bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nurse staffing levels within acute care: results of a national day of care survey
Authors: Hegarty Hannah , Knight Thomas , Atkin Catherine , Kelly Tash , Subbe Chris , Lasserson Daniel , Holland Mark 
Published: April 2022

Abstract
Introduction
The relationship between nurse staffing levels and patient safety is well recognised. Inadequate provision of nursing staff is associated with increased medical error, as well as higher morbidity and mortality. Defining what constitutes safe nurse staffing levels is complex. A range of guidance and planning tools are available to inform staffing decisions. The Society for Acute Medicine (SAM) recommend a ‘nurse-to-bed‘ratio of greater than 1:6. Whether this standard accurately reflects the pattern and intensity of work on the Acute Medical Unit (AMU) is unclear.

Methods
Nurse staffing levels in AMUs were explored using the Society for Acute Medicine Benchmarking Audit 2019 (SAMBA19). Data from 122 acute hospitals were analysed. Nurse-to-bed ratios were calculated and compared. Estimates of the total nursing time available within the acute care system were compared to estimates of the time required to perform nursing activities.

Results
The total number of AMU beds across all 122 units was 4997. The mean daytime nurse-to-bed ratio was 1:4.3 and the mean night time nurse-to-bed ratio was 1:5.2. The SAM standard of a nurse to bed ratio of greater than 1:6 was achieved in 99 units (81.9%) during daytime hours and achieved by 74 units (60.6%) at night.
The estimated time required to deliver direct clinical care was 35,698 h. A deficit of 4128 h (11.5% of time required) was estimated, representing the time difference between the total number of nursing hours available with current staffing and the estimated time needed for direct clinical care across all participating units.

Conclusion
This UK-wide study suggests a significant proportion of AMUs do not meet the recommenced SAM staffing levels, particularly at night. A difference was observed between the total number of nursing hours within the acute care system and the estimated time required to perform direct nursing activities. This suggests a workforce shortage of nurses within acute care at the system level.
Pyruvate kinase, a metabolic sensor powering glycolysis, drives the metabolic control of DNA replication
Authors: Horemans Steff , Pitoulias Matthaios , Holland Alexandria , Pateau Emilie , Lechaplais Christophe , Ekaterina Dariy , Perret Alain , Soultanas Panos , Janniere Laurent 
Published: April 2022

Abstract
Background
In all living organisms, DNA replication is exquisitely regulated in a wide range of growth conditions to achieve timely and accurate genome duplication prior to cell division. Failures in this regulation cause DNA damage with potentially disastrous consequences for cell viability and human health, including cancer. To cope with these threats, cells tightly control replication initiation using well-known mechanisms. They also couple DNA synthesis to nutrient richness and growth rate through a poorly understood process thought to involve central carbon metabolism. One such process may involve the cross-species conserved pyruvate kinase (PykA) which catalyzes the last reaction of glycolysis. Here we have investigated the role of PykA in regulating DNA replication in the model system Bacillus subtilis.

Results
On analysing mutants of the catalytic (Cat) and C-terminal (PEPut) domains of B. subtilis PykA we found replication phenotypes in conditions where PykA is dispensable for growth. These phenotypes are independent from the effect of mutations on PykA catalytic activity and are not associated with significant changes in the metabolome. PEPut operates as a nutrient-dependent inhibitor of initiation while Cat acts as a stimulator of replication fork speed. Disruption of either PEPut or Cat replication function dramatically impacted the cell cycle and replication timing even in cells fully proficient in known replication control functions. In vitro, PykA modulates activities of enzymes essential for replication initiation and elongation via functional interactions. Additional experiments showed that PEPut regulates PykA activity and that Cat and PEPut determinants important for PykA catalytic activity regulation are also important for PykA-driven replication functions.

Conclusions
We infer from our findings that PykA typifies a new family of cross-species replication control regulators that drive the metabolic control of replication through a mechanism involving regulatory determinants of PykA catalytic activity. As disruption of PykA replication functions causes dramatic replication defects, we suggest that dysfunctions in this new family of universal replication regulators may pave the path to genetic instability and carcinogenesis.
Difference in cardiac remodeling between female athletes and pregnant women: a case control study
Authors: Toncelli Loira , Pasquini Lucia , Masini Giulia , Orlandi Melissa , Paci Gabriele , Mecacci Federico , Pedrizzetti Gianni , Galanti Giorgio 
Published: April 2022

Abstract
Objectives
The aim of this study was to detect possible differences in reversible cardiac remodeling occurring in sport training and twin pregnancy. Background: cardiac remodeling occurs in athletes and pregnant women due to training and fetal requirements, respectively. These changes could be apparently similar.

