bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncertain futures: perceptions of refugees in a story completion task
Authors: Parker Samuel , Earnshaw Deborah , Penn Emma , Kumari Roshni
Published: June 2023

Purpose

In recent years the movement of refugees has led to increasing negative media and political discourse about migration in the United Kingdom, particularly as the number of refugees crossing the English Channel has increased. Despite this hostility, little is known about how the UK public perceive the journeys made by refugees or the refugees themselves.

Design/methodology/approach

In this study the authors used a story completion method to analyse perceptions and understandings of refugees. Participants were given the opening of a story about refugees crossing the English Channel and were asked to complete the remainder of the story. In total, 84 participants completed stories that ranged in length from two to 423 words. The stories were analysed using reflexive thematic analysis.

Findings

Each of the completed stories was analysed using reflexive thematic analysis and three themes were generated: Conflicting emotions: Uncertainty and the relief of reaching safety after a traumatic journey; The spectre of illegality: Borders and the uncertainty of what happens next; and Welcome or unwelcome?: Cultural values of welcome and hospitality.

Originality/value

The authors argue that this original use of the story completion method highlights how participants draw on cultural narratives of hospitality and welcome and that their stories are constructed using emotional categories that are in contrast to the more binary constructions of refugees that are present in media and government discourse about refugees and the English Channel crossings.
Evaluating the use of the ABCD2 score as a clinical decision aid in the emergency department: Retrospective observational study
Authors: Wahi Siddhant , Michaleff Zoe A , Lomax Paige , Brand Adam , van der Merwe Madeleen , Jones Mark , Glasziou Paul , Keijzers Gerben
Published: June 2023

Objective

Clinical decision aids (CDAs) can help clinicians with patient risk assessment. However, there is little data on CDA calculation, interpretation and documentation in real‐world ED settings. The ABCD2 score (range 0–7) is a CDA used for patients with transient ischaemic attack (TIA) and assesses risk of stroke, with a score of 0–3 being low risk. The aim of this study was to describe ABCD2 score documentation in patients with an ED diagnosis of TIA.

Methods

Retrospective observational study of patients with a working diagnosis of a TIA in two Australian EDs. Data were gathered using routinely collected data from health informatics sources and medical records reviewed by a trained data abstractor. ABCD2 scores were calculated and compared with what was documented by the treating clinician. Data were presented using descriptive analysis and scatter plots.

Results

Among the 367 patients with an ED diagnosis of TIA, clinicians documented an ABCD2 score in 45% (95% CI 40–50%, n = 165). Overall, there was very good agreement between calculated and documented scores (Cohen's kappa 0.90). The mean documented and calculated ABCD2 score were similar (3.8, SD = 1.5, n = 165 vs 3.7, SD = 1.8, n = 367). Documented scores on the threshold of low and high risk were more likely to be discordant with calculated scores.

Conclusions

The ABCD2 score was documented in less than half of eligible patients. When documented, clinicians were generally accurate with their calculation and application of the ABCD2. No independent predictors of ABCD2 documentation were identified.
Patterns of practice regarding use of radiation therapy following radical prostatectomy: A survey of Radiation Oncologists and Urologists in Australia and New Zealand
Authors: Lawless Anna , Kneebone Andrew , Armstrong Shreya , Chander Sarat , Christie David , Finnigan Renee , Hayden Amy , Higgs Braden , Knox Matthew , Sasso Giuseppe , Sidhom Mark , Shakespeare Thomas P , Holt Tanya
Published: June 2023

Introduction

This study aimed to investigate the patterns of practices of radiation oncologists (ROs) and urologists in Australia and New Zealand with respect to the utilisation of post‐prostatectomy radiation therapy (RT) and help guide the development of an update to the existing Faculty of Radiation Oncology Genito‐Urinary Group post‐prostatectomy guidelines.

Methods

ROs and urologists with subspecialty practice in prostate cancer from Australia and New Zealand were invited to participate in an online survey comprised of clinical scenarios regarding post‐prostatectomy RT.

Results

Sixty‐five ROs and 28 urologists responded to the survey. In the setting of low‐risk biochemical relapse, the threshold for initiating RT was lower for ROs than urologists. ROs were more likely than urologists to recommend adjuvant RT for node‐positive disease. When salvage RT was advised for a pT3N0R1 recurrence, there was no consensus amongst ROs on whether to add either ADT or nodal treatment over prostate bed RT alone. For a solitary PSMA‐avid pelvic lymph node recurrence, whole pelvis RT with androgen deprivation therapy was the preferred treatment option (72% ROs, 43% urologists). Most ROs (92%) recommended conventionally fractionated RT to 66–70 Gy, with a boost to any PSMA PET avid recurrent disease.

Conclusion

This survey highlights the marked discordance in practice for the management of prostate cancer relapse post‐prostatectomy. This is seen not only between specialties but also within the radiation oncology community. This emphasises the need for an updated evidence‐based guideline to be produced.
Is HbA1c associated with birth weight? A multivariable analysis of Pakistani pregnant women
Authors: Silke Olivia , Yim Ilona S. , Shaikh Kiran , Lalani Sharifa , Ghani Farooq , Wanyonyi Sikolia , Samia Pauline , Merali Mohamoud , Omuse Geoffrey , Okoko Christine , Forcheh Ntonghanwah , Premji Shahirose S. ,   the Maternal‐infant Global Health Team (MiGHT) Collaborators in Research
Published: June 2023

Aim

Globally, one in seven infants is born with low birth weight and 3%–7% of infants are born with high birth weight, with the greatest burden noted in low‐ and middle‐income countries. This study investigated the association between maternal prenatal glucose regulation and birth weight and the moderating effect of fetal sex among Pakistani women.

