bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of lipoprotein subclasses with risk of all‐cause and cardiovascular disease mortality in individuals with type 2 diabetes: A prospective cohort study
Authors: Li Rui , Chen Jun‐Xiang , Lu Qi , Geng Ting‐Ting , Xia Peng‐Fei , Wang Yi , Chen Liang‐Kai , Shan Zhi‐Lei , Pan An , Liu Gang
Published: July 2023

Aim

Although lipoproteins are well‐established risk factors for cardiovascular disease (CVD) mortality, conventional measurements failed to identify lipoprotein particle sizes. This study aimed to investigate associations of lipoprotein subclasses categorized by particle sizes with risk of all‐cause and CVD mortality in individuals with type 2 diabetes.

Methods

This study included 6575 individuals with type 2 diabetes from the UK Biobank. Concentrations of very low‐, low‐, intermediate‐ and high‐density lipoprotein [very‐low‐density lipoprotein (VLDL), low‐density lipoprotein (LDL), intermediate‐density lipoprotein and high‐density lipoprotein (HDL)] particles in 14 subclasses and lipid constituents within each subclass were measured by quantitative nuclear magnetic resonance. Multivariable‐adjusted Cox proportional‐hazard regression models were used to estimate the hazard ratio (HR) for per standard deviation increment of log‐transformed lipoprotein subclasses with risk of mortality. Allp‐values were adjusted by the false discovery rate method.

Results

During a median follow‐up of 11.4 years, 943 deaths were documented, including 310 CVD deaths. Small HDL particles were inversely associated with CVD mortality, with HR (95% CI) of 0.78 (0.69, 0.87), whereas very large and large HDL particles were positively associated with CVD mortality with HR (95% CI) of 1.28 (1.12, 1.45) and 1.19 (1.05, 1.35), respectively. A similar pattern was observed for all‐cause mortality [small HDL particle (HR, 95% CI): 0.79, 0.74‐0.85; large HDL particle: 1.15, 1.07‐1.24; very large HDL particle: 1.26, 1.17‐1.36]. For VLDL and LDL, very small VLDL particle was positively, while medium LDL particle was inversely associated with all‐cause mortality, but not associated with CVD mortality. The pattern of association with all‐cause and CVD mortality for cholesterol and triglyceride within lipoprotein particles was similar to those for lipoprotein particles themselves.

Conclusions

The associations between lipoprotein particles, particularly HDL particles, with all‐cause and CVD mortality among patients with type 2 diabetes were significantly varied by particle sizes, highlighting the importance of particle size as a lipoprotein metric in mortality risk discrimination.
Hot money inflows and bank risk‐taking: Germany from the 1920s to the Great Depression
Authors: Postel‐Vinay Natacha , Collet Stéphanie
Published: July 2023

This paper explores the origins of German banks’ risk‐taking in the years preceding the 1931 crisis. The 1920s were marked by a large and prolonged increase in capital flows into Germany, chiefly from the United States and the United Kingdom. This coincided, at the individual bank level, with a rise in leverage and a fall in liquidity. We examine possible connections between the two phenomena. Our analysis is based on a combination of historiographical work and statistical modelling based on a newly hand‐collected bimonthly dataset on German reporting banks from 1925 to 1935. Bank by bank we examine the effects of foreign inflows on decisions related to leverage, lending, and liquidity. The Dawes Plan of 1924 and the relative absence of a too‐big‐to‐fail (TBTF) environment allow us to mitigate endogeneity concerns. We suggest that while capital inflows did not seem to impact banks’ liquidity decisions, their impact on leverage was non‐negligeable.
Long‐term clinical outcomes and healthcare utilization of sickle cell disease patients with COVID‐19: A 2.5‐year follow‐up study
Authors: Feit Avery , Gordon Moshe , Alamuri Tharun T. , Hou Wei , Mitchell William B. , Manwani Deepa , Duong Tim Q.
Published: July 2023

Objectives

This study investigated whether patients with sickle cell disease (SCD) had elevated risk of worse long‐term clinical outcomes and healthcare utilization 2.5 years post‐SARS‐CoV‐2 infection.

Methods

This study consisted of 178 patients with SCD who tested positive for COVID‐19 between February 1, 2020 and January 30, 2022 in a major academic health system in New York City. The control cohort consisted of two‐to‐one matches of 356 SCD patients without a COVID‐19 positive test. The last follow‐up was July 18, 2022. The primary outcome was mortality. Secondary outcomes were annualized emergency department visits due to pain, pain hospital admission, length of stay due to pain, acute chest syndrome, episodic transfusion, and episodic exchange transfusion.

Results

There was no significant difference in mortality between SCD patients with and without COVID‐19 (p > .05). There were no significant differences in secondary outcomes between pre‐ and postpandemic (p > .05). There were also no significant differences in these outcomes between SCD patients with and without COVID‐19 (p > .05). SCD care utilization was not significantly associated with COVID‐19 hospitalization status (p > .05).

