bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards a United Nations Internal Regulation for Artificial Intelligence
Authors: Fournier-Tombs Eleonore
Published: August 2021

This article sets out the rationale for a United Nations Regulation for Artificial Intelligence, which is needed to set out the modes of engagement of the organisation when using artificial intelligence technologies in the attainment of its mission. It argues that given the increasing use of artificial intelligence by the United Nations, including in some activities considered high risk by the European Commission, a regulation is urgent. It also contends that rules of engagement for artificial intelligence at the United Nations would support the development of ‘good artificial intelligence’, by giving developers clear pathways for authorisation that would build trust in these technologies. Finally, it argues that an internal regulation would build upon the work in artificial intelligence ethics and best practices already initiated in the organisation that could, like the Brussels Effect, set an important precedent for regulations in other countries.
Hansen's disease – a forgotten disease?
Authors: Ferreira Paula Marques , Rato Inês Rueff , Rigor Joana , Mota Margarida
Published: August 2021

Hansen's disease, also known as leprosy, is an infection caused by the bacteria Mycobacterium leprae. The authors present the case of a 52-year-old man, born in Tondela and living in Espinho, with no pathological antecedents. The clinical picture began in April 2017, when macular lesions appeared in the lower limbs and rapidly progressed to the trunk and upper limbs, associated with complaints of pruritus but without alterations in the analytical study. After several topical and systemic treatments with glucocorticoids, antifungals, antibacterials and unsuccessful antihistamines, he was referred to an external consultation of Dermatology. He performed a biopsy of one of the lesions that revealed the definitive diagnosis: “Lepromatous Leprosy”. After the biopsy result, he started triple treatment with rifampicin, clofazimine and dapsone with improvement of the condition.
Bortezomib and rituximab in de novo adolescent/adult CD20-positive, Ph-negative pre-B-cell acute lymphoblastic leukemia
Authors: Jain Hasmukh , Sengar Manju , Goli Vasu Babu , Thorat Jayashree , Tembhare Prashant , Shetty Dhanlaxmi , Bonda V. N. Avinash , Nayak Lingaraj , Subramanian P. G. , Bagal Bhausaheb , Patkar Nikhil , Sharma Neha , Gupta Himanshi , Gujral Sumeet
Published: August 2021

The expression of CD20 in precursor B-cell acute lymphoblastic leukemia (B-ALL) is associated with poor outcomes. The addition of rituximab to intensive chemotherapy in CD20+ ALL has led to improved outcomes in several studies. However, there is no clear evidence regarding the optimal number of doses and its benefit without an allogeneic stem cell transplant. Achieving measurable residual disease (MRD)-negative status postinduction would reduce the requirement for a transplant. Novel approaches are needed to induce a higher proportion of MRD-negative complete remission in patients with high-risk ALL. Given bortezomib’s activity in relapsed ALL and its synergism with rituximab in B-cell lymphomas, the addition of bortezomib to rituximab and chemotherapy may provide an incremental benefit in CD20+ precursor B-ALL. We conducted a phase 2 study to test the activity of bortezomib and rituximab in combination with a pediatric-inspired regimen during induction therapy in newly diagnosed adolescents and adults (aged >14 years) with CD20+, Philadelphia-negative precursor B-ALL; bone marrow MRD negativity at the end of induction was the primary end point. From December 2017 through August 2019, a total of 35 patients were enrolled. End-of-induction MRD-negative status was achieved in 70.9% of patients, as opposed to 51.7% in the historical cohort treated with chemotherapy alone. MRD-negative rates improved to 87.5% post-consolidation. At a median follow-up of 21 months, event-free survival and overall survival rates were 78.8% (95% confidence interval, 66-94) and 78.7% (95% confidence interval, 65.8-94), respectively. There was no significant increase in toxicity with bortezomib and rituximab compared with the historical cohort. The incidence of neuropathy was 26% (all less than grade 3). The combination of bortezomib, rituximab, and a pediatric-inspired ALL regimen was active and well tolerated in de novo CD20+ Philadelphia-negative precursor B-ALL. This trial was registered with the Clinical Trials Registry-India as CTRI/2017/04/008393(http://ctri.nic.in/Clinicaltrials).
IFN-γ signature in the plasma proteome distinguishes pediatric hemophagocytic lymphohistiocytosis from sepsis and SIRS
Authors: Lin Howard , Scull Brooks P. , Goldberg Baruch R. , Abhyankar Harshal A. , Eckstein Olive E. , Zinn Daniel J. , Lubega Joseph , Agrusa Jennifer , El Mallawaney Nader , Gulati Nitya , Forbes Lisa , Chinn Ivan , Chakraborty Rikhia , Velasquez Jessica , Goldman Jordana , Bashir Dalia , Lam Fong , Muscal Eyal , Henry Michael. M. , Greenberg Jay N. , Ladisch Stephan , Hermiston Michelle L. , Meyer Lauren K. , Jeng Michael , Naqvi Ahmed , McClain Kenneth , Nguyen Trung , Wong Hector , Man Tsz-Kwong , Jordan Michael B. , Allen Carl E.
Published: August 2021