Methods

Secondary data from a prospective longitudinal study of healthy pregnant women from Pakistan (N = 189) was used. Participants provided a blood sample (12–19 weeks' gestational age) for the assessment of HbA1c (%). Birth weight (g) was collected following delivery.

Results

Higher maternal HbA1c was associated with higher birth weight (b = 181.81, t[189] = 2.15, p = 0.03), which was moderated by fetal sex (b = −326.27, t[189] = −2.47, p = 0.02), after adjusting for gestational age at birth, ethnicity, and pregnancy weight. Among women carrying a male fetus, every 1% increase in HbA1c predicted a 182 g increase in birth weight (b = 181.81, t[189] = 2.15, p = 0.03).

Conclusions

Results extend research from high‐income countries and indicate that fetal sex may have implications for glucose regulation in early to mid‐pregnancy. Future research should examine sociocultural factors, which could elucidate potential mediating factors in the relation between HbA1c and birth weight in healthy pregnancies.
Spatial configuration of hundreds charts influences children's knowledge of base‐ten concepts
Authors: Osana Helena P. , Wagner Vera , Navarrete‐Ulloa Jairo A.
Published: June 2023

The hundreds chart is a valuable tool for teachers in elementary mathematics classrooms. The present study investigated the effects of spatial configurations of virtual hundreds charts on children's knowledge of base‐ten concepts. Kindergarten and first‐grade students were assigned to three instructional conditions in which they worked with a researcher to solve arithmetic word problems. The charts used in the conditions differed by the spatial configuration of the numbers: (a) top down, with numbers increasing from top to bottom; (b) bottom up, with increases from bottom to top; and (c) explicit bottom‐up, with a bottom‐up chart and an explicit visual cue that prompted a comparison between the “up‐is‐more” structure to a cylinder filling with water. Participants were more likely to count by tens than by ones to solve problems when the numbers in the chart increased from top to bottom than when they increased from bottom to top. No effects of spatial configuration on place‐value knowledge was observed. One account of the findings is that participants were more accustomed to the movements in the top‐down chart because they matched the direction in which children learn to read. The role of spatial affordances of instructional materials in children's mathematics learning is discussed.
Comparison of Deformation Patterns Excited in the Human Brain In Vivo by Harmonic and Impulsive Skull Motion
Authors: Escarcega Jordan D. , Knutsen Andrew K. , Alshareef Ahmed A. , Johnson Curtis L. , Okamoto Ruth J. , Pham Dzung L. , Bayly Philip V.
Published: June 2023

Noninvasive measurements of brain deformation in human participants in vivo are needed to develop models of brain biomechanics and understand traumatic brain injury (TBI). Tagged magnetic resonance imaging (tagged MRI) and magnetic resonance elastography (MRE) are two techniques to study human brain deformation; these techniques differ in the type of motion and difficulty of implementation. In this study, oscillatory strain fields in the human brain caused by impulsive head acceleration and measured by tagged MRI were compared quantitatively to strain fields measured by MRE during harmonic head motion at 10 and 50 Hz. Strain fields were compared by registering to a common anatomical template, then computing correlations between the registered strain fields. Correlations were computed between tagged MRI strain fields in six participants and MRE strain fields at 10 Hz and 50 Hz in six different participants. Correlations among strain fields within the same experiment type were compared statistically to correlations from different experiment types. Strain fields from harmonic head motion at 10 Hz imaged by MRE were qualitatively and quantitatively similar to modes excited by impulsive head motion, imaged by tagged MRI. Notably, correlations between strain fields from 10 Hz MRE and tagged MRI did not differ significantly from correlations between strain fields from tagged MRI. These results suggest that low-frequency modes of oscillation dominate the response of the brain during impact. Thus, low-frequency MRE, which is simpler and more widely available than tagged MRI, can be used to illuminate the brain's response to head impact.
In Search of a Universal Rough Wall Model
Authors: Yang Xiang I. A. , Zhang Wen , Yuan Junlin , Kunz Robert F.
Published: June 2023

This work compares various existing rough-wall models on a large collection of rough surfaces with different characteristics and studies the potential of these models in accommodating new datasets. We consider three empirical roughness correlations, two physics-based models, and one data-driven machine-learning model on 68 rough surfaces inside and outside the Roughness Database1. Results show that correlation-type models and machine-learning models do not extrapolate outside the dataset against which they are calibrated or trained. In contrast, the physics-based sheltering model performs well in extrapolation. Recalibrating a roughness correlation against a large dataset proves unfruitful. However, retraining a machine learning model yields good results. We do not pursue further retraining and recalibrating of a physics-based model, as it requires new physical insights. Overall, our findings suggest that a universal rough-wall model is yet to be found. The capability of extrapolation will likely come from incorporating physics. Data, on the other hand, benefits machine learning models.
Interfacial Fracture Caused by Electromigration at Copper Interconnects
Authors: Wang Yuexing , Li Bofeng , Zhifeng Yao , Yao Yao
Published: June 2023

