bluuebunny/crossref_metadata_2025 huggingface dataset:
What controls forest litter decomposition? A coordinated distributed teabag experiment across ten mountains
Authors: Ma Shiyu , Chen Shengbin , Ding Yi , He Zhongsheng , Hu Gang , Liu Jie , Luo Ya‐huang , Song Kun , Yang Yongchuan , Huang Xiaolei , Gao Meixiang , Liu Lan , Chen Bo , He Xianjin , Lu Xiaorong , Lv Bingwei , Ma Liang‐Liang , Meng Yani , Tian Zhongping , Zhang Hong‐wei , Zhang Xijin , Zhang Yansong , Zhang Zhaochen , Li Shaopeng , Zhang Jian
Published: September 2024

Litter decomposition in mountainous forest ecosystems is an essential process that affects carbon and nutrient cycling. However, the contribution of litter decomposition to terrestrial ecosystems is difficult to estimate accurately because of the limited comparability of different studies and limited data on local microclimatic and non‐climatic factors. Here, we designed a coordinated experiment within subtropical and tropical forests across ten mountains to evaluate variation in litter decomposition rates and stabilization. We tested whether elevations, soil microclimate, soil physiochemistry, tree species diversity, and microhabitat affect decomposition rates and stabilization by using the Tea bag index as a standardized protocol. We found that the associations of decomposition rates and stabilization with elevation and each environmental factor varied between mountains. Elevation significantly affected decomposition rates and stabilization in the western mountains, where soil microclimate also played a dominant role due to relatively cold environments. Across all mountains, decomposition rates decreased while stabilization increased with increasing elevation. In terms of microclimate, decomposition rates increased with increasing soil temperature and temperature variation during the growing season, whereas stabilization decreased with increasing soil temperature and moisture variation. In terms of non‐climatic factors, decomposition rates increased with increasing tree species diversity, whereas stabilization decreased with soil pH and slope. Our findings enhance the general understanding of how different factors control forest litter decomposition, highlighting the dominant role of soil microclimate in controlling carbon and nutrient cycling in cold environments and high elevations.
Australasian Histories of Antarctica and the Southern Ocean World
Authors: Howitt Rohan
Published: September 2024

Australia and New Zealand have deep historical connections—geological, environmental, cultural, political, and economic—with Antarctica and the Southern Ocean. Yet while Australasia and the Southern Ocean are historically entangled, their historiographies are largely estranged. This article provides a survey of Australian and New Zealand histories of Antarctica, the subantarctic, and the Southern Ocean. I argue that historians in and of Australasia have contributed significantly to understandings of the region's southern hinterland, including the histories and legacies of Antarctic whaling, sealing, science, exploration, politics, and culture. These same connections and entanglements have rarely been used to shed light on Australian and New Zealand histories, but can offer new perspectives on Australasian histories of intercultural contact and exchange, mobilities, the frontier, imperialism, and internationalism. I argue that conceptualising Australia, New Zealand, and Antarctica as littorals of a ‘terraqueous’ Southern Ocean World provides a way to both generate new insights into this region's history and draw new connections with global, world, and oceanic histories.
How pain and body representations transform each other: A narrative review
Authors: Beccherle Maddalena , Scandola Michele
Published: September 2024

Pain, as a multidimensional and subjective experience, intertwines with various aspects of body representation, involving sensory, affective and motivational components. This review explores the bidirectional relationship between pain and body representations, emphasizing the impact of the sense of ownership on pain perception, the transformative impact of pain on motor imagery, the effects associated with vicarious pain perception on body representations and the role of pain in the maintenance of body representations in specific clinical conditions. Literature indicates complex interactions between pain and body representations, with the sense of ownership inducing analgesic effects in some cases and hyperalgesia in others, contingent upon factors such as the appearance of the affected limb. Pain sensations inform the body on which actions might be executed without harm, and which are potentially dangerous. This information impacts on motor imagery too, showing reduced motor imagery and increased reaction times in tasks where motor imagery involves the painful body parts. Finally, contrary to the conventional view, according to which pain impairs body representation, evidence suggests that pain can serve as an informative somatosensory index, preserving or even enhancing the representation of the absent or affected body parts. This bidirectional relationship highlights the dynamic and multifaceted nature of the interplay between pain and body representations, offering insights into the adaptive nature of the central nervous system in response to perceived bodily states.
The “saint” of Livingstonia: Assembling, memorializing, and representation of missionary paraphernalia at the Stone House Museum in Malawi
Authors: Mtotha Comfort Tamanda
Published: September 2024

