bluuebunny/crossref_metadata_2025 huggingface dataset:
3D analysis of maxillomandibular morphology in hyperdivergent and hypodivergent individuals: A cross‐sectional study
Authors: Reis Alyson de Souza , Copello Flavio de Mendonca , de Castro Amanda Cunha Regal , Cevidanes Lucia Helena Soares , do Rego Marcus Vinicius , Visconti Maria Augusta , Ruellas Antônio Carlos de Oliveira
Published: May 2023

Introduction

The aim of this cross‐sectional study was to investigate maxillomandibular morphology in hyperdivergent and hypodivergent individuals, using 3D surface models generated by cone‐beam computed tomography (CBCT).

Methods

The sample consisted of 60 CBCTs (30 males, 30 females) patients aged 12–30 years, divided into two groups comprising hyperdivergent (≥35°) and hypodivergent (≤30°) individuals, according to the mandibular plane (MP) angle. Multiplanar reconstructions were used to mark the landmarks, and 3D surface models were created to evaluate structures of the maxillomandibular complex, including condyle, ramus, symphysis and palatal height. Intergroup comparisons were performed by independent t‐test. Pearson's correlation test was used (P < .05) to evaluate the correlation of the MP angle with the angles and linear measurements of other structures.

Results

Significant differences were found between the groups regarding condylar width, ramus height, condylar plus ramus height, mandibular length, gonial angle, palatal plane angle and palatal‐mandibular angle. No differences (P > .05) were found for the condylar height, symphysis inclination angle or palatal height. Correlations (P < .05) were found between the MP angle and structures of the maxillomandibular complex.

Conclusions

Hyperdivergent (MP ≥ 35°) and hypodivergent (MP ≤ 30°) individuals present different skeletal morphology regarding condylar width, ramus height, condylar plus ramus height, mandibular length, gonial angle, palatal plane angle and palatal‐mandibular angle. There is a significant correlation between MP angle and morphological structures such as condyle, ramus, symphysis, palatal plane angle and palatal‐mandibular angle.
Dorsal root ganglion stimulation for the treatment of chronic pelvic pain: A systematic review
Authors: Ghorayeb Joe H. , Chitneni Ahish , Rupp Adam , Parkash Anishinder , Abd‐Elsayed Alaa
Published: May 2023

Background

Chronic pelvic pain (CPP) is a difficult condition to treat. Due to complex pelvic innervation, dorsal column spinal cord stimulation (SCS) has not been shown to produce the same effect as dorsal root ganglion stimulation (DRGS) given emerging evidence suggesting that applying DRGS may result in favorable outcomes for individuals with CPP. The aim of this systematic review is to investigate the clinical use and effectiveness of DRGS for patients with CPP.

Materials and Methods

A systematic review of clinical studies demonstrating the use of DRGS for CPP. Searches were conducted using four electronic databases (PubMed, EMBASE, CINAHL, and Web of Science) across August and September 2022.

Results

A total of nine studies comprising 65 total patients with variable pelvic pain etiologies met the inclusion criteria. The majority of subjects implanted with DRGS reported >50% mean pain reduction at variable times of follow‐up. Secondary outcomes reported throughout studies including quality of life (QOL) and pain medication consumption were reported to be significantly improved.

Conclusions

Dorsal root ganglion stimulation for CPP continues to lack supportive evidence from well‐designed, high‐quality studies and recommendations from consensus committee experts. However, we present consistent evidence from level IV studies showing success with the use of DRGS for CPP in reducing pain symptoms along with reports of improved QOL through periods as short as 2 months to as long as 3 years. Because the available studies at this time are of low quality with a high risk of bias, we strongly recommend the facilitation of high‐quality studies with larger sample sizes in order to better ascertain the utility of DRGS for this specific patient population. At the same time, from a clinical perspective, it may be reasonable and appropriate to evaluate patients for DRGS candidacy on a case‐by‐case basis, especially those patients who report CPP symptoms that are refractory to noninterventional measures and who may not be ideal candidates for other forms of neuromodulation.
Alethic desires, framing effects, and deflationism: Reply to Asay
Authors: Wyatt Jeremy
Published: May 2023

Jamin Asay has recently argued that deflationists about the concept of truth cannot satisfactorily account for our alethic desires, i.e., those of our desires that pertain to the truth of our beliefs. In this brief reply, I show how deflationists can draw on well‐established psychological findings on framing effects to explain how the concept of truth behaves within the scope of our alethic desires.
Ketogenic diet acutely improves gas exchange and sleep apnoea in obesity hypoventilation syndrome: A non‐randomized crossover study
Authors: Osman Adam , Gu Chenjuan , Kim David E. , Duan Daisy , Barron Bobbie , Pham Luu V. , Polotsky Vsevolod Y. , Jun Jonathan C.
Published: May 2023

Background and Objective

Obesity hypoventilation syndrome (OHS) causes hypercapnia which is often refractory to current therapies. We examine whether hypercapnia in OHS can be improved by a ketogenic dietary intervention.