Methods
21 female elite athletes (23.2 ± 5.3 years), 25 women with twin pregnancies (35.4 ± 5.7 years) and 25 healthy competitive female athletes (controls), age-matched with pregnant women (34.9 ± 7.9 years), were enrolled. This latter group was included to minimize the effect of age on cardiac remodeling. All women evaluated through anamnestic collection, physical examination, 12 leads ECG, standard echocardiogram and strain analysis. Sphericity (SI) and apical conicity (ACI) indexes were also calculated.

Results
Pregnant women showed higher LA dimension (p < 0.001) compared to both groups of athletes. LV e RV GLS were significantly different in pregnant women compared to female athletes (p = 0.02 and 0.03, respectively). RV GLS was also different between pregnant women and controls (p = 0.02). Pregnant women showed significantly higher S′ wave compared to female athletes (p = 0.02) but not controls. Parameters of diastolic function were significantly higher in athletes (p = 0.08 for IVRT and p < 0.001 for E/A,). SI was lower in athletes in both diastole (p = 0.01) and systole (p < 0.001), while ACIs was lower in pregnant women (p = 0.04).

Conclusions
Cardiac remodeling of athletes and pregnant women could be similar at first sight but different in LV shape and in GLS, highlighting a profound difference in longitudinal deformation between athletes and pregnant women. This difference seems not to be related with age. These findings suggest that an initial maternal cardiovascular maladaptation could occur in the third trimester of twin pregnancies.
Microparticles: biogenesis, characteristics and intervention therapy for cancers in preclinical and clinical research
Authors: Hu Yan , Sun Yajie , Wan Chao , Dai Xiaomeng , Wu Shuhui , Lo Pui-Chi , Huang Jing , Lovell Jonathan F. , Jin Honglin , Yang Kunyu 
Published: April 2022

AbstractExtracellular vesicles (EVs), spherical biological vesicles, mainly contain nucleic acids, proteins, lipids and metabolites for biological information transfer between cells. Microparticles (MPs), a subtype of EVs, directly emerge from plasma membranes, and have gained interest in recent years. Specific cell stimulation conditions, such as ultraviolet and X-rays irradiation, can induce the release of MPs, which are endowed with unique antitumor functionalities, either for therapeutic vaccines or as direct antitumor agents. Moreover, the size of MPs (100–1000 nm) and their spherical structures surrounded by a lipid bilayer membrane allow MPs to function as delivery vectors for bioactive antitumor compounds, with favorable phamacokinetic behavior, immunostimulatory activity and biological function, without inherent carrier-specific toxic side effects. In this review, the mechanisms underlying MP biogenesis, factors that influence MP production, properties of MP membranes, size, composition and isolation methods of MPs are discussed. Additionally, the applications and mechanisms of action of MPs, as well as the main hurdles for their applications in cancer management, are introduced.Graphical Abstract
Lymph node-targeted neoantigen nanovaccines potentiate anti-tumor immune responses of post-surgical melanoma
Authors: Chu Yanhong , Qian Lingyu , Ke Yaohua , Feng Xiaoyu , Chen Xinjie , Liu Fangcen , Yu Lixia , Zhang Lianru , Tao Yaping , Xu Rui , Wei Jia , Liu Baorui , Liu Qin 
Published: April 2022

Abstract
Background
Neoantigens are considered ideal targets for immunotherapy, especially tumor vaccine, because of their strong specificity and immunogenicity. Here, we developed a neoantigen nanovaccine used liposomes with lymph-node targeting characteristic.

Methods
Our nanovaccine was composed of neoantigens, an amphiphilic liposome and an adjuvant Montanide™ ISA 51. Small animal imaging system and immunofluorescence staining were used to identify the distribution of nanovaccines. A subcutaneous-tumor-resection mouse model of melanoma was established to evaluate the anti-tumor efficacy. Flow cytometry was performed to assay the immune responses initiated by nanovaccines.