This article examines the Stone House Museum in Livingstonia, Malawi. The Museum is in a historic Stone House National Monument, a former residence of Reverend Robert Laws, one of the pioneer missionaries of the Livingstonia Mission. The article illustrates how objects, formerly relics of missionary heroism meant to inspire sacrifice and commitment, became “leftover” objects and were later re‐made into museum pieces in the 1970s. Through a haphazard process of professionalizing the Museum to attract new publics in the 1990s and early 2000s, these objects became alienating and disconnected when put behind glass. The Museum echoed the Victorian ethos of romanticizing and prioritizing missionaries' “heroic” efforts over the stories of local people and culture. The material objects of the local Malawian community in the Museum were essentially put into a timeless past, tribal representations, and merely cast as a complementary background to the missionaries' activities. This article relies on an ethnographic methodology of museum histories, analysis of exhibitions and engagements with the Museum's publics. It reveals that the collection and displays of the local community were assembled as an adjunct to missionary paraphernalia. The Museum, despite its claims to be aligned with the post‐colonial, kept its publics “out of history.”
Transition of care in adolescents with epidermolysis bullosa: The provider perspective
Authors: Perez Victoria A. , Mulinda Carly , Bruckner Anna L. , Diaz Lucia Z. , Hook Kristen P. , Lara‐Corrales Irene , Levy Moise L. , Price Harper N. , Morel Kimberly D. , Levin Laura E.
Published: September 2024

The characteristics of epidermolysis bullosa (EB) demand higher than average provider support for transition from pediatric to adult care. We administered an online Qualtrics survey to members of the Epidermolysis Bullosa Clinical Research Consortium (EBCRC), a group of providers who care for patients with EB, in order to examine their practices and perspectives on transition of care (TOC) and identify barriers to successful implementation. Sixteen of eighteen medical centers completed the survey. Eighty‐eight percent of center representatives expressed concerns about their patients transitioning/transferring from the pediatric to adult‐centered care. Thirty‐eight percent of providers reported having a formal TOC program in place. Our findings support the desire for formal TOC programs, the need for a team‐based approach and, in particular, identification of adult providers to participate in the transition to improve this often challenging time.
How many is too many? A review of the significant numbers in pediatric skin lesions and their recommended evaluation
Authors: Mulinda Carly , Yun Sonora , Fenner Justine , Garzon Maria C. , Scollan Margaret E. , Levin Laura E.
Published: September 2024

Pediatric dermatologists are frequently consulted to evaluate children for cutaneous signs of systemic disorders. Numerical thresholds of significance have been described in the dermatologic literature for various skin findings where the likelihood of an associated extracutaneous abnormality or known genetic syndrome increases significantly. Knowledge of these numerical thresholds facilitates diagnosis and management, which improves clinical outcomes and avoids severe complications. This review highlights the clinical presentation, complications, evaluation, and numerical significance, when applicable, for the following skin findings: infantile hemangiomas, capillary malformations, café‐au‐lait macules, hypopigmented macules, juvenile xanthogranulomas, pilomatricomas, and angiofibromas.
Microbiota‐immune‐brain interactions: A new vision in the understanding of periodontal health and disease
Authors: Breivik Torbjørn Jarle , Gjermo Per , Gundersen Yngvar , Opstad Per Kristian , Murison Robert , Hugoson Anders , von Hörsten Stephan , Fristad Inge
Published: September 2024

This review highlights the significance of interactions between the microbiota, immune system, nervous and hormonal systems, and the brain on periodontal health and disease. Microorganisms in the microbiota, immune cells, and neurons communicate via homeostatic nervous and hormonal systems, regulating vital body functions. By modulating pro‐inflammatory and anti‐inflammatory adaptive immune responses, these systems control the composition and number of microorganisms in the microbiota. The strength of these brain‐controlled responses is genetically determined but is sensitive to early childhood stressors, which can permanently alter their responsiveness via epigenetic mechanisms, and to adult stressors, causing temporary changes. Clinical evidence and research with humans and animal models indicate that factors linked to severe periodontitis enhance the responsiveness of these homeostatic systems, leading to persistent hyperactivation. This weakens the immune defense against invasive symbiotic microorganisms (pathobionts) while strengthening the defense against non‐invasive symbionts at the gingival margin. The result is an increased gingival tissue load of pathobionts, including Gram‐negative bacteria, followed by an excessive innate immune response, which prevents infection but simultaneously destroys gingival and periodontal tissues. Thus, the balance between pro‐inflammatory and anti‐inflammatory adaptive immunity is crucial in controlling the microbiota, and the responsiveness of brain‐controlled homeostatic systems determines periodontal health.
Joint kinematic responses of Olympic medallist skiers to repeated slalom runs
Authors: Alhammoud Marine , Trama Robin , Hautier Christophe André , Girard Olivier , Racinais Sébastien , Hansen Clint , Meyer Frédéric , Farooq Abdulaziz , Coint Jérémy , Trameau Thibaut , Brun Loïc , Morel Baptiste
Published: September 2024

This case study aims to examine changes in the lower limb joint kinematic profile and performance stability induced by repeated ski runs in two world‐class alpine skiers. Two Olympic medallist alpine skiers were tested during their slalom training, with continuous recording of right knee and hip angles, along with turn time and run time. The eight runs of the training session were analysed with linear mixed models. Results showed no effect of runs repetition on performance (i.e., run and turn time; P ≥ 0.279). There was no global effect of runs repetition on minimal and maximal angles for either the knee or the hip (P > 0.151). There was an interaction between run and leg for the maximal angle of both the knee and hip (P ≤ 0.047), which increased across runs for the outside leg and decreased for the inside leg. The maximal angular velocity for both the knee and hip increased with runs repetition in extension (P ≤ 0.028). There were no overall changes in maximal angular velocity in flexion with runs repetition (P ≥ 0.264), but there was an interaction between run and leg for the knee (P < 0.001) due to faster eccentric velocities across runs for the outside leg and slower velocities for the inside leg. In conclusion, the observed joint kinematic alterations without concomitant performance impairment support the concept of multiple movement strategies in athletes to achieve similar performance, especially under fatigue conditions.
Optimizing 3D Laser Foil Printing Parameters for AA 6061: Numerical and Experimental Analysis
Authors: Lin Yi-Cheng , Raza M. Mohsin , Hung Chia-Hung , Wang Yu-Xiang , Lo Yu-Lung
Published: September 2024