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by pathologic immune activation in which prompt recognition and initiation of immune suppression is essential for survival. Children with HLH have many overlapping clinical features with critically ill children with sepsis and systemic inflammatory response syndrome (SIRS) in whom alternative therapies are indicated. To determine whether plasma biomarkers could differentiate HLH from other inflammatory conditions and to better define a core inflammatory signature of HLH, concentrations of inflammatory plasma proteins were compared in 40 patients with HLH to 47 pediatric patients with severe sepsis or SIRS. Fifteen of 135 analytes were significantly different in HLH plasma compared with SIRS/sepsis, including increased interferon-γ (IFN-γ)–regulated chemokines CXCL9, CXCL10, and CXCL11. Furthermore, a 2-analyte plasma protein classifier including CXCL9 and interleukin-6 was able to differentiate HLH from SIRS/sepsis. Gene expression in CD8+ T cells and activated monocytes from blood were also enriched for IFN-γ pathway signatures in peripheral blood cells from patients with HLH compared with SIRS/sepsis. This study identifies differential expression of inflammatory proteins as a diagnostic strategy to identify critically ill children with HLH, and comprehensive unbiased analysis of inflammatory plasma proteins and global gene expression demonstrates that IFN-γ signaling is uniquely elevated in HLH. In addition to demonstrating the ability of diagnostic criteria for HLH and sepsis or SIRS to identify groups with distinct inflammatory patterns, results from this study support the potential for prospective evaluation of inflammatory biomarkers to aid in diagnosis of and optimizing therapeutic strategies for children with distinctive hyperinflammatory syndromes.
Outcomes after first-line immunochemotherapy for primary mediastinal B-cell lymphoma: a LYSA study
Authors: Camus Vincent , Rossi Cédric , Sesques Pierre , Lequesne Justine , Tonnelet David , Haioun Corinne , Durot Eric , Willaume Alexandre , Gauthier Martin , Moles-Moreau Marie-Pierre , Antier Chloé , Lazarovici Julien , Monjanel Hélène , Bernard Sophie , Tardy Magalie , Besson Caroline , Lebras Laure , Choquet Sylvain , Le Du Katell , Bonnet Christophe , Bailly Sarah , Damaj Ghandi , Laribi Kamel , Maisonneuve Hervé , Houot Roch , Chauchet Adrien , Jardin Fabrice , Traverse-Glehen Alexandra , Decazes Pierre , Becker Stéphanie , Berriolo-Riedinger Alina , Tilly Hervé
Published: August 2021

Primary mediastinal B-cell lymphoma (PMBL) is a rare type of aggressive lymphoma typically affecting young female patients. The first-line standard of care remains debated. We performed a large multicenter retrospective study in 25 centers in France and Belgium to describe PMBL patient outcomes after first-line treatment in real-life settings. A total of 313 patients were enrolled and received rituximab (R) plus ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone) (n = 180) or CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) delivered every 14 days (R-CHOP14, n = 76) or 21 days (R-CHOP21, n = 57) and consolidation strategies in modalities that varied according to time and institution, mainly guided by positron emission tomography. Consolidation autologous stem cell transplantation was performed for 46 (25.6%), 24 (31.6%), and 1 (1.8%) patient in the R-ACVBP, R-CHOP14, and R-CHOP21 groups, respectively (P < .001); only 17 (5.4%) patients received mediastinal radiotherapy. The end-of-treatment complete metabolic response rates were 86.3%, 86.8%, and 76.6% (P = .23) in the R-ACVBP, R-CHOP14, and R-CHOP21 groups. The median follow-up was 44 months, and the R-ACVBP, R-CHOP14, and R-CHOP21 three-year progression-free survival probabilities were 89.4% (95% confidence interval [CI], 84.8-94.2), 89.4% (95% CI, 82.7-96.6), and 74.7% (95% CI, 64-87.1) (P = .018). A baseline total metabolic tumor volume (TMTV) ≥360 cm3 was associated with a lower progression-free survival (hazard ratio, 2.18; 95% CI, 1.05-4.53). Excess febrile neutropenia (24.4% vs 5.3% vs 5.3%; P < .001) and mucositis (22.8% vs 3.9% vs 1.8%; P < .001) were observed with R-ACVBP compared with the R-CHOP regimens. Patients with PMBL treated with dose-dense immunochemotherapy without radiotherapy have excellent outcomes. R-ACVBP acute toxicity was higher than that of R-CHOP14. Our data confirmed the prognostic importance of baseline TMTV.
Genome-wide identification, characterization and expression analysis of MATE family genes in apple (Malus × domestica Borkh)
Authors: Zhang Weihan , Liao Liao , Xu Jinsheng , Han Yuepeng , Li Li
Published: August 2021

Background

As an important group of the multidrug efflux transporter family, the multidrug and toxic compound extrusion (MATE) family has a wide range of functions and is distributed in all kingdoms of living organisms. However, only two MATE genes in apple have been analyzed and genome-wide comprehensive analysis of MATE family is needed.

Results

In this study, a total of 66 MATE (MdMATE) candidates encoding putative MATE transporters were identified in the apple genome. These MdMATE genes were classified into four groups by phylogenetic analysis with MATE genes in Arabidopsis. Synteny analysis reveals that whole genome duplication (WGD) and segmental duplication events played a major role in the expansion of MATE gene family in apple. MdMATE genes show diverse expression patterns in different tissues/organs and developmental stages. Analysis of cis-regulatory elements in MdMATE promoter regions indicates that the function of MdMATE genes is mainly related to stress response. Besides, the changes of gene expression levels upon different pathogen infections reveal that MdMATE genes are involved in biotic stress response.