The present investigation delves into the failure model of cracking at the Cu/dielectric interface, specifically at the anode end of a copper interconnect that is triggered by electromigration. The study employs the continuous dislocation model to determine the stress field caused by interfacial mass diffusion that exists within and outside of the copper line. Apart from the anticipated tensile or compressive stress on the cathode or anode side, an anomalous stress singularity is identified at the interface between the dielectric layer and the anode end of the copper line. This singular stress distribution leads to cracking in the compressive portion of the dielectric layer at the anode end under the influence of electromigration. The theoretical predictions are in good agreement with experimental data, and a novel failure criterion akin to the stress intensity factor in fracture mechanics is formulated.
Peak intensities in Auger electron spectroscopy for quantification: Relationship between differentiated spectral intensities and direct peak areas
Authors: Watanabe Katsumi , Watanabe Daisuke , Mamiya Kazutoshi , Koizumi Seiji , Sanada Noriaki , Suzuki Mineharu
Published: June 2023

In Auger electron spectroscopy, qualitative analyses are performed by using high-energy resolution direct spectra with a spherical capacitor analyzer (SCA). Although it is used to carry out quantitative analyses with differentiated spectra, high-energy resolution spectra measured with an SCA differ from those obtained with conventional energy resolution measurements using a cylindrical mirror analyzer. When we attempt quantitative analyses by applying direct spectra, this does not allow the use of previously accumulated analytical parameters for differentiated spectra, such as relative sensitivity factors. Therefore, we clarified the relationship between Auger direct spectral intensities and differentiated spectral intensities, and we defined a correction factor enabling the use of the analytical parameters given by differentiated spectra to direct spectra. To estimate the direct spectral area contributing to a quantitative analysis, the background of the direct spectrum is subtracted by the Shirley method, similar to the spectral treatment used in x-ray photoelectron spectroscopy. The correction factor is expressed as the ratio of the normalized peak area and normalized differentiated peak-to-peak intensity, which is actually measured and determined in every laboratory and with any instrument.
Quantitative measurement of the requirement of diverse protein degradation pathways in MHC class I peptide presentation
Authors: Mamrosh Jennifer L. , Sherman David J. , Cohen Joseph R. , Johnston James A. , Joubert Marisa K. , Li Jing , Lipford J. Russell , Lomenick Brett , Moradian Annie , Prabhu Siddharth , Sweredoski Michael J. , Vander Lugt Bryan , Verma Rati , Deshaies Raymond J.
Published: June 2023

Peptides from degradation of intracellular proteins are continuously displayed by major histocompatibility complex (MHC) class I. To better understand origins of these peptides, we performed a comprehensive census of the class I peptide repertoire in the presence and absence of ubiquitin-proteasome system (UPS) activity upon developing optimized methodology to enrich for and quantify these peptides. Whereas most class I peptides are dependent on the UPS for their generation, a surprising 30%, enriched in peptides of mitochondrial origin, appears independent of the UPS. A further ~10% of peptides were found to be dependent on the proteasome but independent of ubiquitination for their generation. Notably, clinically achievable partial inhibition of the proteasome resulted in display of atypical peptides. Our results suggest that generation of MHC class I•peptide complexes is more complex than previously recognized, with UPS-dependent and UPS-independent components; paradoxically, alternative protein degradation pathways also generate class I peptides when canonical pathways are impaired.
A missense mutation in
RRM1
contributes to animal tameness
Authors: Dou Mingle , Li Ming , Zheng Zhuqing , Chen Qiuming , Wu Yongji , Wang Jinxin , Shan Huiquan , Wang Fei , Dai Xuelei , Li Yunjia , Yang Zhirui , Tan Guanghui , Luo Funong , Chen Lei , Shi Yun Stone , Wu Jiang Wei , Luo Xiong-Jian , Asadollahpour Nanaei Hojjat , Niyazbekova Zhannur , Zhang Guojie , Wang Wen , Zhao Shanting , Zheng Wenxin , Wang Xihong , Jiang Yu
Published: June 2023

The increased tameness to reduce avoidance of human in wild animals has been long proposed as the key step of animal domestication. The tameness is a complex behavior trait and largely determined by genetic factors. However, the underlying genetic mutations remain vague and how they influence the animal behaviors is yet to be explored. Behavior tests of a wild-domestic hybrid goat population indicate the locus under strongest artificial selection during domestication may exert a huge effect on the flight distance. Within this locus, only one missense mutation
RRM1
I241V
which was present in the early domestic goat ~6500 years ago. Genome editing of
RRM1
I241V
in mice showed increased tameness and sociability and reduced anxiety. These behavioral changes induced by
RRM1
I241V
were modulated by the alternation of activity of glutamatergic synapse and some other synapse-related pathways. This study established a link between
RRM1
I241V
and tameness, demonstrating that the complex behavioral change can be achieved by mutations under strong selection during animal domestication.
Whole-body gene expression atlas of an adult metazoan
Authors: Ghaddar Abbas , Armingol Erick , Huynh Chau , Gevirtzman Louis , Lewis Nathan E. , Waterston Robert , O’Rourke Eyleen J.
Published: June 2023