This study utilizes a technology known as 3D laser foil printing (LFP) to create precise structures by layering metal foils using laser welding. Metal foils have the advantages of rapid cooling and efficient heat conduction, allowing for the formation of fine-grained structures. However, when dealing with materials like aluminum alloys in laser processes, defects can arise as a result of their high reflectivity. To address this challenge, laser circular oscillation welding (LCOW) is applied to the LFP process. LCOW's circular motions with higher scanning frequencies widen the keyholes and reduce some defects such as spattering, bubble formation, and microcracks. Simulation predictions with an error margin of approximately 10% in comparison to experimental results demonstrate the reliability of the model. Furthermore, the study integrates circular packing design with artificial neural networks to create comprehensive processing maps tailored to different criteria for extracting optimal welding parameters. As a result, for the optimized processing parameters screened using the above systematic process, no cracks were observed on the upper surface of the 3D LFP parts produced with a laser power of 800 W and a scanning speed of 550 mm/s, and only 0.12% porosity was observed from the cross section of the sample. Future research will focus on incorporating simulation results to model microstructures more precisely and continually refining LCOW parameters as new materials and technologies emerge, ensuring the ongoing enhancement of weld quality in the 3D LFP process.
Modelling approaches to multibeam echosounders for sound field characterization
Authors: Smith Michael
Published: September 2024

Concern over the impact of multibeam echosounders (MBES) on marine life has increased in recent years. A thorough impact assessment of acoustic sources requires both accurate modeling of the source and radiated sound field, and a biological assessment. The Joint Industry Program Acoustic Modelling Workshop in 2022 provided a set of verification scenarios for a deep-water MBES to compare modelling approaches and assess agreement across models. This work presents several relevant models designed to compute both the MBES beam patterns and propagated acoustic field. Key acoustic metrics used in impact assessment were calculated and compared using these models. The work confirmed that geometrical acoustics is well suited to the unique radiation patterns of MBES. Ray-tracing programs are relevant as well at short ranges and at long horizontal distances in the presence of large sound speed gradients. The estimation of cumulative sound exposure along a survey track is most often dominated by exposure to the main transmit beam of each sector. Accurate modelling of the near field was demonstrated to have a direct impact on final acoustic metrics and threshold ranges for various marine mammal hearing groups.
The history in our genes
The Genetic Book of the Dead: A Darwinian Reverie
Richard Dawkins
Yale University Press, 2024. 360 pp.
Authors: Ball Philip
Published: September 2024

An adaptationist returns with a reverent ode to evolution
In Other Journals
Authors: Jiang Di , Maroso Mattia , Kelly Priscilla N. , Smith Keith T. , Szuromi Phil , Nusinovich Yevgeniya , Suleymanov Yury
Published: September 2024

Editors’ selections from the current scientific literature
Genomes were ‘scrambled’ when worms left the sea
Authors: Wilcox Christie
Published: September 2024

Chromosomal chaos may have aided their moves to fresh water and land
Impact of gated FDG PET/CT on the staging of patients with suspected or proven newly diagnosed advanced epithelial ovarian, fallopian tube, and primary peritoneal cancer: results from a non-randomized, phase II clinical trial
Authors: Virili Florencia , Obermair Andreas , Sanjida Saira , Nicklin James L , Garrett Andrea , Land Russell , Tang Amy , Campbell Louise , Gebski Val , Thomas Paul
Published: September 2024

Objective

Imaging for staging ovarian cancer is important to determine the extent of disease. The primary objective of this study was to compare gated 18F-fluorodeoxyglucose positron emission tomography coupled with computed tomography (FDG PET/CT) and standard CT scan with intravenous contrast to diagnose thoracic involvement in patients with advanced ovarian cancer prior to treatment. The secondary objective was to estimate changes in the International Federation of Gynecology and Obstetrics (FIGO) stage and clinical management resulting from gated PET/CT.

Methods

The IMAGE trial is a non-randomized phase II clinical trial comparing standard CT scanning with gated PET/CT in diagnosing thoracic involvement in a non-selected group of patients with suspected ovarian cancer on a contrast CT scan. Three sets of PET images were obtained comprising an ungated 2 min whole body image, a static 7.5 min image of the upper abdomen and thorax, and a gated end-expiratory image over the upper abdomen and thorax. Images were evaluated for specificity, sensitivity, diagnostic accuracy, and the proportion of patients with changes in FIGO stage and subsequent clinical management was compared between imaging techniques.

