bluuebunny/crossref_metadata_2025 huggingface dataset:
Data efficiency and extrapolation trends in neural network interatomic potentials
Authors: Vita Joshua A , Schwalbe-Koda Daniel
Published: August 2023

Recently, key architectural advances have been proposed for neural network interatomic potentials (NNIPs), such as incorporating message-passing networks, equivariance, or many-body expansion terms. Although modern NNIP models exhibit small differences in test accuracy, this metric is still considered the main target when developing new NNIP architectures. In this work, we show how architectural and optimization choices influence the generalization of NNIPs, revealing trends in molecular dynamics (MD) stability, data efficiency, and loss landscapes. Using the 3BPA dataset, we uncover trends in NNIP errors and robustness to noise, showing these metrics are insufficient to predict MD stability in the high-accuracy regime. With a large-scale study on NequIP, MACE, and their optimizers, we show that our metric of loss entropy predicts out-of-distribution error and data efficiency despite being computed only on the training set. This work provides a deep learning justification for probing extrapolation and can inform the development of next-generation NNIPs.
Physics-informed neural networks for modeling astrophysical shocks
Authors: Moschou S P , Hicks E , Parekh R Y , Mathew D , Majumdar S , Vlahakis N
Published: August 2023

Physics-informed neural networks (PINNs) are machine learning models that integrate data-based learning with partial differential equations (PDEs). In this work, for the first time we extend PINNs to model the numerically challenging case of astrophysical shock waves in the presence of a stellar gravitational field. Notably, PINNs suffer from competing losses during gradient descent that can lead to poor performance especially in physical setups involving multiple scales, which is the case for shocks in the gravitationally stratified solar atmosphere. We applied PINNs in three different setups ranging from modeling astrophysical shocks in cases with no or little data to data-intensive cases. Namely, we used PINNs (a) to determine the effective polytropic index controlling the heating mechanism of the space plasma within 1% error, (b) to quantitatively show that data assimilation is seamless in PINNs and small amounts of data can significantly increase the model’s accuracy, and (c) to solve the forward time-dependent problem for different temporal horizons. We addressed the poor performance of PINNs through an effective normalization approach by reformulating the fluid dynamics PDE system to absorb the gravity-caused variability. This led to a huge improvement in the overall model performance with the density accuracy improving between 2 and 16 times. Finally, we present a detailed critique on the strengths and drawbacks of PINNs in tackling realistic physical problems in astrophysics and conclude that PINNs can be a powerful complimentary modeling approach to classical fluid dynamics solvers.
A study of transfer learning in digital rock properties measurement
Authors: Haq M I K , Yulita I N , Dharmawan I A
Published: August 2023

The measurement of physical parameters of porous rock, which constitute reservoirs, is an essential part of hydrocarbon exploration. Typically, the measurement of these physical parameters is carried out through core analysis in a laboratory, which requires considerable time and high costs. Another approach involves using digital rock models, where the physical parameters are calculated through image processing and numerical simulations. However, this method also requires a significant amount of time for estimating the physical parameters of each rock sample. Machine learning, specifically convolutional neural network (CNN) algorithms, has been developed as an alternative method for estimating the physical parameters of porous rock in a shorter time frame. The advancement of CNN, particularly through transfer learning using pre-trained models, has contributed to rapid prediction capabilities. However, not all pre-trained models are suitable for estimating the physical parameters of porous rock. In this study, transfer learning was applied to estimate parameters of sandstones such as porosity, specific surface area, average grain size, average coordination number, and average throat radius. Six types of pre-trained models were utilized: ResNet152, DenseNet201, Xception, InceptionV3, InceptionResNetV2, and MobileNetV2. The results of this study indicate that the DenseNet201 model achieved the best performance with an error rate of 2.11%. Overall, this study highlights the potential of transfer learning to ultimately lead to more efficient and effective computation.
Dynamics of the black soliton in a regularized nonlinear Schrödinger equation
Authors: Pelinovsky Dmitry , Plum Michael
Published: August 2023

We consider a family of regularized defocusing nonlinear Schrödinger (NLS) equations proposed in the context of the cubic NLS equation with a bounded dispersion relation. The time evolution is well-posed if the black soliton is perturbed by a small perturbation in the Sobolev spaceHs(R)H^s(\mathbb {R})withs>12s > \frac {1}{2}. We prove that the black soliton is spectrally stable (unstable) if the regularization parameter is below (above) some explicitly specified threshold. We illustrate the stable and unstable dynamics of the perturbed black solitons by using the numerical finite-difference method. The question of orbital stability of the black soliton is left open due to the mismatch of the function spaces for the energy and momentum conservation.
Simple blow-up solutions of singular Liouville equations
Authors: Wu Lina
Published: August 2023

In a recent series of important works Wei-Zhang [Adv. Math. 380 (2021), Paper No. 107606, 45; Proc. Lond. Math. Soc. (3) 124 (2022), pp. 106–131; Laplacian vanishing theorem for quantized singular Liouville equation, Preprint, arXiv:2202.10825, 2022] proved several vanishing theorems for non-simple blow-up solutions of singular Liouville equations. It is well known that a non-simple blow-up situation happens when the spherical Harnack inequality is violated near a quantized singular source. In this article, we further strengthen the conclusions of Wei-Zhang by proving that if the spherical Harnack inequality does hold, there exist blow-up solutions with non-vanishing coefficient functions.
Gradient higher integrability for double phase problems on metric measure spaces
Authors: Kinnunen Juha , Nastasi Antonella , Pacchiano Camacho Cintia
Published: August 2023

