Restriction Patterns Research Articles

Age-related changes in species-typical behaviours in the 5xFAD mouse model of Alzheimer’s disease from 4 to 16 months of age

Alzheimer’s disease (AD) patients show age-related decreases in the ability to perform activities of daily living and the decline in these activities is related to the severity of neurobiological deterioration underlying the disease. The 5xFAD mouse model of AD shows age-related impairments in sensory- motor and cognitive function, but little is known about changes in species-typical behaviours that may model activities of daily living in AD patients. Therefore, we examined species-typical behaviours used as indices of exploration (rearing) and compulsivity (grooming) across six tests of anxiety-like behaviour or motor function in female 5xFAD mice from 3 to 16 months of age. Robust decreases in rearing were found in 5xFAD mice across all tests after 9 months of age, although few differences were observed in grooming. A fine-scale analysis of grooming, however, revealed a previously unresolved and spatially restricted pattern of grooming in 5xFAD mice at 13–16 months of age. We then examined changes in species-typical behaviours in the home-cage, and show impaired nest building in 5xFAD mice at all ages tested. Lastly, we examined the relationship between reduced species typical behaviours in 5xFAD mice and the presentation of freezing behaviour, a commonly used measure of memory for conditioned fear. These results showed that along with cognitive and sensory-motor behaviour, 5xFAD mice have robust age-related impairments in species-typical behaviours. Therefore, species typical behaviours in 5xFAD mice may help to model the decline in activities of daily living observed in AD patients, and may provide useful behavioural phenotypes for evaluating the pre-clinical efficacy of novel therapeutics for AD.

Abstract 6727: QL335, a novel T cell engager with enhanced safety profile targeting MSS colorectal cancer

Abstract Colorectal cancer (CRC) is the fourth leading cause of death in the world with a global mortality rate of over 700,000 annually. While recent advancement in diagnosis and prevention has reduced the overall number of deaths, the lack of effective and durable treatment has not significantly improved survival rate. Emerging modalities in immunotherapy such as T cell engagers have paved new ways for disease management. However, a common challenge to advancing T cell engagers in the clinic is poor target specificity and high toxicity associated with non-specific T cell activation and cytokine release. To overcome these shortcomings, we have developed QL335, a bispecific antibody bridging LY6G6D antigen on tumor cells and CD3 on T cells. LY6G6D or Lymphocyte Antigen 6 Family Member G6D, is a GPI-anchored membrane protein that, according to TCGA RNAseq data, is highly expressed in microsatellite stable (MSS) colorectal cancer but not in normal tissues. We analyzed LY6G6D expression by IHC in over 200 CRC patient tumors and 40+ normal tissue samples from different organs, confirming its highly restricted CRC expression pattern. We constructed our bispecific antibody in a 2+1 format, comprising two high affinity LY6G6D binding domains and one reduced affinity CD3 binding domain. Such format allows for higher tumor accumulation while mitigating non-specific T cell activation in the periphery. In vitro evaluation showed that QL335 induced potent yet highly specific T cell activation and killing of only target cells expressing LY6G6D. QL335 demonstrated robust anti-tumor efficacy in vivo against human colon cancer xenograft models with human PBMC reconstitution. Importantly, QL335 was well tolerated in cynomolgus monkeys dosed up to 50 mg/kg, supporting the enhanced safety profile by design of this therapeutic candidate. QL335 is currently being evaluated in a phase 1 clinical trial. Citation Format: Shenda Gu, Guangjie Guo, Helena Yee, Hieu V. Tran, Shihao Chen, Chuanzeng Cao, Ke Liu, Chunyan Jin, Weihua Lun, Ruixue Ma, Lele Ren. QL335, a novel T cell engager with enhanced safety profile targeting MSS colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6727.

