bluuebunny/crossref_metadata_2025 huggingface dataset:
Human gelatin-based composite hydrogels for osteochondral tissue engineering and their adaptation into bioinks for extrusion, inkjet, and digital light processing bioprinting
Authors: Bedell Matthew L , Torres Angelica L , Hogan Katie J , Wang Ziwen , Wang Bonnie , Melchiorri Anthony J , Grande-Allen K Jane , Mikos Antonios G
Published: August 2022

The investigation of novel hydrogel systems allows for the study of relationships between biomaterials, cells, and other factors within osteochondral tissue engineering. Three-dimensional (3D) printing is a popular research method that can allow for further interrogation of these questions via the fabrication of 3D hydrogel environments that mimic tissue-specific, complex architectures. However, the adaptation of promising hydrogel biomaterial systems into 3D-printable bioinks remains a challenge. Here, we delineated an approach to that process. First, we characterized a novel methacryloylated gelatin composite hydrogel system and assessed how calcium phosphate and glycosaminoglycan additives upregulated bone- and cartilage-like matrix deposition and certain genetic markers of differentiation within human mesenchymal stem cells (hMSCs), such as RUNX2 and SOX9. Then, new assays were developed and utilized to study the effects of xanthan gum and nanofibrillated cellulose, which allowed for cohesive fiber deposition, reliable droplet formation, and non-fracturing digital light processing (DLP)-printed constructs within extrusion, inkjet, and DLP techniques, respectively. Finally, these bioinks were used to 3D print constructs containing viable encapsulated hMSCs over a 7 d period, where DLP printed constructs facilitated the highest observed increase in cell number over 7 d (∼2.4×). The results presented here describe the promotion of osteochondral phenotypes via these novel composite hydrogel formulations, establish their ability to bioprint viable, cell-encapsulating constructs using three different 3D printing methods on multiple bioprinters, and document how a library of modular bioink additives affected those physicochemical properties important to printability.
A review on applications of gold nanoparticles-based biosensor for pathogen detection
Authors: Najafabad Marjan Bagheri , Rastin Sepide Jafarzadeh , Taghvaei Fatemeh , Khiyavi Azim Akbarzadeh
Published: August 2022

Pathogens are one of the leading causes of death globally. Early detection of pathogens seems to be necessary. Detection of bacteria and harmful viruses like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a fast manner is very critical for early diagnosis of infections to prevent spreading. Current tools for the detection of pathogens are challenging in terms of specificity, rapidity, and simplicity. For this purpose, biosensors have shown advances in rapid diagnosis, high sensitivity, and selectivity detection of pathogens. Nanoparticles-based biosensors are very useful in detecting pathogens due to their capability to provide a simple, rapid, and specific colour changes in response to environmental alternations. Functionalised gold nanoparticles (AuNPs) are highly accurate and sensitive biosensors for the detection of a wide range of pathogens. This review summarises optical and non-optical AuNPs biosensors for the detection of pathogens. Moreover, we focus on technologies that aim to detect pathogens using AuNPs-based biosensor and some representative examples.
Effects of geometric parameters on photoemission of AlGaN nanowire array photocathode
Authors: Cao Zhihao , Liu Lei , Lu Feifei
Published: August 2022

In recent years, with the continuous development of solar blind ultraviolet photodetectors, III-V compounds are widely used as semiconductor materials. The nanowire array structure has excellent ‘light trapping effect’. However, if the distance of nanowire is too close, the secondary absorption problem of the nanowire will occur. If the distance of nanowire is too far, the number of photocarriers generated in the nanowire array per unit volume will be reduced. Meanwhile, the absorption capacity of the nanowire structure with different shapes is different. Based on this background, we studied the influence of the period and geometry of AlGaN nanowires with different Al components on the optical response properties. The finite time domain difference (FDTD) method was used to compare the quantum efficiency and collection efficiency of AlGaN nanowires with different Al components, we found that the quantum efficiency of the hexagonal nanowire array with Al component of 0.42 is as high as 45%, which is the highest in our structure. At the same time, its cutoff wavelength is at 280 nm, which has excellent solar blindness. Therefore, the study in this paper can provide some theoretical reference for the experiment and preparation of AlGaN photocathode.
Self-absorption effects of laser-induced breakdown spectroscopy under different gases and gas pressures
Authors: WANG Songning , ZHANG Dianxin , CHEN Nan , HE Yaxiong , ZHANG Hong , KE Chuan , XU Tao , CHEN Yongliang , ZHAO Yong
Published: August 2022

The self-absorption effect is one of the main factors affecting the quantitative analysis accuracy of laser-induced breakdown spectroscopy. In this paper, the self-absorption effects of laser-induced 7050 Al alloy plasma under different pressures in air, Ar, and N2 have been studied. Compared with air and N2, Ar significantly enhances the spectral signal. Furthermore, the spectral self-absorption coefficient is calculated to quantify the degree of self-absorption, and the influences of gas species and gas pressure on self-absorption are analyzed. In addition, it is found that the spectral intensity fluctuates with the change of pressure of three gases. It can also be seen that the fluctuation of spectral intensity with pressure is eliminated after correcting, which indicates that the self-absorption leads to the fluctuation of spectral intensity under different pressures. The analysis shows that the evolution of optical thin spectral lines with pressure in different gases is mainly determined by the gas properties and the competition between plasma confinement and Rayleigh–Taylor instability.
Optimal design and performance evaluation of free-space quantum key distribution systems
Authors: Scriminich Alessia , Foletto Giulio , Picciariello Francesco , Stanco Andrea , Vallone Giuseppe , Villoresi Paolo , Vedovato Francesco
Published: August 2022