We study local and global higher integrability properties for quasiminimizers of a class of double phase integrals characterized by nonstandard growth conditions. We work purely on a variational level in the setting of a metric measure space with a doubling measure and a Poincaré inequality. The main novelty is an intrinsic approach to double phase Sobolev-Poincaré inequalities.
Nuclear damage in LMNA mutant iPSC-derived cardiomyocytes is associated with impaired lamin localization to the nuclear envelope
Authors: Wallace Melanie , Zahr Hind , Perati Shriya , Morsink Chloé D. , Johnson Lindsey E. , Gacita Anthony M. , Lai Shuping , Wallrath Lori L. , Benjamin Ivor J. , McNally Elizabeth M. , Kirby Tyler J. , Lammerding Jan
Published: August 2023

The LMNA gene encodes the nuclear envelope proteins Lamins A and C, which comprise a major part of the nuclear lamina, provide mechanical support to the nucleus, and participate in diverse-intracellular signaling. LMNA mutations give rise to a collection of diseases called laminopathies, including dilated cardiomyopathy ( LMNA-DCM) and muscular dystrophies. Although nuclear deformities are a hallmark of LMNA-DCM, the role of nuclear abnormalities in the pathogenesis of -DCM remains incompletely understood. Using induced-pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from LMNA-mutant patients and healthy controls, we show that LMNA mutant iPSC-CM nuclei have altered shape or increased size compared with healthy control iPSC-CM nuclei. The LMNA mutation exhibiting the most severe nuclear deformities, R249Q, additionally caused reduced nuclear stiffness and increased nuclear fragility. Importantly, for all cell lines, the degree of nuclear abnormalities corresponded to the degree of Lamin A/C and Lamin B1 mislocalization from the nuclear envelope. The mislocalization was likely due to altered assembly of Lamin A/C. Collectively, these results point to the importance of correct lamin assembly at the nuclear envelope in providing mechanical stability to the nucleus and suggests that defects in nuclear lamina organization may contribute to the nuclear and cellular dysfunction in LMNA-DCM.
Axonal transport of Frizzled5 by Alcadein α-containing vesicles is associated with kinesin-1
Authors: Shiraki Yuzuha , Mitsuma Monet , Takada Ritsuko , Hata Saori , Kitamura Akira , Takada Shinji , Kinjo Masataka , Taru Hidenori , Müller Ulrike C. , Yamamoto Tohru , Sobu Yuriko , Suzuki Toshiharu
Published: August 2023

Alcadein α (Alcα) and amyloid-β protein precursor (APP) are cargo receptors that associate vesicles with kinesin-1. These vesicles, which contain either Alcα or APP, transport various proteins/cargo molecules into axon nerve terminals. Here, we analyzed immune-isolated Alcα- and APP-containing vesicles of adult mouse brains with LC–MS/MS and identified proteins present in vesicles that contained either Alcα or APP. Among these proteins, Frizzled-5 (Fzd5), a Wnt receptor, was detected mainly in Alcα vesicles. Although colocalization ratios of Fzd5 with Alcα are low in the neurites of differentiating neurons by a low expression of Fzd5 in embryonic brains, the suppression of Alcα expression decreased the localization of Fzd5 in neurites of primary cultured neurons. Furthermore, Fzd5-EGFP expressed in primary cultured neurons was preferentially transported in axons with the transport velocities of Alcα vesicles. In synaptosomal fractions of adult-mice brains that express higher levels of Fzd5, the amount of Fzd5 and the phosphorylation level of calcium/calmodulin-dependent protein kinase-II were reduced in the Alcα-deficient mice. These results suggest that reduced transport of Fzd5 by Alcα-containing vesicles associated with kinesin-1 in axon terminals may impair the response to Wnt ligands in the noncanonical Ca2+-dependent signal transduction pathway at nerve terminals of mature neurons.
Beyond Diagnosis: Representing the Hotline in The Slender Thread
Authors: Zeavin Hannah
Published: August 2023

Revisiting the little-noted 1965 film, The Slender Thread, this article argues that its representation of the suicide hotline constellates midcentury anxieties concerning psychiatric care, race, and gender. The Slender Thread provides a story of the suicide hotline at an “early crossroads” in the history of the suicide hotline as it “turned . . . toward cure and the carceral while gloving that power within the protocol of this radical care.”