A cross-sectional study on the correlation of pulmonary function with duration of Rheumatoid arthritis

Rheumatoid arthritis (R.A.) is characterized by chronic inflammatory symmetrical peripheral polyarthritis associated with systemic involvement. Pulmonary involvement is one of them. Therefore, early assessment of pulmonary function may help identify the type of respiratory involvement and hence can contribute to properly managing pulmonary complications.The study aims to evaluate the type and extent of pulmonary function abnormality in relation to the duration of Rheumatoid Arthritis. Settings and Design: tertiary care treating hospital- a cross-sectional observational study A cross-sectional study was conducted at Department of General Medicine in forty R.A. cases in whom spirometry was performed and values of spirometry results were statistically compared with the duration of R.A. using S.P.S.S. software. Cases were grouped into three categories based on the duration of the disease. Category A –less than 5 yrs, category B– 5 to 9 yrs and category C – more than 9 yrs duration. In category A, abnormal pulmonary function test (PFT) was observed in 43.5% of cases in the form of obstructive 17.4%, restrictive 17.4% and mixed pattern in 8.7% of cases. In category B, the restrictive pattern was found in 63.6% and a mixed pattern in 9.1% of cases. However, abnormal pulmonary function test (PFT) was observed in all cases in category C, with obstructive pattern in 16.7%, restrictive 66.7% and mixed 16.7% cases. From the study, it was found that early pulmonary involvement occurs in R.A. With an increase in the duration of R.A., pulmonary involvement becomes a more severe and restrictive pattern. Most cases with a duration of more than 9yrs had significant pulmonary involvement either in the form of restrictive or obstructive pattern. Hence PFT should be done at the earliest as a routine and repeated periodically in R.A. cases.

PULMONARY FUNCTION IN RHEUMATOID ARTHRITS: A CROSS-SECTIONAL STUDY

Objective: Rheumatoid arthritis (RA) is an autoimmune disease with many extraarticular manifestations. Pulmonary involvement is seen in 60-80% cases with and without symptoms. This research studies the pattern of PFT (Pulmonary Function Test) in RA and find the correlation between PFT and Disease activity. Secondary objectives were to evaluate the effect of use of Methotrexate (MTx) on disease activity and PFT.
 Methods: An outpatient-based descriptive cross-sectional study was conducted in General Medicine department at a tertiary centre among 100 eligible patients. Disease activity score was recorded using DAS-28 (Disease Activity Score-28) and CDAI (Clinical Disease Activity Index). Patients underwent PFT by Spirometry thereafter.
 Results: 45 % patients had restrictive pattern and 55% had normal PFT. None had an obstructive pattern. The mean FVC (Forced Vital Capacity), FEV1 (Forced Expiratory Volume in the first second), FEV1/FVC ratio, PEFR (Peak Expiratory Flow Rate) and FEF 25-75% (Forced mid expiratory flow) were 78.83±14.37, 79.24±16.96, 103.56±11.03, 71.73±22.39 and 76.56±23.72 respectively. Both FVC and FEV1 were found to be significantly associated with age, disease duration, CDAI score, MTx dose and duration (P<0.05). Age, ESR(erythrocyte sedimentation rate) and MTx dose were significantly associated with FEV1/FVC ratio (P<0.05). Age, duration of disease, ESR. MTx dose and duration were significantly associated with PEFR (P<0.05). Lastly age, CDAI score, MTx dose and duration were significantly associated with FEF 25-75% (P<0.05).
 Conclusion: Restrictive pattern (45%) was the most common defect on PFT among RA patients. Severity of lung disease depends on age, MTx dose, disease activity (ESR, CDAI), duration of disease and MTx duration.

Clinical phenotypes of nontuberculous mycobacterial disease by cluster analysis based on pulmonary function

