Recovery Phase Research Articles

Enhancement of the reactivation process of long-term starved anammox granular sludge with gravel balls: Microbial succession and metabolic impact

Anaerobic ammonium oxidation (Anammox) process is an economical and energy-efficient method of wastewater nitrogen removal. However, they are highly susceptible to starvation stress caused by sudden environmental changes. Rapid reactivation of starved anammox sludge is a crucial method to address seed sludge shortages and expand practical applications. This study investigated the impact of gravel balls on the reactivation of long-term starved anammox granular sludge (628 days). The results showed that gravel balls enhanced the recovery of nitrogen removal performance in starved anammox sludge, with nitrogen removal efficiency being 19.88% higher than the control group at the end of the recovery phase. The gravel balls also increased extracellular polymeric substance (EPS) secretion, contributing to the stability of the anammox system. Furthermore, the gravel balls promoted the proliferation of anammox bacteria, with the relative abundance of anammox bacteria reaching 38.25% on the 80th day. The analyses of microbial functions indicated that gravel balls facilitated cross-feeding and co-metabolism among microbes, while enhancing quorum sensing associated with anammox bacteria, forming a multifunctional community network centered on anammox bacteria. This indicates that gravel balls can effectively accelerate the reactivation process of long-term starved anammox sludge, aiding the reutilization of long-term starved anammox sludge.

The Effect of War on Spatial Differentiation of Real Estate Values and Urban Disorder in the Damascus Metropolitan Area

The Syrian war, which commenced in 2011, transformed the Damascus real estate market due to heightened insecurity and tenure disputes. Using the hedonic price models, including 2411 housing transactions over the period 2010–2022, this study aims to understand the spatial dynamics of the real estate market in wartime. Our findings indicate that war variables have had a significant impact on the differentiation of property prices. Notably, property attributes have a more substantial impact on real estate values than district location, with severely damaged buildings in Damascus City resulting in an 89% decline in prices, while prices in Rural Damascus districts have decreased by 50%. Additionally, this study examines the urban texture of Damascus using correlation and homogeneity statistics derived from the gray-level co-occurrence matrix obtained from Google Earth Engine. Our findings show that correlations were highly differentiated, particularly among Rural Damascus districts, with a total decline of 87.2%. While homogeneity values decreased overall between 2015 and 2019, they improved slightly after 2019. This study guides decision makers in mitigating severe property value variations across war-affected urban areas by fostering spatial justice in property rights and promoting balanced investment and sustainable real estate development during the post-war recovery phase.

Surgical Recovery Through the Lens of Patients with Colorectal Disease: A Qualitative Study in an Enhanced Recovery after Surgery Setting.

As perioperative care shifts to a more patient-centered model, understanding needs and experiences of patients is vital. Gaining such insight can enhance the alignment of care with patient priorities, encouraging adherence to recovery-oriented interventions. We aimed to explore patient-defined recovery and the elements that modify the recovery process for patients with colorectal disease under Enhanced Recovery After Surgery (ERAS) care. A qualitative study was conducted at an ERAS-participating hospital in Alberta, Canada, between April 2018 to June 2019. A co-design focus group set the research direction and semi-structured interviews were conducted postoperatively in hospital or within 3 months post-discharge. Diverse patient ages and colorectal conditions were targeted through purposive sampling. Interviews were transcribed verbatim and analyzed through manifest and latent content analysis. Twenty patients with mean age 62 (SD:13) years and 45% with cancer (n=17 interview, n=2 focus group and interview, n=1 focus group only) were enrolled. Recovery was defined by patients as the return to normal routines and four themes were identified. First, Phases of recovery: recovery was described as multidimensional phases distinctively as early, late/long-term, and the endpoint. Second, Recovery facilitators: recovery was supported through positive mindsets, conscious recovery, and taking an active role. Third, Recovery barriers: recovery was hindered by negative mindsets and treatment side-effects. Finally, Recovery catalysts: communication, autonomy, and expectations facilitated active or passive recovery. Our patient-oriented recovery model may contribute a new dimension to the ERAS framework by capturing patients' recovery experiences. Further research is encouraged to explore its value in enhancing patient-centered care within ERAS.