Methods

We conducted a single‐arm crossover clinical trial to examine the impact of a ketogenic diet on CO2 levels in patients with OHS. Patients were instructed to adhere to 1 week of regular diet, 2 weeks of ketogenic diet, followed by 1 week of regular diet in an ambulatory setting. Adherence was assessed with capillary ketone levels and continuous glucose monitors. At weekly visits, we measured blood gases, calorimetry, body composition, metabolic profiles, and sleep studies. Outcomes were assessed with linear mixed models.

Results

A total of 20 subjects completed the study. Blood ketones increased from 0.14 ± 0.08 during regular diet to 1.99 ± 1.11 mmol/L (p < 0.001) after 2 weeks of ketogenic diet. Ketogenic diet decreased venous CO2 by 3.0 mm Hg (p = 0.008), bicarbonate by 1.8 mmol/L (p = 0.001), and weight by 3.4 kg (p < 0.001). Sleep apnoea severity and nocturnal oxygen levels significantly improved. Ketogenic diet lowered respiratory quotient, fat mass, body water, glucose, insulin, triglycerides, leptin, and insulin‐like growth factor 1. Rebound hypercapnia was observed after resuming regular diet. CO2 lowering was dependent on baseline hypercapnia, and associated with circulating ketone levels and respiratory quotient. The ketogenic diet was well tolerated.

Conclusion

This study demonstrates for the first time that a ketogenic diet may be useful for control of hypercapnia and sleep apnoea in patients with obesity hypoventilation syndrome.
Context‐dependent shifts in self‐regulatory personality processes during COVID‐19: Changes in control predict dynamic shifts in goal reengagement capacity
Authors: Hamm Jeremy M. , Barlow Meaghan A. , Garcia Odalis G. , Duggan Katherine A.
Published: May 2023

The ability to reengage with new attainable goals after major setbacks is a core self‐regulatory trait linked to health and well‐being. Yet little is known about the extent to which such goal reengagement capacities may shift over time in response to changing contextual circumstances. Using a nationally‐representative sample of U.S. adults aged 18–80 (n = 293), the present 1‐year study examined whether changes in opportunity to influence life circumstances (perceived control) were coupled with dynamic shifts in goal reengagement capacity for individuals who differed in their levels of control at pandemic onset. Results from multilevel models showed that within‐person increases in perceived control during the pandemic predicted corresponding within‐person increases in goal reengagement capacity. Moderation models showed that the positive within‐person association between perceived control and goal reengagement was pronounced for individuals with lower levels of control at pandemic onset who may be particularly sensitive to periods of opportunity to pursue new attainable goals. Findings inform theories of personality and self‐regulation in pointing to contextual circumstances under which goal reengagement capacity exhibits dynamic shifts in populations who differ in their perceived opportunities for control.
New insights on the evolution of nucleolar dominance in newly resynthesized hexaploid wheat Triticum zhukovskyi
Authors: Huang Yuhong , Liu Yang , Guo Xianrui , Fan Chaolan , Yi Congyang , Shi Qinghua , Su Handong , Liu Chang , Yuan Jing , Liu Dengcai , Yang Wuyun , Han Fangpu
Published: May 2023

Nucleolar dominance (ND) is a widespread epigenetic phenomenon in hybridizations where nucleolus transcription fails at the nucleolus organizer region (NOR). However, the dynamics of NORs during the formation of Triticum zhukovskyi (GGAuAuAmAm), another evolutionary branch of allohexaploid wheat, remains poorly understood. Here, we elucidated genetic and epigenetic changes occurring at the NOR loci within the Am, G, and D subgenomes during allopolyploidization by synthesizing hexaploid wheat GGAuAuAmAm and GGAuAuDD. In T. zhukovskyi, Au genome NORs from T. timopheevii (GGAuAu) were lost, while the second incoming NORs from T. monococcum (Am Am) were retained. Analysis of the synthesized T. zhukovskyi revealed that rRNA genes from the Am genome were silenced in F1 hybrids (GAuAm) and remained inactive after genome doubling and subsequent self‐pollinations. We observed increased DNA methylation accompanying the inactivation of NORs in the Am genome and found that silencing of NORs in the S1 generation could be reversed by a cytidine methylase inhibitor. Our findings provide insights into the ND process during the evolutionary period of T. zhukovskyi and highlight that inactive rDNA units may serve as a ‘first reserve’ in the form of R‐loops, contributing to the successful evolution of T. zhukovskyi.
La Ética Pública como Deber de Priorizar Las Razones Públicas
Authors: Giuffré Ignacio , R. Zelaya Juan
Published: May 2023

A partir del estudio del caso argentino, argumentamos que la noción de la ética pública predominante se centra en la corrupción, entendida como enriquecimiento de la persona que ejerce la función pública. Frente a esta noción limitada de la ética pública, proponemos entenderla como el deber de ejercer la función estatal conforme a razones públicas. De esta noción más amplia, derivamos tres propuestas para asegurar una función pública ética. Por un lado, una regulación abarcadora y precisa de los conflictos de intereses en el ejercicio de la función pública. Por otro lado, la implementación de mecanismos de participación social en la configuración y control de las decisiones públicas. Por último, nuestro proyecto exige una autoridad de aplicación independiente, autónoma y autárquica.
Resignificar el Derecho a La Educación Y Resignificar lo Humano
Authors: Portilla Faicán Gladys
Published: May 2023