BackgroundNontuberculous mycobacterial pulmonary disease (NTM-PD) often exhibits pulmonary function impairment, such as obstructive or restrictive pattern, with variation among patients according to the damaged lesions in the lung. MethodsPatients with NTM-PD were consecutively enrolled between September 2019 and December 2020 at the Respiratory Infection Clinic of our hospital. Patients’ data were comprehensively collected through laboratory examinations, PFT, chest computed tomography, and questionnaires for the assessment of subjective symptoms and health-related quality of life (HRQOL). Hierarchical cluster analysis was performed using PFT parameters to compare the clinical findings among clusters. ResultsData of 104 patients were analyzed and classified into four clusters. The restrictive pattern with decreased forced expiratory volume in 1 s (FEV1) group showed high serum C-reactive protein and low albumin levels, severe radiological findings, and low HRQOL. In the restrictive pattern with preserved FEV1 group, HRQOL was as low as that in the restrictive pattern with decreased FEV1 group, and bacterial exacerbation was observed relatively frequently. HRQOL in the obstructive impairment group was maintained in comparison with that in the normal group. ConclusionNTM-PD phenotypes were identified using cluster analysis based on PFT. Two different severe phenotypes were also observed. In the early stages of NTM-PD, PFT may be useful in recognizing disease progression.

The relationship between increased iron load and respiratory function tests in patients diagnosed with transfusion dependent thalassemia

Aims: Thalassaemia syndromes are the most common single gene disorders affecting more than 200 million people worldwide. Beta thalassaemia (BT) is the most common cause of transfusion-dependent thalassaemia (TDT). It has been reported in studies that iron accumulation occurs in the lungs, especially in the alveolo-capillary membrane, and the frequency of parenchymal disease increases in patients receiving frequent blood transfusions. In our study, we aimed to investigate whether there is a correlation between iron overload and pulmonary function in patients with TDT.
 Methods: The study included 61 patients aged between 18 and 45 years with a diagnosis of TDT who were followed up in the hematology clinic of our tertiary care center between 2018 and 2023. Based on spirometry measurements, the pattern of respiratory impairment was defined and correlated with serum ferritin levels. 
 Results: The mean age of the 61 patients included in the study was 24.83±6.02 years and 33 were female and 28 were male. The mean ferritin value was 3150.88±2553.51 ng/ml. The annual number of transfusions was 15.39±1.90. According to the PFT results, mean FVC % value was 81.59±9.28, mean FEV1 % value was 82.11±7.6, mean FEV1/FVC % value was 102.55±7.63. Mean ferritin values were found to be significantly higher in patients diagnosed with TDT with restrictive lung pattern (p=0.004). 
 Conclusion: Our study showed that high ferritin levels are related to increased restrictive lung disease in the adult age group.

Case reports involving coinfection with Avibacterium paragallinarum and Ornithobacterium rhinotracheale in broiler chickens and Avibacterium endocarditis in broiler breeding hens in Poland

ABSTRACT The study describes three clinical cases of infection with Avibacterium spp.. In case no. 1, respiratory clinical signs and high mortality (0.7–4.2% daily; total 21.2%) in Ross 308 broiler chickens were shown to be caused by coinfection with sequence type 9 of O. rhinotracheale presumptive serotype A and A. paragallinarum presumptive serotype B. The identical (pulsed-field gel electrophoresis) restriction pattern (pulsotype) of seven A. paragallinarum isolates indicated that infectious coryza in broilers was caused by the same clone. In cases 2 and 3, sudden increased deaths in Ross 308 broiler breeders (especially males) with lesions in the endocardium (valvular or mural endocarditis) were shown to be caused by A. endocarditis. Among nine antibiotics tested, florfenicol was the only antibiotic to which all A. paragallinarum and O. rhinotracheale isolates were susceptible. Out of the eight antibiotics tested, 11 A. endocarditis isolates from both clinical cases of infective endocarditis were susceptible to penicillin, amoxicillin, doxycycline and florfenicol. The A. endocarditis isolates tested in both clinical cases had different PFGE patterns (pulsotypes), but identical within a case. The causes of infectious coryza and infective endocarditis in the cases presented have not been determined. In the prevention of infectious diseases in large-scale livestock farming, it is very important to follow the rules of biosecurity.

A Community-Based Cross-Sectional Study on Respiratory Health and Spirometry-Assessed Pulmonary Function Among Textile Workers in Tamil Nadu, India.