This is the Poitier Effect: Black fury is and must be sublated into Black care to bypass revolutionary action and insurrection.
Diagnosing America: The Literatures of Mental Health in the US
Authors: Mendelman Lisa , Hutner Gordon
Published: August 2023

Once one is alive to it, scholarship on the literatures of mental health in the US seems to be everywhere, though it is evolving out of so many different sources that its parameters as a subfield can be hard to establish. That is, many studies not overtly focused on psychology and well-being investigate these concerns—from studies of national political mindsets to gendered, racialized, and otherwise biopolitically defined life experiences. The ever-widening scope of the health humanities can also be seen either to include an expanding ring of mental health studies or, in a post-Cartesian world, to be nearly synonymous with studies of psychic life. The scholarly turns to neuroscience, affect, and ontology express a similar set of interests, even as they align with a broader cultural attention to the so-called mental health epidemic that the COVID-19 pandemic, climate disasters, race-based violence, and our myriad other global health crises exacerbate.In part, our present interest reflects what many might consider as an overdue reckoning with the literary representations of the inequitable psychological vulnerabilities of US existence.
Comics and American Cultural Policy
Authors: Beaty Bart
Published: August 2023

This review considers the contributions of two 2021 monographs—Christopher J. Gilbert’s Caricature and National Character: The United States at War and Paul Hirsch’s Pulp Empire: A Secret History of Comic Book Imperialism—each of which examines the role of cartooning in shaping attitudes towards warfare, imperialism, and nationalism in the US in the twentieth century.The highly repetitive and remarkably codified nature of the comic-book story is . . . the thing that made it attractive for propagandistic purposes.
Pollination mechanism inSerapiaswith no pollinaria reconfiguration
Authors: Lanzino Micaela , Palermo Anna Maria , Pellegrino Giuseppe
Published: August 2023

Orchidaceae, one of the most numerous families in the world’s flora, have evolved various pollination strategies to favour cross-pollination, such as deceptive pollination and pollinarium reconfiguration. Among the terrestrial orchids of the Mediterranean, only species belonging to the genus Serapias show a strategy defined as shelter imitation. The floral elements form a tubular structure that insects use during their resting phases. The purpose of this article was to clarify the mechanisms that guarantee pollination with particular attention to the morphological interactions between orchids and pollinators and whether pollinaria reconfiguration is necessary in the promotion of cross-pollination in Serapias. Breeding system experiments and hand-pollination treatments indicated that Serapias was highly self-compatible, shows low value of natural fruit set and is pollinator limited. Time-lapse photos showed that the pollinarium had no refolding of the stipe or caudicle after its removal from the flower. The morphology of the flower determined the attack of the pollinarium on the occiput/vertex of insect. When the insect left the flower, the pollinarium was unable to encounter the stigma. When the insect made a second visit to another flower, the pollen masses of the first pollinarium ended up on the stigma and at the same time, the insect picked up a second pollinarium. Our observations and analyses suggested that morphological interactions between flower and pollinator are crucial to the success of pollination and to prevent self-pollination and thus that pollinarium reconfiguration is unnecessary in shelter deceptive orchids, such as Serapias species, for the promotion of cross-pollination. Serapias represent a case of interactions between plant and pollinator; the formation of the tubular shape of the flower is an essential preadaptation for the development of resting site mimicry originating exclusively in Serapias among Mediterranean orchids.
Adjusting for gene-specific covariates to improve RNA-seq analysis
Authors: Jeon Hyeongseon , Lim Kyu-Sang , Nguyen Yet , Nettleton Dan
Published: August 2023

This article suggests a novel positive false discovery rate (pFDR) controlling method for testing gene-specific hypotheses using a gene-specific covariate variable, such as gene length. We suppose the null probability depends on the covariate variable. In this context, we propose a rejection rule that accounts for heterogeneity among tests by using two distinct types of null probabilities. We establish a pFDR estimator for a given rejection rule by following Storey’s q-value framework. A condition on a type 1 error posterior probability is provided that equivalently characterizes our rejection rule. We also present a suitable procedure for selecting a tuning parameter through cross-validation that maximizes the expected number of hypotheses declared significant. A simulation study demonstrates that our method is comparable to or better than existing methods across realistic scenarios. In data analysis, we find support for our method’s premise that the null probability varies with a gene-specific covariate variable.

Availability and implementation

The source code repository is publicly available at https://github.com/hsjeon1217/conditional_method.
AARDVARK: an automated reversion detector for variants affecting resistance kinetics
Authors: Moreno Thaidy , Magana Joaquin , Quigley David A
Published: August 2023

Resistance to two classes of FDA-approved therapies that target DNA repair-deficient tumors is caused by mutations that restore the tumor cell's DNA repair function. Identifying these “reversion” mutations currently requires manual annotation of patient tumor sequence data. Here we present AARDVARK, an R package that automatically identifies reversion mutations from DNA sequence data.

Availability and implementation

AARDVARK is implemented in R (≥3.5). It is available on GitHub at https://github.com/davidquigley/aardvark. It is licensed under the MIT license.
Correlations among chromosome numbers, nuclear DNA contents and climatic variables of South American Cactaceae in a phylogenetic context
Authors: Las Peñas María Laura , Bauk Karen , Rossi , Nicola , Bernardello Gabriel
Published: August 2023