Conclusions

SCD patients with SARS‐CoV‐2 infection incurred no additional risk of worse long‐term outcomes compared to matched controls of SCD patients not infected by SARS‐CoV‐2.
Calibrating epigenetic clocks with training data error
Authors: Mayne Benjamin , Berry Oliver , Jarman Simon
Published: July 2023

Animal age data are valuable for management of wildlife populations. Yet, for most species, there is no practical method for determining the age of unknown individuals. However, epigenetic clocks, a molecular‐based method, are capable of age prediction by sampling specific tissue types and measuring DNA methylation levels at specific loci. Developing an epigenetic clock requires a large number of samples from animals of known ages. For most species, there are no individuals whose exact ages are known, making epigenetic clock calibration inaccurate or impossible. For many epigenetic clocks, calibration samples with inaccurate age estimates introduce a degree of error to epigenetic clock calibration. In this study, we investigated how much error in the training data set of an epigenetic clock can be tolerated before it resulted in an unacceptable increase in error for age prediction. Using four publicly available data sets, we artificially increased the training data age error by iterations of 1% and then tested the model against an independent set of known ages. A small effect size increase (Cohen's d >0.2) was detected when the error in age was higher than 22%. The effect size increased linearly with age error. This threshold was independent of sample size. Downstream applications for age data may have a more important role in deciding how much error can be tolerated for age prediction. If highly precise age estimates are required, then it may be futile to embark on the development of an epigenetic clock when there is no accurately aged calibration population to work with. However, for other problems, such as determining the relative age order of pairs of individuals, a lower‐quality calibration data set may be adequate.
Democratizing accounting technologies: A case of a performance evaluation system for academics
Authors: Mai Kate Thuy , Hoque Zahirul
Published: July 2023

This paper explores how a country's constitutionally imposed democracy in an academic performance evaluation system was designed and practiced. Building upon agonistic democracy and deliberative democracy perspectives, a qualitative inductive case study in a Vietnamese public university involved 52 interviews, direct observations, and the analysis of archival documents. The findings revealed three dimensions of democracy in the university's performance evaluation system, namely, democratic context, democratic discourse, and democratic outcomes. The university enforced democracy in its performance evaluation system for academics in line with the country's constitutional obligation. In such an explicit democratic context, there happened democratic discourse (debating academics’ performance in public forums) and implicit discourse (informal social interactions). The outcome of this democracy at the practice level resulted from temporary consensus supported by shared cultural values within the country's socio‐political context with an understanding that it will change as with any change in the macro or micro contexts. These findings contribute to the literature by providing insights into how individuals pursue democracy in an accounting tool legally built to promote democracy through their multiple voices and collective wisdom. Thus, democratizing accounting technologies and processes, such as an academic performance evaluation system, can effectively promote democracy in multi‐cultural workplaces across the globe.
Global warming and arctic terns: Estimating climate change impacts on the world's longest migration
Authors: Morten Joanne M. , Buchanan Pearse J. , Egevang C. , Glissenaar Isolde A. , Maxwell Sara M. , Parr Nicole , Screen James A. , Vigfúsdóttir Freydís , Vogt‐Vincent Noam S. , Williams Daniel A. , Williams Ned C. , Witt Matthew J. , Hawkes Lucy A. , Thurston William
Published: July 2023

Climate change is one of the top three global threats to seabirds, particularly species that visit polar regions. Arctic terns migrate between both polar regions annually and rely on productive marine areas to forage, on sea ice for rest and foraging, and prevailing winds during flight. Here, we report 21st‐century trends in environmental variables affecting arctic terns at key locations along their Atlantic/Indian Ocean migratory flyway during the non‐breeding seasons, identified through tracking data. End‐of‐century climate change projections were derived from Earth System Models and multi‐model means calculated in two Shared Socioeconomic Pathways: ‘middle‐of‐the‐road’ and ‘fossil‐fuelled development’ scenarios. Declines in North Atlantic primary production emerge as a major impact to arctic terns likely to affect their foraging during the 21st century under a ‘fossil‐fuelled development’ scenario. Minimal changes are, however, projected at three other key regions visited by arctic terns (Benguela Upwelling, Subantarctic Indian Ocean and the Southern Ocean). Southern Ocean sea ice extent is likely to decline, but the magnitude of change and potential impacts on tern survival are uncertain. Small changes (<1 m s−1) in winds are projected in both scenarios, but with minimal likely impacts on migration routes and duration. However, Southern Ocean westerlies are likely to strengthen and contract closer to the continent, which may require arctic terns to shift routes or flight strategies. Overall, we find minor effects of climate change on the migration of arctic terns, with the exception of poorer foraging in the North Atlantic. However, given that arctic terns travel over huge spatial scales and live for decades, they integrate minor changes in conditions along their migration routes such that the sum effect may be greater than the parts. Meeting carbon emission targets is vital to slow these end‐of‐century climatic changes and minimise extinction risk for a suite of polar species.
BioDeepTime: A database of biodiversity time series for modern and fossil assemblages
Authors: Smith Jansen , Rillo Marina C. , Kocsis Ádám T. , Dornelas Maria , Fastovich David , Huang Huai‐Hsuan M. , Jonkers Lukas , Kiessling Wolfgang , Li Qijian , Liow Lee Hsiang , Margulis‐Ohnuma Miranda , Meyers Stephen , Na Lin , Penny Amelia M. , Pippenger Kate , Renaudie Johan , Saupe Erin E. , Steinbauer Manuel J. , Sugawara Mauro , Tomašovỳch Adam , Williams John W. , Yasuhara Moriaki , Finnegan Seth , Hull Pincelli M.
Published: July 2023

Motivation

We have little understanding of how communities respond to varying magnitudes and rates of environmental perturbations across temporal scales. BioDeepTime harmonizes assemblage time series of presence and abundance data to help facilitate investigations of community dynamics across timescales and the response of communities to natural and anthropogenic stressors. BioDeepTime includes time series of terrestrial and aquatic assemblages of varying spatial and temporal grain and extent from the present‐day to millions of years ago.