Introduction The textile industry is one of the largest economic activities. Still, the laborers involved in it are exposed to various health-damaging air pollutants, putting them at risk of health issues including morbidities of the respiratory system. Therefore, this study aimed to assess the pulmonary function parameters of the workers involved in textile manufacturing-related jobs. Methodology A cross-sectional study was carried out among adult individuals who had been working in textile manufacturing-related jobs as their main work. The details such as sociodemographic, clinical, workplace conditions, and smoking habits were collected, as well as chest auscultation and lung spirometry using a hand-held spirometer. The participants who had normal and abnormal lung function patterns were statistically analyzed for potential influencing factors. Results The findings of the study conducted from 95 eligible participants identified that the pulmonary function parameters assessed by spirometry were in the abnormal range among 84 (88%) participants. Around 72 (82%) of them had a restrictive pattern, and six (6%) had both restrictive and obstructive (mixed) patterns of lung disease. Smokers and those who lacked cross-ventilation and/or fresh source of air in the workplace were more likely to have abnormal lung function. Participants who had their workplace and residence as same had significantly 6.44 (95% CI: 1.24, 33.36) times higher odds of having abnormal lung function in spirometry. Conclusion As workers involved in household-run textile manufacturing jobs are found to be at a higher risk of developing abnormal lung function, using personal protective equipment, following occupational safety measures, and improving the working environment to acceptable standards are essential to safeguard the respiratory health of laborers in such unorganized sectors.

Lung Function Evaluated By Structured Light Plethysmography in Children After Lung Surgery: A Preliminary Analysis.

Background: Structured light plethysmography (SLP) is a novel light-based method that captures chest wall movements to evaluate tidal breathing. Methods: Thirty-two children who underwent lung surgery were enrolled. Their clinical history was collected along with spirometry and SLP. Results: Median age of surgery was 9 months (interquartile range 4-30). Most frequent diagnosis was congenital pulmonary airway malformation (14/32), then pulmonary sequestration (9/32), tumor (5/32), and bronchogenic cyst (4/32). The most frequent surgical approach was lobectomy (59%), segmentectomy (38%), and complete resection (3%). More than 80% had surgery when younger than 3 years of age. Eight patients had short-term complications (pleural effusion was the most frequent), while long-term effects were reported in 15 patients (19% recurrent cough, 13% thoracic deformities, 13% airway infections, 9% wheezing, 6% reduced exercise tolerance, and 3% columnar deformities). Spirometry was normal in 9/22 patients. Nine patients had a restrictive pattern, while 4 showed a mild bronco-reactivity. Ten patients did not perform spirometry because of young age. SLP revealed the presence of obstructive pattern in 10% of patients (IE50 > 1.88) and showed a significant difference between the two hemithorax in 29% of patients. Discussion: SLP may be a new method to evaluate lung function, without collaboration and radiation exposure, in children who underwent lung resection, also in preschool age.

Progressive pulmonary fibrosis in patients with connective tissue disease-associated interstitial lung disease: An explorative study.

The aim of this study was to identify differences and similarities between connective tissue disease (CTD) patients with and without progressive pulmonary fibrosis (PPF) by applying the new guidelines. Patient characteristics and disease courses from medical records of 50 CTD-associated Interstitial lung disease (ILD) patients (33 females, 17 males; mean age: 60.1±12.9 years) were longitudinally studied between January 2018 and May 2022. Respiratory involvement in CTD patients was described, and differences in CTD patients who developed PPF compared to those who did not were identified by the 2022 ATS (American Thoracic Society)/ERS (European Respiratory Society)/JRS (Japanese Respiratory Society)/ALAT (Asociación Latinoamericana de Thórax) Guidelines on Idiopathic Pulmonary Fibrosis and Progressive Pulmonary Fibrosis in Adults. In the majority (74%) of patients, CTD was diagnosed before ILD onset. Nonspecific interstitial pneumonia was the most common high resolution computer tomography pattern, followed by the usual interstitial pneumonia pattern. On pulmonary function test, 38% had a restrictive pattern at baseline. Patients without PPF tended to have worse lung function at baseline and increased macrophage count in bronchoalveolar lavage than patients with PPF. In patients without PPF, disease progression may be missed, resulting in inadequate management. Interdisciplinary management of patients with CTD with the participation of pulmonologists and precise lung function diagnostics is recommended.