Conclusions

In this work, we systematically identified MdMATE genes in apple genome using a set of bioinformatics approaches. Our comprehensive analysis provided valuable resources for improving disease resistance in apple and further functional characterization of MATE genes in other species.
Clinical characteristics of acute liver failure associated with hepatitis A infection in children in Mogadishu, Somalia: a hospital-based retrospective study
Authors: Keles Esra , Hassan-Kadle Mohamed A. , Osman Marian Muse , Eker Hasan Huseyin , Abusoglu Zeynep , Baydili Kursad Nuri , Osman Aamir Muse
Published: August 2021

Background

Hepatitis A is one of the most common infectious causes of acute hepatitis, and currently, a neglected global public health problem necessitating an urgent response in Somalia. Hepatitis A infection and its rare complication of acute liver failure in children are largely based on very limited data. The aim of the study was therefore to investigate the Hepatitis A infection and its rare complication of acute liver failure in children in Somalia.

Methods

This retrospective study was conducted on children aged 0–18 years who were admitted to the pediatric departments of the Somalia Mogadishu-Turkey Training and Research Hospital, Somali, from June 2019 and December 2019. Patients who were tested for hepatitis A infection during the study period and had complete data were included. Children with chronic disease, primary or secondary immunodeficiency, blood transfusion history, and missing data were excluded. Abstracted data including patients' demographics, clinical presentation, laboratory results, ultrasonographic findings, length of hospital stay, clinical course and outcome were retrieved from the hospital database system.

Results

Of the 13,047 children, 219 were analyzed. Of the 219 Hepatitis A cases, 25 (11%) were diagnosed with pediatric acute liver failure (PALF). The mean age of children with Hepatitis A was 6.7 years. The majority of cases were reported in the 5–9 (39.7%) year age range. Hepatic encephalopathy, length of hospital stay, levels of albumin, and values of PT, aPPT, and INR were significantly higher in children with acute live failure. The presence of cholecystitis and cholecystitis with ascites in the sonographic evaluation were poor prognostic markers for acute liver failure.

Conclusions

This study revealed hepatitis A virus infection and its related acute liver failure among hospitalized children in Somalia of which 11% had PALF. Hence, the introduction of Hepatitis A vaccination, which is the main public health tool, into the national immunization program, the improvement of hygiene conditions, raising awareness of the disease, and increasing health literacy are necessary to prevent the consequence of the Hepatitis A virus in children.
The epigenetic immunomodulator, HBI-8000, enhances the response and reverses resistance to checkpoint inhibitors
Authors: Bissonnette Reid P. , Cesario Rosemary M. , Goodenow Bob , Shojaei Farbod , Gillings Mireille
Published: August 2021

Background

Treatment with immune checkpoint inhibitors (ICIs) targeting CTLA-4 and the PD-1/PD-L1 axis is effective against many cancer types. However, due in part to unresponsiveness or acquired resistance, not all patients experience a durable response to ICIs. HBI-8000 is a novel, orally bioavailable class I selective histone deacetylase inhibitor that directly modifies antitumor activity by inducing apoptosis, cell cycle arrest, and resensitization to apoptotic stimuli in adult T cell lymphoma patients. We hypothesized that HBI-8000 functions as an epigenetic immunomodulator to reprogram the tumor microenvironment from immunologically cold (nonresponsive) to hot (responsive).

Method

Mice bearing syngeneic tumors (MC38 and CT26 murine colon carcinoma and A20 B-cell lymphoma were treated daily with HBI-8000 (orally), alone or in combination with PD-1, PD-1 L, or CTLA-4 antibodies. MC38 tumors were also analyzed in nanoString gene expression analysis.

Results

HBI-8000 augmented the activity of ICI antibodies targeting either PD-1, PD-L1 or CTLA-4, and significantly increased tumor regression (p < 0.05) in the above models. Gene expression analysis of the treated MC38 tumors revealed significant changes in mRNA expression of immune checkpoints, with enhanced dendritic cell and antigen-presenting cell functions, and modulation of MHC class I and II molecules.

Conclusions

These findings suggest that HBI-8000 mediates epigenetic modifications in the tumor microenvironment, leading to improved efficacy of ICIs, and provide strong rationale for combination therapies with ICIs and HBI-8000 in the clinical setting.

Precis

As an HDACi, HBI-8000 plays an important role in priming the immune system in the tumor microenvironment. The current preclinical data further justifies testing combination of HBI-8000 and ICIs in the clinic.
Prevalence and associated factors for climatic droplet keratopathy in Kazakhs adults: a cross-sectional study in Tacheng, Xinjiang, China
Authors: Hua Zhixiang , Han Xiaoyan , Li Guoqing , Lv Li , He Xiaolan , Gu Laman , Luo Jianfeng , Yang Jin
Published: August 2021

Background

Investigation of the prevalence of climatic droplet keratopathy (CDK) in Tacheng, Xinjiang, China.

Methods

A total of 1030 participants, in their 40s or older, from the Kazakh ethnic group in Tacheng, were randomly sampled by stratification method. Ophthalmic examinations and surveys were carried out on these participants. Factors associated with CDK were analyzed with logistic regression models.

Results

CDK was found in 66 (6.4%; 95% confidence interval [CI]: 4.9–7.9%) Kazakh individuals.

