bluuebunny/crossref_metadata_2025 huggingface dataset:
Can artificial intelligence prediction of successful atrial fibrillation catheter ablation therapy be interpretable?
Authors: Ogbomo-Harmitt S , Muffoletto M , Zeidan A , Qureshi A , King A , Aslanidi O
Published: December 2022

Background

Radiofrequency catheter ablation (RFCA) therapy is the first-line treatment for atrial fibrillation (AF), the most common type of cardiac arrhythmia globally. However, the procedure currently has low success rates in dealing with persistent AF, with a reoccurrence rate of ∼50% post-ablation. Therefore, artificial intelligence (AI), particularly deep learning (DL), has increasingly been applied to improve and optimise treatments for AF. However, AI is limited by its black-box nature. Therefore, a factor hindering the broad clinical application of DL in AF is the lack of assurance that the DL model is using physiological relevant features when making its prediction. In order to provide this assurance, its decision process needs to be interpretable and have biomedical relevance.

Aim

This study aims to explore interpretability in DL prediction of successful ablation therapy for AF and evaluate if pro-arrhythmogenic regions in the left atrium (LA) were used in its decision process.

Methods

LA models with segmented fibrotic tissue were derived from 122 late gadolinium-enhanced magnetic resonance (LGE MR) images of persistent AF patients. To increase the dataset size, an additional 199 synthetic LA tissue models were generated from the LGE MR images. Two ablation strategies were simulated: fibrosis-based ablation (FIBRO) and a rotor-based ablation (ROTOR). RFCA strategy success was determined by its ability to terminate persistent AF in 2s with less than 40% of the tissue ablated [1]. A convolutional neural network (CNN) was developed to predict the success of each RFCA strategy, and gradient weighted class activation maps (GradCAM) were used to assess if the CNN was using locations of pro-arrhythmogenic regions in its decision process on an independent test set of 50 LA tissue models.

Results

For predicting the success of the FIBRO strategy, the CNN model had an AUC (area under the receiver operating characteristic curve) of 0.92±0.02, recall of 0.89±0.03 and precision of 0.82±0.02. For the ROTOR strategy, the AUC was 0.77±0.02, the recall was 0.93±0.04 and the precision was 0.76±0.02. Finally, the independent test set's GradCAM saliency maps showed that 62±25% and 71±13% of ablation lesions (known from the LA model simulations, but unseen by the CNN during training) coincided with informative regions in the saliency maps for the FIBRO and ROTOR strategies, respectively (Figure 1).

Conclusion

The most informative regions of the saliency maps coincided with the successful ablation lesions, suggesting that the DL model was able to identify ablated pro-arrhythmogenic regions by leveraging structural features of LGE MR images. In the future, this technique could provide a clinician with a decision support tool and increase confidence in the AI prediction.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): UK Medical Research Council
Right heart catherisation – a virtual reality
Authors: Brown M , Krishnananthan N , Paul V
Published: December 2022

Introduction

Right heart catheterisation (RHC) is the gold standard for assessing patients with pulmonary hypertension. Doctors require training in this procedure in a safe and friendly environment with minimal risk to patients. Due to the Covid pandemic, formal RHC teaching workshops were cancelled in our country, so we sought to develop a Virtual Reality Right Heart Catheterisation (VRRHC) training program to fulfil this area of need without the need for face to face contact. The aim was to improve training, competency and confidence in this technique with improved diagnostic skills and reduction of procedural errors.

Method

We approached a health technology company to design a VRRHC training module based on our current RHC simulation workshops. Phase 1 required virtual insertion of RHC via the right internal jugular vein using micro-puncture, double Seldinger technique under ultrasound guidance, followed by insertion of the RHC to the right atrium, right ventricle and pulmonary artery with pulmonary artery occlusion using real time pressure tracings and fluoroscopy. Thermodilution cardiac outputs and chamber saturations were also performed.

The proprietary platform technology was delivered via a laptop and VR headset. Clinicians perform the VRRHC with imaging, monitoring and haptic feedback with the collection of real time performance tracking allowing user data (e.g. failed steps and proficiency scores) to be captured and subsequently visualised in the learning management system.

We collected analytics and data on user engagement, experience and retention, targeted learning outcomes and learning curve, reduction in operating costs, reduction in procedure times due to higher proficiency, early diagnosis of pulmonary hypertension, reduced complications, improved interpretation and diagnosis.

Results

The program was launched in October 2021. Preliminary data shows a learning curve is associated with both using VR (10–15 minutes) and the RHC procedure itself. Initial time to completion of the RHC was 30–40 mins, reducing to 20–30 minutes with experience and 15 minutes in experts. Completion rates increase with experience from 40–50% to 100% and error rates reduce with frequency of completion.