Mlf mediates proteotoxic response via formation of cellular foci for protein folding and degradation in Giardia.

Myeloid leukemia factor 1 (Mlf1) was identified as a proto-oncoprotein that affects hematopoietic differentiation in humans. However, its cellular function remains elusive, spanning roles from cell cycle regulation to modulation of protein aggregate formation and participation in ciliogenesis. Given that structurally conserved homologs of Mlf1 can be found across the eukaryotic tree of life, we decided to characterize its cellular role underlying this phenotypic pleiotropy. Using a model of the unicellular eukaryote Giardia intestinalis, we demonstrate that its Mlf1 homolog (GiMlf) mainly localizes to two types of cytosolic foci: microtubular structures, where it interacts with Hsp40, and ubiquitin-rich, membraneless compartments, found adjacent to mitochondrion-related organelles known as mitosomes, containing the 26S proteasome regulatory subunit 4. Upon cellular stress, GiMlf either relocates to the affected compartment or disperses across the cytoplasm, subsequently accumulating into enlarged foci during the recovery phase. In vitro assays suggest that GiMlf can be recruited to membranes through its affinity for signaling phospholipids. Importantly, cytosolic foci diminish in the gimlf knockout strain, which exhibits extensive proteomic changes indicative of compromised proteostasis. Consistent with data from other cellular systems, we propose that Mlf acts in the response to proteotoxic stress by mediating the formation of function-specific foci for protein folding and degradation.

Disease progression associated cytokines in COVID-19 patients with deteriorating and recovering health conditions.

Understanding the immune response to COVID-19 is challenging due to its high variability among individuals. To identify differentially expressed cytokines between the deteriorating and recovering phases, we analyzed the Electronic Health Records (EHR) and cytokine profile data in a COVID-19 cohort of 444 infected patients and 145 non-infected healthy individuals. We categorized each patient's progression into Deterioration Phase (DP) and Recovery Phase (RP) using longitudinal neutrophil, lymphocyte and lactate dehydrogenase levels. A random forest model was built using healthy and severe patients to compute the contribution of each cytokine toward disease progression using Shapley Additive Explanations (SHAP). SHAP values were used for supervised clustering to identify DP and RP-related samples and their associated cytokines. The identified clusters effectively discriminated DP and RP samples, suggesting that the cytokine profiles differed between deteriorating and recovering health conditions. Especially, CXCL10, GDF15, PTX3, and TNFSF10 were differentially expressed between the DP and RP samples, which are involved in the JAK-STAT, NF- B, and MAPK signaling pathways contributing to the inflammatory response. Collectively, we characterized the immune response in terms of disease progression of COVID-19 with deteriorating and recovering health conditions.

A hot deformation constitutive model applicable for complete austenite and dynamic ferrite transformation interval

Dynamic ferrite transformation is a vital microstructure evolution mechanism for carbon alloy steels and an essential technology for manufacturing high-performance steel materials. In practice, carbon steel hot working processes are usually carried out at various temperatures, involving the evolutionary behavior of the single-phase austenite and the ferrite dynamic transformation process. Few models can simultaneously predict the microstructural state and deformation resistance in the single-phase austenitic interval and the dynamic ferrite transformation interval. The deformation mechanisms involve work-hardening, dynamic recovery, and dynamic recrystallization of austenite and ferrite phases, as well as the dynamic transformation of austenite to ferrite and coordinated deformation between the two phases. Therefore, this paper extends the application range of the model based on the viscoplastic unified constitutive model by considering the above deformation mechanisms. The constitutive model proposed in this paper applies to both the single-phase austenite interval and the dynamic ferrite transformation interval. Moreover, it can accurately predict carbon alloy steel's microstructure state and deformation resistance in different intervals. This paper can help to construct a hot deformation constitutive model in a wide range of deformation temperature intervals of steel materials.