After multiple regression model analysis, it demonstrated that age (< 0.001), exposure time (< 0.001), exposure protection (< 0.001), and vegetable intake (< 0.001) were of correlation with CDK, of which age (OR = 1.21[CI]: 1.16–1.27) and long-term outdoor exposure (OR = 2.42[CI]: 1.26–4.67) were the risk factors, and that vegetable intake (OR = 0.29[CI]: 0.14–0.59) and wearing a hat (OR = 0.24[CI]: 0.10–0.56) were protective factors.

Conclusions

This study has revealed the risk and protective factors of CDK, providing a new insight on related research.
Analysis of spatial-temporal distribution of notifiable respiratory infectious diseases in Shandong Province, China during 2005–2014
Authors: Li Xiaomei , Chen Dongzhen , Zhang Yan , Xue Xiaojia , Zhang Shengyang , Chen Meng , Liu Xuena , Ding Guoyong
Published: August 2021

Background

Little comprehensive information on overall epidemic trend of notifiable respiratory infectious diseases is available in Shandong Province, China. This study aimed to determine the spatiotemporal distribution and epidemic characteristics of notifiable respiratory infectious diseases.

Methods

Time series was firstly performed to describe the temporal distribution feature of notifiable respiratory infectious diseases during 2005–2014 in Shandong Province. GIS Natural Breaks (Jenks) was applied to divide the average annual incidence of notifiable respiratory infectious diseases into five grades. Spatial empirical Bayesian smoothed risk maps and excess risk maps were further used to investigate spatial patterns of notifiable respiratory infectious diseases. Global and local Moran’sIstatistics were used to measure the spatial autocorrelation. Spatial-temporal scanning was used to detect spatiotemporal clusters and identify high-risk locations.

Results

A total of 537,506 cases of notifiable respiratory infectious diseases were reported in Shandong Province during 2005–2014. The morbidity of notifiable respiratory infectious diseases had obvious seasonality with high morbidity in winter and spring. Local Moran’sIanalysis showed that there were 5, 23, 24, 4, 20, 8, 14, 10 and 7 high-risk counties determined for influenza A (H1N1), measles, tuberculosis, meningococcal meningitis, pertussis, scarlet fever, influenza, mumps and rubella, respectively. The spatial-temporal clustering analysis determined that the most likely cluster of influenza A (H1N1), measles, tuberculosis, meningococcal meningitis, pertussis, scarlet fever, influenza, mumps and rubella included 74, 66, 58, 56, 22, 64, 2, 75 and 56 counties, and the time frame was November 2009, March 2008, January 2007, February 2005, July 2007, December 2011, November 2009, June 2012 and May 2005, respectively.

Conclusions

There were obvious spatiotemporal clusters of notifiable respiratory infectious diseases in Shandong during 2005–2014. More attention should be paid to the epidemiological and spatiotemporal characteristics of notifiable respiratory infectious diseases to establish new strategies for its control.
The impact of an online intervention on the medical, dental and health sciences students about interprofessional education; a quasi-experimental study
Authors: Guraya Salman Y. , David Leena R. , Hashir Shermin , Mousa Noha A. , Al Bayatti Saad Wahbi , Hasswan Ahmed , Kaouas Mujtaba
Published: August 2021

Background

Interprofessional education (IPE) encompasses integration, communication, mutual trust and shared decision-making with a common goal of improved patient care and safety. Despite its crucial role, IPE has not gained its anticipated popularity. This study aims to determine the impact of an online educational intervention about IPE on medical, dental and health sciences students in the University of Sharjah (UoS).

Methods

This quasi-experimental research was conducted in three phases; a pre-intervention phase where the Readiness for Interprofessional Learning Scale (RIPLS) inventory was administered online to the medical, dental and health sciences students of UoS; an intervention phase where an online workshop was organized via Microsoft Teams®; and a post-intervention phase where RIPLS was used to gather the students’ attitudes towards IPE. The independentttest was used to compare the responses between genders and junior and senior students. A paired samplettest was used to determine the impact of the intervention on the students’ understandings and attitudes about IPE.

Results

Out of 800 invited students, 530 students responded to the pre-intervention RIPLS survey. A comparison of the pre-post intervention for the RIPLS subscales of teamwork and collaboration, professional identification, and professional roles showed a significant improvement of students’ attitudes withp-values 0.03, 0.00 and 0.00, respectively. All workshop moderators scored a median of 4 or 5 to the essential elements of IPE during intervention except for a median of 3 for group dynamics.

Conclusion

The present data, derived from the application of a brief online educational intervention, underpins the readiness and positive attitudes of undergraduate medical students towards IPE. The positive impact of online intervention necessitates the development of a structured and unified IPE curriculum to enhance the receptiveness and application of IPE in the medical field.
Modeling and prediction of pressure injury in hospitalized patients using artificial intelligence
Authors: Anderson Christine , Bekele Zerihun , Qiu Yongkai , Tschannen Dana , Dinov Ivo D.
Published: August 2021

Background

Hospital-acquired pressure injuries (PIs) induce significant patient suffering, inflate healthcare costs, and increase clinical co-morbidities. PIs are mostly due to bed-immobility, sensory impairment, bed positioning, and length of hospital stay. In this study, we use electronic health records and administrative data to examine the contributing factors to PI development using artificial intelligence (AI).