En este ensayo teórico se aborda la cuestión del sentido que tiene el derecho a la educación en las declaratorias de organismos oficiales y la necesidad de resignificar su sentido estratégico fundamental para el real ejercicio de los demás derechos. El objeto de estudió es el sentido del derecho a la educación en relación con el cumplimiento los demás derechos humanos. El objetivo de este trabajo es poner en cuestión el rol del derecho a la educación para resignificarlo como el derecho que conduce al ejercicio de los demás derechos humanos. En lo metodológico, se recurrió a la revisión de fuentes bibliográficas, principalmente, de Naciones Unidas y organismos relaciones y otras posturas que contribuyen al análisis crítico de la noción y el rol del derecho a la educación de cara a la Agenda 2030 y los Objetivos de Desarrollo Sostenible centrando el foco de atención en el Objetivo 4, Educación de calidad. Entre los principales resultados están la correlación entre el derecho a la educación y los demás derechos humanos y la necesidad de resignificar el derecho a la educación como uno objetivo estratégico de cara a la Agenda 2030. Se arribó a las siguientes conclusiones, a) el derecho humano a la educación debe ser resignificado como un derecho superlativo en cuanto vía al logro de los demás derechos humanos en un mundo cada vez más deshumanizado y b) para ir de las declaratorias a la cotidianidad de la vida humana, los compromisos deben ser vinculantes para los Estados.

PALABRAS CLAVE: compromisos vinculantes, educación de calidad como derecho superlativo, resignificar el derecho a la educación.
Construcción de Ciudadanía Y Derechos Humanos
Authors: Alfaro Griselda
Published: May 2023

El presente trabajo pretende dar cuenta de la importancia de las prácticas de derechos humanos realizadas desde la Defensoría del Pueblo en conjunto con la Universidad Nacional de Tucumán en espacios de educación virtual no formal con el Curso Construcción de Ciudadanía, dirigidos a toda la comunidad, a partir de la habilitación de la palabra, para la promoción, difusión y promoción de los derechos, así como, el reconocimiento de las obligaciones y la adquisición de herramientas de convivencia social en un Estado de Democracia.

PALABRAS CLAVE: Derechos Humanos; Derecho a la Educación; Defensoría del Pueblo- Ciudadanía.
Generation of Intense Few-Cycle Terahertz Radiation in Organic Crystals Pumped by 1.24-μm Multigigawatt Chirped Laser Pulses
Authors: Rumiantsev B. V. , Pushkin A. V. , Suleimanova D. Z. , Zhidovtsev N. A. , Potemkin F. V.
Published: May 2023

It has been shown that the spectrum of intense few-cycle terahertz radiation generated in a DAST organic crystal can be controlled by chirping 1.24-μm pump femtosecond laser radiation of a chromium forsterite laser system. It has been found that an increase in the linear chirp of generating radiation results in the narrowing of the spectrum of terahertz radiation and its redshift. The simulation of the generation of terahertz radiation within the model of three-wave mixing has shown that this effect is due to a change in the phase matching width of the degenerate generation of the difference frequency of terahertz range. In addition, the comparative analysis of terahertz radiation spectra generated in DAST, DSTMS, OH1, and BNA organic crystals indicates that the spectral–temporal properties of terahertz radiation can be more roughly controlled by choosing an appropriate crystal. The proposed approach to control the terahertz radiation spectrum by chirping the pump pulse provides the foundation for spectroscopic studies using intense terahertz radiation with controlled spectral–temporal properties.
Diagnostic accuracy of small-for-gestational-age status for infant mortality and school-age outcomes of live births <28 weeks’ gestation: a cohort study
Authors: Doyle Lex W , Chen Julie , Boland Rosemarie Anne , Kane Stefan Charles , Mainzer Rheanna , Roberts Gehan , Josev Elisha K , Clark Marissa , Anderson Peter J , Cheong Jeanie Ling Yoong
Published: May 2023

Objectives

To determine the diagnostic accuracy of small-for-gestational-age (SGA; <10th centile) status for infant mortality and adverse school-age outcomes in infants born extremely preterm (EP; <28 weeks’ gestation).

Design

Geographical cohort studies.

Setting

The state of Victoria, Australia.

Patients

For mortality, live births 22–27 weeks’ gestation from 2009 to 2017 offered active care after birth. For school-age outcomes, survivors to 8 years’ corrected age born in 1991–1992, 1997 or 2005.

Exposures

SGA <10th centile on four commonly used growth references: three derived from neonatal data (Fenton, UK-WHO and Intergrowth Newborn Size) and one from fetal data (Intergrowth Estimated Fetal Weight).

Main outcome measures

(a) Infant mortality; (b) major neurodevelopmental disability, and poor performance on tests of IQ, academic achievement, motor function, and executive function.

Results

Infant mortality data were available for 2040 infants, and neurodevelopmental data for 499 children. Diagnostic accuracy of SGA status was low overall and varied with the growth reference. Positive predictive values for infant mortality ranged from 18% to 21%, only marginally higher than its 18% prevalence. Compared with a prevalence of 17%, positive predictive values for major neurodevelopmental disability ranged from 30% to 38% for the neonatal growth references but was only 20% for Intergrowth Estimated Fetal Weight. SGA status was also associated with lower IQ, poor academic achievement and poor motor performance.