Cactaceae are American members of arid and semi-arid regions and are also present in tropical forests and temperate climates. The taxonomy is complex owing to large morphological variability, and polyploidy is a significant mechanism in cactus speciation associated with geographical and environmental range expansions. In South America, Cactaceae have a wide distributional range and provide an informative model in which to examine the correlation between ploidy levels and genome sizes with geographical and bioclimatic variables. We tested whether ploidy levels and DNA contents are related to elevation and the 19 WorldClim variables, and we mapped chromosome numbers and amounts of DNA on a molecular phylogeny to interpret their evolution. We performed Pearson correlation tests between the response variables and each climatic variable and used a multivariate analysis to assess the pattern of variation among variables and chromosome numbers. Our data suggest that polyploidy had independent origins within each subfamily. Chromosome numbers were related to variables associated with temperature, whereas DNA contents were related mostly to precipitation. A negative correlation was observed between the amount of DNA in one chromosome set and the increase in the ploidy level. Based on the results, the small genome can be considered ecologically important as an adaptation to higher temperatures and droughts.
Assessing blood oxygen level–dependent signal variability as a biomarker of brain injury in sport-related concussion
Authors: Anderson Evan D , Talukdar Tanveer , Goodwin Grace , Di Pietro Valentina , Yakoub Kamal M , Zwilling Christopher E , Davies David , Belli Antonio , Barbey Aron K
Published: August 2023

Mild traumatic brain injury is a complex neurological disorder of significant concern among athletes who play contact sports. Athletes who sustain sport-related concussion typically undergo physical examination and neurocognitive evaluation to determine injury severity and return-to-play status. However, traumatic disruption to neurometabolic processes can occur with minimal detectable anatomic pathology or neurocognitive alteration, increasing the risk that athletes may be cleared for return-to-play during a vulnerable period and receive a repetitive injury. This underscores the need for sensitive functional neuroimaging methods to detect altered cerebral physiology in concussed athletes. The present study compared the efficacy of Immediate Post-concussion Assessment and Cognitive Testing composite scores and whole-brain measures of blood oxygen level–dependent signal variability for classifying concussion status and predicting concussion symptomatology in healthy, concussed and repetitively concussed athletes, assessing blood oxygen level–dependent signal variability as a potential diagnostic tool for characterizing functional alterations to cerebral physiology and assisting in the detection of sport-related concussion. We observed significant differences in regional blood oxygen level–dependent signal variability measures for concussed athletes but did not observe significant differences in Immediate Post-concussion Assessment and Cognitive Testing scores of concussed athletes. We further demonstrate that incorporating measures of functional brain alteration alongside Immediate Post-concussion Assessment and Cognitive Testing scores enhances the sensitivity and specificity of supervised random forest machine learning methods when classifying and predicting concussion status and post-concussion symptoms, suggesting that alterations to cerebrovascular status characterize unique variance that may aid in the detection of sport-related concussion and repetitive mild traumatic brain injury. These results indicate that altered blood oxygen level–dependent variability holds promise as a novel neurobiological marker for detecting alterations in cerebral perfusion and neuronal functioning in sport-related concussion, motivating future research to establish and validate clinical assessment protocols that can incorporate advanced neuroimaging methods to characterize altered cerebral physiology following mild traumatic brain injury.
NDN-RBE: An Accountable Privacy Aware Access Control Framework For NDN
Authors: Sultan Nazatul Haque , Varadharajan Vijay , Dulal Saurab , Camtepe Seyit , Nepal Surya
Published: August 2023

Named Data Networking (NDN) is an emerging network architecture. An important characteristic of NDN is its in-network cache, which enables Data packets to be available from multiple locations on the Internet. Hence the enforcement of access control mechanisms becomes even more critical in the NDN. This paper proposes a novel access control scheme referred to as Role-Based Encryption for NDN (NDN-RBE), which uses a broadcast encryption mechanism to achieve secure data access control. Our scheme uses the role inheritance property of the traditional Role-Based Access Control (RBAC) model to achieve efficient data access control over hierarchical content. This makes our scheme particularly suitable for large-scale real-world content-centric services like Netflix. Our scheme also supports additional design features such as anonymous signature-based authentication, batch signature verification and two types of privilege revocations. In addition, our formal security analysis demonstrates that our scheme is provably secure against Chosen Plaintext Attacks. Our performance and functionality comparison show that our scheme outperforms other notable existing works in terms of security, functionality, computation, communication and storage overhead. Furthermore, our experimental results show an improvement in content delivery time of the order of 15 percent compared with the other closely related works.
Signed Rhyme and Rhythm With Deaf Children: Early Childhood Teacher Interviews
Authors: Holcomb Leala , Higgins Michael
Published: August 2023

Early childhood programs promote language play opportunities due to the well-documented positive influences on cognition, language, and literacy development. This qualitative investigation explores language play through the form of signed rhyme and rhythm among young deaf children. Teachers specializing in deaf education within an early childhood program were interviewed to assess their knowledge and implementation of signed rhyme and rhythm in their pedagogical practices. The results reveal that despite recognizing numerous advantages and deeming signed rhyme and rhythm as essential for deaf children’s development, these teachers perceive themselves as lacking adequate knowledge and preparation to effectively incorporate this approach in their classrooms. To address this gap, professional development opportunities should be provided to develop knowledge and confidence in teachers, empowering them to effectively implement signed rhyme and rhythm with deaf children.
Defining Comprehensive Disease Control for Use as a Treatment Target for Ulcerative Colitis in Clinical Practice: International Delphi Consensus Recommendations
Authors: Schreiber Stefan , Danese Silvio , Dignass Axel , Domènech Eugeni , Fantini Massimo C , Ferrante Marc , Halfvarson Jonas , Hart Ailsa , Magro Fernando , Lees Charlie W , Leone Salvo , Pierik Marieke J , Peters Michele , Field Polly , Fishpool Helen , Peyrin-Biroulet Laurent
Published: August 2023

Background and Aims

Treatment of ulcerative colitis [UC] requires a patient-centric definition of comprehensive disease control that considers improvements in aspects not typically captured by classical landmark trial endpoints. In an international initiative, we reviewed aspects of UC that affect patients and/or indicate mucosal inflammation, to achieve consensus on which aspects to combine in a definition of comprehensive disease control, using a modified Delphi process.