Gene activity defines cell identity, drives intercellular communication, and underlies the functioning of multicellular organisms. We present the single-cell resolution atlas of gene activity of a fertile adult metazoan:
Caenorhabditis elegans
. This compendium comprises 180 distinct cell types and 19,657 expressed genes. We predict 7541 transcription factor expression profile associations likely responsible for defining cellular identity. We predict thousands of intercellular interactions across the
C. elegans
body and the ligand-receptor pairs that mediate them, some of which we experimentally validate. We identify 172 genes that show consistent expression across cell types, are involved in basic and essential functions, and are conserved across phyla; therefore, we present them as experimentally validated housekeeping genes. We developed the WormSeq application to explore these data. In addition to the integrated gene-to-systems biology, we present genome-scale single-cell resolution testable hypotheses that we anticipate will advance our understanding of the molecular mechanisms, underlying the functioning of a multicellular organism and the perturbations that lead to its malfunction.
VANGL2 inhibits antiviral IFN-I signaling by targeting TBK1 for autophagic degradation
Authors: Hu Zhiqiang , Xie Yingchao , Lu Jiansen , Yang Jianwu , Zhang Jiahuan , Jiang Huaji , Li Hongyu , Zhang Yufeng , Wu Dan , Zeng Ke , Bai Xiaochun , Yu Xiao
Published: June 2023

Stringent control of type I interferon (IFN-I) signaling is critical to potent innate immune responses against viral infection, yet the underlying molecular mechanisms are still elusive. Here, we found that Van Gogh–like 2 (VANGL2) acts as an IFN-inducible negative feedback regulator to suppress IFN-I signaling during vesicular stomatitis virus (VSV) infection. Mechanistically, VANGL2 interacted with TBK1 and promoted the selective autophagic degradation of TBK1 via K48-linked polyubiquitination at Lys
372
by the E3 ligase TRIP, which serves as a recognition signal for the cargo receptor OPTN. Furthermore, myeloid-specific deletion of VANGL2 in mice showed enhanced IFN-I production against VSV infection and improved survival. In general, these findings revealed a negative feedback loop of IFN-I signaling through the VANGL2-TRIP-TBK1-OPTN axis and highlighted the cross-talk between IFN-I and autophagy in preventing viral infection. VANGL2 could be a potential clinical therapeutic target for viral infectious diseases, including COVID-19.
Structural pseudocapacitors with reinforced interfaces to increase multifunctional efficiency
Authors: Yao Lulu , Zheng Kai , Koripally Nandu , Eedugurala Naresh , Azoulay Jason D. , Zhang Xinyu , Ng Tse Nga
Published: June 2023

Structural supercapacitors hold promise to expand the energy capacity of a system by integrating load-bearing and energy-storage functions in a multifunctional structure, resulting in weight savings and safety improvements. Here, we develop strategies based on interfacial engineering to advance multifunctional efficiency. The structural electrodes were reinforced by coating carbon-fiber weaves with a uniquely stable conjugated redox polymer and reduced graphene oxide that raised pseudocapacitive capacitance and tensile strength. The solid polymer electrolyte was tuned to a gradient configuration, where it facilitated high ionic conductivity at the electrode-electrolyte interfaces and transitioned to a composition with high mechanical strength in the bulk for load support. The gradient design enabled the multilayer structural supercapacitors to reach state-of-the-art performance matching the level of monofunctional supercapacitors. In situ electrochemical-mechanical measurements established the device durability under mechanical loads. The structural supercapacitor was made into the hull of a model boat to demonstrate its multifunctionality.
Bioinspired helical-artificial fibrous muscle structured tubular soft actuators
Authors: Hu Zhiming , Zhang Yanlin , Jiang Hanqing , Lv Jiu-an
Published: June 2023

Biological tubular actuators show diverse deformations, which allow for sophisticated deformations with well-defined degrees of freedom (DOF). Nonetheless, synthetic active tubular soft actuators largely only exhibit few simple deformations with limited and undesignable DOF. Inspired by 3D fibrous architectures of tubular muscular hydrostats, we devised conceptually new helical-artificial fibrous muscle structured tubular soft actuators (HAFMS-TSAs) with locally tunable molecular orientations, materials, mechanics, and actuation via a modular fabrication platform using a programmable filament winding technique. Unprecedentedly, HAFMS-TSAs can be endowed with 11 different morphing modes through programmable regulation of their 3D helical fibrous architectures. We demonstrate a single “living” artificial plant rationally structured by HAFMS-TSAs exhibiting diverse photoresponsive behaviors that enable adaptive omnidirectional reorientation of its hierarchical 3D structures in the response to environmental irradiation, resembling morphing intelligence of living plants in reacting to changing environments. Our methodology would be significantly beneficial for developing sophisticated soft actuators with designable and tunable DOF.
Emergence of Inducible Macrolide Resistance in Mycobacterium chelonae Due to Broad-Host-Range Plasmid and Chromosomal Variants of the Novel 23S rRNA Methylase Gene,
erm
(55)
Authors: Brown-Elliott Barbara A. , Wallace Richard J. , Wengenack Nancy L. , Workman Sean D. , Cameron Andrew D. S. , Bush Georgie , Hughes M. Dolores , Melton Stephanie , Gonzalez-Ramirez Bibiana , Rodriguez Eliana , Somayaji Kavya , Klapperich Courtney , Viers Mary , Bolaji Ayooluwa J. , Rempel Emma , Alexander David C.
Published: June 2023