Conclusions

Among infants born EP, the diagnostic accuracy of SGA status was low for both infant mortality and adverse neurodevelopmental outcomes at school age, but importantly varied with the growth reference used to identify SGA status.
Genotypes and phenotypes ofDNM1encephalopathy
Authors: Kim Jeehyun , Teng Lip-Yuen , Shaker Bilal , Na Dokyun , Koh Hyun Yong , Kwon Soon Sung , Lee Joon Soo , Kim Heung Dong , Kang Hoon-Chul , Kim Se Hee
Published: May 2023

Background

Variants in the dynamin-1 (DNM1) gene typically cause synaptopathy, leading to developmental and epileptic encephalopathy (DEE). We aimed to determine the genotypic and phenotypic spectrum ofDNM1encephalopathy beyond DEE.

Methods

Electroclinical phenotyping and genotyping of patients with aDNM1variant were conducted for patients undergoing next-generation sequencing at our centre, followed by a systematic review.

Results

Six patients with heterozygousDNM1variants were identified in our cohort. Three had a typical DEE phenotype characterised by epileptic spasms, tonic seizures and severe-to-profound intellectual disability with pathogenic variants located in the GTPase or middle domain. The other three patients had atypical phenotypes of milder cognitive impairment and focal epilepsy. Genotypically, two patients with atypical phenotypes had variants located in the GTPase domain, while the third patient had a novel variant (p.M648R) in the linker region between pleckstrin homology and GTPase effector domains. The third patient with an atypical phenotype showed normal development until he developed febrile status epilepticus. Our systematic review on 55 reported cases revealed that those with GTPase or middle domain variants had more severe intellectual disability (p<0.001) and lower functional levels of ambulation (p=0.001) or speech and language (p<0.001) than the rest.

Conclusion

DNM1-related phenotypes encompass a wide spectrum of epilepsy and neurodevelopmental disorders, with specific variants underlying different phenotypes.
Effects of bat white-nose syndrome on hibernation and swarming aggregations of bats in Ontario
Authors: Hooton Lauren A. , Adams Amanda A. , Cameron Amy , Fraser Erin E. , Hale Lesley , Kingston Steve , Fenton M. Brock , McGuire Liam P. , Stukenholtz Erin E. , Davy Christina M.
Published: May 2023

Emerging infectious diseases can have substantial impacts on wildlife health, but also provide an opportunity to understand how populations respond to novel selective pressures. White-nose syndrome (WNS) has decimated some populations of bats in eastern North America, but impacts vary among species. We counted bats in 11 hibernacula in Ontario, Canada, before and after WNS arrived, and compared the relative abundance of 5 bat species captured pre-WNS (1966–1968 and 2007–2009) and post-WNS (2017–2019) during swarming at one of these hibernacula. Counts of hibernating bats declined by 87%–100% after WNS arrived. However, we observed a recent, gradual increase in bat counts in the two largest, monitored hibernacula. During swarming, little brown bat ( Myotis lucifugus (Le Conte, 1831)) was the most frequently captured bat in all sampling periods. Capture frequency of northern long-eared bat ( Myotis septentrionalis (Trouessart, 1897)) declined precipitously after WNS arrived, while eastern small-footed bat ( Myotis leibii (Audubon and Bachman, 1842) represented a higher proportion of bat captures in 2017–2019 compared to other sampling periods. Our data suggest potential adaptation of some bat populations to WNS, but also highlight the importance of protecting bats and their habitat during the active season to facilitate population recovery.
Meissner effect and holographic dual for the Melvin–Kerr–Newman–Taub–NUT spacetimes
Authors: Ghezelbash Masoud , Siahaan Haryanto M.
Published: May 2023

We investigate correspondence between the Melvin–Kerr–Newman–Taub–NUT spacetime, and the conformal field theory. The near horizon geometry of extremal Melvin–Kerr–Newman–Taub–NUT spacetime possesses the $$SL\left( 2,{{\mathbb {R}}}\right) \times U\left( 1\right) $$

S
L

2
,
R

×
U

1

isometry, which allows one to employ the asymptotic symmetry group method, in establishing the holographic correspondence for the spacetime. We also use the alternative way of the stretched horizon method, to compute the extremal entropy of the black hole. We find perfect agreement between the results of asymptotic symmetry group and the stretched horizon methods, to establish the holography for the extremal Melvin–Kerr–Newman–Taub–NUT black hole. The black hole Meissner effect for the Melvin–Kerr–Taub–NUT black hole is also discussed.
A Simple 2-Approximation for Maximum-Leaf Spanning Tree
Authors: Liao I-Cheng , Lu Hsueh-I
Published: May 2023