Estrogen receptor α aggravates intestinal inflammation via promoting the activation of NLRP3 inflammasome

Activation of the NLRP3 inflammasome and estrogen receptor α (ERα) has been shown to increase the risk of inflammatory bowel diseases (IBD) or promote disease recurrence. In previous work, we demonstrated that ERα regulated the transcription of NLRP3. However, the precise mechanism by which ERα modulates NLRP3 in IBD models remains unclear. In this study, we induced IBD in wild-type mice using DSS or TNBS, followed by treatment with the ERα-specific agonist PPT. The results showed that IBD symptoms and intestinal inflammation responses were significantly exacerbated after PPT treatment. Furthermore, the activation of ERα by PPT led to a marked increase in the expression of NLRP3 and pro-inflammatory cytokines, including IL-1β and IL-18, suggesting that ERα activation exacerbated intestinal inflammation and impaired mucosal healing during the recovery phase of inflammation. In contrast, ERα-knockout mice exhibited only mild symptoms when exposed to DSS or TNBS, with a concurrent reduction in NLRP3 expression, indicating that ERα plays a role in inflammation susceptibility. Similar findings were observed in NCM-460 cells, where the inflammation response was attenuated in ERα-knockdown cells. Importantly, we demonstrated that ERα interacted with the NLRP3 inflammasome and promoted its assembly. Collectively, we propose an underlying pathogenesis of IBD, that is, ERα can interact with the NLRP3 inflammasome and promote its expression and assembly, thereby exacerbating intestinal inflammation in IBD models. Therefore, ERα could serve as a potential therapeutic target for NLRP3 inflammasome-associated intestinal inflammation.

Early robotic gait training after stroke (ERA Stroke): study protocol for a randomized clinical trial

BackgroundWalking impairment after stroke is associated with substantial limitations in functional independence, quality of life, and long-term survival. People in the subacute phase after stroke who are unable to walk are most likely to benefit the greatest from use of overground robotic gait training (RGT). This study will provide preliminary evidence regarding the clinical use and efficacy of RGT during the subacute phase of stroke recovery as well as observational findings associated with the safety, tolerability, feasibility, and cost of delivering RGT during inpatient stroke rehabilitation.MethodsThis prospectively registered randomized controlled trial will enroll 54 patients admitted to inpatient rehabilitation within six months of stroke. Admitted patients will be screened at admission to inpatient rehabilitation for eligibility. Consented patients will be randomized based on stroke severity to receive either RGT or usual care for 90 minutes per week of gait training intervention during inpatient rehabilitation length of stay. Patients will complete assessments on walking and health outcomes at admission and discharge from inpatient rehabilitation and at 1- and 3-month follow-up. Intent-to-treat and per protocol analysis will be performed to evaluate safety [rate of adverse events, visual analog scale, and treatment completion rate], walking function [gait speed via 10-Meter Walk Test, Functional Ambulation Category, gait endurance via 6-Minute Walk Test] and health outcomes [Modified Rankin Scale, Stroke Rehabilitation Assessment of Movement, Continuity Assessment Record and Evaluation Tool, 5 Times Sit-to-Stand Test, Berg Balance Scale, and Stroke Impact Scale–16], and cost-analysis.DiscussionThis study will provide foundational evidence regarding the clinical use and efficacy of a RGT program during the subacute phase of stroke recovery with specific findings associated with the safety, tolerability, feasibility, and cost-analysis of delivering RGT during inpatient stroke rehabilitation.Trial registrationNCT06430632.

