain, serum inflammatory markers and metabolomics, quality of life, and gut microbiota will be assessed at baseline, 3 months, 6 months (end of prebiotic supplementation), and 3 months following the end of the prebiotic supplementation.

Clinical significance

There is growing pressure on health care systems for aggressive OA treatment such as total joint replacement. Less aggressive, yet effective, conservative treatment options have the potential to address the growing prevalence of co-morbid obesity and knee OA by delaying the need for joint replacement or ideally preventing its need altogether. The results of this clinical trial will provide the first evidence regarding the efficacy of prebiotic supplementation on knee joint function and pain in adults with obesity and knee OA. If successful, the results may provide a simple, safe, and easy to adhere to intervention to reduce knee joint pain and improve the quality of life of adults with co-morbid knee OA and obesity.

Trial registration

Clinical Trials.gov NCT04172688. Registered on 21 November 2019.
The use of virtual reality to reduce stress among night-shift anesthesiologists: study protocol for a crossover trial
Authors: Chen Chaojin , Chen Liubing , Shen Ning , Luo Chenfang , Wang Ren , Fang Hongyi , Zhang Qi , Hei Ziqing
Published: April 2021

Background

Because of the lack of anesthesia workforce, anesthesiologists are forced to work overtime and more night shifts, which can disturb their biological rhythm and cause severe stress and depression, potentially leading to negative and even devastating outcomes for both themselves and patients. Virtual reality (VR), a new method to reduce stress and pain for patients, has been widely used in biomedical fields. The purpose of this study is to evaluate the potential effectiveness of VR technology in reducing stress among night-shift anesthesiologists.

Methods

In this randomized controlled, crossover, single-center clinical trial, a total of 30 anesthesiologists will be enrolled and randomized in a 1:1 allocation to either the VR immersion group (intervention group) or the routine night-shift group (control group) with a washout of 1 week. Anesthesiologists in the intervention group will undergo VR immersion twice, while anesthesiologists in the control group will not watch VR videos during the night shift. The primary outcome will be the difference in the NASA Task Load Index (NASA-TLX) score between the two groups. Secondary outcomes will include the Chinese Perceived Stress Scale (CPSS), perceived stress scores (visual analogue scale (VAS)), and Multidimensional Fatigue Inventory (MFI-20) scores; levels of satisfaction among the participants; incidence of arrhythmia; and incidence of chest tightness, headache, and palpitations.

Discussion

It is unknown whether the use of VR technology during the night shift can reduce stress among anesthesiologists. With the widespread use of VR technology, a positive result in this trial could spur hospitals to apply VR technology to reduce stress among night-shift doctors in every department and provide a relatively relaxed working environment.

Trial registration

Chinese Clinical Trial Registry ChiCTR2000031025. Registered on 21 March 2020
Waste biorefinery towards a sustainable circular bioeconomy: a solution to global issues
Authors: Leong Hui Yi , Chang Chih-Kai , Khoo Kuan Shiong , Chew Kit Wayne , Chia Shir Reen , Lim Jun Wei , Chang Jo-Shu , Show Pau Loke
Published: April 2021

Global issues such as environmental problems and food security are currently of concern to all of us. Circular bioeconomy is a promising approach towards resolving these global issues. The production of bioenergy and biomaterials can sustain the energy–environment nexus as well as substitute the devoid of petroleum as the production feedstock, thereby contributing to a cleaner and low carbon environment. In addition, assimilation of waste into bioprocesses for the production of useful products and metabolites lead towards a sustainable circular bioeconomy. This review aims to highlight the waste biorefinery as a sustainable bio-based circular economy, and, therefore, promoting a greener environment. Several case studies on the bioprocesses utilising waste for biopolymers and bio-lipids production as well as bioprocesses incorporated with wastewater treatment are well discussed. The strategy of waste biorefinery integrated with circular bioeconomy in the perspectives of unravelling the global issues can help to tackle carbon management and greenhouse gas emissions. A waste biorefinery–circular bioeconomy strategy represents a low carbon economy by reducing greenhouse gases footprint, and holds great prospects for a sustainable and greener world.
Microbiota-associated risk factors for asymptomatic gut colonisation with multi-drug-resistant organisms in a Dutch nursing home
Authors: Ducarmon Quinten R. , Terveer Elisabeth M. , Nooij Sam , Bloem Michelle N. , Vendrik Karuna E. W. , Caljouw Monique A. A. , Sanders Ingrid M. J. G. , van Dorp Sofie M. , Wong Man C. , Zwittink Romy D. , Kuijper Ed J.
Published: April 2021

Background

Nursing home residents have increased rates of intestinal colonisation with multidrug-resistant organisms (MDROs). We assessed the colonisation and spread of MDROs among this population, determined clinical risk factors for MDRO colonisation and investigated the role of the gut microbiota in providing colonisation resistance against MDROs.

