F1000Research

IntroductionThe increased demand for mechanical ventilation caused by the SARS-CoV-2 pandemic could generate a critical situation where patients may lose access to mechanical ventilators. Combined ventilation, in which two patients are ventilated simultaneously but independently with a single ventilator has been proposed as a life-saving bridge while waiting for new ventilators availability. New devices have emerged to facilitate this task and allow individualization of ventilatory parameters in combined ventilation. In this work we run computer-based electrical simulations of combined ventilation. We introduce an electrical model of a proposed mechanical device which is designed to individualize ventilatory parameters, and tested it under different circumstances. Materials and MethodsWith an electronic circuit simulator applet, an electrical model of combined ventilation is created using resistor-capacitor circuits. A device is added to the electrical model which is capable of individualizing the ventilatory parameters of two patients connected to the same ventilator. Through computational simulation, the model is tested in different scenarios with the aim of achieving adequate ventilation of two subjects under different circumstances: 1) two identical subjects; 2) two subjects with the same size but different lung compliance; and 3) two subjects with different sizes and compliances. The goal is to achieve the established charge per unit of size on each capacitor under different levels of end-expiratory voltage (as an end-expiratory pressure analog). Data collected included capacitor charge, voltage, and charge normalized to the weight of the simulated patient. ResultsSimulations show that it is possible to provide the proper charge to each capacitor under different circumstances using an array of electrical components as equivalents to a proposed mechanical device for combined ventilation. If the pair of connected capacitors have different capacitances, adjustments must be made to the source voltage and/or the resistance of the device to provide the appropriate charge for each capacitor under initial conditions. In pressure control simulation, increasing the end-expiratory voltage on one capacitor requires increasing the source voltage and the device resistance associated with the other simulated patient. On the other hand, in the volume control simulation, it is only required to intervene in the device resistance. ConclusionsUnder simulated conditions, this electrical model allows individualization of combined mechanical ventilation.

Limited knowledge exist on HTN-related knowledge and health behaviors among African American adult stroke survivors with hypertension condition living in rural Alabama. To address this gap, we conducted a small pilot study with a mixed methods design for needs assessment of stroke survivors with a hypertension condition living in rural areas of Alabama. We followed the community engagement strategy approach to conduct our study. After the approval from the Institutional Review Board, participants were recruited (N=25) using convenience sampling. We conducted surveys, followed by sequential interviews of our participants. Our needs assessment focused on knowledge and actual behaviors related to hypertension management among this population. This paper presents findings from the quantitative and qualitative data collected for this needs assessment study. Data collection included: (i) HTN Knowledge-Level Scale test (HK-LS), (ii) HTN Self-Care Activity Level Effects (H-SCALE), and (iii) The Southampton Stroke Self-Management Questionnaire. Interested participants ( n=14) were interviewed using a PI-developed semi-structured interview guide. Descriptive and inferential statistics were used to analyze the data collected from the surveys. The majority of participants (76%) had low level knowledge related to hypertension. Most participants also demonstrated limited adherence to hypertension behaviors including hypertension medication adherence (76%), DASH Diet (84%), physical activity ( 56%), and 72% had smoking habits. Our findings from qualitative interview data revealed the major themes of lack of knowledge related to hypertension management and post-stroke life management, lack of adherence to prescribe hypertension treatment, lack of continuity of care after discharge from hospital, and lack of social support. These results indicated poor adherence to prescribed hypertension management behaviors. These findings highlight the need for a larger-scale study to assess heart health knowledge further and to identify the specific needs and preferences of this underserved population, an essential step toward developing tailored, community-informed interventions.