Impact of Using Global Lung Initiative Race-neutral Equations for Chronic Respiratory Disease in Western India.

The Global Lung Initiative (GLI) race-neutral equations are considered to be race agnostic, using inverse probability weight, and have lower limits of normality (LLN) different from the GLI mixed equations. In this observational study, we analyzed the impact of using GLI equations to interpret spirometry of 1,169 patients with chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), COPD suspects, small airway obstruction, posttubercular lung disease, and preserved ratio with impaired spirometry (PRISm) (46% females, average age 46 years). Predicted normal and the LLN using GLI equations were significantly higher than those using Indian equations. The GLI race-neutral equations changed the category in 35.17% of males and 42.64% of females compared to Indian equations. The GLI mixed equations categorized a greater percentage of patients to have a mixed ventilatory pattern compared to the GLI race-neutral equations. There was a significant change in the grading of the severity of COPD using Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages based on the percentage of predicted values of FEV1. Although GLI race-neutral equations have greater concordance with Indian equations than GLI Mixed equations, these substantially overdiagnose abnormal ventilatory patterns on spirometry in adult Indians in western India with chronic respiratory disease. A substantial number of patients with normal or obstructive patterns on spirometry are recategorized to have mixed or restrictive patterns. The use of GLI race-neutral equations increases the severity of airflow limitation in COPD patients. GLI race-neutral predictions for FEV1 result in substantially fewer patients demonstrating postbronchodilator responsiveness (PBDR).

Gas dynamics at starting and terminating phase of a supersonic exhaust diffuser with a conical nozzle

This research investigates the process of starting and breakdown of second throat diffuser during high-altitude test of conical nozzle with a high expansion ratio. The subscale experimental setup includes a conical nozzle with an expansion ratio of 53, plus a second throat diffuser with a contraction ratio of 1.85, using compressed air as the working fluid. Numerical simulation has been employed to identify the flow physics during the unsteady process of diffuser startup and breakdown. According to the results, the starting process is divided into three distinct stages. In the first stage, the exhausted flow from the nozzle enters the vacuum chamber, leading to an increase in vacuum chamber pressure. The second stage, corresponding to the period before full flow establishment in the conical nozzle, exhibits a relatively constant slope. In the final stage, associated with the transition from over-expanded to under-expanded states, the slope of the rate of evacuation development descends. Next, the vacuum degradation in termination process has been analyzed, and it has been found to include three stages: high slope, middle slope, and low slope. The flow physics during the start process, similar to the results observed in other conical nozzles, exhibits only a Mach reflection structure. However, during the termination process, the flow physics involve a combination of both structures, including Mach reflection and Cap Shock. The results indicate that during the start, an internal shock only interacts with the separation shock, and no special change occurs in the Mach reflection structure. In contrast, during the termination process, unlike what has been reported in previous studies on conical nozzles, the structure of cap shock waves and restricted shock separation patterns are also observed. Another distinction between the starting and termination processes is related to the pressure distribution in the diffuser wall. The wall pressure at the diffuser inlet during the termination process has been reported to be 90% higher than during the starting process.

Factors related to lung function outcomes in critically ill COVID-19 patients in South Korea.

New variants of the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic continue to emerge. However, little is known about the effect of these variants on clinical outcomes. This study evaluated the risk factors for poor pulmonary lung function test (PFT). The study retrospectively analyzed 87 patients in a single hospital and followed up by performing PFTs at an outpatient clinic from January 2020 to December 2021. COVID-19 variants were categorized as either a non-delta variant (November 13, 2020-July 6, 2021) or the delta variant (July 7, 2021-January 29, 2022). The median age of the patients was 62 years, and 56 patients (64.4%) were male. Mechanical ventilation (MV) was provided for 52 patients, and 36 (41.4%) had restrictive lung defects. Forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO ) were lower in patients on MV. Male sex (odds ratio [OR], 0.228) and MV (OR, 4.663) were significant factors for decreased DLCO . The duration of MV was associated with decreased FVC and DLCO . However, the type of variant did not affect the decrease in FVC (P=0.750) and DLCO (P=0.639). Among critically ill COVID-19 patients, 40% had restrictive patterns with decreased DLCO . The reduction of PFT was associated with MV, type of variants.

