bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomes reveal metabolic capabilities of
Yarrowia lipolytica
for biological upcycling of polyethylene into high-value chemicals
Authors: Walker Caleb , Mortensen Max , Poudel Bindica , Cotter Christopher , Myers Ryan , Okekeogbu Ikenna O. , Ryu Seunghyun , Khomami Bamin , Giannone Richard J. , Laursen Siris , Trinh Cong T.
Published: October 2023

Polyolefins derived from plastic wastes are recalcitrant for biological upcycling. However, chemical depolymerization of polyolefins can generate depolymerized plastic (DP) oil, comprising of a complex mixture of saturated, unsaturated, even, and odd hydrocarbons suitable for biological conversion. While DP oil contains a rich carbon and energy source, it is inhibitory to cells. Understanding and harnessing robust metabolic capabilities of microorganisms to upcycle the hydrocarbons in DP oil, both naturally and unnaturally occurring, into high-value chemicals are limited. Here, we discovered that an oleaginous yeast,
Yarrowia lipolytica,
undergoing short-term adaptation to DP oil robustly utilized a wide range of hydrocarbons for cell growth and production of citric acid and neutral lipids. When growing on hydrocarbons,
Y. lipolytica
partitioned into planktonic and oil-bound cells with each exhibiting distinct proteomes and amino acid distributions invested in establishing these proteomes. Significant proteome reallocation toward energy and lipid metabolism, belonging to 2 of the 23 Eukaryotic Orthologous Groups classes C and I, enabled robust growth of
Y. lipolytica
on hydrocarbons, with n-hexadecane as the preferential substrate. This investment was even higher for growth on DP oil where classes C and I were ranked one and two, respectively, and many associated proteins and pathways were expressed and upregulated including the hydrocarbon degradation pathway, Krebs cycle, glyoxylate shunt and, unexpectedly, propionate metabolism. However, a reduction in proteome allocation for protein biosynthesis, at the expense of the observed increase toward energy and lipid metabolisms, might have caused the inhibitory effect of DP oil on cell growth.

IMPORTANCE

Sustainable processes for biological upcycling of plastic wastes in a circular bioeconomy are needed to promote decarbonization and reduce environmental pollution due to increased plastic consumption, incineration, and landfill storage. Strain characterization and proteomic analysis revealed the robust metabolic capabilities of
Yarrowia lipolytica
to upcycle polyethylene into high-value chemicals. Significant proteome reallocation toward energy and lipid metabolisms was required for robust growth on hydrocarbons with n-hexadecane as the preferential substrate. However, an apparent over-investment in these same categories to utilize complex depolymerized plastic (DP) oil came at the expense of protein biosynthesis, limiting cell growth. Taken together, this study elucidates how
Y. lipolytica
activates its metabolism to utilize DP oil and establishes
Y. lipolytica
as a promising host for the upcycling of plastic wastes.
A single dietary factor, daily consumption of a fermented beverage, can modulate the gut bacteria and fecal metabolites within the same ethnic community
Authors: Das Santanu , Özkurt Ezgi , Joishy Tulsi Kumari , Mukherjee Ashis K. , Hildebrand Falk , Khan Mojibur R.
Published: October 2023

In this study, the impact of traditional rice-based fermented alcoholic beverages (two types of Apong drink: Poro and Nogin) on the gut microbiome and health of the Mishing community in India was examined. Two groups (
n
= 71 in each group, 58 females and 84 males) that consumed one of these beverages were compared to a control group (
n
= 24, all males) that did not consume either beverage. Gut microbial composition was analyzed by sequencing 16S rRNA of fecal metagenomes and analyzing untargeted fecal metabolites, and short-chain fatty acids (SCFAs). We also collected data on anthropometric measures and serum biochemical markers. Our results showed that Apong drinkers had higher blood pressure, but lower blood glucose and total protein levels than other non-drinkers. Also, gut microbiome composition was found to be affected by the choice of Apong
,
with Apong drinkers having a more diverse and distinct microbiome compared to non-drinkers. Apong drink type or being a drinker or not explained even a higher variation of fecal metabolome composition than microbiome composition and Apong drinkers had lower levels of the SCFA isovaleric acid than non-drinkers. Overall, this study shows that a single dietary factor can significantly impact the gut microbiome of a community and highlights the potential role of traditional fermented beverages in modulating gut bacteria.

IMPORTANCE

Our study investigated how a traditional drink called Apong, made from fermented rice, affects the gut and health of the Mishing community in India. We compared two groups of people who drink Apong to a group of people who do not drink it. To accomplish this, we studied the gut bacteria, fecal metabolites, and blood samples of the participants. It was found that the people who drank Apong had higher blood pressure but lower blood sugar and protein levels than people who did not drink it. We also found that the gut microbiome composition of people who drank Apong was different from those who did not drink it. Moreover, people who drank Apong had lower levels of isovaleric acid in their feces. Overall, this study shows that a traditional drink like Apong can affect the gut bacteria of a community.
Identification of key residues of B cell epitopes in hemagglutinin of H6 influenza A virus
Authors: Wan Zhimin , Gong Jianxi , Sang Jianjun , Jiang Wenjie , Zhao Zhehong , Tang Ting , Li Yafeng , Zhao Yichao , Kan Qiuqi , Xie Quan , Li Tuofan , Shao Hongxia , Gao Wei , Qin Aijian , Ye Jianqiang
Published: October 2023