Mouse genome modification requires costly equipment and highly skilled personnel to manipulate zygotes. A number of zygote electroporation techniques were reported to be highly efficient in gene delivery. One of these methods called i-GONAD (improved Genome-editing via Oviductal Nucleic Acids Delivery) describes electroporation-based gene transfer to zygotes in utero. Here we adopted this technology for mouse genome-editing from scratch minimizing the cost of equipment, operator skill and animal use. We chose the CRISPR/Cas9 system as a genome editing tool and i-GONAD as a gene delivery method to produce IL10 gene knockout in C57BL/6 mice. Four animals out of 13 delivered pups (30.8%) were genetically compromised at IL10 gene locus suggesting the feasibility of the approach. This report provides one of the possible technical settings for those who aim at establishing in-house mouse transgenesis pipeline at minimal cost from scratch. For citationPopova J.V., Bets V.D., Omelina E.S., Boldyreva L.V., Kozhevnikova E.N. Mouse Genome Editing from Scratch. Journal of Experimental Biology. Year; issue (number): page. DOI

ObjectiveTo evaluate the feasibility of implementing a self-management intervention to improve mobility in the community for stroke survivors. MethodsA sequential mixed methods design was used (a pilot randomised controlled trial and focus groups). Participants were adult stroke survivors within six months post discharge from hospital with functional and cognitive capacity for self-management. The intervention included education sessions, goal setting and action planning, group sessions, self-monitoring and follow up. The control group received usual care and both groups enrolled for 3 months in the study. Feasibility outcomes (recruitment and retention rates, randomisation and blinding, adherence to the intervention, collection of outcome measures, and the fidelity and acceptability of the intervention). Participants assessed at baseline, 3 months and 6 months for functional mobility and walking, self-efficacy, goal attainment, cognitive ability, and general health. A descriptive analysis was done for quantitative data and content analysis for the qualitative data. Findings of quantitative and qualitative data were integrated to present the final results of the study. ResultsTwenty-four participants were recruited and randomised into two groups (12 each). It was feasible to recruit from hospital and community and to deliver the intervention remotely. Randomisation and blinding were successful. Participants were retained (83%) at 3 months and (79.2%) at 6 months assessments. Adherence to the intervention varied due to multiple factors. Focus groups discussed participants motivations for joining the programme, their perspectives on the intervention (fidelity and acceptability) and methodology, perceived improvements in mobility, facilitators and challenges for self-management, and suggestions for improvement. ConclusionThe self-management intervention seems feasible for implementation for stroke survivors in the community. Participants appreciated the support provided and perceived improvement in their mobility. The study was not powered enough to draw a conclusion about the efficacy of the program and a future full-scale study is warranted.

IntroductionRegulation is important for medical software, but advances in software, notably developments in artificial intelligence (AI), are developing quickly. There are concerns that regulatory processes are not keeping up and that there is a need for more pro-innovation approaches. MethodsWe conducted a survey (n = 34) and four focus groups to discuss experiences of regulation among UK-based developers. ResultsIn the survey, 35% agreed/strongly agreed that they were confident in their knowledge of relevant regulation, while 50% agreed/strongly agreed that poor regulation was allowing bad products to come to market. The focus groups identified 10 themes around challenges with current processes: the process of obtaining regulatory approval is uncertain; lack of knowledge about regulatory approval; difficulties in obtaining reliable advice; complexity and slow pace of approvals; difficult to get NHS clinician involvement; process is costly and difficult to fund; implications for competition; international differences; incentives to develop lower classification products; and lack of harmonisation between NHS and MHRA. Respondents suggestions for solutions to improve processes fell under four themes: financial and structural support; regulatory collaboration and commissioner involvement; process efficiency and adaptability; and education and guidance. DiscussionDevelopers are unhappy with the process of regulation for medical software in the UK, finding it confusing and expensive. They feel systems compare poorly to international comparators. Integration between the MHRA system and NHS commissioning is considered poor.