Main Types of Variables Included

BioDeepTime currently contains 7,437,847 taxon records from 10,062 assemblage time series, each with a minimum of 10 time steps. Age constraints, sampling method, environment and taxonomic scope are provided for each time series.

Spatial Location and Grain

The database includes 8752 unique sampling locations from freshwater, marine and terrestrial ecosystems. Spatial grain represented by individual samples varies from quadrats on the order of several cm2to grid cells of ~100 km2.

Time Period and Grain

BioDeepTime in aggregate currently spans the last 451 million years, with the 10,062 modern and fossil assemblage time series ranging in extent from years to millions of years. The median extent of modern time series is 18.7 years and for fossil series is 54,872 years. Temporal grain, the time encompassed by individual samples, ranges from days to tens of thousands of years.

Major Taxa and Level of Measurement

The database contains information on 28,777 unique taxa with 4,769,789 records at the species level and another 271,218 records known to the genus level, including time series of benthic and planktonic foraminifera, coccolithophores, diatoms, ostracods, plants (pollen), radiolarians and other invertebrates and vertebrates. There are to date 7012 modern and 3050 fossil time series in BioDeepTime.

Software Format

SQLite, Comma‐separated values.
SAME/DIFFERENCE? TOWARD A SAPPHIC/NONBINARY SEXUALITY OF HISTORY
Authors: LANSER SUSAN S.
Published: July 2023

What is the next step when one has published a strong intervention in a field but later recognizes that one's angle of vision deserves new scrutiny? In this article, which began as a roundtable talk, I return to The Sexuality of History: Modernity and the Sapphic, 1565–1830 (2014) to interrogate its “same‐sex” logic through a nonbinary/trans lens. My book argues that seventeenth‐ and eighteenth‐century representations of the sapphic became a flash point for European cultures grappling with questions of power and governance, desire and duty, mobility and difference in an age of colonialism, racial capitalism, revolution, and reaction. In figuring the sapphic exclusively through notions of sameness, however, The Sexuality of History does not do justice to trans and nonbinary figures both historical and fictional. Is there a place among sapphic subjects for these figures, and, if so, with what implications? I argue here for a both/and approach that requires recoding certain figures as nonbinary while still insisting on their efficacy as signs of the sapphic. This recoding encourages a more nuanced exploration of the cultural work performed by sapphic representations and a more expansive conception of what I have called a sapphic episteme. Such revisionist thinking may be useful at a time of social and theoretical tensions at the intersections of “lesbian” and “trans.”
Safety and efficacy of AK0529 in respiratory syncytial virus‐infected infant patients: A phase 2 proof‐of‐concept trial
Authors: Huang Li‐Min , Schibler Andreas , Huang Yi‐Chuan , Tai Andrew , Chi Hsin , Chieng Chae‐Hee , Wang Jinn‐Li , Goldbart Aviv , Tang Swee‐Ping , Huang Yhu‐Chering , George Shane , Alabaz Derya , Bentur Lea , Su Siew‐Choo , de Bruyne Jessie , Karadag Bulent , Gu Feng , Zou Gang , Toovey Stephen , DeVincenzo John P. , Wu Jim Z.
Published: July 2023

Background

Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality in young children. There is currently no effective therapy available.

Methods

This was a Phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1–24 months, hospitalized with RSV infection. In Part 1, patients (n = 24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In Part 2, patients (n = 48) were randomized 2:1 to receive AK0529 at 0.5, 1, or 2 mg/kg bid or placebo for 5 days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, and respiratory signs and symptoms were assessed daily during treatment.

Results

No safety or tolerability signals were detected for AK0529: grade ≥3 treatment‐emergent adverse events occurring in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In Part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 h was observed. A −4.0 (95% CI: −4.51, −2.03) median reduction in Wang Respiratory Score from baseline to 96 h was observed in the 2 mg/kg group compared with −2.0 (95% CI: −3.42, −1.82) in the placebo group.

Conclusions

AK0529 was well tolerated in hospitalized RSV‐infected infant patients. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and Wang Respiratory Score.

Clinical Trials Registration

NCT02654171.
A meta‐analysis of the effect of laparoscopic gastric resection on the surgical site wound infection in patients with advanced gastric cancer
Authors: Han Xue , Kong Defeng , He Xuefeng , Xie Shiyu , Li Chunlin
Published: July 2023

By conducting a meta‐analysis of relevant clinical studies on the treatment of advanced gastric cancer (GC) using laparoscopic and open surgeries, we aimed to evaluate the impact of these two surgical approaches on postoperative surgical site infections (SSIs) in patients with advanced GC. We aimed to provide evidence‐based support for preventing SSIs in postoperative patients with advanced GC. From database establishment until May 2023, we systematically searched PubMed, Cochrane Library, MEDLINE, Embase, China National Knowledge Infrastructure, and Wanfang Data databases for relevant studies comparing laparoscopic and open surgeries for the treatment of advanced GC. Two researchers independently performed the literature screening and data extraction based on predefined inclusion and exclusion criteria. The meta‐analysis was conducted using STATA 17.0. Twenty articles involving 3084 patients met the inclusion criteria, including 1462 patients in the laparoscopic group and 1622 cases in the open surgery group. The meta‐analysis results revealed that the incidence of postoperative SSIs was significantly lower in the laparoscopic group than in the open surgery group (odds ratio = 0.341, 95% confidence interval: 0.219–0.532, p < 0.001). The current evidence indicates that laparoscopic radical gastrectomy can significantly reduce the incidence of postoperative site infections in patients with advanced GC.
Screening of the shared pathogenic genes of ulcerative colitis and colorectal cancer by integrated bioinformatics analysis
Authors: Shi Xu , Yu Jun , Lu Chen , Luo Qian , Xu Caihong , Li Jie , Wang Wei
Published: July 2023