Methods

We used advanced data science techniques to first preprocess the data and then train machine learning classifiers to predict the probability of developing PIs. The AI training was based on large, incongruent, incomplete, heterogeneous, and time-varying data of hospitalized patients. Both model-based statistical methods and model-free AI strategies were used to forecast PI outcomes and determine the salient features that are highly predictive of the outcomes.

Results

Our findings reveal that PI prediction by model-free techniques outperform model-based forecasts. The performance of all AI methods is improved by rebalancing the training data and by including the Braden in the model learning phase. Compared to neural networks and linear modeling, with and without rebalancing or using Braden scores, Random forest consistently generated the optimal PI forecasts.

Conclusions

AI techniques show promise to automatically identify patients at risk for hospital acquired PIs in different surgical services. Our PI prediction model provide a first generation of AI guidance to prescreen patients at risk for developing PIs.

Clinical impact

This study provides a foundation for designing, implementing, and assessing novel interventions addressing specific healthcare needs. Specifically, this approach allows examining the impact of various dynamic, personalized, and clinical-environment effects on PI prevention for hospital patients receiving care from various surgical services.
Implementation of a patient-collected audio recording audit & feedback quality improvement program to prevent contextual error: stakeholder perspective
Authors: Ball Sherry L. , Weiner Saul J. , Schwartz Alan , Altman Lisa , Binns-Calvey Amy , Chan Carolyn , Falck-Ytter Corinna , Frenchman Meghana , Gee Bryan , Jackson Jeffrey L. , Jordan Neil , Kass Benjamin , Kelly Brendan , Safdar Nasia , Scholcoff Cecilia , Sharma Gunjan , Subramaniam Soumya , Weaver Frances , Wopat Maria
Published: August 2021

Background

Using patient audio recordings of medical visits to provide clinicians with feedback on their attention to patient life context in care planning can improve health care delivery and outcomes, and reduce costs. However, such an initiative can raise concerns across stakeholders about surveillance, intrusiveness and merit. This study examined the perspectives of patients, physicians and other clinical staff, and facility leaders over 3 years at six sites during the implementation of a patient-collected audio quality improvement program designed to improve patient-centered care in a non-threatening manner and with minimal effort required of patients and clinicians.

Methods

Patients were invited during the first and third year to complete exit surveys when they returned their audio recorders following visits, and clinicians to complete surveys annually. Clinicians were invited to participate in focus groups in the first and third years. Facility leaders were interviewed individually during the last 6 months of the study.

Results

There were a total of 12 focus groups with 89 participants, and 30 leadership interviews. Two hundred fourteen clinicians and 800 patients completed surveys. In a qualitative analysis of focus group data employing NVivo, clinicians initially expressed concerns that the program could be disruptive and/or burdensome, but these diminished with program exposure and were substantially replaced by an appreciation for the value of low stakes constructive feedback. They were also significantly more confident in the value of the intervention in the final year (p = .008), more likely to agree that leadership supports continuous improvement of patient care and gives feedback on outcomes (p = .02), and at a time that is convenient (p = .04). Patients who volunteered sometimes expressed concerns they were “spying” on their doctors, but most saw it as an opportunity to improve care. Leaders were supportive of the program but not yet prepared to commit to funding it exclusively with facility resources.

Conclusions

A patient-collected audio program can be implemented when it is perceived as safe, not disruptive or burdensome, and as contributing to better health care.
The association between mechanical ventilator compatible bed occupancy and mortality risk in intensive care patients with COVID-19: a national retrospective cohort study
Authors: Wilde Harrison , Mellan Thomas , Hawryluk Iwona , Dennis John M. , Denaxas Spiros , Pagel Christina , Duncan Andrew , Bhatt Samir , Flaxman Seth , Mateen Bilal A. , Vollmer Sebastian J.
Published: August 2021

Background

The literature paints a complex picture of the association between mortality risk and ICU strain.

In this study, we sought to determine if there is an association between mortality risk in intensive care units (ICU) and occupancy of beds compatible with mechanical ventilation, as a proxy for strain.

Methods

A national retrospective observational cohort study of 89 English hospital trusts (i.e. groups of hospitals functioning as single operational units). Seven thousand one hundred thirty-three adults admitted to an ICU in England between 2 April and 1 December, 2020 (inclusive), with presumed or confirmed COVID-19, for whom data was submitted to the national surveillance programme and met study inclusion criteria. A Bayesian hierarchical approach was used to model the association between hospital trust level (mechanical ventilation compatible), bed occupancy, and in-hospital all-cause mortality. Results were adjusted for unit characteristics (pre-pandemic size), individual patient-level demographic characteristics (age, sex, ethnicity, deprivation index, time-to-ICU admission), and recorded chronic comorbidities (obesity, diabetes, respiratory disease, liver disease, heart disease, hypertension, immunosuppression, neurological disease, renal disease).

Results

One hundred thirty-five thousand six hundred patient days were observed, with a mortality rate of 19.4 per 1000 patient days. Adjusting for patient-level factors, mortality was higher for admissions during periods of high occupancy (> 85% occupancy versus the baseline of 45 to 85%) [OR 1.23 (95% posterior credible interval (PCI): 1.08 to 1.39)]. In contrast, mortality was decreased for admissions during periods of low occupancy (< 45% relative to the baseline) [OR 0.83 (95% PCI 0.75 to 0.94)].