For an [Formula: see text]-edge connected simple graph [Formula: see text], finding a spanning tree of [Formula: see text] with the maximum number of leaves is MAXSNP-complete. The problem remains NP-complete even if [Formula: see text] is planar and the maximal degree of [Formula: see text] is at most four. Lu and Ravi gave the first known polynomial-time approximation algorithms with approximation factors [Formula: see text] and [Formula: see text]. Later, they obtained a [Formula: see text]-approximation algorithm that runs in near-linear time. The best known result is Solis-Oba, Bonsma, and Lowski’s [Formula: see text]-time [Formula: see text]-approximation algorithm. We show an alternative simple [Formula: see text]-time [Formula: see text]-approximation algorithm whose analysis is simpler. This paper is dedicated to the cherished memory of our dear friend, Professor Takao Nishizeki.
Mitigating Query-based Neural Network Fingerprinting via Data Augmentation
Authors: Wang Meiqi , Qiu Han , Zhang Tianwei , Qiu Meikang , Thuraisingham Bhavani
Published: May 2023

Protecting the intellectual property (IP) of deep neural network (DNN) models becomes essential and urgent with the rapidly increasing cost of DNN training. Fingerprinting is one promising IP protection method that queries suspicious models with specific fingerprint samples to infer and verify IP by comparing the predictions with pre-defined labels. Based on utilizing unique features of target models, various DNN fingerprinting methods are proposed to effectively verify the IP of models remotely with a meager false-positive ratio. In this paper, we propose a novel attack to mitigate query-based fingerprinting methods based on data augmentation methods. We propose a randomized transformation on input samples to significantly mislead the fingerprint samples’ prediction and compromise the IP verification. Then, our attack can keep the model utility with an acceptable accuracy drop in the data-free scenario (i.e. without any samples) or achieve much higher precision in the data-limited scenario (i.e. with a small number of samples with the same distribution). An intensive evaluation of three well-known model structures and three well-known datasets shows that our attack can effectively mitigate five query-based DNN fingerprinting methods in top-tier conferences.
Towards Food Image Retrieval via Generalization-Oriented Sampling and Loss Function Design
Authors: Song Jiajun , Li Zhuo , Min Weiqing , Jiang Shuqiang
Published: May 2023

Food computing has increasingly received widespread attention in the multimedia field. As a basic task of food computing, food image retrieval has wide applications, that is, food image retrieval can help users to find the desired food from a large number of food images. Besides, the retrieved information can be applied to establish a richer database for the subsequent food content-related recommendation. Food image retrieval aims to achieve better performance on novel categories. Thus, it is worth studying to transfer the embedding ability from the training set to the unseen test set, that is, the generalization of the model. Food is influenced by various factors, such as culture and geography, leading to great differences between domains, such as Asian food and western food. Therefore, it is challenging to study the generalization of the model in food image retrieval. In this article, we improve the classical metric learning framework and propose a generalization-oriented sampling strategy, which boosts the generalization of the model by maximizing the intra-class distance from a proportion of positive pairs to avoid the excessive distance compression in the embedding space. Considering that the existing optimization process is in an opposite direction to our proposed sampling strategy, we further propose an adaptive gradient assignment policy named
gradient-adaptive optimization
, which can alleviate the intra-class distance compression during optimization by assigning different gradients to different samples. Extensive evaluation on three popular food image datasets demonstrates the effectiveness of the proposed method. We also experiment on three popular general datasets to prove that solving the problem from the generalization can also improve the performance of general image retrieval. Code is available at
https://github.com/Jiajun-ISIA/Generalization-oriented-Sampling-and-Loss
.
Modulatory effect of trans-spinal magnetic intermittent theta burst stimulation on diaphragmatic activity following cervical spinal cord contusion in the rat
Authors: Lee Kun-Ze
Published: May 2023

Transcranial magnetic intermittent theta burst stimulation can enhance the excitability of the cortical region. However, it is unclear whether this approach can modulate spinal neuroplasticity. The present study was designed to investigate hether trans-spinal magnetic intermittent theta burst stimulation can modulate respiratory motor outputs in the rodent model of cervical spinal cord injury. The effect of trans-spinal magnetic intermittent theta burst stimulation on diaphragmatic activity was assessed in adult rats with unilateral cervical spinal cord contusion at 2 weeks post-injury. The result demonstrated that unilateral cervical spinal cord contusion significantly attenuated the inspiratory activity and motor evoked potential of the diaphragm. Trans-spinal magnetic intermittent theta burst stimulation significantly enhanced the inspiratory activity of the diaphragm in cervical spinal cord contused rats. Moreover, inspiratory bursting could be recruited by trans-spinal magnetic intermittent theta burst stimulation in the contused rats without diaphragmatic activity. Notably, the whole body metabolism was also increased by trans-spinal magnetic intermittent theta burst stimulation. These results suggested that trans-spinal magnetic intermittent theta burst stimulation can be considered as a rehabilitative strategy for improving the respiratory activity after cervical spinal cord injury.