H6 influenza A viruses are enzootic and genetically diverse in both domestic poultry and wild birds, occasionally causing spillovers to mammals, including humans, posing threat to public health. However, the antigenic sites of the hemagglutinin (HA) of H6 are poorly understood. In this study, a panel of murine monoclonal antibodies (MAbs) with different reactivity spectra against HA of H6 was generated and nine key residues of antigenic epitopes in H6 were identified through escape mutants of these MAbs. Of these, residues 139 and 140 belonged to antigenic Sa, residue 89 belonged to antigenic Cb, residue 149 belonged to Ca2, while residue 221 belonged to Ca1 regarding the H1 antigenic sites. However, the other four residues 69, 120, 124, and 246 were not located in the identified antigenic regions of H1. Although most HA variants of the escape mutants had the preference for avian-like receptor, whereas escape mutants m3B9 and m4C2 increased the binding affinity for both avian and human-like receptors, and m1A5 and m6D11 decreased the binding affinity for avian-like receptors. Moreover, a single dose of MAbs 4C2 or 6E3 could fully protect mice against lethal challenge of mouse-adapted A/Eurasian teal/Jiangxi/2018WB0417(H6N2) (MA E-Teal/417) in the prophylactic treatment and also could provide partial protection in the therapeutic treatment. Overall, the generated MAbs and the identified key residues of antigenic epitopes not only provide novel insights into the key markers for monitoring the antigenic variation of H6 but also demonstrate the potential for developing MAb-based passitive treatments for H6.

IMPORTANCE

Since the escape immunity of influenza A viruses (IAVs) is mainly caused by the continuous antigenic variations in HA, the identification of key antigenic epitopes is crucial for better understanding of the escape immunity and vaccine development for IAVs. The antigenic sites of several HA subtypes, including H1, H3, H5, and H9, have been well characterized, whereas those of H6 subtype are poorly understood. Here, we mapped nine key residues of antigenic epitopes in H6 through escape mutants using a panel of MAbs. Moreover, MAbs 4C2 and 6E3, targeting 140 and 89 residues, respectively, could protect mice against lethal challenge of MA E-Teal/417. These key residues of antigenic epitopes identified here provide the molecular targets for further elucidating the antigenic evolution of H6 and better preparing the vaccine against H6 IAV.
Chlamydia suisdisplays high transformation capacity with complete cloning vector integration into the chromosomalrrn-nqrFplasticity zone
Authors: Marti Hanna , Biggel Michael , Shima Kensuke , Onorini Delia , Rupp Jan , Charette Steve J. , Borel Nicole
Published: October 2023

Chlamydia, comprising several human and zoonotic pathogens, is a genus of the conserved bacterial phylum Chlamydiota. Their obligate intracellular niche serves as a barrier for natural genetic exchange via horizontal gene transfer (HGT), and further limits the development and application of genetic tools. To date, the only example for recent inter-phylum HGT among the Chlamydiota is tetracycline resistance in the potentially zoonotic speciesChlamydia suis, a close phylogenetic relative of humanC. trachomatis, which causes bacterial sexually transmitted infections and ocular trachoma. Tetracycline resistance in porcineC. suisstrains has been described worldwide and is always part of a genomic island dividinginvasin(inv), located within a chromosomal region between the rRNA operon (rrn) and thenqrFreductase. Here, we aimed to expand the still modest number of available genetic manipulation systems forChlamydiaby generating allele-replacement and integration vectors forC. suis. These vectors comprised homologousC. suissequences of the chromosomal region of interest, anE. coliorigin of replication (ori) and selection markers but lacked the native chlamydial plasmids or itsori. We first recovered allele-replacement mutants using a vector that targets the tryptophan (trp) operon ofC. suis. The vector was further successfully maintained as a free plasmid inC. trachomatiswithout allele replacement, suggesting complex plasmid dynamics in the absence of a chlamydialori. Moreover, we showed that the hypervariablerrn-nqrFintergenic region ofC. suisis highly susceptible to transformation, resulting in complete vector integration upstream ofnqrFwithout interruption of the targetedinvgene.

IMPORTANCE

The obligate intracellularChlamydiagenus contains many pathogens with a negative impact on global health and economy. Despite recent progress, there is still a lack of genetic tools limiting our understanding of these complex bacteria. This study provides new insights into genetic manipulation ofChlamydiawith the opportunistic porcine pathogenChlamydia suis, the only chlamydial species naturally harboring an antibiotic resistance gene, originally obtained by horizontal gene transfer.C. suisis transmissible to humans, posing a potential public health concern. We report thatC. suiscan take up vectors that lack the native plasmid, a requirement for most chlamydial transformation systems described to date. Additionally, we show thatC. trachomatis, the most common cause for bacterial sexually transmitted infections and infectious blindness worldwide, can be transformed withC. suisvectors. Finally, the chromosomal region that harbors the resistance gene ofC. suisis highly susceptible to complete vector integration.
Brucella
spp. are facultative anaerobic bacteria under denitrifying conditions
Authors: Freddi Luca , de la Garza-García Jorge A. , Al Dahouk Sascha , Occhialini Alessandra , Köhler Stephan
Published: October 2023