Ulcerative colitis (UC) is one of the high‐risk pathogenic factors for colorectal cancer (CRC). However, the shared gene and signalling mechanisms between UC and CRC remain unclear. The goal of this study was to delve more into the probable causal relationship between UC and CRC. CRC and UC datasets were downloaded from the Gene Expression Omnibus database. Using R software and Perl, differentially expressed genes (DEGs) in both UC and CRC tissues were re‐annotated and screened. The biological activities and signalling pathways involved in DEGs were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The STRING database and Cytoscape software were used to construct the gene interaction network. A total of 384 DEGs were selected for further investigation, and functional analysis revealed that inflammatory and immunological responses were crucial in the development of the two diseases. Moreover, the top 15 key genes involved in the UC and CRC were screened using cytoHubba, including IL1B, CXCL10, CCL20, MMP9, ICAM1, CCL4, CXCR1, MMP3, TLR2, PTGS2, IL1RN, IL6, COL1A2, TIMP1 and CXCL1. The identification of these genes in the present study may provide a novel perspective for the prediction, prevention and personalized medicine of UC and CRC patients.
Successful introduction of sensor‐augmented pump therapy in a patient with diabetes and needle phobia: A case report
Authors: Sugai Keiji , Shikuma Junpei , Hiroike Satoshi , Abe Hironori , Suzuki Ryo
Published: July 2023

Needle phobia is a specific phobia classified as an anxiety disorder in the Diagnostic and Statistical Manual of Mental Disorders‐5, and can be a serious problem for patients requiring insulin injections. However, there have been few reports to date on the management of adults with diabetes and needle phobia. We here report a case of a woman with pancreatic diabetes who developed needle phobia and could no longer perform self‐injections. She started to use a sensor‐augmented pump (SAP), and was able to perform a puncture for the insulin pump and the continuous glucose monitoring sensor by herself. The SAP treatment achieved self‐management, better glycemic control, and high treatment satisfaction quantified using the Diabetes Treatment Satisfaction Questionnaire in this patient. Our case suggests the therapeutic potential of SAP in adults with needle phobia and diabetes requiring insulin therapy.
Worn denture teeth of a full‐arch implant‐supported fixed dental prosthesis: A technique to restore
Authors: Goodrick Adam M. , Nadjmi Sassan
Published: July 2023

Worn denture teeth continue to be a significant complication with implant‐supported prostheses. This article discusses a case report that used an intraoral scanning system to restore an existing maxillary implant‐supported prosthesis with significant posterior occlusal wear.  IPS e.max (Ivoclar Vivadent, Schaan, Liechtenstein) restorations were fabricated and cemented to the prepared posterior denture teeth to re‐establish the occlusal vertical dimension and to help prevent further wear of the occlusal surfaces.
Bacterial infection‐related glomerulonephritis in patients with diabetes
Authors: John Elenjickal Elias , Roy Sanjeet , Eapen Jeethu Joseph , Karuppusami Reka , Jose Nisha , Mani Selvin Sundar Raj , Johny Joseph , Alam Rizwan , Yusuf Sabina , Thomas Athul , Valson Anna T. , David Vinoi George , Varughese Santosh , Alexander Suceena
Published: July 2023

Aim

Diabetic patients are prone to infections, thus making them a unique cohort at risk of developing bacterial infection‐related glomerulonephritis (IRGN).

Methods

In total, 1693 adult diabetic patients underwent kidney biopsy between 2005 and 2021 at our tertiary care hospital in South India. Of these, 121 consecutive cases which met criteria of bacterial IRGN were included in this study.

Results

The mean age of the cohort was 53.1 ± 10.1 years and 83/121 (68.5%) were males. Majority (98.3%) had type 2 diabetes for a median duration of 6 (IQR, 2–12) years. The most common sites of infection were skin (47/121, 38.8%) and urinary tract (15/121, 12.4%). Fifty percent (58/121) of patients had underlying advanced diabetic kidney disease (DKD). Isolated C3 deposits (without immunoglobulin) occurred in 66/121 (54.5%) patients predominantly in advanced DKD patients. IgA‐dominant glomerulonephritis occurred in only 9/121 (7.4%) patients. Short‐course oral steroid was given to 86/121 (71.1%) patients. Steroid related dysglycemia and immunosuppression related infections occurred in 9/61 (14.8%) and 16/61 (26.2%) patients respectively. Of the 90 patients with follow up details >3 months, 46 (51.1%) progressed to kidney failure over a median period of 0.5 (IQR, 0–7.2) months. Patients diagnosed in the latter half of our study period (2013–2021) were older, less commonly presented with fever, had more pronounced hypocomplementemia and severe renal histology predominantly with a ‘starry sky’ immunofluorescence pattern.