BackgroundThe majority of propofol utilization as an induction anesthetic in cardiac surgery, particularly in cardiopulmonary bypass surgery led to several risks to the patient. The most common risk is dropped mean arterial pressure, even with the high risk of cardiac arrest. ObjectiveDetermining the influences of ejection fraction value on the amount of propofol requirement as an induction agent based on the patients primary outcome (BIS spectral index) and the secondary outcomes (mean arterial pressure and heart rate) DesignProspective study, analytical observational with multivariate linear regression analysis, and multicenter study Setting2 hospitals, including 1 teaching hospital and 1 private hospital Patientsall patients who underwent cardiopulmonary bypass surgery and are eligible for the inclusion criteria MeasurementsDoses of Propofol as an anesthesia induction, mean arterial pressure (MAP) prior to surgery, heart rate (HR) prior to surgery, BIS Spectral Index prior to surgery, MAP after induction, HR after induction, and BIS Spectral Index after induction ResultsThese data were analyzed using MATLAB R2022a software to obtain R2 (determining the effect size or influences) and p-value for each condition of ejection fraction value and the clinical responses. The data of this observational study is divided into six groups : 1. the effect size of ejection fraction value < 50% on BIS index obtained R2 0.9231 and p-value 0.88, 2. the effect size of ejection fraction value [&ge;] 50% on BIS index obtained R2 0.7794 and p-value 0.01, 3. the effect size of ejection fraction value < 50% on mean arterial pressure obtained R2 0.00024 and p-value 0.97, 4. The effect size of ejection fraction value [&ge;] 50% on mean arterial pressure obtained R2 0.0786 and p-value 0.005, 5. The effect size of ejection fraction value < 50% on heart rate obtained R2 0.3992 and p-value 0.06, 6. The effect size of ejection fraction value [&ge;] 50% on heart rate obtained R2 0.1757 and p-value 7.0776e-04. ConclusionsPropofol extremely impacts BIS index value compared to the patients mean arterial pressure or heart rate at the induction doses of propofol in general anesthesia for patients with a reduced ejection fraction

ObjectiveRecent studies have shown a potential link between gut microbiome and colorectal cancer (CRC). Initially, a wide array of research into this topic was discovered from the past decade, illustrating a keen interest in the potential causal relationship between the gut microbiome and CRC. However, the cancer research community is lacking a summarised systematic review of this kind which aims to explore the evidence linking the human gut microbiome to risk of CRC. DesignThis systematic review was carried out with two independent reviewers assessing the database outcomes from Medline and EMBASE during May 2020. A meta-analysis was undertaken studying the link between Helicobacter pylori and CRC; processed through Stata. Results31 papers were included in the systematic review, followed by 12 for the meta-analysis. From these papers, Fusobacterium and Bacteroides were reported most frequently as enriched in CRC versus control. The meta-analysis showed an Odds Ratio of 1.49 (95% CI 1.19 - 1.86), including a total of 20,001 events. This meta-analysis concluded that H. pylori infection significantly increases the risk of CRC, albeit with evidence of publication bias. ConclusionsBacteria have been discovered to increase the risk of CRC, however a definitive causal relationship cannot be concluded or excluded using case-control studies. To fully understand the potential link of the bacteria listed, alterations in research design and execution are required. The assessment found a need for a large-scale cohort study conducted over a significant period of time to thoroughly evaluate the potential relationship between gut microbiome and CRC risk. O_TEXTBOXSignificance of studyWhat is already known on this subject? [tpltrtarr]Roughly 10% of all cancer deaths in the UK are attributed to colorectal cancer (CRC), with CRC being the third most common cancer worldwide. [tpltrtarr]The risk of developing CRC has been closely linked to the composition of the gut microbiome [tpltrtarr]H. pylori is a known causative agent of gastric cancer What are the new findings? [tpltrtarr]To the best of the researchers knowledge, this is the first systematic review of this type conducted into this topic, investigating the genera/species of bacteria in the human gut microbiome and the risk of CRC. [tpltrtarr]This systematic review found a strong association between Fusobacterium and Bacteroides, amongst other species, and CRC. [tpltrtarr]The meta-analysis found a significant link between H. pylori infection and increased risk of CRC. How might this impact on clinical practice in the foreseeable future? [tpltrtarr]This systematic review provides potentially actionable evidence in the personalised management of patients to reduce their risk of CRC. [tpltrtarr]This review has highlighted the need for a large population prospective cohort study, with standardised sampling methods. [tpltrtarr]The meta-analysis reinforces the importance of H. pylori testing and eradication in those deemed at high risk of CRC C_TEXTBOX