Results

A total of 84 patients were enrolled based on a standard CT scan, 67 of whom were eligible for gated PET/CT scans. Diagnostic accuracy with gated PET/CT was more than 80% for lesions in lung, liver, extra-abdominal sites, and pleura, but less than 50% for extra-abdominal lymph nodes. Compared with CT scan at baseline, 46% of patients who had 7.5 min gated PET/CT had disease upstaged from stage III to IV, and 8% had disease downstaged from stage IV to III. However, this led to a change of management in only 5% of patients.

Conclusions

Gated PET/CT enables upstaging; however, in our institution it altered clinical management only in a minority of patients.

Trial registration number

NCT02258165.
Prognosis prediction and immunotherapy optimisation for cryptogenic new-onset refractory status epilepticus
Authors: Jang Yoonhyuk , Ahn Soo Hyun , Park Kyung-Il , Jang Bum-Sup , Lee Han Sang , Bae Jae-Han , Lee Yoonkyung , Sunwoo Jun-Sang , Jun Jin-Sun , Kim Keun Tae , Mon Su Yee , You Ji Hye , Kim Tae-Joon , Shin Hyunsuk , Han Dohyun , Cho Yong Won , Dubey Divyanshu , Chu Kon , Lee Sang Kun , Lee Soon-Tae
Published: September 2024

Background

Cryptogenic new-onset refractory status epilepticus (cNORSE) currently lacks comprehensive knowledge regarding its clinical dynamics, prognostic factors and treatment guidance. Here we present the longitudinal clinical profiles, predictive factors for outcomes and the optimal duration of immunotherapy in patients with cNORSE.

Methods

This retrospective secondary endpoint analysis investigated patients with cNORSE identified from a prospective autoimmune encephalitis cohort at a national referral centre in Korea. The main outcomes included longitudinal functional scales, seizure frequency and the number of antiseizure medications. Measures encompassed NORSE-related clinical parameters such as the duration of unconsciousness, immunotherapy profiles, cytokine/chemokine analysis, and serial MRI scans.

Results

A total of 74 patients with cNORSE were finally analysed (mean age: 38.0±18.2; 36 (48.6%) male). All patients received first-line immunotherapy, and 91.9% (68/74) received second-line immunotherapy. A total of 83.8% (62/74) regained consciousness within a median duration of 30 days (14–56), and 50% (31/62) achieved good outcome (mRS ≤2) at 2 years. Poor 1-year outcomes (mRS ≥3) were predicted by the presence of mesial temporal lobe (mTL) and extra-mTL lesions at 3-month MRI, and prolonged unconsciousness (≥60 days). Those with mTL atrophy exhibited a higher seizure burden post-NORSE. The optimal duration of immunotherapy appeared to be between 18 weeks and 1-year post-NORSE onset.

Conclusions

This study elucidates longitudinal clinical dynamics, functional outcomes, prognostic factors and immunotherapy response in patients with cNORSE. These findings might contribute to a more standardised understanding and clinical decision-making for cNORSE.
Optical properties of CdSe 2D nanoplatelets rolled into nanoscrolls in electric field
Authors: Daibagya D. S. , Ambrozevich S. A. , Zakharchuk I. A. , Osadchenko A. V. , Vasiliev R. B. , Selyukov A. S.
Published: September 2024

In this paper, we investigated the luminescence and kinetic properties of 1.1-nm-thick colloidal CdSe nanoplatelets rolled up into scrolls in an external electric field in the range of 0–150[Formula: see text]kV/cm. Luminescence spectroscopy revealed that placing CdSe nanoscrolls in an external electric field leads to quenching of the intensity of luminescence bands with an increasing electric field, whereas time-correlated single photon counting measurements demonstrate the acceleration of the relaxation processes of electronic excitation. These effects are due to a reduction in the overlap integral between the electron and hole wavefunctions which is the reason for the emergent field-induced luminescence quenching.
Investigation of dielectric properties of varieties of milk powder at various frequencies
Authors: Pachauri Oshin , Bhargava Nidhi
Published: September 2024

The dielectric properties of a material determine its response of the material to the Electromagnetic field (EM field). It comprises dielectric constant ([Formula: see text]), which is the ability to store energy of EM fields, and dielectric loss ([Formula: see text]) which is the amount of dissipated Electromagnetic energy in the form of heat. Dielectric properties are affected by various factors such as frequency, temperature, bulk density, moisture content, etc. Dielectric constant and dielectric loss were determined in this study for milk powders viz. Whole Milk Powder, Skim Milk Powder, and Infant Milk Powder at various microwave frequencies (5.68, 7.45, 10.25[Formula: see text]GHz). The method used to determine dielectric properties is the Two-point Method which is implemented on a microwave bench. It became apparent that when frequency increases dielectric constant decreases and dielectric loss first decreases and then increases. It was also observed that the fat content can have an impact on the milk powders’ dielectric properties.
Dynamic Response Analysis of Laminated Composite Sandwich Plate with Different Lattices Truss Cores Using a Semi-Analytical Method
Authors: Huang Zhou , Lei Yaxi , Liu Yong , Shi Xianjie
Published: September 2024