Conclusion

Superimposed bacterial IRGN on underlying DKD is associated with poor renal outcomes. Use of short course steroid was associated with significant toxicity.
Developmental diet, life stage and thermal acclimation affect thermal tolerance of the fall armyworm, Spodoptera frugiperda
Authors: Phungula Siphephelo M. , Krüger Kerstin , Nofemela Robert S. , Weldon Christopher W.
Published: July 2023

Insect thermal tolerance affects survival and distribution of species but can vary within and between individuals due to the environmental conditions they experience. The fall armyworm (FAW), Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), recently invaded Africa and its local hotspots are associated with weather and crop phenology. We investigated the effects of larval diet (maize plants, wheat plants or chickpea‐based artificial diet), life stages and acclimation temperature on thermal tolerance traits of FAW to explore how these variables might contribute to its presence in the field. First and sixth instar larvae and adults reared on each diet at 25°C were acclimated for 24 h at 20, 25 or 30°C. We then recorded the critical thermal minimum (CTmin) and critical thermal maximum (CTmax) of individuals. Sixth instars had the highest CTmin but the effects of acclimation and diet on this trait depended on the life stage being tested. CTmin of first instars increased with acclimation temperature when fed on an artificial diet, but sixth instars and adults were not affected by acclimation or larval diet. CTmax was lowest among adults but acclimation and diet again had effects that differed between life stages. CTmax of first instars and adults increased with acclimation temperature but not in sixth instars. Sixth instars and adults reared on the artificial diet had the highest CTmax but diet had no effect on first instar CTmax. Our results show the complexity of thermal tolerance across FAW life stages and suggest the need to consider local temperature variation and available dietary resources when predicting their potential distribution.
C‐type natriuretic peptide induces inotropic and lusitropic effects in human 3D‐engineered cardiac tissue: Implications for the regulation of cardiac function in humans
Authors: Bachmann Julian C. , Kirchhoff Jeppe E. , Napolitano Julia E. , Sorota Steve , Gordon William M. , Feric Nicole , Aschar‐Sobbi Roozbeh , Lv Juan , Cao Zhiyou , Coppieters Ken , Borghetti Giulia , Nyberg Michael
Published: July 2023

The role of C‐type natriuretic peptide (CNP) in the regulation of cardiac function in humans remains to be established as previous investigations have been confined to animal model systems. Here, we used well‐characterized engineered cardiac tissues (ECTs) generated from human stem cell‐derived cardiomyocytes and fibroblasts to study the acute effects of CNP on contractility. Application of CNP elicited a positive inotropic response as evidenced by increases in maximum twitch amplitude, maximum contraction slope and maximum calcium amplitude. This inotropic response was accompanied by a positive lusitropic response as demonstrated by reductions in time from peak contraction to 90% of relaxation and time from peak calcium transient to 90% of decay that paralleled increases in maximum contraction decay slope and maximum calcium decay slope. To establish translatability, CNP‐induced changes in contractility were also assessed in rat ex vivo (isolated heart) and in vivo models. Here, the effects on force kinetics observed in ECTs mirrored those observed in both the ex vivo and in vivo model systems, whereas the increase in maximal force generation with CNP application was only detected in ECTs. In conclusion, CNP induces a positive inotropic and lusitropic response in ECTs, thus supporting an important role for CNP in the regulation of human cardiac function. The high degree of translatability between ECTs, ex vivo and in vivo models further supports a regulatory role for CNP and expands the current understanding of the translational value of human ECTs.
Enhanced structural and optical properties of semipolar (112¯2) AlGaN film with insertion of AlN/AlGaN superlattice
Authors: Luo Xuguang , Zhang Xiong , Fang Ruiting , Chen Lin , Xu Shenyu , Cui Jia , Lou Zhiyi , Xu Yifeng , Wang Shuchang , Hu Guohua
Published: July 2023

The high-quality semipolar (112¯2) AlGaN films with high Al contents were successfully deposited on (101¯0) m-plane sapphire substrates with the insertion of AlN/AlGaN superlattice (SL) by metal-organic chemical vapor deposition technology. The dependence of structural and optical properties of the (112¯2) AlGaN film on the deposition parameters for the inserted AlN/AlGaN SL was investigated extensively premised on the characterization results of the optical microscope, atomic force microscopy, relative optical transmittance spectroscopy, high-resolution x-ray diffraction, and photoluminescence spectroscopy. It was discovered that the insertion of the AlN/AlGaN SL grown under an optimized stabilization time of 10 s between the deposition of AlN and AlGaN sublayers could be used to make significant enhancements in surface morphological characteristics, crystal quality, and optical properties of the (112¯2) AlGaN film. The mechanism for the defects reduction in the (112¯2) AlGaN film was revealed to be owing to the increase in bending and annihilating probability of the threading dislocations, basal-plane stacking faults, and other structural defects promoted by introducing sufficiently high desorbed Ga atom-induced vacancy concentration in the optimized thermal treatment process.
Stuck in a corner: Anthropogenic noise threatens narwhals in their once pristine Arctic habitat
Authors: Tervo Outi M. , Blackwell Susanna B. , Ditlevsen Susanne , Garde Eva , Hansen Rikke G. , Samson Adeline L. , Conrad Alexander S. , Heide-Jørgensen Mads Peter
Published: July 2023