National science and technology council (111-2636-B-110-001)

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
The Role of Superior Cervical Ganglion in the Chronic Sensitization of Carotid Bodies Post-Acute Lung Injury
Authors: Kamra Kajal , Karpuk Nikolay , Zucker Irving , Schultz Harold , Wang Hanjun
Published: May 2023

Background/hypothesis of the study: Acute lung injury (ALI) increases respiratory rate (RR), induces hypoxemia. This stimulates carotid body (CB) chemoreflex to maintain oxygen homeostasis. Our previous study indicates a sensitized chemoreflex during the recovery of ALI. Chronic chemoreflex hyperactivity negatively affects the overall quality of life. The neural mechanisms underlying the sensitized CB chemoreflex during the recovery from ALI remain a gap in knowledge. Electrical stimulation of the superior cervical ganglion (SCG) sensitizes the CB chemoreflex in rats. We hypothesized that the SCG causes the CB chemoreflex sensitization post-ALI. Methods and Results: We performed a bilateral SCG ganglionectomy (SCGx) or sham-SCGx (Sx) in our male SD rats 2 weeks before inducing ALI (W-2). After 2 weeks of recovery, ALI was induced using a single intra-tracheal instillation of bleomycin (day 1) and measured the resting respiratory variables- RR, TV (Tidal Volume), and MV (Minute Ventilation). The chemoreflex response to 10% hypoxia and 5% normoxic hypercapnia were measured on W(-3) (pre-SCGx), W0 (post-SCGx/pre-ALI) and W4 (post-ALI) using whole-body plethysmography (WBP). Ganglionectomy did not alter the resting lung parameters and the chemoreflex response to either gas challenge in normal, healthy rats. An increase in resting RR at W1 post-ALI was not significantly different between Sx and SCGx rats. At W4 post-ALI, there were no significant differences in resting lung parameters between Sx and SCGx rats. Consistent with our previous study, the CB chemoreflex response to hypoxia and normoxic hypercapnia in Sx rats at W4 post-ALI was sensitized (p<0.01). However, the chemoreflex sensitivity significantly lowered in SCGx rats in response to hypoxia (p=0.01) and normoxic-hypercapnia (p=0.002). Conclusion(s): The CB chemoreflex sensitization during the recovery from the ALI may be mediated by the SCG. Further understanding of the underlying mechanism will provide important information to develop therapeutic approaches to pulmonary disease to improve clinical outcomes.

This study was supported by: NIH Grant- RO1 HL-152160 and RO1 HL-126796; Lieberman Grant 2021- Dept. of Anesthesiology, UNMC; American Heart Association- Pre-doctoral fellowship, AHA.

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
A multimodal neural network that distinguishes between type 1 and type 2 diabetes in young persons using MRI and clinical data
Authors: Sadria Mehrshad , Bjornstad Petter , Pottumarthi Prasad , Lu-Ping Li , Pyle Laura , Vigers Timothy , Layton Anita
Published: May 2023

Early diabetic kidney disease (DKD) is common in young persons with type 1 (T1D) and type 2 diabetes (T2D) and accentuates their lifetime risk of kidney failure, requiring dialysis or a kidney transplant. Although clinical manifestations of DKD are similar in T1D and T2D, the structural lesions may differ, and it remains unclear whether DKD in T1D and T2D represent distinct diseases. Accordingly, the objective of this study is to build machine learning (ML) models using clinical and kidney MRI data to classify diabetes status, as well as structural and functional kidney differences of individuals with T1D versus T2D. We hypothesize that a highly accurate multimodal neural network can be constructed that integrates clinical and functional kidney MRI images.Data were obtained from several studies at University of Colorado in youth with T1D (n=102), T2D (n=91) as well as non-diabetic controls (n=60). A total of 253 participants were included in the analyses. First, we applied to clinical data (CASPER, IMPROVE-T2D, CROCODILE, and RENAL-HEIR trials) logistic regression and 7 ML models: extreme gradient boosting machine (XGBoost), XGBoost with grid search, k-nearest neighbors (KNN), support vector machine (SVM), decision tree, random forest, and a 3-layer neural network (NN-EHR). When a small subset of the clinical data was used as features, the NN-EHR yielded the highest accuracy of 84%. Next, we considered the MRI images (27,000 images from the 253 individuals). We applied three convoluted NN to perform the classification: AlexNet, VGG16, and a 4-layer Neural Network for Diabetes Detection (NN4DD). Considering the images alone, VGG16 and NN4DD both achieved an accuracy of > 80%. Additionally, by integrating the clinical data and the MRI images, the fusion neural network achieved an accuracy of almost 100%. Finally, an interpretability analysis of NN4DD indicated notable differences in kidney structure and function among the three groups.Although the cost of MRI is prohibitive and thus impractical for diabetes diagnosis, these results provide a proof-of-concept that fused neural networks that integrate multimodal data can be a valuable diagnostic tool, and provide structural and functional insight on kidney differences between T1D and T2D.

This research is sponsored in part by the Natural Sciences and Engineering Council (Canada) and the National Institutes of Health (USA).