Methods

We conducted a prospective cohort study in a Dutch nursing home. Demographical, epidemiological and clinical data were collected at four time points with 2-month intervals (October 2016–April 2017). To obtain longitudinal data, faecal samples from residents were collected for at least two time points. Ultimately, twenty-seven residents were included in the study and 93 faecal samples were analysed, of which 27 (29.0%) were MDRO-positive. Twelve residents (44.4%) were colonised with an MDRO at at least one time point throughout the 6-month study.

Results

Univariable generalised estimating equation logistic regression indicated that antibiotic use in the previous 2 months and hospital admittance in the previous year were associated with MDRO colonisation. Characterisation of MDRO isolates through whole-genome sequencing revealedEscherichia colisequence type (ST)131 to be the most prevalent MDRO and ward-specific clusters ofE. coliST131 were identified. Microbiota analysis by 16S rRNA gene amplicon sequencing revealed no differences in alpha or beta diversity between MDRO-positive and negative samples, nor between residents who were ever or never colonised. Three bacterial taxa (Dorea, AtopobiaceaeandLachnospiraceaeND3007 group) were more abundant in residents never colonised with an MDRO throughout the 6-month study. An unexpectedly high abundance ofBifidobacteriumwas observed in several residents. Further investigation of a subset of samples with metagenomics showed that variousBifidobacteriumspecies were highly abundant, of whichB. longumstrains remained identical within residents over time, but were different between residents.

Conclusions

Our study provides new evidence for the role of the gut microbiota in colonisation resistance against MDROs in the elderly living in a nursing home setting.Dorea,AtopobiaceaeandLachnospiraceaeND3007 group may be associated with protection against MDRO colonisation. Furthermore, we report a uniquely high abundance of severalBifidobacteriumspecies in multiple residents and excluded the possibility that this was due to probiotic supplementation.
Clinical characteristics and outcome of IgG4-related disease with hypocomplementemia: a prospective cohort study
Authors: Peng Linyi , Lu Hui , Zhou Jiaxin , Zhang Panpan , Li Jieqiong , Liu Zheng , Wu Di , Zhang Shangzhu , Yang Yunjiao , Bai Wei , Wang Li , Fei Yunyun , Zhang Wen , Zhao Yan , Zeng Xiaofeng , Zhang Fengchun
Published: April 2021

Background

Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized systemic, immune-mediated, and fibro-inflammatory disease. Hypocomplementemia was found in part of IgG4-RD patients especially in the setting of active disease.

Objectives

This study aimed to clarify the clinical features, treatment efficacy, and outcome in IgG4-RD patients with hypocomplementemia.

Methods

312 IgG4-RD patients were recruited in our prospective cohort conducted in Peking Union Medical College Hospital. Patients were divided into hypocomplementemia group and normal complement group according to serum C3 and C4 levels measured at baseline before treatment. Low serum C3 levels (< 0.73 g/L) and/or C4 levels (< 0.10 g/L) were defined as hypocomplementemia. Demographic data, clinical characteristics, laboratory parameters, treatment, and outcome of two groups were analyzed and compared.

Results

Hypocomplementemia was identified in 65 (20.8%) cases of untreated IgG4-RD patients at baseline. The average age of hypocomplementemia group was 55.85 ± 10.89 years, with male predominance (72.3%). Compared with normal complement group, patients with hypocomplementemia were likely to have more involved organs, higher IgG4-RD responder index (IgG4-RD RI), and higher laboratory parameters such as counts of eosinophils, inflammatory markers, immunoglobulin G (IgG), IgG1, IgG3, IgG4, and IgE. In addition, lymph nodes, lacrimal gland, submandibular gland, parotid gland, paranasal sinus, bile ducts, and prostate gland were more commonly affected (p < 0.05). Serum C3 and C4 showed a significant positively correlation with each other. Both C3 and C4 were negatively correlated with the number of involved organs, IgG, IgG3, IgG4, and IgG4-RD RI, as well as positively correlated with IgA and hypersensitive C reactive protein (hsCRP). 64 (98.5%) patients responded quickly to initial therapy at a 3-month follow-up. Fifteen (23.1%) patients relapsed during follow-up with mean recurrence time of 14.2 ± 13.8 months. Compared with normal complement group, there was no significant difference of relapse rate in two groups (P = 0.401).