Conclusion

A Virtual Reality Right Heart Catheter training program is safe, feasible and non-invasive. Increased experience results in increased completion rates, reduced procedure time and reduced errors. Using this program will potentially have beneficial effects on doctor training, outcomes, patient safety and health economics with no risk to a real patient.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Janssen Pharmaceuticals
Telemedical monitoring and coaching improves survival and hospitalisation rates in heart failure
Authors: Knoll K , Rosner S , Trenkwalder T , Lennerz C , Dittrich D , Kloss C , Doerr M , Schunkert H , Reinhard W
Published: December 2022

Aims

To investigate the effectiveness of a combined telemonitoring and telecoaching programme for chronic heart failure patients at high risk for hospitalisation compared to usual care in a real life setting. The applied telehealth programme consisted of regular individualised telecoaching sessions as well as daily remote telemonitoring of heart failure signs and symptoms.

Methods

Between January 2018 and September 2020, 6,065 heart failure patients were enrolled in a combined telehealth programme and retrospectively compared to a propensity matched usual care group (n=6,065). All participants were members of a statutory health insurance. Median follow-up was 442 days (IQR 309–681). Endpoints were all cause mortality, number and duration of hospitalisations.

Results

After 1 year the combined telecoaching and telemonitoring programme significantly reduced all-cause mortality probability compared to usual care (11.0 vs. 5.8%, p<0.001). The corresponding number-needed to treat to prevent one death in one year was 19.3. In addition, the number of hospitalisations for heart failure (17.9 vs. 21.8 per 100 patient years, p<0.001) and all cause hospitalisations (129.0 vs. 133.2, p=0.015), as well as their duration (2.0 vs. 2.6 days per year p<0.001, and 12.0 vs. 13.4 days per year p>0.001, respectivel y) were significantly lower in the telehealth group than in the usual care group.

Conclusion

In ambulatory heart failure patients at high risk for hospitalisation, a combined telemonitoring and telecoaching programme led to a reduction of heart failure hospitalisations and all-cause mortality compared to standard care.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Health Care Systems GmbH (HCSG), Pullach i. Isartal
Performance of a multisensor implantable defibrillator algorithm for HF monitoring in presence of comorbidities
Authors: Santobuono V E , Tavoletta V , Manzo M , Calo' L , Bertini M , Santini L , Savarese G , Dello Russo A , Viscusi M , Lavalle C , Amellone C , Calvanese R , Valsecchi S , Favale S
Published: December 2022

Background

Cardiovascular and non-cardiovascular comorbidities are common in heart failure (HF) patients and impact disease severity and prognosis. Select modern implantable defibrillators (ICDs) are equipped with multisensor algorithms for HF monitoring. The HeartLogic index combines multiple ICD-based sensor data (heart rate, heart sounds, thoracic impedance, respiration, activity), and the associated alert has proved to be a sensitive and timely predictor of impending HF decompensation in cardiac resynchronization therapy (CRT-D) patients The algorithm was developed using data from CRT-D patients; the performance in non-CRT ICD patients and the impact of selected comorbidities on performance requires further study.

Methods

The HeartLogic feature was activated in 568 ICD patients (410 with CRT) from 26 centers. The median follow-up was 25 months [25th–75th percentile: 15–35].

Results

During follow-up, 97 hospitalizations were reported (53 cardiovascular) and 55 patients died. We recorded 1200 HeartLogic alerts (0.71 alerts/patient-year) in 370 patients. Overall, the time IN the alert state was 13% of the total observation period. The rate of cardiovascular hospitalizations or death was 0.48/patient-year (95% CI: 0.37–0.60) with the HeartLogic IN alert state and 0.04/patient-year (95% CI: 0.03–0.05) OUT of alert state, with an incidence rate ratio of 13.35 (95% CI: 8.83–20.51, p<0.001). Among patient characteristics, atrial fibrillation (AF) at implantation (HR: 1.62, 95% CI: 1.27–2.07, p<0.001) and chronic kidney disease (CKD) (HR: 1.53, 95% CI: 1.21–1.93, p<0.001) independently predicted alerts. HeartLogic alerts were not associated with CRT vs. non-CRT device implantation (HR: 1.03, 95% CI: 0.82–1.30, p=0.775). The comparisons of the clinical event rates in the IN alert state with those in the OUT of alert state yielded incidence rate ratios ranging from 9.72 to 14.54 (all p<0.001) in all groups of patients stratified by: CRT/non-CRT, AF/non-AF, CKD/non-CKD. Indeed, after multivariate correction for CKD and AF at implantation, the time IN the HeartLogic alert state >13% was associated with the occurrence of the combined endpoint of cardiovascular hospitalization or death (HR: 2.54, 95% CI: 1.61–4.01, p<0.001).

Conclusions

The burden of HeartLogic alerts appears similar between CRT and non-CRT patients, while patients with AF and CKD seem more exposed to alerts. Nonetheless, the ability of the HeartLogic algorithm to identify patients during periods of significantly increased risk of clinical events is confirmed regardless of the type of device, the presence of AF, or CKD.

Funding Acknowledgement

Type of funding sources: None.
Use of a device-based remote management heart failure care pathway is associated with reduced hospitalization and improved patient outcomes: TriageHF Plus real-world evaluation
Authors: Ahmed F Z , Sammut-Powell C , Martin G P , Callan P , Cunnington C , Kale M , Gerritse B , Lanctin D , Soken N , Campbell N G , Taylor J K
Published: December 2022

Background

Heart failure (HF) is a leading cause of hospital admission. However, prompt identification of worsening HF using implantable device data and proactive intervention may reduce hospitalizations.