Free-space ground-to-ground links will be an integral part of future quantum communication networks. The implementation of free-space and fiber links in daylight inter-modal configurations is however still hard to achieve, due to the impact of atmospheric turbulence, which strongly decreases the coupling efficiency into the fiber. In this work, we present a comprehensive model of the performance of a free-space ground-to-ground quantum key distribution (QKD) system based on the efficient-BB84 protocol with active decoy states. Our model takes into account the atmospheric channel contribution, the transmitter and receiver telescope design constraints, the parameters of the quantum source and detectors, and the finite-key analysis to produce a set of requirements and optimal design choices for a QKD system operating under specific channel conditions. The channel attenuation is calculated considering all effects deriving from the atmospheric propagation (absorption, beam broadening, beam wandering, scintillation, and wavefront distortions), as well as the effect of fiber-coupling in the presence of a partial adaptive optics correction with finite control bandwidth. We find that the channel fluctuation statistics must be considered to correctly estimate the effect of the saturation rate of the single-photon detectors, which may otherwise lead to an overestimation of the secret key rate. We further present strategies to minimize the impact of diffuse atmospheric background in daylight operation by means of spectral and temporal filtering.
Collective dynamics in plasmas—III. Collisionless kinetic effects
Authors: Bers Abraham
Published: August 2022

This chapter provides a physical description and analysis of the basic collisionless kinetic effects in collective plasma modes—the effects of phase-resonant wave-particle interactions (WPI) and finite Larmor radius (FLR), which are of importance in high-temperature plasmas. These kinetic effects were alluded to only in the previous chapters by cautioning that certain results from a hydrodynamic description may have to be modified or supplemented. Such effects appear as an integral part of a kinetic mode description of plasma dynamics, a more complex model description than the hydrodynamic one. The specific and simpler treatments of kinetic effects allow the illustration and evaluation of their consequences on the many hydrodynamic modes presented in the previous chapter, and include drawing attention to the nonlinear aspects of kinetic dynamics.
Kinetic theory of collisions and transport—I. Fully-ionized plasmas
Authors: Bers Abraham
Published: August 2022

This chapter explores the kinetic theory of collisions and transport for fully-ionized plasmas. It first derives the Fokker–Planck collision equation analyzed in previous chapters by presenting them in two commonly used forms—the Landau form, and the form in terms of Rosenbluth potentials—and examines electrical conductivity through the Spitzer–Härm problem. The chapter then discusses the collisional transport theory, which entails slowly-varying (low-frequency and long-wavelength) hydrodynamics in a short mean-free-path limit. It shows that responses to drives such as the thermodynamics equilibrium entail the collisional transport coefficients of electrical conductivity, particle and heat diffusivities, and viscosity that enter into, and that specify the hydrodynamic transport equations. The kinetic theory analysis of arriving at the electrical conductivity of a fully-ionized plasma is carried out and used to appreciate some general aspects in the analysis and computation required for finding any transport coefficient.
Mathematical Appendices
Authors: Bers Abraham
Published: August 2022

This concluding chapter addresses accounting for the remaining single-charged particle fields in a plasma, which are neglected in a fluid kinetic description: those associated with radiations and fluctuations. These cover topics such as complex Fourier–Laplace transforms, Bessel functions, and the Jacobi elliptic functions. It also contains summaries of various applied mathematics topics and techniques that are used throughout the text. References are also given to textbooks that cover the topics at the end of each section. Students are expected to have had an exposure to these topics in applied mathematics courses taken and/or in such courses that they take concurrently with their graduate studies in plasma physics and fusion plasma electrodynamics.
New horizons in the ageing autonomic nervous system: orthostatic hypotension and supine hypertension
Authors: Dani Melanie , Taraborrelli Patricia , Panagopoulos Dimitrios , Dirksen Andreas , Torocastro Miriam , Sutton Richard , Lim Phang Boon
Published: August 2022

Blood pressure regulation is an automatic, moment-by-moment buffering of the blood pressure in response to physiological changes such as orthostasis, exercise and haemorrhage. This finely orchestrated reflex is called the baroreflex. It is a regulated arc of afferent, central and efferent arms. Multiple physiological changes occur with ageing that can disrupt this reflex, making blood pressure regulation less effective. In addition, multiple changes can occur with ageing-related diseases such as neurodegeneration, atherosclerosis, deconditioning and polypharmacy. These changes commonly result in orthostatic hypotension, hypertension or both, and are consistently associated with multiple adverse outcomes. In this article, we discuss the healthy baroreflex, and physiological and pathophysiological reasons for impaired baroreflex function in older people. We discuss why the common clinical manifestations of orthostatic hypotension and concomitant supine hypertension occur, and strategies for balancing these conflicting priorities. Finally, we discuss strategies for treating them, outlining our practice alongside consensus and expert guidance.
Examining the prevalence and correlates of multimorbidity among community-dwelling older adults: cross-sectional evidence from the Canadian Longitudinal Study on Aging (CLSA) first-follow-up data
Authors: Im James H B , Rodrigues Rebecca , Anderson Kelly K , Wilk Piotr , Stranges Saverio , Nicholson Kathryn
Published: August 2022

Introduction

multimorbidity has become an increasingly important issue for many populations around the world, including Canada. The objectives of this study were to estimate the prevalence of multimorbidity at first follow-up and to identify factors associated with multimorbidity using data from the Canadian Longitudinal Study on Aging (CLSA).