Macrolides are a mainstay of therapy for infections due to nontuberculous mycobacteria (NTM). Among rapidly growing mycobacteria (RGM), inducible macrolide resistance is associated with four chromosomal 23S rRNA methylase (
erm
) genes.
An apicomplexan bromodomain protein, TgBDP1, associates with diverse epigenetic factors to regulate essential transcriptional processes in
Toxoplasma gondii
Authors: Fleck Krista , McNutt Seth , Chu Feixia , Jeffers Victoria
Published: June 2023

The protozoan pathogen
Toxoplasma gondii
relies on tight regulation of gene expression to invade and establish infection in its host. The divergent gene regulatory mechanisms of
Toxoplasma
and related apicomplexan pathogens rely heavily on regulators of chromatin structure and histone modifications. The important contribution of histone acetylation for
Toxoplasma
in both acute and chronic infection has been demonstrated, where histone acetylation increases at active gene loci. However, the direct consequences of specific histone acetylation marks and the chromatin pathway that influences transcriptional regulation in response to the modification are unclear. As a reader of lysine acetylation, the bromodomain serves as a mediator between the acetylated histone and transcriptional regulators. Here we show that the bromodomain protein, TgBDP1, which is conserved among Apicomplexa and within the Alveolata superphylum, is essential for
Toxoplasma
asexual proliferation. Using cleavage under targets and tagmentation, we demonstrate that TgBDP1 is recruited to transcriptional start sites of a large proportion of parasite genes. Transcriptional profiling during TgBDP1 knockdown revealed that loss of TgBDP1 leads to major dysregulation of gene expression, implying multiple roles for TgBDP1 in both gene activation and repression. This is supported by interactome analysis of TgBDP1 demonstrating that TgBDP1 forms a core complex with two other bromodomain proteins and an ApiAP2 factor. This core complex appears to interact with other epigenetic factors such as nucleosome remodeling complexes. We conclude that TgBDP1 interacts with diverse epigenetic regulators to exert opposing influences on gene expression in the
Toxoplasma
tachyzoite.

IMPORTANCE

Histone acetylation is critical for proper regulation of gene expression in the single-celled eukaryotic pathogen
Toxoplasma gondii
. Bromodomain proteins are “readers” of histone acetylation and may link the modified chromatin to transcription factors. Here, we show that the bromodomain protein TgBDP1 is essential for parasite survival and that loss of TgBDP1 results in global dysregulation of gene expression. TgBDP1 is recruited to the promoter region of a large proportion of parasite genes, forms a core complex with two other bromodomain proteins, and interacts with different transcriptional regulatory complexes. We conclude that TgBDP1 is a key factor for sensing specific histone modifications to influence multiple facets of transcriptional regulation in
Toxoplasma gondii
.
Symbiosis of Carpenter Bees with Uncharacterized Lactic Acid Bacteria Showing NAD Auxotrophy
Authors: Kawasaki Shinji , Ozawa Kaori , Mori Tatsunori , Yamamoto Arisa , Ito Midoriko , Ohkuma Moriya , Sakamoto Mitsuo , Matsutani Minenosuke
Published: June 2023

Recent investigations found unique microbiomes in carpenter bees, but the description of individual microbes, including isolation and genomics, remains largely unknown. Here, we found that the Japanese
Xylocopa
species also harbor core gut microbiomes.
Supplemental Material: Limited sulfur degassing and muted environmental impact of Ontong Java Plateau lavas
Authors: Eguchi James , al. et
Published: June 2023

Detailed methods and spreadsheets with data used in main text.  
Supplemental Material: Li isotope ratios of spring fluids as an effective tracer of slab-derived subducted sources across the Costa Rica forearc
Authors: Helper Jacob P. , Barnes Jaime , al. et
Published: June 2023

Detailed methods, Figures S1–S3, Tables S1–S4.  
Associations between modest reductions in kidney function and adverse outcomes in young adults: retrospective, population based cohort study
Authors: Hussain Junayd , Grubic Nicholas , Akbari Ayub , Canney Mark , Elliott Meghan J , Ravani Pietro , Tanuseputro Peter , Clark Edward G , Hundemer Gregory L , Ramsay Tim , Tangri Navdeep , Knoll Greg A , Sood Manish M
Published: June 2023

Objective

To study age specific associations of modest reductions in estimated glomerular filtration rate (eGFR) with adverse outcomes.

Design

Retrospective, population based cohort study.

Setting

Linked healthcare administrative datasets in Ontario, Canada.

Participants

Adult residents (18-65 years) with at least one outpatient eGFR value (categorized in 10 unit increments from 50 mL/min/1.73m
2
to >120 mL/min/1.73m
2
), with no history of kidney disease.

Main outcome measures

eGFRs and hazard ratios of composite adverse outcome (all cause mortality, any cardiovascular event, and kidney failure) stratified by age (18-39 years, 40-49 years, and 50-65 years), and relative to age specific eGFR referents (100-110 mL/min/1.73m
2
) for ages 18-39 years, 90-100 for 40-49 years, 80-90 for 50-65 years).