Results
Nanovaccines could traffic to lymph nodes, be uptaken by CD11c+ DCs and promote DCs maturity. After the treatment of our neoantigen nanovaccines, the average recurrence time was extended from 11 to 16 days and the median survival time was even prolonged 7.5 days relative to the control group (NS group). Nanovaccines increased neoantigen-specific T cells to 10-fold of free vaccines, and upregulated Th1 cytokines, such as IFN-γ and TNF-α. The anti-tumor activity of spleen lymphocytes in the nanovaccine group was significantly stronger than that of other groups. However, some immune-inhibitory cells or molecules in tumor microenvironment have been detected upregulated under the immune pressure of neoantigen nanovaccines, such as Tregs and PD-L1. The efficacy of the neoantigen nanovaccine combined with anti-PD1 antibody or Treg inhibiting peptide P60 was better than that of the single treatment.

Conclusions
We developed a general vaccine strategy, triggering specific T cell responses, and provided feasible combination strategies for better anti-tumor efficacy.

Graphical abstract
Diversity and ethnomycological importance of mushrooms from Western Himalayas, Kashmir
Authors: Ullah Tariq Saiff , Firdous Syeda Sadiqa , Shier Wayne Thomas , Hussain Javeed , Shaheen Hamayun , Usman Muhammad , Akram Maryam , Khalid Abdul Nasir 
Published: April 2022

Abstract
Background
Wild edible mushrooms (WEM) are economically significant and used in traditional medicines worldwide. The region of Jammu and Kashmir (Western Himalayas) is enriched with the diversity of edible mushrooms, collected by the rural people for food and income generation. This is the first detailed study on diversity and ethno-medicinal uses of mushrooms from the State of Jammu and Kashmir.

Methods
Consecutive surveys were conducted to record ethnomycological diversity and socio-economic importance of wild edible mushrooms value chain in rural areas of Azad Jammu and Kashmir during 2015–2019. Ethnomycological data were collected with a semi-structured questionnaire having a set of questions on indigenous mycological knowledge and collection and retailing of wild edible mushrooms. A total of 923 informants from the study area provided the results identifying the gender, type of mushroom species, medicinal uses, and marketing of mushrooms. Diversity of mushrooms was studied by using quadrat and transect methods. Principal component analysis (PCA) and detrended correspondence analysis (DCA) were also applied to the dataset to analyse the relationship between species distribution, the underlying environmental factors, and habitat types. PCA identified the major species-specific to the sites and put them close to the sites of distribution.

Results
A total of 131 mushroom species were collected and identified during 2015–2019 from the study area. Ninety-seven species of mushrooms were reported new to the State of Azad Jammu and Kashmir. The dominant mushroom family was Russulaceae with 23 species followed by Agaricaceae, 16 species. Major mushroom species identified and grouped by the PCA were Coprinus comatus, Lactarius sanguifluus, Amanita fulva, Armillaria gallica, Lycoperdon perlatum, Lycoperdon pyriforme, and Russula creminicolor. Sparassis crispa, Pleurotus sp, and Laetiporus sulphureus were recorded most edible and medicinally significant fungi. Morels were also expensive and medicinally important among all harvested macro-fungal species. These were reported to use against common ailments and various health problems.

Conclusions
Collection and retailing of WEM contribute to improving the socio-economic status, providing alternative employment and food security to rural people of the area. These mushrooms are used as a source of food and traditional medicines among the rural informants and could be used as a potential source of antibacterial and anticancer drugs in the future.
The preemptive effects of oral pregabalin on perioperative pain management in lower limb orthopedic surgery: a systematic review and meta-analysis
Authors: Chen Zhao , Chen Jialei , Luo Rong , Jiang Jiabao , Xiang Zhou 
Published: April 2022

Abstract
Background
To systematically review the literature and provide a comprehensive understanding of the preemptive effects of oral pregabalin on perioperative pain management in lower limb orthopedic surgery.

Method
We searched three electronic databases for randomized controlled trials comparing the results of preoperative pregabalin and placebo in patients undergoing lower limb orthopedic surgery. Data analyses were conducted using RevMan 5.4.