ObjectiveTo explore the current research status and future development trend of artificial intelligence in neurorehabilitation. MethodsTo collect and organize the literature on AI in neurorehabilitation from the core collection of Web of Science (WOS) database in the past ten years, and summarize the current status and predict the future development trend of AI in neurorehabilitation by using VOSviewer software and CiteSpace software in Java language environment. ResultsA total of 326 documents were retrieved, with the highest number of publications in 2014 (81); the scholars with the most publications were LiChong and PanYu (6); the institution with the most publications was Tsinghua University (8); the journal with the most publications was Sensors (26); and the number of Chinese research in the field of AI applied to neurorehabilitation is leading in the world. The keyword analysis shows that the research hotspots of AI applied to neurorehabilitation in recent years are mainly in brain-computer interface, deep learning, and robotics. ConclusionRecently, artificial intelligence in neurorehabilitation has developed rapidly, and the number of papers has increased year by year, mainly focusing on brain-computer interface, deep learning, and robotics.

Africas diverse pathogen and human genetics present significant opportunities for genomic medicine research using artificial intelligence (AI). We surveyed 250 genomics researchers across 46 of the 55 African Union Member States to assess the state of AI use. The survey revealed that only 4% of respondents reported high familiarity with the application of AI for genomics and bioinformatics.

BackgroundPhysical activity has been shown to prevent mortality and morbidity among people with hypertension. Hypertension has been identified to affect about 33% of the adult population across the globe and 26.4% in Uganda. An increase in hypertension and its adverse outcomes have been observed and reported in Southwestern Uganda. This may be due to physical inactivity. However, there is limited evidence demonstrating physical activity among patients with hypertension within Southwestern Uganda. The current study investigated the extent of physical activity and associated factors among patients attending hypertension clinics in Mbarara City, Southwestern Uganda. ObjectiveTo investigate the extent of physical activity and associated factors among patients attending hypertension clinics in Mbarara City, Southwestern Uganda. MethodsA descriptive, quantitative cross-sectional study was conducted. Participants data was obtained using a structured researcher-administered questionnaire consisting of the International Physical Activity Questionnaire (IPAQ) long form, Motivation for Physical Activity Questionnaire (RM4-FM) and the Barrier to Being Active Quiz (BBAQ). Frequency distribution tables, Fischers exact test and multivariate logistic regression were used to describe data and establish associations during data analysis. A p-value less than 0.05 with 95% confidence interval was considered to be statistically significant. ResultsLess than half of the participants (45.39%) were found to be physically active. Level of education, having heard of physical activity, place of residence, sedentary behaviour and social influence were associated with physical activity with the Fischers exact test (p-value<0.05). On multivariate adjustment, only level of education (aOR=1.374; CI=1.055-1.790; p-value=0.018) and sedentary behaviour (aOR=0.276; CI=0.126-0.606; p-value=0.001) remained significant factors associated with physical activity. Majority of those who were active reported to be autonomously motivated. Most reported barriers were lack of skill, social influence and lack of willpower. ConclusionMore than half of the patients with hypertension were physically inactive and almost half were inactive and sedentary. This is a double disaster especially for patients with hypertension; therefore, emphasis should be put on educating the public about the benefits of physical activity and availing a variety of physical activity options that engage all demographic groups.