Results

From 1 January 2008 to 31 March 2021, among 8 703 871 adults (mean age 41.3 (standard deviation 13.6) years; mean index eGFR 104.2 mL/min/1.73m
2
(standard deviation 16.1); median follow-up 9.2 years (interquartile range 5.7-11.4)), modestly reduced eGFR measurements specific to age were recorded in 18.0% of those aged 18-39, 18.8% in those aged 40-49, and 17.0% in those aged 50-65. In comparison with age specific referents, adverse outcomes were consistently higher by hazard ratio and incidence for ages 18-39 compared with older groups across all eGFR categories. For modest reductions (eGFR 70-80 mL/min/1.73m
2
), the hazard ratio for ages 18-39 years was 1.42 (95% confidence interval 1.35 to 1.49), 4.39 per 1000 person years; for ages 40-49 years was 1.13 (1.10 to 1.16), 9.61 per 1000 person years; and for ages 50-65 years was 1.08 (1.07 to 1.09), 23.4 per 1000 person years. Results persisted for each individual outcome and in many sensitivity analyses.

Conclusions

Modest eGFR reductions were consistently associated with higher rates of adverse outcomes. Higher relative hazards were most prominent and occurred as early as eGFR <80 mL/min/1.73m
2
in younger adults, compared with older groups. These findings suggest a role for more frequent monitoring of kidney function in younger adults to identify individuals at risk to prevent chronic kidney disease and its complications.
Subsidised housing and diabetes mortality: a retrospective cohort study of 10 million low-income adults in Brazil
Authors: Flores-Ortiz Renzo , Fiaccone Rosemeire L , Leyland Alastair , Millett Christopher , Hone Thomas , Schmidt Maria Inês , Ferreira Andrêa J F , Ichihara Maria Y , Teixeira Camila , Sanchez Mauro N , Pescarini Julia , Aquino Estela M L , Malta Deborah C , Velasquez-Melendez Gustavo , de Oliveira Juliane Fonseca , Craig Peter , Ribeiro-Silva Rita C , Barreto Mauricio L , Katikireddi Srinivasa Vittal
Published: June 2023

Introduction

Housing-related factors can be predictors of health, including of diabetes outcomes. We analysed the association between subsidised housing residency and diabetes mortality among a large cohort of low-income adults in Brazil.

Research design and methods

A cohort of 9 961 271 low-income adults, observed from January 2010 to December 2015, was created from Brazilian administrative records of social programmes and death certificates. We analysed the association between subsidised housing residency and time to diabetes mortality using a Cox model with inverse probability of treatment weighting and regression adjustment. We assessed inequalities in this association by groups of municipality Human Development Index. Diabetes mortality included diabetes both as the underlying or a contributory cause of death.

Results

At baseline, the mean age of the cohort was 40.3 years (SD 15.6 years), with a majority of women (58.4%). During 29 238 920 person-years of follow-up, there were 18 775 deaths with diabetes as the underlying or a contributory cause. 340 683 participants (3.4% of the cohort) received subsidised housing. Subsidised housing residents had a higher hazard of diabetes mortality compared with non-residents (HR 1.17; 95% CI 1.05 to 1.31). The magnitude of this association was more pronounced among participants living in municipalities with lower Human Development Index (HR 1.30; 95% CI 1.04 to 1.62).

Conclusions

Subsidised housing residents had a greater risk of diabetes mortality, particularly those living in low socioeconomic status municipalities. This finding suggests the need to intensify diabetes prevention and control actions and prompt treatment of the diabetes complications among subsidised housing residents, particularly among those living in low socioeconomic status municipalities.
‘You have to use everything and come to some equilibrium’: a qualitative study on hypoglycemia self-management in users of continuous glucose monitor with diverse hypoglycemia experiences
Authors: Lin Yu Kuei , Agni Annika , Chuisano Samantha , de Zoysa Nicole , Fetters Michael , Amiel Stephanie A , Pop-Busui Rodica , DeJonckheere Melissa
Published: June 2023

Introduction

Although continuous glucose monitoring systems (CGMs) can help reduce hypoglycemia, about one-quarter of people with type 1 diabetes (T1D) who use CGMs still either spend at least 1% of the time with dangerously low blood glucose or develop severe hypoglycemia. This study explored experiences around hypoglycemia self-management in people who are living with T1D and using CGMs to identify factors contributing to hypoglycemia development.

Research design and methods

Purposive sampling and semistructured interviews with 28 respondents with T1D and using CGMs were conducted to explore experiences around hypoglycemic episodes and hypoglycemia self-management during CGM use. Open coding and thematic analysis were employed to identify emergent themes related to hypoglycemia experiences.

Results

About one-third of respondents each respectively spent 0%, 0.1%–0.9% and ≥1% of time in level 2 hypoglycemia; 39% had impaired awareness of hypoglycemia and 32% had severe hypoglycemia in the past 6 months. Four themes were generated: (1) prioritizing symptoms over CGM data (subthemes: hypoglycemia symptoms for confirming hypoglycemia and prompting management actions; minimal management actions without hypoglycemia symptoms); (2) distraction from the demands of daily life; (3) concerns about hypoglycemia management choices (subthemes: fear of rebound hyperglycemia; other health consequences related to sugary food consumption; aversions to treatment foods and treatment food consumption); and (4) social influences on management choices (subthemes: positively perceived social support and inclusion; unwanted attention to oneself or concerns about inconveniencing others; social stigma and criticism related to hypoglycemia and CGM use).