Tracking the impact of typhoons on maize growth and recovery using Sentinel-1 and Sentinel-2 data: A case study of Northeast China

The increasing frequency of typhoon events, attributed to global climate change, has significantly affected agricultural production, predominantly resulting in substantial negative consequences. Accurate and timely assessment of crop damage is crucial for understanding economic implications, devising effective agricultural strategies, and enhancing resilience amid mounting climate uncertainties. This study investigates the utility of Sentinel-1 Synthetic Aperture Radar (SAR) and Sentinel-2 MultiSpectral Instrument (MSI) data in tracking maize damage severity following typhoon events. By employing continuous field sampling techniques and conducting visual interpretation of high-resolution remote sensing imagery, sample sets representing a spectrum of maize damage severity were systematically established. The application of time series analysis on Sentinel data enables a comprehensive exploration of spectral and polarization responses, providing insights into the correlation with maize damage severity. Segmentation of the maize damage timeline into pre-disaster, disaster, and recovery periods, coupled with optimization of relevant feature parameters, was undertaken to bolster monitoring precision. Leveraging the Google Earth Engine (GEE) cloud platform, a Random Forest algorithm was used to develop a model for monitoring maize damage severity across different post-typhoon periods, yielding maps delineating the distribution and magnitude of maize damage in Northeast China. Results indicate that integrating spectral indices from the pre-disaster phase with backscatter variations of polarization bands during various post-typhoon periods enhances maize damage assessment. Maize damage severity is notably elevated during the disaster period, achieving an overall accuracy of 87.22 %. While mitigated during the recovery phase, localized exacerbation occurs in severely affected regions, yielding an overall accuracy of 88.54 %. Analysis incorporating terrain and meteorological data reveals that post-typhoon maize disasters predominantly occur in low-lying and flat areas, with meteorological factors, particularly maximum wind speed and daily cumulative precipitation, exerting significant influence on damage severity. This study underscores the critical role of SAR and optical data fusion in elucidating typhoon-induced crop damage dynamics, thereby providing essential insights for proactive mitigation strategies against future agricultural losses.

Metallothionein family genes in kiwifruit: characterization and determining their roles in plant's response to different stresses.

Kiwifruit growth and development are severely affected by various biotic and abiotic stresses, especially cold stress and the bacterial disease caused by Pseudomonas syringae pv. actinidiae (Psa). Metallothioneins (MTs) are a group of cysteine-rich proteins that play crucial roles in stress response, metal detoxification, and homeostasis in plants. However, the protective role of these MTs in kiwifruit remains to be elucidated. In the present study, four AcMT genes were identified in the Hongyang kiwifruit genome, namely, two Type 2 isoforms (AcMT2 and AcMT2a) and two Type 3 isoforms (AcMT3a and AcMT3b) located separately on four different chromosomes. The hormones and stress response cis-elements within the promoter regions of these AcMTs were characterized. It was revealed that the four AcMT genes exhibited different expression patterns in different tissues: AcMT2 and AcMT2a were expressed at much higher levels in the fruit, male flower, female flower, root, and bark, while AcMT3a was expressed mainly in the fruit and AcMT3b was expressed highly in the bark. The expression patterns of these AcMT genes after exposure to Psa infection and different phytohormones, including gibberellic acid A3(GA3), ethylene (ET), and abscisic acid (ABA), were evaluated. It was revealed that in response to Psa infection, the main AcMTs in each tissue (those with expression levels higher compared to the other MTs in that tissue) were downregulated during the early stage in kiwifruits, followed by a recovery phase. In addition, most AcMTs were downregulated after exposure to ET and GA3, while type 2 AcMTs (AcMT2 and AcMT2a) were upregulated after treatment with ABA. The overexpression of AcMTs in Escherichia coli presented a higher tolerance to H2O2, heavy metals, low temperature, and high temperature. Collectively, these findings demonstrated the protective roles of AcMTs in terms of stress resistance conferred through plant hormone-related signal pathways.