This paper presents a semi-analytical approach to analyze the dynamic response characteristics of lattice composite sandwich plates with varying lattice truss cores. Under the premise of satisfying the classical laminate theory assumptions of Allen, the lattice truss core is considered an equivalent homogenized structure. Then, the displacement equations for the sandwich plate utilize the first-order shear deformation theory (FSDT). The energy equation for the sandwich plate is constructed using the Lagrange energy method and solved through the Rayleigh–Ritz method. To mimic arbitrary boundary conditions, artificial boundary spring techniques are utilized. The spectral geometry method (SGM) is utilized to describe the displacement field of dynamic equations and boundary conditions. Legendre polynomials are chosen to construct admissible displacement functions for the structure, supplemented by auxiliary polynomials to eliminate discontinuities at the boundaries. The method’s validity is verified through comparisons with relevant literature and finite element method (FEM). Based on free vibration analysis, both steady-state and transient displacement responses of laminated composite sandwich plates are examined, considering the influences of structural parameters and boundary conditions on dynamic response characteristics. These works can provide suitable theoretical references for the engineering field.
Numerical Simulation Method for the Rain Wind-Induced Vibration of Three-Dimensional Flexible Stay Cable at Different Wind Speeds
Authors: Pan Zichen , Guan Jian , Wang Jian , Wang Canchen , Guo Xiaoyu
Published: September 2024

Rain–wind-induced vibration (RWIV) is a phenomenon of cable vibration with a large amplitude and low frequency. The RWIV involves gas, liquid, and solid phases. Therefore, it is very difficult to reproduce the RWIV by using the method of numerical simulation. In the previous research, based on the lubrication theory, researchers have established a theory model for RWIV of a rigid segment of 3D cables. Based on the previous researches, a new numerical simulation method of 3D flexible cable is proposed, which can reflect the interaction between the gas, the liquid, and the solid. The aerodynamics force is calculated by the COMSOL. The evolution of the water film is calculated by MATLAB. In the previous researches, the variation of cable shape was not considered. The cable vibration is obtained by solving the vibration equation of a 1-DOF system. In this paper, the cable is considered to generate the variation in the shape of the cable. The results of cable vibration are obtained by establishing a 3D flexible cable model in ANSYS. By using the new numerical simulation method, the RWIV phenomenon of 3D flexible cable is reproduced. The revolution of the water film, the variation of cable lift, and the cable vibration are calculated at different wind speeds. The spatial shape of cable vibration at every time is obtained. By the analysis of numerical simulation results, the mechanism of RWIV is explained again. Then, by comparing with the previous numerical simulation method, the advantage of the simulation method of RWIV of 3D flexible cable is reflected. Finally, by comparing the numerical simulation results with the results of the wind tunnel test of Gao et al., the accuracy of the simulation method of RWIV of 3D flexible cable is verified.
Nonlinear Stochastic Oscillation of a Single-Degree-of-Freedom Dielectric Elastomer Generator
Authors: Hao Ying , Yu Xinmiao
Published: September 2024

This paper investigates the stochastic nonlinear dynamic response of a single-degree-of-freedom dielectric elastomer generator under the combined action of harmonic excitation and stochastic disturbance. First, the nonlinear vibration model of a single-degree-of-freedom dielectric elastomer generator is established. The average method and fourth-order Runge–Kutta method are used to analyze the influence of pre-stretching, the initial membrane length, the charge amount, and the external excitation amplitude on the system response. Considering stochastic disturbance, the stochastic average method is applied to determine the probability density function (PDF) of the system’s steady-state response, and Monte Carlo numerical simulations are compared with the theoretical calculations for verification. The oscillation amplitude of the steady-state response can be increased by increasing the pre-stretching, harmonic excitation amplitude, and stochastic disturbance intensity. In the case of stochastic disturbance, as the intensity of the disturbance increases, the system becomes more likely to exhibit large amplitude responses for longer durations.
Dynamic Responses of Vehicles on Curved Railway Bridges: Focusing on Wind Direction
Authors: Xu Xinyu , Zhu Siyu , Li Yongle
Published: September 2024

The Wind–Vehicle–Bridge (WVB) coupling method is extensively applied in engineering practices for the dynamic analysis of railway bridges. However, research on the dynamic behaviors of the vehicle on curved bridges in wind conditions remains limited due to the complexities of interactions involved. In this study, the railway alignment and an actual curved bridge were chosen and modeled. The framework of the WVB system was detailed, and four excitation cases were investigated, considering mean wind, fluctuating wind and track irregularities. Three distinct scenarios, including vehicle on a curved bridge subjected to Inward Blowing Wind (IBW), Outward Blowing Wind (OBW) and vehicle on a straight bridge subjected to wind, were explored. The main conclusions are as follows: (1) wind direction significantly affects wheel unloading rate, lateral force, and derailment coefficient; (2) under mean wind condition, critical wind speed increases with the vehicle speed increasing under IBW, while it decreases with the vehicle speed increasing under OBW; (3) Combined wind and track irregularities reveal that wind direction significantly influences dynamic responses, and lower speeds are not necessarily equal to safer conditions for vehicles on curved bridges.
A primer: peer review process for Advances in Physiology Education
Authors: Wilson Thad E. , Harrison-Bernard Lisa M.
Published: September 2024