Results
Twenty-one randomized controlled trials met our inclusion criteria. The cumulative opioid consumption within 24 and 48 h postoperatively in the pregabalin group was significantly less than that in the placebo group. The pooled static pain intensity at all time points within the first day was significantly lower in the pregabalin group than in the placebo group. Lower dynamic pain intensity at 48 h was detected in the pregabalin group than in the placebo group. Meanwhile, pregabalin led to a lower incidence of nausea but appeared to be associated with a higher incidence of dizziness and sedation. Subgroup analyses showed that no difference was detected between subgroups stratified by dosing regimen or pregabalin dose in the results of opioid consumption, pain intensity and incidence of complications.

Conclusion
This meta-analysis supports the use of pregabalin preoperatively in patients undergoing lower limb orthopedic surgery. However, it was wary of the resulting increase in dizziness and sedation. There is no evidence to support the continued use of pregabalin postoperatively or using more than 150 mg of pregabalin per day.
Trial registration: This study was registered on 09 November 2021 with INPLASY (registration number: INPLASY2021110031).
Gut bacteriobiota and mycobiota are both associated with Day-28 mortality among critically ill patients
Authors: Prevel Renaud , Enaud Raphaël , Orieux Arthur , Camino Adrian , Berger Patrick , Boyer Alexandre , Delhaes Laurence , Gruson Didier 
Published: April 2022

Abstract
Introduction
Gut microbiota is associated with host characteristics such as age, sex, immune condition or frailty and is thought to be a key player in numerous human diseases. Nevertheless, its association with outcome in critically ill patients has been poorly investigated. The aim of this study is to assess the association between gut microbiota composition and Day-28 mortality in critically ill patients.

Methods
Rectal swab at admission of every patient admitted to intensive care unit (ICU) between October and November 2019 was frozen at − 80 °C. DNA extraction was performed thanks to QIAamp® PowerFecal® Pro DNA kit (QIAgen®). V3–V4 regions of 16SRNA and ITS2 coding genes were amplified by PCR. Sequencing (2x250 bp paired-end) was performed on MiSeq sequencer (Illumina®). DADA2 pipeline on R software was used for bioinformatics analyses. Risk factors for Day-28 mortality were investigated by logistic regression.

Results
Fifty-seven patients were consecutively admitted to ICU of whom 13/57 (23%) deceased and 44/57 (77%) survived. Bacteriobiota α-diversity was lower among non-survivors than survivors (Shannon and Simpson index respectively, p < 0.001 and p = 0.001) as was mycobiota α-diversity (respectively p = 0.03 and p = 0.03). Both gut bacteriobiota and mycobiota Shannon index were independently associated with Day-28 mortality in multivariate analysis (respectively OR: 0.19, 97.5 CI [0.04–0.60], p < 0.01 and OR: 0.29, 97.5 CI [0.09–0.75], p = 0.02). Bacteriobiota β-diversity was significantly different between survivors and non-survivors (p = 0.05) but not mycobiota β-diversity (p = 0.57). Non-survivors had a higher abundance of Staphylococcus haemolyticus, Clostridiales sp., Campylobacter ureolyticus, Akkermansia sp., Malassezia sympodialis, Malassezia dermatis and Saccharomyces cerevisiae, whereas survivors had a higher abundance of Collinsella aerofaciens, Blautia sp., Streptococcus sp., Faecalibacterium prausnitzii and Bifidobacterium sp.

Conclusion
The gut bacteriobiota and mycobiota α diversities are independently associated with Day-28 mortality in critically ill patients. The causal nature of this interference and, if so, the underlying mechanisms should be further investigated to assess if gut microbiota modulation could be a future therapeutic approach.
Confirmed severe acute respiratory syndrome coronavirus 2 encephalitis in cerebrospinal fluid: a case report
Authors: Ayuningtyas Triana , Natadidjaja Ronald Irwanto , Octaviani Chyntia , Sahli Felly , Adlani Hadianti 
Published: April 2022

Abstract
Background
Patients with severe acute respiratory syndrome coronavirus 2 infection show various clinical manifestations, including neurological . Altered consciousness due to severe acute respiratory syndrome coronavirus 2 encephalitis is a very threatening condition if not treated immediately.

Case presentation
We present the case of a 34-year-old Asian female who tested positive for severe acute respiratory syndrome coronavirus 2 infection using a nasopharyngeal swab sample and presented with acute changes in consciousness without typical respiratory symptoms. Empiric therapy was immediately and simultaneously given with cerebrospinal fluid analysis using polymerase chain reaction, which later also showed positive results for severe acute respiratory syndrome coronavirus 2 infection.