Mathematical Model of Horizontal Track Conflict Prevention Algorithm in Detect-and-Avoid Framework

With the proliferation of Unmanned Aerial Vehicle (UAV) technology, the demand for effective collision avoidance technology has intensified. The DAIDALUS algorithm, devised by NASA Langley Research Center under the Detect-and-Avoid (DAA) framework, provides conflict prevention bands for remotely piloted UAVs navigating in intricate airspace. The algorithm computes the bands in two distinct phases: Conflict and Recovery. The formal model for both phases has been established and implemented through iterative programming approaches. However, the mathematical model remains incomplete. Therefore, based on the model, this paper proposes the mathematical model for the two phases of the horizontal track conflict prevention algorithm. Firstly, Cauchy’s inequality is proposed to formulate the model that addresses trajectory conflicts considering the UAV non-instantaneous maneuvering dynamics model, and then a prudent maneuvering strategy is designed to optimize the model for the recovery phase. Finally, the execution procedure of the algorithm within the two-stage mathematical model is also detailed. The results demonstrate that the proposed model achieves a higher precision in the preventive bands, implements an effective collision avoidance strategy, and consistently aligns with the DAIDALUS model while offering a larger buffer time or distance. This work theoretically validates the formal model of the DAIDLAUS algorithm and provides insights for further refinement.

The Online Health Information-Seeking Behaviors of People Who Have Experienced Stroke: Qualitative Interview Study.

Stroke is a leading cause of death and disability worldwide. As health resources become digitized, it is important to understand how people who have experienced stroke engage with online health information. This understanding will aid in guiding the development and dissemination of online resources to support people after stroke. This study aims to explore the online health information-seeking behaviors of people who have experienced stroke and any related barriers or navigational needs. Purposeful sampling was used to recruit participants via email between March and November 2022. The sampling was done from an existing cohort of Australian stroke survivors who had previously participated in a randomized controlled trial of an online secondary prevention program. The cohort consisted of people with low levels of disability. Semistructured one-on-one interviews were conducted via phone or video calls. These calls were audio recorded and transcribed verbatim. The data were analyzed by 2 independent coders using a combined inductive-deductive approach. In the deductive analysis, responses were mapped to an online health information-seeking behavior framework. Inductive thematic analysis was used to analyze the remaining raw data that did not fit within the deductive theoretical framework. A sample of 15 relatively independent, high-functioning people who had experienced stroke from 4 Australian states, aged between 29 and 80 years, completed the interview. A broad range of online health information-seeking behaviors were identified, with most relating to participants wanting to be more informed about medical conditions and symptoms of their own or of a family member or a friend. Barriers included limited eHealth literacy and too much generalization of online information. Online resources were described to be more appealing and more accessible if they were high-quality, trustworthy, easy to use, and suggested by health care providers or trusted family members and friends. Across the interviews, there was an underlying theme of disconnection that appeared to impact not only the participants' online health information seeking, but their overall experience after stroke. These responses were grouped into 3 interrelated subthemes: disconnection from conventional stroke narratives and resources, disconnection from the continuing significance of stroke, and disconnection from long-term supports. People who have experienced stroke actively engage with the internet to search for health information with varying levels of confidence. The underlying theme of disconnection identified in the interviews highlights the need for a more comprehensive and sustained framework for support after stroke beyond the initial recovery phase. Future research should explore the development of tailored and relatable internet-based resources, improved communication and education about the diversity of stroke experiences and ongoing risks, and increased opportunities for long-term support.

The effect of deep versus awake removal of the laryngeal mask airway on the incidence of emergence delirium in paediatric tonsillectomy: A randomised controlled trial.