The Autism Spectrum Disorder and Its Possible Origins in Pregnancy.

Autism Spectrum Disorder (ASD) belongs to the group of neurodevelopmental disorders, and has a high prevalence, affecting 1 in 100 children according to data from the World Health Organization (WHO). To be diagnosed with ASD, the child must have persistent deficits in communication and social interactions, and restricted and repetitive patterns of behavior, interests, or activities. Despite its prevalence, the etiology of ASD is still uncertain, with multifactorial characteristics, including those associated with the gestational period, where maternal exposure to biological, chemical, or physical hazards occurs, some of which have already been proposed as causes of ASD outcomes. Since pregnancy requires a balance between the maternal-fetal binomial, the breakdown of this balance caused by such environmental hazards can lead to altered fetal neurodevelopment, including ASD. With this firmly in mind, this review aims to compile the most recent data on the gestational causes that may be associated with the development of ASD to help health professionals identify risk factors and act for the prevention and management of ASD.

Understanding and supporting the diversity of the autistic spectrum

Autism is a neurodevelopmental disorder that affects people's communication, social interaction and behavior. This article aims to explore autism in detail, addressing its characteristics, causes, diagnosis and impact on people's lives. In developing the article, a comprehensive review of available literature was carried out, including scientific studies, reports from health organizations and personal experiences of autistic individuals and their families. The introduction presented an overview of autism, emphasizing the importance of understanding the complexity of the autism spectrum, which encompasses a wide variety of individual profiles and characteristics. The need to promote the inclusion and acceptance of people on the autism spectrum in society was also highlighted. In developing the article, the main characteristics of autism were discussed, including difficulties in verbal and non-verbal communication, challenges in social interaction, restricted and repetitive patterns of behavior, sensory sensitivities and variations in cognitive development. The importance of early diagnosis and multidisciplinary assessment to identify autism and initiate appropriate interventions was addressed. The possible causes of autism were also explored, such as genetic, environmental and neurobiological factors, highlighting the complexity and multifactorial nature of the disorder. Another point discussed in the development of the article were the approaches and interventions used to support people on the autism spectrum. Behavioral strategies, specialized therapies, educational support, environmental adaptations and social inclusion programs were mentioned as important components to promote the development and quality of life of autistic people. The importance of the teacher's role in the classroom was highlighted, emphasizing the need for an inclusive and individualized approach. Strategies such as adapting the environment, clear communication, individualized instruction and promoting social interaction were discussed as ways to support autistic students in the school environment. The conclusion reinforced the importance of promoting an inclusive society aware of the needs of autistic people. The need for greater awareness, acceptance and support to overcome the challenges and barriers faced by autistic people in society was highlighted. It was also highlighted that when provided with appropriate support and an inclusive environment, autistic people have the potential to flourish, contribute and achieve a full and meaningful life. Finally, bibliographic references were provided to support and validate the information presented in the article.