This mini-review offers a comprehensive and current overview of the peer review process and the qualifications required to serve as a journal reviewer for Advances in Physiology Education. The guidelines are specifically designed for early career professionals new to manuscript reviewing, as well as seasoned research manuscript reviewers who are new to educational manuscript evaluation. Peer review is a cornerstone of scientific publishing, ensuring both quality and rigor. It is both a privilege and a responsibility for all members of the scientific community.
Development of Polisher and Process Optimization for Polishing of Foxtail Millet
Authors: Shivashankar Sanganamoni , Shahi N. C. , Rao B. Dayakar , Suresh Kancherla , Lohani U. C. , Niranjan Thota , Pathare Pankaj B. , Mahanti Naveen Kumar
Published: September 2024

Foxtail millet is a type of minor millet that has nutritional‐rich characteristics. The bran layer in millets contains a considerable amount of antinutritional properties, and grain/flour/product spoilage occurs due to fat in the bran layer. Therefore, the removal of bran from millets can enhance their shelf life. Bran removal from foxtail millet is challenging because of its tiny size. Hence, the study targeted optimizing polishing process parameters for foxtail millet. The effect of process variables such as grain moisture content (8%–16% w.b.), emery roller speed (800–2400 rpm), and polishing time (1–8 min) on polishing characteristics (degree of polishing, head yield, middling yield, and broken content) and proximate composition (protein, fat, crude fiber, ash, and carbohydrate contents) of foxtail millets was studied using the central composite rotatable design (CCRD). Emery roller speed and polishing time significantly affected all responses (p < 0.01). In contrast, grain moisture content had a significant effect only on the degree of polishing (p < 0.05), head, and middling yields (p < 0.01). A numerical optimization technique was adopted to optimize the process parameters of the polisher. The optimum operating conditions were 10% grain moisture content, 1650 rpm of emery roller speed, and 2 min of polishing time. A validation study conducted at optimized conditions revealed no significant difference between the predicted and actual values of responses and considerably less broken content (9.26%). The results of the present study indicate that machinery modified and processes optimized during the study are fairly accepted and can be used to upscale the machine for industrial use.
Abstract A010 The role of TP53 on transposable elements in pediatric cancer
Authors: Laverty Brianne , Yadahalli Shilpa , Subasri Vallijah , Malkin David
Published: September 2024

Background: Transposable elements (TEs) are dynamic repetitive regions which generate mutations and structural variants. TP53 plays a crucial role in suppressing TE movement to maintain genomic stability. The relationship between TP53 and TEs has been extensively studied in tumours, but not the germline. Individuals with germline TP53 pathogenic variants have Li-Fraumeni Syndrome (LFS), a cancer predisposition syndrome with a high lifetime risk of cancer in various tissues. This study aims to characterize the TE landscape in individuals with Li-Fraumeni Syndrome and determine how this contributes to their increased cancer risk. Methods: MELT and xTea were used to identify TEs in children with (n=48) or without (n=198) a germline TP53 variant. TE calls were merged with SURVIVOR and variants were annotated with AnnotSV. To assess the influence of TP53 on TE location, we quantified TEs across genomic windows and identified the top 100 significantly different regions with the Mann-Whitney U test, adjusting for multiple comparisons. We used these regions to develop a gradient-boosted tree model with 5-fold cross-validation to predict TP53 status. Results: Individuals with germline TP53 variants harboured significantly fewer ALU and LINE1 elements in their germline genome compared to the control dataset (p<0.001). The phenomenon was consistent across chromosomes and significant in chromosomes 5 and 11 (FDR<0.05). A gradient-boosted tree model was able to differentiate patients with and without a germline TP53 variant with an AUPRC of 0.77 on an unseen test set. Conclusion: Germline TP53 variants may effect the frequency and location of germline TE insertions, which may influence nearby genomic variations and lead to cancer development. Analyzing TEs in individuals with LFS will enhance our understanding of accelerated cancer development in these patients, informing future research for diagnostic and therapeutic approaches.

Citation Format: Brianne Laverty, Shilpa Yadahalli, Vallijah Subasri, David Malkin. The role of TP53 on transposable elements in pediatric cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A010.
Abstract A029 Investigating the role of environmental toxicant exposures and STAG2 loss in sarcomagenesis
Authors: Kohrn Rachael , Ohm Joyce
Published: September 2024