Conclusion

Increasing occupancy of beds compatible with mechanical ventilation, a proxy for operational strain, is associated with a higher mortality risk for individuals admitted to ICU. Further research is required to establish if this is a causal relationship or whether it reflects strain on other operational factors such as staff. If causal, the result highlights the importance of strategies to keep ICU occupancy low to mitigate the impact of this type of resource saturation.
Brucella melitensis UGPase inhibits the activation of NF-κB by modulating the ubiquitination of NEMO
Authors: Zhou Yucheng , Bu Zhaoyang , Qian Jing , Cheng Yuening , Qiao Lianjiang , Yang Sen , Cheng Shipeng , Wang Xinglong , Ren Linzhu , Yang Yanling
Published: August 2021

Background

UTP-glucose-1-phosphoryl transferase (UGPase) catalyzes the synthesis of UDP-glucose, which is essential for generating the glycogen needed for the synthesis of bacterial lipopolysaccharide (LPS) and capsular polysaccharide, which play important roles in bacterial virulence. However, the molecular function of UGPase in Brucella is still unknown.

Results

In this study, the ubiquitination modification of host immune-related protein in cells infected with UGPase-deleted or wild-type Brucella was analyzed using ubiquitination proteomics technology. The ubiquitination modification level and type of NF-κB Essential Modulator (NEMO or Ikbkg), a molecule necessary for NF-κB signal activation, was evaluated using Coimmunoprecipitation, Western blot, and dual-Luciferase Assay. We found 80 ubiquitin proteins were upregulated and 203 ubiquitin proteins were downregulated in cells infected with B. melitensis 16 M compared with those of B. melitensis UGPase-deleted strain (16 M-UGPase−). Moreover, the ubiquitin-modified proteins were mostly enriched in the categories of regulation of kinase/NF-κB signaling and response to a bacterium, suggesting Brucella UGPase inhibits ubiquitin modification of related proteins in the host NF-κB signaling pathway. Further analysis showed that the ubiquitination levels of NEMO K63 (K63-Ub) and Met1 (Met1-Ub) were significantly increased in the 16 M-UGPase−-infected cells compared with that of the 16 M-infected cells, further confirming that the ubiquitination levels of NF-κB signaling-related proteins were regulated by the bacterial UGPase. Besides, the expression level of IκBα was decreased, but the level of p-P65 was significantly increased in the 16 M-UGPase−-infected cells compared with that of the 16 M- and mock-infected cells, demonstrating that B. melitensis UGPase can significantly inhibit the degradation of IκBα and the phosphorylation of p65, and thus suppressing the NF-κB pathway.

Conclusions

The results of this study showed that Brucella melitensis UGPase inhibits the activation of NF-κB by modulating the ubiquitination of NEMO, which will provide a new scientific basis for the study of immune mechanisms induced by Brucella.
Prevalence and correlates of non-fatal overdose among people who use drugs: findings from rapid assessments in Massachusetts, 2017–2019
Authors: Shrestha Shikhar , Stopka Thomas J. , Hughto Jaclyn M. W. , Case Patricia , Palacios Wilson R. , Reilly Brittni , Green Traci C.
Published: August 2021

Background

People who experience non-fatal overdose (NFOD) are at high risk of subsequent overdose. With unprecedented increases in fentanyl in the US drug supply, many Massachusetts (MA) communities have seen a surge in opioid-related overdoses. The objective of this study was to determine factors associated with lifetime and past year NFOD in at-risk MA communities.

Methods

We conducted multiple rapid assessments among people who use drugs (PWUD) in eight MA communities using non-probability sampling (purposive, chain referral, respondent-driven) methods. We collected sociodemographic, substance use, overdose history, substance use treatment, and harm reduction services utilization data. We examined the prevalence of NFOD (lifetime and past year) and identified factors associated with NFOD through multivariable logistic regression analyses in a subset of 469 study participants between 2017 and 2019.

Results

The prevalence of lifetime and last year non-fatal opioid overdose was 62.5% and 36.9%, respectively. Many of the study participants reported heroin (64%) and fentanyl (45%) use during the 30 days preceding the survey. Nonprescription buprenorphine and fentanyl use were independently associated with higher odds of lifetime NFOD, while marijuana use was associated with lower odds of lifetime NFOD (p < 0.05). Injection as the route of administration, benzodiazepine, nonprescription buprenorphine, heroin, and fentanyl use were independently associated with higher odds, while methadone use was associated with lower odds of past year NFOD (p < 0.05).

Conclusion

We documented a high prevalence of past year and lifetime NFOD among PWUD in MA. Our findings provide indicators that can help inform interventions to prevent overdoses among PWUD, including overdose prevention, medication treatment, and naloxone distribution.
Circ-RNF111 aggravates the malignancy of gastric cancer through miR-876-3p-dependent regulation of KLF12
Authors: Wu Guoxian , Zhang Aimin , Yang Yinglin , Wu Dongping
Published: August 2021

Background

The aberrant expression of circular RNAs (circRNAs) plays vital roles in the advancement of human cancers, including gastric cancer (GC). In this study, the functions of circRNA ring finger protein 111 (circ-RNF111) in GC were investigated.