Both citation and funding metrics converge in shaping current perceptions of academic success. We aimed to evaluate what proportion of the most-cited USA-based biomedical scientists are funded by biomedical federal agencies and whether funded scientists are more cited than not funded ones. We linked a Scopus-based database on top-cited researchers (n=75,316 USA-based) and the NIH RePORTER database of 33 biomedical federal agencies (n=204,603 grant records) with matching based on name and institution. The 40,887 USA-based top-cited scientists who were allocated to any of 69 scientific subfields highly related to biomedicine were considered in the main analysis. The proportion of USA-based top-cited biomedical scientists (based on career-long citation impact) who had received any federal funding from biomedical research agencies was 63% for any funding (1996-2022), 21% for recent funding (2015-2022), and 14% for current funding (2021-2022). Respective proportions were 65%, 31%, and 21%, when top-cited scientists based on recent single year impact were considered. There was large variability across scientific subfields. No subfield had more than 31% of its top-cited USA-based scientists (career-long impact) currently funded. Funded top-cited researchers were overall more cited than non-funded top-cited scientists, e.g. mean (median) 14,420 (8983) versus 8,445 (4613) (p<0.001) and a substantial difference remained (, after adjusting for subfield and years since first publication. Differences were more prominent in some specific biomedical subfields. Overall, biomedical federal funding has offered support to approximately two-thirds of the top-cited biomedical scientists at some point during the last quarter century, but only a small minority of top-cited scientists have current federal biomedical funding. The large unevenness across subfields needs to be addressed with ways that improve equity, efficiency, excellence, and translational potential.

BackgroundDysarthria is a neurological speech impairment which can have a pervasive impact on an individuals independence, psychological well-being and social participation following a stroke. Speech and language therapy (SLT) in the acute hospital phase aims to provide the stroke survivor with the means to communicate effectively and reintegrate socially following their discharge. However, there is limited understanding of how patients perceive their experience of SLT at this time and how effectively it addresses their needs. AimTo explore the patients experience of dysarthria in the acute hospital phase following a stroke and perceptions of the SLT received during this time. MethodsParticipants for this qualitative study were recruited as hospital in-patients from the acute SLT service caseload. Semi-structured interview data was analysed with reflexive thematic analysis and themes constructed. Results & DiscussionThe themes of speech as a competing priority, feeling disempowered in rehabilitation and the need for human connection and their relevance for clinical practice are discussed. Speech difficulties are perceived as one of several priorities competing for participants time and energy with the impact of speech often minimised. Feelings of disempowerment come from both internal and external factors, but the importance of hope and belief in potential recovery was emphasised. The expressed need for human connections highlights the need for positive social communication experiences and the value of a communication affirming rehabilitation setting. ConclusionsThese themes highlight the multidimensional impact of dysarthria and how it is inextricably linked to the wider psychological, and social dimensions of stroke. SLT during acute hospital rehabilitation must go beyond the physical impairment and address the patients evolving priorities, their self-esteem, capacity for positive self-management and social reintegration.

Backgroundcharacteristic feature of COVID-19 during its progression in severity is the cytokine storm (via interleukin-6, IL-6) which is responsible for secondary acute respiratory distress syndrome (ARDS) [4]. Tocilizumab has an antagonist effect on the IL-6 receptor. With present review and metanalysis, we intend to update the current status on the clinical efficacy of tocilizumab in the treatment of Covid 19 infections in the published literature of case series. MATERIALS AND METHODSThe following inclusion criteria were used: (i) case series studies (number of reported patients in each study equal to or greater than ten (ii) use of tocilizumab alone or in combination with standard of care therapy (iii) Covid 19 adult patients (iv) the studies with endpoints on all-cause mortality, need for mechanical ventilation, clinical improvements. Data synthesis and statistical analysisMeta-analysis was performed using a random effects model and the DerSimonian and Laird method. RESULTS18 were selected for the quantitative analysis (meta-analysis). 14 studies were retrospective and 4 were prospective Meta-analysisThe mortality rate of COVID-19 patients with tocilizumab was 21% (251/1212) Asymmetric funnel plot in the cylindrical form due to publication bias In conclusionthe present synthesis provide us useful insights with the other available evidence to refine our strategy and equip ourselves effectively with tocilizumab to defeat COVID 19 to save humanity. LimitationsThe included studies utilized varied doses of tocilizumab (single or double), and duration drug availability issues emerged in some centers, which may have influenced both sample sizes and study designs. Clinical implicationsIncorporated studies without control groups into systematic reviews and quantitative synthesis especially when there are no other studies to consider can provide information for formulating effective treatment strategies for management of COVID 19 infections through the use of tocilizumab.