Bacteria of the genus
Brucella
are responsible for human and animal brucellosis worldwide and comprise the well-characterized, so-called classical species belonging to the core clade, with a host range limited to mammals, and the novel atypical strains mainly considered as non-zoonotic to date, but able to colonize non-traditional hosts such as amphibians. Despite marked phenotypical differences between the two groups,
Brucella
species display a high degree of genome identity, including genes encoding reductases involved in the denitrification pathway, a respiratory process able to reduce nitrate to nitrogen under anoxic conditions.
Brucella
spp. have always been considered as strictly aerobic pathogens. Our study, however, describes for the first time that atypical
Brucella
spp. grow well under anoxia, but in a strictly nitrate-dependent manner, whereas classical species show a heterogeneous behavior. The rate of anaerobic growth of the atypical species
Brucella microti
was dependent on nitrate concentration, highlighting a more efficient denitrification pathway with rapid consumption of intermediate nitrite, whereas the classical species
Brucella suis
exhibited lower, nitrate concentration-independent growth coupled with nitrite accumulation. Transcriptional studies performed under anoxic conditions revealed a higher expression of genes participating in the last three denitrification steps in
B. microti
, as compared to
B. suis
, which correlates with the rapid and efficient consumption of nitrite in this atypical species and its rapid growth.

IMPORTANCE

Respiration is a fundamental and complex process that bacteria use to produce energy. Despite aerobic respiration being the most common, some bacteria make use of a mode of respiration in the absence of oxygen, called anaerobic respiration, which can yield advantages in adaptation to various environmental conditions. Denitrification is part of this respiratory process ensuring higher respiratory flexibility under oxygen depletion. Here, we report for the first time the evidence of anaerobic growth of
Brucella
spp. under denitrifying conditions, which implies that this genus should be reconsidered as facultative anaerobic. Our study further describes that efficient denitrification is not equally found within the
Brucella
genus, with atypical species showing a greater ability to denitrify, correlated with higher expression of the genes involved, as compared to classical species.
PRMT5 regulates the polysaccharide content by controlling the splicing of thaumatin-like protein in
Ganoderma lucidum
Authors: Liu Rui , Yang Zhengyan , Yang Tao , Wang Zi , Chen Xin , Zhu Jing , Ren Ang , Shi Liang , Yu Hanshou , Zhao Mingwen
Published: October 2023

In the current study, the silencing of protein arginine methyltransferase 5 (PRMT5) decreased the polysaccharide content of
Ganoderma lucidum
compared to that of the wild-type (WT) strain. Furthermore, RNA-seq screening showed that the glycan degradation process-related gene thaumatin-like protein (
TLP
) was alternatively spliced in WT strains via retained introns, leading to the production of a longer
TLP1
isoform and a shorter
TLP2
isoform; however, only the
TLP2
isoform was observed in
PRMT5
i strains. Experiments examining the polysaccharide content of the TLP silencing,
TLP1
overexpression (OE-
TLP1
), and
TLP2
overexpression (OE-
TLP2
) transformants revealed that
TLP2
plays a more important role than
TLP1
in polysaccharide degradation. Through a combination of yeast two-hybrid, bimolecular fluorescence complementation and surface plasmon resonance assays, we found that
TLP2
directly physically interacted with phosphoglucose isomerase (PGI), a key enzyme in polysaccharide synthesis, and thereby increased PGI activity. However, TLP1 failed to interact with PGI, and PGI activity was not affected. Further inspection showed that the polysaccharide content was decreased in the OE-
TLP2
strains but not significantly changed in the OE-
TLP1
strains compared with that in the WT strains. In addition, the polysaccharide content of the
PRMT5-TLP
-cosilenced strains was not significantly different from that of the WT strains. These results demonstrate that PRMT5 modulates
TLP
processing of pre-mRNA transcripts and thereby decreases the polysaccharide content.

IMPORTANCE

PRMT5 contributes to secondary metabolite biosynthesis in
Ganoderma lucidum
. However, the mechanism through which PRMT5 regulates the biosynthesis of secondary metabolites remains unclear. In the current study,
PRMT5
silencing led to a significant decrease in the biosynthesis of polysaccharides from
G. lucidum
through the action of the alternative splicing of
TLP
. A shorter
TLP2
isoform can directly bind to PGI and regulated polysaccharide biosynthesis. These results suggest that PRMT5 enhances PGI activity by regulating TLP binding to PGI. The results of the current study reveal a novel target gene for PRMT5-mediated alternative splicing and provide a reference for the identification of PRMT5 regulatory target genes.
Racial differences in low value care among older adult Medicare patients in US health systems: retrospective cohort study
Authors: Ganguli Ishani , Mackwood Matthew B , Yang Ching-Wen Wendy , Crawford Maia , Mulligan Kathleen L , O’Malley A James , Fisher Elliott S , Morden Nancy E
Published: October 2023

Objective

To characterize racial differences in receipt of low value care (services that provide little to no benefit yet have potential for harm) among older Medicare beneficiaries overall and within health systems in the United States.

Design

Retrospective cohort study

Setting

100% Medicare fee-for-service administrative data (2016–18).

Participants

Black and White Medicare patients aged 65 or older as of 2016 and attributed to 595 health systems in the United States.

Main outcome measures

Receipt of 40 low value services among Black and White patients, with and without adjustment for patient age, sex, and previous healthcare use. Additional models included health system fixed effects to assess racial differences within health systems and separately, racial composition of the health system’s population to assess the relative contributions of individual patient race and health system racial composition to low value care receipt.