Methods

this study included 27,701 community-dwelling participants in the first follow-up of the CLSA. Multimorbidity was operationalised using two definitions (Public Health and Primary Care), as well as the cut-points of two or more chronic conditions (MM2+) and three or more chronic conditions (MM3+). The prevalence of multimorbidity was calculated at first follow-up and multivariable regression models were used to identify correlates of multimorbidity occurrence.

Results

the prevalence of multimorbidity at first follow-up was 32.3% among males and 39.3% among females when using the MM2+ Public Health definition, whereas the prevalence was 67.2% among males and 75.8% among females when using the MM2+ Primary Care definition. Older age, lower alcohol consumption, lower physical activity levels, dissatisfaction with sleep quality, dissatisfaction with life and experiencing social limitations due to health conditions were significantly associated with increased odds of multimorbidity for both males and females, regardless of the definition of multimorbidity used.

Conclusion

various sociodemographic, behavioural and psychosocial factors are associated with multimorbidity. Future research should continue to examine how the prevalence of multimorbidity changes with time and how these changes may be related to specific risk factors. This future research should be supplemented with studies examining the longitudinal impacts of multimorbidity over time.
Shared decision-making for the treatment of proximal femoral fractures in frail institutionalised older patients: healthcare providers’ perceived barriers and facilitators
Authors: Spronk Inge , Loggers Sverre A I , Joosse Pieter , Willems Hanna C , Van Balen Romke , Gosens Taco , Ponsen Kornelis J , Steens Jeroen , van de Ree C L P (Marc) , Zuurmond Rutger G , Verhofstad Michael H J , Van Lieshout Esther M M , Polinder Suzanne
Published: August 2022

Introduction

Proximal femoral fractures are common in frail institutionalised older patients. No convincing evidence exists regarding the optimal treatment strategy for those with a limited pre-fracture life expectancy, underpinning the importance of shared decision-making (SDM). This study investigated healthcare providers’ barriers to and facilitators of the implementation of SDM.

Methods

Dutch healthcare providers completed an adapted version of the Measurement Instrument for Determinants of Innovations questionnaire to identify barriers and facilitators. If ≥20% of participants responded with ‘totally disagree/disagree’, items were considered barriers and, if ≥80% responded with ‘agree/totally agree’, items were considered facilitators.

Results

A total of 271 healthcare providers participated. Five barriers and 23 facilitators were identified. Barriers included the time required to both prepare for and hold SDM conversations, in addition to the reflective period required to allow patients/relatives to make their final decision, and the number of parties required to ensure optimal SDM. Facilitators were related to patients’ values, wishes and satisfaction, the importance of SDM for patients/relatives and the fact that SDM is not considered complex by healthcare providers, is considered to be part of routine care and is believed to be associated with positive patient outcomes.

Conclusion

Awareness of identified facilitators and barriers is an important step in expanding the use of SDM. Implementation strategies should be aimed at managing time constraints. High-quality evidence on outcomes of non-operative and operative management can enhance implementation of SDM to address current concerns around the outcomes.
Effectiveness of exergaming-based interventions for mobility and balance performance in older adults with Parkinson’s disease: systematic review and meta-analysis of randomised controlled trials
Authors: Zhang Jiaxin , Luximon Yan , Pang Marco Y C , Wang Hailiang
Published: August 2022

Background

exergaming-based interventions (EbIs) have been proposed to improve older adults’ mobility and balance performance. However, the effectiveness of such interventions for older adults with Parkinson’s disease (OAPD) remains unclear.

Methods

seven databases (Web of Science, Medline, Academic Search Premier, CINAHL Complete, PsycINFO, PsychARTICLE and PubMed) were searched up to 7 April 2022. We assessed mobility and balance performance between EbIs groups and control groups or traditional physical training interventions (TPTIs) groups by comparing the outcomes of the Timed Up and Go (TUG), 6-Minute Walk Test (6MWT), Berg Balance Scale (BBS), gait velocity, stride length and Functional Gait Assessment (FGA).

Results

we scanned 1,190 articles and meta-analysed 19 trials (sample size = 781). In general, the results revealed statistical differences between EbIs groups and TPTIs groups in the TUG [mean difference (MD) = −1.030 s; 95% confidence interval (CI) = −2.029 to −0.031; P = 0.043; high quality of evidence], 6MWT (MD = 63.483 m; 95% CI = 9.542 to 117.425; P = 0.021; moderate quality of evidence), BBS (MD = 2.129; 95% CI = −1.293 to 2.965; P < 0.001; high quality of evidence) and FGA (MD = 2.099 95% CI = −0.306 to 3.893; P = 0.022; moderate quality of evidence). No significant difference was discovered between EbIs groups and TPTIs groups in enhancing gait velocity and stride length.