Humans are exposed to a variety of environmental toxicants which have been implicated in contributing to cancer development. A possible explanation for this link is that adaptive epigenetic changes occur in stem cell populations upon toxicant exposure. These cells are particularly vulnerable during developmental stages, leading to abnormal gene expression later in life. Environmental exposures have been associated with the initiation of sarcoma development. This study will focus on Ewing Sarcoma (ES), as this malignancy has a low mutational burden relative to other cancer types and is thought to be linked to agricultural chemicals. We are also focusing on stromal antigen 2 (STAG2), which is found to be frequently mutated in ES in addition to multiple other tumor types. Patients with STAG2-mutated ES have higher rates of metastatic disease and worse outcomes, but the reason for this remains poorly understood. STAG2 plays a role in the regulation of genomic organization, DNA repair, and modulation of replication stress (RS). It has also been shown that STAG2 loss may lead to dysregulation of the cGAS-STING pathway, which is critical for tumor immunosurveillance. We are testing the effects of environmental toxicants in mesenchymal stem cells (MSCs), the putative cell of origin for ES and many other sarcomas. We have successfully used CRISPR/Cas9 to generate STAG2 knockout MSCs. With this model, we are testing the effects of STAG2 loss and toxicant exposure on levels of RS, epigenomic instability, and innate immune suppression in MSCs. Our results indicate that these toxicants alter the cell cycle dynamics of MSCs, and that these alterations change depending on STAG2 status. We have also observed changes in the DNA damage response of STAG2-mutant MSCs when exposed to environmental toxicants. Interestingly, effects were seen even at sub-lethal doses that may reflect common, low-level exposures. We believe that our data will contribute to the understanding of the mechanism by which environmental toxicants facilitate malignant transformation of Ewing sarcoma and other pediatric sarcomas.

Citation Format: Rachael Kohrn, Joyce Ohm. Investigating the role of environmental toxicant exposures and STAG2 loss in sarcomagenesis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A029.
Abstract A066 Acquired resistance to temozolomide in the Th-MYCN mouse as a clinically-relevant platform to evaluate novel therapeutic strategies against high-risk neuroblastoma
Authors: Poon Evon , Liang Tong , Barone Giuseppe , Costa Barbara M. , Heuss Sara , Robinson Simon P. , Lin Charles , Workman Paul , Jamin Yann , Chesler Louis
Published: September 2024

Advances in preclinical models that recapitulate chemorefractory and relapsed disease are needed to better predict the efficacy of an expanding and promising armamentarium of drug candidates being tested in early-phase pediatric clinical trials. Here, we used longitudinal magnetic resonance imaging to design an individualized, dose-escalating treatment regimen that induces evolution of neuroblastoma in the Th-MYCN genetically-engineered mouse model, concomitant with the acquisition of resistance to temozolomide, a standard chemotherapy used in treatment of refractory, relapsed neuroblastoma patients within European early-phase clinical trials. MRI longitudinally identified the development of intra-tumoral heterogeneity. Molecular profiling of expanding, treatment-refractory regions identified prominent up-regulation of the nor-adrenergic core regulatory signature and deregulation of the CDK2 pathway. Treatment with a CDK2/9 inhibitor led to significant response and an overall survival benefit in temozolomide-resistant Th-MYCN tumors and allografts generated from these resistant tumours. These findings demonstrate the utility of genetically-engineered mouse models as platforms to dissect the evolution of chemoresistance in neuroblastoma and they provide a mechanistic rationale to support the evaluation of CDK2/9 in ongoing paediatric phase I studies of chemotherapy combined with temozolomide in relapsed, treatment refractory neuroblastoma patients.

Citation Format: Evon Poon, Tong Liang, Giuseppe Barone, Barbara M. Costa, Sara Heuss, Simon P. Robinson, Charles Lin, Paul Workman, Yann Jamin, Louis Chesler. Acquired resistance to temozolomide in the Th-MYCN mouse as a clinically-relevant platform to evaluate novel therapeutic strategies against high-risk neuroblastoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A066.
Abstract A072 The PIK3CA/AKT pathway drives therapy resistance in rhabdomyosarcoma
Authors: Wang Yueyang , Yang Qiqi , Yan Chuan , Langenau David M.
Published: September 2024

Olaparib and temozolomide (OT) combination therapy is in clinical trial evaluation for adolescent rhabdomyosarcoma (RMS) muscle cancers. Unfortunately, resistance to OT has been reported in other cancers, with no counterstrategies available. Using preclinical mouse xenograft experiments, we show that OT is effective at curbing RMS growth, yet a subset of tumors develop resistance that is associated with transcriptomic changes that occur in the absence of recurrent genomic mutation. Importantly, a vast majority of resistant RMS models upregulate the PIK3CA/AKT pathway, which in turn activates NRF2 transcription factor phosphorylation and subsequent transcriptional expression of multidrug resistance ABC transport proteins that rapidly efflux drugs from cells. Using dynamic real-time imaging of tumor growth and assessing drug responses at single-cell resolution in human cell line models, we found that the PIK3CA inhibitor alpelisib re-sensitized resistant RMS cells to OT therapy by suppressing the expression of ABC transport proteins. Excitingly, RMS uses the same PIK3CA/AKT pathway activation to drive resistance to standard-of-care combination therapy vincristine, actinomycin D, and cyclophosphamide (VAC) and the combination of OT + alpelisib effectively killed VAC-resistant RMS. Alpelisib also re-sensitized resistant RMS to chemotherapy in preclinical xenograft mouse models resulting in reduced tumor burden and extended disease-free survival. Our work defines a common resistance pathway in RMS and has credentialled a new preclinical strategy to kill therapy-resistant RMS.