Results

The cohort included 9 833 304 patients (6.8% Black; 57.9% female). Of 40 low value services examined, Black patients had higher adjusted receipt of nine services and lower receipt of 20 services than White patients. Specifically, Black patients were more likely to receive low value acute diagnostic tests, including imaging for uncomplicated headache (6.9%
v
3.2%) and head computed tomography scans for dizziness (3.1%
v
1.9%). White patients had higher rates of low value screening tests and treatments, including preoperative laboratory tests (10.3%
v
6.5%), prostate specific antigen tests (31.0%
v
25.7%), and antibiotics for upper respiratory infections (36.6%
v
32.7%; all P<0.001). Secondary analyses showed that these differences persisted within given health systems and were not explained by Black and White patients receiving care from different systems.

Conclusions

Black patients were more likely to receive low value acute diagnostic tests and White patients were more likely to receive low value screening tests and treatments. Differences were generally small and were largely due to differential care within health systems. These patterns suggest potential individual, interpersonal, and structural factors that researchers, policy makers, and health system leaders might investigate and address to improve care quality and equity.
Evaluation of the Strengthening a Palliative Approach in Long Term Care (SPA-LTC) programme: a protocol of a cluster randomised control trial
Authors: Kaasalainen Sharon , Wickson-Griffiths Abigail , Hunter Paulette , Thompson Genevieve , Kruizinga Julia , McCleary Lynn , Sussman Tamara , Venturato Lorraine , Shaw Sally , Boamah Sheila A , Bourgeois-Guérin Valérie , Hadjistavropoulos Thomas , Macdonald Marilyn , Martin-Misener Ruth , McClement Susan , Parker Deborah , Penner Jamie , Ploeg Jenny , Sinclair Shane , Fisher Kathryn
Published: October 2023

Introduction

Despite the high mortality rates in long-term care (LTC) homes, most do not have a formalised palliative programme. Hence, our research team has developed the Strengthening a Palliative Approach in Long Term Care (SPA-LTC) programme. The goal of the proposed study is to examine the implementation and effectiveness of the SPA-LTC programme.

Methods and analysis

A cross-jurisdictional, effectiveness-implementation type II hybrid cluster randomised control trial design will be used to assess the SPA-LTC programme for 18 LTC homes (six homes within each of three provinces). Randomisation will occur at the level of the LTC home within each province, using a 1:1 ratio (three homes in the intervention and control groups). Baseline staff surveys will take place over a 3-month period at the beginning for both the intervention and control groups. The intervention group will then receive facilitated training and education for staff, and residents and their family members will participate in the SPA-LTC programme. Postintervention data collection will be conducted in a similar manner as in the baseline period for both groups. The overall target sample size will be 594 (297 per arm, 33 resident/family member participants per home, 18 homes). Data collection and analysis will involve organisational, staff, resident and family measures. The primary outcome will be a binary measure capturing any emergency department use in the last 6 months of life (resident); with secondary outcomes including location of death (resident), satisfaction and decisional conflict (family), knowledge and confidence implementing a palliative approach (staff), along with implementation outcomes (ie, feasibility, reach, fidelity and perceived sustainability of the SPA-LTC programme). The primary outcome will be analysed via multivariable logistic regression using generalised estimating equations. Intention-to-treat principles will be used in the analysis.

Ethics and dissemination

The study has received ethical approval. Results will be disseminated at various presentations and feedback sessions; at provincial, national and international conferences, and in a series of manuscripts that will be submitted to peer-reviewed, open access journals.

Trial registration number

NCT039359.
Association of serum magnesium levels with acute ischaemic stroke in patients with type 2 diabetes mellitus: a propensity score-matched case–control study
Authors: Ibrahim Anisha , Legha R , Ravi Renju , Raj Jeffrey Pradeep , Pushparajan Libby
Published: October 2023

Introduction

Magnesium (Mg) deficiency has been found to be associated with many clinical conditions, such as type 2 diabetes mellitus (T2DM), cardiovascular diseases and likewise. Studies evaluating the association between serum Mg levels and ischaemic stroke in T2DM from India are limited, and this formed the aim of this study.

Methods

We conducted a case–control study among patients with T2DM where cases had a history of acute ischaemic stroke in the preceding 2 years and controls with no such history. Data regarding sociodemographic and clinical details and laboratory parameters, including serum Mg concentration, were collected using a semistructured questionnaire. Furthermore, propensity score matching (PSM) was done to match the controls with the cases.

Results

We enrolled a total of 200 participants (cases: 75 and controls: 125), but after PSM, 149 participants (cases: 75 and control:74) were analysed. The serum Mg concentrations were significantly low (p<0.001) among the cases (mean (SD)=1.74 (0.22)) when compared with the controls (mean (SD)=1.95 (0.13)). For every 0.1 mg/dL decrease in serum Mg concentration, the odds of ischaemic stroke increase by approximately 1.918 times (95% CI 1.272 to 2.890; p=0.002).

Conclusions

The mean Mg level in the ischaemic stroke group was significantly low compared with the no stroke group in patients with T2DM. We recommend further controlled studies to evaluate the role of Mg supplementation in the management of acute ischaemic stroke.
Scabies in the Amhara region of northern Ethiopia: a cross-sectional study of prevalence, determinants, clinical presentation and community knowledge
Authors: Yirgu Robel , Middleton Jo , Fekadu Abebaw , Cassell Jackie A , Tesfaye Abraham , Jones Christopher Iain , Bremner Stephen , Enbiale Wendemagegn , Davey Gail
Published: October 2023

Background

The WHO aims to prevent, eliminate or control neglected tropical diseases, including scabies, by 2030. However, limited epidemiological data presented a challenge to control efforts, especially in high burden countries. There was a major scabies outbreak in northern Ethiopia starting in 2015 and prevalence has since increased across much of the country.