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed for the levels of circ-RNF111, microRNA-876-3p (miR-876-3p) and krueppel-like factor 12 (KLF12) mRNA. RNase R assay was conducted for the feature of circ-RNF111. Cell Counting Kit-8 (CCK-8) assay, colony formation assay, wound-healing assay, and transwell assay were applied for cell viability, colony formation, migration, and invasion, respectively. Flow cytometry analysis was used to analyze cell apoptosis and cell cycle process. The glycolysis level was examined using specific commercial kits. Western blot assay was carried out to measure the protein levels of hexokinase 2 (HK-2) and KLF12. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to verify the combination between miR-876-3p and circ-RNF111 or KLF12. Murine xenograft model was constructed for the role of circ-RNF111 in vivo. Immunohistochemistry (IHC) was used for KLF12 level.

Results

Circ-RNF111 was higher expressed in GC tissues and cells than normal tissues and cells. Silencing of circ-RNF111 restrained cell viability, colony formation, migration, invasion, cell cycle process and glycolysis and induced apoptosis in GC cells in vitro. Circ-RNF111 positively regulated KLF12 expression via absorbing miR-876-3p. MiR-876-3p downregulation reversed the impacts of circ-RNF111 silencing on GC cell malignant phenotypes. MiR-876-3p overexpression repressed GC cell growth, metastasis and glycolysis, inhibited apoptosis and arrested cell cycle, while KLF12 elevation weakened the effects. Besides, circ-RNF111 knockdown inhibited tumor growth in vivo.

Conclusion

Circ-RNF111 knockdown relieved the development of GC by regulating miR-876-3p/KLF12 axis.
Monomorphic epitheliotropic intestinal T-cell lymphomas: a case report
Authors: Zhong Haibin , Zheng Yang , Zhang Feiran
Published: August 2021

Background

Monomorphic epitheliotropic intestinal T-cell lymphomas (MEITL) is a rare and aggressive subtype of lymphoma. The most common site of origin is small intestine. Patients are often presented with diagnosis of intestinal perforation with abdominal pain as the main consulting symptoms. Because of the deficiency of specific diagnostic measures and effective management, diagnosis is often confirmed in advanced stage with poor prognosis.

Case presentation

Here, we introduce a patient who has suffered from abdominal pain and diarrhea, and eventually been diagnosed as Monomorphic epitheliotropic intestinal T-cell lymphomas.

Conclusion

MEITL is rare in clinical practice with deficiency of early diagnostic measures and poor prognosis. Therefore, any patient with ambiguous gastrointestinal symptoms or perforation of the digestive tract where the primary lesion is difficult to identify should be alert to the possibility of this disease.
Provider REport of Sustainment Scale (PRESS): development and validation of a brief measure of inner context sustainment
Authors: Moullin Joanna C. , Sklar Marisa , Ehrhart Mark G. , Green Amy , Aarons Gregory A.
Published: August 2021

Background

Implementation scientists and practitioners often rely on frontline providers for reporting on implementation outcomes. Furthermore, measures of sustainment are few, and available sustainment measures are mainly setting or evidenced-based practice (EBP) specific, require organizational and system-level knowledge to complete, and often lack psychometric rigor. The aim of this study was to develop a brief, pragmatic, and generalizable measure for completion by frontline service providers of the implementation outcome, sustainment.

Methods

We utilized a Rasch measurement theory approach to scale the development and testing of psychometric parameters. Sustainment items were developed to be relevant for direct service providers to complete. In order to promote generalizability, data were collected and items were tested across four diverse psychosocial evidence-based practices (motivational interviewing [MI], SafeCare®, classroom pivotal response training [CPRT], and an individualized mental health intervention for children with autism spectrum disorder [AIM-HI]) and in four service settings (substance use disorder treatment, child welfare, education, and specialty mental health). Associations between the sustainment measure and sustainment leadership, sustainment climate, and attitudes towards the adoption and use of each of the EBPs were assessed to confirm construct validity.

Results

Three items for the Provider REport of Sustainment Scale (PRESS) were assessed for measuring the core component of sustainment: continued use of the EBP. Internal consistency reliability was high. The scale indicated fit to the Rasch measurement model with no response dependency, ordered thresholds, no differential item functioning, and supported unidimensionality. Additionally, construct validity evidence was provided based on the correlations with related variables.

Conclusion

The PRESS measure is a brief, three-item measure of sustainment that is both pragmatic and useable across different EBPs, provider types, and settings. The PRESS captures frontline staffs’ report of their clinic, team, or agency’s continued use of an EBP. Future testing of the PRESS for concurrent and predictive validity is recommended.
Influence of target dose heterogeneity on dose sparing of normal tissue in peripheral lung tumor stereotactic body radiation therapy
Authors: Wei Zhigong , Peng Xingchen , Wang Yan , Yang Lianlian , He Ling , Liu Zheran , Wang Jingjing , Mu Xiaoli , Li Ruidan , Xiao Jianghong
Published: August 2021

Objective

To evaluate the influence of target dose heterogeneity on normal tissue dose sparing for peripheral lung tumor stereotactic body radiation therapy (SBRT).

Methods

Based on the volumetric-modulated arc therapy (VMAT) technique, three SBRT plans with homogeneous, moderate heterogeneous, and heterogeneous (HO, MHE, and HE) target doses were compared in 30 peripheral lung tumor patients. The prescription dose was 48 Gy in 4 fractions. Ten rings outside the PTV were created to limit normal tissue dosage and evaluate dose falloff.