Neuroimaging in uncontrolled hyperglycemia: a case series and literature review

BackgroundThere are wide-ranging differential diagnoses for the myriad of neurological symptoms associated with non-ketotic hyperglycemia. Similarly, various secondary complications of diabetic ketoacidosis present with nonspecific clinical symptoms. These are inadvertently misdiagnosed as epilepsies and strokes with associated hyperglycemia. Direct association between these nonspecific symptoms and hyperglycemia has been proved by demonstrating their resolution with correction of the latter. This case series portrays the spectrum of few rare neuroimaging findings of uncontrolled hyperglycemia, which helps in proper and prompt diagnoses.Case presentationFive diabetic patients with uncontrolled hyperglycemia were observed. Striatal hyperdensity on computed tomography or striatal T1 hyperintensity on magnetic resonance imaging was observed in three patients who presented with movement disorders. The abnormality was bilateral in one case. These observations were consistent with hyperglycemia-induced hemichorea–hemiballismus syndrome. In another patient who had presented with focal seizures, magnetic resonance imaging revealed subcortical T2/FLAIR hypointensity in bilateral occipital regions, which has been described to be characteristic for non-ketotic hyperglycemia-related seizures. Yet another patient who had been treated for diabetic ketoacidosis had developed bilateral lower-limb weakness. In correlation with a background of rapid correction of hyponatremia, magnetic resonance imaging revealed symmetric areas of altered signal intensity in the bilateral perirolandic region showing an open ring pattern of diffusion restriction, suggesting extrapontine myelinolysis.ConclusionsIn all the cases, the clinical differentials were wide. Neuroimaging was mandatory in establishing hyperglycemia as the underlying cause for the movement disorders and seizures. Also, neuroimaging aided in timely identification of extra-pontine myelinolysis, which might have prevented further central pontine involvement in the patient with diabetic ketoacidosis.

Cluster Analysis to Identify Long COVID Phenotypes Using 129Xe Magnetic Resonance Imaging: A Multi-centre Evaluation.

Long COVID impacts ∼10% of people diagnosed with COVID-19, yet the pathophysiology driving ongoing symptoms is poorly understood. We hypothesised that 129Xe magnetic resonance imaging (MRI) could identify unique pulmonary phenotypic subgroups of long COVID, therefore we evaluated ventilation and gas exchange measurements with cluster analysis to generate imaging-based phenotypes. COVID-negative controls and participants who previously tested positive for COVID-19 underwent 129XeMRI ∼14-months post-acute infection across three centres. Long COVID was defined as persistent dyspnea, chest tightness, cough, fatigue, nausea and/or loss of taste/smell at MRI; participants reporting no symptoms were considered fully-recovered. 129XeMRI ventilation defect percent (VDP) and membrane (Mem)/Gas, red blood cell (RBC)/Mem and RBC/Gas ratios were used in k-means clustering for long COVID, and measurements were compared using ANOVA with post-hoc Bonferroni correction. We evaluated 135 participants across three centres: 28 COVID-negative (40±16yrs), 34 fully-recovered (42±14yrs) and 73 long COVID (49±13yrs). RBC/Mem (p=0.03) and FEV1 (p=0.04) were different between long- and COVID-negative; FEV1 and all other pulmonary function tests (PFTs) were within normal ranges. Four unique long COVID clusters were identified compared with recovered and COVID-negative. Cluster1 was the youngest with normal MRI and mild gas-trapping; Cluster2 was the oldest, characterised by reduced RBC/Mem but normal PFTs; Cluster3 had mildly increased Mem/Gas with normal PFTs; and Cluster4 had markedly increased Mem/Gas with concomitant reduction in RBC/Mem and restrictive PFT pattern. We identified four 129XeMRI long COVID phenotypes with distinct characteristics. 129XeMRI can dissect pathophysiologic heterogeneity of long COVID to enable personalised patient care.

Pulmonary Function and Diffusing Capacity of Carbon Monoxide in Hypersensitivity Pneumonitis: An Observational Study of 152 Patients.