Methods

The Delphi panel comprised 12 gastroenterologists and one patient advocate. Two gastroenterologists were elected as chairs and did not vote. To inform statements, we asked 18 patients and the panel members about their experiences of remission and reviewed published literature. Panel members voted on statements anonymously in three rounds, with a live discussion before Round 3. Consensus was met if ≥67% of the panel agreed. Statements without consensus in Rounds 1 and 2 were revised or discarded after Round 3.

Results

The panel agreed to measure individual patient benefit using a definition of comprehensive disease control that combines aspects currently measured in trials [rectal bleeding, stool frequency, disease-related quality of life, endoscopy, histological inflammatory activity, inflammatory biomarkers, and corticosteroid use] with additional patient-reported symptoms [bowel urgency, abdominal pain, extraintestinal manifestations, fatigue, and sleep disturbance]. The panel agreed on scoring systems and thresholds for many aspects.

Conclusions

Using a robust methodology, we defined comprehensive disease control in UC. Next, we will combine the measurement and scoring of these aspects into a multicomponent tool and will adopt comprehensive disease control as a treatment target in clinical practice and trials.
Thiopurines Have Sustained Long-term Effectiveness in Patients with Inflammatory Bowel Disease, Which is Independent of Disease Duration at Initiation: A Propensity Score Matched Analysis
Authors: Ranjan Mukesh Kumar , Kumar Peeyush , Vuyyuru Sudheer Kumar , Kante Bhaskar , Mundhra Sandeep K , Golla Rithvik , Virmani Shubi , Sharma Raju , Sahni Peush , Das Prasenjit , Kalaivani Mani , Upadhyay Ashish Datt , Makharia Govind , Kedia Saurabh , Ahuja Vineet
Published: August 2023

Background and Aims

Thiopurines are viable option for the treatment of inflammatory bowel disease [IBD] in resource-limited countries. However, data on the effect of disease duration at thiopurines initiation on long-term effectiveness are limited.

Method

We performed a propensity matched analysis of a retrospective cohort of patients with ulcerative colitis [UC] and Crohn’s disease [CD]. Patients initiated on thiopurines early in the disease course [≤2 years] were compared with those started late [>2 years]. Effectiveness was defined as no requirement for hospitalisation, anti-tumour necrosis factor [TNF] agents, or surgery, and minimum steroid requirement [≤1 steroid course in 2 years] during follow-up.

Results

A total of 988 [UC: 720, CD: 268] patients were included (male: 665 [60.8%], median age: 40 [32–51] years, median follow-up: 40 [19–81] months). Overall effectiveness at 5 and 10 years was 79% and 72% in UC, and 69% and 63% in CD, respectively. After propensity score matching, there was no difference in 5- and 10-year effectiveness between early and late thiopurine initiation groups either for UC [81% and 80% vs 82% and 74%; p = 0.92] or CD [76% and 66% vs 72% and 51%, p = 0.32]. Male sex for UC (negative: hazard ratio [HR]: 0.67, 95% confidence interval [CI): 0.45–0.97; p = 0.03), and ileal involvement [positive: HR: 3.03, 95% CI: 1.32–6.71; p = 0.008], steroid-dependent disease [positive: HR: 2.70, 95% CI: 1.26–5.68; p = 0.01] and adverse events [negative: HR: 0.47, 95% CI:0.27–0.80; p = 0.005] for CD were predictors of thiopurine effectiveness.

Conclusion

Thiopurines have sustained long-term effectiveness in both UC and CD. However, early thiopurine initiation had no better effect on long-term disease outcome compared with late initiation.
Clinical considerations during spontaneous coronary artery dissection in the post-partum period: a case report
Authors: Schamroth Pravda Nili , Houri Ohad , Kornowski Ran , Porter Avital
Published: August 2023

Background

Spontaneous coronary artery dissection (SCAD) is a common and under-recognized cause of myocardial infarction during the post-partum period.

Case summary

We report a case of a young women presenting with chest pain in the post-partum period. Her clinical appearance was that of a myocardial infarction, and angiography was indicative of a Type 2 SCAD. The patients had persistent chest pain, reduced left ventricular function, and critical left anterior descending artery stenosis. Percutaneous coronary intervention was done with caution. Shared decision-making with the patient helped guide the medical treatment plan and follow-up.

Discussion

We discuss the clinical considerations surrounding the management of this patient.
Testing an Intervention to Improve Posthospital Outcomes in Persons Living With Dementia and Their Family Care Partners
Authors: Boltz Marie , Mogle Jacqueline , Kuzmik Ashley , BeLue Rhonda , Leslie Douglas , Galvin James E , Resnick Barbara
Published: August 2023

Background and Objectives

Hospitalized persons living with dementia are at risk for functional decline, behavioral symptoms of distress, and delirium, all persisting in the postacute period. In turn, family care partners (FCPs) experience increased anxiety and lack of preparedness for caregiving, compounding existing strain and burden. Family-centered Function-focused Care (Fam-FFC) purposefully engages FCPs in assessment, decision-making, care delivery, and evaluation of function-focused care during and after hospitalization (within 48 hours of discharge, weekly telephone calls for a total of 7 additional weeks, then monthly for 4 months). The objective of this study was to test the efficacy of Fam-FFC.