The validated TriageHF algorithm in enabled ICD/CRT devices uses sensor data to risk stratify patients for HF hospitalization in the next 30 days. TriageHF Plus is a novel device-based HF care pathway (DHFP) that uses “high” risk status as the trigger for remote intervention (see Figure 1 for pathway overview). Outcomes after DHFP implementation in a clinical setting have not been examined.

Purpose

To evaluate the impact of TriageHF Plus clinical pathway on hospitalisation rates.

Methods

A prospective, multi-center evaluation comparing monthly hospitalization rates for patients enrolled in a DHFP with a concurrent standard of care (SoC) cohort and characterizing staffing resources necessary to implement the DHFP. The DHFP cohort received telephonic assessment and guideline-directed clinical care upon transition to high-risk status. Propensity scores (PS) were applied to DHFP and SoC cohorts to allow unbiased comparison. A negative binomial model was fitted to the monthly number of all-cause hospitalizations with treatment group (DHFP vs. SoC) as a covariate, using PS as weights.

Results

Between 09/11/2019 and 06/24/2021, 758 patients were included in the study (443 DHFP, 315 SoC). Proportion CRT 76%/ 89% and LVEF <50% 78%/ 66% for DHFP/ SoC, respectively.

196 high risk transmissions prompted telephone assessment, with successful contact in 182; of which, 79 (43%) identified an explanatory acute medical issue. A secondary intervention was undertaken in 44/79 (56%). High risk transmissions took on average 19 minutes per clinical assessment (initial telephone triage and 30 day follow up). The rate of hospitalizations was 58% lower in the DHFP group, compared with SoC, after PS adjustment (IRR 0.42, 95% CI: 0.23, 0.76, p=0.004), see Figure 2. Sensitivity analyses showed Covid-19 had little effect on results.

Conclusions

This is the first prospective, real-world evaluation of a device-based HF care pathway to report a reduction in hospitalizations and does so with minimal staffing time. Integrated into existing HF services, device-based remote monitoring of HF patients can improve outcomes.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Medtronic
Effects of the COVID-19 pandemic on offering and acceptance in a cardiac rehabilitation programme: introduction of a remote CR programme
Authors: Sestayo Fernandez M , Alonso Vazquez M , Gonzalez Maestro A , Gonzalez Salvado V , Gonzalez Juanatey J R , Pena Gil C
Published: December 2022

Background

The impact of the COVID-19 pandemic on multimodal cardiac rehabilitation (CR) programmes has forced a continuous readjustment of clinical practice. Our regional healthcare system was faced with providing quality remote CR to ischaemic heart disease (IHD) patients in a scattered, mostly rural population, for which three new CR modalities replaced the previous in-person CR program: 1) telephone follow-up programme, 2) TELEA online platform for patient follow-up and 3) TELEA online follow-up & online training sessions.

Purpose

To study the impact of the COVID-19 pandemic on CR offering and acceptance and the reasons for patient refusal, and to assess the outcome of new remote CR modalities in this setting.

Methods

Single center, observational retrospective study from all consecutive patients with IHD eligible for CR from 2015 to 2021. A descriptive analysis of patient baseline characteristics, CR modality, offering and acceptance rates, and reasons for refusal per year was performed. Additionally, a comparative analysis of “pre-COVID period” (Jan 2015–Feb 2020) vs. “COVID period” (Mar 2020–Dec 2021) was performed to assess the impact of the pandemic on patient recruitment and the usefulness of remote CR modalities to enhance participation.

Results

N=2626 patients (20% women, 69.7±45.8 years) were offered CR from 2015 to 2021. CR offering decreased from the pre-COVID (78.6%) to the COVID period (52.6%), while participation increased (67.9% and 79.7%, respectively) Figure 1. Reasons for CR refusal significantly changed with an odds ratio (OR) of 5.63 and confidence interval (CI) 95% (3.2–9.9). In the pre-COVID period main reasons for CR refusal was “transportation difficulties” (47%); while during the COVID-19 period, the main reason shifted to “lack of interest” (78.2%) (Table 1).

Conclusions

Offering CR decreased during the COVID pandemic possibly due to stricter inclusion criteria. However, the implementation of new remote CR modalities allowed not only to maintain similar levels of acceptance but also to improve it despite the unfavourable setting, and helped to amend transportation difficulties as the leading reason for refusal. Remote CR may be a useful tool, combined with in-person programs, to enhance participation in CR.