Objective

To estimate scabies prevalence, identify its predictors, and assess community perception of, and knowledge about, the infestation.

Design

Population-based cross-sectional study.

Study setting

Ayu Guagusa district, Amhara region, northern Ethiopia.

Participants

1437 people who were members of 381 randomly selected households participated in the study. Five trained mid-level health workers clinically diagnosed people with scabies.

Outcome measures

Clinically diagnosed scabies infestation.

Data analysis

Multi-level logistic regression models were fitted to adjust for individual and household-level confounding variables, and identify predictors of scabies infestation.

Results

Scabies prevalence was 13.4% (95% CI 11.8 to 15.5). Households of more than five people (adjusted OR (aOR)=3.5, 95% CI 1.2 to 10.2) were associated with increased odds of developing scabies, however, females had lower odds (aOR=0.5 95% CI 0.3 to 0.8). Scabietic lesions most frequently involved the trunk (62.0%), and vesicles were the most common types of lesions (67.7%). Two-thirds of adult study participants had heard about scabies and most obtained scabies related information from informal sources. Only 32% of cases sought care for scabies from any source.

Conclusion

Scabies prevalence was high, signifying the need for community-based control interventions. Host density and sex were important predictors of scabies. Despite the favourable attitude toward the effectiveness of scabies treatment, healthcare seeking was low.
Outer retinal corrugations in late-onset retinal degeneration: a diagnostic finding demonstrated with multimodal imaging
Authors: Duncan Holly Joan , McNally Thomas W , Ferrara Mariantonia , Kotagiri Ajay
Published: October 2023

Objective

Late-onset retinal degeneration (L-ORD) is a rare autosomal dominant retinal degeneration that presents in the sixth decade and leads to severe visual loss. The objective of this paper is to describe outer retinal corrugations as a diagnostic feature of L-ORD.

Methods

This retrospective study reviewed consecutive patients diagnosed with L-ORD, confirmed through complete ophthalmic examination, multimodal imaging and genetic tests. Multimodal imaging investigations included spectral domain-optical coherence tomography (SD-OCT) and ultra-wide-field colour and autofluorescence fundus photographs.

Results

A total of 13 eyes of 9 patients with L-ORD had outer retinal corrugations identified on OCT scans.

Conclusion

Outer retinal corrugations may be a diagnostic finding for L-ORD. The detection of this sign may aid diagnosis and characterisation of this disease and help in the differential diagnosis with other acquired pathologies.
Alarm burden and the nursing care environment: a 213-hospital cross-sectional study
Authors: Ruppel Halley , Dougherty Maura , Bonafide Christopher P , Lasater Karen B
Published: October 2023

Background

High rates of medical device alarms in hospitals are a well-documented threat to patient safety. Little is known about organisational features that may be associated with nurses’ experience of alarm burden.

Aims

To evaluate the association between nurse-reported alarm burden, appraisals of patient safety, quality of care and hospital characteristics.

Methods

Secondary analysis of cross-sectional survey data from 3986 hospital-based direct-care registered nurses in 213 acute care hospitals in New York and Illinois, USA. We evaluated associations of alarm burden with appraisals of patient safety and quality of care and hospital characteristics (work environment, staffing adequacy, size, teaching status) using χ2tests.

Results

The majority of respondents reported feeling overwhelmed by alarms (83%), delaying their response to alarms because they were unable to step away from another patient/task (76%), and experiencing situations where a patient needed urgent attention but no one responded to an alarm (55%). Nurses on medical-surgical units reported these experiences at higher rates than nurses working in intensive care units (p<0.001). Alarm burden items were significantly associated with poorer nurse-reported patient safety, quality of care, staffing and work environment. Findings were most pronounced for situations where a patient needed urgent attention but no one responded to the alarm, which was frequently/occasionally experienced by 72% of those who rated their hospital’s safety as poor versus 38% good, p<0.001; 80% who rated overall quality of care poor/fair versus 46% good/excellent, p<0.001 and 65% from poor work environments versus 42% from good work environments, p<0.001.

Conclusion

Most nurses reported feeling overwhelmed by medical device alarms, and our findings suggest that alarm burden may be more pronounced in hospitals with unfavourable working conditions and suboptimal quality and safety. Because this was a cross-sectional study, further research is needed to explore causal relationships and the role of modifiable systems factors in reducing alarm burden.
PD-1-expressing macrophages and CD8 T cells are independent predictors of clinical benefit from PD-1 inhibition in advanced mesothelioma
Authors: Homicsko Krisztian , Zygoura Panagiota , Norkin Maxim , Tissot Stephanie , Shakarishvili Nicholas , Popat Sanjay , Curioni-Fontecedro Alessandra , O'Brien Mary , Pope Anthony , Shah Riyaz , Fisher Patricia , Spicer James , Roy Amy , Gilligan David , Rusakiewicz Sylvie , Fortis Ekaterina , Marti Nesa , Kammler Roswitha , Finn Stephen P , Coukos Georges , Dafni Urania , Peters Solange , Stahel Rolf A
Published: October 2023

Background

Few tissue biomarkers exist to date that could enrich patient with cancer populations to benefit from immune checkpoint blockade by programmed cell death protein 1/ligand-1 (PD-/L-1) inhibitors. PD-L1 expression has value in this context in some tumor types but is an imperfect predictor of clinical benefit. In malignant pleural mesothelioma, PD-L1 expression is not predictive of the benefit from PD-1 blockade. We aimed to identify novel markers in malignant pleural mesothelioma to select patients better.