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
An orthostatic load of 1/4G and 1/3G differentially activates vascular and cardiac components of cardiopulmonary reflexes
Authors: Jain Mansi , Chandran Dinu , Jaryal Ashok , Deepak Kishore
Published: May 2023

Introduction – Orthostatic load of varying degree affects cardiopulmonary reflexes and baroreflex. Cardiopulmonary reflexes initiate even before the baroreflex activation in response to volume changes in body caused by changed G load. The cardiopulmonary reflex has two effector components i.e., Heart and Vasculature. Lower body negative pressure (LBNP) is a non-invasive tool used to study the physiological effects of varying G loads. Aim & Objective - The study was designed to explore the varying orthostatic load triggering cardiopulmonary reflexes. Material & Methods - 33 healthy human volunteers were recruited. Continuous heart rate and blood pressure – Systolic, diastolic and mean blood pressure (measured as the area under curve of the pulse waveform) were recorded. Orthostatic load of 1/4G and 1/3G were chosen in order to prevent fall in blood pressure and baroreflex activation. The measurements were taken in supine resting state (0 mmHg), at -10 mmHg (1/4 G) and -15 mmHg (1/3G). Heart rate variability was calculated from the Lead II ECG with the help of Labchart Pro 8 ® software. Peripheral vascular resistance (PVR) was estimated indirectly from arterial pressure waveform. Statistical analysis was performed using Graphpad Prism. Results – At 1/4G of orthostatic load (-10 mmHg of oscillatory LBNP) activation of vascular component (PVR) of cardiopulmonary reflex was found with no changes in the cardiac component (HRV). At 1/3G of orthostatic load (-15 mmHg of oscillatory LBNP), there were activation of the cardiac component (LF:HRV, LF/HF:HRV) associated with further increase in the vascular component (PVR). Conclusion – Data suggests that 1/3G and 1/4G orthostatic load applied using LBNP despite no change in blood pressure, causes differential activation of vasculature and cardiac effector components of cardiopulmonary reflexes

No funding received for carrying out the study

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
The effect of inhaled 7% CO2 on salivary cortisol and amylase in Behaviorally Inhibited and Non-Behaviorally Inhibited Humans
Authors: Harshberger Mary , Apostoli Giana , Ehlert Luke , Wolf Olivia , Wiseman Connor , Martino Paul , Miller Daniel , Miller Justin , Terrill Sarah , Allen Michael , Hodges Matthew
Published: May 2023

Behavioral inhibition (BI) is believed to be a genetically determined temperament characteristic that affects roughly 33% of the human population. These individuals are associated with a higher vulnerability to stressful stimuli compared to non-behaviorally inhibited (NBI) individuals. Our previous study demonstrated that BI individuals experienced decreased heart rate variability (HRV) compared to NBI individuals. Our study suggested that female BI individuals have significantly lower parasympathetic nervous system (PNS) activity, however, it is unknown how BI affects perceived stress. In order to better understand behavioral inhibition in humans, our laboratory explored salivary cortisol and amylase levels in response to stressful stimuli of breathing-enhanced CO2 (carbon dioxide). We hypothesized that BI individuals have a greater increase in both salivary cortisol and amylase after exposure to a stressful stimulus when compared to NBI individuals. Prior to the experiment, participants completed AMBI and RMBI forms. These forms indicate BI tendencies to participants, where AMBI is scored out of 32, where 15.5 is the threshold for BI tendencies, and RMBI is scored out of 36, 11.5 being the threshold. Salivary samples were taken at the beginning and end of the study. They were set up on a breathing apparatus and began to breathe room air for a 15 minute control period. Following this, participants either continued to breathe room air as the control group or were given 7% CO2, and then exposed to room air again. Overall, there was no difference in salivary cortisol and amylase between NBI and BI subjects following the onset of 7% CO2. Our data suggests that 7% CO2 may be too much of a respiratory stressor to reveal any physiological differences between the two groups. Ongoing studies will evaluate cortisol and amylase output after the CO2 dose response curve.

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Non-biased RNA-Seq Analysis of Cardiac Tissues post Acute Lung Injury
Authors: Xia Zhiqiu , Zucker Irving , Lisco Steven , Wang Han-Jun
Published: May 2023

Patients suffering from acute lung injury (ALI) are at a high risk of developing cardiac arrhythmias. Our recent study demonstrated that bleomycin (Bleo)-induced ALI in rats exhibited significantly more spontaneous premature ventricular contractions (PVCs) from one to three weeks post induction. Although spontaneous PVCs disappeared at 4 weeks post ALI, PVCs were evoked again by electrical stimulation of the decentralized stellate ganglia in Bleo-exposed rats but not in normal rats. In the current study, we aimed to utilize non-biased RNA-Seq analysis to identify potential gene candidates in cardiac tissues, which may be associated with cardiac arrhythmia during the recovery from ALI. We created an ALI rat model using a single tracheal instillation of bleomycin (2.5 mg/kg), with saline as a vehicle (Veh) control. Blood troponin level was measured between Veh- and Bleo-treated rats at Week 1 (W1) post Veh/Bleo. Cardiac tissues were harvested at W4 post Veh/Bleo for RNA-seq analysis and following PCR validation. At W1 post ALI, cardiac troponin level was significantly increased in Bleo-treated rats whereas it was undetectable in Veh-treated (Control) rats. RNA-seq analysis indicated 11 downregulated (AABR07045427, Habp2, AC130862, Per2, Coch, Phactr3, Angptl7, LOC103690108, Mthfd2, Sorcs1, U6) and 13 upregulated (Calhm5, Metazoa_SRP, Tgm1, Pcare, Drd4, Selplg, AABR07027722; Rn5-8s, 5_8S_rRNA) genes in cardiac tissues at 4 weeks post ALI vs Veh. PCR validated that the gene expressions of Habp2, Coch, Phactr3, LOC103690108, Mthfd2 were significantly downregulated and the gene expressions of Pcare, Drd4 were significantly upregulated in the hearts of Bleo-treated rats at W4 post ALI. Our study demonstrated that multiple gene changes in cardiac tissues are associated with cardiac injury and arrhythmogenesis in bleomycin-induced ALI in male rats. Future studies will further determine the cause-effect relationship between these altered genes and cardiac arrhythmia post ALI.