Conclusions

Clinical characteristics of IgG4-related disease with hypocomplementemia differ from normal complement group. Serum C3 and C4 at baseline before treatment could be biological markers for disease activity. IgG4-RD with hypocomplementemia responded well to treatment and had no significant difference of relapse rate in IgG4-RD with normal complement.
Distinct chemical composition and enzymatic treatment induced human endothelial cells survival in acellular ovine aortae
Authors: Heidarzadeh Morteza , Rahbarghazi Reza , Saberianpour Shirin , Delkhosh Aref , Amini Hassan , Sokullu Emel , Hassanpour Mehdi
Published: April 2021

Objective

The current experiment aimed to assess the impact of detergents such as 3% Triton X-100, 1% peracetic acid, 1% Tween-20, and 1% SDS in combination with Trypsin–EDTA on acellularization of ovine aortae after 7 days.

Results

Hematoxylin–Eosin staining showed an appropriate acellularization rate in ovine aortae, indicated by a lack of cell nuclei in the tunica media layer. DAPI staining confirmed the lack of nuclei in the vascular wall after being exposed to the combination of chemical and enzymatic solutions. Verhoeff-Van Gieson staining showed that elastin fibers were diminished in acellular samples compared to the control group while collagen stands were unchanged. CCK-8 survival assay showed enhanced viability in human umbilical vein endothelial cells 5 days after being cultured on decellularized samples compared to the cells cultured on a plastic surface (p < 0.05). SEM imaging showed flattening of endothelial cells on the acellular surface.
Differential sensitivity of cinnamaldehyde-evoked calcium fluxes to ruthenium red in guinea pig and mouse trigeminal sensory neurons
Authors: Bahia Parmvir K. , Taylor-Clark Thomas E.
Published: April 2021

Objective

Transient receptor potential ankyrin 1 (TRPA1) is an excitatory ion channel expressed on a subset of sensory neurons. TRPA1 is activated by a host of noxious stimuli including pollutants, irritants, oxidative stress and inflammation, and is thought to play an important role in nociception and pain perception. TRPA1 is therefore a therapeutic target for diseases with nociceptive sensory signaling components. TRPA1 orthologs have been shown to have differential sensitivity to certain ligands. Cinnamaldehyde has previously been shown to activate sensory neurons via the selective gating of TRPA1. Here, we tested the sensitivity of cinnamaldehyde-evoked responses in mouse and guinea pig sensory neurons to the pore blocker ruthenium red (RuR).

Results

Cinnamaldehyde, the canonical TRPA1-selective agonist, caused robust calcium fluxes in trigeminal neurons dissociated from both mice and guinea pigs. RuR effectively inhibited cinnamaldehyde-evoked responses in mouse neurons at 30 nM, with complete block seen with 3 μM. In contrast, responses in guinea pig neurons were only partially inhibited by 3 μM RuR. We conclude that RuR has a decreased affinity for guinea pig TRPA1 compared to mouse TRPA1. This study provides further evidence of differences in ligand affinity for TRPA1 in animal models relevant for drug development.
Two-stage window screening and development trajectories in early identification of autism spectrum disorder among Han Chinese children
Authors: Lung For-Wey , Shu Bih-Ching
Published: April 2021

Objective

An understanding of the trajectory and norm of development in children is needed in order to understand the concept of the spectrum in the diagnosis of autism spectrum disorder (ASD). Children’s developmental growth trajectory was measured from six to 66 months in the Taiwan Birth Cohort Study dataset (N = 11,145). Additionally, over 4 years of follow-up, the negative predictive value of using the Parental Concern Checklist and Taiwan Birth Cohort Study Developmental Instrument was also investigated as the first stage of screening in a two-stage window screening method for ASD diagnosis.

Results

The growth trajectory showed that children’s language development began to increase at 18 months, and peaked at 36 months. On the other hand, social development showed steady growth from 18 to 66 months. The increase in the trajectory of children’s language development prior to age three, when compared with other developmental dimensions, may increase the difficulty of diagnosing ASD. The two-stage window screening method can be used in settings where the screening sample is large, such as in community or primary care settings, and has been found to be time- and cost-efficient. Better understanding of children’s developmental trajectory can enhance detection and intervention for ASD.
Somatic production of reactive oxygen species does not predict its production in sperm cells across Drosophila melanogaster lines
Authors: Turnell Biz R. , Kumpitsch Luisa , Ribou Anne-Cécile , Reinhardt Klaus
Published: April 2021

Objective

Sperm ageing has major evolutionary implications but has received comparatively little attention. Ageing in sperm and other cells is driven largely by oxidative damage from reactive oxygen species (ROS) generated by the mitochondria. Rates of organismal ageing differ across species and are theorized to be linked to somatic ROS levels. However, it is unknown whether sperm ageing rates are correlated with organismal ageing rates. Here, we investigate this question by comparing sperm ROS production in four lines of Drosophila melanogaster that have previously been shown to differ in somatic mitochondrial ROS production, including two commonly used wild-type lines and two lines with genetic modifications standardly used in ageing research.