Funding Acknowledgement

Type of funding sources: None.
Employment Decline During the Great Recession: the Role of Firm Size Distribution
Authors: Xu Wenjian
Published: December 2022

Over 8,000,000 jobs were lost in the Great Recession, creating widespread economic hardship. This paper documents a novel and robust empirical regularity that highly concentrated local labour markets experienced larger employment declines during the Great Recession. Through setting up a model with heterogeneous firms facing idiosyncratic productivity shocks, I show that firm size distribution summarised by the Herfindahl-Hirschman index plays a crucial role in the reallocation of workers, and it magnifies negative idiosyncratic shocks and attenuates positive ones. I undertake a series of empirical tests to rule out alternative explanations, and show that large employment losses in concentrated labour markets are not driven by highly concentrated industry locations being hit harder during the Great Recession, having smaller labour markets or higher firm leverage ratios. The effect of concentration level is larger in sectors with higher labour supply elasticity, or a higher variance of productivity shocks, and rises during the Great Recession compared to other periods, consistent with my model’s predictions.
Eliminating the ecological hazards of Heterosigma akashiwo bloom by a microbial algicide: removal of nitrite contamination, redirection of carbon flow and restoration of metabolic generalists
Authors: Cai Guanjing , Yu Xiaoqi , Cai Runlin , Wang Hui
Published: December 2022

Harmful algal blooms (HABs) attracted much attention due to their extensive ecological hazards and the increasing influences on global biogeochemical cycles with the intensification of human impact and global warming. Lysing algal cells with species-specific microbial algicide seemed to be promising to eliminate HABs, but the potential ecotoxicity was rarely studied. In this study, microcosms simulating Heterosigma akashiwo blooms were established to reveal the influences of a microbial algicide from Streptomyces sp. U3 on the biological, physicochemical parameters and bacterial community. The results showed that H. akashiwo bloom accumulated nitrite to a lethal dose, produced bio-labile DOM with widespread influences and enriched pathogenic Coxiella to a high abundance. Lysing H. akashiwo cells by microbial algicide induced a bacterial bloom, eliminated nitrite contamination, enhanced the recalcitrance of DOM, and restored bacterial population from a Gammaproteobacteria-dominant community during bloom back to an Alphaproteobacteria-dominant community similar to the non-bloom seawater. Succession of bacterial genera further suggested that the variation from algal exudates to lysates promoted the restoration of metabolic generalists, which redirected the carbon flow to a less ecologically impactive path. This study revealed the benefits of using microbial algicide to remediate the ecological hazards of HABs, which provided references for future application.
A Least-Cost Dynamic Optimization Approach for Obtaining a Desired Balanced Uneven-Aged Structure
Authors: Lamsal Basanta , Wagner John E , Germain René
Published: December 2022

There has been increasing interest among foresters and landowners in modifying existing even-aged forest structures to multi-aged or uneven-aged structures. Maintaining a continuous forest structure often provides a wider array of forest values over the long term. The conversion process is challenging in regions of the Northeast United States characterized by forests composed of dense diseased beech thickets and low-vigor deformed overstory trees. Abundance of noncommercial beech may result in negative cash flows during the conversion process to achieve a desired balanced uneven-aged structure. The Forest Vegetation Simulator was used to model growth and yield. Given the possibility of negative cash flows, a least-cost dynamic program with a penalty function was used to determine least-cost time paths for two management scenarios, one characterized by the successful removal of beech and the other simulating the continued presence of beech. Incorporating a penalty function allowed creating a continuum of least-cost paths from a zero penalty with the greatest weight given to net revenue goals to the largest penalty with the greatest weight given to ecological goals. Sensitivity analyses revealed least-cost paths were more stable given changes in prices and wages when greater emphasis was placed on the ecological goals associated with the target structure.
Effects of 1-methylcyclopropene treatment on the quality of red ‘Fuji’ apples fruit during short-term storage
Authors: Peng Zhenzhen , Fu Daqi
Published: December 2022

Objectives

The aim of this study is to determine the mechanism through which 1-methylcyclopropene (1-MCP) affects the quality of red ‘Fuji’ apples, which were stored for a short duration.

Materials and Methods

Red ‘Fuji’ apples were treated with 1-MCP (1.0 μl/L), stored at 25 °C for 0, 12, 24, 48, 72, and 96 h, and ethylene production was measured. An integrated metabolomic and transcriptomic analysis was performed on apples stored for 24 h.

Results

The release of ethylene was significantly delayed from red ‘Fuji’ apples subjected to 1-MCP treatment. By performing an integrated transcriptome and metabolome analyses, we identified 117 differentially expressed genes (DEGs) and 44 differentially accumulated metabolites (DAMs). By performing functional enrichment analysis, we found that DEGs were involved in the following pathways: carbon metabolism (LPD2, gpmA, LTA2, ACC, PSAT1, MdCAS2), phytohormone signal transduction (EBF1), amino acid metabolism (MdACS-1), fatty acid metabolism (LOX1.5, KCS4, KAS1), energy metabolism (Lhcb1, Lhcb6, PsbY, GPDHC1, PUMP5), metabolic pathways (TRE1, HEXO1) and cell wall metabolism (CSLG2). Thus, these DEGs were involved in the ripening of fruits, and they controlled the quality of fruits at the post-harvest stage. The metabolites were enriched with DAMs. These were found to be individually involved in the metabolic pathway, secondary metabolite biosynthesis, phenylpropanoid biosynthesis, flavonoids, and flavonol synthesis.