BackgroundEarly career researchers in Health Data Science (HDS) struggle to effectively manage their learning process due to the novel and interdisciplinary nature of this field. To date, there is limited understanding about learning strategies in health data science. Therefore, we aim to uncover learning strategies that early career researchers employ to address their educational challenges, as well as shed light on their preferences regarding HDS teaching approach and course design. MethodIn this study, we conducted a qualitative content analysis through semistructured interviews with ten early career researchers, including individuals pursuing masters, PhD, and postdoctoral research programmes in HDS, across two higher education institutions in the United Kingdom. Interviews were carried out in person from June 2023 to August 2023. Data were analysed qualitatively using NVivo software. Descriptive statistics were employed for quantitative analysis. ResultsRegarding learning strategies, we identified ten main categories with 22 codes, including collaboration, information seeking, active learning, focus granularity, elaboration, organisation, order granularity, goal orientation, reviewing, and deep learning strategies. Regarding course design and teaching, we discovered four categories with 14 codes, including course materials, duration and complexity, online discussion, and teaching approaches. ConclusionsEarly career researchers used a range of learning strategies aligned with well-established learning theories, such as peer learning, information seeking, and active learning. It is also evident that learners in HDS favour interactive courses that provide them with hands-on experience and interactive discussion. The insights derived from our findings can enhance the quality of education in HDS.

In 2018 we analysed the three main repositories for the human proteome, Ensembl/GENCODE, RefSeq and UniProtKB. They disagreed on the coding status of one of every eight annotated coding genes. The analysis inspired bilateral collaborations between annotation groups. Here we have repeated our analysis with updated versions of the three reference coding gene sets. Superficially, little appears to have changed. Although there are slightly fewer genes predicted as coding overall, the three groups still disagree on the status of 2,606 annotated genes. However, a comparison without read-through genes and immunoglobulin fragments shows that the three reference sets have merged or reclassified more than 700 genes since the last analysis and that just 0.6% of Ensembl/GENCODE coding genes are not also annotated by the other two reference sets. We used eight features indicative of non-coding genes to examine the 21,873 coding genes annotated across the three reference sets. We found that more than 2,000 had one or more potential non-coding features. While some of these genes will be protein coding, we believe that most are likely to be non-coding genes or pseudogenes. Our results suggest that annotators still vastly overestimate the number of true coding genes.

ObjectiveEvidence on the association between the gut microbiome and metabolic conditions has been increasing during the past decades. Unlike the straightforward identification of beneficial non-pathogenic bacteria as a potential probiotic for clinical use, the analysis of gut microbiome diversity is more complex and required a better understanding of various measures. We aim to summarize an elaborated list of gut microbiome diversity measures. DesignSystematic search was conducted in three databases: PubMed, Embase, and Cochrane Central Register of Clinical Trials for randomized controlled trials, quasi-experimental and observational studies for the relationship between gut microbiota and metabolic diseases published in 2019 with the English language. ResultsThe measurement methods of alpha diversity and beta diversity were explored. Of 5929 potential studies, 47 were included in the systematic review (14632 patients). Of 13 alpha diversity measures, the Shannon index was the most commonly used in 37 studies (78.7%), followed by Chao1 index (19 studies), Operational Taxonomic Unit (OTU) richness (15 studies), Simpson index (13 studies), and Abundance-based Coverage Estimators (ACE) index (10 studies). Of 2 beta diversity measures, the UniFrac was the most commonly used in 24 studies (unweighted 17 studies and weighted 16 studies), followed by Bray-Curtis dissimilarity (16 studies). ConclusionVarious measurement of gut microbiome diversity have been used in the literature. All measurements have unique characteristics, advantages, and disadvantages which lead to different usage frequency. The measures were chosen considering cost, simplicity, and types of research. Significance of this studyO_ST_ABSWhat is already known on this subject?C_ST_ABS{blacktriangleright} Alpha diversity, including Shannon index diversity, chao1 diversity, etc., is the average species diversity within a habitat type at a local scale while beta-diversity, such as Bray-Curtis dissimilarity and UniFrac, indicates the differentiation between microbial communities from different environments. {blacktriangleright}Alpha- and beta-diversity are the two most diverse measures of gut microbiota diversity with no consensus on which measurement methods should be used in metabolic condition study. What are the new findings?{blacktriangleright} Distinct characteristics, advantages, and disadvantages of each microbiome diversity measurement method lead to a variety of usage frequencies in metabolic condition studies. Shannon diversity is the most widely used alpha diversity while there is no predilection for beta diversity. How might it impact on clinical practice in the foreseeable future?{blacktriangleright} Further researchers on metabolic condition with microbiome diversity measurement will have impartial evidence on which measurement methods are most rationally appropriate for their studies regarding simplicity, cost, and efficacy.