Conclusions

Despite using CGMs, people with T1D can face a complex biopsychosocial process of managing hypoglycemia. Interventions for addressing psychosocial and behavioral barriers are needed to improve hypoglycemia self-management in those who continue to face challenges in minimizing hypoglycemia while using CGMs.
Implementation of point-of-care testing and prevalence of cryptococcal antigenaemia among patients with advanced HIV disease in Mumbai, India
Authors: Acharya Shrikala , Allam Ramesh Reddy , Karanjkar Vijay Kumar , Rathod Dhirubhai , Mahajan Raman , Deshpande Prashant , Palkar Amol , Todmal Shashikant , Koli Sagar , Dhande Sachin , Dale Jayesh , Yeldandi Vijay V , Harshana Amit , Agarwal Reshu , Upadhyaya Sunita , Nyendak Melissa
Published: June 2023

Objectives

To describe the implementation of screening for cryptococcal antigenaemia by point-of-care (POC) serum cryptococcal antigen (CrAg) lateral flow assay, measure the prevalence and factors associated with serum cryptococcal antigenaemia in the routine programmatic setting.

Design

Cross-sectional study.

Setting

Seventeen publicly funded antiretroviral therapy (ART) centres in Mumbai, India.

Participants

Serum CrAg screening was offered to all adolescents (>10 years of age) and adults with advanced HIV disease (AHD) (CD4 <200 cells/mm3or with WHO clinical stage III/IV) regardless of symptoms of cryptococcal meningitis.

Primary and secondary outcome measures

The primary outcome was to describe the implementation of serum CrAg screening and secondary outcome was to measure the prevalence of serum cryptococcal antigenaemia and its risk factors.

Results

A total of 2715 patients with AHD were tested for serum CrAg by POC assay. Of these, 25 (0.9%) had a CrAg positive result. Among CrAg-positive patients, only one had symptoms. Serum CrAg positivity was 3.6% (6/169) and 1.6% (6/520) among those presenting with CD4 <100 cells/mm3in the treatment naïve and treatment experienced group, respectively. On multivariable analysis, CD4 count <100 cells/mm3(OR: 2.3, 95% CI 1.01 to 5.3; p=0.05) and people living with HIV who were treatment naïve (OR: 2.5, 95% CI 1.04 to 6.0; p=0.04) were significantly associated with a positive serum CrAg result. Lumbar puncture was obtained in 20/25 patients within 4 days (range: 1–4 days) of positive serum CrAg result and one person was confirmed to have meningitis. All serum CrAg-positive patients who had a negative cerebrospinal fluid CrAg were offered pre-emptive therapy.

Conclusions

Implementation of a POC CrAg assay was possible with existing ART centre staff. Initiation of pre-emptive therapy and management of cryptococcal antigenaemia are operationally feasible at ART centres. The Indian National AIDS Control Programme may consider reflexive CrAg screening of all AHD patients with CD4 <100 cells/mm3.
Feasibility study and determination of prerequisites of telecare programme to enhance patient management in lung transplantation: a qualitative study from the perspective of Iranian healthcare providers
Authors: Gholamzadeh Marsa , Safdari Reza , Amini Shahideh , Abtahi Hamidreza
Published: June 2023

Background

Non-adherence to treatment plans, follow-up visits and healthcare advice is a common obstacle in the management of lung transplant patients. This study aims to investigate experts’ views on the needs and main aspects of telecare programmes for lung transplantation.

Design

A qualitative study incorporating an inductive thematic analysis.

Setting

Lung transplant clinic and thoracic research centre.

Participants

Clinicians: four pulmonologists, two cardiothoracic surgeons, two general physicians, two pharmacotherapists, one cardiologist, one nurse and one medical informatician.

Method

This study adopted a focus group discussion technique to gather experts’ opinions on the prerequisites and features of a telecare programme in lung transplantation. All interviews were coded and combined into main categories and themes. Thematic analysis was performed to extract the key concepts using ATLAS.Ti. Ultimately, all extracted themes were integrated to devise a conceptual model.

Results

Ten focus groups with 13 participants were conducted. Forty-six themes and subthemes were extracted through the thematic analysis. The main features of the final programme were extracted from expert opinions through thematic analysis, such as continuous monitoring of symptoms, drug management, providing a specific care plan for each patient, educating patients module, creating an electronic medical record to collect patient information, equipping the system with decision support tools, smart electronic prescription and the ability to send messages to the care team. The prerequisites of the system were summarised in self-care activities, clinician’s tasks and required technologies. In addition, the barriers and benefits of using a telecare system to enhance the quality of care were determined.

Conclusion

Our investigation recognised the main factors that must be considered to design a telecare programme to provide ideal continuous care for lung transplant patients. Users should further explore the proposed model to support the development of telecare interventions at the point of care.
Sex differences in sledging injuries: a retrospective 10-season study from a Swiss level 1 trauma centre
Authors: Klukowska-Rötzler Jolanta , Buerzle Annika , Exadaktylos Aristomenis Konstantinos , Niemann Steffen , Bürgi Flavia , Jakob Dominik Andreas
Published: June 2023

Objectives

Sledging is a popular and traditional winter sport in Switzerland. This study examines injury patterns of patients who presented to a tertiary trauma centre in Switzerland following sledging trauma, focusing on sex differences.