Conclusions

EbIs are statistically better than TPTIs in improving OAPD’s performance in TUG, 6MWT, BBS and FGA, whereas only the change between EbIs and TPTIs in 6MWT can reach the value of minimal clinically important difference. Further studies are needed to better assess the effectiveness of exergaming-based interventions.
Association of multimorbidity patterns with incident disability and recovery of independence among middle-aged and older adults
Authors: Zhou Jiayi , Wei Melissa Y , Zhang Jingyi , Liu Hua , Wu Chenkai
Published: August 2022

Objective

to identify multimorbidity patterns among middle-aged and older adults in China and examine how these patterns are associated with incident disability and recovery of independence.

Methods

data were from The China Health and Retirement Longitudinal Study. We included 14,613 persons aged ≥45 years. Latent class analysis (LCA) was conducted to identify multimorbidity patterns with clinical meaningfulness. Multinomial logistic models were used to determine the adjusted association between multimorbidity patterns and incident disability and recovery of independence.

Results

we identified four multimorbidity patterns: ‘low morbidity’ (67.91% of the sample), ‘pulmonary–digestive–rheumatic’ (17.28%), ‘cardiovascular–metabolic–neuro’ (10.77%) and ‘high morbidity’ (4.04%). Compared to the ‘low morbidity’ group, ‘high morbidity’ (OR = 2.63, 95% CI = 1.97–3.51), ‘pulmonary–digestive–rheumatic’ (OR = 1.89, 95% CI = 1.63–2.21) and ‘cardiovascular–metabolic–neuro’ pattern (OR = 1.61, 95% CI = 1.31–1.97) had higher odds of incident disability in adjusted multinomial logistic models. The ‘cardiovascular–metabolic–neuro’ (OR = 0.60, 95% CI = 0.44–0.81), ‘high morbidity’ (OR = 0.68, 95% CI = 0.47–0.98) and ‘pulmonary–digestive–rheumatic’ group (OR = 0.75, 95% CI = 0.60–0.95) had lower odds of recovery from disability than the ‘low morbidity’ group. Among people without disability, the ‘cardiovascular–endocrine–neuro’ pattern was associated with the highest 2-year mortality (OR = 2.42, 95% CI = 1.56–3.72).

Conclusions

multimorbidity is complex and heterogeneous, but our study demonstrates that clinically meaningful patterns can be obtained using LCA. We highlight four multimorbidity patterns with differential effects on incident disability and recovery from disability. These studies suggest that targeted prevention and treatment approaches are needed for people with multimorbidity.
DBFE: distribution-based feature extraction from structural variants in whole-genome data
Authors: Piernik Maciej , Brzezinski Dariusz , Sztromwasser Pawel , Pacewicz Klaudia , Majer-Burman Weronika , Gniot Michal , Sielski Dawid , Bryzghalov Oleksii , Wozna Alicja , Zawadzki Pawel
Published: August 2022

Motivation

Whole-genome sequencing has revolutionized biosciences by providing tools for constructing complete DNA sequences of individuals. With entire genomes at hand, scientists can pinpoint DNA fragments responsible for oncogenesis and predict patient responses to cancer treatments. Machine learning plays a paramount role in this process. However, the sheer volume of whole-genome data makes it difficult to encode the characteristics of genomic variants as features for learning algorithms.

Results

In this article, we propose three feature extraction methods that facilitate classifier learning from sets of genomic variants. The core contributions of this work include: (i) strategies for determining features using variant length binning, clustering and density estimation; (ii) a programing library for automating distribution-based feature extraction in machine learning pipelines. The proposed methods have been validated on five real-world datasets using four different classification algorithms and a clustering approach. Experiments on genomes of 219 ovarian, 61 lung and 929 breast cancer patients show that the proposed approaches automatically identify genomic biomarkers associated with cancer subtypes and clinical response to oncological treatment. Finally, we show that the extracted features can be used alongside unsupervised learning methods to analyze genomic samples.

Availability and implementation

The source code of the presented algorithms and reproducible experimental scripts are available on Github at https://github.com/MNMdiagnostics/dbfe.

Supplementary information

Supplementary data are available at Bioinformatics online.
Neural Collective Matrix Factorization for integrated analysis of heterogeneous biomedical data
Authors: Mariappan Ragunathan , Jayagopal Aishwarya , Sien Ho Zong , Rajan Vaibhav
Published: August 2022

Motivation

In many biomedical studies, there arises the need to integrate data from multiple directly or indirectly related sources. Collective matrix factorization (CMF) and its variants are models designed to collectively learn from arbitrary collections of matrices. The latent factors learnt are rich integrative representations that can be used in downstream tasks, such as clustering or relation prediction with standard machine-learning models. Previous CMF-based methods have numerous modeling limitations. They do not adequately capture complex non-linear interactions and do not explicitly model varying sparsity and noise levels in the inputs, and some cannot model inputs with multiple datatypes. These inadequacies limit their use on many biomedical datasets.

Results

To address these limitations, we develop Neural Collective Matrix Factorization (NCMF), the first fully neural approach to CMF. We evaluate NCMF on relation prediction tasks of gene–disease association prediction and adverse drug event prediction, using multiple datasets. In each case, data are obtained from heterogeneous publicly available databases and used to learn representations to build predictive models. NCMF is found to outperform previous CMF-based methods and several state-of-the-art graph embedding methods for representation learning in our experiments. Our experiments illustrate the versatility and efficacy of NCMF in representation learning for seamless integration of heterogeneous data.