Niche-conservative species are especially susceptible to changes in their environment, and detecting the negative effects of new stressors in their habitats is vital for safeguarding of these species. In the Arctic, human disturbance including marine traffic and exploration of resources is increasing rapidly due to climate change–induced reduction of sea ice. Here, we show that the narwhal,
Monodon monoceros
, is extremely sensitive to human-made noise. Narwhals avoided deep diving (> 350 m) with simultaneous reduction of foraging and increased shallow diving activity as a response to either ship sound alone or ship sound with concurrent seismic airgun pulses. Normal behavior decreased by 50 to 75% at distances where received sound levels were below background noise. Narwhals were equally responsive to both disturbance types, hence demonstrating their acute sensitivity to ship sound. This sensitivity coupled with their special behavioral-ecological strategy including a narrow ecological niche and high site fidelity makes them thus especially vulnerable to human impacts in the Arctic.
Phosphorylated nuclear DICER1 promotes open chromatin state and lineage plasticity of AT2 tumor cells in lung adenocarcinomas
Authors: Reyes-Castro Raisa A. , Chen Shin-Yu , Seemann Jacob , Kundu Samrat T. , Gibbons Don L. , Arur Swathi
Published: July 2023

KRAS/ERK pathway phosphorylates DICER1, causing its nuclear translocation, and phosphomimetic
Dicer1
contributes to tumorigenesis in mice. Mechanisms through which phospho-DICER1 regulates tumor progression remain undefined. While DICER1 canonically regulates microRNAs (miRNA) and epithelial-to-mesenchymal transition (EMT), we found that phosphorylated nuclear DICER1 (phospho–nuclear DICER1) promotes late-stage tumor progression in mice with oncogenic
Kras
, independent of miRNAs and EMT. Instead, we observe that the murine AT2 tumor cells exhibit altered chromatin compaction, and cells from disorganized advanced tumors, but not localized tumors, express gastric genes. Collectively, this results in subpopulations of tumor cells transitioning from a restricted alveolar to a broader endodermal lineage state. In human LUADs, we observed expression of phospho–nuclear DICER1 in advanced tumors together with the expression of gastric genes. We define a multimeric chromatin-DICER1 complex composed of the Mediator complex subunit 12, CBX1, MACROH2A.1, and transcriptional regulators supporting the model that phospho–nuclear DICER1 leads to lineage reprogramming of AT2 tumor cells to mediate lung cancer progression.
Cleavage of cFLIP restrains cell death during viral infection and tissue injury and favors tissue repair
Authors: Martinez Lagunas Kristel , Savcigil Deniz Pinar , Zrilic Matea , Carvajal Fraile Carlos , Craxton Andrew , Self Emily , Uranga-Murillo Iratxe , de Miguel Diego , Arias Maykel , Willenborg Sebastian , Piekarek Michael , Albert Marie Christine , Nugraha Kalvin , Lisewski Ina , Janakova Erika , Igual Natalia , Tonnus Wulf , Hildebrandt Ximena , Ibrahim Mohammed , Ballegeer Marlies , Saelens Xavier , Kueh Andrew , Meier Pascal , Linkermann Andreas , Pardo Julian , Eming Sabine , Walczak Henning , MacFarlane Marion , Peltzer Nieves , Annibaldi Alessandro
Published: July 2023

Cell death coordinates repair programs following pathogen attack and tissue injury. However, aberrant cell death can interfere with such programs and cause organ failure. Cellular FLICE-like inhibitory protein (cFLIP) is a crucial regulator of cell death and a substrate of Caspase-8. However, the physiological role of cFLIP cleavage by Caspase-8 remains elusive. Here, we found an essential role for cFLIP cleavage in restraining cell death in different pathophysiological scenarios. Mice expressing a cleavage-resistant cFLIP mutant,

Cflip
D377A

, exhibited increased sensitivity to severe acute respiratory syndrome coronavirus (SARS-CoV)–induced lethality, impaired skin wound healing, and increased tissue damage caused by
Sharpin
deficiency. In vitro, abrogation of cFLIP cleavage sensitizes cells to tumor necrosis factor(TNF)–induced necroptosis and apoptosis by favoring complex-II formation. Mechanistically, the cell death–sensitizing effect of the D377A mutation depends on glutamine-469. These results reveal a crucial role for cFLIP cleavage in controlling the amplitude of cell death responses occurring upon tissue stress to ensure the execution of repair programs.
Fractal-like geometry as an evolutionary response to predation?
Authors: Lemanis Robert , Zlotnikov Igor
Published: July 2023

Fractal-like, intricate morphologies are known to exhibit beneficial mechanical behavior in various engineering and technological domains. The evolution of fractal-like, internal walls of ammonoid cephalopod shells represent one of the most clear evolutionary trends toward complexity in biology, but the driver behind their iterative evolution has remained unanswered since the first hypotheses introduced in the early 1800s. We show a clear correlation between the fractal-like morphology and structural stability. Using linear and nonlinear computational mechanical simulations, we demonstrate that the increase in the complexity of septal geometry leads to a substantial increase in the mechanical stability of the entire shell. We hypothesize that the observed tendency is a driving force toward the evolution of the higher complexity of ammonoid septa, providing the animals with superior structural support and protection against predation. Resolving the adaptational value of this unique trait is vital to fully comprehend the intricate evolutionary trends between morphology, ecological shifts, and mass extinctions through Earth’s history.
Wrap-like transfer printing for three-dimensional curvy electronics
Authors: Chen Xingye , Jian Wei , Wang Zhijian , Ai Jun , Kang Yu , Sun Pengcheng , Wang Zhouheng , Ma Yinji , Wang Heling , Chen Ying , Feng Xue
Published: July 2023