In breast cancer loss of the long-arm of chromosome 16 is frequently observed, suggesting this is the location of tumour suppressor gene or genes. Previous studies localised two or three minimal regions for the LOH genes in the vicinity of 16q22.1 and 16q24.3, however the identification of the relevant tumour suppressor genes has proved elusive. The current availability of large datasets from breast cancers, that include both gene expression and gene dosage of the majority of genes on the long-arm of chromosome 16 (16q), provides the opportunity to revisit the identification of the critical tumour suppressor genes in this region. Utilising such data it was found 37% of breast cancers are single copy for all genes on 16q and this was more frequent in the luminal A and B subtypes. Since luminal breast cancers are associated with a superior prognosis this is consistent with previous data associating loss of 16q with breast cancers of better survival. Previous chromosomal studies found a karyotype with a der t(1;16) to be the basis for a proportion of breast cancers with loss of 16q. Use of data indicating the dosage of genes 21.9% of breast cancers were consistent with a der t(1;16) as the basis for loss of 16q. In such cases there is both loss of one dose of 16q and three doses of 1q suggesting a tumour suppressor function associated with long-arm of chromosome 16 and an oncogene function for 1q. Previous studies have approached the identification of tumour suppressor genes on 16q by utilising breast cancers with partial loss of 16q with the assumption regions demonstrating the highest frequency of loss of heterozygosity pinpoint the location of tumour suppressor genes. Sixty one of 816 breast cancers in this study showed partial loss of 16q defined by dosage of 357 genes. There was no compelling evidence for "hot-spots" of localised LOH which would pinpoint major tumour suppressor genes. Comparison of gene expression data between various groups of breast cancers based on 16q dosage was used to identify possible tumour suppressor genes. Combining these comparisons, together with known gene functional data, allowed the identification of eleven potential tumour suppressor genes spread along 16q. It is proposed that breast cancers with a single copy of 16q results in the simultaneous reduction of expression of several tumour suppressor genes. The existence of multiple tumour suppressor genes on 16q would severely limit any attempt to pinpoint tumour suppressor genes locations based on localised hot-spots of loss of heterozygosity. Interestingly, the majority of the identified tumour suppressor genes are involved in the modulation of wild-type p53 function. This role is supported by the finding that 80.5% of breast cancers with 16q loss have wild-type p53. TP53 is the most common mutated gene in cancer. In cancers with wild-type p53 would require other strategies to circumvent the key tumour suppressor role of p53. In breast cancers with complete loss of one dose of 16q it is suggested this provides a mechanism that contributes to the amelioration of p53 function.