This study was supported by NIH grant R01 HL-152160 and in part, by NIH grants R01 HL126796.

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Studies on the Mechanism of Lactate-Induced Increase in Ca2+ Oscillations in Carotid Body Type 1 Cells
Authors: Shun Justin , Kang Dawon , Kim Donghee
Published: May 2023

Blood lactate concentration under normal conditions is ~1 mM and increases during hypoxia and exercise due to elevated anaerobic metabolism. Recent studies suggest that lactate acts directly on carotid body Type 1 chemoreceptor (CB) cells and elevates cytosolic [Ca2+], which increases transmitter secretion from CB cells, carotid sinus afferent nerve activity and ventilation. The mechanism by which lactate increases [Ca2+] is still uncertain. Chang et al (2015) reported that lactate binds to Gs-coupled receptor (OlfR78 in rat/mice) whose signaling leads to a rise in [Ca2+]. Torres-Torrelo et al (2021) reported that lactate enters the cell via the monocarboxylate transporter and increases the ratio of NADH to NAD+, which opens cation channels to cause cell depolarization and Ca2+ influx. Another potential mechanism is that lactate itself inhibits K+ channels and/or activates non-selective cation channels to depolarize CB cells and increase Ca2+ influx. Here we studied the effects of lactate on ion channels, cell Em and Ca2+ oscillations in CB cells. Ion channel and Em studies: Sodium lactate (10 mM, pH 7.4) produced a mild depolarization (<10 mV) in ~30% of CB cells. In HEK cells expressing TASK-1/3, lactate (10 mM) caused mild inhibition of the whole-cell current and cell depolarization (as detected by Fluovolt fluorescence). Lactate activated a 20-pS Ca2+-sensitive monovalent cation channel (CaMCC) in ~50% of CB cells. [Ca2+] oscillations: Lactate (1-20 mM) increased the frequency of Ca2+ oscillations in CB cells (and thus averaged [Ca2+]), and this effect was blunted by removal of extracellular Ca2+, nifedipine and 2-APB. Forskolin that elevated cytosolic [cAMP] had no effect on Ca2+ oscillations, and H-89 (PKA inhibitor) did not block lactate- and hypoxia-induced increase in Ca2+ oscillations. Summary: Our studies do not support the OlfR78-Gs-cAMP signaling pathway in lactate-induced increase in Ca2+ oscillations and [Ca2+] in CB cells. Our study supports a mechanism in which lactate activates CaMCC, possibly initiated by inhibition of TASK and/or other signals, to cause cell depolarization that increases Ca2+ influx and the frequency of Ca2+ oscillations.

NIH and Rosalind Franklin University of Medicine and Science

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Role of the median preoptic nucleus in the development of chronic DOCA-salt hypertension
Authors: Collister John , Fritcher Nora , Nahey David
Published: May 2023

Lesions of the anteroventral third ventricle (AV3V region) are known to prevent many forms of experimental hypertension, including mineralocorticoid (DOCA-salt) hypertension in the rat. However, AV3V lesions include the organum vasculosum of the lamina terminalis (OVLT), portions of the median preoptic nucleus (MnPO), as well as efferent fibers from the subfornical organ (SFO), thereby limiting the ability to define the individual contribution of these structures to the prevention of experimental hypertension. We have previously reported that the SFO does not contribute to the chronic hypertensive response to DOCA-salt in rats, and yet the OVLT plays a significant role in the development of DOCA-salt hypertension. Since efferent fibers of the OVLT project to and through the MnPO, the present study was designed to test the hypothesis that the MnPO is necessary for DOCA-salt hypertension in the rat. Male Sprague-Dawley rats underwent unilateral nephrectomy followed by a week of recovery, and subsequent SHAM (n=5) or electrolytic lesion of the MnPO (MnPOx; n=7). Throughout another week of recovery and during the experimental protocol, rats consumed a 2% NaCl diet and 0.9% NaCl drinking solution. 24-hour mean arterial pressure (MAP) was recorded telemetrically 5 days before and 21 days after DOCA implantation (100 mg/rat; SQ). No differences in the 5-day average control MAP were observed between groups (MnPOx: 104 ± 1 mmHg; SHAM: 107±2 mmHg). The chronic pressor response to DOCA was attenuated in MnPOx rats by day 11 of treatment and continued such that MAP increased 25±3 mmHg in SHAM rats by day 21 of DOCA compared to 14±3 mmHg in MnPOx rats. These results support the hypothesis that the MnPO is an important brain site of action for the pathogenesis of DOCA-salt hypertension in the rat.

University of Minnesota Grant In Aid #546839

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.