Results

Somatic ROS production was previously shown to be lower in wild-type Oregon-R than in wild-type Dahomey flies; decreased by the expression of alternative oxidase (AOX), a protein that shortens the electron transport chain; and increased by a loss-of-function mutation in dj-1β, a gene involved in ROS scavenging. Contrary to predictions, we found no differences among these four lines in the rate of sperm ROS production. We discuss the implications of our results, the limitations of our study, and possible directions for future research.
The impact of CBP expression in estrogen receptor-positive breast cancer
Authors: Ramadan Wafaa S. , Talaat Iman M. , Hachim Mahmood Y. , Lischka Annette , Gemoll Timo , El-Awady Raafat
Published: April 2021

Background

The development of new biomarkers with diagnostic, prognostic and therapeutic prominence will greatly enhance the management of breast cancer (BC). Several reports suggest the involvement of the histone acetyltransferases CREB-binding protein (CBP) and general control non-depressible 5 (GCN5) in tumor formation; however, their clinical significance in BC remains poorly understood. This study aims to investigate the value of CBP and GCN5 as markers and/or targets for BC prognosis and therapy. Expression of CBP, GCN5, estrogen receptor α (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in BC was analyzed in cell lines by western blot and in patients’ tissues by immunohistochemistry. The gene amplification data were also analyzed for CBP and GCN5 using the publicly available data from BC patients.

Results

Elevated expression of CBP and GCN5 was detected in BC tissues from patients and cell lines more than normal ones. In particular, CBP was more expressed in luminal A and B subtypes. Using chemical and biological inhibitors for CBP, ERα and HER2 showed a strong association between CBP and the expression of ERα and HER2. Moreover, analysis of theCREBBP(for CBP) andKAT2A(for GCN5) genes in a larger number of patients in publicly available databases showed amplification of both genes in BC patients. Amplification ofCREBBPgene was observed in luminal A, luminal B and triple-negative but not in HER2 overexpressing subtypes. Furthermore, patients with highCREBBPorKAT2Agene expression had better 5-year disease-free survival than the low gene expression group (p = 0.0018 andp < 0.00001, respectively).

Conclusions

We conclude that the persistent amplification and overexpression of CBP in ERα- and PR-positive BC highlights the significance of CBP as a new diagnostic marker and therapeutic target in hormone-positive BC.
Parthenogenetic mosaicism: generation via second polar body retention and unmasking of a likely causative PER2 variant for hypersomnia
Authors: Masunaga Yohei , Kagami Masayo , Kato Fumiko , Usui Takeshi , Yonemoto Takako , Mishima Kazuo , Fukami Maki , Aoto Kazushi , Saitsu Hirotomo , Ogata Tsutomu
Published: April 2021

Background

Parthenogenetic mosaicism is an extremely rare condition identified only in five subjects to date. The previous studies indicate that this condition is mediated by parthenogenetic activation and is free from a specific phenotype ascribed to unmaking of a maternally inherited recessive variant in the parthenogenetic cell lineage.

Results

We examined a 28-year-old Japanese 46,XX female with Silver-Russell syndrome and idiopathic hypersomnia. The results revealed (1) predominance of maternally derived alleles for all the differentially methylated regions examined; (2) no disease-related copy-number variant; (3) two types of regions for all chromosomes, i.e., four BAF (B-allele frequency) band regions with single major microsatellite peaks of maternal origin and single minor microsatellite peaks of non-maternal (paternal) origin, and six BAF band regions with single major microsatellite peaks of maternal origin and two minor microsatellite peaks of maternal and non-maternal (paternal) origin; (4) an unmasked extremely rare PER2 variant (c.1403G>A:p.(Arg468Gln)) with high predicted pathogenicity; (5) mildly affected local structure with altered hydrogen bonds of the p.Arg468Gln-PER2 protein; and (6) nucleus-dominant subcellular distribution of the p.Arg468Gln-PER2 protein.

Conclusions

The above findings imply that the second polar body retention occurred around fertilization, resulting in the generation of the parthenogenetic cell lineage by endoreplication of a female pronucleus and the normal cell lineage by fusion of male and female pronuclei, and that the homozygous PER2 variant in the parthenogenetic cells is the likely causative factor for idiopathic hypersomnia.