Conclusions

The results indicate that 1-MCP inhibits the biosynthesis of ethylene and suppresses energy metabolism. Moreover, it also downregulates metabolic pathways and the enzymatic genes related to fruit quality. Therefore, 1-MCP delays the ripening of fruits at the post-harvest stage. This study helps us understand how 1-MCP treatment affects the ripening and quality of fruits.
Variation in mutational (co)variances
Authors: Mallard François , Noble Luke , Baer Charles F , Teotónio Henrique
Published: December 2022

Because of pleiotropy, mutations affect the expression and inheritance of multiple traits and, together with selection, are expected to shape standing genetic covariances between traits and eventual phenotypic divergence between populations. It is therefore important to find if the M matrix, describing mutational variances of each trait and covariances between traits, varies between genotypes. We here estimate the M matrix for six locomotion behavior traits in lines of two genotypes of the nematode Caenorhabditis elegans that accumulated mutations in a nearly neutral manner for 250 generations. We find significant mutational variance along at least one phenotypic dimension of the M matrices, but neither their size nor their orientation had detectable differences between genotypes. The number of generations of mutation accumulation, or the number of MA lines measured, was likely insufficient to sample enough mutations and detect potentially small differences between the two M matrices. We then tested if the M matrices were similar to one G matrix describing the standing genetic (co)variances of a population derived by the hybridization of several genotypes, including the two measured for M, and domesticated to a lab-defined environment for 140 generations. We found that the M and G were different because the genetic covariances caused by mutational pleiotropy in the two genotypes are smaller than those caused by linkage disequilibrium in the lab population. We further show that M matrices differed in their alignment with the lab population G matrix. If generalized to other founder genotypes of the lab population, these observations indicate that selection does not shape the evolution of the M matrix for locomotion behavior in the short-term of a few tens to hundreds of generations and suggests that the hybridization of C. elegans genotypes allows selection on new phenotypic dimensions of locomotion behavior.
Behavioural plasticity in the use of a neritic foraging area by loggerhead sea turtles: insights from 37 years of capture–mark–recapture in the Adriatic Sea (Mediterranean Sea)
Authors: Baldi Giulia , Furii Giovanni , Del Vecchio Massimo , Salvemini Pasquale , Vallini Carola , Angelini Valeria , Pari Sauro , Lombardi Moraes Kamyla , Profico Chiara , Olivieri Vincenzo , Margaritoulis Dimitris , Rees Alan F , Çurri Anxhela , Hochscheid Sandra , Freggi Daniela , Lazar Bojan , Luschi Paolo , Casale Paolo
Published: December 2022

Assessing sea turtle movements and connectivity among different areas is pivotal to understanding their biology and implementing efficient conservation actions. In the Adriatic Sea, one of the most important sea turtle foraging areas in the Mediterranean, a total of 311 capture–mark–recapture (CMR) records (mostly bycatch) from 294 loggerhead turtles (Caretta caretta) in the period 1984–2021 were analysed. A general fidelity pattern to Adriatic subareas was indicated by a significantly shorter CMR distance than the potential dispersal distance and by the significantly higher proportion of re-encounters in the same area of release than expected. No seasonal pattern was detected between subareas, and shorter re-encounter distances were observed in turtles released and re-encountered in the same season, suggesting different winter and summer residential areas. Results suggest that turtles frequenting the Adriatic can go anywhere in the Mediterranean basin and may exhibit a wandering behaviour regardless of their size. A substantial connectivity with nesting sites in Greece was observed, confirming with empirical evidence that this is the most important breeding area for turtles foraging in the Adriatic Sea. This study highlights the value of cooperation among different groups and shows a main behavioural pattern of fidelity to neritic foraging grounds.
Comparison of Quantitative Values of Headspace Gas Chromatography--Mass Spectrometry and a Formate Quantification Kit in Blood Formate Quantification
Authors: Yoshida Haruhi , Harada Kazuo , Sakamoto Yukari , Yoshimura Jumpei , Shimazu Takeshi , Matsumoto Hiroshi
Published: December 2022

Methanol poisoning is caused by the toxicity of formate, a by-product of methanol metabolism. Measurement of blood formate concentrations is required for emergency treatment and investigation of the cause of death. In this study, we measured concentrations of formate in the plasma of a patient with methanol poisoning using headspace gas chromatography--mass spectrometry (HS-GC--MS) and a formate assay kit. Results showed a discrepancy as the quantitative values of the kit were higher than those of HS-GC--MS. Metabolic profiling of low-molecular-weight organic compounds in patient plasma samples showed that the concentrations of lactate were correlated with the values obtained using the kit. We observed a progression when lactate and lactate dehydrogenase were added to the kit reaction simultaneously, even in the absence of formate. Moreover, disulfiram, an aldehyde dehydrogenase inhibitor, suppressed the values of patient plasma samples in the formate assay kit, implying that formate production from remaining methanol in patient plasma samples via formaldehyde occurred during the kit reaction. The reactions of the kit with lactate and methanol were undesirable for accurate measurement of formate concentration in the sample. However, considering that elevated concentrations of lactate and remaining methanol both cause acidosis and are dangerous to the body, cross-reactions with lactate and methanol in the formate assay kit may be acceptable for rapid diagnosis in facilities where HS-GC--MS and other physical and chemical equipment are unavailable.
A Retrospective Analysis of Sternal Lesions Detected on Breast MRI in Patients Without History of Cancer
Authors: Jen Aaron , Kochkodan-Self Jeanne , Mandell Jacob C
Published: December 2022

Objective

To determine the imaging characteristics and stability over time of sternal lesions identified on breast MRI in patients without history of cancer.