Methods

We performed a multiplex-immune histochemistry analysis of tumor samples from the phase III PROMISE-meso study, which randomized 144 pretreated patients to receive either pembrolizumab or standard second-line chemotherapy. Our panel focused on CD8+T cell, CD68+macrophages, and the expression of PD-1 and PD-L1 on these and cancer cells. We analyzed single and double positive cells within cancer tissues (infiltrating immune cells) and in the stroma. In addition, we performed cell neighborhood analysis. The cell counts were compared with clinical outcomes, including responses, progression-free and overall survivals.

Results

We confirmed the absence of predictive value for PD-L1 in this cohort of patients. Furthermore, total CD8 T cells, CD68+macrophages, or inflammatory subtypes (desert, excluded, inflamed) did not predict outcomes. In contrast, PD-1-expressing CD8+T cells (exhausted T cells) and PD-1-expressing CD68+macrophages were both independent predictors of progression-free survival benefit from pembrolizumab. Patients with tumors simultaneously harboring PD1+T cells and PD-1+macrophages benefited the most from immune therapy.

Conclusion

We analyzed a large cohort of patients within a phase III study and found that not only PD-1+CD8 T cells but also PD-1+CD68+ macrophages are predictive. This data provides evidence for the first time for the existence of PD-1+macrophages in mesothelioma and their clinical relevance for immune checkpoint blockade.
Construct validity and responsiveness of feasible composite disease activity measures for use in daily clinical practice in patients with psoriatic arthritis
Authors: Kasiem Fazira R. , Kok Marc R. , Luime Jolanda J. , Tchetverikov Ilja , Korswagen Lindy-Anne , Denissen Natasja H.A.M. , Goekoop-Ruiterman Yvonne P.M. , van Oosterhout Maikel , Fodili Faouzia , Hazes Johanna M.W. , Tillett William , Vis Marijn
Published: October 2023

Objective

There is a need for a widely accepted comprehensive disease activity measure for use in daily practice in patients with psoriatic arthritis (PsA). For this reason, the 3-item Visual Analogue Scale (3VAS) and 4-item Visual Analogue Scale (4VAS) were developed. This study aimed to test construct validity and responsiveness of the 3VAS and 4VAS in a population of patients with newly diagnosed PsA receiving usual care.

Methods

Components of the 3VAS (physician global, patient global, patient skin) and 4VAS (physician global, patient pain, patient joint, patient skin) were scored on 0–10 VAS scales. Agreement of low disease activity (LDA) state between 3VAS/4VAS and other composite measures was tested using Venn diagrams. Construct validity and responsiveness (3-month interval) were assessed using Spearman correlation coefficients and standardised response means (SRM) with effect sizes (ES), respectively, following hypothesis generation. Both 3VAS/4VAS were also compared with several patient-reported outcome measures.

Results

Data from 629 patients were used. Both 3VAS (ES=0.48, SRM 0.52) and 4VAS (ES=0.48, SRM=0.50) showed responsiveness similar to Disease Activity in PSoriatic Arthritis (DAPSA) and Disease Activity Score-28 (DAS28). Both measures had a strong correlation with DAPSA (r=0.80–0.87), Psoriatic Arthritis Disease Activity Score (PASDAS) (r=0.89) and Routine Assessment of Patient Index Data 3 (RAPID3) (r=0.84–0.92). 3VAS and 4VAS had the highest agreement with PASDAS in categorising patients to LDA at 12 months.

Conclusion

This is the first study assessing the performance of the 3VAS and 4VAS in an observational cohort of patients with early PsA. Both measures have promising performance characteristics, showing strong correlations and good discrimination with existing composite measures. The 4VAS may be the preferred version with better face validity.
Glucocorticoid trajectories over 2 years in patients with rheumatoid arthritis in a real-life setting
Authors: Delteil Alycia , Lambert Celine , Pereira Bruno , Couderc Marion , Malochet-Guinamand Sandrine , Pickering Marie Eva , Villedon Marc , Mathieu Sylvain , Soubrier Martin , Tournadre Anne
Published: October 2023

Objectives

To analyse glucocorticoid (GC) use and trajectories in a real-life cohort of rheumatoid arthritis (RA).

Methods

Patients with RA included in the longitudinal RCVRIC cohort for initiating or changing biological disease-modifying antirheumatic drugs, were compared for the use of GCs at baseline. Among the GC users, the GC dose was analysed over 2 years of follow-up by group-based trajectory models. Characteristics and outcomes were compared between the trajectories.

Results

Among the 184 patients (RA duration 4.2 years (1.3; 12.6), Disease Activity Scores (DAS)28-C reactive protein (CRP) 4.24±2.14), 81 (44%) were on GCs. The GC users were significantly older, had higher CRP and Health Assessment Questionnaire (HAQ), more hypertension and lower lumbar T-score, but similar activity and erosive scores. Among the GC users, two trajectories were identified: trajectory 1 (n=20, 25%) with GC discontinuation in the first year and trajectory 2 (n=61, 75%) with maintenance of low-dose GCs at 2 years. Trajectory 2 was significantly associated with higher HAQ, a longer GC duration and a less frequent methotrexate association. After adjustment for HAQ, GC duration and MTX use, good EULAR responses were less frequent at 6 months and 1 year in the GC maintenance trajectory (38.3% vs 81.3%, p=0.03; 42.0% vs 82.4%, p=0.02). Diabetes, fractures and increased body mass index were noted in trajectory 2.