Citation Format: Yueyang Wang, Qiqi Yang, Chuan Yan, David M. Langenau. The PIK3CA/AKT pathway drives therapy resistance in rhabdomyosarcoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A072.
Abstract A081 Biomarker-driven targeting of NAD metabolism in rhabdomyosarcoma
Authors: Vasquez Juan C. , Bhardwaj Prateek , Zhao Sophia , Noronha Katelyn , Lucas Karlie , Sundaram Ranjini , Heer Collin , Morotti Raffaella , Spurrier Josh , Bindra Ranjit S
Published: September 2024

Introduction/Background: New treatments are needed to improve survival in rhabdomyosarcoma (RMS). Cells primarily synthesize nicotinamide adenine dinucleotide (NAD+) through the Preiss-Handler and Salvage pathways driven by nicotinic acid phosphoribosyltransferase (NAPRT) and nicotinamide phosphoribosyltransferase (NAMPT), respectively. NAMPT inhibitors (NAMPTi) have been tested in clinical trials, but their efficacy has been limited by lack of appropriate biomarkers for patient selection. Here, we sought to determine if RMS harbors NAPRT silencing that confers a synthetic lethal interaction with NAMPTi. Methods: NAPRT expression was evaluated by immunohistochemistry (IHC) in human tumor samples. In vitro cell viability assays were performed in RMS cell lines using a panel of NAMPT inhibitors. RMS cells isogenic for NAPRT expression were generated via overexpression or CRISPR/Cas9 KO. For in vivo experiments, orthotopic tumor-bearing mice were treated with vehicle control or OT-82 at 25 mg/kg/dose by oral gavage with or without nicotinic acid (NA) at 25 mg/kg/dose once daily for 3 days per week. Results: In vitro, NAPRT negative isogenic RMS cells showed an exquisite sensitivity to a panel of NAMPT inhibitors. When NA was supplemented to model physiologic conditions, NAPRT+ cells were rescuved while cells harboring loss of NAPRT remained sensitive. In vivo, NAMPTi treatment induced significant tumor regression and improved survival in a NAPRT null RMS xenograft model even in the presence of NA, while NAPRT+ tumors did not response to NAMPTi when combined with NA supplementation. IHC staining in a collection of RMS tissue microarrays obtained from the Children’s Oncology Group demonstrated loss of NAPRT protein expression in roughly 25% of tumors.Conclusion: Overall, these data suggest that NAPRT loss may serve as a therapeutic target in RMS by inducing a synthetic lethal interaction with NAD+ depleting agents. Future studies will determine if NA supplementation can mitigate toxicity and widen the therapeutic index, paving the way for the development of biomarker-driven clinical trials in RMS.

Citation Format: Juan C. Vasquez, Prateek Bhardwaj, Sophia Zhao, Katelyn Noronha, Karlie Lucas, Ranjini Sundaram, Collin Heer, Raffaella Morotti, Josh Spurrier, Ranjit S Bindra. Biomarker-driven targeting of NAD metabolism in rhabdomyosarcoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A081.
Abstract B040: Rural-urban differences in multiple symptoms occurrence in pediatric cancer survivors after treatment completion in Nebraska, United States
Authors: Napit Krishtee , Coulter Don , Cordts Katrina , Dai Daisy , Farazi Evi , Watanabe-Galloway Shinobu
Published: September 2024

Background Pediatric cancer is the leading cause of death by disease among children. With advanced treatments, survivors are living longer. However, they often experience multiple symptoms even after the treatment completion. Little is known about whether rural-urban residences are associated with multiple symptoms occurrence in pediatric cancer survivors. Methods We conducted a cross-sectional study of 130 pediatric cancer survivors aged 10-25 who completed treatment within eight years from 2 major hospitals in Nebraska. We used a survey to collect data during their hospital visit and the validated Memorial Symptom Assessment Scale tool to collect information on 30 symptoms. We used the PedsQoL instrument to measure the quality of life. We conducted a multiple linear regression model to find the association between rurality and multiple symptoms and to identify factors associated with multiple symptoms at a level of significance with a p-value of less than 0.05 and an adjusted beta coefficient. Results The mean age of participants was 15.00, the mean year since diagnosis and treatment completion was 4.52 and 2.92, respectively, and the mean number of symptoms was 6.18.Difficulty concentrating (49.23%), lack of energy (46.92%), and feeling drowsy (46.92%) were the most common symptoms. The mean total quality of life score was 82.16 out of 100. In the unadjusted model, the association of residence and multiple symptoms was not found to be significant, but when adjusted for possible confounders such as age, race, ethnicity, education, diagnosis, body mass index, health-related quality of life, the association was found to be significant indicating there are a higher number of symptoms in pediatric cancer survivors residing in rural areas compared to urban areas. Quality of life is also poorer when the number of symptoms is higher. Conclusion Even after the treatment completion, multiple symptoms occur in pediatric cancer survivors, and the number of symptoms is higher for those residing in rural areas.Further exploration is needed because of the higher number of symptoms in those residing in rural areas. The association of multiple symptoms with other neighborhood-level socio-demographic indices, such as the area deprivation index, should also be assessed.

Citation Format: Krishtee Napit, Don Coulter, Katrina Cordts, Daisy Dai, Evi Farazi, Shinobu Watanabe-Galloway. Rural-urban differences in multiple symptoms occurrence in pediatric cancer survivors after treatment completion in Nebraska, United States [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr B040.