Research Design and Methods

A cluster randomized controlled trial included 455 dyads of persons living with dementia and FCPs in 6 medical units in 3 hospitals. Patient outcomes included return to baseline physical function, behavioral symptoms of distress, depressive symptoms, and delirium severity. Family care partner measures included preparedness for caregiving, anxiety, strain, and burden.

Results

Multilevel level modeling demonstrated that the likelihood of returning to baseline function across time for Fam-FFC participants was twice that of the control group by the end of 6 months (OR = 2.4, p = .01, 95% CI 1.2–4.7). Family-centered Function-focused Care was also associated with fewer symptoms of distress (b = −1.1, SE = 0.56, p = .05) but no differences in the amount of moderate physical activity, depressive symptoms, and delirium severity. Preparedness for caregiving increased significantly only from 2 to 6 months (b = 0.89, SE = 0.45, d = 0.21, overall p = .02) in the intervention group, with no group differences in anxiety, strain, and burden.

Discussion and Implications

Family-centered Function-focused Care may help prevent some of the postacute functional decline and behavioral symptoms in hospitalized persons living with dementia. Further research is needed to promote sustained improvements in these symptoms with more attention to the postacute needs of the care partner.
Promoter variations in DBR2-like affect artemisinin production in different chemotypes of Artemisia annua
Authors: Wang Xingwen , Wu Lan , Xiang Li , Gao Ranran , Yin Qinggang , Wang Mengyue , Liu Zhaoyu , Leng Liang , Su Yanyan , Wan Huihua , Ma Tingyu , Chen Shilin , Shi Yuhua
Published: August 2023

Artemisia annua is the only known plant source of the potent antimalarial artemisinin, which occurs as the low- and high-artemisinin producing (LAP and HAP) chemotypes. Nevertheless, the different mechanisms of artemisinin producing between these two chemotypes were still not fully understood. Here, we performed a comprehensive analysis of genome resequencing, metabolome, and transcriptome data to systematically compare the difference in the LAP chemotype JL and HAP chemotype HAN. Metabolites analysis revealed that 72.18% of sesquiterpenes was highly accumulated in HAN compared to JL. Integrated omics analysis found a DBR2-Like (DBR2L) gene may be involved in artemisinin biosynthesis. DBR2L was highly homologous with DBR2, belonged to ORR3 family, and had the DBR2 activity of catalyzing artemisinic aldehyde to dihydroartemisinic aldehyde. Genome resequencing and promoter cloning revealed that complicated variations existed in DBR2L promoters among different varieties of A. annua and were clustered into three variation types. The promoter activity of diverse variant types showed obvious differences. Furthermore, the core region (−625 to 0) of the DBR2L promoter was identified and candidate transcription factors involved in DBR2L regulation were screened. Thus, the result indicates that DBR2L is another key enzyme involved in artemisinin biosynthesis. The promoter variation in DBR2L affects its expression level, and thereby may result in the different yield of artemisinin in varieties of A. annua. It provides a novel insight into the mechanism of artemisinin-producing difference in LAP and HAP chemotypes of A. annua, and will assist in a high yield of artemisinin in A. annua.
Segmentectomy for cancer control in radiologically pure-solid clinical stage IA3 lung cancer
Authors: Kamigaichi Atsushi , Mimae Takahiro , Tsubokawa Norifumi , Miyata Yoshihiro , Adachi Hiroyuki , Shimada Yoshihisa , Ito Hiroyuki , Ikeda Norihiko , Okada Morihito
Published: August 2023

OBJECTIVES

This study aimed to compare cancer control after segmentectomy and lobectomy in patients with radiologically pure-solid clinical stage IA3 non-small-cell lung cancer (NSCLC).

METHODS

Patients with radiologically pure-solid clinical stage IA3 NSCLC who underwent lobectomy or segmentectomy at 3 institutions between 2010 and 2019 were identified. We estimated propensity scores to adjust for confounding variables regarding tumour malignancy, including age, sex, smoking history, tumour size, maximum standardized uptake value on 18F-fluorodeoxyglucose positron emission tomography, lymph node dissection, histological type and lymphatic, vascular and pleural invasion. Cumulative incidence of recurrence (CIR) was evaluated as a primary end point.

RESULTS

Among 412 patients, postoperative recurrence occurred in 7 of 44 patients (15.9%) undergoing segmentectomy, and 71 of 368 patients (19.3%) undergoing lobectomy. CIR was comparable between patients undergoing segmentectomy (5-year rate, 21.9%) and those undergoing lobectomy (5-year rate, 20.8%; P = 0.88). Locoregional recurrence did not differ between patients undergoing segmentectomy (6.8%) and those undergoing lobectomy (9.0%). In multivariable analysis, segmentectomy (versus lobectomy) was not identified as an independent prognostic factor for CIR (hazard ratio, 1.045; 95% confidence interval, 0.475–2.298; P = 0.91). In propensity score matching of 40 pairs, CIR was not significantly different between patients undergoing segmentectomy (5-year rate, 20.7%) and those undergoing lobectomy (5-year rate, 18.4%; P = 0.81).