Results

When MHE and HE plans were compared to HO plans, the conformity index of the PTV was increased by approximately 0.08. The median mean lung dose (MLD), V5, V10, V20 of whole lung, D2%, D1cc, D2cc of the rib, V30 of the rib, D2% and the maximum dose (Dmax) of the skin, and D2% and Dmax of most mediastinal organs at risk (OARs) and spinal cord were reduced by up to 4.51 Gy or 2.8%. Analogously, the median Dmax, D2% and mean dose of rings were reduced by 0.71 to 8.46 Gy; and the median R50% and D2cm were reduced by 2.1 to 2.3 and 7.4% to 8.0%, respectively. Between MHE and HE plans there was little to no difference in OARs dose and dose falloff beyond the target. Furthermore, the dose sparing of rib V30 and the mean dose of rings were negatively correlated with the rib and rings distance from tumor, respectively.

Conclusions

For peripheral lung tumor SBRT, target conformity, normal tissue dose, and dose falloff around the target could be improved by loosening or abandoning homogeneity. While there was negligible further dose benefit for the maximum target dose above 125% of the prescription, dose sparing of normal tissue derived from a heterogeneous target decreased as the distance from the tumor increased.
Evaluation of inter- and intra-fraction 6D motion for stereotactic body radiation therapy of spinal metastases: influence of treatment time
Authors: Hadj Henni Ahmed , Gensanne David , Roge Maximilien , Hanzen Chantal , Bulot Guillaume , Colard Elyse , Thureau Sebastien
Published: August 2021

Background

The objective of this study was to analyze the amplitude of translational and rotational movements occurring during stereotactic body radiotherapy (SBRT) of spinal metastases in two different positioning devices. The relevance of intra-fractional imaging and the influence of treatment time were evaluated.

Methods

Twenty patients were treated in the supine position either (1) on a body vacuum cushion with arms raised and resting on a clegecel or (2) on an integrated SBRT solution consisting of a SBRT table top, an Orfit™ AIO system, and a vacuum cushion. Alignments between the cone beam computed tomography (CBCT) and the planning computed tomography allowed corrections of inter- and intra-fraction positional shifts using a 6D table. The absolute values of the translational and rotational setup errors obtained for 329 CBCT were recorded. The translational 3D vector, the maximum angle, and the characteristic times of the treatment fractions were calculated.

Results

An improvement in the mean (SD) inter-fraction 3D vector (mm) from 7.8 (5.9) to 5.9 (3.8) was obtained by changing the fixation devices from (1) to (2) (p < 0.038). The maximum angles were less than 2° for a total of 87% for (1) and 96% for (2). The mean (SD) of the intra-fraction 3D vectors (mm) was lower for the new 1.1 (0.8) positioning fixation (2) compared to the old one (1) 1.7 (1.7) (p = 0.004). The angular corrections applied in the intra-fraction were on average very low (0.4°) and similar between the two systems. A strong correlation was found between the 3D displacement vector and the fraction time for (1) and (2) with regression coefficients of 0.408 (0.262–0.555, 95% CI) and 0.069 (0.010–0.128, 95% CI), respectively. An accuracy of 1 mm would require intra-fraction imaging every 5 min for both systems. If the expected accuracy was 2 mm, then only system (2) could avoid intra-fractional imaging.

Conclusions

This study allowed us to evaluate setup errors of two immobilization devices for spine SBRT. The association of inter- and intra-fraction imaging with 6D repositioning of a patient is inevitable. The correlation between treatment time and corrections to be applied encourages us to move toward imaging modalities which allow a reduction in fraction time.
Lung transplant after long-term veno-venous extracorporeal membrane oxygenation: a case report
Authors: Yoshiyasu Nobuyuki , Sato Masaaki , Anraku Masaki , Ichiba Shingo , Nakajima Jun
Published: August 2021

Background

Although the number of patients who undergo extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation is increasing worldwide, there are few reports on lung transplantation after long-term ECMO (more than 1 month). We report a rare case of successful bilateral lung transplantation in a Japanese patient after 5 months of veno-venous (VV)-ECMO support.

Case presentation

A 27-year-old man who underwent bone marrow transplantation (BMTx) with fully matched human leukocyte antigen typing was diagnosed with bronchiolitis obliterans caused by chronic graft-versus-host disease 3 years after the BMTx. One year later, his respiratory condition had exacerbated, with carbon dioxide retention that required conventional mechanical ventilation. He was then deemed a suitable candidate for lung transplantation by a multidisciplinary transplantation selection committee. While waiting for donor lungs, his hypercapnia and acidosis became barely manageable under care with mechanical ventilation and ultimately he was switched to VV-ECMO. He remained on VV-ECMO for the next 5 months, during which period the circuit was switched nine times. In addition, sophisticated intensive care was required to manage multiple episodes of sepsis and coagulopathy. A suitable donor was identified 5 months later, and bilateral lung transplantation was initiated with continuous VV-ECMO. The procedure itself was extremely challenging owing to severe adhesions resulting from previous thoracotomy, inflammation, infection, and intrapulmonary hemorrhage. The operative time for the transplantation was about 19 h. Currently, at 2 years 8 months postoperatively, the patient is alive and well.

Conclusion

Transplant surgery in this patient was extremely challenging because of the presence of severe pleural adhesions and stiff native lungs secondary to hemorrhagic complications due to the prolonged ECMO support. Surgeons must recognize that lung transplantation after long-term ECMO bridging can be technically more complicated and challenging than shorter-term ECMO.