Hypersensitivity pneumonitis (HP) is an inflammatory and/or fibrotic lung disease. The restrictive lung function with low diffusing capacity of carbon monoxide (DLCO) is common in interstitial lung diseases (ILD). There are limited data on pulmonary function test (PFT) in HP and its role for diagnosis is questionable. We analyzed the data of 152 HP patients for type of defect, lung volume, and DLCO. The present study is a retrospective analysis of 152 patients at one of the tertiary chest institutes in India. All diagnosed cases with at least spirometry were included. PFT findings were classified and graded as obstructive, restrictive, and mixed patterns. The correlation of PFT was calculated with disease duration and 6MWT distance. The majority were female [106 (70%)], with a mean age of 47.8 ± 12.3 years. Spirometry with lung volume data were available for 97% patients. PFT was abnormal in 118 (80%) cases. Among the patterns of abnormality, the most common type was restrictive (74%) followed by mixed (15%) and obstructive (11%) with the majority in the severe to very severe grade. The mean total lung capacity (TLC) and residual volume (RV) were reduced, with the grade more severe when the pattern of abnormality was restrictive while the RV/ TLC was higher suggestive of air tapping. DLCO data were available for 132 (87%) cases, with levels decreased in 67%. The severity of DLCO was highest when the pattern of abnormality was restrictive. One of the PFT parameters was abnormal in 137 (90%) cases, with isolated decreased DLCO levels seen in 16 (10%) cases. Forced vital capacity (FVC), TLC, and DLCO showed positive correlation with 6MWT distance (FVC r = .22, P = .02; TLC r = .28, P = .003; DLCO r = .30, P = .002). The PFT abnormality is seen in >80% of HP patients. All types of abnormality were seen, with the restrictive pattern being the most common. Isolated decreased DLCO levels were seen in 10% of cases. We advised to do full PFT for diagnosis and followup of HP.

Supervised Local Training With Backward Links for Deep Neural Networks

The restricted training pattern in the standard BP requires end-to-end error propagation, causing large memory costs and prohibiting model parallelization. Existing local training methods aim to resolve the training obstacles by completely cutting off the backward path between modules and isolating their gradients. These methods prevent information exchange between modules and result in inferior performance. This work proposes a novel local training algorithm, BackLink, which introduces inter-module backward dependency and facilitates information to flow backward along with the network. To preserve the computational advantage of local training, BackLink restricts the error propagation length within the module. Extensive experiments performed in various deep convolutional neural networks demonstrate that our method consistently improves the classification performance of local training algorithms over other methods. For example, our method can surpass the conventional greedy local training method by 6.45% in accuracy in ResNet32 classifying CIFAR100 and recent work by 2.58% in ResNet110 classifying STL-10 with much lower complexity, respectively. Analysis of computational costs reveals that small overheads are incurred in GPU memory costs and runtime on multiple GPUs. Our method can lead up to a 79% reduction in memory cost and 52% in simulation runtime in ResNet110 compared to the standard BP. Therefore, our method could create new opportunities for improving training algorithms towards better efficiency for real-time learning applications.

Movement patterns of the rodent Trinomys dimidiatus in Atlantic Forest

AbstractAnimal movements of wild species are in theory related to individual and species' traits such as sex and reproductive condition, and temporal variation in resource availability or population density. Understanding how individuals move within an area throughout life, how frequent exploratory and dispersive movement are in the population and which individual traits and environmental conditions influence movement are of great importance for understanding how animals respond to environmental changes. Using capture‐mark‐recapture data of Trinomys dimidiatus gathered for 8 years in a montane Atlantic Forest area, we describe movement patterns by comparing two distance metrics (ORL—Observed Range Length and SDT—Mean Successive Distance/Time); we also evaluate the influences of sex on these distance metrics and residence time and number of captures on ORL. Additionally, model selection was used to evaluate the role of individual traits and environmental factors on T. dimidiatus' movements. We recorded 44 individuals (60.27%) with restricted movement pattern and 29 individuals (39.73%) with broad movement pattern within our grid. Broad movement pattern was observed in individuals with both long and short residence time. Males presented larger distance metrics and movements than females. Individuals with greater residence time presented larger ORL, mainly males. Heavier individuals of both sexes presented larger movements than lighter ones, especially males. Males presented shorter movements in periods of increased rainfall, but females' movements did not respond to rainfall variations. Overall, body mass was more important than rainfall in determining movements. The results here show that T. dimidiatus may present different movement patterns, including exploratory or dispersive movements to a new core area. Also, we highlight the importance of individual traits and environmental factors and reinforce sexual differences in individuals' movements and lifetime use of space.