Emergence delirium, characterised by inconsolable crying, perceptual disturbances and thrashing, occurs in young children during the recovery phase from general anaesthesia. Our aim was to determine whether timing of laryngeal mask airway removal (deeply anaesthetised versus awake) influenced the incidence of emergence delirium in children after tonsillectomy. A single-centre, randomised controlled trial was conducted at Albury Wodonga Health, a regional hospital in Australia. Included patients were two to seven years old, American Society of Anesthesiologists physical status classification 1-2, undergoing elective tonsillectomy (with or without adenoidectomy or grommet insertion) under general anaesthesia. Patients were randomised to have their laryngeal mask removed whilst deeply anaesthetised (in the operating theatre) or after awakening (in the post-anaesthesia care unit (PACU)). Pediatric Anesthesia Emergence Delirium score was determined at 5 and 20 min after eye opening, and frequency of complications (cough, vomiting, excessive salivation, oxygen desaturation and laryngospasm) in the PACU were recorded. Sixty-two patients were randomised to deep laryngeal mask removal and 62 to awake. In the awake versus deep groups, 33 (53%) versus 40 (65%) participants had emergence delirium at 5 min (odds ratio (OR) 0.63, 95% confidence interval (CI) 0.30 to 1.29, P = 0.20). At 20 min, 18 (29%) vs. 19 (31%) participants had emergence delirium (OR 0.93, 95% CI 0.43 to 2.00, P = 0.88). A greater incidence of most PACU complications was observed in the awake versus deep group; cough (24% vs. 8%), vomiting (8% vs. 0%), excessive salivation (23% vs. 8%) and oxygen desaturation (16% vs. 0%). We found no significant difference between the two techniques in terms of preventing emergence delirium. However, other PACU complications were more frequent with awake removal.

Personalized Nutrition in the Pediatric ICU: Steering the Shift from Acute Stress to Metabolic Recovery and Rehabilitation.

Nutrition significantly impacts the outcomes of critically ill children in intensive care units (ICUs). Due to the evolving metabolic, neuroendocrine, and immunological disorders associated with severe illness or trauma, there are dynamically changing phases of energy needs requiring tailored macronutrient intake. This study aims to assess the changing dietary needs from the acute phase through recovery, provide recommendations for implementing evidence-based strategies to ensure adequate energy and nutrient provision in pediatric ICUs, and optimize patient outcomes. A comprehensive search of the MEDLINE-PubMed database was conducted, focusing on randomized controlled trials, meta-analyses, and systematic reviews related to the nutrition of critically ill children. The study highlights recent guidelines using the GRADE approach, supplemented by relevant adult studies, current clinical practices, challenges, gaps in knowledge, and future directions for research aimed at improving nutritional interventions. Early personalized, incremental enteral feeding helps mitigate the negative energy balance during the acute phase, aids organ function restoration in the stabilization phase, and supports growth during the recovery phase and beyond. Conversely, early full nutritional support, high protein doses, or isolated micronutrient administration have not demonstrated benefits due to anabolic resistance in these patients. Moreover, early parenteral nutrition during the acute phase may suppress autophagy and lead to worse outcomes. Accurate assessment of nutritional status and monitoring of daily energy and protein needs are crucial. Strong evidence supports the establishment of a dedicated nutritional team and the implementation of individualized nutritional protocols in the ICU to reduce morbidity and mortality in critically ill children.

Increasing temperature threatens post‐fire auto‐successional dynamics of a Mediterranean obligate seeder

Abstract Reproductive traits influence plant auto‐successional dynamics in post‐fire regeneration. Obligate seeding species rely on their seedbank and on the climatic conditions following the fire to ensure a successful recovery, defining the window of opportunity for seedling emergence. In the Mediterranean basin, emergence opportunities generally begin with autumnal rains. However, climate change‐induced increases in temperature and drought could jeopardise the regeneration capacity of seeding species by causing temporal shifts in emergence opportunities or by modifying wildfire seasonality. This study aimed to explore the impact of experimentally induced climate change on regeneration dynamics of Aleppo pine (Pinus halepensis), a serotinous Mediterranean obligate seeder. In March 2021, we set up an 18‐month climate change simulation experiment with 15 open‐top chambers (OTC), each paired with a control subplot (CON) on top of Aleppo pines that were naturally regenerating after a stand‐replacing wildfire in SW Catalonia (June 2019). We tagged 178 young Aleppo pine recruits in OTC and CON subplots (98 and 81 respectively), classified according to their initial size, to periodically measure height growth and survival throughout the experiment duration. Furthermore, Aleppo pine seeds were seasonally sown (7900 total seeds) in 10 subplot pairs between May 2021 and April 2022, to monthly monitor temporal patterns of seedling emergence and survival. We found that OTCs reduced overall emergence rates and caused the loss of the autumnal window of opportunity for the emergence of Aleppo pine seedlings. Furthermore, seedlings which emerged within OTCs faced higher mortality rates in all seasons, with only 1% of seedlings surviving compared with 21.1% of seedlings in control plots. The OTC‐induced conditions were also detrimental to the survival of recruited seedlings, especially those with a smaller initial size, although no significant effects of temperature increase were found on growth. Synthesis. Climate change is likely to interfere with the post‐fire regeneration dynamics of obligate seeders by shortening the temporal window of opportunities for emergence and by enhancing the bottleneck effects throughout the recruitment process in the early phases of pine demographic recovery. Altogether, it could threaten post‐fire regeneration by increasing the hazard of a demographic collapse of Aleppo pine.