CONCLUSIONS

Cancer control may be comparable between segmentectomy and lobectomy in patients with radiologically pure-solid clinical stage IA3 NSCLC. Further studies are warranted to clarify the survival benefits of segmentectomy in these patients.
Linear and Quadratic Chabauty for Affine Hyperbolic Curves
Authors: Leonhardt Marius , Lüdtke Martin , Müller J Steffen
Published: August 2023

We give sufficient conditions for finiteness of linear and quadratic refined Chabauty–Kim loci of affine hyperbolic curves. We achieve this by constructing depth $\leq 2$ quotients of the fundamental group, following a construction of Balakrishnan–Dogra in the projective case. We also apply Betts’ machinery of weight filtrations to give unconditional explicit upper bounds on the number of $S$-integral points when our conditions are satisfied.
Evolution of Spatial Risk of Malaria Infection After a Pragmatic Chemoprevention Program in Response to Severe Flooding in Rural Western Uganda
Authors: Xu Erin , Goel Varun , Baguma Emmanuel , Ayebare Emmanuel , Hollingsworth Brandon D , Brown-Marusiak Amanda , Giandomenico Dana , Reyes Raquel , Ntaro Moses , Mulogo Edgar M , Boyce Ross M
Published: August 2023

Background

Malaria epidemics result from extreme precipitation and flooding, which are increasing with global climate change. Local adaptation and mitigation strategies will be essential to prevent excess morbidity and mortality.

Methods

We investigated the spatial risk of malaria infection at multiple timepoints after severe flooding in rural western Uganda employing longitudinal household surveys measuring parasite prevalence and leveraging remotely sensed information to inform spatial models of malaria risk in the 3 months after flooding.

Results

We identified clusters of malaria risk emerging in areas (1) that showed the greatest changes in Normalized Difference Vegetation Index from pre- to postflood and (2) where residents were displaced for longer periods of time and had lower access to long-lasting insecticidal nets, both of which were associated with a positive malaria rapid diagnostic test result. The disproportionate risk persisted despite a concurrent chemoprevention program that achieved high coverage.

Conclusions

The findings enhance our understanding not only of the spatial evolution of malaria risk after flooding, but also in the context of an effective intervention. The results provide a “proof of concept” for programs aiming to prevent malaria outbreaks after flooding using a combination of interventions. Further study of mitigation strategies—and particularly studies of implementation—is urgently needed.
Mitochondrial transport of catalytic RNAs and targeting of the organellar transcriptome in human cells
Authors: Głodowicz Paweł , Kuczyński Konrad , Val Romain , Dietrich André , Rolle Katarzyna
Published: August 2023

Mutations in the small genome present in mitochondria often result in severe pathologies. Different genetic strategies have been explored, aiming to rescue such mutations. A number of these strategies were based on the capacity of human mitochondria to import RNAs from the cytosol and designed to repress the replication of the mutated genomes or to provide the organelles with wild-type versions of mutant transcripts. However, the mutant RNAs present in mitochondria turned out to be an obstacle to therapy and little attention has been devoted so far to their elimination. Here, we present the development of a strategy to knockdown mitochondrial RNAs in human cells using the transfer RNA-like structure of Brome mosaic virus or Tobacco mosaic virus as a shuttle to drive trans-cleaving ribozymes into the organelles in human cell lines. We obtained a specific knockdown of the targeted mitochondrial ATP6 mRNA, followed by a deep drop in ATP6 protein and a functional impairment of the oxidative phosphorylation chain. Our strategy provides a powerful approach to eliminate mutant organellar transcripts and to analyse the control and communication of the human organellar genetic system.
Quercetin Mitigates Oxidative Stress, Inflammation, Apoptosis, and Histopathological Alterations Induced by Chronic Titanium Dioxide Nanoparticle Exposure in the Rat Spleen
Authors: Jaber Fatima A
Published: August 2023

Titanium dioxide nanoparticles (nano-TiO2) have become widespread but are accompanied by various health concerns. Quercetin (QT), a naturally occurring flavonoid in fruits and vegetables, exhibits potent antioxidant properties. This research examined the toxic impacts of nano-TiO2 on the structure and function of the spleen in adult male rats and assessed the possible protective effects of QT. A set of randomly grouped rats was established, consisting of a control group, a QT group (50 mg/kg/day), a nano-TiO2 group (300 mg/kg/day), and a QT-nano-TiO2 group. These substances were orally administered to the respective groups for 90 days. Nano-TiO2 significantly induced oxidative stress in the spleen, leading to reduced levels of serum immunoglobulins. Additionally, there was a notable increase in the expression of apoptotic markers and proinflammatory cytokines. These biochemical disturbances were accompanied by morphological changes in the spleens of rats exposed to nano-TiO2. However, coadministration of QT and nano-TiO2 effectively mitigated most nano-TiO2-induced alterations in the spleen, including apoptotic and proinflammatory responses, antioxidant imbalance, serum immunoglobulin levels, and histopathological changes. It can be concluded that QT has the potential to function as a protective agent against the detrimental impacts of nano-TiO2 on the spleen by improving the antioxidant defense mechanism and modulating the apoptotic and inflammatory responses.
A systematic review of targeted therapy for vestibular schwannoma in patients with NF2-related schwannomatosis
Authors: Chiranth Shivani , Langer Seppo W , Poulsen Hans Skovgaard , Urup Thomas
Published: August 2023

Background

One of the hallmarks of NF2-related Schwannomatosis (NF2-related SWN) is bilateral vestibular schwannomas (VS) that can cause progressive hearing impairment in patients. This systematic review was performed to investigate the efficacy and toxicity of tested targeted agents.