Methods

An IRB-approved retrospective analysis of all breast MRIs performed at our institution from September 1, 2017 to December 1, 2021 that included one of several key words related to the sternum. Studies with history of non-dermatologic malignancy including breast cancer, absence of a true sternal lesion, or presence of symptoms during the examination were excluded. Imaging was reviewed for size, distribution, signal characteristics, and presence of contrast enhancement, perilesional edema, periosteal edema, or intralesional fat. Available comparison imaging, clinical history, and follow-up recommendations were reviewed. Descriptive statistics were used to summarize lesion data.

Results

Of 60 lesions included from 60 patients, 40 lesions with more than two years of comparison imaging were either stable or decreased in size and none demonstrated change in signal characteristics. The majority of these presumed benign lesions demonstrated hypointense signal on T1-weighted sequences (21/40, 52.5%), hyperintense signal on fluid-sensitive sequences (33/40, 82.5%), contrast enhancement (32/40, 80.0%), and absence of clear intralesional fat (29/40, 72.5%). One patient who did not have comparison imaging was diagnosed with malignancy (multiple myeloma) eight months following their MRI. This lesion demonstrated uniquely diffuse and heterogeneous enhancement but did not undergo biopsy.

Conclusion

Sternal lesions in women without history of non-dermatologic malignancy have a very low likelihood of malignancy. Common imaging characteristics of the presumed benign lesions can inform imaging recommendations when incidental sternal lesions are discovered.
Using International Environmental Law to Enhance Biodiversity and Nature Conservation During Armed Conflict
Authors: Hulme Karen
Published: December 2022

Biodiversity and nature are severely impacted by armed conflict, particularly those fought in biodiversity-rich environments. Whether harm is caused directly by bullets and bombs, through the seepage of toxic chemicals into rivers and soils, the ground-churning tracks of tanks, or the ‘conservation vacuum’ the result is often the same — severe, possibly permanent, ecological change. International humanitarian law (IHL) has consistently come up short in delivering environmental protection on the battlefield. Can international environmental law (IEL) fare any better? The International Law Commission (ILC) and the International Committee of the Red Cross (ICRC) have both submitted major new guidelines in the last two years, following more than a decade of in-depth analysis of the IHL rules governing protection of the environment in relation to armed conflict. However, neither body was able to analyse the applicability of IEL obligations during armed conflict. Several authors have more recently entered this space, but none have so far undertaken a rule-by-rule analysis and spanning such a range of treaties. This article assesses the potential of the main biodiversity and nature conservation treaties to offer further environmental protection during armed conflict. Identifying complementary IEL obligations, particularly in relation to the conduct of hostilities, could be valuable to both mirror and reinforce IHL protections, and would ensure that IEL treaty bodies and third states have a basis upon which to promote conservation work with the parties to the conflict.
Mifepristone, preemption, and public health federalism
Authors: Zettler Patricia J , Beckmeyer Annamarie , Brown Beatrice L , Sarpatwari Ameet
Published: December 2022

On June 24, 2022, the Supreme Court issued an opinion in which five justices voted to overturn Roe v Wade. Even before the final opinion issued, scholars and advocates had begun to consider legal strategies that might mitigate the decision’s anticipated harmful consequences. One such strategy involves challenging state restrictions on Food and Drug Administration (FDA)-approved pregnancy termination drugs on preemption grounds. This article begins by exploring how these challenges might fare—considering both drug-specific restrictions and complete bans on abortion—arguing that there are compelling legal grounds on which courts should conclude that many state restrictions are preempted. Importantly, although these state restrictions have arisen within a larger debate about reproductive health care, this is far from the only area in which states seek to regulate prescription drugs. States have long regulated drugs in ways that diverge from FDA, arguably increasingly so in recent years. Accordingly, the article investigates the implications that preemption challenges in the abortion context may have for other areas of state drug regulation, making the case that the benefits of public health federalism need not be undermined by successful preemption challenges in the abortion arena.
Tandem chimeric antigen receptor (CAR) T cells targeting EGFRvIII and IL-13Rα2 are effective against heterogeneous glioblastoma
Authors: Schmidts Andrea , Srivastava Ambike A , Ramapriyan Rishab , Bailey Stefanie R , Bouffard Amanda A , Cahill Daniel P , Carter Bob S , Curry William T , Dunn Gavin P , Frigault Matthew J , Gerstner Elizabeth R , Ghannam Jack Y , Kann Michael C , Larson Rebecca C , Leick Mark B , Nahed Brian V , Richardson Leland G , Scarfò Irene , Sun Jing , Wakimoto Hiroaki , Maus Marcela V , Choi Bryan D
Published: December 2022

Background

Chimeric antigen receptor (CAR) T cells have achieved remarkable responses in patients with hematological malignancies; however, the potential of this therapeutic platform for solid tumors like glioblastoma (GBM) has been limited, due in large part to the targeting of single antigens in a heterogeneous disease. Strategies that allow CAR T cells to engage multiple antigens concomitantly may broaden therapeutic responses and mitigate the effects of immune escape.