BackgroundPreprints are scientific manuscripts that are made available on open-access servers but are not yet peer reviewed. While preprints are becoming more prevalent uptake is not uniform or optimal. Understanding researchers opinions and attitudes towards preprints is valuable to their successful implementation. Understanding knowledge gaps and researchers attitudes toward preprinting can assist stakeholders like journals, funding agencies, and universities to implement preprints more effectively. Here, we aim to collect perceptions and behaviours regarding preprints in across an international sample of biomedical researchers. MethodsBiomedical authors were identified by a keyword-based, systematic search from the MEDLINE database, and their emails were extracted to invite them to our survey. A cross-sectional anonymous survey was distributed to all identified biomedical authors to collect their knowledge, attitudes, and opinions about preprinting. ResultsThe survey was completed by 730 biomedical researchers with a response rate of 3.20% and demonstrated a wide range of attitudes and opinions about preprints with authors from various disciplines and career stages around the world. Most respondents were familiar with the concept of preprints, but most had not published a preprint before. The lead author of the project and journal policy had the most impact on decisions to post a preprint, while employers/research institute had the least impact. Supporting open science practices was the highest ranked incentive, while increases to authors visibility was highest ranked motivation for publishing preprints. ConclusionWhile many biomedical researchers recognize the benefits of preprints, there is still hesitation among others to engage in this practice. This may be due to the general lack of peer review of preprints and little enthusiasm from external organizations, such as journals, funding agencies, and universities. Future work is needed to determine optimal ways to increase researchers attitudes through modifications to current preprint systems and policies.

IntroductionRapid and safe endotracheal intubation is of paramount importance in the general anaesthesia practices. Safety of such practices while performing surgical procedures in people with critical coronary lesions assumes increased significance.The use of succinylcholine and rocuronium are common but the association with the application of these medications and concomitant haemodynamic changes on major adverse cardiac events (MACE) has not been adequately studied. The aim of this study is to assess the safety and efficacy of succinylcholine in comparison with rocuronium for MACE in cardiac surgical population. MethodsRetrospective analysis of data collected from administrative and surgical databases of a tertiary care centre. The patients were divided in two groups,wherein the Group A constituted patients who belonged to succinylcholine and Group B represents the patients who were treated with rocuronium.The baseline demographic characteristics, MACE including intubation difficulty score and Cormack Lahne grade of intubation were recorded. ResultsA total of 134 patients were included in the study. Baseline characters were similar in both the groups. There were 2 deaths in the succinylcholine group while 3 in the rocuronium group. The MACE was not statistically significant (p= 0.0505) in both groups. Cormack Lahane scale and intubation difficulty scale were similar in both groups. ConclusionSuccinylcholine was found to be equally efficient and safe in comparison with rocuronium in terms of MACE during coronary artery bypass surgery.

ObjectiveThe aim of this study was to evaluate the effectiveness of the "Dique Filipeia" rehabilitation protocol in patients with COVID-19 admitted to reference hospitals. MethodsThis is an experimental study with COVID-19 patients admitted to the hospitals wards being considered eligible. The study outcomes were assessed between patients undergoing the rehabilitation protocol (Dique Filipeia group) and patients who did not receive the protocol (control group). The rehabilitation protocol consisted in classifying patients daily into four levels of severity through peripheral oxygen saturation. Severity was classified by the oxygen flow needed to maintain a saturation greater than or equal to the cut-off point of 93%. A standardized ventilatory support and functional rehabilitation exercises were performed for each severity level patient, followed by an attempt to wean oxygen. ResultsA total of 727 patients were analyzed in the study. The Dique Filipeia group presented a lower total (132.7 {+/-} 35.3 vs 307.0 {+/-} 114.3 m3/patient; effect size 1.73) and daily (2.9 {+/-} 1.0 vs 6.8 {+/-} 3.1 m3/day/patient; effect size 1.46) oxygen expenditure than the control group. The Dique Filipeia patients presented higher hospital discharge (64.9 {+/-} 9.3 vs 35.4 {+/-} 7.5%; effect size 3.46) and lower length of stay (15.8 {+/-} 4.2 vs 29.1 {+/-} 3.4 days; effect size 3.47) than the control group. The Dique Filipeia group patients, who were demanding oxygen therapy, were using 6.2 {+/-} 4.3 L/min of oxygen at day 1. There was a statistically significant reduction from day 2 (p = 0.0001) and oxygen flow was reduced below 1L/min after day 7. ConclusionsThe implementation of a standardized rehabilitation protocol reduced oxygen expenditure, increased hospital discharge and reduced the length of hospital stay. Dique Filipeia is a practical, feasible and safe protocol.