Methods

The systematic search was conducted on PubMed and EMBASE Ovid databases from inception to October 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The incidence of outcomes in studies involving bevacizumab and other targeted therapies was extracted. The bevacizumab results were pooled, and 95% confidence intervals (95% CI) were calculated.

Results

Sixteen studies (8 prospective and 8 retrospective) testing 6 drugs were selected out of 721 search results. There were 10 studies concerning bevacizumab, with a total of 200 patients. The pooled radiographic response rate (RR) was 38% (95% CI: 31 – 45%) and the pooled hearing response rate (HR) was 45% (95% CI: 36 - 54%). The most frequent bevacizumab-related toxicities were hypertension and menorrhagia. Of other targeted therapies showing activity, lapatinib had a RR of 6% and a HR of 31%. A VEGFR vaccine showed RR in 29% and HR in 40% of patients. Both agents had a manageable safety profile.

Conclusions

Bevacizumab, in comparison to other targeted agents, showed the highest efficacy. Lower dosage of bevacizumab shows comparable efficacy and may reduce toxicity. Other targeted agents, administered alone or as combination therapy, have the potential to improve outcomes for VS in patients with NF2-related SWN, but future clinical studies are needed.
Phase evolution and enhanced room temperature piezoelectric properties response of lead-free Ru-doped BaTiO3 ceramic
Authors: Brajesh Kumar , Ranjan Sudhir , Garg Ashish
Published: August 2023

Recent years have witnessed considerable work on the development of lead-free piezoelectric ceramic materials and their structure–property correlations. The development of piezo response is a strong function of phase evolution in these materials. In this work, we report the effect of Ru doping and consequent phase evolution on the maximization of piezoelectric response of polycrystalline lead-free barium titanate, depicted as Ba(RuxTi1-x)O3 (BRT). The samples were prepared in a narrow compositional range of 0 ≤ x ≤ 0.03 using the conventional solid-state reaction method. Ru doping increases the leakage current of BaTiO3 samples attributed to increased oxygen vacancy concentration due to substitution of Ti4+ by Ru3+. Detailed structural analysis reveals that samples exhibiting coexistence of tetragonal (space group: P4mm) and orthorhombic (space group: Amm2) structured phases near room temperature reveal relatively enhanced piezoelectric properties. The BRT sample with Ru content of 2 mol% yields a maximum longitudinal piezoelectric coefficient, d33 of ∼269 pC/N, a high strain value of 0.16% with a large remnant polarization of ∼19 µC/cm2 and a coercive field of 5.8 kV/cm. We propose that the ‘4d’ orbital of Ruthenium plays a crucial role in improving the functional properties and in decreasing the ferroelectric Curie temperature. Our work provides clues into tailoring the phase evolution for designing lead-free piezoelectric materials with enhanced piezoelectric properties.
Effect of distance to tertiary centre on enrolment of paediatric patients with relapsed or refractory cancer on early phase clinical trials in British Columbia
Authors: D’Alessandro Paul R , Bone Jeffrey N , Davis Jessica F , Potts James E , Deyell Rebecca J
Published: August 2023

Objectives

Access to early phase trials for children with relapsed, refractory or progressive (RRPD) cancer is limited in Canada. Patients and families face barriers to access trials, which are poorly understood. The aims of this study were to assess availability of early phase trials and examine the impact of distance from home to study centre on trial enrolment among paediatric oncology patients with RRPD.

Methods

Oncology patients ≤18 years at diagnosis who later had RRPD were identified retrospectively via registry at the only quaternary paediatric oncology centre in British Columbia (BC). We determined if distance to home, as calculated using geocoding software, was predictive of trial offer or enrolment.

Results

Between January 2015 and July 2021, 266 patients experienced 396 RRPD events. Seventy-five patients (28.2%) were eligible for an early phase trial at least once. At first eligible event, 61 patients (22.9%) were offered trial (median age 11.8 years; 69.0% male; 46.0% with CNS tumour) and thirty patients (11.3%) enrolled. Distance was not associated with odds of offer (OR 1.01, CI 0.98 to 1.05) or enrolment (OR 0.99, CI 0.95 to 1.03) on univariate or multivariable analysis adjusted for sex and disease (OR 0.93, CI 0.86 to 1.00). For offered patients, 2-year event-free survival (EFS) and overall survival (OS) were 39.1% (CI 28.0% to 54.8%) and 51.8% (CI 39.9% to 67.2%), respectively. EFS/OS did not differ with distance or enrolment, but varied by disease (EFS P = 0.002, OS P < 0.0001).

Conclusions

Children in BC with cancer and RRPD have limited access to early phase trials. Distance was not predictive of enrolment, suggesting that families travel to access therapy.