Availability and implementation

https://github.com/ajayago/NCMF_bioinformatics.

Supplementary information

Supplementary data are available at Bioinformatics online.
Gene therapy targeting the blood–brain barrier improves neurological symptoms in a model of genetic MCT8 deficiency
Authors: Sundaram Sivaraj M , Arrulo Pereira Adriana , Müller-Fielitz Helge , Köpke Hannes , De Angelis Meri , Müller Timo D , Heuer Heike , Körbelin Jakob , Krohn Markus , Mittag Jens , Nogueiras Ruben , Prevot Vincent , Schwaninger Markus
Published: August 2022

A genetic deficiency of the solute carrier monocarboxylate transporter 8 (MCT8), termed Allan–Herndon–Dudley syndrome, is an important cause of X-linked intellectual and motor disability. MCT8 transports thyroid hormones across cell membranes. While thyroid hormone analogues improve peripheral changes of MCT8 deficiency, no treatment of the neurological symptoms is available so far. Therefore, we tested a gene replacement therapy in Mct8- and Oatp1c1-deficient mice as a well-established model of the disease. Here, we report that targeting brain endothelial cells for Mct8 expression by intravenously injecting the vector AAV-BR1-Mct8 increased tri-iodothyronine (T3) levels in the brain and ameliorated morphological and functional parameters associated with the disease. Importantly, the therapy resulted in a long-lasting improvement in motor coordination. Thus, the data support the concept that MCT8 mediates the transport of thyroid hormones into the brain and indicate that a readily accessible vascular target can help overcome the consequences of the severe disability associated with MCT8 deficiency.
Coronavirus Disease 2019 Burden Among Unaccompanied Minors in US Custody
Authors: Foppiano Palacios Carlo , Tucker Elizabeth W , Travassos Mark A
Published: August 2022

Background

Before the coronavirus disease 2019 (COVID-19) pandemic, crowded and unsanitary living conditions lacking medical expertise made US detention centers hotbeds for infectious disease outbreaks. There have been 30 000 COVID-19 cases, positivity rates exceeding 50%, and 9 deaths in Immigration and Customs Enforcement custody, but the extent of disease among children under the care of the Office of Refugee Resettlement (ORR) has not been well-documented. We sought to evaluate the burden of COVID-19 among unaccompanied minors under the ORR’s responsibility.

Methods

We analyzed SARS-CoV-2 testing results of refugees and asylum seekers in facilities associated with the ORR from February 1, 2020, to November 18, 2020, courtesy of a Freedom of Information Act request.

Results

ORR facilities performed 7132 SARS-CoV-2 tests from March 13, 2020, to November 18, 2020. Overall, the SARS-CoV-2 positivity rate was 13.4%. Factors associated with higher positivity rates were age group (16–17 years old); identifying as male; undergoing testing in April, August, or September; staying in a for-profit versus a nonprofit facility; and detention in certain facilities. The mean detention time with a positive test was 14.8 ± 3.2 days. Greater than 10% of positive tests were in long-term detainees.

Conclusions

The high SARS-CoV-2 test positivity rate raises concerns about an inability to limit the spread of SARS-CoV-2 within detention facilities housing unaccompanied migrant children, particularly those run by for-profit companies. Mandated measures for social distancing and vaccination among detainees and detention facility employees are needed to limit the spread of the virus.
Clinical and Molecular Analyses of Recurrent Gram-Negative Bloodstream Infections
Authors: Bock Andrew , Hanson Blake M , Ruffin Felicia , Parsons Joshua B , Park Lawrence P , Sharma-Kuinkel Batu , Mohnasky Michael , Arias Cesar A , Fowler Vance G , Thaden Joshua T
Published: August 2022

Background

The causes and clinical characteristics of recurrent gram-negative bacterial bloodstream infections (GNB-BSI) are poorly understood.

Methods

We used a cohort of patients with GNB-BSI to identify clinical characteristics, microbiology, and risk factors associated with recurrent GNB-BSI. Bacterial genotyping (pulsed-field gel electrophoresis [PFGE] and whole-genome sequencing [WGS]) was used to determine whether episodes were due to relapse or reinfection. Multivariable logistic regression was used to identify risk factors for recurrence.

Results

Of the 1423 patients with GNB-BSI in this study, 60 (4%) had recurrent GNB-BSI. Non-White race (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.38–4.01; P = .002), admission to a surgical service (OR, 2.18; 95% CI, 1.26–3.75; P = .005), and indwelling cardiac device (OR, 2.73; 95% CI, 1.21–5.58; P = .009) were associated with increased risk for recurrent GNB-BSI. Among the 48 patients with recurrent GNB-BSI whose paired bloodstream isolates underwent genotyping, 63% were due to relapse (30 of 48) and 38% were due to reinfection (18 of 48) based on WGS. Compared with WGS, PFGE correctly differentiated relapse and reinfection in 98% (47 of 48) of cases. Median time to relapse and reinfection was similar (113 days; interquartile range [IQR], 35–222 vs 174 days; IQR, 69–599; P = .13). Presence of a cardiac device was associated with relapse (relapse: 7 of 27, 26%; nonrelapse: 65 of 988, 7%; P = .002).