Methods

Here we have developed a novel, dual-specific, tandem CAR T (TanCART) cell with the ability to simultaneously target both EGFRvIII and IL-13Rα2, two well-characterized tumor antigens that are frequently found on the surface of GBM cells but completely absent from normal brain tissues. We employed both standard immunological assays and multiple orthotopic preclinical models including patient-derived xenograft to demonstrate efficacy of this approach against heterogeneous tumors.

Results

Tandem CAR T cells displayed enhanced cytotoxicity in vitro against heterogeneous GBM populations, including patient-derived brain tumor cultures (P < .05). Compared to CAR T cells targeting single antigens, dual antigen engagement through the tandem construct was necessary to achieve long-term, complete, and durable responses in orthotopic murine models of heterogeneous GBM, including patient-derived xenografts (P < .05).

Conclusions

We demonstrate that TanCART is effective against heterogeneous tumors in the brain. These data lend further credence to the development of multi-specific CAR T cells in the treatment of GBM and other cancers.
The sleep homeostatic response to sleep deprivation in humans is heritable
Authors: Goldschmied Jennifer R , Kuna Samuel T , Maislin Greg , Tanayapong Pongsakorn , Pack Allan I , Younes Magdy
Published: December 2022

Study Objectives

Following sleep deprivation, increases in delta power have historically been used to index increases in sleep pressure. Research in mice has demonstrated that the homeostatic delta power response to sleep deprivation is heritable. Whether this is true in humans is unknown. In the present study, we used delta power and ORP, a novel measure of sleep depth, to investigate the effects of acute sleep deprivation on sleep depth and to assess the heritability of sleep homeostasis in humans.

Methods

ORP and delta power were examined during baseline and recovery sleep following 38 h of sleep deprivation in 57 monozygotic and 38 dizygotic same-sex twin pairs. Two complementary methods were used to estimate the trait heritability of sleep homeostasis.

Results

During recovery sleep, ORP was lower and delta power was higher than at baseline, indicating deeper sleep. However, at the end of the recovery night, delta power reached baseline levels but ORP demonstrated incomplete recovery. Both ORP and delta power showed a broad sense heritability of sleep homeostasis following sleep deprivation. The classical approach demonstrated an h2 estimate of 0.43 for ORP and 0.73 for delta power. Mixed-effect multilevel models showed that the proportion of variance attributable to additive genetic transmission was 0.499 (95% CI = 0.316–0.682; p < .0001) for ORP and 0.565 (95% CI = 0.403–0.726; p < .0001 for delta power.

Conclusions

These results demonstrate that the homeostatic response to sleep deprivation is a heritable trait in humans and confirm ORP as a robust measure of sleep depth.
Safety of Stromal Vascular Fraction Cell Therapy for Chronic Kidney Disease of Unknown Cause (Mesoamerican Nephropathy)
Authors: Carstens Michael H , García Nelson , Mandayam Sreedhar , Workeneh Biruh , Pastora Indiana , Calderón Carlos , Bertram Kenneth A , Correa Diego
Published: December 2022

Chronic kidney disease of unknown cause (CKDu), also known as Mesoamerican nephropathy, typically presents as an ischemic nephropathy with chronic tubulointerstitial fibrosis in normotensive patients, rapidly progressing to kidney failure. In this first-in-human, open-label, safety study, we followed 18 patients with CKDu (stages 3-5) for 36 months after receiving a single infusion of angiogenic/anti-fibrotic autologous adipose-derived stromal vascular fraction (SVF) cells into their kidneys bilaterally via renal artery catheterization. SVF therapy was safe and well tolerated. There were no SVF-related serious adverse events and no procedural complications. Color Doppler evaluation at 2 months demonstrated increased perfusion to the interlobar and/or arcuate artery levels in each kidney evaluated (36/36) with a reduction in resistance index at the hilar artery (35/36) kidneys. Beyond 12 months, patients with initial eGFR <30 mL/minute/1.73 m2 deteriorated, whereas those ≥30 mL/minute/1.73 m2 further sustained their renal function, suggesting a possible renal protective effect in that group.
Striving toward Community-Engaged and Participatory Methods: Considerations for Researchers in Academic Settings
Authors: Narendorf Sarah C , Ali Samira , Lea Charles H , Pritzker Suzanne
Published: December 2022

Community-engaged and participatory methods are increasingly used by academic researchers. Power dynamics in academia shape the landscape in which researchers implement these methods, yet are rarely understood and intentionally addressed. Through the lens of social work researchers at different career stages, this article describes how power relations within academia present challenges to community-engaged and participatory research across four stages of the research process (participant/researcher relationship, study formulation, conducting research, and publication/dissemination). These challenges are located within four domains of power identified by intersectionality scholars: Institutional policies such as those for tenure and promotion and for research administration presented challenges with the structural domain. Decisions about how to implement and enforce policies and operationalize what counts for tenure and promotion were identified as challenges within the disciplinary domain. Norms about who belongs on a university campus and what types of research are valued exemplified the cultural domain, while dynamics about who is viewed as an expert exemplified challenges the interpersonal domain. Across the research process, the article identifies potential solutions and suggests strategies for intentional consideration by academic researchers and their institutions to conduct meaningful, inclusive, and socially just research that shares power with community.
An approach of dynamic response analysis of nonlinear structures based on least square Volterra kernel function identification
Authors: Zhang Zhenhao , Xiong Jun , Zhao Zhenpeng , Wang Fuming , Zeng Yi , Zhao Bing , Ke Lu
Published: December 2022