Three-dimensional (3D) curvy electronics has wide-ranging application in biomedical health care, soft machine, and high-density curved imager. Limited by material properties, complex procedures, and coverage ability of existing fabrication techniques, the development of high-performance 3D curvy electronics remains challenging. Here, we propose an automated wrap-like transfer printing prototype for fabricating 3D curvy electronics. Assisted by a gentle and uniform pressure field, the prefabricated planar circuits on the petal-like stamp are integrated onto the target surface intactly with full coverage. The driving pressure for the wrapping is provided by the strain recovery of a prestrained elastic film triggered by the air pressure control. The wrapping configuration and strain distribution of the stamp are simulated by finite element analysis, and the pattern and thickness of the stamps are optimized. Demonstration of this strategy including spherical meander antenna, spherical light-emitting diode array, and spherical solar cell array illustrates its feasibility in the development of complex 3D curvy electronics.
A polysaccharide utilization locus from
Chitinophaga pinensis
simultaneously targets chitin and β-glucans found in fungal cell walls
Authors: Lu Zijia , Kvammen Alma , Li He , Hao Mengshu , Inman Annie R. , Bulone Vincent , McKee Lauren S.
Published: July 2023

In nature, complex carbohydrates are rarely found as pure isolated polysaccharides. Instead, bacteria in competitive environments are presented with glycans embedded in heterogeneous matrices such as plant or microbial cell walls. Members of the Bacteroidota phylum thrive in such ecosystems because they are efficient at extracting nutrients from complex substrates, secreting consortia of synergistic enzymes to release metabolizable sugars. Carbohydrate-binding modules (CBMs) are used to target enzymes to substrates, enhancing reaction rate and product release. Additionally, genome organizational tools like polysaccharide utilization loci (PULs) ensure that the appropriate set of enzymes is produced when needed. In this study, we show that the soil bacterium
Chitinophaga pinensis
uses a PUL and several CBMs to coordinate the activities of enzymes targeting two distinct polysaccharides found in fungal cell walls. We describe the enzymatic activities and carbohydrate-binding behaviors of components of the fungal cell wall utilization locus (FCWUL), which uses multiple chitinases and one β-1,3-glucanase to hydrolyze two different substrates. Unusually, one of the chitinases is appended to a β-glucan-binding CBM, implying targeting to a bulk cell wall substrate rather than to the specific polysaccharide being hydrolyzed. Based on our characterization of the PUL’s outer membrane sensor protein, we suggest that the FCWUL is activated by β-1,3-glucans, even though most of its enzymes are chitin-degrading. Our data showcase the complexity of polysaccharide deconstruction in nature and highlight an elegant solution for how multiple different glycans can be accessed using one enzymatic cascade.

IMPORTANCE

We report that the genome of the soil bacterium
Chitinophaga pinensis
encodes three multi-modular carbohydrate-active enzymes that work together to hydrolyze the major polysaccharide components found in fungal cell walls (FCWs). The enzymes are all encoded by one polysaccharide utilization locus and are co-expressed, potentially induced in the presence of β-1,3-glucans. We present biochemical characterization of each enzyme, including the appended carbohydrate-binding modules that likely tether the enzymes to a FCW substrate. Finally, we propose a model for how this so-called fungal cell wall utilization locus might enable
C. pinensis
to metabolize both chitin and β-1,3-glucans found in complex biomass in the soil.
Evaluating the impact of including non-randomised studies of interventions in meta-analysis of randomised controlled trials: a protocol for a meta-epidemiological study
Authors: Yao Minghong , Wang Yuning , Busse Jason W , Briel Matthias , Mei Fan , Li Guowei , Zou Kang , Li Ling , Sun Xin
Published: July 2023

Introduction

Although interest in including non-randomised studies of interventions (NRSIs) in meta-analysis of randomised controlled trials (RCTs) is growing, estimates of effectiveness obtained from NRSIs are vulnerable to greater bias than RCTs. The objectives of this study are to: (1) explore how NRSIs can be integrated into a meta-analysis of RCTs; (2) assess concordance of the evidence from non-randomised and randomised trials and explore factors associated with agreement; and (3) investigate the impact on estimates of pooled bodies of evidence when NRSIs are included.

Methods and analysis

We will conduct a systematic survey of 210 systematic reviews that include both RCTs and NRSIs, published from 2017 to 2022. We will randomly select reviews, stratified in a 1:1 ratio by Core vs non-Core clinical journals, as defined by the National Library of Medicine. Teams of paired reviewers will independently determine eligibility and abstract data using standardised, pilot-tested forms. The concordance of the evidence will be assessed by exploring agreement in the relative effect reported by NRSIs and RCT addressing the same clinical question, defined as similarity of the population, intervention/exposure, control and outcomes. We will conduct univariable and multivariable logistic regression analyses to examine the association of prespecified study characteristics with agreement in the estimates between NRSIs and RCTs. We will calculate the ratio of the relative effect estimate from NRSIs over that from RCTs, along with the corresponding 95% CI. We will use a bias-corrected meta-analysis model to investigate the influence on pooled estimates when NRSIs are included in the evidence synthesis.