Conclusions

In this study, recurrent GNB-BSI was most commonly due to relapse. PFGE accurately differentiated relapse from reinfection when compared with WGS. Cardiac device was a risk factor for relapse.
Challenging austerity under the COVID-19 state
Authors: Warner Mildred E , Kelly Paige M , Zhang Xue
Published: August 2022

The COVID-19 pandemic represented a short-term shift in US social policy. Under the CARES Act and the American Rescue Plan Act (ARPA), the federal government prioritised households by raising the floor for child support and unemployment benefits, and restoring fiscal federalism by providing increased funds to state and local governments. Our 2021 nationwide survey finds local governments with more citizen participation and Black Lives Matter protests plan to prioritise social equity investments, while those with more Trump voters plan to prioritise physical infrastructure with their ARPA funds. COVID-19 led to new policy approaches that expand government investment. While the federal changes for households (expanded unemployment insurance and child tax credits) ended in 2021, the increased aid to state and local governments continues. These have the potential to help reshape citizen expectations and repair federal–state–local relations.
Effect of Macrotroponin in a Cohort of Community Patients with Elevated Cardiac Troponin
Authors: Lam Leo , Tse Rexson , Gladding Patrick , Kyle Campbell
Published: August 2022

Background

Macrotroponin is an important cause of discrepancy between current high-sensitivity cardiac troponin (hs-cTn) assays, however, its clinical significance is unclear. This study examined the effects of macrotroponin and repeat testing by different hs-cTnI assays in a cohort of community patients with elevated hs-cTnI.

Methods

The first residual serum specimen from each patient in the community admitted to hospital with elevated hs-cTnI (Siemens hs-cTnI Centaur) was retested after immunoglobulin depletion and by 5 other hs-cTn assays. Low recovery of cTnI (<40%) following immunoglobulin depletion was considered as macrotroponin. A retrospective chart review was performed for these participants. Investigator-adjudicated diagnosis served as the reference standard.

Results

In our cohort of community patients with elevated troponin (n = 188), participants with macrotroponin (n = 99) often had a multifactorial or indeterminate myocardial injury (56% vs 25%) and were less likely to have acute coronary syndrome (9% vs 28%). On repeat testing of cTn on other platforms, better diagnostic performance (c-statistics) for ischemic and non-ischemic cardiac causes was observed on the Beckman Access hs-cTnI (0.74; 95% confidence interval [CI] 0.67–0.81) or the Abbott hs-cTnI Architect (0.75; CI 0.68–0.82) compared to the Siemens hs-cTnI Vista (0.62; CI 0.54–0.70; P < 0.05). This could be attributed to differences in assay reactivity for macrotroponin. Interestingly, better diagnostic performance was observed in patients without macrotroponin. Although a small number of deaths occurred (n = 16), participants with macrotroponin had better overall survival.

Conclusions

In the low-risk setting, the presence of macrotroponin was clinically associated with multifactorial or indeterminate causes of troponin elevation.
The comparative energetics of the carnivorans and pangolins
Authors: Kooijman Sebastiaan A L M , Augustine Starrlight
Published: August 2022

Patterns in eco-physiological traits of pangolins and carnivorans are studied, which are functions of underlying Dynamic Energy Budget parameters. The data, parameter values and traits are accessible in the open access Add-my-Pet collection, which currently contains 7 out of 8 species of pangolins and 131 of the extant 276 species of carnivorans and 653 of the extant 6400 species of mammals. Paucity of data and species not included reflect the actual state of knowledge: many species are endangered and/or little measured data is readily available. Although musteloids and pinnipeds form the clade Mustelida, they appear at opposite ends of the classical multidimensional scaling diagram, using 14 traits on all mammals. Yet, in general, the energetic parameters bear a strong taxonomic signal. The weight at birth is proportional to ultimate weight: small for carnivorans and pangolins; extra small for bears; and much larger, but typical for mammals, for the pinnipeds and sea otters. How respiration scales with size is taxon-specific, and we discuss how the body-size scaling of reserve capacity interferes with the waste-to-hurry pattern. Despite their high allocation to soma, the life time cumulated mass of neonates of pangolins and carnivorans equals their own ultimate weight; pinnipeds allocate more to maturation and reproduction. Applying models to support conservation efforts entails needing realistic parameter values. This study contributes to the emerging field of assessing the realism of parameters in biological and evolutionary context.
Intestinal Epithelial Responses to IL-17 in Adult Stem Cell-derived Human Intestinal Organoids
Authors: Lee Chansu , Song Joo Hye , Cha Yeo-Eun , Chang Dong Kyung , Kim Young-Ho , Hong Sung Noh
Published: August 2022

Background

Th17 cells and their signature cytokine, interleukin-17A [IL-17], are considered as the main pathogenic factors in inflammatory bowel diseases [IBDs]. However, IL-17 neutralising antibodies, a theoretically curative medication for IBDs, paradoxically aggravated intestinal inflammation. The mechanisms by which IL-17 mediates the protective and pathological effects of IL-17 remain unclear in the intestinal epithelium.

Methods

The intestinal epithelial responses induced by IL-17 were evaluated using the human small intestinal organoid [enteroid] model.