Analysis of the dynamic response of a complex nonlinear system is always a difficult problem. By using Volterra functional series to describe a nonlinear system, its response analysis can be similar to using Fourier/Laplace transform and linear transfer function method to analyse a linear system's response. In this paper, a dynamic response analysis method for nonlinear systems based on Volterra series is developed. Firstly, the recursive formula of the least square method is established to solve the Volterra kernel function vector, and the corresponding MATLAB programme is compiled. Then, the Volterra kernel vector corresponding to the nonlinear response of a structure under seismic excitation is identified, and the accuracy and applicability of using the kernel vector to predict the response of a nonlinear structure are analysed. The results show that the Volterra kernel function identified by the derived recursive formula can accurately describe the nonlinear response characteristics of a structure under an excitation. For a general nonlinear system, the first three order Volterra kernel function can relatively accurately express its nonlinear response characteristics. In addition, the obtained Volterra kernel function can be used to accurately predict the nonlinear response of a structure under the similar type of dynamic load.
Exploring the stimulative effect on following drivers in a consecutive lane change using microscopic vehicle trajectory data
Authors: Gu Ruifeng , Li Ye , Cen Xuekai
Published: December 2022

Improper lane-changing behaviours may result in breakdown of traffic flow and the occurrence of various types of collisions. This study investigates lane-changing behaviours of multiple vehicles and the stimulative effect on following drivers in a consecutive lane-changing scenario. The microscopic trajectory data from the HighD dataset are used for driving behaviour analysis. Two discretionary lane-changing vehicle groups constitute a consecutive lane-changing scenario, and not only distance- and speed-related factors but also driving behaviours are taken into account to examine the impacts on the utility of following lane-changing vehicles. A random parameters logit model is developed to capture the driver's psychological heterogeneity in the consecutive lane-changing situation. Furthermore, a lane-changing utility prediction model is established based on three supervised learning algorithms to detect the improper lane-changing decision. Results indicate that 1) the consecutive lane-changing behaviours have a significant negative effect on the following lane-changing vehicles after lane change; 2) the stimulative effect exists in a consecutive lane-change situation and its influence is heterogeneous due to different psychological activities of drivers; and 3) the utility prediction model can be used to detect an improper lane-changing decision.
A bearing fault diagnosis method based on a convolutional spiking neural network with spatial–temporal feature-extraction capability
Authors: Zhang Changfan , Xiao Zunguang , Sheng Zhenwen
Published: December 2022

Convolutional neural networks (CNNs) are widely used in the field of fault diagnosis due to their strong feature-extraction capability. However, in each timestep, CNNs only consider the current input and ignore any cyclicity in time, therefore producing difficulties in mining temporal features from the data. In this work, the third-generation neural network—the spiking neural network (SNN)—is utilized in bearing fault diagnosis. SNNs incorporate temporal concepts and utilize discrete spike sequences in communication, making them more biologically explanatory. Inspired by the classic CNN LeNet-5 framework, a bearing fault diagnosis method based on a convolutional SNN is proposed. In this method, the spiking convolutional network and the spiking classifier network are constructed by using the integrate-and-fire (IF) and leaky-integrate-and-fire (LIF) model, respectively, and end-to-end training is conducted on the overall model using a surrogate gradient method. The signals are adaptively encoded into spikes in the spiking neuron layer. In addition, the network utilizes max-pooling, which is consistent with the spatial-temporal characteristics of SNNs. Combined with the spiking convolutional layers, the network fully extracts the spatial-temporal features from the bearing vibration signals. Experimental validations and comparisons are conducted on bearings. The results show that the proposed method achieves high accuracy and takes fewer time steps.
Design of concise robust control for longitudinal motion of YuKun
Authors: Liu Chenfei , Xiao Peikun , Zhang Xianku , Wang Pengqi , Wang Jiafu , Hu Dinghuo
Published: December 2022

With the rapid development of the shipping industry, the safety and comfort of ship transportation have been paid more and more attention, and the pitch and heave motion of ships are the most serious factors. In this paper, the longitudinal motion mathematical model of YuKun is established. By assigning the zero-pole to the left half-plane and using the properties of the symmetric matrix, the shaping weighting functions matrix is designed to stabilize the multi-input multi-output (MIMO) system of YuKun. Finally, a new concise robust controller is designed using the steady output of the shaped system. The simulation results show that under the control of the concise robust controller, the pitch angle and heave of YuKun decrease by 79.9% and 86.2%, respectively. Theoretical analysis and simulation results show that the concise robust controller has a good control effect on the longitudinal motion of YuKun, and is simple and easy to use, with clear engineering significance.