Low-dose neutron irradiation effects on the elastoplastic deformation mechanisms of aluminum-doped gallium nitride under contact loading

The elastoplastic deformation mechanisms of irradiated aluminum (Al)-doped gallium nitride (GaN) under contact loading are investigated in this work using the nanoindentation simulations, which is of great significance for understanding the mechanical properties of the Al-doped GaN and guiding the design of durable and high-performance GaN-based devices. The mechanical behaviors of the Al-doped GaN with different doping concentrations are analyzed, including the indentation hardness, Young's modulus, elastic recovery rates, phase transformations, and stress distribution. It is found that Al doping increases their hardness, Young's modulus, and elastic recovery rates, and leads to an enlargement of the phase transformation regions, which is dominated by the high coordination number (CN) phase transformations. Furthermore, the effects of low-dose neutron irradiation on their elastoplastic deformation mechanisms are studied by triggering cascade collisions within the structure. When subjected to such irradiation, structural changes occur in the Al-doped GaN, their indentation hardness, Young's modulus, and elastic recovery rates increase remarkably, and its phase transformation mechanism is changed remarkably. The dislocation behaviors of the doped and undoped GaN are different under neutron irradiation. This study is important for capturing the mechanical stability and integrity of Al-doped GaN in an irradiation environment, as well as developing GaN-based devices with superior irradiation resistance.

Predicting chemotherapy-induced thrombotoxicity by NARX neural networks and transfer learning

BackgroundThrombocytopenia is a common side effect of cytotoxic chemotherapies, which is often dose-limiting. Predicting an individual’s risk is of high clinical importance, as otherwise, a small subgroup of patients limits dosages for the overall population for safety reasons.MethodsWe aim to predict individual platelet dynamics using non-linear auto-regressive networks with exogenous inputs (NARX). We consider different architectures of the NARX networks, namely feed-forward networks (FNN) and gated recurrent units (GRU). To cope with the relative sparsity of individual patient data, we employ transfer learning (TL) approaches based on a semi-mechanistic model of hematotoxicity. We use a large data set of patients with high-grade non-Hodgkin’s lymphoma to learn the respective models on an individual scale and to compare prediction performances with that of the semi-mechanistic model.ResultsOf the examined network models, the NARX with GRU architecture performs best. In comparison to the semi-mechanistic model, the network model can result in a substantial improvement of prediction accuracy for patients with irregular dynamics, given well-spaced measurements. TL improves individual prediction performances.ConclusionNARX networks can be utilized to predict an individual’s thrombotoxic response to cytotoxic chemotherapy treatment. For reasonable model learning, we recommend at least three well-spaced measurements per cycle: at baseline, during the nadir phase and during the recovery phase. We aim at generalizing our approach to other treatment scenarios and blood lineages in the future.

Cardiac Arrhythmias and Autonomic Dysfunction Associated With COVID-19: A Scientific Statement From the American Heart Association.