Ethics and dissemination

Ethics approval is not required. The findings of this study will be disseminated through peer-reviewed publications, conference presentations and condensed summaries for clinicians, health policymakers and guideline developers regarding the design, conduct, analysis, and interpretation of meta-analysis that integrate RCTs and NRSIs.
Implementation of consensus-based perioperative care pathways to reduce clinical variation for elective surgery in an Australian private hospital: a mixed-methods pre–post study protocol
Authors: Pagano Lisa , Hemmert Cameron , Hirschhorn Andrew , Francis-Auton Emilie , Arnolda Gaston , Long Janet C , Braithwaite Jeffrey , Gumley Graham , Hibbert Peter D , Churruca Kate , Hutchinson Karen , Partington Andrew , Hughes Cliff , Gillatt David , Ellis Louise A , Testa Luke , Patel Romika , Sarkies Mitchell N
Published: July 2023

Introduction

Addressing clinical variation in elective surgery is challenging. A key issue is how to gain consensus between largely autonomous clinicians. Understanding how the consensus process works to develop and implement perioperative pathways and the impact of these pathways on reducing clinical variation can provide important insights into the effectiveness of the consensus process. The primary objective of this study is to understand the implementation of an organisationally supported, consensus approach to implement perioperative care pathways in a private healthcare facility and to determine its impact.

Methods

A mixed-methods Effectiveness-Implementation Hybrid (type III) pre–post study will be conducted in one Australian private hospital. Five new consensus-based perioperative care pathways will be developed and implemented for specific patient cohorts: spinal surgery, radical prostatectomy, cardiac surgery, bariatric surgery and total hip and knee replacement. The individual components of these pathways will be confirmed as part of a consensus-building approach and will follow a four-stage implementation process using the Exploration, Preparation, Implementation and Sustainment framework. The process of implementation, as well as barriers and facilitators, will be evaluated through semistructured interviews and focus groups with key clinical and non-clinical staff, and participant observation. We anticipate completing 30 interviews and 15–20 meeting observations. Administrative and clinical end-points for at least 152 participants will be analysed to assess the effectiveness of the pathways.

Ethics and dissemination

This study received ethical approval from Macquarie University Human Research Ethics Medical Sciences Committee (Reference No: 520221219542374). The findings of this study will be disseminated through peer-reviewed publications, conference presentations and reports for key stakeholders.
Unsupervised field-based exercise challenge tests to support the detection of exercise-induced lower airway dysfunction in athletes
Authors: Reier-Nilsen Tonje , Stang Julie Sørbø , Flatsetøy Hanne , Isachsen Martine , Ljungberg Henrik , Bahr Roald , Nordlund Björn
Published: July 2023

Background

Athletes are at risk for developing exercise-induced lower airway narrowing. The diagnostic assessment of such lower airway dysfunction (LAD) requires an objective bronchial provocation test (BPT).

Objectives

Our primary aim was to assess if unsupervised field-based exercise challenge tests (ECTs) could confirm LAD by using app-based spirometry. We also aimed to evaluate the diagnostic test performance of field-based and sport-specific ECTs, compared with established eucapnic voluntary hyperpnoea (EVH) and methacholine BPT.

Methods

In athletes with LAD symptoms, sensitivity and specificity analyses were performed to compare outcomes of (1) standardised field-based 8 min ECT at 85% maximal heart rate with forced expiratory volume in 1 s (FEV1) measured prechallenge and 1 min, 3 min, 5 min, 10 min, 15 min and 30 min postchallenge, (2) unstandardised field-based sport-specific ECT with FEV1measured prechallenge and within 10 min postchallenge, (3) EVH and (4) methacholine BPT.

Results

Of 60 athletes (median age 17.5; range 16–28 years.; 40% females), 67% performed winter-sports, 43% reported asthma diagnosis. At least one positive BPT was observed in 68% (n=41/60), with rates of 51% (n=21/41) for standardised ECT, 49% (n=20/41) for unstandardised ECT, 32% (n=13/41) for EVH and methacholine BPT, while both standardised and unstandardised ECTs were simultaneously positive in only 20% (n=7/35). Standardised and unstandardised ECTs confirmed LAD with 54% sensitivity and 70% specificity, and 46% sensitivity and 68% specificity, respectively, using EVH as a reference, while EVH and methacholine BPT were both 33% sensitive and 85% specific, using standardised ECTs as reference.

Conclusion

App-based spirometry for unsupervised field-based ECTs may support the diagnostic process in athletes with LAD symptoms.

Trial registration number

NCT04275648.
Adaptive Total-Variation and Nonconvex Low-Rank Model for Image Denoising
Authors: Fang Li , Xianghai Wang
Published: July 2023

In recent years, image denoising methods based on total variational regularization have attracted extensive attention. However, the traditional total variational regularization method is an approximate solution based on convex method, and does not consider the particularity of the region with rich details. In this paper, the adaptive total-variation and nonconvex low-rank model for image denoising is proposed, which is a hybrid regularization model. First, the image is decomposed into sparse terms and low rank terms, and then the total variational regularization is used to denoise. At the same time, an adaptive coefficient based on gradient is constructed to adaptively judge the flat area and detail texture area, slow down the denoising intensity of detail area, and then play the role of preserving detail information. Finally, by constructing a nonconvex function, the optimal solution of the function is obtained by using the alternating minimization method. This method not only effectively removes the image noise, but also retains the detailed information of the image. The experimental results show the effectiveness of the proposed model, and SNR and SSIM of the denoised image are improved.