Conclusion

GCs were used in almost half of patients with established RA in real-world practice. For the majority of GC users, a long-term low dose of GCs is maintained over 2 years. These results highlight the difficulties with stopping GCs, the lack of consensus for the efficacy–safety balance of GCs, and the need to individualise the best GC tapering.
Risk of major adverse cardiovascular events in patients with rheumatoid arthritis treated with conventional synthetic, biologic and targeted synthetic disease-modifying antirheumatic drugs: observational data from the German RABBIT register
Authors: Meissner Yvette , Schäfer Martin , Albrecht Katinka , Kekow Joern , Zinke Silke , Tony Hans-Peter , Strangfeld Anja
Published: October 2023

Objective

To estimate the effects of Janus kinase inhibitors (JAKi), tumour necrosis factor inhibitors (TNFi), other biologic(b) or conventional synthetic(cs) disease-modifying antirheumatic drugs (DMARDs) on the risk of major adverse cardiovascular events (MACE) in patients with rheumatoid arthritis (RA).

Methods

Cohort study analysing episodes of DMARD-treatment initiated between January 2017 and April 2022 in the biologics register Rheumatoid Arthritis: Observation of Biologic Therapy. Incidence rates (IRs) per 100 patient-years with 95% CIs were calculated for overall patients and those with cardiovascular risk (age ≥50 years and ≥1 cardiovascular risk factor). MACE risk was estimated as HRs by inverse probability of treatment weight-adjusted Andersen-Gill models.

Results

A total of 154 MACE occurred among 14 203 treatment episodes (21 218 patient-years). IRs were 0.68 (0.47; 0.95), 0.62 (0.45; 0.83), 0.76 (0.53; 1.06) and 0.95 (0.68; 1.29) for JAKi, TNFi, bDMARDs and csDMARDs, respectively. IRs were higher in cardiovascular risk patients. Adjusted HRs (95% CI) comparing JAKi, bDMARDs and csDMARDs with TNFi were 0.89 (0.52 to 1.52), 0.76 (0.45; to1.27) and 1.36 (0.85 to 2.19) in overall, and 0.74 (0.41 to 1.31), 0.75 (0.45 to 1.27) and 1.21 (0.74 to 1.98) in cardiovascular risk patients. HRs were not increased in patients ≥65 years, with cardiovascular history or smokers, and also not when using csDMARD as reference instead of TNFi. IRs for baricitinib, tofacitinib and upadacitinib were 0.49 (0.25 to 0.85), 0.98 (0.58 to 1.55) and 0.53 (0.15 to 1.36), respectively.

Conclusion

In this German observational cohort study, MACE did not occur more frequently with JAKi compared with other DMARDs. However, individual JAKis showed different unadjusted IRs.
Effect of feeding history on metabolic rate of largemouth bass (Micropterus nigricans): implications for bioenergetics models
Authors: Ranney Steven H. , Chipps Steven R. , Wahl David H.
Published: October 2023

Metabolic rate is a key parameter in fish energy budgets that strongly influences the output of bioenergetics models. In this study, we tested the hypothesis that metabolic rate varies with growth history of age-1 largemouth bass Micropterus nigricans Cuvier, 1828. Two groups of fish were fed alternating maintenance or ad libitum rations of fathead minnow Pimephales promelas Rafinesque, 1820, so that over a 9-week period, initial and ending size of fish was similar. After 9 weeks, oxygen consumption was measured using static, closed respirometry. Although final body weight was similar between the two groups (means, 104–108 g), specific oxygen consumption for fish fed maintenance rations (0.094 mg O2 g−2 h−1) was 38% less than that measured for fish fed ad libitum (0.152 mg O2 g−2 h−1). Bioenergetics estimates of food consumption were similar to observed values for fish fed ad libitum (∼7% error), but for fish fed maintenance rations, the model overestimated food consumption by 65%. By accounting for changes in metabolic rate owing to reduced feeding, error in model estimates of food consumption was reduced. These findings shed new insight into factors associated with consumption-dependent error in bioenergetics models and highlight the importance of feeding history on metabolic rate of fish. Incorporating growth-dependent metabolism into bioenergetics models can improve model accuracy and allow fisheries biologists to make more informed decisions regarding fish growth and energetics.
Robotic pick-and-handover maneuvers with camera-based intelligent object detection and impedance control
Authors: Chen Qiguang , Wan Lucas , Pan Ya-Jun
Published: October 2023

A vision-based impedance control method is applied to a 7-degree-of-freedom Franka Emika (FE) Panda robotic manipulator to complete pick-and-handover tasks with human-like grasping of fruits. The interfaces between different hardware, controllers, and path planners are developed using robot operating systems (ROS). An RGB camera is applied using the YOLOv5 (You Only Look Once v5) object detection algorithm, which is trained for various fruits and human hands and then employed for identifying the location of the targeted objects. A qb-SoftHand robotic hand is used as the end-effector for the grasping tasks. By integrating these components together with ROS, the FE Panda robot successfully achieves autonomous human-like handover tasks, as shown in the experimental results.
Schwinger displacement of the quark–gluon vertex
Authors: Aguilar A. C. , Ferreira M. N. , Ibañez D. , Papavassiliou J.
Published: October 2023