Cardiac arrhythmias are commonly noted in patients during infections with and recovery from COVID-19. Arrhythmic manifestations span the spectrum of innocuous and benign to life-threatening and deadly. Various pathophysiological mechanisms have been proposed. Debate continues on the impact of incident and exacerbated arrhythmias on the acute and chronic (recovery) phase of the illness. COVID-19 and COVID-19 vaccine-associated myocardial inflammation and autonomic disruption remain concerns. As the pandemic has transformed to an endemic, with discovery of new SARS-CoV-2 variants, updated vaccines, and potent antiviral drugs, vigilance for COVID-19-associated arrhythmic and dysautonomic manifestations remains. The objective of this American Heart Association scientific statement is to review the available evidence on the epidemiology, pathophysiology, clinical presentation, and management of cardiac arrhythmias and autonomic dysfunction in patients infected with and recovering from COVID-19 and to provide evidence-based guidance. The writing committee's consensus on implications for clinical practice, gaps in knowledge, and directions for future research are highlighted.

Comparing Brain Activation Patterns in Stress-Induced and Post-Stress Recovery States of Highly and Moderately Stressed Individuals

Our study aimed to identify the mechanisms of stress-induced and post-stress recovery states by evaluating voxel type and the total number of voxels activated based on Perceived Stress Scale scores. Functional MRI (fMRI) was used to measure the brain activation patterns in participants grouped into moderate- and high-stress categories. The number of activation voxels in the parahippocampal gyrus of the limbic lobe was greater in the high-stress group than in the moderate-stress group. Moreover, only the high-stress group showed the characteristic activation of the left precuneus. The moderate-stress group showed a greater number of activation voxels than the high-stress group for the occipital, frontal, and limbic lobes, while the reverse was true for the parietal lobe. In the post-stress recovery phase, the left lingual, inferior frontal, and middle frontal gyri were activated, and the number of activation voxels in these areas was greater in the high-stress group than in the moderate-stress group. The characteristic activation of the declive in the left cerebellum was observed in the moderate-stress group, whereas the activation of the right cuneus was dominant in the high-stress group. Our findings suggest that perceived stress may play an important role in determining the neural mechanisms underlying stress and post-stress recovery, providing insights into the complex interplay between the psychological and neural processes occurring in response to stress.

Excitation-contraction coupling inhibitors potentiate the actions of botulinum neurotoxin type A at the neuromuscular junction.

Botulinum neurotoxin type A1 (BoNT/A) is one of the most potent neurotoxins known. At the same time, it is also one of the safest therapeutic agents used for the treatment of several human disorders and in aesthetic medicine. Notwithstanding great effectiveness, strategies to accelerate the onset and prolong BoNT/A action would significantly ameliorate its pharmacological effects with beneficial outcomes for clinical use. Here, we combined BoNT/A with two fast-acting inhibitors of excitation-contraction coupling inhibitors (ECCI), either the μ-conotoxin CnIIIC or dantrolene, and tested the effect of their co-injection on a model of hind-limb paralysis in rodents using behavioural, biochemical, imaging and electrophysiological assays. The BoNT/A-ECCI combinations accelerated the onset of muscle relaxation. Surprisingly, they also potentiated the peak effect and extended the duration of the three BoNT/A commercial preparations OnabotulinumtoxinA, AbobotulinumtoxinA and IncobotulinumtoxinA. ECCI co-injection increased the number of BoNT/A molecules entering motoneuron terminals, which induced a faster and greater cleavage of SNAP-25 during the onset and peak phases, and prolonged the attenuation of nerve-muscle neurotransmission during the recovery phase. We estimate that ECCI co-injection yields a threefold potentiation in BoNT/A pharmacological activity. Overall, our results show that the pharmacological activity of BoNT/A can be combined and synergized with other bioactive molecules and uncover a novel strategy to enhance the neuromuscular effects of BoNT/A without altering the neurotoxin moiety or intrinsic activity, thus maintaining its exceptional safety profile.