Results

Organoid-forming efficiency, cell viability, and proliferation of enteroids were decreased in proportion to IL-17 concentration. The IL-17 induced cytotoxicity was predominantly mediated by pyroptosis with activation of CASP1 and cleavage of GSDMD. Bulk RNA-sequencing revealed the enrichment of secretion signalling in IL-17 treated enteroids, leading to mucin exocytosis. Among its components, PIGR was up-regulated significantly as the concentration of IL-17 increased, resulting in IgA transcytosis. Mucin exocytosis and IgA transcytosis have a protective role against enteric pathogens. Single-cell RNA sequencing identified that CASP1-mediated pyroptosis occurred actively in intestinal stem cells [ISCs] and enterocytes. IL-17 neutralising antibody completely restored IL-17 induced cytotoxicity, but suppressed mucin secretion and IgA transcytosis. Pyroptosis inhibition using CASP1 inhibitors significantly improved IL-17 induced cytotoxicity without diminishing its beneficial effects.

Conclusions

IL-17 induces the pyroptosis of ISCs and enterocytes, as well as mucin secretion of goblet cells and IgA transcytosis of epithelial cells. Paradoxical gastrointestinal effects of IL-17 neutralising antibodies may be associated with inhibition of mucin secretion and IgA transcytosis. The inhibition of pyroptosis using CASP1 inhibitors prevents IL-17 induced cytotoxicity without compromising its beneficial effects.
Placebo Rates in Randomized Controlled Trials of Proctitis Therapy: A Systematic Review and Meta-Analysis Placebo Response in Proctitis
Authors: De Silva Theshani A , Alphonsus Lotus , Ma Christopher , Hogan Malcolm , Sedano Rocio , Narula Neeraj , Danese Silvio , Peyrin-Biroulet Laurent , MacDonald John K , Singh Siddharth , Jairath Vipul
Published: August 2022

Background and Aims

Treatment options for proctitis are limited. To assist trial design for novel therapeutics, we conducted a systematic review and meta-analysis of proctitis randomized controlled trials [RCTs] to quantify placebo rates and identify factors influencing them.

Methods

We searched MEDLINE, EMBASE and CENTRAL from inception to June 2021. Placebo-controlled trials of pharmacological interventions for proctitis were eligible. Placebo clinical response and remission rates for induction and maintenance trials were extracted and pooled using a random-effects model. Mixed-effects meta-regression was used to evaluate the impact of patient and study-level characteristics.

Results

Twenty RCTs [17 induction and four maintenance phases] were included. The most common intervention was aminosalicylates and most studies investigated topical medications. The pooled placebo clinical response and remission rates for induction trials were 28% (95% confidence interval [CI] 22–35%; n = 17) and 20% [95% CI 12–32%; n = 9], respectively. Pooled placebo endoscopic response and remission rates were 32% [95% CI 26–39%, n = 12] and 18% [95% CI 9–33%, n = 6], respectively. For maintenance trials, the pooled placebo clinical remission rate was 29% [95% CI 16–46%, n = 17]. Trials published after 2005 and trials with a longer duration of follow-up were associated with significantly lower placebo response rates. Nineteen of 20 studies were assessed as having an unclear risk of bias, reflecting the historical nature of trials.

Conclusions

Placebo response and remission rates in proctitis trials are influenced by trial phase and the endpoint being assessed. These contemporary rates will inform trial design for novel therapeutics for treatment of proctitis, which is a large unmet need.
Mending the broken valentine heart: a case report
Authors: Marwaha Sarandeep , Bhatia Raghav , Papadakis Michael , Marciniak Anna
Published: August 2022

Background

Mortality from myocardial infarction (MI) has been decreasing since the introduction of primary percutaneous intervention. Late complications still pose a dilemma, such as deterioration of left ventricle (LV) function, LV aneurysms, and LV thrombus formation. If not adequately managed in a timely manner, this can result in life-threatening consequences. Restoration of LV function by surgical resection of the infarcted LV wall is an option for a few complicated cases, with variable outcomes.

Case summary

A 66-year-old man presented with dyspnoea 2 years after his initial MI, which was treated with a drug-eluting stent to his left circumflex artery. His Warfarin had been stopped after 6 months of treatment of a small LV thrombus, which was noted at the time of his initial infarction. His echocardiogram on admission demonstrated severe LV systolic impairment of 23% (which had deteriorated from 40%) with a giant true aneurysm of the basal to mid-lateral wall, which resembled a Valentine heart. The presence of a large, organized thrombus filling the aneurysm complicated the case further. The patient underwent a resection of the LV aneurysm and thrombus. He remained asymptomatic and maintained a significant improvement of his LV function to 47% at his 5 months scan.