Conclusions
It is important to consider the diagnosis of severe acute respiratory syndrome coronavirus 2 encephalitis when a patient presents with acute altered consciousness and no typical respiratory symptoms. Early empiric therapy can improve patient outcomes.
Impact of health system engagement on the health and well-being of people who use drugs: a realist review protocol
Authors: Salvalaggio Ginetta , Ferguson Lawrence , Brooks Hannah L. , Campbell Sandra , Gladue Vanessa , Hyshka Elaine , Lam Linda , Morris Heather , Nixon Lara , Springett Jane 
Published: April 2022

Abstract
Background
Although community-level benefits of health system engagement (i.e., health service planning, delivery, and quality improvement, engaged research and evaluation, and collaborative advocacy) are well established, individual-level impacts on the health and well-being of community members are less explored, in particular for people who use or have used illegal drugs (PWUD). Capacity building, personal growth, reduced/safer drug use, and other positive outcomes may or may not be experienced by PWUD involved in engagement activities. Indeed, PWUD may also encounter stigma and harm when interacting with healthcare and academic structures. Our objective is to uncover why, how, and under what circumstances positive and negative health outcomes occur during health system engagement by PWUD.

Methods
We propose a realist review approach due to its explanatory lens. Through preliminary exploration of literature, lived experience input, and consideration of formal theories, an explanatory model was drafted. The model describes contexts, mechanisms, and health outcomes (e.g., mental health, stable/safer drug use) involved in health system engagement. The explanatory model will be tested against the literature and iteratively refined against formal theories. A participatory lens will also be used, wherein PWUD with lived experience of health system engagement will contribute throughout all stages of the review.

Discussion
We believe this is the first realist review to explore the contextual factors and underlying mechanisms of health outcomes for PWUD who participate in health system engagement. A thorough understanding of the relevant literature and theoretical underpinnings of this process will offer insights and recommendations to improve the engagement processes of PWUD.
Incidence and outcomes of critical illness in Indigenous Peoples: a systematic review protocol
Authors: Bowker Samantha L. , Williams Kienan , Wingert Aireen , Boyd Jamie M. , Potestio Melissa L. , Gates Michelle , Wright Erica , Bagshaw Sean M. 
Published: April 2022

Abstract
Background
Indigenous Peoples experience health inequities across the continuum of health services. Improvements for Indigenous patients and their families during vulnerable experiences with the healthcare system may have a significant impact on the patient experience and outcomes. Improved understanding of the occurrence of critical illness in Indigenous Peoples and their use of critical care services, as a strategic priority, may aid in the development of initiatives for improving health equity. A global focus was selected to learn from Indigenous populations’ experiences with critical care, as the understanding of critical illness among Indigenous Peoples in Canada is not well understood. This protocol outlines a systematic review focused on describing the incidence of critical illness and utilization of critical care services among Indigenous Peoples.

Methods
Ovid MEDLINE/PubMed, Ovid EMBASE, Google Scholar, and Cochrane Central Register of Controlled Trials will be searched. Relevant Canadian sites for gray literature (National Collaborating Centre for Indigenous Health, First Nations Health Authority, Canadian Institutes of Health Research Institute of Indigenous Peoples’ Health, National Association of Friendship Centres, the Alberta First Nations Information Governance Centre, Métis Nation of Alberta) will also be searched. We will include studies of adults (≥18 years) either without critical illness (i.e., general population) or with critical illness (i.e., admitted to an intensive care unit (ICU)). The exposure of interest will be Indigenous identity. Primary outcome measures are ICU admission and ICU mortality. Because heterogeneity in populations, comparisons, and outcome measures is anticipated, it is likely that the findings will be summarized using a narrative synthesis. A meta-analysis will be performed if there is sufficient evidence on one or more outcomes of interest.

Discussion
This systematic review will provide a better understanding of the epidemiology, risk factors, and outcomes of critical illness and utilization of critical care services among Indigenous Peoples. The knowledge generated will be applied to a broader program of work designed to create ethical space to co-design, implement, and evaluate a culturally competent, safe, and innovative model for critical care services for Indigenous People.

Systematic review registration
PROSPERO CRD42021254661