Methods

Retrospective single-centre study over 10 winters (2012–2022), including all patients experiencing sledging-related trauma. Injury history was collected and analysed from the patient data and demographic information. The Abbreviated Injury Scale and the Injury Severity Score (ISS) were used to classify injury types and severity.

Results

193 patients were identified with sledging injuries. The median age was 46 (IQR 28–65), and 56% were female. The most frequent mechanism of injury was a fall (70%), followed by collision (27%) and other fall on slopes (6%). Lower extremities (36%), trunk (20%) and head/neck (15%) were the most frequently injured body areas. Fourteen per cent of patients were admitted with head injuries, whereas females were significantly more likely to present with head injuries than males (p=0.047). Males were significantly more often admitted with fractures to the upper extremities than females (p=0.049). The median ISS was 4 (IQR 1–5), without significant differences between males and females (p=0.290). The hospital admission rate was 28.5% for sledging-related injuries. The median length of stay for patients admitted to the hospital was 5 (IQR 4–8) days. The total cost for all patients was CHF1 292 501, with a median of CHF1009 per patient (IQR CHF458–CHF5923).

Conclusion

Sledging injuries are common and may result in serious injuries. The lower extremities, trunk and head/neck are frequently injured and could be specifically protected with safety devices. Multiple injuries were statistically more frequent in women compared with men. Males were significantly more often admitted with fractures to the upper extremities, and females were more likely to sustain head injuries. The findings can help to develop data-driven measures to prevent sledging accidents in Switzerland.
Systematic review of preoperative n-3 fatty acids in major gastrointestinal surgery
Authors: George Jason , White Daniel , Fielding Barbara , Scott Michael , Rockall Timothy , Whyte Martin Brunel
Published: June 2023

Objectives

Perioperative nutrition aims to replenish nutritional stores before surgery and reduce postoperative complications. ‘Immunonutrition’ (including omega-3 fatty acids) may modulate the immune system and attenuate the postoperative inflammatory response. Hitherto, immunonutrition has overwhelmingly been administered in the postoperative period—however, this may be too late to provide benefit.

Design

A systematic literature search using MEDLINE and EMBASE for randomized controlled trials (RCTs).

Setting

Perioperative major gastrointestinal surgery.

Participants

Patients undergoing major gastrointestinal surgery.

Interventions

Omega-3 fatty acid supplementation commenced in the preoperative period, with or without continuation into postoperative period.

Main outcome measures

The effect of preoperative omega-3 fatty acids on inflammatory response and clinical outcomes.

Results

833 studies were identified. After applying inclusion and exclusion criteria, 12 RCTs, involving 1456 randomized patients, were included. Ten articles exclusively enrolled patients with cancer. Seven studies used a combination of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) as the intervention and five studies used EPA alone. Eight out of 12 studies continued preoperative nutritional support into the postoperative period.

Of the nine studies reporting mortality, no difference was seen. Duration of hospitalisation ranged from 4.5 to 18 days with intervention and 3.5 to 23.5 days with control. Omega-3 fatty acids had no effect on postoperative C-reactive protein and the effect on cytokines (including tumor necrosis factor-α, interleukin (IL)-6 and IL-10) was inconsistent. Ten of the 12 studies had low risk of bias, with one study having moderate bias from allocation and blinding.

Conclusions

There is insufficient evidence to support routine preoperative omega-3 fatty acid supplementation for major gastrointestinal surgery, even when this is continued after surgery.

PROSPERO registration number

CRD42018108333.
Genomic approaches to cancer and minimal residual disease detection using circulating tumor DNA
Authors: Semenkovich Nicholas P , Szymanski Jeffrey J , Earland Noah , Chauhan Pradeep S , Pellini Bruna , Chaudhuri Aadel A
Published: June 2023

Liquid biopsies using cell-free circulating tumor DNA (ctDNA) are being used frequently in both research and clinical settings. ctDNA can be used to identify actionable mutations to personalize systemic therapy, detect post-treatment minimal residual disease (MRD), and predict responses to immunotherapy. ctDNA can also be isolated from a range of different biofluids, with the possibility of detecting locoregional MRD with increased sensitivity if sampling more proximally than blood plasma. However, ctDNA detection remains challenging in early-stage and post-treatment MRD settings where ctDNA levels are minuscule giving a high risk for false negative results, which is balanced with the risk of false positive results from clonal hematopoiesis. To address these challenges, researchers have developed ever-more elegant approaches to lower the limit of detection (LOD) of ctDNA assays toward the part-per-million range and boost assay sensitivity and specificity by reducing sources of low-level technical and biological noise, and by harnessing specific genomic and epigenomic features of ctDNA. In this review, we highlight a range of modern assays for ctDNA analysis, including advancements made to improve the signal-to-noise ratio. We further highlight the challenge of detecting ultra-rare tumor-associated variants, overcoming which will improve the sensitivity of post-treatment MRD detection and open a new frontier of personalized adjuvant treatment decision-making.