Discussion

The importance of imaging post-large MI and follow-up imaging once thrombus resolution has occurred is crucial. Patients with large LV aneurysm associated with severe refractory LV impairment and LV thrombus should be considered for LV aneurysmectomy for prognostic benefit and symptom relief.
Interactions of the bacteriome, virome, and immune system in the nose
Authors: Flynn Matthew , Lyall Zinnia , Shepherd Gwendolyn , Lee Osher Ngo Yung , Marianna Da Fonseca Ioannou , Dong Yijia , Chalmers Stuart , Hare Jamie , Thomson Jack , Millar Freya
Published: August 2022

Emerging evidence suggests that the nasal microbiome may influence host susceptibility to initial development and severity of respiratory viral infections. While not as extensively studied as the microbiota of the alimentary tract, it is now clearly established that the microbial composition of this niche is influenced by medical, social and pharmacological influences, predisposing some sub-populations to respiratory infections. The resulting specific microbial profiles may explain variance in susceptibility to viral infection. This review summaries the evolution and constituents of the commensal nasal microbiome; the bacterial-virus, bacterial-host and interbacterial interactions which potentiate disease; and considers the effects of interventions such as vaccination and probiotics.
Influence of Freedom of Movement on the Health of People With Dementia: A Systematic Review
Authors: van Liempd Suzan , Verbiest Marjolein , Stoop Annerieke , Luijkx Katrien
Published: August 2022

Background and Objectives

To protect residents with dementia from harm, nursing homes (NHs) often have closed-door policies. However, current research suggests a positive influence of freedom of movement, that is, the right to (decide to) independently move from one place to another, on the health of NH residents with dementia. This systematic review aims to collate, summarize, and synthesize the scientific evidence published to date on the influence of freedom of movement on health among NH residents with dementia.

Research Design and Methods

Multiple databases were searched up until March 2021. Peer-reviewed qualitative, quantitative, and mixed methods studies were included. Health was operationalized using the Positive Health framework, encompassing 6 dimensions: bodily functions, mental functions and perception, existential dimension, quality of life, social and societal participation, and daily functioning. The quality of included studies was assessed using the Mixed Methods Appraisal Tool.

Results

Sixteen studies were included of good to excellent quality. Compared to closed NHs, freedom of movement in semiopen and open NHs may have a positive influence on bodily functions, mental functions and perception, quality of life, and social and societal participation. The influence on daily functioning and on the existential dimension remains unclear.

Discussion and Implications

Freedom of movement of NH residents with dementia is often studied as part of a larger context in which other factors may contribute to health benefits. More research is therefore needed to unravel the underlying mechanisms of the positive influence of freedom of movement on health.
The Lesser-Known Transitions: Organismal Form and Function across Abiotic Gradients
Authors: Easterling C M , Kolmann M A , O'Donnell M K
Published: August 2022

From minute-to-minute changes, or across daily, seasonal, or geological timescales, animals are forced to navigate dynamic surroundings. Their abiotic environment is continually changing. These changes could include alterations to the substrates animals locomote on, flow dynamics of the microhabitats they feed in, or even altitudinal shifts over migration routes. The only constancy in any organism's day-to-day existence is the heterogeneity of the habitats they move through and the gradients in the physical media (e.g., air and water) they live in. We explored a broad range of organismal transitions across abiotic gradients and investigated how these organisms modify their form, function, and behavior to accommodate their surrounding media. We asked the following questions: (1) What are some challenges common to animals in changing media or moving between media? (2) What are common solutions to these recurring problems? (3) How often are these common solutions instances of either convergence or parallelism? Our symposium speakers explored these questions through critical analysis of numerous datasets spanning multiple taxa, timescales, and levels of analysis. After discussions with our speakers, we suggest that the role of physical principles (e.g., drag, gravity, buoyancy, and viscosity) in constraining morphology and shaping the realized niche has been underappreciated. We recommend that investigations of these transitions and corresponding adaptations should include comparisons at multiple levels of biological organization and timescale. Relatedly, studies of organisms that undergo habitat and substrate changes over ontogeny would be worthwhile to include in comparisons. Future researchers should ideally complement lab-based morphological and kinematic studies with observational and experimental approaches in the field. Synthesis of the findings of our speakers across multiple study systems, timescales, and transitional habitats suggests that behavioral modification and exaptation of morphology play key roles in modulating novel transitions between substrates.
Estimating the Drivers of Diversification of Stoneflies Through Time and the Limits of Their Fossil Record
Authors: Jouault Corentin , Nel André , Legendre Frédéric , Condamine Fabien L
Published: August 2022

Deciphering the timing of lineage diversification and extinction has greatly benefited in the last decade from methodological developments in fossil-based analyses. If these advances are increasingly used to study the past dynamics of vertebrates, other taxa such as insects remain relatively neglected. Our understanding of how insect clades waxed and waned or of the impact of major paleoenvironmental changes during their periods of diversification and extinction (mass extinction) are rarely investigated. Here, we compile and analyze the fossil record of Plecoptera (1,742 vetted occurrences) to investigate their genus-level diversification and diversity dynamics using a Bayesian process-based model that incorporates temporal preservation biases. We found that the Permian-Triassic mass extinction has drastically impacted Plecoptera, while the Cretaceous Terrestrial Revolution corresponds with a turnover of plecopteran fauna. We also unveiled three major gaps in the plecopteran fossil record: the Carboniferous-Permian transition, the late Early Cretaceous, and the late Cenomanian to Bartonian, which will need to be further investigated. Based on the life history of extant Plecoptera, we investigate the correlations between their past dynamic and a series of biotic (Red Queen hypothesis) and abiotic (Court Jester hypothesis) factors. These analyses highlight the major role of continental fragmentation in the evolutionary history of stoneflies, which is in line with phylogeny-based biogeographic analyses showing how vicariance drove their diversification. Our study advocates analyzing the fossil record with caution, while attempting to unveil the diversification and extinction periods plus the likely triggers of these past dynamics of diversification.