The action of the Schwinger mechanism in pure Yang–Mills theories endows gluons with an effective mass, and, at the same time, induces a measurable displacement to the Ward identity satisfied by the three-gluon vertex. In the present work we turn to Quantum Chromodynamics with two light quark flavors, and explore the appearance of this characteristic displacement at the level of the quark–gluon vertex. When the Schwinger mechanism is activated, this vertex acquires massless poles, whose momentum-dependent residues are determined by a set of coupled integral equations. The main effect of these residues is to displace the Ward identity obeyed by the pole-free part of the vertex, causing modifications to its form factors, and especially the one associated with the tree-level tensor. The comparison between the available lattice data for this form factor and the Ward identity prediction reveals a marked deviation, which is completely compatible with the theoretical expectation for the attendant residue. This analysis corroborates further the self-consistency of this mass-generating scenario in the general context of real-world strong interactions.
Investigating and controlling the quantum resources of bipartite-qubit detectors of scalar fields in the process of spacetime expansion
Authors: Yang Huan , Xing Ling-Ling , Kong Min , Zhang Gang , Ye Liu
Published: October 2023

Quantum resources construct new avenues to explore the cosmos. Considering bipartite-qubit detectors subjected to scalar fields in an expanding spacetime, quantum resources (including quantum coherence, quantum discord, Bell-nonlocality, and nonlocal advantage of quantum coherence) of the system are characterized. The influences of various cosmic parameters on these quantum resources are investigated. Besides, we use the filtering operation to propose a strategy that can be used to control these quantum resources. The results reveal that quantum coherence and quantum discord can not disappear at different expansion rapidity, expansion volumes, and particle masses of scalar field. Conversely, one can not capture Bell-nonlocality and nonlocal advantage of quantum coherence at higher expansion rapidity, larger expansion volume, and smaller particle mass. The dissipation of quantum resources can be resisted via the filtering operation. One can use the filtering operation to remarkably strengthen these quantum resources of the system.
Muscle Belly Repair: Biomechanical Assessment of the Anchor Suture and the Modified Kessler Techniques
Authors: JULIEN Terrill P. , LI Guoan , MUDGAL Chaitanya S.
Published: October 2023

Background: Treatment of muscle belly lacerations remains a problem for surgeons. Inadequate repair of lacerations can cause functional disability. To date, there is no consensus on the method of repair for these injuries. We have previously described a technique of repairing mid-substance muscle belly lacerations. The aim of this study was to determine the ultimate strength of an intact muscle belly and to compare the anchor suture (AS) technique with the modified Kessler (MK) technique.

Methods: Fifteen fresh frozen hind-legs from adolescent pigs were divided into three groups and used for the testing. Each group consisted of five specimens. Group one was the intact control group, group two was repaired with the MK technique and group three was repaired with the AS technique. Following repair, the muscles were secured in a custom-made fixation apparatus and underwent linear tensioning at a rate of 25 mm/min, generating a load-displacement curve for each specimen. The data regarding ultimate strength, modes of failure and number of intact suture/anchor constructs (for groups 2 and 3) was calculated.

Results: The ultimate strength of the intact muscle group of was found to be 608.1 ± 107.9  N. This was significantly (p < 0.05) higher than the pull-out strength of the MK and AS groups. The pull-out strength of the AS group was 143.1 ± 36.7 N, nearly twice that of the MK group 69.8 ± 16.4 N (p = 0.11). Suture pull-out was the most common mode of failure.

Conclusions: The AS technique was found to have both higher strain and nearly twice the ultimate pull-out strength compared to the MK repair group. We suggest the AS technique as a viable technique for mid-substance muscle belly repairs.
Distraction Osteogenesis for the Brachytelephalangic Thumb – A Case Report
Authors: YAMAZUMI Saori , MATSUURA Shintaro , MIYAWAKI Takeshi
Published: October 2023

Brachytelephalangy is a congenital condition characterised by the shortening of the distal phalanges, which affects appearance but does not cause severe functional disability. Therefore, most hand surgeons do not consider it to require surgical treatment, and there are limited options to improve the appearance of the affected digits. We present the case of a 55-year-old male patient with congenital brachytelephalangy of the thumb, who underwent a bone lengthening procedure using distraction osteogenesis with the Ilizarov minifixator. The distal phalanx was carefully osteotomised and gradually lengthened up to 5 mm with no adverse events observed. The patient was satisfied with the natural appearance of his thumb after the surgery. This gradual callus distraction method is a radical solution for people with brachytelephalangy, particularly after epiphyseal closure and can manage the external fixator on their own.

Level of Evidence: Level V (Therapeutic)
Plexiform Schwannoma of Digital Nerve
Authors: SAEKI Yuji , HATTORI Yasunori , MANE Satish Annabhau , DOI Kazuteru
Published: October 2023

Plexiform schwannoma is an uncommon benign tumour that grows in a plexiform pattern. We report a 47-year-old man with a mass on the palmar aspect of the metacarpophalangeal joint of the right index finger that had been growing gradually for more than 10 years. The mass was palpated from the distal carpal tunnel to the ulnar aspect of the proximal interphalangeal joint of the index finger, with tingling and numbness sensation. The tumour was a multinodular tumour involving the first common palmar digital nerve to the ulnar proper palmar digital nerve. It was resected and reconstructed with a sural nerve graft. Plexiform schwannoma is rare in the digital nerve, with only six cases reported. Generally, classic schwannomas can be enucleated without causing neurologic deficits; however, plexiform schwannoma may require nerve resection. There have been reports of recurrence of plexiform schwannoma; definitive resection and long-term follow-up are necessary.

Level of Evidence: Level V (Therapeutic)